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Biomedical subjects

W Zhu

Publications and source records attributed to W Zhu.

At least 73 records · Page 4Linked to original sources

De-novo humoral immune responses to cancer-associated autoantigens during transition from chronic liver disease to hepatocellular carcinoma.

A feature of hepatocellular carcinoma (HCC) is that antecedent liver cirrhosis and chronic hepatitis are common precursor conditions and during transition to malignancy some patients develop autoantibodies which were not present during the preceding chronic liver disease phase. Serum samples from such patients can be used to immunoscreen cDNA expression libraries to identify genes encoding the new autoantigens. We demonstrate here the de novo appearance of antibodies to p62, a cytoplasmic protein which has been shown to bind to a developmentally regulated fetal species of insulin-like growth factor II (IGF-II) mRNA. Another antibody appearing during the transition period was against CENP-F, a cell cycle-related nuclear protein with maximum expression in the G2 and M phases of the cell cycle and previously shown to have a high association with malignancy. In three additional patients in whom serial serum samples were examined, new appearance of anti-p62 was detected in two patients and anti-CENP-F in one patient. This study demonstrates that transition to malignancy can be associated with autoantibody responses to certain cellular proteins which might have some role in tumorigenesis.

Antigens, Neoplasm↗

Non-MAO A binding of clorgyline in white matter in human brain.

Clorgyline is an irreversible inhibitor of monoamine oxidase (MAO A) which has been labeled with carbon-11 (C-11) and used to measure human brain MAO A with positron emission tomography (PET). In this study we compared [11C]clorgyline and deuterium-substituted [11C]clorgyline ([11C]clorgyline-D2) to better understand the molecular link between [11C]clorgyline binding and MAO A. In PET studies of five normal healthy volunteers scanned with [11C]clorgyline and [11C]clorgyline-D2 2 h apart, deuterium substitution generally produced the expected reductions in the brain uptake of [11C]clorgyline. However, the reduction was not uniform with the C-11 binding in white matter being significantly less sensitive to deuterium substitution than other brain regions. The percentages of the total binding attributable to MAO A is largest for the thalamus and smallest for the white matter and this is clearly seen in PET images with [11C]clorgyline-D2. Thus deuterium-substituted [11C]clorgyline selectively reduces the MAO A binding component of clorgyline in the human brain revealing non-MAO A binding which is most apparent in the white matter. The characterization of the non-MAO A binding component of this widely used MAO A inhibitor merits further investigation.

Adult↗

Rasch calibration and optimal categorization of an instrument measuring women's exercise perseverance and barriers.

The purposes of this study were: (a) to determine the optimal categorization of an instrument measuring women's exercise perseverance and barriers using the Rasch analysis and (b) to examine urban women's exercise perseverance and barriers. A 23-item barrier instrument with five response categories was administered to 479 women from a metropolitan area. The data analysis started from collapsing the original five adjacent categories into three and four categories and 11 sets of original and collapsed data were analyzed using the Rasch rating scale model. The model-data fit, category and separation statistics, and parameter estimates provided by Rasch analyses were used to determine the optimal categorization of the instrument. Instead of the original five-category construct, which had a disordered internal construct, a collapsed three-category construct (i.e., Very Often/Often, Sometimes/Rarely, and Never) was found to have the optimal categorization. The time barrier domain was found to be the most severe barrier domain, but the barrier "lack of self-discipline" was the most severe individual barrier. Rasch calibration provides a new way to construct an instrument with optimal categorization, to describe the nature of barrier items and the respondents' attribute being measured, and to develop a practical and informative scoring sheet.

Calibration↗

Fitness portfolio calibration for first- through sixth-grade children.

The purpose of this study was to develop and calibrate health-relatedfitness portfolios for 1st-6th grade students using the many-faceted Rasch model, and examine advantages and disadvantages of a portfolio assessment system based on Rasch calibration. Nine hundred ninety-five studentsfrom 23 schools infirst-sixth grade, who completed three-six of nine health-related fitness portfolios, participated in this study. Ten physical education teachers performed the grading across various portfolios and grade levels. Students'portfolios were rated using 23 predeveloped rubrics, and their scores linked through several common portfolios that were used across schools. The rating scores were analyzed using the many-faceted Rasch model, with four defined facets: portfolio, rubric, student, and rater The model-data fit was very good, and a consistent grade difference wasfound, that is, older students scored higher in fitness knowledge than younger ones. With Rasch calibration, measurement problems in conventional portfolio assessments can be eliminated, and a valid and reliable assessment system can be developed. In addition, several other measurement advantages are provided by Rasch calibration (e.g., related facets can be examined and controlled simultaneously). A large sample size and a more complex process, however, are required in the calibration stage of developing such a system using the Rasch model.

