Cohort profile: the Asia Pacific Cohort Studies Collaboration.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
X Fang
Publications and source records attributed to X Fang.
Nucleostemin mRNA is expressed in both normal and malignant renal tissues.
Nucleostemin (NS), a p53-binding protein, has been shown essential for stem and cancer cell proliferation and implicated in oncogenesis. To explore potential contributions of NS to the development of clear cell renal cell carcinomas (ccRCCs), we determined NS expression in ccRCC cell lines, and in paired normal and malignant renal tissues from 31 patients with ccRCC. Nucleostemin mRNA and/or protein expression was observed in all four cell lines and 27 of 31 (87%) tumour specimens. Surprisingly, 16 of 31 (52%) adjacent normal renal samples also expressed NS mRNA and its levels in four of them were comparable with those in paired tumour tissues. Three of the patients had detectable NS mRNA in their normal renal tissues whereas lacked its expression in the matched tumours. Compared to the oncogene c-MYC expression in these same samples, NS expression showed a much less specificity for ccRCC. We further demonstrated that NS mRNA expression was closely associated with cellular proliferation in normal fibroblasts or T lymphocytes and renal cell carcinoma cell lines. Collectively, NS expression widely occurs in normal and malignant renal tissues, and is likely a proliferation marker rather than a unique regulator of cell proliferation and survival in stem and cancer cells.
Adult↗
Mechanisms regulating energy metabolism by adiponectin in obesity and diabetes.
Nutritional control of molecular events has become of great interest given the increased incidence of diet-induced obesity, and consequently Type 2 (non-insulin-dependent) diabetes, in recent years. The altered adipose tissue content in obese individuals results in an altered profile of circulating adipokines, and here we focus on adiponectin, whose circulating levels decrease in obese individuals. Adiponectin is a 30 kDa protein but circulates primarily as hexameric, oligomeric and, to a lesser extent, trimeric forms. Full-length adiponectin can also be cleaved to produce a fragment containing the globular domain that exerts potent metabolic effects. Adiponectin has insulin-mimetic and -sensitizing actions including stimulation of glucose uptake in skeletal muscle and suppression of glucose production in liver. Hence, adiponectin has attracted great interest as an antidiabetic agent. Adiponectin acts via two receptor isoforms, AdipoR1 (adiponectin receptor 1) and AdipoR2, which have distinct tissue distributions and affinities for recognition of the various adiponectin forms. Expression of AdipoR isoforms can be regulated by hyperinsulinaemia and hyperglycaemia with the consequence of increased sensitivity or resistance to specific forms of adiponectin. In summary, regulation of adiponectin or AdipoR expression may be of great importance in the development of metabolic perturbations characteristic of Type 2 diabetes in obese individuals.
Adiponectin↗
HIV-related knowledge, stigma, and willingness to disclose: A mediation analysis.
Increasing HIV knowledge is a focus of many HIV education and prevention efforts. While the bivariate relationship of HIV serostatus disclosure with HIV-related knowledge and stigma has been reported in the literature, little is known about the mediation effect of stigma on the relationship of HIV knowledge with HIV serostatus disclosure. Data from 4,208 rural-to-urban migrants in China were analyzed to explore this issue. Overall, 70% of respondents reported willingness to disclose their HIV status if they were HIV-positive. Willingness to disclose was negatively associated with misconceptions about HIV transmission and stigma. Stigma mediated the relationship between misconceptions and willingness to disclose among women but not men. The mediation effect of stigma suggests that stigmatization reduction would be an important component of HIV prevention approaches. Gender inequality needs to be addressed in stigmatization reduction efforts.
Adolescent↗
The P2Y purinergic receptor expressed by enteric neurones in guinea-pig intestine.
