Biomedical subjects

Jun Zhang

Publications and source records attributed to Jun Zhang.

At least 415 records · Page 23Linked to original sources

PubMed2002

Predictors of herbicide exposure in farm applicators.

OBJECTIVES: Most epidemiological studies of pesticides have used self-reports rather than quantitative measurements to assess exposures. The purpose of this study was to identify factors likely to affect exposure under actual field conditions and to measure the sensitivity and specificity of self-reported indications of exposure against urinary measures of herbicide exposure. METHODS: A sub-set of the participants in a retrospective cohort study of Ontario farm families volunteered for a pesticide exposure assessment study. Immediately prior, and subsequent to, handling the phenoxy-herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) or 4-chloro-2-methylphenoxyacetic acid (MCPA) for the first time during the season, 126 pesticide applicators provided pre-exposure spot urine samples and a subsequent consecutive 24-h urine sample. At the same time, they completed a questionnaire on pesticide use and handling practices for the first day of pesticide application. RESULTS: Assuming that the presence of 2,4-D in the urine was a measure of true exposure and that questionnaire indications of 2,4-D use were the exposure classification subject to error, then the questionnaire's prediction of exposure had a sensitivity of 56.7% and specificity of 86.4%. The comparable values for MCPA were sensitivity and specificity of 91.6% and 67.4%, respectively. In multivariate models, the variables pesticide formulation, protective clothing/gear, application equipment, handling practice, and personal hygiene practice were significant as predictors of urinary herbicide levels in the first 24 h after application (or spraying) had been initiated (adjusted R(2)=44% for MCPA and 39% for 2,4-D). CONCLUSIONS: Although similar domains of factors were associated with exposure in both models, the specific factors identified and the signs of the coefficients were sufficiently different between the final models for each herbicide that additional investigations appear to be warranted to determine the sources of the differences and assess the validity of the models and their ability to be generalised.

2,4-Dichlorophenoxyacetic Acid↗

PubMed2002

Mitochondrial PKCepsilon and MAPK form signaling modules in the murine heart: enhanced mitochondrial PKCepsilon-MAPK interactions and differential MAPK activation in PKCepsilon-induced cardioprotection.

Although activation of protein kinase C (PKC) epsilon and mitogen-activated protein kinases (MAPKs) are known to play crucial roles in the manifestation of cardioprotection, the spatial organization of PKCepsilon signaling modules in naïve and protected myocardium remains unknown. Based on evidence that mitochondria are key mediators of the cardioprotective signal, we hypothesized that PKCepsilon and MAPKs interact, and that they form functional signaling modules in mitochondria during cardioprotection. Both immunoblotting and immunofluorescent staining demonstrated that PKCepsilon, ERKs, JNKs, and p38 MAPK co-localized with cardiac mitochondria. Moreover, transgenic activation of PKCepsilon greatly increased mitochondrial PKCepsilon expression and activity, which was concomitant with increased mitochondrial interaction of PKCepsilon with ERKs, JNKs, and p38 as determined by co-immunoprecipitation. These complex formations appeared to be independent of PKCepsilon activity, as the interactions were also observed in mice expressing inactive PKCepsilon. However, although both active and inactive PKCepsilon bound to all three MAPKs, increased phosphorylation of mitochondrial ERKs was only observed in mice expressing active PKCepsilon but not in mice expressing inactive PKCepsilon. Examination of potential downstream targets of mitochondrial PKCepsilon-ERK signaling modules revealed that phosphorylation of the pro-apoptotic protein Bad was elevated in mitochondria. Together, these data show that PKCepsilon forms subcellular-targeted signaling modules with ERKs, leading to the activation of mitochondrial ERKs. Furthermore, formation of mitochondrial PKCepsilon-ERK modules appears to play a role in PKCepsilon-mediated cardioprotection, in part by the phosphorylation and inactivation of Bad.

Animals↗

PubMed2002

Nitric oxide (NO) induces nitration of protein kinase Cepsilon (PKCepsilon ), facilitating PKCepsilon translocation via enhanced PKCepsilon -RACK2 interactions: a novel mechanism of no-triggered activation of PKCepsilon.

