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Biomedical subjects

Z Zhuo

Publications and source records attributed to Z Zhuo.

14 recordsLinked to original sources
PubMed2001

Long-term low-dose IL-2 enhances immune function in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by hypogammaglobulinemia and lack of antibody production. Numerous T cell defects have been described, including reduced gene expression and production of IL-2. Since some of the T cell defects could be explained by lack of IL-2, we have been investigating the effects of in vivo IL-2 treatment. Here, a long-acting form of IL-2, PEG-IL-2, was given for 12-18 months to 15 randomly chosen CVID subjects, in comparison to 39 CVID subjects who served as controls. After 6 to 12 months of treatment, T cell proliferative responses to mitogens and to IL-2 were significantly enhanced; proliferative responses to tetanus and candida antigens increased up to 50-fold. Four of eight subjects immunized with the neoantigen bacteriophage φX 174 displayed increased antibody responses after treatment. Treated subjects recorded reduced, but not overall statistically significant, days of bronchitis, diarrhea, and joint pain. These data indicate that IL-2 might serve as an adjuvant to therapy in some subjects with CVID, enhancing T cell functions and reversing T cell anergy in most.

Adolescent↗
PubMed2001

Hepatitis B virus transgenic mice for the model of anti-hepatitis B virus drug study.

OBJECTIVE: To establish hepatitis B virus (HBV) transgenic mice models and to investigate if the model can be used for the evaluation of anti-HBV drugs. METHODS: HBV transgenic mice models were produced by microinjection to analyze the integration, expression of HBV in the transgenic mice by nested PCR, southern blot, immunohistochemistry, and ELISA. Sixty mice whose HBV DNA, HBsAg were positive were divided into 6 groups randomly, in which 3 groups were given drugs: lamivudine administrated by perfusion of stomach tube (100mg x kg(-1) x day(-1) for 21 days); thymosine administrated by abdomen injection (3mg x day(-1) for 90 days); and DNA vaccine of 100 microg by muscle injection. The other 3 groups were negative control. RESULTS: Lamivudine, thymosine and DNA vaccine made HBV DNA become negative in the serum of HBV transgenic mice. The negative ratio was highest in lamivudine treatment group. HBV DNA became positive again when lamivudine terminated. CONCLUSION: Limvudine, thymosine, and DNA vaccine can inhibit HBV replication. Transgenic mice might be used as the model for anti-HBV drug screening and evaluation.

Animals↗
PubMed1994

An evaluation of drug injection behaviors and HIV infection. National AIDS Research Consortium.

This paper investigates domains of drug injection behavior and the association of derived factors to HIV serostatus. Two sets of data were randomly selected and matched from a national data set of over 40,000 drug injectors. One set was HIV seropositive and the other HIV seronegative heterosexual injectors. Samples were matched to control for the effects of race/ethnicity, gender, and age on serostatus. Factor analysis was used to investigate relationships among drug injection behaviors. Four independent factors were found. Two factors were found to be statistically related to HIV serostatus in high seroprevalence areas. None of the needle use factors was found to be significantly associated with serostatus in low seroprevalence areas.

Adult↗
PubMed1993

Simulation of stochastic micropopulation models--I. The SUMMERS simulation shell.

A generic, abstract model and the simulation shell based on it, both called SUMMERS, are used as a framework for the implementation of stochastic micropopulation models; in these, each individual is followed separately while moving through a sequence of states. The shell supports groups of interacting members, individual characteristics and multiple simultaneous activities. Stochastic decisions may be made using Monte Carlo rules. Keywords control the simulations and the reports generated. A sensitivity analysis utility allows assessment of the dependency of outcomes on model features. Extensive use has been made of software engineering techniques. Specializations of SUMMERS are described in subsequent papers.

Data Collection↗
PubMed1993

Simulation of stochastic micropopulation models--II. VESPERS: epidemiological model implementations for spread of viral infections.

This second paper concerning stochastic micropopulation simulations describes VESPERS, which can serve as a framework for simulation models of the epidemic spread of infection. The versions described are implemented using the simulation shell, SUMMERS, which includes the generic commonalities of several micropopulation models. Population members in VESPERS move through states related to the individual's status relative to the infective agent. Features of the models include mixing groups, member demographics, susceptibility and infectiousness, and co-circulation of infectious agents. The sensitivity of the simulation outcomes to quantitative features of the model has been analyzed. The user can select reports of desired distributions and averages of simulation outcomes.

Demography↗
PubMed1993

Simulation of stochastic micropopulation models--III. COGNET: an artificial neural network for visual recognition.

COGNET, based on a neural network first described by Fukushima, demonstrates the relationship between connectionist and other micropopulation models. Its success and physiological orientation led to an implementation using the SUMMERS simulation shell. After self-supervised learning, COGNET uses forward and backward propagation of signals to recognize partial and noisy patterns, and to reconstruct the originals. Stochastic features include variable thresholds for neuronal firing and occasional cell death. The successful implementation of COGNET demonstrates the generality of the concepts embodied in SUMMERS, which in turn promotes the reusability of software and facilitates the extension of computational models in biomedical research. COGNET itself forms a framework for building other physiologically oriented neural network models.

Computer Simulation↗
PubMed1993

Dynamic investigation on chromosome aberration of a human retinoblastoma cell line So-Rb50.

G-banding and karyotype analyses of cells in seventeen passages of SO-Rb50 during a long period of culture for about four years were performed. Three chromosome markers 13q14-, 1p36+ and 12p13+ were found. Cells possessed 13q14- reduced to zero after the 200th passage while 1p+ and 12p+ cells increased to 100% after 30 and 200 passages respectively. Abnormal chromosomes, ring chromosomes, chromosome radiuses and double minutes were also observed. These chromosomal changes were more often seen before the 200th passage. The significance of these changes are discussed.