Electrophysiological recording methods provided evidence for presynaptic release of ATP from enteric neurones and postganglionic sympathetic fibres in the enteric nervous system (ENS) of guinea-pig intestine (J Physiol Lond 2003; 550: 493-504). The released ATP acted at postsynaptic P2Y(1) receptors to evoke slow synaptic excitation in neurones in the submucosal division of the ENS. Here, we report the cloning and characterization of the P2Y(1) receptor, which was found in the guinea-pig submucosal layer. A 1178 bp cDNA clone was isolated from guinea-pig submucosal RNA by reverse transcription polymerase chain reaction (RT-PCR). The cDNA contained an open-reading frame of 1119 bp, encoding a 373 amino acid polypeptide of the same length and with 95% identity to the human P2Y(1) receptor. Stable expression of the guinea-pig cDNA in human embryonic kidney (HEK)293 cells was accompanied by a marked increase in sensitivity for elevation of free intracellular calcium evoked by ATP or related nucleotides. The potency order for ATP and its analogues was: 2-methio-adenosine diphosphate > 2-methio-adenosine triphosphate > ADP > ATP-gamma-S > ATP. The selective P2Y(1) receptor antagonist, MRS2179, was a competitive antagonist for the receptor with a pA(2) value of 6.5. The results add to existing evidence for expression of a functional P2Y(1) purinergic receptor in neurones of the submucosal division of the ENS.
Amino Acid Sequence↗
Oxidative stress related DNA adducts in the liver of female rats fed with sunflower-, rapeseed-, olive- or coconut oil supplemented diets.
Both animal and epidemiological studies support an effect of fatty acid composition in the diet on cancer development, in particular on colon cancer. We investigated the modulating effect of supplementation of the diet of female F344 rats with sunflower-, rapeseed-, olive-, or coconut oil on the formation of the promutagenic, exocyclic DNA adducts in the liver, an organ where major metabolism of fatty acids takes place. 1,N(6)-ethenodeoxyadenosine (etheno-dA), 3,N(4)-ethenodeoxycytidine (etheno-dC) and 1,N(2)-propandodeoxyguanosine from 4-hydroxy-2-nonenal (HNE-dGp) were determined as markers for DNA-damage derived from lipid peroxidation products and markers for oxidative stress. 8-Oxo-deoxyguanosine (8-Oxo-dG) was also measured as direct oxidative stress marker. The body weight of the rats was not influenced by the four diets containing the different vegetable oils during the 4-week feeding period. Highest adduct levels of etheno-dC (430 +/- 181 adducts/10(9) parent bases), HNE-dGp (617 +/- 96 adducts/10(9) parent bases) and 8-Oxo-dG (37,400 +/- 12,200 adducts/10(9) parent bases) were seen in rats on sunflower oil diet (highest linoleic acid content). Highest adducts levels of etheno-dA (133 +/- 113 adducts/10(9) parent bases) were found in coconut oil diet (lowest content of linoleic acid). Weakly positive correlations between linoleic acid content in the four diet groups were only observed for levels of HNE-dGp and 8-Oxo-dG. Neither the diet based on olive oil (which contains mainly oleic acid) nor the diet based on rapeseed oil (containing alpha-linolenic acid) exerted any significant protective effect against oxidative DNA damage. Our results indicate that a high linoleic acid diet may contribute to oxidative stress in the liver of female rats leading to a marginal increase in oxidative DNA-damage.
Animals↗
Electrophysiological differences between nociceptive and non-nociceptive dorsal root ganglion neurones in the rat in vivo.
Intracellular recordings were made from 1022 somatic lumbar dorsal root ganglion (DRG) neurones in anaesthetized adult rats, classified from dorsal root conduction velocities (CVs) as C, Adelta or Aalpha/beta, and according to their responses to mechanical and thermal stimuli as nociceptive (including high-threshold mechanoreceptive (HTM) units), and non-nociceptive (including low-threshold mechanoreceptive (LTM) and cooling units). Of these, 463 met electrophysiological criteria for analysis of action potentials (APs) evoked by dorsal root stimulation. These included 47 C-, 71 Adelta- and 102 Aalpha/beta-nociceptive, 10 C-, 8 Adelta- and 178 Aalpha/beta-LTM, 18 C- and 19 Adelta- unresponsive, and 4 C-cooling units. Medians of AP and afterhyperpolarization (AHP) durations and AP overshoots were significantly greater for nociceptive than LTM units in all CV groups. AP overshoots and AHP durations were similar in nociceptors of all CV groups whereas AP durations were greater in slowly conducting, especially C-fibre, nociceptors. C-cooling units had faster CVs, smaller AP overshoots and shorter AP durations than C-HTM units. A subgroup of Aalpha/beta-HTM, moderate pressure units, had faster CVs and AP kinetics than other Aalpha/beta-HTM units. Of the Aalpha/beta-LTM units, muscle spindle afferents had the fastest CV and AP kinetics, while rapidly adapting cutaneous units had the slowest AP kinetics. AP variables in unresponsive and nociceptive units were similar in both C- and Adelta-fibre CV groups. The ability of fibres to follow rapid stimulus trains (fibre maximum following frequency) was correlated with CV but not sensory modality. These findings indicate both the usefulness and limitations of using electrophysiological criteria for identifying neurones acutely in vitro as nociceptive.
