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Biomedical subjects

X Wu

Publications and source records attributed to X Wu.

At least 469 records · Page 26Linked to original sources

Deconvolution analysis for absorption and metabolism of aspirin in microcapsules.

We have previously proposed a novel deconvolution method, which can estimate first-pass metabolism of orally administered drugs. In the present study, we examined whether this deconvolution method is useful for evaluating oral dosage forms. The absorption and first-pass metabolism of orally administered aspirin formulated in several forms were analyzed. Two types of microcapsules consisting of Eudragit L100 alone and Eudragit L100/ethylcellulose (4:6) were prepared as sustained release formulations, for comparison with aspirin in powder form. The deconvolution analysis revealed that absorption of aspirin was sustained by encapsulating it in microcapsules. Interestingly, it also revealed that the percentage metabolized during absorption was different among the three types of formulations. Thus, the deconvolution method has enabled a comprehensive analysis of orally administered drugs. This method is believed to contribute to the evaluation of oral drug formulations.

Absorption↗

Evaluation of a new self-expandable silicone stent in an experimental tracheal stenosis.

STUDY OBJECTIVES: To assess the usefulness of an animal model for testing new tracheobronchial stents. SETTING: Animal laboratory of a university hospital. ANIMALS AND INTERVENTIONS: In a series with 12 mini-pigs, we induced a stable fibromalacic tracheal stenosis that was 50% to 70% of the normal tracheal diameter. After dilation we inserted a 16 x 40-mm self-expandable silicone stent into the stenotic part of the trachea in 10 of the mini-pigs. Five of the stents had a smooth outer surface, and five had additional silicone retaining spikes. Because of a long stenosis in two of the mini-pigs, two overlapping stents (one smooth and one with spikes) were inserted. MEASUREMENTS AND RESULTS: Stent deployment was successful and resulted in the disappearance of the slight to moderate stridor in all of the mini-pigs. Over a mean (+/- SD) observation period of 24 days (range, 10 to 41 days), all of the mini-pigs redeveloped stridor. Three of them died unexpectedly of suffocation: in all three a smooth stent had migrated, leading to total obstruction of the stenosis. In total, five of the six smooth stents migrated, and only one of the six spiked stents migrated. There was considerable granulation tissue formation at the ends of all of the stents. In the two control mini-pigs, a 12 x 35-mm Dumon stent was inserted. Both Dumon stents migrated, and one of them had considerable granuloma formation at its ends. At the end of the observation period, all stents were removed endoscopically and were found not to have deteriorated over time. CONCLUSIONS: Our model proved to be suitable for the evaluation of the technical aspects of the Polyflex stent. Spikes on the outer stent surface are more effective in preventing migration than smooth-surface stents. Long-term compatibility, however, seems to be difficult to test with our model because both the Polyflex and the Dumon stents had excessive granulation tissue formation at both ends, a factor which--in the case of the Dumon stent--does not occur to such a degree in benign human airway stenoses. Our results indicate a need for prospective long-term studies in benign human airway stenoses.

Animals↗

Genetic susceptibility to tobacco carcinogenesis.

Lung cancer risk is thus defined by the balance between metabolic activation and detoxification of xenobiotic compounds and by the efficiency of DNA repair. It is most likely that multiple susceptibility factors must be accounted for to represent the true dimensions of gene-environment interactions. The ability to identify smokers with the highest risks of developing cancer has substantial preventive implications. These subgroups could be targeted for the most intensive screening and smoking cessation interventions and could be enrolled into chemoprevention trials. Studying susceptibility to common cancers and widely prevalent exposures may provide further insights into the basic mechanisms of carcinogenesis. Issues that will need to be addressed in the very near future include risk communication to study subjects and the ethical, legal, and social consequences of such testing.

Bleomycin↗

[Computerized ribosomal RNA secondary structure modeling of mutants found in Rett syndrome patients and their mothers].

OBJECTIVE: To identify the secondary structure of rRNA mutants, mtDNA2835(C-->T) and mtDNA2706(A-->G) found in Rett syndrome patients and their mothers. METHODS: Both wild type mtDNA sequence of rRNA gene and mutated sequence were input into computer (converted into RNA sequences) and analyzed by the sofware DNASIS v6. 14. The unique prediction size is set 300 bases and the maximum bulge and interior loop size,30 bases. RESULTS: Similar to the positive controls, the mtDNA2835(C-->T) made the 16S rRNA secondary structure totally different,and the energy changes a lot. On the contrary, the mtDNA2706(A-->G) altered little of secondary structure with a small energy shift. CONCLUSION: Computerized folding programs have provided us with a quick prediction of rRNA structure changes induced by these two mutations. Of them, the mtDNA2835(C-->T) might relate to the pathogenesis of Rett syndrome, but the mtDNA2706(A--> G) might be less meaningful.

