Search PubMed⌕ Search

Biomedical subjects

Y Cao

Publications and source records attributed to Y Cao.

At least 73 records · Page 4Linked to original sources
PubMed2001

3D-QSAR model of flavonoids binding at benzodiazepine site in GABAA receptors.

With flavone as a structural template, three-dimensional quantitative structure-activity relationship (3D-QSAR) studies and ab initio calculations were performed on a series of flavonoids. A reasonable pharmacophore model was built through CoMFA, CoMSIA, and HQSAR analyses and electrostatic potential calculations. A plausible binding mode for flavonoids with GABA(A) receptors was rationalized. On the basis of the commonly recognized binding site, the specific S1 and S2 subsites relating to substituent positions were proposed. The different binding affinities could be explained according to the frontier orbitals and electrostatic potential (ESP) maps. The ESP could be used as a novel starting point for designing more selective BZ-binding-site ligands.

Benzodiazepines↗
PubMed2001

Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF.

Most endocrine hormones are produced in tissues and organs with permeable microvessels that may provide an excess of hormones to be transported by the blood circulation to the distal target organ. Here, we investigate whether leptin, an endocrine hormone, induces the formation of vascular fenestrations and permeability, and we characterize its angiogenic property in the presence of other angiogenic factors. We provide evidence that leptin-induced new blood vessels are fenestrated. Under physiological conditions, capillary fenestrations are found in the leptin-producing adipose tissue in lean mice. In contrast, no vascular fenestrations were detected in the adipose tissue of leptin-deficient ob/ob mice. Thus, leptin plays a critical role in the maintenance and regulation of vascular fenestrations in the adipose tissue. Leptin induces a rapid vascular permeability response when administrated intradermally. Further, leptin synergistically stimulates angiogenesis with fibroblast growth factor (FGF)-2 and vascular endothelial growth factor (VEGF), the two most potent and commonly expressed angiogenic factors. These findings demonstrate that leptin has another new function-the increase of vascular permeability.

Adipose Tissue↗
PubMed2001

Perchlorophenalenyl radical.

We report the preparation and solid-state characterization of the perchlorophenalenyl radical (1). The radical is initially obtained as a yellow-green solid by reduction of the perchlorophenalenium salt (12(+)). This solid sublimes in a sealed tube to give black shiny hexagonal crystals of the perchlorophenalenyl radical (1). The structure consists of 1-dimensional stacks of the monomeric radical. The peri-chlorine atoms force the phenalenyl system to be strongly nonplanar leading to a large separation between adjacent molecules within the stacks (3.78 A), and the molecules adopt two distinct stacking motifs (quasisuperimposed and rotated by 60 degrees with respect to neighbors). Because of the packing frustration in the lattice and the large intermolecular spacing, the solid shows Curie paramagnetism in the temperature range 100-400 K, before antiferromagnetic coupling sets in at low temperatures. Due to the narrow bandwidth that results from the isolation of the individual molecules, the solid is a Mott-Hubbard insulator, with a room-temperature conductivity of rho(RT) = 10(-10) S/cm.

Journal Article↗
PubMed2001

[Horizontal transmission of live attenuated hepatitis A vaccine virus].

OBJECTIVE: To investigate the horizontal transmission of virus after inoculation with live attenuated hepatitis A vaccine. METHODS: One hundred and ninety nine children aged 4 approximately 7 years without anti-HAV and with normal ALT level have been screened out at two trial fields in Anning, Kunming and divided into vaccine group (82 children) and contact group (117 children) to observe the horizontal transmission of the live attenuated hepatitis A vaccine virus (H2 strain). Four supernatant specimens of HAV positive fecal suspension derived from individual vaccines and contacts were taken and injected intravenousely into 8 common marmoset (Callithrix jacchus) for detecting the virulence level of HAV. RESULTS: The rates of seroconversion were 97.6% (80/82) for vaccine group 6 weeks after inoculation and 13.7% (16/117) for contact group at the ninth week of observation. The detection rates of fecal HAV were 89.5% (34/38) and 70.7% (53/75), respectively. No liver functional abnormality has been found in either groups. The responses of 8 marmosets separately infected with fecal shedding HAV of 2 vaccines and 2 contacts have been examined with neither elevations of serum liver enzyme nor liver histopathological changes but delay seroconversions as well as low titers of anti-HAV. CONCLUSION: The safety and immunogenicity live attenuated hepatitis A vaccine (H2 strain) were good. The vaccine virus could actively propagate but keep the stability of attenuated characteristics in human bodies, and might result in horizontal transmission but not induce hepatitis A in crowd.

