Biomedical subjects

Ming Zhang

Publications and source records attributed to Ming Zhang.

At least 217 records · Page 12Linked to original sources

PubMed2003

[Vitamin D receptor gene Bsm I polymorphism and the susceptibility to prostate cancer in northern Chinese Han population].

OBJECTIVES: To investigate Bsm I single nucleotide polymorphism (SNP) of vitamin D receptor gene (VDRG) in low-risk Chinese Han population and its relationship to the susceptibility to prostate cancer (PCa), and to discuss the possible reason for the racial difference of PCa. METHODS: One hundred and three patients with PCa and 106 normal controls, mainly from Northern Chinese Han population, were enrolled in this study. Their blood samples were obtained, all of which were genotyped for Bsm I SNP by denaturing high performance liquid chromatography(DHPLC) methods using case-control study. RESULTS: The distribution of genotype and allele had no significant difference between PCa patients and normal controls (P > 0.05). The frequencies for the bb, Bb and BB genotypes in PCa patients and normal controls were 92.23%/94.34%, 7.77%/5.66%, and 0/0, respectively. The frequencies for B and b allele were 3.88%, 96.12% and 2.91%, 97.09%, respectively. CONCLUSIONS: The results indicate no significant relationship between the VDRG polymorphisms and PCa in Northern Chinese Han population. The distribution of VDRG Bsm I SNP varies in different ethnic populations, which may be one reason for the racial difference of PCa.

Aged↗

PubMed2003

[Expression of main heat stress proteins and p53 in nasopharyngeal carcinoma].

OBJECTIVE: To investigate the expression and the significance of main heat stress proteins (HSPs) and p53 in nasopharyngeal carcinoma. METHOD: Tissues homogenate and western blot were used to determine the level of HSPs and p53. RESULT: HSP27 and p53 elevated remarkably (P < 0.05) while HSP90 and HSP70 showed no significance between nasopharyngeal carcinoma and control tissues. Elevated level of HSP27 and p53 don't correlated with histological type and clinical stage. CONCLUSION: Expression of HSPs and p53 show some difference in nasopharyngeal carcinoma tissue. These data suggest that HSPs and p53 may play a role in the development of nasopharyngeal carcinoma.

Adolescent↗

PubMed2003

[The 3D finite element stress analysis of transtibial monolimb].

In this study, a 3D model of a transtibial monolimb and residual limb was constructed. The stresses on all nodes of the model under the simulus of the load at the Mid-Stance were computed through 3D finite element analysis (FEA). The stress distribution on the internal and external surfaces of the model was obtained. The results indicate that the stresses on socket are lower than those on prosthetic shank; high stress regions are located on the underneath of prosthetic shank and the border section of socket and prosthetic shank. These data will be useful for CAD\CAM system of monolimb designing.

Artificial Limbs↗

PubMed2003

[Express of plasma ROS, SOD and GSH-PX in patients with nasopharyngeal carcinoma].

OBJECTIVE: To investigate the levels of plasma reactive oxygen species(ROS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in patients with nasopharyngeal carcinoma (NPC) and to observe the state of metabolism of free radical in patients with NPC and the effects of them on nasopharyngeal carcinoma. METHOD: The levels of plasma ROS, SOD and GSH-PX in 40 patients with NPC and 20 normal controls were identified by Fenton reaction method, xanthine oxidase method and dithiocarbamate method respectively. RESULT: Plasma ROS activity[(11,327.835 +/- 483.777)/(U.ml-1)] in NPC increased significantly in comparison with the control group [(10,262.712 +/- 525.287)/(U.ml-1)] (P < 0.05). Plasma SOD and GSH-PX activities [(76.619 +/- 22.283)/(NU.ml-1), (98.653 +/- 46.374)/AU] in NPC decreased significantly in comparison with the control group [(154.603 +/- 27.241)/(NU.ml-1), (307.872 +/- 116.275)/AU] (P < 0.05). But there was no significant difference of the levels of plasma ROS[(10,987.235 +/- 469.340)/(U.ml-1), (10,081.53 +/- 488.409)/(U.ml-1), (12,085.044 +/- 564.721)/(U.ml-1)], SOD[(79.517 +/- 20.368)/(NU.ml-1), (67.975 +/- 24.202)/(NU.ml-1), (58.692 +/- 29.946)/(NU.ml-1)] and GSH-PX[(101.362 +/- 59.859)/AU, (89.338 +/- 42.259)/AU, (101.890 +/- 33.559)/AU] in different pathological kinds of NPC. CONCLUSION: The metabolism of free radical is disturbed and the ability of anti-oxidation injury decreases significantly in patients with NPC, so anti-oxidation treatment should be given to suppress the development of NPC.

