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Biomedical subjects

Z Chen

Publications and source records attributed to Z Chen.

At least 91 records · Page 5Linked to original sources
PubMed2003

Sleep-deprived mice show altered cytokine production manifest by perturbations in serum IL-1ra, TNFa, and IL-6 levels.

Serum cytokine and chemokine levels were examined in mice following 36 h of sleep deprivation, or after exposure to a known physical stressor (rotational stress). Significant changes in inflammatory cytokines/chemokines (IL-1beta, TNFalpha, IL-1ra, IL-6, and MIP-1beta, MCP-1) were observed following each manipulation, but qualitative and quantitative differences were seen. Interestingly, only physical stress was associated with measured increases in serum corticosterone levels, and with independent evidence (using in vitro immune allostimulation) for a generalized immunosuppression secondary to the experimental manipulation. Our data suggest that altered cytokine production following sleep perturbation occurs by a different mechanism from that (HPA axis) commonly attributed to stress per se.

Acebutolol↗
PubMed2003

Characterization of adenovirus p21 gene transfer, biodistribution, and immune response after local ocular delivery in New Zealand white rabbits.

Previous studies suggest that local gene therapy with rAd-p21(WAF1/Cip-1) [. Arch. Ophthalmol. 120, (2002) 941-949] may provide an effective adjunctive anti-proliferative treatment to prevent glaucoma surgery failure. To further investigate rAd-p21 in this indication, we have characterized several parameters of local gene delivery to conjunctiva including, vector delivery and transgene expression in target tissue, inflammatory response, biodistribution to non-target tissues, and immune response. Quantitative PCR and RT-PCR assays were employed to evaluate rAd-p21 dissemination and gene transfer following a single subconjunctival injection. In target tissue, significant levels of rAd-p21 DNA were found in 6/6 animals 1 and 4 days after injection. rAd-p21 DNA and RNA could be detected in the un-injected contralateral eye but at levels that were 10000-100000 lower than in the injected eye. Expression of human p21 transgene in conjunctival fibroblasts was confirmed by immunohistochemistry. Biodistribution of rAd-p21 following subconjunctival injection was substantially limited to ocular tissue. In 1/6 rabbits, rAd-p21 DNA was found in whole blood, liver, and spleen at levels that were barely detectable. All non-target organs were negative on day 4. In contrast, in a rabbit injected intravenously as a positive control, all blood samples and tissues samples were positive. rAd-p21 delivery to conjunctiva followed by filtration surgery caused an early acute inflammatory response, which by day 14 was indistinguishable from placebo-treated eyes. Neutralizing anti-adenovirus antibodies were detected following administration of rAd-p21 to conjunctiva, however, vector delivery and transgene expression were unaffected in a subsequent administration to the contralateral eye in the same animal. These results show that local delivery to conjunctiva may be a suitable delivery mode for ocular gene therapy.

Adenoviridae↗
PubMed2003

Nociceptin/orphanin FQ knockout mice display up-regulation of the opioid receptor-like 1 receptor and alterations in opioid receptor expression in the brain.

The opioid receptor-like 1 receptor is a novel member of the opioid receptor family and its endogenous peptide ligand has been termed nociceptin and orphanin FQ. Activation of the opioid receptor-like 1 receptor by nociceptin/orphanin FQ in vivo produces hyperalgesia when this peptide is given supraspinally but analgesia at the spinal level. Nociceptin/orphanin FQ also reverses stress-induced analgesia, suggesting that the peptide has anti-opioid properties. Nociceptin/orphanin FQ knockout mice show alterations in pain sensitivity and stress responses and display increased morphine dependence, suggesting an interaction of the nociceptin/orphanin FQ system with classical opioid receptor function. To determine if the behavioural phenotype of nociceptin/orphanin FQ knockout mice reflects changes in either opioid receptor-like 1 or classical opioid receptor expression, we have carried out quantitative autoradiography of the opioid receptor-like 1, mu-, delta- and kappa-opioid receptors in the brains of these animals. Receptor density was measured on coronal sections from wild-type, heterozygous and homozygous mice using [(3)H]nociceptin, [(3)H][D-Ala(2)-N-methyl-Phe(4)-Gly(5) ol] enkephalin, [(3)H]deltorphin-I, or [(3)H](-)-N-methyl-N-[7-(1-pyrrodinyl)-1-oxospiro[4,5]dec-8-yl]-4-benzofuranacetamide to label opioid receptor-like 1, mu-, delta- and kappa-receptors, respectively. A region-specific up-regulation of the opioid receptor-like 1 receptor (up to 135%) was seen in brains from homozygous mice. Mu-Receptors also showed significant differences between genotypes whilst changes in delta- and kappa- receptors were minor. In conclusion the region-specific up-regulation of the opioid receptor-like 1 receptor indicates a tonic role for nociceptin/orphanin FQ in some brain structures and may suggest the peptide regulates the receptor expression in these regions. The changes in the opioid receptor-like 1 receptor may relate to the anxiogenic phenotype of these animals but the observed change in mu-receptors does not correlate with altered morphine responses.

