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Z Q Wang

Publications and source records attributed to Z Q Wang.

At least 19 recordsLinked to original sources
PubMed2006

Poly(ADP-ribose) polymerase-1 plays a role in suppressing mammary tumourigenesis in mice.

The DNA strand break-binding molecule, poly(ADP-ribose) polymerase-1 (PARP-1), plays a role in DNA repair, chromosomal stability, transcription and cell death. Accumulating evidence suggests that dysfunction of PARP-1 contributes to tumorigenesis. Here, we report that PARP-1 deficiency causes mammary carcinoma formation in female mice, and that the introduction of Trp53 mutations accelerates the onset and shortens the latency of mammary tumorigenesis. We show that PARP-1 deficiency results in chromosomal aneuploidy and centrosome amplification, which are substantiated by the inactivation of Trp53 in primary mammary epithelial (PME) cells. In addition, PARP-1 deficiency compromises p53 activation and impairs BRCA1 recruitment to the sites of DNA damage in PME cells. PARP-1 complementation partly rescues the defective DNA damage response mediated by p53 and BRCA1. The present study thus identifies a role of PARP-1 in suppressing mammary tumorigenesis in vivo and suggests that dysfunction of PARP-1 may be a risk factor for breast cancer in humans.

Animals↗
PubMed2006

Kink formation and motion in carbon nanotubes at high temperatures.

We report that kink motion is a universal plastic deformation mode in all carbon nanotubes when being tensile loaded at high temperatures. The kink motion, observed inside a high-resolution transmission electron microscope, is reminiscent of dislocation motion in crystalline materials: namely, it dissociates and multiplies. The kinks are nucleated from vacancy creation and aggregation, and propagate in either a longitudinal or a spiral path along the nanotube walls. The kink motion is related to dislocation glide and climb influenced by external stress and high temperatures in carbon nanotubes.

Journal Article↗
PubMed2006

Superplastic carbon nanotubes.

The theoretical maximum tensile strain--that is, elongation--of a single-walled carbon nanotube is almost 20%, but in practice only 6% is achieved. Here we show that, at high temperatures, individual single-walled carbon nanotubes can undergo superplastic deformation, becoming nearly 280% longer and 15 times narrower before breaking. This superplastic deformation is the result of the nucleation and motion of kinks in the structure, and could prove useful in helping to strengthen and toughen ceramics and other nanocomposites at high temperatures.

Journal Article↗
PubMed2006

The epidemiology of human trichinellosis in China during 2000-2003.

The endemic foci of trichinellosis continue to be mainly located in the southwestern, the central and northeastern China. The seroepidemiological surveys of T. spiralis infection in humans were carried out in six Provinces or Municipals (P/M) of China during 2000-2003, the overall seroprevalence was 3.57%. From 2000 to 2003, 17 outbreaks of human trichinellosis, with 828 cases and 11 deaths, were recorded in 8 P/A of China. All of 11 deaths occurred in the southwestern China (1 case in Sichuan, 4 cases in Tibet and 6 cases in Yunnan), where the ethnic groups have the habit of eating raw meat. Pork is the predominant source of outbreaks of human trichinellosis in China. Out of 17 outbreaks, 13 (76.47%) outbreaks were caused by eating raw or poorly cooked pork, 2 (11.77%) outbreaks caused by eating raw dog meat and 2 (11.77%) outbreaks by eating game meat (wild boar and bear), suggesting the increasing significance of dog and game meat as source of infection for human trichinellosis. The partial effects of health education interventions for control of trichinellosis have been achieved in some counties of Yunnan province. The number of inhabitants eating raw meat has decreased from 72.74% (1561/2146) before interventions to 47.43% (489/1031) after interventions. The decrease of incidence of trichinellosis in China during the past 4 years was probably due to a combination of factors, including the reduction in the prevalence of Trichinella infection in domestic swine, the strengthened meat inspection, the increased use of home freezers and the development of heath education practice.

