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Biomedical subjects

Hui Wang

Publications and source records attributed to Hui Wang.

At least 379 records · Page 21Linked to original sources
PubMed2002

Regulation of CC chemokine receptor 5 and CD4 expression and human immunodeficiency virus type 1 replication in human macrophages and microglia by T helper type 2 cytokines.

Macrophages, microglia, and other mononuclear phagocytes serve as cellular reservoirs for viral persistence in patients with acquired immunodeficiency syndrome. To understand host mechanisms that affect human immunodeficiency virus type 1 (HIV-1) pathogenesis by modulating expression of coreceptors, cytokine regulation of CC chemokine receptor 5 (CCR5) and CD4 expression on monocytes, monocyte-derived macrophages (MDMs), and microglia was investigated. Interleukin (IL)-4 and IL-10 enhanced the entry and replication of HIV-1 in microglia through up-regulation of CD4 and CCR5 expression, respectively. IL-4 stimulated HIV-1 replication in MDMs but down-regulated CD4 and CCR5 expression and inhibited virus entry, whereas IL-10 had the opposite effects. Thus, mechanisms independent of CCR5 and CD4 expression levels are involved in pathways that regulate HIV-1 replication in MDMs. CCR5 up-regulation by IL-10 was associated with increased migration of microglia in response to macrophage inflammatory protein-1beta. These findings suggest that increased production of T helper type 2 cytokines in the later stages of disease can enhance virus entry and replication in mononuclear phagocytes and facilitate chemotactic migration.

CD4 Antigens↗
PubMed2002

Radiolabeled 2'-fluorodeoxyuracil-beta-D-arabinofuranoside (FAU) and 2'-fluoro-5-methyldeoxyuracil-beta -D-arabinofuranoside (FMAU) as tumor-imaging agents in mice.

PURPOSE: The purpose of the present study was to evaluate, in conjunction with the National Cancer Institute, the feasibility of using two thymidine analogs, 2'-fluorodeoxyuracil-beta-D-arabinofuranoside (FAU, NSC-678515) and 2'-fluoro-5-methyldeoxyuracil-beta-D-arabinofuranoside (FMAU, NSC-678516), as 18-fluorine-labeled positron emission tomography (PET) imaging agents. METHODS: The in vivo distribution and DNA incorporation of [2-(14)C]FAU, [2-(14)C]FMAU, and [2-(14)C]thymidine (as a control) were studied in SCID mice bearing human xenografts of T-cell leukemia CCRF-CEM. Levels of drug-associated radioactivity in blood, tumor and normal tissues including liver, kidneys, heart, lungs, spleen, brain, and skeletal muscle were determined. RESULTS: At 1 h after dosing, radioactivity from all three compounds was distributed in a generally nonspecific manner, except that spleen and tumor tissue had relatively high concentrations of radioactivity from [(14)C]thymidine. At 4 h after dosing, the concentrations of radioactivity from [(14)C]thymidine and [(14)C]FMAU were relatively high in spleen and tumor tissue, and that from [(14)C]FAU was highest in tumor tissue. The tumor/skeletal muscle concentration ratios were 2.25+/-0.69 and 3.07+/-0.42 for [(14)C]FAU and [(14)C]FMAU, respectively. At 24 h after dosing, only spleen and tumor tissues contained appreciable amounts of radioactivity from either compound. In tumor tissue, the levels of radioactivity from [(14)C]FMAU were two- to threefold greater than those from [(14)C]thymidine or [(14)C]FAU. Examination of purified genomic DNA from tumor, liver, kidneys, brain, and skeletal muscle showed that, at 24 h after dosing, only DNA from tumor tissue contained appreciable concentrations of radioactivity. Radioactivity from [(14)C]FMAU in tumor DNA was 45% greater than that from [(14)C]thymidine and about threefold greater than that from [(14)C]FAU. CONCLUSIONS: The extent of accumulation of [(14)C]FMAU in tumor tissue and incorporation into tumor DNA indicate that [(18)F]FMAU could be useful as a functional PET tumor-imaging agent.