Calibration↗

Silymarin inhibits function of the androgen receptor by reducing nuclear localization of the receptor in the human prostate cancer cell line LNCaP.

A number of reports have shown that the polyphenolic flavonoid silymarin (SM) is an effective anticancer agent. Agents with novel mechanisms of blocking androgen receptor (AR) function may be useful for prostate cancer prevention and therapy. Previous studies showed that silibinin (SB), the major active component of SM, could inhibit cell proliferation of a human prostate cancer cell line, LNCaP, by arresting the cell cycle at the G(1) phase without causing cell death. This study further delineates the potential molecular mechanism by which SM and SB exhibit antiproliferative effects on androgen-responsive prostate cancer cells by inhibiting function of the AR. We observed that SM and SB inhibited androgen-stimulated cell proliferation as well as androgen-stimulated secretion of both prostate-specific antigen (PSA) and human glandular kallikrein (hK2). Additionally, for the first time, we show that an immunophilin, FKBP51, is androgen regulated and that this up-regulation is suppressed by SM and SB. We further demonstrate that transactivation activity of the AR was diminished by SM and SB using gene transfer of PSA promoter and hK2 androgen-responsive element constructs. However, expression and steroid-binding ability of total AR were not affected by SM in western blotting and ligand-binding assays. Intriguingly, we found that nuclear AR levels are significantly reduced by SM and SB in the presence of androgens using western blotting assay and immunocytochemical staining. This study provides a new insight into how SM and SB negatively modulate androgen action in prostate cancer cells.

Androgen Receptor Antagonists↗

Abalone, Haliotis discus hannai Ino, can synthesize myo-inositol de novo to meet physiological needs.

The experiments were conducted to investigate the effects of dietary myo-inositol on the survival, growth, proximate composition and de novo synthesis of myo-inositol in abalone, Haliotis discus hannai Ino. The possible inositol-synthesizing capacity of intestinal microflora was also examined. Seven semipurified diets were formulated to provide graded levels of myo-inositol (28.7-1020.1 mg/kg diet). A control diet, the basal diet supplemented with 4 g/kg tetracycline hydrochloride, was employed to suppress synthesis of myo-inositol by intestinal bacteria. Abalone juveniles of similar size (weight, 144.6 +/- 0.8 mg; shell length, 10.92 +/- 0.10 mm) were distributed in a flow-through system using a completely randomized design with eight treatments and three replicates per treatment. They were fed the appropriate diets once daily for 16 wk. Survival, growth, crude protein, lipid, moisture of whole soft body and visceral inositol content were independent of myo-inositol supplementation (P > 0.05). The addition of the antibiotic also did not affect the survival, growth and whole soft body composition. It indicated that intestinal microflora contributed little to the myo-inositol nutrition in abalone. The present study, for the first time, demonstrated de novo synthesis of myo-inositol in mollusks because the visceral tissue of abalone showed high levels of myo-inositol synthetase activities (combined activities of myo-inositol-1-phosphate synthetase and inositol-1-phosphatase), ranging from 74.0 to 98.2 micromol/(h x g protein). The enzyme activity significantly and negatively correlated with dietary myo-inositol level (r = -0.81). Hence, dietary myo-inositol is not essential for abalone because tissue synthesis of the vitamin appears to be sufficient to support normal growth and health of this mollusk.

Animals↗

Effect of mycophenolate mofetil on nitric oxide production and inducible nitric oxide synthase gene expression during renal ischaemia-reperfusion injury.