Animals↗
PubMed2005

Vaccination of mice with DNA vaccine induces the immune response and partial protection against T. spiralis infection.

Trichinellosis is a serious parasitic zoonosis which is widely distributed in the world. Pork still is the predominant source of outbreaks of human trichinellosis in many countries. Vaccines are urgently needed to prevent swine from Trichinella infection. The gene (TspE1) encoding a 31 kDa antigen of T. spiralis was cloned to a eukaryotic expression plasmid pcDNA3 as DNA vaccine. The ability of the DNA vaccine to express antigen in mammalian CHO cells was previously confirmed by indirect fluorescencent antibody test (IFAT) and Western blotting. To evaluate its immunogenicity and its host protective potential, BALB/c mice were immunized with the DNA vaccine by intramuscular injection and gene-gun delivery. The serum antibody response was assayed by IFAT, enzyme linked immunosorbant assay (ELISA) and Western blotting. The cellular immune response was investigated by splenocyte proliferation assay. Vaccine administration by either route induced both humoral and cellular immune response against TspE1, which provided the partial protection against challenge infection with T. spiralis, as shown by significant reduction of larval burden in muscles. Thus, DNA immunization may offer an attractive alternative strategy against swine trichinellosis.

Animals↗
PubMed2005

The epidemiology of animal trichinellosis in China.

The epidemiology of animal trichinellosis in China based mainly upon original Chinese literature published between 1937 and 2004 is reviewed. The seroprevalence of Trichinella infection in herbivores was 0.7% (2/300) in cattle and 0.8% (4/500) in sheep. The prevalence of trichinellosis in naturally infected cattle was 1.2% (2/163). Trichinella larvae were detected in 1.4% (3/215) of sheep and in 2.1% (1/47) of beef cattle sold at markets. Canine trichinellosis was recorded in 13 Provinces, Autonomous Regions or Municipalities (P/A/M) and the average prevalence of the infection in dogs slaughtered in abattoirs was 16.2% (5654/34,983) ranging from 1.2% to 44.8%, with the highest prevalence located in northeast China. The prevalence in dog meat sold at markets was 3.5% (988/27,898) in 5 P/A. Feline Trichinella infection was reported in 10 P/A/M. The prevalence of Trichinella infection in rats varied from 1.1% (51/459) to 15.1% (50/332). Trichinella larvae were detected in 1.5% (9/587) of house rats (Rattus norvegicus) as well as in 0.8% (3/369) of wild rats (Apodemus chevrieri), and the infection was recorded also in other wildlife (foxes, bears, wild boar, weasels, raccoon dogs, muntjak and bamboo rats). Trichinella larvae were detected in 2.6% (4/156) of weasels (Mustela sibirica), 1.5% (2/135) of shrews (Tupaia belangeri) and 7.7% (1/13) of moles (Parascapter leucurus). All Trichinella isolates from domestic pigs were identified as T. spiralis. Some Trichinella isolates from dogs in north-eastern China were identified as T. nativa, which has muscle larvae that are highly resistant to freezing. Twenty-seven outbreaks of human trichinellosis associated with mutton, dog and game meat occurred in China between 1964 and 2004, but the quarantine of Trichinella larvae in such meat is not mandatory in China at present.

Animals↗
PubMed2004

Effects of insulin sensitizers on plaque vulnerability associated with elevated lipid content in atheroma in ApoE-knockout mice.

