Biomedical subjects

J Gong

Publications and source records attributed to J Gong.

At least 37 records · Page 2Linked to original sources

PubMed2001

Structure/function of human herpesvirus-8 MIP-II (1-71) and the antagonist N-terminal segment (1-10).

Kaposi's sarcoma-associated herpesvirus encodes a chemokine called vMIP-II that has been shown to be a broad range human chemokine receptor antagonist. Two N-terminal peptides, vMIP-II(1-10) and vMIP-II(1-11)dimer (dimerised through Cys11) were synthesised. Both peptides are shown to bind the CXC chemokine receptor 4 (CXCR4). vMIP-II(1-10) was 1400-fold less potent than the native protein whilst the vMIP-II(1-11)dimer was only 180-fold less potent. In addition, both peptides are CXCR4 antagonists. Through analysis of non-standard, long mixing time two-dimensional nuclear Overhauser enhancement spectroscopy experiments, 13C relaxation data and amide chemical shift temperature gradients for the N-terminus of vMIP-II, we show that this region populates a turn-like structure over residues 5-8, both in the presence and absence of the full protein scaffold. This major conformation is likely to be in fast exchange with other conformational states but it has not previously been detected in monomeric chemokine structures. This and other studies [Elisseeva et al. (2000) J. Biol. Chem. 275, 26799-26805] suggest that there may be a link between the structuring of the short N-terminal chemokine peptides and their ability to bind their receptor.

Binding Sites↗

PubMed2001

Vaccination with allogeneic dendritic cells fused to carcinoma cells induces antitumor immunity in MUC1 transgenic mice.

Fusions of autologous tumor cells with allogeneic dendritic cells (DC) represent an approach for the induction of antitumor immunity. In the present studies, we investigated the antitumor effects of vaccinating MUC1-transgenic (MUC1.Tg) mice with MC38/MUC1 carcinoma cells fused to allogeneic DC from BALB/c mice (allo-DC, H-2(d)) or syngeneic DC from C57BL/6 mice (syn-DC, H-2(b)). Both allo and syn fusion cells (FC/MUC1) expressed MHC class II, costimulatory molecules, and the MUC1 antigen. Allo-FC/MUC1 exhibited dual expression of MHC class I haplotypes (H-2(d)/H-2(b))and MUC1 antigen. By contrast, only H-2(b) and MUC1 antigen were expressed by syn-FC/MUC1. CTLs from MUC1.Tg mice immunized with allo- or syn-FC/MUC1 fusion cells lysed MC38/MUC1 targets. Moreover, immunization with allo- or syn-FC/MUC1 was effective in eliminating established MUC1-positive pulmonary metastases in MUC1.Tg mice. These results indicate that immunization of MUC1.Tg mice with syn- or allo-FC/MUC1 is effective in reversing immunologic unresponsiveness to MUC1 antigen and inducing immunity against MUC1-positive tumors. The findings in the present study have broader clinical implications for fusion cell vaccines.

Animals↗

PubMed2001

Hazard of smoking initiation by age among adolescents in Wuhan, China.

BACKGROUND: Knowledge about age of smoking initiation among adolescents in China is helpful for exploring cultural differences in adolescent smoking behavior and informative for global tobacco control. However, little has been documented on this issue. METHOD: Adolescents (6,473) attending grades 7, 8, and 9 completed the baseline survey of a longitudinal, randomized smoking prevention trial. Data were collected in classrooms with a paper-and-pencil questionnaire. A survival model was used in the statistical analysis. RESULTS: The hazard of smoking initiation for boys showed a pattern previously observed in the United States: very low (<2%) before 7 years of age, increasing rapidly after age 10, and peaking at 14-15 years of age. The hazard for girls was below or around 1% until 12 years of age before it increased. The hazard levels were similar for adolescents both in urban and in rural areas, but higher for those in grade 7 than in grades 8 and 9. CONCLUSIONS: Chinese boys in Wuhan, China, experienced a hazard pattern of smoking initiation by age similar to those observed in the United States, while Chinese girls there experienced a rather low risk of smoking initiation. The hazard pattern suggests that the best time for smoking prevention is between 10 and 15 years of age. Adolescents in lower grades are at higher risk of early smoking initiation, suggesting a potential cohort effect in adolescent smoking initiation in Wuhan, China.