Activation of protein kinase C (PKC) epsilon by nitric oxide (NO) has been implicated in the development of cardioprotection. However, the cellular mechanisms underlying the activation of PKCepsilon by NO remain largely unknown. Nitration of protein tyrosine residues has been shown to alter functions of a variety of proteins, and NO-derived peroxynitrite is known as a strong nitrating agent. In this investigation, we demonstrate that NO donors promote translocation and activation of PKCepsilon in an NO- and peroxynitrite-dependent fashion. NO induces peroxynitrite-mediated tyrosine nitration of PKCepsilon in rabbit cardiomyocytes in vitro, and nitrotyrosine residues were also detected on PKCepsilon in vivo in the rabbit myocardium preconditioned with NO donors. Furthermore, coimmunoprecipitation of PKCepsilon and its receptor for activated C kinase, RACK2, illustrated a peroxynitrite-dependent increase in PKCepsilon-RACK2 interactions in NO donor-treated cardiomyocytes. Moreover, using an enzyme-linked immunosorbent assay-based protein-protein interaction assay, PKCepsilon proteins treated with the peroxynitrite donor SIN-1 exhibited enhanced binding to RACK2 in an acellular environment. Our data demonstrate that post-translational modification of PKCepsilon by NO donors, namely nitration of PKCepsilon, facilitates its interaction with RACK2 and promotes translocation and activation of PKCepsilon. These findings offer a plausible novel mechanism by which NO activates the PKC signaling pathway.

Amino Acid Sequence↗

PubMed2002

A simple route towards tubular ZnO.

Thermal treatment of Zn(NH3)(4)2+ precursor in ethanol solvent led to the formation of the tubular ZnO which exhibited strong ultraviolet photoluminescence around 385 nm at room temperature; TEM images showed the hollow tubules with approximately 450 nm in diameter and approximately 4 microns in length were built up by ZnO polycrystals.

Journal Article↗

PubMed2002

Tumor p16M is a possible marker of advanced stage in non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: The inactivation of the tumor suppressor gene p16 by methylation (p16M) has been recognized recently as an important process in the oncogenesis for a variety of carcinomas. There have been few reports of its use in lung cancer. We investigate p16M in patients with non-small cell lung cancer (NSCLC). METHODS: p16M in tumor, plasma, and pleural lavage fluid from patients with resectable NSCLC were investigated by using methylation-specific polymerase chain reaction. RESULTS: Of the 33 patients studied, 14 (42%) had p16M tumors. There was a significant association between p16M tumors and advanced TNM staging (stage III or IV, P=0.047, Fisher exact test). Circulating p16M was identified in 2 of the 14 patients with p16M tumor and was also associated with advanced TNM staging (P=0.049). The presence of plasma p16M in NSCLC patients and in p16M tumor patients was associated with poor survival and shorter disease-free survival (P=0.0028, P=0.0039, Kaplan-Meier log rank). In addition, p16M was present in three preresectional and four postresectional lavage samples. Preresectional p16M was associated with poor survival and shorter disease-free survival (P=0.0085). p16M tumor involving the visceral pleura was significantly associated with positive p16M postresectional lavage. CONCLUSIONS: Positive tumor and plasma p16M indicate advanced staging in NSCLC. Patients with plasma and preresection pleural lavage p16M have shorter survival. Further research in this direction is warranted.

Adult↗

PubMed2002

Bioluminescence of Aequorea macrodactyla, a common jellyfish species in the East China Sea.