Acute coronary syndromes are generally precipitated by rupture of lipid-laden, relatively acellular, vulnerable atherosclerotic plaques with thin fibrous caps. We investigated whether a high-fat diet alters insulin sensitivity and whether insulin sensitizers (troglitazone and rosiglitazone) alter the composition of otherwise lipidladen atherosclerotic plaques in mice deficient in apolipoprotein E (ApoE). ApoE-knockout mice were fed a high-fat (n=30) or standard chow (n=10) diet for two weeks. Thereafter, those fed the high-fat diet were treated with troglitazone (n=10), rosiglitazone (n=10) or no drug (n=10) for 16 weeks beginning at 8 weeks of age. Carbohydrate metabolism was assessed with intraperitoneal glucose tolerance tests and insulin tolerance tests. Plaque composition was characterised with confocal laser scanning microscopy. The high-fat diet induced insulin resistance in the absence of weight gain. Compared with control animals on the high-fat diet, animals given troglitazone (400 mg/kg/day) or rosiglitazone (4 mg/kg/day) had significantly less area under the curve (AUC) for insulin ( p<0.05) and glucose disposal ( p<0.05). Despite significant increases in insulin sensitivity with drug treatment, no change in HDL-cholesterol and triglyceride levels, nor reduction in atheroma size or lipid content was noted. Thus, improvement in insulin resistance induced by a high-fat diet in this animal model of vasculopathy did not alter plaque composition.

Animals↗
PubMed2004

The prevalence and spectrum of alpha and beta thalassaemia in Guangdong Province: implications for the future health burden and population screening.

AIM: Thalassaemia is a good candidate disease for control by preventive genetic programmes in developing countries. Accurate population frequency data are needed for planning the control of thalassaemia in the high risk Guangdong Province of southern China. METHODS: In total, 13397 consecutive samples from five geographical areas of Guangdong Province were analysed for both haematological and molecular parameters. RESULTS: There was a high prevalence of carriers of alpha thalassaemia (8.53%), beta thalassaemia (2.54%), and both alpha and beta thalassaemia (0.26%). Overall, 11.07% of the population in this area were heterozygous carriers of alpha and beta thalassaemia. The mutation spectrum of alpha and beta thalassaemia and its constitution were fully described in this area. This study reports the true prevalence of silent alpha thalassaemia in the southern China population for the first time. In addition, two novel mutations that give rise to alpha thalassaemia, one deletion resulting in beta thalassaemia, and a rare deletion (--(THAI) allele) previously unreported in mainland China were detected. The frequency of the most common mutation, the Southeast Asian type of deletion (--(SEA), accounting for 48.54% of all alpha thalassaemias) was similar to the total of two alpha(+) thalassaemia deletions (-alpha(3.7) and -alpha(4.2), accounting for 47.49% of alpha thalassaemia). CONCLUSION: Both alpha and beta thalassaemia are widely distributed in Guangdong Province of China. The knowledge gained in this study will enable the projected number of pregnancies at risk to be estimated and a screening strategy for control of thalassaemia to be designed in this area.

Adult↗
PubMed2002

Models of growth hormone and IGF-1 deficiency: applications to studies of aging processes and life-span determination.

The remarkable progress in understanding the genetic basis of life-span determination in invertebrates indicates that impairments in the insulin-insulin-like growth factor 1 (IGF-1) signaling cascade increase longevity. Similarities among insulin and IGF-1-like signaling pathways in invertebrates and mammals raise the possibility that modifications of these pathways may extend life span in mammals. Investigators using Ames, Snell, and growth hormone receptor knockout models have concluded that decreased growth hormone and IGF-1 are responsible for increased life span. In this review, we critique the dwarf models and, based on multiple endocrine deficiencies and developmental anomalies, conclude that these models may not be sufficient to assess the consequences of growth hormone or IGF-1 deficiency on either biological aging or life span. We attempt to resolve some of these issues by presenting an alternative animal model of growth hormone-IGF-1 deficiency. Finally, we propose an integrated explanation of growth hormone and IGF-1's contribution to the aging phenotype and life-span determination.

Aging↗
PubMed2002

Cancer incidence and risk estimation among medical x-ray workers in China, 1950-1995.