Adult↗

PubMed2003

[Establishment of drug screening model based on transcriptional regulation of estrogen responsive element].

OBJECTIVE: AIM To establish a drug screening model based on transcriptional regulation of estrogen responsive element (ERE) and use it to screen compounds for discovering new ligands of estrogen receptor (ER) subtypes. METHOD: A recombinant reporter vector pERE-TAL-SEAP was constructed by inserting a synthetic sequence composed of five tandem copies of EREs upstream of promoter of the reporter vector pTAL-SEAP. The pERE-TAL-SEAP and the internal control plasmid pCMV were transiently co-transfected into Hela cells expressing ER subtype or ER subtype, and the effects of pure ER agonists 17estradiol, phytoestrogen genistein and pure ER antagonist ICI182, 780 on reporter gene SEAP expression were observed. RESULT: In the Hela cells expressing ER alpha or ER beta subtype, the expression of SEAP gene were induced in a dose dependent manner by 17-estrodiol with a maximal effect at approximately 10 nmol.L-1 and with EC50 of (80.58 +/- 8.51) pmol.L-1 and (103.90 +/- 5.29) pmol.L-1, respectively, so done by phytoestrogen genistein with a maximal effect at 1 mumol.L-1 and with EC50 of (10.86 +/- 0.75) nmol.L-1 and (39.38 +/- 2.26) nmol.L-1, respectively. The maximal level induced by estrodiol and genistein were about 7-14 fold higher than that of vehicle. The pure antiestrogen ICI182, 780 at concentration of 1 mumol.L-1 completely blocked the inductions of 17-estrodiol and genistein. CONCLUSION: The cellular drug screening model can be established by transfecting reporter vector pERE-TAL-SEAP in Hela cell lines expressing ER alpha or ER beta. The cell lines can be used to screen compounds with estrogenicity by testing SEAP activity in the culture media of cells growing in microtitier wells. The system should provide an efficient model for screening and analyzing the activity of large numbers of ligands of ER.

Drug Evaluation, Preclinical↗

PubMed2002

Functional activity of natural antibody is altered in Cr2-deficient mice.

The major source of natural IgM Abs are B-1 cells, which differ from conventional B cells in their anatomic location, cell surface phenotype, restricted usage of particular V(H) genes and limited use of N-region addition during V-D-J rearrangement. The origin of B-1 cells is unclear. However, they are capable of self-renewal and their development is sensitive to signaling via the B cell receptor, as genetic defects that impair the strength of the signal often result in limited development. These findings suggest that B-1 cells require either an intrinsic signal, or contact with Ag, for positive selection and expansion and/or maintenance in the periphery. In support of interaction with cognate Ag, deficiency in the complement receptors CD21/CD35 results in a 30-40% decrease in the CD5(+) B-1 population. To determine whether this reduction reflects a loss of certain specificities or simply a proportional decline in the repertoire, we examined peritoneal B cells isolated from Cr2(+) and Cr2(def) mice for recognition of a B-1 cell Ag, i.e., phosphatidylcholine, and assayed for injury in an IgM natural Ab-dependent model of reperfusion injury. We found a similar frequency of phosphatidylcholine-specific CD5(+) B-1 cells in the two strains of mice. By contrast, the Cr2(def) mice have reduced injury in the IgM-dependent model of reperfusion injury. Reconstitution of the deficient mice with pooled IgM or adoptive transfer of Cr2(+) peritoneal B cells restored injury. These results suggest that complement receptors CD21/CD35 are important in maintenance of the B-1 cell repertoire to some, but not all, specificities.

