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Biomedical subjects

Wei Han

Publications and source records attributed to Wei Han.

At least 109 records · Page 6Linked to original sources
PubMed2004

[Experiment of simultaneous denitrifying phosphorus accumulation].

Denitrifying phosphorus accumulation (DNPA) and the factors affecting it were studied in a SBR with synthetic wastewater. The results showed that the sludge acclimatized under anaerobic/aerobic operation with good phosphorus removal ability, showed DNPA soon when fed nitrate instead of aeration following the anaerobic stage. Anaerobic stage was a vital premise to DNPA. If DNPA sludge was fed with nitrate prior to anaerobic stage, the DNPA would weaken even disappear. When acetate was used as sole carbon resource in the influent and nitrate did not exist in anaerobic, 1 hour of anaerobic time was optimal. NO3- -concentration in the anoxic was one of the factors affecting DNPA. When nitrate concentration was advanced from 5mg/L to 20mg/L, the percentage of DNPA increased from 11.9% to 48.7% under the condition of anaerobic(2h)-anoxic(1h)-aerobic(2h). But when the NO3- -concentration was enhanced upwards of 20mg/L, the efficiency cannot be improved. Induced DNPA did not disappear even though there was aerobic stage following anoxic stage, but the shorter the aerobic stage lasted the higher proportions of phosphorus removal via DNPA to total removal.

Bacteria, Aerobic↗
PubMed2003

A novel peroxisome proliferator-activated receptor alpha/gamma dual agonist demonstrates favorable effects on lipid homeostasis.

Patients with type 2 diabetes mellitus exhibit hyperglycemia and dyslipidemia as well as a markedly increased incidence of atherosclerotic cardiovascular disease. Here we report the characterization of a novel arylthiazolidinedione capable of lowering both glucose and lipid levels in animal models. This compound, designated TZD18, is a potent agonist with dual human peroxisome proliferator-activated receptor (PPAR)-alpha/gamma activities. In keeping with its PPARgamma activity, TZD18 caused complete normalization of the elevated glucose in db/db mice and Zucker diabetic fatty rats. TZD18 lowered both cholesterol and triglycerides in hamsters and dogs. TZD18 inhibited cholesterol biosynthesis at steps before mevalonate and reduced hepatic levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Moreover, TZD18 significantly suppressed gene expression of fatty acid synthesis and induced expression of genes for fatty acid degradation and triglyceride clearance. Studies on 17 additional PPARalpha or PPARalpha/gamma agonists showed that lipid lowering in hamsters correlated with the magnitude of hepatic gene expression changes. Importantly, the presence of PPARgamma agonism did not affect the relationship between hepatic gene expression and lipid lowering. Taken together, these data suggest that PPARalpha/gamma agonists, such as TZD18, affect lipid homeostasis, leading to an antiatherogenic plasma lipid profile. Agents with these properties may provide favorable means for treatment of type 2 diabetes and dyslipidemia and the prevention of atherosclerotic cardiovascular disease.

Animals↗
PubMed2003

Using denaturing HPLC for SNP discovery and genotyping, and establishing the linkage disequilibrium pattern for the all-trans-retinol dehydrogenase (RDH8) gene.

All-trans-retinol dehydrogenase (RDH8) is a visual cycle enzyme that reduces all-trans-retinal to all-trans-retinol. As part of an on-going effort to map genes involved in complex eye diseases, myopia in particular, using association studies, single nucleotide polymorphisms (SNPs) were identified and linkage disequilibrium (LD) pattern was established within and around the RDH8 gene. We used denaturing high-performance liquid chromatography (DHPLC) to screen SNPs in four DNA pools each consisting of DNA from five individuals and genotyped the identified SNPs in 150 Chinese subjects from Hong Kong. Fifteen SNPs were identified: seven were common with the minor allele frequency >0.05 and ten were novel. Common SNPs were included in LD and haplotype analysis using the ASSOCIATE and EH programmes. Four SNPs in the 3' region exhibited significant LD and formed a haplotype block, while three common SNPs in the 5' region did not exhibit useful LD. The LD pattern around the RDH8 gene suggested that one SNP from the 3'region and two to three SNPs from the 5' region were needed in association studies involving RDH8. Our results demonstrated the efficiency of DHPLC in screening SNPs when coupled with DNA pooling strategy and in genotyping SNPs.

Alcohol Oxidoreductases↗
PubMed2003

Aryloxazolidinediones: identification of potent orally active PPAR dual alpha/gamma agonists.