Animals↗
PubMed2003

Socioeconomic status & returning for a second screen in the Ontario breast screening program.

In a retrospective cohort study involving 57902 women initially screened between January 1, 1995 and December 31 1997 by the Ontario Breast Screening Program (OBSP), we examined the relationship between geographically derived socioeconomic status (SES) and returning for a second screen. We controlled for age, rurality, preferred language, initial mammography results, previous mammography history, and referral by a health professional. Although SES was related to returning, rurality was an effect modifier of this relationship, a finding not previously reported. Compared to women in the highest ('richest') quintile, urban women in the first and second quintile were less likely to return; this relationship was not found in rural women. Low SES women, particularly in urban areas, should be specifically targeted to increase their likelihood of re-attendance for breast cancer screening within an organized program.

Aged↗
PubMed2003

Fourier-transform Raman and infrared spectroscopic analysis of 2-nitro-tetraphenylporphyrin and metallo-2-nitro-tetraphenylporphyrins.

The Fourier-transform Raman (FT-Raman) and infrared (FT-IR) spectra of 2-nitro-tetraphenylporphyrin (2-NO(2)-TPP), nickel-2-nitro-tetraphenylporphyrin (Ni-2-NO(2)-TPP), zinc-2-nitro-tetraphenylporphyrin (Zn-2-NO(2)-TPP) and copper-2-nitro-tetraphenylporphyrin (Cu-2-NO(2)-TPP) were acquired for the first time and carefully assigned and discussed. The effects of a beta-NO(2) group and the influence of the central metal on the molecular symmetry and vibrational spectra of the porphyrin macrocycle were also examined. The bands at 1323-1339, 1516-1526 and 961-971 cm(-1) were attributed to the symmetric and asymmetric stretching vibration of the NO(2) group and to the stretching vibration of the C(beta)-N bond, respectively, which connects the NO(2) group with the beta-carbon of the porphyrin macrocycle. These bands can act as a marker to distinguish beta-NO(2) TPPs from other beta-substituent TPPs. Cu-2-NO(2)-TPP has a C(4nu) molecular symmetry, which is different from those of Ni-2-NO(2)-TPP and Zn-2-NO(2)-TPP, i.e. D(4h).

Organometallic Compounds↗
PubMed2003

Efficient and long-term intracardiac gene transfer in delta-sarcoglycan-deficiency hamster by adeno-associated virus-2 vectors.

Intracardiac gene transfer and gene therapy have been investigated with different vector systems. Here we used adeno-associated virus (AAV) vectors to deliver either a reporter gene or a therapeutic gene into the heart of golden Syrian hamsters. The method of gene delivery was direct infusion of the AAV2 vectors into the coronary artery ex vivo in a heterotopically transplanted heart. When an AAV2 vector carrying the Lac-Z gene driven by CMV promoter was delivered into the heart of healthy hamsters, effective gene transfer was achieved in up to 90% of the cardiomyocytes. Lac-Z gene expression persisted for more than 1 year without immune rejection or promoter shutoff. Furthermore, when an AAV2 vector carrying human delta-sarcoglycan gene was similarly delivered into the heart of Bio14.6 Syrian hamster, a congestive heart failure and limb girdle muscular dystrophy animal model, widespread therapeutic gene transfer was achieved in a majority of the cardiomyocytes. Efficient expression of the human delta-sarcoglycan gene in the dystrophic hamster hearts restored the entire sarcoglycan complex that was missing due to the primary deficiency of delta-sarcoglycan. Transgene expression persisted for 4 months (the duration of the study) without immune rejection or promoter shutoff. These results indicate that AAV is a promising vector system for cardiac gene therapy.

Animals↗
PubMed2003

The Great Wall of China: a physical barrier to gene flow?