Action Potentials↗
Workplace and HIV-related sexual behaviours and perceptions among female migrant workers.
Data from 1,543 female migrants working in eight occupational clusters in Beijing and Nanjing, China were analysed to examine the association of workplace with HIV-related behaviours and perceptions. For sexually experienced women (n = 666, 43.2%), those working in entertainment establishments or personal service (e.g., nightclubs, dancing halls, barbershops, beauty salons, massage parlours, etc.) engaged in risky sexual practices twice as frequently as those working in non-entertainment establishments (e.g. restaurants, stalls, domestic service, factories, etc.). About 10% of women in the entertainment establishments reported having sold sex, 30% having multiple sexual partners and 40% having sex with men with multiple sexual partners. The rate of consistent condom use was less than 15%. They also tended to have a higher level of perceptions of both peer risk involvement and positive expectancy of risk behaviours, and lower perceptions of severity of STDs and HIV. For women who were not sexually experienced, those working in 'stalls' or 'domestic service' tended to perceive higher peer risk involvement, less severity of HIV infection, and less effectiveness of protective behaviour. The occupational pattern of sexual risk behaviours and perceptions observed in the current study indicates employment conditions are associated with HIV risk. Intervention strategies should be tailored to address occupational-related factors.
Adolescent↗
An optical technique for in situ monitoring of trace metals in effluent.
An optical technique for real time elemental analysis in water environment is evaluated. This is based on laser-induced breakdown in water and the subsequent monitoring of atomic emission lines from the elemental species. Metals, such as copper, lead, iron, sodium etc, in water samples were detected and quantified from their relevant strong atomic emission lines. Experimental results show that metal concentrations in water at a level of a few mg l(-1) are detectable in a non-optimized but versatile experimental system. Elemental constituents in a sample of water effluent from a metal polishing factory for discharge in to streams was analysed and presented. A prototype of a portable system based on original equipment manufacturer's components has been constructed and its potential as a cost-effective effluent discharge monitor for selected elements is evaluated.
Environmental Monitoring↗
Relation of sexual risks and prevention practices with individuals' stigmatising beliefs towards HIV infected individuals: an exploratory study.
OBJECTIVE: To investigate how an individual's stigmatising beliefs towards people living with HIV are related to his or her own sexual risk and protective behaviours. METHODS: A cross sectional survey was conducted to assess HIV related stigmatising beliefs, risk sexual behaviours, and preventive practices among sexually experienced rural to urban migrants aged 18-30 years in 2002 in Beijing and Nanjing, two large Chinese cities. RESULTS: Among 2153 migrants, 7.2% reported having had more than one sexual partner in the previous month, 9.9% had commercial sex partners, and 12.5% had an episode of a sexually transmitted disease (STD). Only 18% reported frequently or always using condoms, with 20% sometimes or occasionally using them. 57% of the Chinese migrants were willing to take a voluntary HIV test, and 65% had HIV related stigmatising beliefs towards people living with HIV. Multiple logistic regression analysis depicts that individual's stigmatising beliefs towards people with HIV were positively associated with having had an episode of an STD, having multiple sex partners, or having had commercial sex partners, and were negatively associated with condom use and the willingness to accept an HIV test. CONCLUSION: The finding that one's own stigmatising belief is a potential barrier to HIV related preventive practices highlights the difficulties and challenges in implementing behavioural interventions.