Adoptive Transfer↗

PubMed2002

Hypermethylation and histone deacetylation lead to silencing of the maspin gene in human breast cancer.

Maspin is a member of the serine protease inhibitor family with tumor suppressing activity in breast cancer. Maspin expression was found in normal breast epithelial cells, but was frequently decreased in breast cancer cells and lost in metastatic cells. In this study, we examined the regulatory mechanism of maspin expression and described the re-activation of maspin expression in a series of maspin-negative breast cancer cell lines. All of the 6 maspin-negative breast cancer cells showed induction of maspin promoter activity in a promoter reporter assay. In addition, the treatment of 5-aza-2(') deoxycytidine, trichostatin A or a combination of both led to the re-expression of maspin in a series of maspin-negative breast cancer cell lines. These findings indicate that DNA methylation and/or histone deacetylation are/is partially responsible for the silencing of maspin gene expression in breast cancer cells. The re-expression of maspin by pharmacological intervention potentially offers a promising new target as a therapeutic option in breast cancer.

Acetylation↗

PubMed2002

On the mechanism of bile acid inhibition of rat sterol 12alpha-hydroxylase gene (CYP8B1) transcription: roles of alpha-fetoprotein transcription factor and hepatocyte nuclear factor 4alpha.

The sterol 12alpha-hydroxylase (CYP8B1) is a key enzyme of the bile acid biosynthetic pathway. It regulates the composition of bile acids in bile, i.e. ratio between cholic acid (CA) and chenodeoxycholic acid (CDCA). In similarity with cholesterol 7alpha-hydroxylase (CYP7A1), this enzyme is subjected to a negative feedback regulation by bile acids. It has been recently reported that bile acid-activated farnesoid X receptor (FXR) induces the small heterodimer partner (SHP) that interacts with alpha-fetoprotein transcription factor (FTF) and down-regulates CYP7A1 transcription. We studied whether the same mechanism also regulated rat CYP8B1 gene transcription. Feeding rats with CDCA caused a 40-50% decrease of CYP8B1 and hepatocyte nuclear factor 4alpha (HNF4alpha) mRNA expression levels. This was associated with an increase in FTF mRNA expression, but SHP mRNA expression was not altered. Electrophoretic mobility shift assay (EMSA) and transient transfection assay of promoter/reporter genes coupled to mutagenesis analysis identified a putative bile acid response element (BARE) that has an HNF4alpha binding site embedded in two overlapping FTF binding sites. Mutation of the HNF4alpha binding site markedly reduced basal promoter activity and its repression by bile acids. Cotransfection with FTF strongly repressed CYP8B1 transcription. Interestingly, HNF4alpha could overcome the inhibitory effects of FTF and bile acids. We conclude that FTF and HNF4alpha not only play critical roles on CYP8B1 gene transcription, but also mediate bile acid feedback inhibition. This study reveals a novel mechanism by which bile acids inhibit rat CYP8B1 gene transcription by inducing FTF and inhibiting HNF4alpha expression.

Animals↗

PubMed2002

High and selective expression of yeast cytosine deaminase under a carcinoembryonic antigen promoter-enhancer.

Yeast cytosine deaminase (yCD)-based gene therapy offers the potential for selective production of the cytotoxic and radiosensitizing drug 5-fluorouracil (5-FU) from the benign prodrug 5-fluorocytosine within colorectal cancers. Although previous attempts to target therapy to colorectal cancer using the carcinoembryonic antigen (CEA) promoter have demonstrated specificity, this has been achieved at the cost of 10- to 300-fold loss in activity compared with strong but nonspecific rous sarcoma virus (RSV) or cytomegalovirus promoters. We developed a highly specific and active gene transfer method for colorectal cancer using CEA under control of a promoter-enhancer. We compared the RSV promoter-derived with the CEA promoter-enhancer-derived transgene expression in 10 different cell lines with differing CEA status. We found that the transgene expression resulting from both transient transfection and adenoviral infection with the CEA promoter-enhancer was as strong as the RSV promoter while maintaining specificity for CEA-producing cell lines. For instance, when we compared yCD expression between LoVo (CEA+) and human fibroblast (CEA-), we found a 30-fold-increased yCD expression in LoVo cells from CEA-enhancer adenovirus although there was no difference in the yCD expression between the cell lines when infected with RSV/yCD virus. This specificity was also achieved while maintaining a higher yCD enzyme activity than we obtained with RSV/yCD adenovirus in an HT-29 intrahepatic tumor model. We then compared the response of HT-29 xenografts to treatment with 5-fluorocytosine and yCD adenovirus driven by either the RSV or the CEA promoter-enhancer and found similar tumor growth inhibition. These findings suggest that the CEA promoter-enhancer strategy confers specificity while preserving activity and is worth exploring in additional animal and, potentially, clinical trials.