One population from each of six plant species along both sides of the Juyong-guan Great Wall, together with one population from each of five species along both sides of a path on a mountain top near Juyong-guan, were selected to study the effect of the Great Wall as a barrier on genetic differentiation between two subpopulations using RAPD markers. Significant genetic differentiation was found between the subpopulations on both sides of the Great Wall. A wind-pollinated woody species, Ulmus pumila, showed less genetic differentiation than four insect-pollinated species: Prunus armeniaca, Ziziphus jujuba, Vitex negundo, and Heteropappus hispidus. Cleistogenes caespitosa, a wind-pollinated perennial herb, displayed more genetic differentiation between subpopulations than the insect-pollinated species because of its propagation strategy. Although AMOVA analysis showed that subpopulations divided by a mountain path had diverged genetically, the variance component between the subpopulations on both sides of the Great Wall was significantly larger than that between the subpopulations at the control site. Therefore, it is reasonable to deduce that the Juyong-guan Great Wall has served as a physical barrier to gene flow between subpopulations separated for more than 600 years.

Biological Evolution↗
PubMed2003

Arsenic trioxide-induced mitotic arrest and apoptosis in acute promyelocytic leukemia cells.

Arsenic trioxide (As(2)O(3)), an effective drug for the treatment of acute promyelocytic leukemia (APL), can induce apoptosis and partial differentiation in APL cells in vitro and in vivo. However, As(2)O(3) also induces apoptosis in cancer cells other than APL with complex mechanisms, which seem to be cell type dependent. In this study, we report that APL cells (NB4 cell line) are arrested at early mitotic phase before the collapse of mitochondrial transmembrane potential (Deltavarphi(m)) and apoptosis after treatment with pharmacological concentrations (1.0-2.0 micro M) of As(2)O(3). We have also made the following new discoveries: (1) 0.5 micro M As(2)O(3) that fails to induce apoptosis has no effects on cell cycle distribution. (2) With inhibition of As(2)O(3)-induced Deltavarphi(m) collapse and apoptosis, dithiothreitol also effectively inhibits As(2)O(3)-induced mitotic arrest, suggesting that both As(2)O(3)-induced apoptosis and mitotic arrest involve proteins with thiol groups. (3) 1.5 mM caffeine that relieves cells from G(2)/M arrest also inhibits As(2)O(3)-induced Deltavarphi(m) collapse and apoptosis, (4) 1.0 micro M As(2)O(3) increases the expression of both cyclin B(1) and hCDC20 whereas it inhibits Tyr15 phosphorylation of p34(cdc2). In conclusion, our results strongly support that there is a tight link between As(2)O(3)-induced apoptosis and mitotic arrest, the latter being one of common mechanisms for As(2)O(3)-induced apoptosis in cancer cells.

Antineoplastic Agents↗
PubMed2003

Major form of NUP98/HOXC11 fusion in adult AML with t(11;12)(p15;q13) translocation exhibits aberrant trans-regulatory activity.

Three adult patients with de novo acute myeloid leukemia of distinct subtypes harboring t(11;12)(p15;q13) have been investigated to characterize the genes involved in that translocation. Through molecular cytogenetics, a chromosome break was detected at the 3' part of nucleoporin 98 (NUP98) gene at 11p15. Using rapid amplification of cDNA end, we identified the partner gene at 12q13, HOXC11. Molecular analysis showed that exon 12 of NUP98 was fused in-frame to exon 2 of HOXC11 in all three cases with t(11;12)(p15;q13). Therefore, this type of fusion may represent the major form of the NUP98-HOXC11 chimera so far reported. Moreover, two out of three cases had a confirmed deletion of the 3' part of NUP98 gene and more telomeric region of 11p harboring a group of tumor-suppressor genes. Interestingly, the NUP98-HOXC11 protein when assayed in a GAL4 reporter system, showed an aberrant trans-regulatory activity as compared to the wild-type HOXC11 in both COS-7 and HL-60 cells. Therefore, NUP98-HOXC11 may contribute to the leukemogenesis by interfering with the cellular mechanism of transcriptional regulation.

Adult↗
PubMed2003

Cobalt chloride and low oxygen tension trigger differentiation of acute myeloid leukemic cells: possible mediation of hypoxia-inducible factor-1alpha.