Animals↗
PubMed2002

Increased CCR5 affinity and reduced CCR5/CD4 dependence of a neurovirulent primary human immunodeficiency virus type 1 isolate.

Most human immunodeficiency virus type 1 (HIV-1) viruses in the brain use CCR5 as the principal coreceptor for entry into a cell. However, additional phenotypic characteristics are necessary for HIV-1 neurotropism. Furthermore, neurotropic strains are not necessarily neurovirulent. To better understand the determinants of HIV-1 neurovirulence, we isolated viruses from brain tissue samples from three AIDS patients with dementia and HIV-1 encephalitis and analyzed their ability to induce syncytia in monocyte-derived macrophages (MDM) and neuronal apoptosis in primary brain cultures. Two R5X4 viruses (MACS1-br and MACS1-spln) were highly fusogenic in MDM and induced neuronal apoptosis. The R5 viruses UK1-br and MACS2-br are both neurotropic. However, only UK1-br induced high levels of fusion in MDM and neuronal apoptosis. Full-length Env clones from UK1-br required lower CCR5 and CD4 levels than Env clones from MACS2-br to function efficiently in cell-to-cell fusion and single-round infection assays. UK1-br Envs also had a greater affinity for CCR5 than MACS2-br Envs in binding assays. Relatively high levels of UK1-br and MACS2-br Envs bound to CCR5 in the absence of soluble CD4. However, these Envs could not mediate CD4-independent infection, and MACS2-br Envs were unable to mediate fusion or infection in cells expressing low levels of CD4. The UK1-br virus was more resistant than MACS2-br to inhibition by the CCR5-targeted inhibitors TAK-779 and Sch-C. UK1-br was more sensitive than MACS2-br to neutralization by monoclonal antibodies (2F5 and immunoglobulin G1b12 [IgG1b12]) and CD4-IgG2. These results predict the presence of HIV-1 variants with increased CCR5 affinity and reduced dependence on CCR5 and CD4 in the brains of some AIDS patients with central nervous system disease and suggest that R5 variants with increased CCR5 affinity may represent a pathogenic viral phenotype contributing to the neurodegenerative manifestations of AIDS.

AIDS Dementia Complex↗
PubMed2002

Characteristics and mechanism of enzyme secretion and increase in [Ca2+]i in Saikosaponin(I) stimulated rat pancreatic acinar cells.

AIM: This investigation was to reveal the characteristics and mechanism of enzyme secretion and increase in [Ca2+]i stimulated by saikosaponin(I) (SA(I)) in rat pancreatic acini. METHODS: Pancreatic acini were prepared from male Wistar rats. Isolated acinar cells were suspended in Eagle's MEM solution. After adding drugs, the incubation was performed at 37 degrees for a set period of time. Amylase of supernatant was assayed using starch-iodide reaction. Isolated acinar single cell was incubated with Fura-2/AM at 37 degrees, then cells were washed and resuspended in fresh solution and attached to the chamber. Cytoplasm [Ca2+]i of a single cell was expressed by fluorescence ratio F340/F380 recorded in a Nikon PI Ca2+ measurement system. RESULTS: Rate course of amylase secretion stimulated by SA(I) in rat pancreatic acini appeared in bell-like shape. The peak amplitude increased depended on SA(I) concentration. The maximum rate responded to 1 x 10(-5)mol/L SA(I) was 13.1-fold of basal and the rate decreased to basal level at 30 min. CCK-8 receptor antagonist Bt(2)-cGMP markedly inhibited amylase secretion stimulated by SA(I) and the dose-effect relationship was similar to that by CCK-8. [Ca2+]i in a single acinar cell rose to the peak at 5 min after adding 5 x 10(-6)mol/L SA(I) and was 5.1-fold of basal level. In addition, there was a secondary increase after the initial peak. GDP could inhibit both the rate of amylase secretion and rising of [Ca2+]i stimulated by SA(I) in a single pancreatic acinar cell. CONCLUSION: SA(I) is highly efficient in promoting the secretion of enzymes synthesized in rat pancreatic acini and raising intracellular [Ca2+]i. Signaling transduction pathway of SA(I) involves activating special membrane receptor and increase in cytoplasm [Ca2+]i sequentially.