Animals↗
PubMed2001

Direct interaction between the cytoplasmic tail of ADAM 12 and the Src homology 3 domain of p85alpha activates phosphatidylinositol 3-kinase in C2C12 cells.

ADAM 12, a member of the ADAM family of transmembrane metalloprotease-disintegrins, has been implicated previously in the differentiation of skeletal myoblasts. In the present study, we show that the cytoplasmic tail of mouse ADAM 12 interacts in vitro and in vivo with the Src homology 3 domain of the p85alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase. By site-directed mutagenesis, we have identified three p85alpha-binding sites in ADAM 12 involving PXXP motifs located at amino acids 825-828, 833-836, and 884-887. Using green fluorescent protein (GFP)-pleckstrin homology (PH) domain fusion protein as a probe for PI 3-kinase lipid products, we have further demonstrated that expression of ADAM 12 in C2C12 cells resulted in translocation of GFP-PH to the plasma membrane. This suggests that transmembrane ADAM 12, by providing docking sites for the Src homology 3 domain of p85alpha, activates PI 3-kinase by mediating its recruitment to the membrane. Because PI 3-kinase is critical for terminal differentiation of myoblasts, and because expression of ADAM 12 is up-regulated at the onset of the differentiation process, ADAM 12-mediated activation may constitute one of the regulatory mechanisms for PI 3-kinase during myoblast differentiation.

ADAM Proteins↗
PubMed2001

Double-stranded RNA injection produces nonspecific defects in zebrafish.

We have investigated the ability of dsRNA to inhibit gene functions in zebrafish using sequences targeted to the maternal gene pouII-1, the transgene GFP, and an intron of the zebrafish gene terra. We found that embryos injected with all of these dsRNAs at approximately 7.5 pg/embryo or higher had general growth arrest during gastrulation and displayed various nonspecific defects at 24 h postfertilization, although embryonic development was unaffected before the midblastula stage. Reducing dsRNA concentration could alleviate the global defects. Injection of GFP dsRNA (7.5-30 pg/embryo) did not inhibit GFP expression in transgenic fish, although abnormal embryos were induced. Co-injection of GFP mRNA with either GFP or non-GFP dsRNA caused reduction of GFP expression. Whole-mount in situ hybridization clearly showed that embryos injected with dsRNA degraded co-injected and endogenous mRNA without sequence specificity, indicating that dsRNA has a nonspecific effect at the posttranscriptional level. It appears that RNAi is not a viable technique for studying gene function in zebrafish embryos.

Abnormalities, Multiple↗
PubMed2001

Virologic and immunologic effect of antiretroviral therapy on HIV-1 in gut-associated lymphoid tissue.

OBJECTIVES: We evaluated virologic and immunologic responses to antiretroviral therapy in gut-associated lymphoid tissue (GALT) compared with those found in peripheral blood. METHODS: Eight HIV-1-infected individuals were treated with three reverse transcriptase inhibitors and one protease inhibitor. Endoscopic biopsies were performed at baseline, and at months 1, 2, and 6. We measured the level of cell-associated multiply spliced and unspliced HIV-1 mRNA in GALT and in peripheral blood mononuclear cells. Immunologic responses were assessed by flow cytometry. RESULTS: Levels of multiply spliced HIV-1 mRNA declined in parallel fashion both in peripheral blood and GALT. After 6 months of therapy, unspliced HIV-1 mRNA in the GALT was below assay detection although it persisted in peripheral blood mononuclear cells in 4 study subjects. Although the percentage of CD4+ lymphocytes increased significantly in peripheral blood, only modest increases occurred in GALT. The percentage of activated CD8+ T cells decreased significantly in peripheral blood whereas only modest reductions occurred in GALT. CONCLUSIONS: Antiretroviral therapy effectively suppressed HIV-1 replication in GALT. The percentage of CD4+ T cells in peripheral blood uniformly increased in all study subjects, whereas it was more variable in the GALT.