Computer Simulation↗

[Helicobacter pylori and congestive gastropathy].

OBJECTIVE: This study evaluates the prevalence and significance of Helicobacter pylori(H. pylori) infection in patients with portal hypertension. METHODS: 177 patients were selected. Among whom, 135 patients with portal hypertension and 42 noncirrhotic patients with nonulcerative dyspepsia as a control group. In all patients diagnostic upper endoscopy was performed and gastric biopsies were taken for histological examination and diagnosis of H. pylori infection. RESULTS: Of the portal hypertensive patients, 63 patients had congestive gastropathy, 17(27%) of whom were positive for H. pylori infection and 72 patients did not have gastropathy, 18(25%) of whom were positive for H. pylori infection. In the control group 23 of 42(55%) were positive for H. pylori infection. H. pylori was found less frequently in congestive gastropathy patients than in the control group. We also found that the presence and severity of congestive gastropathy is independent of the H. pylori status. CONCLUSION: The role of H. pylori infection in the pathogenesis of congestive gastropathy seems to be unlikely and we suggest that there is no need for its routine eradication in cirrhotic patients.

Adult↗

Ca2+-induced fusion of sulfatide-containing phosphatidylethanolamine small unilamellar vesicles.

The fusogenic properties of sulfatide-containing 1,2-dioleoyl-3-sn -phosphatidylethanolamine (DOPE) small unilamellar vesicles (SUVs) in the presence of CaCl2 were studied by mixing membrane lipids based on an assay of fluorescence resonance energy transfer (FRET). Fusion of the vesicles was also confirmed by mixing aqueous contents with the Tb/dipicolinate (DPA) assay. The half-times of lipid mixing revealed that the fusion rate decreased with increasing molar concentration of sulfatide. This inhibitory effect was more obvious at sulfatide concentrations higher than 30 mol%, where hydration at the membrane surface reached its maximum and the fusion was no longer pH-sensitive in the range of pH 6.0 - 9.0. Similar inhibitory effect was also observed in Ca2+-induced fusion of DOPE/ganglioside GM1 vesicles but at a lower concentration of the glycosphingolipid (20 mol%). In contrast, increasing the concentration of phosphatidylserine (PS) in DOPE/PS SUVs resulted in an increase in the rate of Ca2+-induced lipid mixing and the pH sensitivity of this system was not affected. These results are consistent with an increasing steric hindrance to membrane fusion at higher molar concentration and larger headgroup size of the glycosphingolipids. Interestingly, the pH sensitivity of the sulfatide-containing liposomes was retained when they were allowed to fuse with synaptosomes in the absence of Ca2+ by a mechanism involving protein mediation.

Animals↗

[An investigation of the polymorphism of HLA class II alleles in the Han population in Hubei Province of China].

OBJECTIVE: To investigate the polymorphism of HLA class II alleles in the Han population in Hubei province. METHODS: The alleles of DRB1*(n=168), DQB1*(n=160) and DPB1*(n=93) were typed by using the polymerase chain reaction/sequence specific primer(PCR/SSP) and polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) techniques. RESULTS: 39 HLA-DRB1, 15 DQB1 and 17 DPB1 alleles were found. Alleles with higher frequencies are DRB1*0901 (GF=14%), *1501(GF=11.3%), *0301(GF=7.1%), *0803(GF=4.8%); DQB1*0301(GF=18.8%), *0303(GF=18.4%), *0201(GF=10%), *0302(GF=8.4%); DPB1*0501(GF=31.2%), *0401(GF=15.1%), *0201(GF=14%), *0402(GF=11.8%), respectively. As compared with Caucasians, the Han people in Hubei province have higher gene frequencies of DRB1*0901, *1001, *0803; DQB1*0303, *0502 and DPB1*0501, *0202; and lower gene frequencies of DRB1*0301, *0401, *1301; DQB1*0201, *0603 and DPB1*0401, suggesting that Hubei Hans have their own layout of HLA class II allele frequencies. CONCLUSION: These data may serve as normal reference values for the Han population in south China.

Alleles↗

Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter.

We have demonstrated in the present study that novel organic cation transporter (OCTN) 2 is a transporter for organic cations as well as carnitine. OCTN2 transports organic cations without involving Na(+), but it transports carnitine only in the presence of Na(+). The ability to transport organic cations and carnitine is demonstrable with human, rat, and mouse OCTN2s. Na(+) does not influence the affinity of OCTN2 for organic cations, but it increases the affinity severalfold for carnitine. The short-chain acyl esters of carnitine are also transported by OCTN2. Two mutations, M352R and P478L, in human OCTN2 are associated with loss of transport function, but the protein expression of these mutants is comparable to that of the wild-type human OCTN2. In situ hybridization in the rat shows that OCTN2 is expressed in the proximal and distal tubules and in the glomeruli in the kidney, in the myocardium, valves, and arterioles in the heart, in the labyrinthine layer of the placenta, and in the cortex, hippocampus, and cerebellum in the brain. This is the first report that OCTN2 is a Na(+)-independent organic cation transporter as well as a Na(+)-dependent carnitine transporter and that OCTN2 is expressed not only in the heart, kidney, and placenta but also in the brain.