Adolescent↗

PubMed2001

Preventive antitumor activity against hepatocellular carcinoma (HCC) induced by immunization with fusions of dendritic cells and HCC cells in mice.

BACKGROUND: The prevention of recurrence of hepatocellular carcinoma (HCC) after treatment is very important for improvement of the prognosis of HCC patients. Dendritic cells (DCs) are potent antigen-presenting cells that can prime naive T cells to induce a primary immune response. We attempted to induce preventive antitumor immunity against HCC by immunizing BALB/c mice with fusions of DCs and HCC cells. METHODS: Murine bone marrow-derived DCs and a murine HCC cell line. BNL cells, were fused by treatment with 50% polyethyleneglvcol (PEG). Fusion efficacy was assessed by the analysis of fusions of BNL cells stained with red fluorescent dye and DCs stained with green fluorescent dye. Mice injected intravenously with DC/BNL fusions were challenged by BNL cell inoculation. RESULTS: About 30% of the PEG-treated non-adherent cells with both fluorescences were considered to be fusion cells. The cell fraction of DC/BNL fusions showed phenotypes of DCs, MHC class II, CD80, CD86, and intercellular adhesion molecule (ICAM)-1, which were not expressed on BNL cells. Mice immunized with the fusions were protected against the inoculation of BNL tumor cells, whereas injection with a mixture of DCs and BNL cells not treated with PEG did not provide significant resistance against BNL cell inoculation. Splenocytes from DC/BNL fusion-immunized mice showed lytic activity against BNL cells. CONCLUSIONS: These results demonstrate that immunization with fusions of DCs and HCC cells is capable of inducing preventive antitumor immunity against HCC.

Animals↗

PubMed2001

Preliminary findings in germinal vesicle transplantation of immature human oocytes.

Transplanting a germinal vesicle (GV) from an aged woman's oocyte into a younger ooplasm has been proposed as a possible way to reduce the incidence of oocyte aneuploidy which is considered to be responsible for age-related infertility. In this study, we have assessed the efficiency of each step involved in nuclear transplantation-specifically cell survival, nuclear-cytoplasmic reconstitution, and the capacity of the reconstituted oocytes for in-vitro maturation. In addition, we have evaluated the fertilizability and karyotypic status of the manipulated oocytes by intracytoplasmic sperm injection (ICSI) and fluorescent in-situ hybridization technique respectively. Nuclear transplantation was accomplished with an overall efficiency of 73%. Due to the limited availability of materials, most nuclear transplantation procedures were performed between sibling oocytes. The maturation rate of 62% following reconstitution was comparable with that of control oocytes, as was the incidence of aneuploidy among the reconstituted oocytes. The ICSI results of the reconstituted oocytes yielded a survival rate of 77%, a fertilization rate of 52%, and a satisfactory early embryonic cleavage. Furthermore, in a limited number of observations where the nucleus of an aged oocyte was transferred into a younger ooplasm, there was an appropriate chromosomal segregation. These findings demonstrate that human oocytes reconstituted with GV nuclei are able to undergo maturation, fertilization, and early embryo cleavage, and maintain a normal ploidy. Although in-vitro maturation seems to be a limiting step, this technique would allow us to investigate further the nuclear-ooplasmic relationship during meiotic maturation.

Adult↗

PubMed2001

[Evaluation of dynamic enhanced fast multiplanar spoiling gradient recalled(FMPSPGR) in the diagnosis of small hepatocellular carcinoma].