A series of novel aryloxazolidine-2,4-diones was synthesized. A structure-activity relationship study of these compounds led to the identification of potent, orally active PPAR dual alpha/gamma agonists. Based on the results of efficacy studies in the db/db mice model of type 2 diabetes and the desired pharmacokinetic parameters, compound 12 was selected for further profiling.

Administration, Oral↗
PubMed2003

Canine ventricular KCNE2 expression resides predominantly in Purkinje fibers.

Mutations in minK-related peptide 1 (MiRP1), the product of the KCNE2 gene, have been associated with malignant ventricular arrhythmia syndromes related to impaired repolarization. MiRP1 interacts with a variety of ion-channel alpha-subunits, dysfunction of which could account for arrhythmia syndromes; however, the observation of very low-level expression of MiRP1 in ventricular tissue has led to doubts about its relevance. The specialized His-Purkinje system plays a key role in cardiac electrophysiology and is an important contributor to ventricular arrhythmias related to abnormal repolarization. We examined the relative abundance of MiRP1 in canine Purkinje versus ventricular tissue and found much greater expression at both mRNA and protein levels in Purkinje tissue. Thus, the cardiac Purkinje system is a strong candidate to play a role in arrhythmic syndromes due to MiRP1 abnormalities.

Animals↗
PubMed2003

5-Aryl thiazolidine-2,4-diones as selective PPARgamma agonists.

A series of 5-aryl thiazolidine-2,4-diones containing 4-phenoxyphenyl side chains was designed, synthesized, and evaluated for PPAR agonist activities. One such compound 28 exhibited comparable levels of glucose correction to rosiglitazone in the db/db mouse type 2 diabetes animal model.

Animals↗
PubMed2003

Benzodiazepines as potent and selective bradykinin B1 antagonists.

Antagonism of the bradykinin B(1) receptor was demonstrated to be a potential treatment for chronic pain and inflammation. Novel benzodiazepines were designed that display subnanomolar affinity for the bradykinin B(1) receptor (K(i) = 0.59 nM) and high selectivity against the bradykinin B(2) receptor (K(i) > 10 microM). In vivo efficacy, comparable to morphine, was demonstrated for lead compounds in a rodent hyperalgesia model.

Animals↗
PubMed2003

[Human leukocyte antigen mismatched hemopietic stem cell transplants for the treatment of leukemia].

OBJECTIVE: To explore the feasibility of HLA mismatched hemopietic stem cell transplants for the treatment of leukemia. METHODS: Between July 2000 and December 2001, seven patients received hemopietic stem cell transplants(HSCT) with HLA mismatched family donors, including 3 chronic myelocytic leukemia (CML), 3 acute nonlymphocytic leukemia (ANLL), and 1 acute lymphocytic leukemia (ALL). Stem cell sources were bone marrow(n = 1) or G-CSF mobilized peripheral blood (n = 6). All the patients were conditioned with busulfan (BU) 12 mg.kg-1 and cyclophosphamide (CY) 3.6 g.m-2, of whom 4 were conditioned with additioned antithymocyte globulin(ATG). Graft versus host disease (GVHD) prophylaxis regimen consisted of cyclosporin-A (CSA), methotrexate (MTX) and mycophenolate mofetil(MMF). RESULTS: One patients received 3.41 x 10(8) kg-1 mononuclear cells(MNC) from bone marrow; six patients received a mean number of 8.46 x 10(8) kg-1 (4.3 x 10(8)-15.4 x 10(8) kg-1) MNC from peripheral blood. The mean time of ANC > 0.5 x 10(9) L-1 was day 13 (11-16), and BPC > 20.0 x 10(9) L-1 was day 16 (11-23). All the patients got engraftment successfully and attained CR. Acute I-II GVHD occurred in 3(42.9%) patients, no acute III-IV GVHD occurred and extensive chronic GVHD did in 2(28.6%) patients. All the patients were alive and well after 6-24 months' follow-up. CONCLUSION: (1) BU/CY plus ATG appears to be an effective conditioning regimen for HLA mismatched allogenic stem cell transplants. (2) G-CSF mobilized peripheral blood stem cells may be the source of stem cells even for HLA mismatched hemopietic stem cell transplants.

Bone Marrow Transplantation↗
PubMed2003

Phenylacetic acid derivatives as hPPAR agonists.

Beginning with the weakly active lead structure 1, a new series of hPPAR agonists was developed. In vivo glucose and triglyceride lowering activity was obtained by homologation and oxamination to 3, then conversion to substituted benzisoxazoles 4 and 5. Further manipulation afforded benzofurans 6 and 7. Compound 7 was of comparable potency as a glucose and triglyceride lowering agent in insulin resistant rodents to BRL 49653.