Amylases↗
PubMed2002

Antisense anti-MDM2 mixed-backbone oligonucleotides enhance therapeutic efficacy of topoisomerase I inhibitor irinotecan in nude mice bearing human cancer xenografts: In vivo activity and mechanisms.

Antisense oligonucleotides have been investigated as anticancer agents administered alone or in combination with conventional chemotherapeutics. In the present study, we demonstrated synergistic effects between anti-MDM2 antisense oligonucleotides and the clinically used anticancer agent irinotecan, using nude mouse models of human colon cancers (LS174T and DLD-1). Surprisingly, a 5-base mismatch oligonucleotide also showed similar effects. To elucidate the underlying mechanisms, in vitro and in vivo pharmacokinetic and pharmacodynamic studies were performed. In LS174T cells, the antisense oligonucleotide, but not the mismatch oligonucleotide, specifically inhibited MDM2 expression, resulting in a significant increase in irinotecan-associated p53 activation and p21 induction. In DLD-1 cells, the antisense oligonucleotide specifically inhibited MDM2 expression, resulting in a significant increase in irinotecan-associated p21 induction although mutant p53 levels remained unchanged. Both oligonucleotides increased tissue uptake of irinotecan and the conversion of irinotecan to its active metabolite SN-38. These results suggest that oligonucleotides have a role in irinotecan metabolism and action, providing a basis for future development of antisense oligonucleotides as a sensitizer for irinotecan-based therapy.

Animals↗
PubMed2002

In vitro metabolic characteristics of cytochrome P-450 2A6 in Chinese liver microsomes.

AIM: To investigate the metabolic characteristics of cytochrome P-450 C YP2A6 in human liver microsomes. METHODS: Cytochrome P-450 enzyme activities were measured by biochemical assays. Xenobiotics were employed to observe their effects on CYP2A6 in vitro. The kinetics of coumarin 7-hydroxylase was determined, and the correlation between CYP2A6 and UDP-glucuronosyltransferase (UGT) was analyzed. RESULTS: CYP2A6 activities of human liver microsomes were from 0.47 to 4.14 micromol . min-1 . g-1, with a 8.8-fold variation. The Km and Vmax of CYP2A6 ranged from 0.25 to 1.56 micromol/L and 1.41 to 8.70 micromol . min-1 . g-1, respectively. CYP2A6 activity was markedly inhibited (> 50 %) by pilocarpine, diethyldithio carbamic (DDC), and rifampicin, the IC50 was 5.31 micromol/L, 156.35 micromol/L, and 38.81 micromol/L, respectively. alpha-Naphthoflavone, sulfaphenazole, troleandomycin (TAO), ketoconazole, phenobarbital, prednisolone, and azithromycin had little or no effects on coumarin 7-hydroxylation. A significant correlation was observed between CYP2A6 and UGT2 (r = 0.9453, P < 0.05). CONCLUSION: CYP2A6 activity and kinetics exhibited a considerable variation in human liver microsomes in vitro, and a significant correlation was existed between CYP2A6 and phase II enzyme UGT2. Not only pilocarpine, CYP2A6 specific inhibitor, but also rifampicin and DDC inhibited CYP2A6 activity selectively.

Adult↗
PubMed2002

[Bioindication of organochlorine pesticides by night heron in Taihu wetland ecosystem].

Based on field ecological investigation on the colony of herons in Yuantouzhu of Taihu in 1999, the regurgitated foods by chicks of night heron were collected for prey type identification and chemical analysis. Besides, eggs of night heron, and sediments and waters in foraging habitats were sampled for chemical analysis as well. alpha-HCH, beta-HCH, gamma-HCH, Aldrin, Dieldrin, Endrin, Heptachlor, Heptachlor epoxide, p,p'-DDE, p,p'-DDD, o,p'-DDT and p,p'-DDT were determined in laboratory by gas chromatography. The results indicated that HCH isomers, DDT and its metabolites could be detected in various environments and preys of night heron, although the organochlorined chemicals were banned for almost 20 years. Moreover, The results showed that eggs of night heron could accumulate organochlorine pesticides by as much as a factor of 10(3)-10(4), which can make chemical analysis much easier. So they are good bio-indicators for organochlorine contamination level in wetland environments.