Acetylcarnitine↗

[The genotype-based haplotype relative risk and transmission disequilibrium test analyses of familial febrile convulsions].

OBJECTIVE: To confirm the linkage of familial febrile convulsions to the short arm of chromosome 6(6p) or the long arm of chromosome 8(8q). METHODS: The authors finished genotyping of Pst I locus on the coding region of heat shock protein (HSP) 70, 5'untranslated region of HSP70-1, 3' untranslated region of HSP70-2, D8S84 and D8S85. The data were processed by the genotype-based haplotype relative risk(GHRR) and transmission disequilibrium test(TDT) methods in PPAP. RESULTS: Some signs of association and disequilibrium between D8S85 and FC were shown by GHRR and TDT. CONCLUSION: A suspect linkage of familial febrile convulsions to the long arm of chromosome 8 has been proposed.

Chromosomes, Human, Pair 6↗

Molecular cloning and functional characterization of a polyspecific organic anion transporter from Caenorhabditis elegans.

We have cloned a polyspecific organic anion transporter from Caenorhabditis elegans and elucidated its functional characteristics. The C. elegans anion transporter (CeOAT1) codes for a protein of 526 amino acids containing 12 putative transmembrane domains. It exhibits significant homology at the level of amino acid sequence to the C. elegans organic cation transporter and to the mammalian organic cation and anion transporters. The function of CeOAT1 was investigated by expressing the transporter heterologously in mammalian cells. CeOAT1 transports p-aminohippurate (PAH) in a Na(+)-independent manner. The transport mechanism appears to involve anion exchange because CeOAT1-mediated PAH transport is stimulated by a cell-to-medium concentration gradient of alpha-ketoglutarate or fumarate generated by coexpression in the cells of a mammalian Na(+)-coupled dicarboxylate transporter. CeOAT1 exhibits broad specificity, accepting anions such as folate, indomethacin, furosemide, probenecid, and benzylpenicillin as substrates. The Michaelis-Menten constant for the prototypical organic anion PAH is 0.43+/-0.07 mM. This constitutes the first report of the molecular and functional identification of a polyspecific organic anion transporter in C. elegans.

Animals↗

Genome-wide screen for atopy susceptibility alleles in the Hutterites.

A genome-wide screen for loci influencing positive skin prick tests (SPT) to airborne allergens was conducted in the Hutterites, a founder population of European ancestry. Positive SPT to 14 standardized allergens was measured in 370 subjects in our primary sample and 324 subjects in a replication sample. Evidence for linkage to positive SPT was assessed using the transmission disequilibrium test (TDT) with 337 autosomal markers (average spacing 9.13 cM, SD = 7.8 cM). Three loci showed the strongest overall evidence of linkage to atopy, with at least one allele-specific and a locus-specific p< 1 x 10(-4). This study provides evidence for at least three atopy-susceptibility loci in the Hutterites on chromosomes 1, 6 and 16.

Adult↗

Cloning of Schistosoma japonicum Chinese strain 22.6kD membrane-associated protein (Sj-22.6) gene and its overproduction on Escherichia coli.

A 567bp DNA fragment was amplified from Schistosoma japonicum adult worm mRNA by RT-PCR. Sequence analysis revealed that this fragment contained S. Japonicum Chinese strain membrane-associated protein (Sj-22.6) gene. Then this gene was cloned into the expression vector pGEX-4T, and subsequently expressed in Escherichia coli. The recombinant GST-fusion protein was purified by glutathione agarose affinity chromatography. Its molecular weight was about 48 kD. The yield of expression was around 40 mg/L E.coli culture. The immunological test suggested that the recombinant protein had good antigenity which could make a good basis for the research of its immunological function in Schistosomiasis.

Animals↗

Production of chimeric antibody in cells and larvae of silkworm.

By using the recombinant baculovirus expression system, the chimeric antibody against human small cell lung carcinoma was expressed in the cells and larvae of silkworm Bomyx mori N (BmN). The chimeric antibodies produced in BmN cells and larvae which were infected with recombinant viruses rNPVL2, rNPVH17 and dual-recombinant virus rNPVLH19 were detected by Western blot analysis. The co-expression products of heavy- and light-chain genes in silkworm larvae revealed stronger immune binding activity than the single product of heavy or light chain gene expression.