Cellular and systemic O(2) concentrations are tightly regulated to maintain delicate oxygen homeostasis. Although the roles of hypoxia in solid tumors have been widely studied, few studies were reported regarding the possible effects of hypoxia on leukemic cells. Here, we showed for the first time that low concentrations of cobalt chloride (CoCl(2)), a hypoxia-mimicking agent, and 2-3% O(2) triggered differentiation of various subtypes of human acute myeloid leukemic (AML) cell lines, including NB4, U937 and Kasumi-1 cells, respectively, from M3, M5 and M2b-type AML, but CoCl(2) did not modulate AML subtype-specific fusion proteins promyelocytic leukemia-retinoic acid receptor alpha (PML-RARalpha) and AML1-ETO. Treatment with CoCl(2) also induced primary leukemic cells from some AML patients to undergo differentiation. Similar to what occurs in solid tumor cells, CoCl(2)-mimicked hypoxia also increased the level of hypoxia-inducible factor (HIF)-1alpha protein and its DNA-binding activity in leukemic cells. The CoCl(2) induction of HIF-1alpha protein and its DNA-binding activity were inhibited by 3-morpholinosydnonimine, which also blocked CoCl(2)-induced cell differentiation in leukemic cells. These results provide an insight into a possible link of hypoxia or HIF-1alpha and leukemic cell differentiation, and are possibly of significance to explore clinical potentials of hypoxia or hypoxia-mimicking agents and novel target-based drugs for differentiation therapy of leukemia.

Antigens, CD↗
PubMed2003

Tests for candidate-gene association using case-parents design.

In the case-parents design for testing candidate-gene association, the conditional likelihood method based on genotype relative risks has been developed recently. A specific relation of the genotype relative risks is referred to as a genetic model. The efficient score tests have been used when the genetic model is correctly specified under the alternative hypothesis. In practice, however, it is usually not able to specify the genetic model correctly. In the latter situation, tests such as the likelihood ratio test (LRT) and the MAX3 (the maximum of the three score statistics for dominant, additive, and recessive models) have been used. In this paper, we consider the restricted likelihood ratio test (RLRT). For a specific genetic model, simulation results demonstrate that RLRT is asymptotically equivalent to the score test, and both are more powerful than the LRT. When the genetic model cannot be correctly specified, the simulation results show that RLRT is most robust and powerful in the situations we studied. MAX3 is the next most robust and powerful test. The TDT is the easiest statistic to compute, compared to MAX3 and RLRT. When the recessive model can be eliminated, it is also as robust and powerful as RLRT for other genetic models.

Computer Simulation↗
PubMed2003

Lack of an association between environmental exposure to polychlorinated biphenyls and p,p'-DDE and DNA damage in human sperm measured using the neutral comet assay.

BACKGROUND: Chlorinated organic chemicals, such as polychlorinated biphenyls (PCB), hexachlorobenzene (HCB), dichlorodiphenyl trichloroethane (DDT), and dichlorodiphenyl dichloroethene (DDE, the most stable daughter compound of DDT) are persistent lipophilic compounds found in a large portion of the general population. To explore the hypothesis that environmental exposure to these compounds is associated with altered DNA integrity in human sperm, a study of 212 male partners of a sub-fertile couple who presented to the Massachusetts General Hospital Andrology Laboratory was conducted. METHODS: The neutral single cell microgel electrophoresis assay (comet assay) was used to assess DNA integrity in sperm. VisComet image analysis software was used to measure total comet length, the proportion of DNA present in the comet tail, and tail distributed moment, an integrated measure of length and intensity. RESULTS: In the regression analyses, there were no statistically significant consistent associations between the comet assay parameters and any of the individual PCB congeners, sum of PCB, or p,p'-DDE. CONCLUSION: These results suggest that there are not strong relationships between adult levels of these chlorinated organic compounds and sperm DNA damage as measured by the comet assay.

Adult↗
PubMed2003

A GIS-based modeling system for petroleum waste management. Geographical information system.

With an urgent need for effective management of petroleum-contaminated sites, a GIS-aided simulation (GISSIM) system is presented in this study. The GISSIM contains two components: an advanced 3D numerical model and a geographical information system (GIS), which are integrated within a general framework. The modeling component undertakes simulation for the fate of contaminants in subsurface unsaturated and saturated zones. The GIS component is used in three areas throughout the system development and implementation process: (i) managing spatial and non-spatial databases; (ii) linking inputs, model, and outputs; and (iii) providing an interface between the GISSIM and its users. The developed system is applied to a North American case study. Concentrations of benzene, toluene, and xylenes in groundwater under a petroleum-contaminated site are dynamically simulated. Reasonable outputs have been obtained and presented graphically. They provide quantitative and scientific bases for further assessment of site-contamination impacts and risks, as well as decisions on practical remediation actions.

Decision Support Techniques↗
PubMed2002

A CD200FC immunoadhesin prolongs rat islet xenograft survival in mice.