Adenoviridae↗

PubMed2002

Reduced expression of nuclear cyclic adenosine 5'-monophosphate response element-binding proteins and IFN-gamma promoter function in disease due to an intracellular pathogen.

Mycobacterium tuberculosis-induced IFN-gamma protein and mRNA expression have been shown to be reduced in tuberculosis patients, compared with healthy tuberculin reactors. To determine whether this decrease was associated with reduced activity of the IFN-gamma promoter, we first studied binding of nuclear proteins to the radiolabeled proximal IFN-gamma promoter (-71 to -40 bp), using EMSAs with nuclear extracts of freshly isolated peripheral blood T cells. Nuclear extracts of T cells from most tuberculosis patients showed markedly reduced expression of proteins that bind to the proximal IFN-gamma promoter, compared with findings in nuclear extracts of T cells from healthy tuberculin reactors. These DNA-binding complexes contained CREB proteins, based on competitive EMSAs, supershift assays, and Western blotting with an anti-CREB Ab. Transient transfection of PBLs with a luciferase reporter construct under the control of the IFN-gamma promoter revealed reduced IFN-gamma promoter activity in tuberculosis patients. Transient transfection of Jurkat cells with a dominant-negative CREB repressor plasmid reduced IFN-gamma promoter activity. These data suggest that reduced expression of CREB nuclear proteins in tuberculosis patients results in decreased IFN-gamma promoter activity and reduced IFN-gamma production.

Consensus Sequence↗

PubMed2002

In vivo dissection of the Tat translocation pathway in Escherichia coli.

The bacterial Tat pathway is capable of exporting folded proteins carrying a special twin arginine (RR) signal peptide. By using two in vivo reporter proteins, we assessed factors that affect Tat pathway transport. We observed that, like the intact RR signal peptide, those with a KR or RK substitution were still capable of mediating the translocation of the folded green fluorescent protein (GFP). However, the translocation efficiency decreased in the order of RR>KR>RK. The KK motif was unable to mediate GFP translocation. The translocation of the RR-GFP fusion required TatA, TatB and TatC proteins. By exploiting the periplasmic bactericidal property of colicin V (ColV), we constructed a translocation-suicide probe, RR-ColV. The translocation of RR-ColV fully inhibited the growth of wild-type Escherichia coli and those of the DeltatatD and DeltatatE mutants. In contrast, the deletion of the tatC gene blocked RR-ColV in the cytoplasm and this strain exhibited a normal growth phenotype. Interestingly, the growth of DeltatatA and tatB mutants was inhibited partially by RR-ColV. Moreover, KR, RK and KK motifs were capable of mediating the ColV translocation with a decreasing RR=KR>RK>KK efficiency. In addition to TatE and TatC proteins, either TatA or TatB was sufficient for the translocation of RR-ColV or KR-ColV. In contrast, TatA plus the conserved N-terminal domain of TatB were required to mediate the killing effect of ColV fused to the less-efficient RK signal peptide. Taken together, these results suggest that a fully efficient Tat pathway transport is determined by the sequence of the signal peptide, the composition of the Tat apparatus, and the intrinsic characteristics of exported proteins.

Amino Acid Motifs↗

PubMed2002

Structural microdomains in the lateral plasma membrane of cochlear outer hair cells.