Adolescent↗
Hyperglycemia- and hyperinsulinemia-induced alteration of adiponectin receptor expression and adiponectin effects in L6 myoblasts.
Adiponectin has been shown to regulate glucose and fatty acid uptake and metabolism in skeletal muscle. Here we investigated the role of the recently cloned adiponectin receptor (AdipoR) isoforms in mediating effects of both globular (gAd) and full-length (fAd) adiponectin, and their regulation by hyperglycemia (25 mM, 20 h) and hyperinsulinemia (100 nM, 20 h). We used L6 rat skeletal muscle cells, which were found to express both AdipoR1 and AdipoR2 mRNA in a ratio of over 6:1 respectively. Hyperglycemia and hyperinsulinemia both decreased AdipoR1 receptor expression by approximately 50%, while the latter induced an increase of approximately threefold in AdipoR2 expression. The ability of gAd to increase GLUT4 myc translocation, glucose uptake, fatty acid uptake and oxidation, as well as AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, was decreased by both hyperglycemia and hyperinsulinemia. Interestingly, hyperinsulinemia induced the ability of fAd to elicit fatty acid uptake and enhanced fatty acid oxidation in response to fAd. In summary, our results suggest that both hyperglycemia and hyperinsulinemia cause gAd resistance in rat skeletal muscle cells. However, hyperinsulinemia induces a switch toward increased fAd sensitivity in these cells.
AMP-Activated Protein Kinases↗
Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells.
AIMS/HYPOTHESIS: The aim of this study was to determine whether adiponectin elicits glucose uptake via increased GLUT4 translocation and to investigate the metabolic fate of glucose in skeletal muscle cells treated with globular adiponectin. MATERIALS AND METHODS: Basal and insulin-stimulated 2-deoxy-D: -[(3)H]glucose uptake, cell surface myc-tagged GLUT4 content, production of (14)CO(2) by oxidation of D: -[U-(14)C]glucose and [1-(14)C]oleate, and incorporation of D: -[U-(14)C]glucose into glycogen and lactate were measured in the presence and absence of globular adiponectin. RESULTS: RT-PCR and Western blot analysis revealed that L6 cells and rat skeletal muscle cells express AdipoR1 mRNA and protein. Globular adiponectin increased both GLUT4 translocation and glucose uptake by increasing the transport V(max) of glucose without altering the K(m). Interestingly, the incorporation of D: -[U-(14)C]glucose into glycogen under basal and insulin-stimulated conditions was significantly decreased by globular adiponectin, whereas lactate production was increased. Furthermore, globular adiponectin did not affect glucose oxidation, but enhanced phosphorylation of AMP kinase and acetyl-CoA carboxylase, and fatty acid oxidation. CONCLUSIONS/INTERPRETATION: The present study is the first to show that globular adiponectin increases glucose uptake in skeletal muscle cells via GLUT4 translocation and subsequently reduces the rate of glycogen synthesis and shifts glucose metabolism toward lactate production. These effects are consistent with the increased phosphorylation of AMP kinase and acetyl-CoA carboxylase and oxidation of fatty acids induced by globular adiponectin.
Adenylate Kinase↗
The ADP ribosyltransferase domain of Pseudomonas aeruginosa ExoT contributes to its biological activities.