BACKGROUND: Recent animal data suggest that inducible nitric oxide synthase (iNOS) derived nitric oxide (NO) plays an important role in the pathogenesis of renal ischaemia-reperfusion injury (IRI) and that inhibition of iNOS ameliorates IRI. Mycophenolate mofetil (MMF), a lymphocyte selective anti-proliferative agent, has been shown to inhibit NO production in vitro. The aim of this study is to evaluate the effect of MMF on NO production and iNOS gene expression in vivo during renal IRI. METHODS: Renal IRI was induced by clamping the left renal pedicle of male BALB/c mice for 30 min, followed by 15 min of reperfusion. The mice received placebo or MMF at 40, 80 or 120 mg/kg/day by oral gavage for 5 days before the operation. Sham-operated mice served as the operation control. The amount of NO produced and the level of iNOS gene expression in the kidney tissue during IRI was assessed by spin trapping electron paramagnetic resonance (EPR) spectroscopy and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) respectively. RESULTS: In the sham-operated kidneys, only low levels of NO and iNOS mRNA were detected. In mice with renal IRI, the amount of NO detected was significantly increased, which was reduced in a dose dependent fashion by pre-treatment with MMF. Pre-treatment with MMF also substantially reduced iNOS gene expression in the kidney tissue. CONCLUSIONS: We conclude that pre-treatment with MMF inhibits the production of NO and the induction of iNOS gene expression in the kidney during IRI. These results suggest that MMF might have the potential to ameliorate renal IRI.

Animals↗

Deflection characteristics of a trapezoidal multilayer in-plane bending piezoelectric actuator.

A novel multilayer split-morph actuator has been designed and fabricated using the thick film screen-printing technology. Deflection characteristics of the split-morph actuator have been investigated by theoretical analysis and experimental measurement. The results indicate that the tip displacement is inversely proportional to the thickness of each piezoelectric layer, but is independent of the number of layers and the total thickness of the actuator. The displacement/voltage sensitivity of the trapezoidal actuator is larger than that of the rectangular design, assuming both have the same width of clamped end and the same thickness of the piezoelectric layers. The maximum displacement/voltage sensitivity of 0.157 micron/V was obtained with a split-morph actuator with 30-micron thick layers. The proposed actuator is a promising candidate for the secondary fine-tuning actuator of a dual stage head-positioning servo system in high density hard disk drives.

Journal Article↗

A finite element analysis of the time-delay periodic ring arrays for guided wave generation and reception in hollow cylinders.

A new guided wave transducer model, time-delay periodic ring arrays (TDPRAs), is proposed and investigated in this paper for guided cylindrical wave generation and reception in hollow cylinders with application interests focusing on non-destructive testing (NDT) of piping/tubing. A finite element simulation has been performed for axisymmetric guided-mode excitation and reception with TDPRAs. By arranging a proper configuration of the time-delay profile and the electric-connection pattern of a ring array, unidirectional excitation and reception of guided waves can be achieved. The numerical results are obtained for the first three axisymmetrical modes and are compared with respect to generation efficiency and mode selectivity. Parametric influences on the performance of TDPRAs are discussed, combining a 2-D phase velocity-frequency spectrum approach with the mode dispersion and displacement structure analyses. The identification of converted modes in guided cylindrical wave reflections with a flexible TDPRA receiver has also been studied through sample notch reflection.

Journal Article↗

Homologues of neisserial heme oxygenase in gram-negative bacteria: degradation of heme by the product of the pigA gene of Pseudomonas aeruginosa.

The oxidative cleavage of heme to release iron is a mechanism by which some bacterial pathogens can utilize heme as an iron source. The pigA gene of Pseudomonas aeruginosa is shown to encode a heme oxygenase protein, which was identified in the genome sequence by its significant homology (37%) with HemO of Neisseria meningitidis. When the gene encoding the neisserial heme oxygenase, hemO, was replaced with pigA, we demonstrated that pigA could functionally replace hemO and allow for heme utilization by neisseriae. Furthermore, when pigA was disrupted by cassette mutagenesis in P. aeruginosa, heme utilization was defective in iron-poor media supplemented with heme. This defect could be restored both by the addition of exogenous FeSO4, indicating that the mutant did not have a defect in iron metabolism, and by in trans complementation with pigA from a plasmid with an inducible promoter. The PigA protein was purified by ion-exchange chromotography. The UV-visible spectrum of PigA reconstituted with heme showed characteristics previously reported for other bacterial and mammalian heme oxygenases. The heme-PigA complex could be converted to ferric biliverdin in the presence of ascorbate, demonstrating the need for an exogenous reductant. Acidification and high-performance liquid chromatography analysis of the ascorbate reduction products identified a major product of biliverdin IX-beta. This differs from the previously characterized heme oxygenases in which biliverdin IX-alpha is the typical product. We conclude that PigA is a heme oxygenase and may represent a class of these enzymes with novel regiospecificity.