BACKGROUND: A solubilized form of the CD200 molecule, CD200Fc, has been shown to suppress allograft rejection and development of collagen-induced arthritis in mice. We investigated whether the same molecule could prolong survival of rat islet xenografts. METHODS: Streptozocin-treated mice, receiving injections with anti-asialo-GM1 antibody, received rat islets ( approximately 400/mouse) under the kidney capsule or injected into the portal vein, along with rapamycin treatment. Thereafter mice received injections of CD200Fc (10 microg/mouse/injection) or control mouse IgG2. Blood glucose was monitored daily. Some mice received additional injections of anti-CD200/-CD200R monoclonal antibodies. RESULTS: Portal vein delivery of islets led to more extended resolution of diabetes than did transplantation under the kidney capsule. CD200Fc further prolonged survival in either case, an effect abolished by anti-CD200 or F(ab')2 anti-CD200R mAbs, but not by whole anti-CD200R (anti-CD200R Ig). Spleen cells taken from CD200Fc-treated mice showed polarization to type-2 cytokine production (interleukin-4, interleukin-10) on restimulation with rat splenocytes in culture, in comparison to cells from control mice (type-1 cytokines, interlulin-2, interferon-gamma). CONCLUSION: CD200:CD200R interactions are important in regulating rat islet xenograft survival.

Animals↗
PubMed2002

Obesity, body size, and risk of postmenopausal breast cancer: the Women's Health Initiative (United States).

OBJECTIVE: Body size is an important modifiable risk factor for breast cancer. Although obesity has generally been found to be associated with increased risk for postmenopausal breast cancer, there remain questions concerning the role of body fat distribution, lifetime weight history, and effects within specific subgroups of women. METHODS: We assessed the relationship of several anthropometric measures and risk of postmenopausal breast cancer in 85,917 women aged 50-79 at entry in the Women's Health Initiative Observational Study. Women were enrolled during 1993-1998 at 40 clinics in the US and 1030 developed invasive breast cancer by April 2000. Upon entry, trained clinical center staff measured each woman's height, weight, and waist and hip circumference. RESULTS: Anthropometric factors were not associated with breast cancer among women who had ever used hormone replacement therapy (HRT). Among HRT non-users, heavier women (baseline body mass index (BMI) >31.1) had an elevated risk of postmenopausal breast cancer (relative risk (RR) = 2.52; 95% confidence interval (CI) = 1.62-3.93), compared to slimmer women (baseline BMI < 22.6). The elevation in risk associated with increasing BMI appeared to be most pronounced among younger postmenopausal women. Change in BMI since age 18, maximum BMI, and weight were also associated with breast cancer in HRT non-users. While both waist and hip circumference were associated with breast cancer risk, their ratio, a measure of fat distribution, was not (RR = 1.33; 95% CI = 0.88-2.01). CONCLUSIONS: Our study confirms previously reported findings that generalized obesity is an important risk factor for postmenopausal breast cancer, but only among women who have never taken HRT. Lifetime weight gain is also a strong predictor of breast cancer. Waist to hip ratio, a measure of weight distribution, does not appear to be related to postmenopausal breast cancer risk.

Aged↗
PubMed2002

Modification of hepatic genomic DNA using RNA/DNA oligonucleotides.

The ideal gene therapy is one that repairs the precise genetic defect without additional modification of the genome. Such a strategy has been developed for correcting single nucleotide mutations by using RNA/DNA oligonucleotides, or chimeraplasts. This approach for in situ repair is based on the delivery of exogenous DNA designed to mediate genomic base conversion, insertion, or deletion, thereby, correcting the genetic mutation. Using in vivo delivery systems to hepatocytes via the asialoglycoprotein receptor, we targeted rat liver DNA and successfully modified the genomic sequence by chimeraplasty. The changes in both the hepatic genes, and their associated phenotypes remained stable for 2 years. In addition, we also examined the potential to alter sequence defects in mitochondrial DNA. Therefore, we determined whether mitochondria possess the enzymatic machinery for chimeraplast-mediated DNA changes. Using an in vitro DNA repair assay of mutagenized plasmids and an Escherichia coli readout system, we showed that extracts from highly purified rat liver mitochondria have the essential enzymatic activity to mediate precise single-nucleotide changes at a frequency similar to liver nuclear extracts. Moreover, single-stranded oligonucleotides carrying a single nucleotide mismatch with the target sequence were capable of promoting gene conversion using either mitochondrial or nuclear extracts. Several approaches now exist for the precise repair of genetic mutations using either single-stranded or RNA/DNA chimeric oligonucleotides.

Animals↗