Animals↗

A double blind observation for therapeutic effects of the tong luo kai bi tablets on rheumatoid arthritis.

The therapeutic effects of the Tong Luo Kai Bi Tablets [symbol: see text] in 120 patients with rheumatoid arthritis were observed in this clinical trial by the randomized double blind method. Both the observed group and the control group each had 60 patients. In the observed group treated with the Tong Luo Kai Bi Tablets, 1 case (1.7%) was cured clinically, 27 cases (45.0%) improved markedly, 26 cases (43.3%) improved, with a total effective rate of 90.0%. In the control group treated with Rheumatic Semen Strychni Tablets [symbol: see text], no case was cured, 16 cases (26.7%) improved markedly, 33 cases (55.0%) improved, with a total effective rate of 81.7%. Statistical data showed the Tong Luo Kai Bi Tablets had much better therapeutic effectiveness clinically than the Rheumatic Semen Strychni Tablets (P < 0.05).

Adult↗

Expression of nerve growth factor from Agkistrodon halys Pallas in E. coli and its purification.

The nerve growth factor (NGF) gene of Agkistrodon halys Pallas was cloned into a secretive prokaryotic expression vector pET-22b+ which carried a C-terminal His. Tag sequence. After transforming into E. coli BL21 (DE3), NGF was induced to express at 30 degrees C by IPTG. SDS-PAGE analysis showed an induced expression product band which constituted about 20% of the total bacterial proteins. However, its molecular weight was larger than what was expected. Moreover, the analysis of product solubility revealed that NGF was in the form of inclusion bodies. The inclusion bodies were solubilized in 6 mumol/L guanidine HCl and purified directly by immobilized metal (Ni2+) chelation affinity chromatography. The product was renatured by dilution and air oxidation in the presence of 5 mumol/L CuSO4, and was proved active by examining the survival rate of PC12 cells in a serum-free medium.

Agkistrodon↗

Effects of intra-hippocampal injection of interleukin-2 on pain threshold and formaldehyde-induced substance P-like immunoreactivity in periaqueductal gray and spinal cord.

AIM: To study the effects of intra-hippocampal injection of interleukin-2 (IL-2) on the substance P-like immunoreactivity (SP-LI) in both periaqueductal gray (PAG) and spinal cord, and on pain threshold in rats. METHODS: Immunohistochemistry technique was used and the paw withdrawal threshold to radiant heat was measured. RESULTS: Microinjection of hIL-2 480 U in hippocampus (Hip) increased the pain threshold (93% +/- 57%, P < 0.01). Injection of formaldehyde (For) in one hindpaw decreased SP-LI neuron number on both sides of PAG (2.9 +/- 2.8 vs 22.1 +/- 0.7, 12.3 +/- 2.0 vs 22.4 +/- 1.0, P < 0.01) and increased SP-LI in ipsilateral spinal cord (0.836 +/- 0.015 vs 0.59 +/- 0.09, P < 0.01). Microinjection of hIL-2 480 U in Hip inhibited the effects of For on the SP-LI on both sides of the PAG (11.3 +/- 2.3 vs 2.9 +/- 2.8, 16.9 +/- 3.4 vs 12.3 +/- 2.0, P < 0.05) and spinal cord (0.71 +/- 0.03 vs 0.836 +/- 0.015, P < 0.01). The combination of intraperitoneal injection of corticotropin and intra-hippocampal injection of IL-2 increased the number of SP-LI neurons in PAG furtherly as compared with IL-2 240 U alone (13.6 +/- 3.6 vs 7.6 +/- 4.3, P < 0.05). CONCLUSION: The analgesic effects of intra-hippocampal injection of IL-2 are mediated, possibly, via the increased of SP in PAG and the decrease of SP in the spinal cord. There is a synergetic relation between IL-2 and corticotropin.

Animals↗

[Effect of human plasma HDL on the HDL receptors of plasma membranes of cholesterol-fed rabbit].

Atherosclerosis(As) rabbit model was developed by high-cholesterol feeding for 12 weeks. The rabbits were injected intravenously with human plasma HDL preparation per week, and then the effects of HDL on the lipids contents of serum, liver and bile nd the activity of HDL receptors on liver plasma membranes of cholesterol-fed rabbit were investigated. The results showed that HDL preparation had no effect on decreasing the lipids contents of serum, but it could low down the lipid depositions in liver, and promote the excretion of lipids from bile. The value of Bmax of HDL receptor showed decreasing trendy and the value of Kd showed increasing trendy in cholesterol-fed rabbits. In HDL-treated rabbits, the value of Bmax increased significantly as compared with that of normal group(P < 0.05), but the value of Kd showed no difference. The results suggested that human plasma HDL could enhance the activity of HDL receptors on the liver plasma membranes of cholesterol-fed rabbit.

Animals↗