Amino Acid Sequence↗

Gene suppression by tristetraprolin and release by the p38 pathway.

Tristetraprolin (TTP) is a zinc finger protein that has been implicated in the control of tumor necrosis factor (TNF) mRNA stability. We show here that TTP protein has a suppressive effect on promoter elements from TNF-alpha and interleukin-8 and that lipopolysaccharide (LPS) stimulation can release this suppression. The release in LPS-stimulated cells was found to be primarily mediated by the p38 pathway because activation of p38 is sufficient to remove the suppressive effect of TTP. Indeed, TTP seems to be a direct substrate of p38 in vivo since it is an excellent substrate of p38 in vitro, and mutation of potential phosphorylation sites in TTP prevents release of the suppression imposed on TNF transcription. We found TTP protein to be present at low levels in the resting macrophage cell line RAW 264.7 and to be quickly induced after LPS stimulation. The kinetics of TTP induction suggests a potential role of TTP as an important player in switching off LPS-induced genes after induction. In conclusion, TTP plays an important role in maintaining gene quiescence, and this quenching effect on transcription can be released by p38 phosphorylation of TTP.

Animals↗

Potential cellular signatures of viral infections in human hematopoietic cells.

Expression profiling of cellular genes was performed using a 10,000 cDNA human gene array in order to identify expression changes following chronic infection of human hematopoietic cells with Kaposi's Sarcoma-associated Virus (KSHV) also known as Human Herpesvirus 8 (HHV8) and Human T cell leukemia virus-1 (HTLV-1). We performed cell-free in vitro infection of primary bone marrow derived CD34+ cells using semi-purified HHV8 and a mature IL-2 dependent T cell line, KIT 225, using highly concentrated viral stocks prepared from an infectious molecular clone of HTLV-1. Thirty days post infection, mRNA was isolated from infected cultures and uninfected controls and submitted for microarray analysis. More than 400 genes were differentially expressed more than two-fold following HHV8 infection of primary bone marrow derived CD34+ cells. Of these 400, interferon regulatory factor 4 (IRF4), cyclin B2, TBP-associated factor, eukaryotic elongation factor and pim 2 were up-regulated more than 3.5 fold. In contrast, less than 100 genes were differentially expressed more than two-fold following chronic infection of a mature T cell line with HTLV-1. Of these, only cdc7 was up-regulated more than 3.5 fold. These data may provide insight into cellular signatures of infection useful for diagnosis of infection as well as potential targets for therapeutic intervention.

Cell Line↗

Projections and pathways of VIP- and nNOS-containing airway neurons in ferret trachea.

Airway ganglia in ferret trachea are organized into two identifiable plexuses, the longitudinal trunk (LT) ganglia and the superficial muscular plexus (SMP) ganglia. LT ganglia contain cholinergic neurons and neurons in SMP ganglia synthesize vasoactive intestinal peptide (VIP) and nitric oxide (NO). Both plexuses of ganglia project to airway smooth muscle, but communications between LT and SMP ganglia have not been extensively studied. Ganglia of the LT were injected with neural tracers, either rhodamine- or biotin-labeled dextran amines, and colocalized with VIP or neuronal NO synthase (nNOS) by immunocytochemistry. Anterograde tracers were found in nerve fibers that formed basket-like complexes associated with neurons of LT and SMP ganglia and were observed in the nerve fibers of smooth muscle and tracheal plexus. Some VIP or nNOS positive neurons in the SMP ganglia contained retrogradely transported tracer. The findings suggest that neurons in the SMP and LT ganglia communicate in a reciprocal fashion and that VIP and nNOS neurons both receive and send neural inputs to neurons of LT, presumably cholinergic, ganglia. These connections probably contribute to the integration of neural control of airway and vascular smooth muscle tone and glandular secretion in the airways.