Cancer incidence (1950-1995) among 27,011 medical diagnostic x-ray workers was compared by means of O/E system with that of 25,782 other medical specialists employed between 1950 and 1980 to provide evidence of human malignant tumors produced by protracted and fractionated exposure to ionizing radiation and to assess resultant cancer risk. Significant cancer risk was seen among diagnostic x-ray workers (RR = 1.2, 95% CI: 1.1-1.3). Significantly elevated risks were found for leukemia and cancers of skin, female breast, lung, liver, bladder, and esophagus; the RRs were 2.2, 4.1, 1.3, 1.2, 1.2, 1.8, and 2.7, respectively. The patterns of risk associated with years since beginning x-ray work and with age and calendar year of initial employment suggest that the excesses of leukemia, skin cancer, and female breast cancer-and possibly thyroid cancer-were related to occupational exposure to x rays. Because of a lack of individual dosimetry for Chinese medical x-ray workers (CMXW) before 1985, the dose was reconstructed by physical and biological retrospective dosimetry methods. The cancer risk of CMXW was estimated based on the reconstructed dose. The average cumulative dose for the earlier cohort (employed before 1970) was 551 mGy, and for the later cohort (employed from 1970 to 1980) it was 82 mGy. The RRs of leukemia and solid cancer were significantly high for the earlier cohort: 2.4 for leukemia, 1.2 for solid cancer. But no significant increase of RR was evident for the later cohort. The RR of leukemia was 1.7 and 1.1 for solid cancer. This means a significant cancer risk can be induced by long term fractionated exposure to ionizing radiation when the cumulative dose reaches a certain level.

Adult↗
PubMed2001

Poly(ADP-ribose) polymerase: a guardian angel protecting the genome and suppressing tumorigenesis.

Poly(ADP-ribosyl)ation is an immediate cellular response to DNA damage generated either exogenously or endogenously. This post-translational modification is catalyzed by poly(ADP-ribose) polymerase (PARP, PARP-1, EC 2.4.2.30). It is proposed that this protein plays a multifunctional role in many cellular processes, including DNA repair, recombination, cell proliferation and death, as well as genomic stability. Chemical inhibitors of the enzyme, dominant negative or null mutations of PARP-1 cause a high degree of genomic instability in cells. Inhibition of PARP activity by chemical inhibitors renders mice or rats susceptible to carcinogenic agents in various tumor models, indicating a role for PARP-1 in suppressing tumorigenesis. Despite the above observations, PARP-1 knockout mice are generally not prone to the development of tumors. An enhanced tumor development was observed, however, when the PARP-1 null mutation was introduced into severely compromised immune-deficient mice (a mutation in DNA-dependent protein kinase) or mice lacking other DNA repair or chromosomal guardian molecules, such as p53 or Ku80. These studies indicate that PARP-1 functions as a cofactor to suppress tumorigenesis via its role in stabilization of the genome, and/or by interacting with other DNA strand break-sensing molecules. Studies using PARP-1 mutants and chemical inhibitors have started to shed light on the role of this protein and of the specific protein post-translational modification in the control of genomic stability and hence its involvement in cancer.

Animals↗
PubMed2001

UV-induced DNA damage and mutations in Hupki (human p53 knock-in) mice recapitulate p53 hotspot alterations in sun-exposed human skin.

The major etiological agent contributing to human nonmelanoma skin cancer is sunlight. The p53 tumor suppressor gene is usually mutated in these tumors, and the mutations are "UV signature" single or tandem transitions at dipyrimidine sequences in the DNA-binding domain (DBD). Cells that harbor these characteristic mutations are already present in sun-exposed skin areas of healthy individuals, and small epidermal patches that are immunoreactive to anti-p53 antibody accrue as exposure increases. To explore carcinogen-specific human p53 mutation patterns experimentally, we generated a knock-in (Hupki) mouse in which the murine DBD of the p53 gene has been replaced by the homologous human p53 DBD segment; thus, the precise base sequence context frequently targeted by mutagens or endogenous mutagenic processes in human carcinogenesis is present in this strain (J. L. Luo et al., Oncogene, 20: 320-328, 2001). Here we show that when epidermal cells of Hupki mice (p53(ki/ki)) are irradiated in vivo with a single acute dose of UVB light, they accumulate UV photoproducts at the same locations of the p53 gene as human cells. Chronic exposure of Hupki mice (4.5 kJ/m(2) 5x/week for 4 weeks) results in the appearance of cell patches that stain intensely with the anti-p53 antiserum CM1. DNA preparations from 2 cm(2) sections of chronically irradiated Hupki epidermis harbor C to T and CC to TT mutations at two mutation hotspots identified in human skin cancer, one at codons 278-279, and one at codons 247-248; the latter is the most frequent UVB-associated mutation site in humans but not in p53 wild-type mice. Thus, Hupki keratinocytes with these p53 mutations encode an aberrant DBD identical in amino acid sequence to the mutant p53 molecules in human UV-induced tumors. The Hupki mouse model offers a new experimental tool in molecular epidemiology and biomedical research.