Adult↗
PubMed2001

Single-coil arterial spin-tagging for estimating cerebral blood flow as viewed from the capillary: relative contributions of intra- and extravascular signal.

The single-capillary model was applied to the exchange microvessels for water in the cerebral parenchyma and used to calculate blood-to-brain flux of water; the theory of the steady-state arterial spin-tagging (AST) technique for estimating cerebral blood flow (CBF) was revised to incorporate the presence of both extravascular (tissue) and capillary signal. A crucial element of the single-coil AST experiment is that magnetization transfer (MT) shortens the effective T1 of the extravascular water, making it one-quarter that of the T1 of capillary blood. Furthermore, the mean capillary transit time is on the order of the T1 of the extravascular water. The single-coil AST experiment is distinguished from other methods which use water as an indicator for measurement of CBF in that the (flow-dependent) populations of inverted protons in the intra- and extravascular compartments can be nearly equal for normal physiological conditions. The following questions are considered: Is single-coil AST contrast linear in resting CBF? Is contrast in the single-coil AST technique likely to be linear under changes in CBF in normal tissue? Is the contrast likely to be linear in such common pathologies as stroke and cerebral tumor? We demonstrate that, if the population of inverted protons in the microvessels is included in the experiment, the voxel population of inverted protons will be approximately linear with flow across a broad range of flow values. We predict that the single-coil AST experiment will systematically overestimate resting CBF for flows in the normal range, that changes in CBF in normal tissue will produce an approximately linear response in AST measurement, and, finally, we predict the operating characteristics of the measurement in common cerebral pathologies.

Animals↗
PubMed2001

Effect of 7,12-dimethylbenz[a]anthracene (DMBA) on gut glutathione metabolism.

BACKGROUND: One mechanism of the mammary carcinogenesis of 7,12-dimethylbenz[a]anthracene (DMBA) is thought to be the generation of reactive oxygen species known to play an important role in initiation and progression. We hypothesized that DMBA would disrupt gut glutathione (GSH) metabolism and this disruption would correlate with mammary cell carcinogenesis. METHODS: Sixty-four Sprague-Dawley rats were randomized to the DMBA versus control groups. At age 50 days, rats were gavaged with a one-time dose of 20 mg DMBA or sesame oil. Rats from each group were sacrificed at 1 week (n = 16), 2 weeks (n = 16), 4 weeks (n = 16), and 11 weeks (n = 16). Tumor appearance, arterial and gut GSH concentration, and gut GSH extraction were measured over time. RESULTS: Gut GSH extraction (normally negative; production) was significantly depressed over the time points, even showing uptake (positive extraction) at Weeks 1 and 2. Tumors developed in all animals in the DMBA group by Week 11. CONCLUSIONS: A one-time oral administration of DMBA has a significant and prolonged depressive effect on gut GSH production that has not previously been described. These data support the hypothesis that the carcinogenic effect of DMBA is mediated, at least in part, by oxidative damage and that the disruption of gut GSH metabolism may play a greater role in carcinogenesis than previously realized.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Combination angiostatin and endostatin gene transfer induces synergistic antiangiogenic activity in vitro and antitumor efficacy in leukemia and solid tumors in mice.

Angiostatin and endostatin are potent endothelial cell growth inhibitors that have been shown to inhibit angiogenesis in vivo and tumor growth in mice. However, tumor shrinkage requires chronic delivery of large doses of these proteins. Here we report synergistic antitumor activity and survival of animals when these factors are delivered in combination to tumors by retroviral gene transfer. We have demonstrated this efficacy in both murine leukemia and melanoma models. Complete loss of tumorigenicity was seen in 40% of the animals receiving tumors transduced by the combination of angiostatin and endostatin in the leukemia model. The synergy was also demonstrated in vitro on human umbilical vein endothelial cell differentiation and this antiangiogenic activity may suggest a mechanism for the antitumor activity in vivo. These findings imply separate pathways by which angiostatin and endostatin mediate their antiangiogenic effects. Together, these data suggest that a combination of antiangiogenic factors delivered by retroviral gene transfer may produce synergistic antitumor effects in both leukemia and solid tumors, thus avoiding long-term administration of recombinant proteins. The data also suggest that novel combinations of antiangiogenic factors delivered into tumors require further investigation as therapeutic modalities.