Studies of the bioluminescent mechanisms of jellyfish have been mainly confined to one species, Aequorea victoria. We describe the luminescent system of another species, Aequorea macrodactyla, which is commonly found in the warmer waters on the coastal region of East China Sea. The luminescent system of this species consists of a green fluorescent protein (GFP) and one or more aequorins. The GFP gene is 1042 bp. It encompasses a coding sequence of 717 bp organized as 3 exons, and it is predicted to specify a 27-kDa peptide, which shares 80% amino acid sequence identity with the GFP of A. victoria. The entire coding sequence was cloned into the pTO-T7 expression vector and expressed in Escherichia coli. Compared with GFP of A. victoria, the purified expressed protein exhibited an excitation peak at a higher wavelength of 476 nm and an emission peak at a lower wavelength of 496 nm, with a higher quantum yield of 1.0. The other photoprotein, aequorin, is encoded in a single open reading frame of 585 bp specifying a 23-kDa apoprotein. The gene was cloned in to the same expression vector and expressed in E. coli. The activity of the photoprotein was reconstituted by incubating the expressed apoprotein with coelenterazine f. In the presence of Ca(2+) the reconstituted aequorin exhibits an emission peak at 470 nm. The kinetics of regeneration and the photoactivities of the reconstituted aequorins of the 2 species of jellyfish are similar. Nevertheless, Aequorea macrodactyla is expected to appear brighter and more "blue" than Aequorea victorea because of the differences in the photoactivity of their GFPs.

Journal Article↗

PubMed2002

What do you think I think you think?: Strategic reasoning in matrix games.

In reasoning about strategic interpersonal situations, such as in playing games, an individual's representation of the situation often includes not only information about the goals and rules of the game, but also a mental model of other minds. Often such mental models involve a hierarchy of reflexive reasoning commonly employed in social situations ("What do you think I think you think..."), and may be related to the developmental notion of 'theory of mind'. In two experiments, the authors formally investigate such interpersonal recursive reasoning in college-age adults within the context of matrix games. Participants are asked to predict the moves of another player (experimenter's confederate) in a two-choice, sequential-move game that may terminate at various stages with different payoffs for each player. Participants are also asked to decide optimally on their own moves based on the prediction made. Errors concerning the prediction, or translation of those predictions into decisions about one's action, were recorded. Results demonstrate the existence of a "default" mental model about the other player in the game context that is dynamically modified as new evidence is accumulated. Predictions about this other player's behavior are, in general, used consistently in decision-making, though the opponent tends to be modeled, by default, to behave in a myopic fashion not anticipating the participant's own action.

Adult↗

PubMed2002

Multifetal pregnancy in older women and perinatal outcomes.

OBJECTIVE: To examine multifetal pregnancy in older women and perinatal outcomes. DESIGN: A cross-sectional study. SETTING: A nationwide vital registry. PATIENT(S): A national population-based database that links the live birth, fetal, and infant death certificates reported of multiple gestations in the United States from 1995 to 1997. It includes 155,777 twin and 5,630 triplet pregnancies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Very preterm birth (<33 weeks), very low birthweight (<1,500 g), and perinatal and infant deaths. RESULT(S): Compared with those with singleton pregnancies, women with multifetal gestation tended to be older, non-Hispanic white, better educated, married, and nulliparous and to have earlier and more frequent prenatal care. Pregnancies conceived by assisted reproductive technology accounted for an increasing number of multiple gestations in older women. In women with lower socioeconomic status, older age was associated with higher risks of poor perinatal outcomes in twin pregnancy (relative risks ranging from 1.0 to 1.9 with a dose-response pattern). However, in women with higher socioeconomic status, older women did not have a higher risk of poor perinatal outcomes than younger women. CONCLUSION(S): The effect of older maternal age on perinatal outcomes in multifetal pregnancies may have been altered by assisted reproductive technology, frequent prenatal surveillance, and advanced neonatal care.

Adult↗

PubMed2002

Survival of other fetuses after a fetal death in twin or triplet pregnancies.

OBJECTIVE: To estimate the frequency of fetal death in multifetal pregnancies and the probability of survival to age 1 year for twins or triplets in which at least one fetal death occurred at 20 weeks' gestation or more. METHODS: We used the Matched Multiple Birth File from the US National Center for Health Statistics, which included 152,233 sets of twins and 5356 sets of triplets registered from 1995 to 1997. The Cox proportional hazards model was used to estimate the adjusted relative risk of death before age 1 year for remaining twins and triplets. RESULTS: Fetal death at 20 weeks' gestation or later was uncommon, occurring in 2.6% of twin and 4.3% of triplet gestations. After adjustment for confounders, the survival of the remaining fetuses was inversely related to the time of the first fetal demise. Same-sex twins were two times more likely than opposite-sex twins to die after an intrauterine demise at 25-32 weeks' gestation and were more than three times more likely to die after a death at 33 weeks' gestation or more. CONCLUSION: After a fetal death in a multifetal pregnancy at 20 weeks' gestation or later, the survival of the remaining fetuses is inversely related to the time the death occurred. Among twins, survival also depends on sex concordance, with opposite-sex twins more likely than same-sex twins to survive.