The basal and lateral regions of the plasma membrane of cochlear outer hair cells are structurally and functionally distinct. The lateral region contains thousands of motor proteins but few voltage-gated channels. The basal region, conversely, contains a high number of voltage-gated channels but is devoid of motor proteins. It has been suggested that the cortical cytoskeleton is responsible for maintaining this regional distinction. Toward elucidating the structure of the outer hair cell's electromotile mechanism, we investigated the physical organization of the lateral plasma membrane in living guinea pig outer hair cells by analyzing the distribution pattern of the anionic long-chain carbocyanine SP-DiIC18(3) within this area, before and after electrical stimulation and with an intact and a disrupted cytoskeleton. We observed punctate, intensely fluorescent patches as well as areas of weaker fluorescence, with clear local maxima and minima, upon labeling the cells with this membrane-soluble probe. This discrete distribution of SP-DilC18(3) suggests that the lateral plasma membrane of guinea pig outer hair cells may be composed of small structural domains (microdomains). Disrupting the cytoskeleton with either trypsin or toxin B from Clostridium difficile did not change this pattern of distribution, thus indicating that this treatment did not facilitate the lateral diffusion of the probes. Electrical stimulation using whole-cell patch-clamp techniques, on the other hand, induced two responses: fast motility and reversible displacement of the fluorescent probes. Both responses were inhibited by internal perfusion with salicylate, while disruption of the cytoskeleton did not inhibit OHC fast motility but affected the electrically induced redistribution of fluorescent probes. Together, these results suggest that the lateral plasma membrane of guinea pig outer hair cells contains structural microdomains and that the cytoskeleton does not appear to be playing a major role in maintaining the lateral separation of these distinct molecular regions.

Animals↗

PubMed2002

Regional differences within the human supraspinous and interspinous ligaments: a sheet plastination study.

The extent to which neighboring muscles and the fascia contribute to the formation of the supraspinous and interspinous ligaments is not clear from the literature. The purpose of this investigation is to examine the midline attachments of tendons and the posterior layer of thoracolumbar fascia in order to determine their respective contributions to the formation of these ligaments throughout the thoracolumbar spine. Study of the dense connective tissue organization in the posterior ligamentous system was carried out on two cadavers serially sectioned into thin (2.5-mm) epoxy resin plastinated slices. Additional observations were taken from a gross anatomical study of the midline anatomy in two adult cadavers. The results show that the spinal attachments of trapezius, rhomboideus major and splenius cervicis combine with the deep fascia to form the supraspinous ligament in the upper thoracic spine. The posterior layer of the thoracolumbar fascia makes a major contribution to the supraspinous and interspinous ligaments in the lower thoracic spine. In addition to the posterior layer of thoracolumbar fascia, longissimus thoracis and multifidus combine to form the lumbar supraspinous and interspinous ligaments. Their spinal attachments produce a system of dense connective tissue with marked regional variation in fiber orientation and arrangement. The findings support the description of the supraspinous and interspinous ligaments as structures formed by both muscle tendons and aponeuroses along the length of the thoracic and lumbar spine, with regional differences in their connective tissue architecture.

Aged↗

PubMed2002

Inhibition of breast tumor progression by systemic delivery of the maspin gene in a syngeneic tumor model.

Maspin has been shown to possess tumor-suppressing activity against breast tumor growth and metastasis. To test the therapeutic value of the maspin gene (SERPINB5) in breast cancer, we established a syngeneic breast tumor metastasis model. This model involved the implantation of mammary tumor cells orthotopically to mammary gland and allowed tumors to grow within the gland and become metastatic to other organs. The mammary tumor cells were initially isolated from MMTV-polyoma virus middle T transgenic mice and were selected in vitro for high invasiveness. Here, we demonstrate that the mammary tumor cells were highly invasive and metastatic. Overall, 100% of tumor-transplanted mice developed lung metastasis. Using nonviral liposome as a carrier, we delivered SERPINB5 to mice bearing mammary tumors. Our data showed that both primary tumor growth and metastasis were significantly inhibited in this syngeneic metastasis model. Such inhibition is mediated by SERPINB5 transgene through increased apoptosis in SERPINB5-treated tumors. Thus, SERPINB5 can be used in gene therapy against breast tumor growth and metastasis.