OBJECTIVE: To analyze the features of small hepotocellular carcinoma (SHCC) by spin echo (SE) sequence and dynamic enhanced FMPSPGR, and to compare the sensitivity for detecting and the accuracy for characterization, further to discuss the value of FMPSPGR in the diagnosis of SHCC. METHODS: SE T(1)WI, T(2)WI and FMPSPGR dynamic imaging of the liver were performed for 58 patients with SHCC. The sensitivity for detecting and accuracy for characterization were statistically compared. RESULTS: Seventy-two lesions were found in 58 patients. In the detection of SHCC, the order of the sensitivity was dynamic enhanced FMPSPGR>SE T(2)WI>no-enhanced FMPSPGR>SE T(1)WI. Dynamic enhanced FMPSPGR was significantly higher than any of the others. There was significant difference between no-enhanced FMPSPGR and SE T(2)WI, but not significant difference between T(2)WI and no-enhanced FMPSPGR. In the characterization of SHCC, the accuracy of pre- and post-contrast FMPSPGR was significantly higher than that of SE (T(1)WI+T(2)WI) with remarkable statistical difference. CONCLUSIONS: FMPSPGR dynamic imaging is superior to SE in the detection and characterization of SHCC. The sensitivity for detecting and the accuracy for characterization will be improved when both FMPSPGR and SE are used.

Adult↗

PubMed2001

IgE-regulated loss, not IgE-regulated synthesis, controls expression of FcepsilonRI in human basophils.

Expression of the high-affinity receptor on basophils and mast cells is modulated by immunoglobulin E (IgE) antibody. Recent studies have shown that modulation occurs through interaction of IgE with the receptor itself, but the mechanisms underlying this control are not understood. Taking both a theoretical and experimental approach, we examined several competing models that focus on whether there is IgE-regulated loss, IgE-regulated synthesis, or both regulated loss and synthesis of the Fc receptor for IgE (FcepsilonRI). We report that removing IgE from occupied FcepsilonRI resulted in an accelerated loss only in the unoccupied receptor, with no loss of occupied receptors and no loss of total receptors when all receptors were occupied. Together with previous studies, these results establish that there was IgE-regulated loss of receptors. An examination of synthetic rates of FcepsilonRIalpha using pulse-labeling with (35)S-methionine indicated no difference in synthetic rates in the presence or absence of IgE. Similarly, the presence or absence of IgE had no influence on the levels of mRNA for either alpha, beta, or gamma subunits of FcepsilonRI. Using model simulations, we found that regulated-synthesis models could be distinguished from regulated-loss/constant-synthesis models on the basis of the relationship between starting FcepsilonRI densities and changes in density after culture for 1 week in the absence of IgE. Experimental data from this type of study fit a regulated-loss model that did not include regulation of synthesis. Taken together, these results suggest that IgE regulates cell surface expression of FcepsilonRI only by regulating the rate that receptor is lost from the cell surface.

Basophils↗

PubMed2001

Cell cycle analysis by cyclin E + A/DNA multiparameter flow cytometry in exponential growth MOLT-4 cells.

OBJECTIVE: To establish a new method for analyzing the cell cycle in tumor which is a kind of cell cycle disease. METHODS: Mixtures of cyclin E and cyclin A antibodies were incubated with fixed MOLT-4 cells, and measured by flow cytometry. RESULTS: We developed a cyclin E + A/DNA flow cytometry analysis method, which may distinguish G0, early G1, late G1, S, G2 and M phase cells, rather than three phases in the DNA content histogram. CONCLUSION: Cyclin E + A/DNA multiparameter flow cytometry can simultaneously differentiate in the same sample six cell groups: G0, early G1, late G1, S, G2 and M phase cells. It performed better than any other cell cycle analysis methods that we have used and has a definite cell biology foundation.

Cell Cycle↗

PubMed2001

[Change of NOS activity in hypoxia and cold-induced blood vessels damage and its biological significance].