Female↗

PubMed2002

Rising rates of labor induction: present concerns and future strategies.

The rate of labor induction nationwide increased gradually from 9.5% to 19.4% between 1990 and 1998. Reasons for this doubling of inductions relate to widespread availability of cervical ripening agents, pressure from patients, conveniences to physicians, and litigious constraints. The increase in medically indicated inductions was slower than the overall increase, suggesting that induction for marginal or elective reasons has risen more rapidly. Data to support or refute the benefits of marginal or elective inductions are limited. Many trials of inductions for marginal indications are either nonexistent or retrospective with small sample sizes, thereby limiting definitive conclusions. Until prospective clinical trials can better validate reasons for the liberal use of labor induction, it would seem prudent to maintain a cautious approach, especially among nulliparous women. Strategies are proposed for developing evidence-based guidelines to reduce the presumed increase in health care costs, risk of cesarean delivery for nulliparas, and overscheduling in labor and delivery.

Adult↗

PubMed2002

TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator.

DR3 is a death domain-containing receptor that is upregulated during T cell activation and whose overexpression induces apoptosis and NF-kappaB activation in cell lines. Here we show that an endothelial cell-derived TNF-like factor, TL1A, is a ligand for DR3 and decoy receptor TR6/DcR3 and that its expression is inducible by TNF and IL-1alpha. TL1A induces NF-kappaB activation and apoptosis in DR3-expressing cell lines, while TR6-Fc protein antagonizes these signaling events. Interestingly, in T cells, TL1A acts as a costimulator that increases IL-2 responsiveness and secretion of proinflammatory cytokines both in vitro and in vivo. Our data suggest that interaction of TL1A with DR3 promotes T cell expansion during an immune response, whereas TR6 has an opposing effect.

Amino Acid Sequence↗

PubMed2002

Cytoplasmic dynein intermediate chain and heavy chain are dependent upon each other for microtubule end localization in Aspergillus nidulans.

The multisubunit microtubule motor, cytoplasmic dynein, targets to various subcellular locations in eukaryotic cells for various functions. The cytoplasmic dynein heavy chain (HC) contains the microtubule binding and ATP binding sites for motor function, whereas the intermediate chain (IC) is implicated in the in vivo targeting of the HC. Concerning any targeting event, it is not known whether the IC has to form a complex with the HC for targeting or whether the IC can target to a site independently of the HC. In the filamentous fungus Aspergillus nidulans, the dynein HC is localized to the ends of microtubules near the hyphal tip. In this study, we demonstrate that our newly identified dynein IC in A. nidulans is also localized to microtubule ends and is required for HC's localization to microtubule ends in living cells. With the combination of two reagents, an HC loss-of function mutant and the green fluorescent protein (GFP)-fused IC that retains its function, we show that the IC's localization to microtubule ends also requires HC, suggesting that cytoplasmic dynein HC-IC complex formation is important for microtubule end targeting. In addition, we show that the HC localization is not apparently altered in the deletion mutant of NUDF, a LIS1-like protein that interacts directly with the ATP-binding domain of the HC. Our study suggests that, although HC-IC association is important for the targeting of dynein to microtubule ends, other essential components, such as NUDF, may interact with the targeted dynein complex to produce full motor activities in vivo.

Amino Acid Sequence↗

PubMed2002

Molecular analysis of the acetolactate synthase gene of Chlamydomonas reinhardtii and development of a genetically engineered gene as a dominant selectable marker for genetic transformation.