China↗
PubMed2002

[Residue and distribution of heavy metals in tissues of night heron chick bred in Yuantouzhu, Wuxi].

This study analyzed Cd, Pb, Cr, Hg and Se in organs and tissues of night heron chick bred in Yuantouzhu, Taihu lake. Cr and Se have higher residue level in all the samples, compared to the residue of Cd, Pb and Cd mainly concentrated in feathers, on the other hand, Se, Hg and Cr were accumulated in livers. The results proofed that feather and liver were the object organs for accumulation of heavy metals. The data showed that Hg and Cd have some relationship with Se in birds. Compared with other studies, residue levels of heavy metals in night heron in Wuxi were not harmful.

Animals↗
PubMed2002

Antisense oligonucleotide targeted to RIalpha subunit of cAMP-dependent protein kinase (GEM231) enhances therapeutic effectiveness of cancer chemotherapeutic agent irinotecan in nude mice bearing human cancer xenografts: in vivo synergistic activity, pharmacokinetics and host toxicity.

The RIalpha-subunit of cAMP-dependent protein kinase (PKA) is overexpressed in various human cancers and PKA has been suggested to be a potential target for cancer therapy. We have shown an antisense oligonucleotide with advanced chemistry (mixed-backbone oligonucleotide) targeted to PKA RIalpha-subunit (GEM231) to have anti-tumor activity in vitro and in vivo. In the present study, we demonstrated synergistic effects between the anti-PKA antisense oligonucleotide and the clinically used anticancer agent irinotecan, using nude mouse models of human cancers of colon (LS174T and DLD-1), breast (MCF-7), prostate (DU-145 and PC-3) and lung (H1299). To elucidate the underlying mechanisms, in vivo pharmacokinetics of irinotecan was determined following pre-treatment of oligo GEM 231 in CD-1 mice and nude mice bearing LS174T xenografts. GEM 231 increased tissue uptake of irinotecan. However, no significant change in host toxicity was observed following combination treatment of irinotecan and GEM231 compared with irinotecan alone. These results suggest that GEM231 have a role in irinotecan metabolism and its antitumor activity, providing a basis for future development of this oligonucleotide as a chemosensitizer for irinotecan-based therapy.

Animals↗
PubMed2002

[The pathology of and the cardio-pulmonary functional changes in acute multiple pulmonary microthromboembolism in a canine model].

OBJECTIVE: To evaluate the effect of acute multiple pulmonary microthromboembolism on circulation, ventilation, lung histology, and the coagulatory and fibrinolytic functions. METHODS: Thirteen dogs were studied, 7 in the embolism group and 6 in the control group. 10 ml of blood was withdrawn from each animal. Thrombi were formed and cut into pieces of 1 mm to 2 mm in size. The thrombi were counted, and 300 thrombi were infused at one time back to the same animal. PAP, PAWP, VO(2), DO(2), D-dimer, protein C, protein S were measured before and immediately, 30 min, 1 hour, 2 hour after embolism. RESULTS: PAP was increased immediately after embolisation, and then decreased at 1 hour. The level of D-dimer was elevated at an early stage. Pulmonary hemorrhage, consolidation and microembolism were observed. CONCLUSIONS: Multiple microthromboembolism caused lung injury and thrombosis. PAP was increased at the early stage, but ventilation was not affected. The level of D-dimer changed at the early stage of thromboembolism.

Acute Disease↗
PubMed2002

Anti-tumor efficacy of a novel antisense anti-MDM2 mixed-backbone oligonucleotide in human colon cancer models: p53-dependent and p53-independent mechanisms.