OBJECTIVES: To explore the therapeutic methods for hypoxia and cold induced blood vessel damage by observing the changes of NO synthase (NOS) activity in hypoxia and development of coldm induced blood vessels damage, and studying the effects of SOD and vitamin C on the changes of NOS activity. METHODS: The main artery was isolated from Wistar rats and exposed to hypoxia and/or cold environment in vitro. LDH activity was measured using an automatic biochemical analyzer and NOS and SOD activities in blood vessels were analyzed respectively by Griess assay and adrenaline autoxidantion method. RESULTS: NOS activity in hypoxia, cold and hypoxia-cold damaged vessels decreased by 18.2%, 19.1% and 25.9% respectively after exposure as compared with the control vessels. The changes of NOS activity were time dependent. The NOS activity in damaged vessels was negatively correlated with LDH activity in the culture medium of the respective vessels. The SOD activity in hypoxia and/or cold damaged vessels also decreased significantly. Giving SOD (200 u/ml) or vitamin C (50 mg/ml) immediately after hypoxia and/or cold exposure increased the NOS activity and SOD activity in the damaged vessels significantly, as compared with the non-treatment controls. CONCLUSIONS: The decrease of NOS activity is closely related to the development of damage induced by hypoxia and/or cold injury. SOD and vitamin C could protect the blood vessels exposed to hypoxia and/or cold from damage, possibly by increasing NOS activity.

Animals↗

PubMed2000

Induction of antitumor immunity by vaccination of dendritic cells transfected with MUC1 RNA.

Dendritic cells (DC) are potent APCs. In this study, murine bone marrow-derived DC were transfected with RNA encoding the MUC1 Ag that is aberrantly overexpressed in human breast and other carcinomas. The MUC1 RNA-transfected DC exhibited cell surface expression of MUC1 and costimulatory molecules. After injection at the base of the tail, the transfected DC were detectable in inguinal lymph nodes by dual immunochemical staining. Vaccination of wild-type mice with MUC1 RNA-transfected DC induced anti-MUC1 immune responses against MUC1-positive MC38/MUC1, but not MUC1-negative, tumor cells. Mice immunized with the transfected DC were protected against challenge with MC38/MUC1 tumor cells. Furthermore, mice with established MC38/MUC1 tumors were eliminated after receiving the vaccination. CTLs isolated from mice immunized with the transfected DC exhibited specific cytolytic activity against MC38/MUC1 tumor cells. In contrast to these findings, there was little if any anti-MUC1 immunity induced with the transfected DC in MUC1 transgenic (MUC1.Tg) mice. However, coadministration of the transfected DC and IL-12 reversed the unresponsiveness to MUC1 Ag in MUC1.Tg mice and induced MUC1-specific immune responses. These findings demonstrate that vaccination of DC transfected with MUC1 RNA and IL-12 reverses tolerance to MUC1 and induces immunity against MUC1-positive tumors.

Animals↗

PubMed2000

Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic cells induce antitumor immunity.

Human ovarian carcinomas express the CA-125, HER2/neu, and MUC1 tumor-associated Ags as potential targets for the induction of active specific immunotherapy. In the present studies, human ovarian cancer cells were fused to human dendritic cells (DC) as an alternative strategy to induce immunity against known and unidentified tumor Ags. Fusions of ovarian cancer cells to autologous DC resulted in the formation of heterokaryons that express the CA-125 Ag and DC-derived costimulatory and adhesion molecules. Similar findings were obtained with ovarian cancer cells fused to allogeneic DC. The fusion cells were functional in stimulating the proliferation of autologous T cells. The results also demonstrate that fusions of ovarian cancer cells to autologous or allogeneic DC induce cytolytic T cell activity and lysis of autologous tumor cells by a MHC class I-restricted mechanism. These findings demonstrate that fusions of ovarian carcinoma cells and DC activate T cell responses against autologous tumor and that the fusions are functional when generated with either autologous or allogeneic DC.

Carcinoma↗

PubMed2000

Mitochondrial genotype associated with longevity and its inhibitory effect on mutagenesis.