ExoT is a type III secreted effector protein found in almost all strains of Pseudomonas aeruginosa and is required for full virulence in an animal model of acute pneumonia. It is comprised of an N-terminal domain with GTPase activating protein (GAP) activity towards Rho family GTPases and a C-terminal ADP ribosyltransferase (ADPRT) domain with minimal activity towards a synthetic substrate in vitro. Consistent with its activity as a Rho family GTPase, ExoT has been shown to inhibit P. aeruginosa internalization into epithelial cells and macrophages, disrupt the actin cytoskeleton through a Rho-dependent pathway, and inhibit wound repair in a scrape model of injured epithelium. We have previously shown that mutation of the invariant arginine of the GAP domain to lysine (R149K) results in complete loss of GAP activity in vitro but only partially inhibits ExoT anti-internalization and cell rounding activity. We have constructed in-frame deletions and point mutations within the ADPRT domain in order to test whether this domain might account for the residual activity observed in ExoT GAP mutants. Deletion of a majority of the ADPRT domain (residues 234 to 438) or point mutations of the ADPRT catalytic site (residues 383 to 385) led to distinct changes in host cell morphology and substantially reduced the ability of ExoT to inhibit in vitro epithelial wound healing over a 24-h period. In contrast, only subtle effects on the efficiency of ExoT-induced bacterial internalization were observed in the ADPRT mutant forms. Expression of each domain individually in Saccharomyces cerevisiae was toxic, whereas expression of each of the catalytically inactive mutant domains was not. Collectively, these data demonstrate that the ADPRT domain of ExoT is active in vivo and contributes to the pathogenesis of P. aeruginosa infections.
ADP Ribose Transferases↗
Correlation of statin-increased platelet APP ratios and reduced blood lipids in AD patients.
Platelets, like neurons, contain 120- to 130- and 110-kd amyloid precursor proteins (APPs). Their ratio is reduced in AD, further reductions correlating with reduced Mini-Mental Status Examination scores [r(11) = 0.69, p < 0.05]. As statins alter APP processing, platelet APPs were analyzed in patients with AD given anticholesterol drugs for 6 weeks. APP ratios increased [t(37) = -3.888, p = 0.0004], proportionally with reduced cholesterol [r(36) = -0.45, p = 0.005]. Longer trials may reveal slowed cognitive loss, validating this index.
Alzheimer Disease↗
cAMP-induced differentiation of human neuronal progenitor cells is mediated by nuclear fibroblast growth factor receptor-1 (FGFR1).
Activation of cAMP signaling pathway and its transcriptional factor cyclic AMP response element binding protein (CREB) and coactivator are key determinants of neuronal differentiation and plasticity. We show that nuclear fibroblast growth factor receptor-1 (FGFR1) mediates cAMP-induced neuronal differentiation and regulates CREB and CREB binding protein (CBP) function in alpha-internexin-expressing human neuronal progenitor cells (HNPC). In proliferating HNPC, FGFR1 was associated with the cytoplasm and plasma membrane. Treatment with dB-cAMP induced nuclear accumulation of FGFR1 and caused neuronal differentiation, accompanied by outgrowth of neurites expressing MAP2 and neuron-specific neurofilament-L protein and enolase. HNPC transfected with nuclear/cytoplasmic FGFR1 or non-membrane FGFR1(SP-/NLS), engineered to accumulate exclusively in the cell nucleus, underwent neuronal differentiation in the absence of cAMP stimulation. In contrast, FGFR1/R4, with highly hydrophobic transmembrane domain of FGFR4, was membrane associated, did not enter the nucleus and failed to induce neuronal differentiation. Transfection of tyrosine kinase-deleted dominant negative receptor mutants, cytoplasmic/nuclear FGFR1(TK-) or nuclear FGFR1(SP-/NLS)(TK-), prevented cAMP-induced neurite outgrowth. Nuclear FGFR1 localized in speckle-like domains rich in phosphorylated histone 3 and splicing factors, regions known for active RNA transcription and processing, and activated the neurofilament-L gene promoter. FGFR1(SP-/NLS) transactivated CRE, up-regulated phosphorylation and transcriptional activity of CREB and stimulated the activity of CBP several-fold. Thus, cAMP-induced nuclear accumulation of FGFR1 provides a signal that triggers molecular events leading to neuronal differentiation.
Active Transport, Cell Nucleus↗
Zona pellucida induces activation of phospholipase A2 during acrosomal exocytosis in guinea pig spermatozoa.