Amino Acid Sequence↗
PubMed2001

A conserved tryptophan in nitric oxide synthase regulates heme-dioxy reduction by tetrahydrobiopterin.

In nitric oxide synthase (NOS), (6R)-tetrahydrobiopterin (H(4)B) binds near the heme and can reduce a heme-dioxygen intermediate (Fe(II)O(2)) during Arg hydroxylation [Wei, C.-C., Wang, Z.-Q., Wang, Q., Meade, A. L., Hemann, C., Hille, R., and Stuehr, D. J. (2001) J. Biol. Chem. 276, 315-319]. A conserved Trp engages in aromatic stacking with H(4)B, and its mutation inhibits NO synthesis. To examine how this W457 impacts H(4)B redox function, we performed single turnover reactions with the mouse inducible NOS oxygenase domain (iNOSoxy) mutants W457F and W457A. Ferrous mutants containing Arg and H(4)B were mixed with O(2)-containing buffer, and then heme spectral transitions, H(4)B radical formation, and Arg hydroxylation were followed versus time. A heme Fe(II)O(2) intermediate was observed in W457A and W457F and had normal spectral characteristics. However, its disappearance rate (6.5 s(-1) in W457F and 3.0 s(-1) in W457A) was slower than in wild-type (12.5 s(-1)). Rates of H(4)B radical formation (7.1 s(-1) in W457F and 2.7 s(-1) in W457A) matched their rates of Fe(II)O(2) disappearance, but were slower than radical formation in wild-type (13 s(-1)). The extent of H(4)B radical formation in the mutants was similar to wild-type, but their radical decayed 2-4 times faster. These kinetic changes correlated with slower and less extensive Arg hydroxylation by the mutants (wild-type > W457F > W457A). We conclude that W457 ensures a correct tempo of electron transfer from H(4)B to heme Fe(II)O(2), possibly by stabilizing the H(4)B radical. Proper control of these parameters may help maximize Arg hydroxylation and minimize uncoupled O(2) activation at the heme.

Animals↗
PubMed2001

Dexamethasone inhibits CD4 T cell deletion mediated by macrophages from human immunodeficiency virus-infected persons.

Prednisolone slows the loss of CD4 T cells in individuals with human immunodeficiency virus (HIV) disease and inhibits antigen-induced apoptosis of recently HIV-infected CD4 cells in vitro. This study investigated whether dexamethasone inhibits the ability of macrophages to delete CD4 T cells via anti-CD4 antibody or immune-complexed HIV envelope protein gp120. Peripheral blood mononuclear cells from HIV-negative persons were incubated with CD4-reactive ch412 monoclonal antibody or with gp120/IgG immune complexes and resident macrophages, with and without dexamethasone. Dexamethasone inhibited CD4 cell deletion in a dose-dependent manner. The deletion of normal CD4 cells by macrophages from HIV-infected patients also was inhibited by dexamethasone. Furthermore, up-regulation of CD95 expression on T cells exposed to anti-CD4 and gp120/IgG, which predisposes T cells to CD95-mediated apoptosis, is inhibited by dexamethasone in a dose-dependent fashion. Dexamethasone inhibits the macrophage-mediated deletion of CD4 lymphocytes in HIV-infected persons.