Animals↗
PubMed2003

Glycine alpha-ketoamides as HCV NS3 protease inhibitors.

Using a tetrapeptide-based alpha-ketoamide template, various amines and amino acids were incorporated to explore the prime side of the HCV NS3 protease catalytic site. Glycine carboxylic acid was found to be the most effective prime group. Further optimization yielded an inhibitor with IC(50) of 0.060 microM.

Amides↗
PubMed2003

Selective I kappa B kinase expression in airway epithelium generates neutrophilic lung inflammation.

To determine whether NF-kappaB activation is sufficient to generate lung inflammation in vivo, we selectively expressed a constitutively active form of IkappaB kinase 1 (cIKK1) or IkappaB kinase 2 (cIKK2) in airway epithelium. After intratracheal administration of adenoviral vectors expressing cIKK1 or cIKK2 to transgenic reporter mice that express Photinus luciferase under the control of an NF-kappaB-dependent promoter, we detected significantly increased luciferase activity over time (up to 96 h). Compared with control mice treated with adenoviral vectors expressing beta-galactosidase, lung bioluminescence and tissue luciferase activity were increased in NF-kappaB reporter mice treated with adenovirus (Ad)-cIKK1 or Ad-cIKK2. NF-kappaB activation in lungs of Ad-cIKK1- and Ad-cIKK2-treated mice was confirmed by immunoblots for RelA and EMSA from lung nuclear protein extracts. Mice treated with Ad-cIKK1 or Ad-cIKK2 showed induction of mRNA expression of several chemokines and cytokines in lung tissue. In lung lavage fluid, mice treated with Ad-cIKK1 or Ad-cIKK2 showed elevated concentrations of NF-kappaB-dependent chemokines macrophage-inflammatory protein 2 and KC and increased numbers of neutrophils. Coadministration of adenoviral vectors expressing a transdominant inhibitor of NF-kappaB with Ad-cIKK1 or Ad-cIKK2 resulted in abrogated NF-kappaB activation and other parameters of lung inflammation, demonstrating that the observed inflammatory effects of Ad-cIKK1 and Ad-cIKK2 were dependent on NF-kappaB activation by these kinases. These data show that selective expression of IkappaB kinases in airway epithelium results in NF-kappaB activation, inflammatory mediator production, and neutrophilic lung inflammation. Therapies targeted to NF-kappaB in lung epithelium may be beneficial in treating inflammatory lung diseases.

Adenoviridae↗
PubMed2003

Construction of a new tumour necrosis factor fusion-protein expression vector for high-level expression of heterologous genes in Escherichia coli.

We report the construction and application of a new fusion-protein expression plasmid (TNFHis) for Escherichia coli. The plasmid contains both P(R) and P(L) promoters and is optimized to allow a higher level of expression of mature coding sequences. It also contains a six-histidine tag for convenient purification as well as thrombin and hydroxylamine recognition sites for cleaving heterologous protein. The potential use of this expression vector is demonstrated by comparing the expression levels of human tumour necrosis factor (TNF), interferon, interleukin 11, colony-forming factor, osteoprotegrin and interleukin 2 in E. coli. Furthermore, all expressed TNF fusion proteins can be detected by anti-TNF alpha antibody or by specific antibodies and purified by Ni(2+)-nitrilotriacetate beads. The expressed TNF fusion proteins can be cleaved by hydroxylamine.

Escherichia coli↗
PubMed2003

Bioluminescent detection of endotoxin effects on HIV-1 LTR-driven transcription in vivo.

We investigated the effects of Gram-negative bacterial lipopolysaccharide (LPS) on luciferase expression in transgenic reporter mice in which luciferase expression is driven by the nuclear factor kappaB (NF-kappaB)-dependent portion of the human immunodeficiency virus-1 (HIV-1) long terminal repeat (HIV-1 LTR). Using these mice, we dissected the sources of luciferase activity at the organ level by (a) assessing luciferase activity in organ homogenates, (b) bioluminescence imaging in vivo, and (c) bioluminescence imaging of individual organs ex vivo. Luciferin dosage was a critical determinant of the magnitude of photon emission from these reporter mice. Photon emission increased at doses from 0.5-6 mg of luciferin given by intraperitoneal (IP) injection. The differential between basal and LPS-induced bioluminescence was maximal at 3-6 mg of luciferin. Luciferase expression was highly inducible in lungs, liver, spleen, and kidneys after a single IP injection of LPS, as assessed by luciferase activity measurements in organ homogenates. Luciferase activity was also induced in the forebrain by treatment with IP LPS. In contrast, aerosolized LPS produced a response localized to the lungs as assessed by both bioluminescence and ex vivo luciferase assay measurements. These studies demonstrate the utility of luciferase reporter mice for determining organ-specific gene expression in response to local and systemic stimuli.