Phospholipase A(2) (PLA(2)) is activated in spermatozoa in response to progesterone and Ca(2+) ionophores, but to our knowledge, no study has yet reported zona pellucida (ZP)-induced activation of PLA(2). We investigated whether PLA(2) is involved in ZP-stimulated acrosomal exocytosis, if Ca(2+) is required for activation of PLA(2), and signal transduction pathways modulating PLA(2) using guinea pig sperm as a model. Spermatozoa were capacitated and labeled in low-Ca(2+) medium with [(14)C]choline chloride or [(14)C]arachidonic acid and were then exposed to millimolar Ca(2+) and various reagents and stimulated with ZP. Precapacitated spermatozoa exposed to millimolar Ca(2+) and stimulated with ZP experienced increases in arachidonic acid (AA) and lysophosphatidylcholine (lysoPC) levels and a parallel decrease in phosphatidylcholine level; these changes are indicative of PLA(2) activation. Simulation with ZP also led to acrosomal exocytosis in a high proportion of spermatozoa. Lipid changes and exocytosis were prevented if spermatozoa were exposed to aristolochic acid, a PLA(2) inhibitor, before treatment with ZP. Stimulation with ZP in medium without added Ca(2+) or in medium with millimolar Ca(2+) and EGTA or La(3+) resulted in no lipid changes or exocytosis. Pretreatment with pertussis toxin, a G(i) protein inhibitor, before stimulation with ZP blocked the release of AA and lysoPC as well as acrosomal exocytosis. Exposure of spermatozoa to the diacylglycerol (DAG) kinase inhibitor R59022 before ZP stimulation led to a significant increase in generation of lysoPC and exocytosis. Taken together, these results indicate very strongly that PLA(2) plays an essential role in ZP-induced exocytosis in spermatozoa, that PLA(2) activation requires Ca(2+) internalization, and that PLA(2) activation is regulated by signal transduction pathways involving G proteins and DAG.
Acrosome Reaction↗
Messenger RNA for progesterone receptor isoforms in the late-gestation rat uterus.
The progesterone receptor (PR) has three isoforms, PR-A, PR-B, and PR-C, which have different physiological effects. PR-A may inhibit PR-B-mediated transcription. Parturition requires withdrawal of progesterone (P4). This could occur through decreased P4 concentrations and/or a change in PR isoforms to diminish the effect of P4. We measured mRNA for PR isoforms in rat uterine tissues through late gestation and investigated the effects of antagonists to estrogen (tamoxifen) and P4 (RU-486). Two specific probes were used for ribonuclease protection assays; one (PR-total) measured PR-A, PR-B, and PR-C, and the other recognized only PR-B. PR-total mRNA increased significantly through late gestation, whereas PR-B was unchanged. The ratio of PR-total to PR-B peaked on the day before parturition. Tamoxifen delayed parturition and inhibited the increase in PR-total without affecting PR-B mRNA. RU-486 caused early parturition associated with increased PR-total mRNA, with no change in PR-B. We conclude that there are significant changes in PR isoforms in late-gestation rat uterus. These changes may be regulated by estrogen and P4 and may influence the timing of parturition.
Animals↗
Femtosecond laser time-of-flight mass spectrometry of labile molecular analytes: laser-desorbed nitro-aromatic molecules.
Femtosecond laser time-of-flight mass spectra of solid samples of trinitrobenzene (TNB), trinitrotoluene (TNT) and trinitrophenol (TNP) have been recorded. Desorption of the solid samples was enacted by the fourth harmonic output (266 nm) of a 5 ns Nd:YAG laser. Subsequent femtosecond post-ionisation of the plume of neutral molecules was achieved using 800 nm laser pulses of 80 fs duration. Mass spectra have been recorded for desorption laser intensities from 2-6 x 10(9) W cm(-2) with ionisation laser intensities between 2 x 10(14) and 6 x 10(15) W cm(-2). Femtosecond laser ionisation has been shown to be capable of generating precursor and characteristic high-mass fragment ions for labile nitro-aromatic molecules commonly used in high-explosive materials. This feature is critical in the future development of femtosecond laser-based analytical instruments that can be used for complex molecular identification and quantitative analysis of environmentally important labile molecules. Furthermore, a comparison of femtosecond post-ionisation mass spectra with standard 70 eV electron impact data has revealed similarities in the spectra and hence the fragmentation processes.
Journal Article↗