Adult↗
PubMed2001

Effects of DNA nonhomologous end-joining factors on telomere length and chromosomal stability in mammalian cells.

DNA repair by nonhomologous end-joining (NHEJ) relies on the Ku70:Ku80 heterodimer in species ranging from yeast to man. In Saccharomyces cerevisiae and Schizosaccharomyces pombe, Ku also controls telomere functions. Here, we show that Ku70, Ku80, and DNA-PKcs, with which Ku interacts, associate in vivo with telomeric DNA in several human cell types, and we show that these associations are not significantly affected by DNA-damaging agents. We also demonstrate that inactivation of Ku80 or Ku70 in the mouse yields telomeric shortening in various primary cell types at different developmental stages. By contrast, telomere length is not altered in cells impaired in XRCC4 or DNA ligase IV, two other NHEJ components. We also observe higher genomic instability in Ku-deficient cells than in XRCC4-null cells. This suggests that chromosomal instability of Ku-deficient cells results from a combination of compromised telomere stability and defective NHEJ.

Animals↗
PubMed2001

Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death.

Poly(ADP-ribose) polymerase (PARP) is responsible for post-translational modification of proteins in the response to numerous endogenous and environmental genotoxic agents. PARP and poly(ADP-ribosyl)ation are proposed to be important for the regulation of many cellular processes such as DNA repair, cell death, chromatin functions and genomic stability. Activation of PARP is one of the early DNA damage responses, among other DNA sensing molecules, such as DNA-PK, ATM and p53. The generation and characterization of PARP deficient mouse models have been instrumental in defining the biological role of the molecule and its involvement in the pathogenesis of various diseases including diabetes, stroke, Parkinson disease, general inflammation as well as tumorigenesis, and have, therefore, provided information for the development of pharmaceutical strategies for the treatment of diseases.

Animals↗
PubMed2001

Knock-in mice with a chimeric human/murine p53 gene develop normally and show wild-type p53 responses to DNA damaging agents: a new biomedical research tool.

The high prevalence and great diversity of p53 tumor suppressor gene mutations in human tumors call for development of therapeutic molecules that rescue function of aberrant p53 protein. P53 mutations also offer new approaches to the study of the origins of mutations in human cancer. An experimental mouse model with a genetically modified but normal functioning p53 gene harboring the human rather than the murine core domain, would be of considerable benefit to research on both cancer therapeutics and etiology; however, it is uncertain whether such mice would permit biological functions of p53 to be retained. Using a Cre/lox P gene-targeting approach, we have constructed a human p53 knock-in (hupki) mouse strain in which exons 4-9 of the endogenous mouse p53 allele were replaced with the homologous, normal human p53 gene sequence. The chimeric p53 allele (p53(KI)) is properly spliced, transcribed in various tissues at levels equivalent to wild-type mice, and yields cDNA with the anticipated sequence, that is, with a core domain matching that of humans. The hupki p53 protein binds to p53 consensus sequences in gel mobility shift assays and accumulates in the nucleus of hupki fibroblasts in response to UV irradiation, as is characteristic of wild-type p53. Induction of various p53-regulated genes in spleen of gamma-irradiated homozygous hupki mice (p53(KI/KI)), and the kinetics of p53-dependent apoptosis in thymocytes are similar to results with wild-type (p53(+/+)) mice, further indicating normal p53 pathway function in the hupki strain. The mice are phenotypically normal and do not develop spontaneous tumors at an early age, in contrast to knock-out (p53(-/-)) strains with a defective p53 gene. The chimeric (p53(KI)) allele thus appears to provide a biological equivalent to the endogenous murine (p53(+)) gene. This strain is a unique tool for examining in vivo spontaneous and induced mutations in human p53 gene sequences for comparison with published human tumor p53 mutation spectra. In addition, the hupki strain paves the way for mouse models in pre-clinical testing of pharmaceuticals designed to modulate DNA-binding activity of human p53.

Animals↗