Genomic and cDNA clones of the acetolactate synthase (ALS) gene of Chlamydomonas reinhardtii have been isolated from a mutant, c85-20 (Hartnett et al., 1987), that is resistant to high concentrations of sulfometuron methyl (SMM) and related sulfonylurea herbicides. Comparison of the ALS gene sequences from the wild-type and the SMM resistant (SMMr) strains revealed two amino acid differences in the mature enzyme, a lysine to threonine change at position 257 (K257T) and a leucine to valine change at position 294 (L294V). Transformation of wild-type C. reinhardtii with the mutant ALS gene produced no transformants with ability to grow in the presence of a minimum toxic concentration of SMM (3 microm). Substitution of the ALS promoter with the promoter of the C. reinhardtii Rubisco small subunit gene (RbcS2) permitted recovery of SMMr colonies. In vitro mutagenesis of the wild-type ALS gene to produce various combinations of mutations (K257T, L294V and W580L) indicated that the K257T mutation was necessary and sufficient to confer the SMMr phenotype. Optimum transformation rates were obtained with two constructs (pJK7 and pRP-ALS) in which all introns in the coding region were present. Rates of transformation with construct pJK7 were approximately 2.5 x 10-4 transformants/cell (i.e. one transformant for each of 4000 initial cells) using electroporation and 8.5 x 10-6 transformants/cell using the glass bead vortexing method. These results suggest that pJK7 and pRP-ALS can serve as important additional dominant selectable markers for the genetic transformation of C. reinhardtii.

Acetolactate Synthase↗

PubMed2002

Reassessing the labor curve in nulliparous women.

OBJECTIVES: Our purpose was to examine the pattern of labor progression in nulliparous parturients in contemporary obstetric practice. STUDY DESIGN: We extracted detailed labor data from 1329 nulliparous parturients with a term, singleton, vertex fetus of normal birth weight after spontaneous onset of labor. Cesarean deliveries were excluded. We used a repeated-measures regression with a 10th-order polynomial function to discover the average labor curve under contemporary practice. With use of an interval-censored regression with a log normal distribution, we also computed the expected time interval of the cervix to reach the next centimeter, the expected rate of cervical dilation at each phase of labor, and the duration of labor for fetal descent at various stations. RESULTS: Our average labor curve differs markedly from the Friedman curve. The cervix dilated substantially slower in the active phase. It took approximately 5.5 hours from 4 cm to 10 cm, compared with 2.5 hours under the Friedman curve. We observed no deceleration phase. Before 7 cm, no perceivable change in cervical dilation for more than 2 hour was not uncommon. The 5th percentiles of rate of cervical dilation were all below 1 cm per hour. The 95th percentile of time interval for fetal descent from station +1/3 to +2/3 was 3 hours at the second stage. CONCLUSION: Our results suggest that the pattern of labor progression in contemporary practice differs significantly from the Friedman curve. The diagnostic criteria for protraction and arrest disorders of labor may be too stringent in nulliparous women.

Adult↗

PubMed2002

Protein kinase C epsilon signaling complexes include metabolism- and transcription/translation-related proteins: complimentary separation techniques with LC/MS/MS.

The serine/threonine kinase protein kinase C epsilon (PKC epsilon) has been shown to be a critical component in the heart's resistance to cell death following ischemic insult. Recent studies have indicated that PKC epsilon forms multi-protein signaling complexes to accomplish signal transduction in cardiac protection. Using two-dimensional electrophoresis (2DE), combined with matrix-assisted laser desorption ionization mass spectrometry (MS), the initial analysis of these complexes identified signaling molecules, structural proteins, and stress-activated proteins. The initial analysis, although fruitful, was limited by the number of proteins revealed on the 2D gels. It was also apparent that many known cardiac protective functions of PKC epsilon could not be fully accounted for by the proteins identified in the initial analysis. Here we reported the identification of an additional 57 proteins in PKC epsilon complexes using complimentary separation techniques, combined with high sensitivity MS. These techniques include 2DE or large format 1D SDS-PAGE followed by LC/MS/MS and solution trypsin digestion followed by LC/MS/MS, all of which yielded novel data regarding PKC epsilon protein complexes. Nanoscale LC/MS/MS for the analysis of gel-isolated proteins was performed with sub-femtomole sensitivity. In contrast to 2DE analyses, the identification of proteins from 1D gels was independent of their visualization via staining and allowed for the identification of proteins with high isoelectric points. We found that PKC epsilon complexes contain numerous structural and signaling molecules that had escaped detection by our previous analyses. Most importantly, we identified two new groups of proteins that were previously unrecognized as components of the PKC epsilon complex: metabolism-related proteins and transcription/translation-related proteins.