Mitochondria are not only the major site of ATP production in cells but also an important source of reactive oxygen species (ROS) under certain pathological conditions. Because mitochondrial DNA (mtDNA) in the mitochondrial matrix is exposed to ROS that leak from the respiratory chain, this extranuclear genome is prone to mutations. Therefore, the mitochondrial genome is a rich source of single nucleotide polymorphisms (SNPs) and the functional significance of SNPs in the mitochondrial genome is comparable to that of SNPs in the entire nuclear genome. To demonstrate the contribution of mitochondrial SNPs to the susceptibility to adult-onset diseases, we analyzed the mtDNA from Japanese centenarians and identified a longevity-associated mitochondrial genotype, Mt5178A. Because this genotype was demonstrated to suppress the occurrence of mtDNA mutations in the oocytes, it also would seem to decelerate the accumulation of mtDNA mutations in the somatic cells with increasing age. This genotype is likely to confer resistance to adult-onset diseases by suppressing obesity and atherosclerosis.

Animals↗

PubMed2000

Long-term treatment with a platelet glycoprotein-receptor antagonist after percutaneous coronary revascularization. EXCITE Trial Investigators. Evaluation of Oral Xemilofiban in Controlling Thrombotic Events.

BACKGROUND: When administered intravenously at the time of percutaneous coronary revascularization, glycoprotein IIb/IIIa receptor antagonists decrease the incidence of death and nonfatal myocardial infarction and the need for urgent revascularization. We hypothesized that long-term administration of oral glycoprotein IIb/IIIa antagonists, which block the aggregation of platelets, might stabilize intravascular plaque and prevent additional ischemic cardiac events. METHODS: We conducted a prospective, double-blind trial in which 7232 patients were randomly assigned to receive 20 mg of oral xemilofiban or placebo 30 to 90 minutes before undergoing percutaneous coronary revascularization, with maintenance doses of 10 or 20 mg of xemilofiban or placebo administered three times daily for up to 182 days. There were two primary composite end points: one was death, nonfatal myocardial infarction, or urgent revascularization at 182 days, and the other was death or nonfatal myocardial infarction at 182 days. RESULTS: Death, myocardial infarction, or urgent revascularization occurred within 182 days in 324 patients who received placebo (Kaplan-Meier cumulative event rate, 13.5 percent), 332 who received 10 mg of xemilofiban (13.9 percent, P=0.82 for the comparison with placebo), and 306 who received 20 mg of xemilofiban (12.7 percent, P=0.36 for the comparison with placebo). The incidence of death or myocardial infarction was also similar in all three groups. Clinically significant hemorrhagic complications and thrombocytopenia were infrequent. CONCLUSIONS: The administration of the glycoprotein IIb/IIIa antagonist xemilofiban before percutaneous coronary revascularization and for up to six months thereafter does not significantly reduce the incidence of important clinical end points.

Administration, Oral↗

PubMed2000

Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells.

We have reported that fusions of murine dendritic cells (DCs) and murine carcinoma cells reverse unresponsiveness to tumor-associated antigens and induce the rejection of established metastases. In the present study, fusions were generated with primary human breast carcinoma cells and autologous DCs. Fusion cells coexpressed tumor-associated antigens and DC-derived costimulatory molecules. The fusion cells also retained the functional potency of DCs and stimulated autologous T cell proliferation. Significantly, the results show that autologous T cells are primed by the fusion cells to induce MHC class I-dependent lysis of autologous breast tumor cells. These findings demonstrate that fusions of human breast cancer cells and DCs activate T cell responses against autologous tumors.

Breast Neoplasms↗

PubMed2000

An association study of polymorphisms in the alpha-antichymotrypsin gene for Alzheimer disease in Han-Chinese.

Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and DNA sequencing were employed to screen the coding region of the alpha-antichymotrypsin (AACT) gene in Han-Chinese population for polymorphism possibly associated with Alzheimer's disease (AD). Consequently, seven polymorphic sites including 25A>G, 39G>A, 370C>T, 662T>G, 892C>T, 923T>C and 1332A>G were detected. Of them, the 25A>G was reported previously and the others are all novel. We subsequently focused on the 25A>G and the 39G>A polymorphism that were of interest to us and conducted an association study of them by another scanning of 246 controls that matched the AD patients. Statistic test showed that both genotype (p=0.0378, Fisher's exact, two tailed) and allele frequency (p=0.0382, Fisher's exact, two tailed) of 39G>A are different between AD patients and the controls. As for 25A>G, lain only the heterozygous genotype A/G associates with AD (p=0.0220, chi(2)), but not the A allele frequency (p=0.1141, chi(2)).

Aged↗

PubMed2000

Estimating significance level and power comparisons for testing multiple endpoints in clinical trials.

Clinical trials generally include several outcome measures of interest for assessing treatment efficacy and harm. Traditionally a single measure, the primary outcome, is selected and used as the basis for the design, including sample size and power. Secondary outcomes are then generally ordered with respect to their clinical relevance and importance. While this has become the traditional paradigm, recent trials have suggested the need for additional approaches. In this setting, two outcomes are viewed as key, either one being sufficient for proof of efficacy, but with an ordering of preference. The basic question, in such cases, is how to control the overall significance level for the trial. We describe and compare two methods for testing primary and secondary endpoints, accounting for their hierarchical nature-the ordering preference. Both methods are sequential, in the sense that the secondary endpoint is only tested when the primary outcome fails to reach significance. The first method uses a global test for the combination of the primary and secondary endpoints, while the second uses a partial Bonferroni correction. Simulation results indicate that the Bonferroni adjustment method performs as well as the global test method in most cases, and even better in some cases.

Clinical Trials as Topic↗

PubMed2000

T cell suppression as a mechanism for tolerance to MUC1 antigen in MUC1 transgenic mice.

C57BL/6 mice transgenic for human MUC1 (MUC1.Tg) have been developed to study immunologic responsiveness to the human MUC1 tumor-associated antigen. In the present studies, MUC1.Tg mice were immunized with purified human MUC1 antigen and irradiated MUC1-positive (MC38/MUC1) tumor cells. Immunization with MUC1 antigen was associated with induction of an anti-MUC1 antibody response and no detectable cytotoxic T cell reactivity. Similar findings were obtained after immunization with irradiated MC38/MUC1 tumor cells. The results also demonstrate that immunization of MUC1.Tg mice with MUC1 is associated with decreased levels of CD8+ T cells. In addition, expression of alphabeta T cell receptors and CD28 were down-regulated on CD8+ T cells as a consequence of MUC1 immunization. These findings support a role for T cell suppression in tolerance to MUC1 antigen in MUC1.Tg mice.

Animals↗

PubMed2000

Immune reconstitution following high-dose chemotherapy with stem cell rescue in patients with advanced breast cancer.

The present study examines the nature of humoral and cellular immune reconstitution in 28 patients with advanced breast cancer following high-dose chemotherapy with stem cell rescue. Patients underwent testing of T, B, NK and dendritic cell function at serial time points until 1 year post transplant or until the time of disease progression. Abnormalities in T cell phenotype and function were observed following high-dose chemotherapy that persisted for at least 6-12 months. The vast majority of patients experienced an inversion of the CD4/CD8 ratio and demonstrated an anergic response to candida antigen. Mean T cell proliferation in response to PHA and to co-culture with allogeneic monocytes was significantly compromised. In contrast, mean IgG and IgA levels were normal 6 months post transplant and NK cell yields and function were transiently elevated following high-dose chemotherapy. Dendritic cells generated from peripheral blood progenitors displayed a characteristic phenotype and were potent inducers of allogeneic T cell proliferation in the post-transplant period. The study demonstrates that patients undergoing autologous transplantation for breast cancer experience a prolonged period of T cell dysfunction. In contrast, B, NK, and DC recover more rapidly. These findings carry significant implications for the design of post-transplant immunotherapy.

Adult↗