Angiogenesis Inhibitors↗
PubMed2001

Effect of transforming growth factor-beta 2 on phagocytosis in cultured bovine trabecular meshwork cells.

The effect of transforming growth factor-beta 2 (TGF-beta 2) on phagocytosis in bovine trabecular meshwork cells in vitro was investigated. After the cultured bovine trabecular meshwork cells were treated with 0 ng/ml, 0.32 ng/ml, 1 ng/ml, 3.2 ng/ml TGF-beta 2 for 24 h, latex beads were added into the incubation medium, and the numbers of the latex beads in 20 adjacent cells were counted under a microscope 24 h later, after treatment with Wright's stain. Our results showed that the average numbers of the latex beads in the trabecular meshwork cells treated with TGF-beta 2 of different concentrations were 53.1 +/- 1.7 beads/cell, 56.4 +/- 2.9 beads/cell and 77.9 +/- 6.5 beads/cell respectively, in comparison with 45.5 +/- 3.3 beads/cell of the control group. TGF-beta 2 significantly increased the number of the latex beads phagocytosed by cultured bovine trabecular meshwork cells in a dose-dependent manner. TGF-beta 2 could promote the phagocytosis of bovine trabecular meshwork cells in vitro. It may be involved in the cellularity decrease of the trabecular meshwork in the patients of primary open angle glaucoma through promoting the phagocytosis of trabecular meshwork cells.

Animals↗
PubMed2001

Binding patterns of 51 monoclonal antibodies to peptide and carbohydrate epitopes of the epithelial mucin (MUC1) on tissue sections of adenolymphomas of the parotid (Warthin's tumours): role of epitope masking by glycans.

Warthin's tumours provide a unique opportunity to distinguish and compare monoclonal antibodies (mAbs) to the epithelial mucin, MUC1. In this study, we have applied the range of anti-MUC1 antibodies submitted to the ISOBM TD-4 Workshop for this purpose. mAbs and lectins against MUC1-associated carbohydrate epitopes were also included. Among 39 mAbs to peptide epitopes of MUC1, eight distinct types of staining patterns towards the two epithelial cell layers of Warthin's tumours could be observed. A majority of 27 mAbs reacted preferentially (17) or exclusively (10) with columnar cells, whereas 10 mAbs favoured basal cells (1 of them almost exclusively). The observed staining patterns revealed no correlation with the epitopes. However, after carbohydrate-specific periodate oxidation, 33 of the mAbs stained columnar and basal cells equally well, indicating that epitope masking by glycan side chains was in most cases responsible for the different staining patterns. The results demonstrate the profound impact of glycosylation on immunohistochemistry. Among carbohydrate epitopes, sialyl-TF, sialyl-Le(x), sialyl-dimeric Le(x) and Tn were expressed on both columnar and basal cells (the s-TF3 isomer on columnar cells only). The carcinoma-associated Thomsen-Friedenreich epitope was absent.

Adenolymphoma↗
PubMed2001

Expression of Xenopus L-arginine:glycine amidinotransferase (XAT) during early embryonic development.

We have isolated a full-length cDNA encoding Xenopus L-arginine:glycine amidinotransferase (XAT), which shares a highly conserved sequence with human, chick and rat amidinotransferase. Although there are some studies about its structure and function in energy metabolism of adult tissues in some other species, little is known about its roles during early embryonic development. Characterization of embryonic expression indicates that XAT is differentially expressed around the yolk plug including the dorsal blastopore area at early gastrula stages and is extensively expressed in the midline of the neural plate of early neurula stages. Sections reveal that its transcripts are located in the notochord. In the tailbud stage signals are found both in the notochord and trunk area, whereas only faint signals can be found in the cephalic part.