BACKGROUND: The MDM2 oncogene is amplified or overexpressed in many human cancers and MDM2 levels are associated with poor prognosis. MDM2 not only serves as a negative regulator of p53 but also has p53-independent activities. This study investigates the functions of the MDM2 oncogene in colon cancer growth and the potential value of MDM2 as a drug target for cancer therapy, by inhibiting MDM2 expression with an antisense anti-human-MDM2 oligonucleotide. MATERIALS AND METHODS: The selected antisense mixed-backbone oligonucleotide was evaluated for its in vitro and in vivo antitumor activity in human colon cancer models: LS174T cell line containing wild-type p53 and DLD-1 cell line containing mutant p53. The levels of MDM2, p53 and p21 proteins were quantified by Western blot analysis. RESULTS: In vitro antitumor activity was found in both cell lines, resulting from specific inhibition of MDM2 expression. In vivo antitumor activity of the oligonucleotide occurred in a dose-dependent manner in both models and synergistically or additive therapeutic effects of MDM2 inhibition and the cancer chemotherapeutic agents 10-hydroxycamptothecin and 5-fluorouracil were also observed. CONCLUSIONS: These results suggest that MDM2 have a role in tumor growth through both p53-dependent and p53- independent mechanisms. We speculate that MDM2 inhibitors have a broad spectrum of antitumor activities in human cancers regardless of p53 status. This study should provide a basis for future development of anti-MDM2 antisense oligonucleotides as cancer therapeutic agents used alone or in combination with conventional chemotherapeutics.

Animals↗
PubMed2002

[Experimental study on microvascular architecture of human and rabbit flaps with two methods].

OBJECTIVE: To study effective method of showing the microvascular architecture of human and rabbit skin flaps. METHODS: According to endogenous alkaline phosphatase activity, Gomori-Takamatsu method and NBT/BCIP method were used to observe the microvascular architecture. RESULTS: Both methods had capability to demonstrate the microvascular architecture of the human skin flap, whereas the examining results of rabbits were negative. CONCLUSIONS: Great difference of endogeneous alkaline phosphatase activity exists in different animals. Gomori-Takamatsu method and NBT/BCIP method are useful in study of microvascular architecture of human skin flaps.

Alkaline Phosphatase↗
PubMed2002

[Activation of phosphatidylinositol 3-kinase in human breast carcinoma].

BACKGROUND & OBJECTIVE: Phosphatidylinositol 3-kinase (PI3-K) has been implicated in the signaling pathways regulating cell growth by virtue of its activation in response to various mitogenic stimuli, but the role of PI3-K in human tumorigenesis has not yet to be defined. This study was designed to investigate the levels of both PI3-K protein and PI3-K mRNA and the activity of PI3-K in human breast tumors. METHODS: Western blot, immunoprecipitation, kinase activity assay, and RT-PCR were used to detect the expression and activity of PI3-K in 37 patients with breast cancers. RESULTS: Significantly increased expression of p85 subunit of PI3-K at levels of both protein and mRNA were found in 32 (86.49%) and 35(94.59%) out of the 37 breast tumors compared with adjacent normal tissue. Significantly higher level of the activity of PI3-kinase was observed in 25(67.57%) out of the 37 cases. CONCLUSIONS: PI3-K was highly activated in breast tumor tissue compared with adjacent normal tissue, suggesting that PI3-K was involved in the signal transduction of breast tumorigenesis. It may be a potential target for new strategies for the treatment of the patients with breast cancers.

Breast Neoplasms↗
PubMed2002

[Relationship of nitric oxide with intrauterine human cytomegalovirus active infection during early pregnancy].