Animals↗

PubMed2002

Synergic analysis of upper limb target-reaching movements.

The topological invariance and synergies of human movements are discussed through the analysis and comparison of upper-limb target-reaching tasks. Five subjects were asked to perform different target-reaching tasks with different indices of difficulty, and the movements were captured using a Vicon 3D motion analysis system. Topological invariance was observed in the trajectories of different task performances. After normalization, the trajectories of the arm tips had very close patterns for different target-reaching tasks. Synergy in the target-reaching movements of the upper limbs was also found among the different joint angles. The joint angles can be fitted using the same format of functions proposed in this study. The parameters in the function can be taken as a characteristic feature of target-reaching movement patterns. A target-reaching movement can be determined by these parameters and the start and end positions.

Adult↗

PubMed2002

Covalent immobilization of chitosan/heparin complex with a photosensitive hetero-bifunctional crosslinking reagent on PLA surface.

Chitosan (CS) was covalently immobilized onto polylactic acid (PLA) film surface using the photosensitive hetero-bifunctional crosslinking reagent, 4-azidobenzoic acid, which was previously bonded to chitosan by reaction between an acid group of the crosslinking reagent and a free amino group of chitosan. The immobilization was accomplished by irradiating with ultraviolet light, the modified chitosan being coated on the film surface to photolyze azide groups, thus crosslinking chitosan and PLA together. The hydroxyl and amino groups of chitosan may provide the opportunity for them being further derived by chemically immobilizing a variety of functional groups. These modifications could be carried out to tailor PLA biomaterial to meet the specific needs of different biomedical applications. For example, chitosan molecules immobilized on the PLA could be modified by heparin (Hp) solution to form a polyelectrolyte complex on the PLA surface. Platelet adhesion assay showed that PLA surface modified by chitosan/heparin complex could inhibit platelet adhesion and activation. Cell culture assay indicated that PLA surface with CS/Hp complex showed enhanced cell adhesion.

Animals↗

PubMed2002

Motion quality evaluation of upper limb target-reaching movements.

Fitts' Law was extended in the polar coordinate system, and a set of indices for human motion evaluation is proposed. In this paper, the index of difficulty and the index of performance are introduced as the general indices for the quality measure of plane target-to-target movement. As an example, the target-reaching movement of the upper limb, which is a basic functional action of upper limbs in the activities of daily living, was experimentally investigated. Five healthy subjects were asked to perform six target-reaching tasks with different indices of difficulty. All movements were recorded using a Vicon motion analysis system. The movement quality was measured using these evaluation indices.

Activities of Daily Living↗

PubMed2002

Apoptosis in the retina during MCMV retinitis in immunosuppressed BALB/c mice.

BACKGROUND: Cytomegalovirus (CMV) retinitis is the most common opportunistic ocular infection observed in immunosuppressed (IS) adult and pediatric patients. Due to the species restriction of the cytomegaloviruses, mice infected with murine CMV (MCMV) have been used to study the pathogenesis of CMV retinitis. OBJECTIVES: The objectives of this study were to determine if retinal glial cells are the targets of MCMV infection and to determine which cells in the retina become apoptotic following inoculation of MCMV via the supraciliary route. STUDY DESIGN: Adult female BALB/c mice were IS with methylprednisolone; one half of the mice were injected with MCMV and one half of the mice were injected with an equivalent volume of tissue culture medium via the supraciliary route. Animals were sacrificed and frozen sections of eyes were stained for MCMV early antigen, RPE65, CD45 or TUNEL; additional slides were double stained with combinations of the above reagents. RESULTS AND CONCLUSIONS: The results indicate that most apoptotic cells in the retina were not virus infected, most apoptotic cells were not infiltrating CD45 positive leukocytes, and retinal glial cells were infected with MCMV but only late in infection. Together, these results suggest that retinal cells that undergo apoptosis during MCMV infection are neurons and that apoptosis of uninfected bystander cells is an important component of the pathogenesis of CMV retinitis.

Animals↗