Amidinotransferases↗
PubMed2001

Development of the phytoplankton community in a pit-lake in relation to water quality changes.

An open pit-lake was formed at a Northern Saskatchewan mine site after flooding with lake water in early 1992. Since then, water and phytoplankton samples have been collected regularly from the artificial lake over seven years. The resulting data set provides a unique opportunity to examine the physical and chemical changes in water quality and phytoplankton community over time. Seventeen major variables were examined in a principal component analysis. Axes 1, 2 and 4 are significantly correlated to other three variables, the number of days (since the first sampling after flooding of the pit), water temperature and depth, respectively. Total suspended solid (TSS), dissolved oxygen, total phosphorus (Total-P), arsenic, and iron decreased over time while Mg, Ca, K, Na, total organic carbon and HCO3 increased. Canonical correspondence analysis was used to infer the relationship between water quality variables and phytoplankton community structure, which changed substantially over the survey period. TSS, Total-P and arsenic were considered to be the key factors driving the change in phytoplankton community composition.

Canada↗
PubMed2001

A sensitive chemiluminescent enzyme immunoassay for the bioanalysis of carboxyl-terminal B-chain analogues of human insulin.

Quantification of analogues of human insulin in biological matrices is complicated by differences in their immunoreactivity and the presence of both the analogue and endogenous concentrations of insulin in test samples. To facilitate pharmacokinetic comparisons of carboxyl-terminal B-chain analogues of human insulin, we undertook development of a sensitive ELISA. The ELISA detection method was optimized systematically to permit routine analysis of 10-microl serum samples. Accordingly, a noncompetitive 'sandwich' chemiluminescent ELISA was validated for the quantification of carboxyl-terminal B-chain insulin analogues in human serum over a concentration range from 5 to 3125 pM. The mean bias (RE%) within the validated range varied from -10.3 to 4.3%, with an intermediate precision (inter-assay CV%) from 4.2 to 11.5%. The two-sided 90% expectation tolerance interval for total measurement error was within +/-25% of the nominal concentration for all levels of validation samples. Insulin lispro, human insulin, proinsulin, despentapeptide insulin (DPI) and porcine insulin displayed comparable crossreactivity in the ELISA. Potential utility of the new assay for insulin bioanalysis in nonhuman species was investigated by assessing the pharmacokinetic profile of DPI in rats following administration of a single subcutaneous dose. The sensitive chemiluminescent detection method is simple to perform and should be readily adaptable for ELISAs of other therapeutic proteins.

Animals↗
PubMed2001

Tissue-specific expression of an Ornithine decarboxylase paralogue, XODC2, in Xenopus laevis.

Ornithine decarboxylase (ODC) is involved in the biosynthesis of polyamines and hence has been found in almost all types of cells studied. Therefore it is frequently used as internal standard. We isolated a cDNA, XODC2, which is a paralogue to ubiquitous ODC and expressed in a spatial and temporal manner during the early embryogenesis of Xenopus laevis. Expression of XODC2was first detected at the animal pole at stage 9. During neurula stages the signals were found both in the extreme anterior and posterior part of the dorsal body axis. In tailbud stages the expression is further shifted to both the tail and head areas and gradually restricted to distinct tissues: forebrain, inner layer of epidermis of the head area, stomodeal-hypophyseal anlage, frontal gland, ear vesicle, branchial arches, the front tip of neural tube and proctodeum. In addition, signals were also found in the inner layer of epidermis underneath the cement gland during early tailbud stages while in later tailbud stages signals were detected at the apical zone of the cement gland. Comparative studies indeed could confirm that XODC1 in contrast to XODC2 is expressed ubiquitously throughout the whole embryos during early development of Xenopus laevis.

Amino Acid Sequence↗
PubMed2001

Profiling brain transcription: neurons learn a lesson from yeast.

The application of microarray technologies to the brain poses unique challenges, because of the complexity of the central nervous system and the availability of resources. Nevertheless, recent studies using DNA chips have made inroads into the molecular characterization of regional and functional brain units, the identification of developmental gene expression patterns, and the discovery of transcriptional differences associated with behavioral and neuropathological traits.

Animals↗