Animals↗
PubMed2003

[Blue-on-yellow perimetry in patients with primary open-angle glaucoma].

OBJECTIVE: To investigate the early changes of the blue-on-yellow (B/Y) perimetry in patients with early primary open-angle glaucoma(POAG). METHODS: Thirty-one cases (45 eyes) of POAG underwent the central 30 degrees field examination of B/Y as well as routine white-on-white (W/W). RESULT: No significant difference of mean index deficiency (MD) between B/Y and W/W perimetry was detected (P>0.05). However, there were marked changes in index GHT (glaucoma hemisphere test) and more defect points in B/Y visual field than those in W/W (P<0.01). CONCLUSION: B/Y perimetry might be more sensitive than W/W perimetry a potentially more and valuable method in detection of early POAG lesion.

Adult↗
PubMed2003

[The immunopotentiation of human B lymphocyte stimulator C-terminal peptide].

The cDNA of human B lymphocyte stimulator C-terminal peptide (C-BLyS) was amplified by nested PCR from cDNA library of human fetal brain. The expression plasmid pT7450-C-BLyS was constructed and transformed into E. coli BL21 CodonPlus (DE3) RIL which can recognize many rare codons. The C-BLyS protein was expressed as inclusion body in E. coli BL21 CodonPlus (DE3) RIL and the inclusion body of C-BLyS was denatured and then refolded by dialysis and purified by ion exchange chromatography. The refolded and purified C-BLyS can specifically bind with BCMA-Fc, a fusion protein of BLyS receptor and human IgG1 Fc. Furthermore, C-BLyS is proved to be an effective stimulator in mouse splenocytes proliferation in vitro and effective immunostimulant in vivo.

Animals↗
PubMed2003

[The effect of antioxidant on optimation of blood preservation].

In order to optimize the preservation of blood, 3 kinds of antioxidant were selected and each of them can be injected directly into vein, then the optimal dose of these antioxidants was chosen using statistical method; ISMC (injectio salvia miltiorrhizae composita), ginaton and the combination of ISMC and ginaton were added into blood as optimal dose, some references as ATP, EI and so on were observed during blood preservation. The results showed that all of the three kinds of antioxidants increased ATP, EI and decreased FHb during blood preservation. It is concluded that both of ISMC and ginaton can effectively optimize the preservation of blood and combination of ISMC and ginaton can produce additive effect.

Adenosine Triphosphate↗
PubMed2003

[Induction of specific cytotoxic T lymphocytes and humoral immune response by MUC1 DNA vaccine in mice].

AIM: To observe the specific cytotoxic T lymphocyte and humoral immune response induced by MUC1 DNA inmunization in mice. METHODS: Female BALB/c mice were immunized intramuscularly with 100 microg pcDNA3.1-MUC1 3 times at intervals of 3 weeks. Three weeks after the last immunization, tumor challenge experiments were performed by inoculation of MUC1 positive breast cancer cell line EMT6. Both humoral immune response and CTL-specific cytotoxicity were detected by immunohistochemical staining and (51)Cr release assay, respectively. RESULTS: The cytotoxicity of MUC1-specific CTLs to EMT6 target cells showed that the cytotoxic effect was different at various ratio of effector cells to target cells. At ratios of 100:1, 50:1, 25:1 and 12.5:1, the specific lysis in MUC1cDNA group reached 54.1%, 39.8%, 26.4% and 20.1%, while two control groups 13.2%, 10%, 8.2%, 7.2% and 11.7%, 9.8%, 7.7%, 7.0%, respectively. The former was markedly higher than the two latters(P<0.01). MUC1 expression was exhibited to be positive in breast cancer tissue by immunohistochemical staining with BALB/c mouse sera against MUC1 cDNA. There was only 40% tumorigenic rate in MUC1 cDNA immunized group, while there 100% in pcDNA3.1(+) and NS control groups. There was a significant difference between MUC1 cDNA group and control groups (P<0.05). CONCLUSION: Specific CTLs and antibody prodution are elicited by MUC1 DNA inmunization. MUC1 cDNA inmunization partly inhibit the growth of implanted tumor in mice.

Animals↗