OBJECTIVE: To study the relationship of nitric oxide (NO) with intrauterine human cytomegalovirus (HCMV) active infection during early pregnancy. METHODS: Reverse transcript polymerase chain reaction (RT-PCR) was used to screen HCMV-mRNA of chorionic villi during early pregnancy in 81 cases who had poor pregnant history. The serum HCMV-IgM was measured by enzyme linked immunoadsorbent assay (ELISA) and the expression of decidual iNOS-mRNA was investigated with in situ hybridization (ISH). RESULTS: (1) Six cases were HCMV-mRNA positive in chorionic villous tissues and 14 cases with serum HCMV-IgM positive among cases, the positive rate of serum HCMV-IgM was 17.3% (14/81). All cases were divided into three groups according to HCMV-mRNA and serum HCMV IgM. Group I: 5 cases with HCMV-mRNA positive and IgM positive, and the transmission rate between pregnant women and fetus was 35.7% (5/14); Group II: 9 cases with HCMV-mRNA negative and IgM positive, Group III: 66 cases with HCMV-mRNA and IgM negative; In addition, 1 case with HCMV-mRNA positive but IgM negative. (2) The expressive quantity of decidual iNOS-mRNA in group I was significantly higher than those in group II and III (P < 0.05). The case with HCMV-mRNA positive and serum IgM negative also has a strong staining of decidual iNOS-mRNA. CONCLUSIONS: NO may play a critical role in intrauterine HCMV active infection, NO could be served as an assistant marker of HCMV infection.

Adult↗
PubMed2002

[Determination of organochlorine pesticides and polychlorinated biphenyl congeners residues in eggs by gas chromatography with electron capture detection (GC-ECD)].

A procedure of clean-up with H2SO4 after extraction with a shaking machine using n-hexane, and fast determination of some organochlorine residues in eggs by GC-ECD with PCB2 and PCB209 as internal standards was established. The test results showed that with this method satisfactory recoveries(84.31%-116.77%), relative standard deviation (6%-18%) and detection limits (0.07 ng/g-0.35 ng/g) could be obtained. In comparing with the Soxhlet method, this method is simpler in pre-treatment, lower in cost and less in sample amount. It can determine organochlorine pesticides and some PCBs in the same extract, simultaneously with enough accuracy, sensitivity and permissible RSD. It is a suitable procedure for determining micro-amounts of organochlorine pollutants in foods. The results showed that p, p'-DDE was detected in maximum; p, p'-DDT next; and PCBs very little, that were usually less than 10 ng/g in the eggs from some Chinese markets. It was found that most of PCBs in eggs were the congeners with 3-5 chlorine atoms.

Chromatography, Gas↗
PubMed2002

[Study of the inhibitory effect of PhAsO on gap junctional communication and its damages to cellular DNA of human skin fibroblast cells].

In order to investigate the toxicity of organic arsenic as well as the mechanism of arsenic carcinogenesis, the GJIC between human skin fibroblast cells is detected by the scrape loading/dye transfer assay and single-cell gel electrophoresis(SCGE) assay is used to detect the DNA strand breaks in human skin fibroblast cells exposed to PhAsO. The results show that gap junctional intercellular communication between human skin fibroblast cells is inhibited by PhAsO significantly with a obvious dose-dependent relationship(P < 0.01), suggesting that PhAsO may act as a tumour promoter. PhAsO could induce DNA strand breaks, but the dose-dependent relationship is not observed. The authors suggest that PhAsO may have tumor promoting activity, and further studies are needed.

Arsenicals↗
PubMed2002

[Effects of L yaojiu of invigorating blood circulation and eliminating blood stasis in old rats].

L Yaojiu was investigated for its effects of invigorating blood circulation and eliminating blood stasis using old rats (aged over ten months) as the model of blood stasis. Three different dosages of L Yao Jiu (14.3, 28.5, 57.0 mg crude drugs/kg) had been administrated orally per day to rats for 12 consecutive days. The changes of the mesenteric microcirculation and the hemorrheology were observed. The content of serum malondialdehyde (MDA) and the activities of serum monoamine oxidase (MAO) and superoxide dismutase (SOD) were determined. The results showed L Yao Jiu could accelerate the blood streams, dilate the capillaries and inhibit erythrocyte aggregations. It also reduced blood viscosity, inhibited platelet aggregations and improved the function of erythrocytes. On the other hand, the activities of total-SOD and Cu-SOD were increased and the content of MDA was decreased. These results suggests that L Yao Jiu could invigorate blood circulation and eliminate blood stasis in old rats.

Aging↗