Amino Acid Sequence↗

PubMed2002

Characterization of monoclonal antibodies against GRIM-19, a novel IFN-beta and retinoic acid-activated regulator of cell death.

A combination of interferon-beta (IFN-beta) and all-trans retinoic acid (IFN/RA) induces tumor cell apoptosis via some unknown mechanisms. Apoptosis is a gene-directed process that limits the proliferation of undesired cells. Several genes are required to regulate cell death in the higher-order animals. Earlier, we employed a gene expression knockout technique to isolate cell death-related genes. A novel gene, the gene associated with retinoid-interferon-induced mortality-19 (GRIM-19), was found to be essential for tumor cell death induced by IFN/RA. Here, we describe the development and characterization of three monoclonal antibodies (mAbs) against GRIM-19. GRIM-19 is present in the nucleus and cytoplasm. Its expression is induced by the IFN/RA combination. We also show that GRIM-19 inhibits the cell-transforming property of viral oncogenic protein viral IFN regulatory factor-1 (vIRF-1) via a physical interaction. mAbs developed in this study should be useful for studying the other physiologic roles of GRIM-19 and serve as a potent tool for studying tumor responses to IFN/RA therapy.

3T3 Cells↗

PubMed2002

Analysis on performance and optimization of frequency-domain near-infrared instruments.

Frequency-domain near-infrared techniques have been widely used to detect the optical properties of biological tissues noninvasively. In this paper we propose an analytical model to evaluate the performance of frequency-domain instruments. Based on the diffusion equation and the transfer properties of optoelectronic components, we treat all parts, including the medium, as two-port networks and apply systematic methods to answer questions concerning frequency-domain instruments. Experiments show that this method can reasonably reflect the properties of the instrument within an accuracy of 7%. This kind of method can be used to design suitable instruments for various applications. We also analyze the selection of the instrument parameters to achieve optimal performance at an efficient cost using this analytical model.

Fiber Optic Technology↗

PubMed2002

Interindividual differences of human flavin-containing monooxygenase 3: genetic polymorphisms and functional variation.

The human flavin-containing monooxygenase (form 3) (FMO3) participates in the oxygenation of nucleophilic heteroatom-containing drugs, xenobiotics, and endogenous materials. Currently, six forms of the FMO gene are known, but it is FMO3 that is the major form in adult human liver that is likely responsible for the majority of FMO-mediated metabolism. The substrate structural feature requirements for human FMO3 is beginning to become known to a greater extent and a few chemicals extensively metabolized by FMO3 have been reported. Expression of FMO3 is species- and tissue-specific, but unlike human cytochrome p450, mammalian FMO3 does not appear to be inducible. Interindividual variation in FMO3-dependent metabolism of drugs, chemicals, and endogenous material is therefore more likely due to genetic effects and not environmental ones. Examples of such interindividual variation come from the study of very rare mutations of the human FMO3 gene that have been associated with deficient N-oxygenation of dietary trimethylamine. Defective trimethylamine N-oxygenation causes trimethylaminuria or "fish-like odor syndrome". Information on human FMO3 mutations from individuals suffering from the condition of trimethylaminuria has provided knowledge about the underlying molecular mechanism(s) for trimethylaminuria. A number of common variants of human FMO3 have been reported. Diversification of the FMO3 gene may have led to selective advantages and new functions. As more examples of human FMO3-mediated metabolism of drugs or new chemical entities are discovered in the future, it is possible that FMO3 allelic variation may be shown to contribute to interindividual and interethnic variability of FMO-mediated metabolism. Human FMO3 may be another example of an environmental gene that participates in a protective mechanism to help humans ward off potentially toxic exposure of chemicals.

Animals↗