Chromosome Aberrations↗
PubMed1992

Biological activities of polyethylene-glycol immunoglobulin conjugates. Resistance to enzymatic degradation.

Serum IgG has been covalently bonded to polyethylene glycols of either 2000 or 8000 molecular weight to produce immunoglobulin conjugates with 4.4-27.2% of primary amines bonded to polyethylene glycol. Polyethylene glycol immunoglobulin conjugates retain the ability, comparable to native IgG, to bind to a range of protein and microbial antigens, but have a reduced ability to bind to Fc receptors or to fix complement C3. When 6.8% or more of available primary amines are conjugated, IgG-PEG conjugates are impervious to trypsin, and at 14% or more conjugation, more resistant than native IgG to pepsin and chymotrypsin. We suggest that PEG-Ig conjugates may be useful for the oral treatment of various gastrointestinal diseases in which secretory humoral immunity is insufficient.

Antigens, Protozoan↗
PubMed1988

Metabolism of 2-acetylaminofluorene in the Chinese hamster ovary cell mutation assay.

Chinese hamster ovary (CHO) cells were exposed to 2-acetylaminofluorene (2-AAF) and 2-aminofluorene (2-AF), and several of their N-oxidized metabolites in order to study the mechanisms by which arylamides and arylamines produce mutations in mammalian cells. The number of mutations induced at the hypoxanthine-guanine phosphoribosyl transferase locus by each compound (mutants/10(6) CHO cells/nmol compound/ml) was estimated to be: N-acetoxy-2-AAF, 310; N-hydroxy-2-AF, 3; N-hydroxy-2-AAF (with and without hepatic S9 activation), 0.7; 2-AAF (with S9), 0.1; and 2-AF (with S9), 0.09. With each compound, DNA adducts were also identified and quantified, and in all cases the major adduct was N-(deoxyguanosin-8-yl)-2-AF. 2-AAF and N-hydroxy-2-AAF also formed minor amounts of N-(deoxyguanosin-8-yl)-2-AAF and 3-(deoxyguanosin-N2-yl)-2-AAF. The relationship between mutation induction and adduct formation for each of the derivatives was similar to that previously reported for N-hydroxy-2-AF. Inclusion of the deacetylase inhibitor, paraoxon, reduced the mutagenicity of 2-AAF, N-hydroxy-2-AAF and N-acetoxy-2-AAF, and the DNA adducts produced by N-acetoxy-2-AAF to background levels. Acetyl coenzyme A increased the mutations and CHO cytosol-mediated DNA binding of N-hydroxy-2-AAF, but did not substantially increase these responses from N-hydroxy-2-AF. N-Hydroxy-2-AAF was not detectably metabolized by CHO cells. Taken together, these data indicate that CHO cells metabolized N-acetoxy-2-AAF to a reactive derivative by N-deacetylation to N-acetoxy-2-AF, while N-hydroxy-2-AF reacted directly with DNA. The major pathway of N-hydroxy-2-AAF activation appeared to be an initial O-acetylation to N-acetoxy-2-AAF and this occurred to only a limited extent in the CHO cells. N-Hydroxy-2-AAF also seemed to form an additional unknown ester intermediate that gave rise to acetylated DNA adducts. The initial step in the activation of 2-AAF and 2-AF was an N-oxidation to N-hydroxy-2-AAF and N-hydroxy-2-AF, respectively. The limited O-acetylase activity in CHO cells appeared to contribute to the low sensitivity of these cells toward mutation induction by arylamines and arylamides.

2-Acetylaminofluorene↗
PubMed1986

Use of the human liver cell line Hep G2 in a modified Salmonella reversion assay.

The human hepatoma cell line Hep G2 was used to activate promutagenic chemicals to mutagens in a modified Salmonella typhimurium reversion assay. Hep G2 cells mediated positive mutagenic responses in tester strain TA98 with 5 and 25 micrograms/plate of 2-aminofluorene, but these responses were consistently lower than those seen using primary rat hepatocytes. In addition, 3 and 6 X 10(6) Hep G2 cells per assay produced positive mutagenic responses with 2-aminoanthracene, benzidine, acetylbenzidine and aflatoxin B1, while benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, 4-aminobiphenyl and 4- and 11-aminobenzo[a]pyrene were nonmutagenic with Hep G2-cell activation. These results indicate that Hep G2 cells may be a useful intact cellular metabolizing system of human origin for predicting the genotoxicity of promutagenic agents, but that the use of Salmonella as a target cell may limit the classes of mutagens detected.

Biotransformation↗
PubMedDate not supplied

Polychotomous multivariate models for coronary heart disease simulation. IV. The impact of physiological aging.

This is an extension of a series of papers dealing with certain models used in the simulation of coronary heart disease. The current study investigates implications of including age as a risk factor in the models discussed in the preceding papers. The effects of using age as a risk factor were investigated in two ways. In one of these, age is interpreted as age of entry into the study; it is similar to the other risk factors in that it is assumed to be constant throughout the study. In the other, age is interpreted as the actual age; thus it increases during the course of simulations. Two polychotomous, multivariate risk functions developed in previous studies, the logistic risk and the Neyman exponential risk, were used to explore the effects of including age as a risk factor. The estimated risk coefficient for age was found to be statistically significant for both functions. The model performance was evaluated by comparing the observational data with outcomes simulated using Monte Carlo techniques. It was found that the logistic risk function failed to describe the observations either with age as a constant or with aging during the simulations. The models including the Neyman exponential risk avoidance fit the data well. The evaluation of the results indicates that aging during the simulations is better than using only the age as the constant value at entry to the study.

Adult↗