Acetylcholine↗

Nitric oxide synthase isoforms during fracture healing.

We have shown previously that nitric oxide (NO) has regulatory effects on fracture healing. Our aim here was to investigate the temporal expression patterns of the three NO synthase (NOS) isoforms that are responsible for the generation of NO by semiquantitative competitive polymerase chain reaction (PCR) and immunoblot analysis after femoral fractures in rats. We found that 4 days after fracture, there were increases in the levels of messenger RNA (mRNA) for all three NOS isoforms, with peaks for the inducible NOS (iNOS; 35-fold increase, p < 0.05) at day 4, the endothelial NOS (eNOS; 5-fold increase, p < 0.05) at day 7, and the neuronal NOS (bNOS; 16-fold increase, p < 0.05) at day 21. At a protein level, the time course expression of NOS isoforms was consistent with the results of those at the mRNA level. In addition, we have previously reported a 2.5-fold increase in NOS activity detected by [3H]arginine to [3H]citrulline conversion at day 15 compared with that at day 4 after fracture. The findings that the expression of NOS isoforms during fracture healing is type specific and time dependent are important and may have clinical applications in the regulation of bone repair by NOS inhibitors or stimulators at different stages after injury.

Animals↗

Concentrations and flux of rare earth elements in a semifield plot as influenced by their agricultural application.

The concentrations of rare earth elements (REs) in atmospheric particles, soil, soil water, surface runoff, and different parts of corn in an experimental plot in the suburb of Beijing, China were measured and the flux of REs was estimated. The concentration of REs in air particles with diameter less than 10 microm is 36 ng/m3 and, by ratio analysis, the origin of REs in the atmosphere was likely local soil. The concentration of soluble REs is 0.69 microg/L in rainwater, 5-7 microg/L in surface runoff, as well as 1-4 microg/L in soil water and the application of RE mixture has no observed influences on their concentrations. The concentration of soluble REs in surface runoff and soil water was dominated by aqueous-solid-phase partitioning. By estimation of the flux, most of the REs applied will remain in the soil phase and continued application of REs will cause an accumulation of REs in agricultural soil.

China↗

Morphine reduces herpes simplex virus-1 pathogenesis in the murine flank.

Here we investigate the effect of morphine on herpes simplex virus-1 (HSV-1) pathogenesis using a murine flank scarification model. Murine flank scarification with HSV-1 results in primary lesions at the site of inoculation within three days and lesions at secondary sites within four days. The lesions are scored based on lesion size. Applying 0.1 mM morphine to the skin one-day post inoculation tested the effect of morphine on the formation of the herpes lesion. On days three through five, mice treated with morphine developed lesions with scores half of that observed in untreated animals, however, skin viral titers on these days were equivalent. Further, 1.0 microM morphine did not effect the replication rate of HSV-1 in Vero cells. Taken together, these data suggest the morphine reduced HSV-1 pathogenesis by modifying the host response to HSV-1 infection and not by reducing viral replication rates.

Animals↗

[Malformed macrocephalous sperm with polytails and chromosomal aberrance].

OBJECTIVE: To investigate the relationship between sperm anomalies and chromosomal aberrance and to further understand the pathological changes of anomalous spermatozoa. METHODS: Light and electronic (SEM or TEM) microscopes were used for morphological analysis. Fluorescence in situ hybridization(FISH) with chromosome X-, Y-specific probes were used for aneuploidy detection in sperms of the patient. RESULTS: Ninety eight point seven five per cent of the Papanicolaou stained sperms were observed to be abnormal; 100% of the sperm heads were abnormal, measured under oil objective (1000 times); 60.25% of the sperms had two or more tails (the maximum being eight tails). SEM and TEM demonstrated that the heads contained a large amount of cytoplasmic structure, the surfaces of heads were uneven, the nuclei were of much irregular shape; besides aberrance in quantity, anomalies occurred with centromeres, mitochondria and flagella in the tails. The results of FISH showed that the aneuploidy rate of sex chromosomes was 61.41% which was parallel to the rate of polytails. CONCLUSION: Even though the chromosomes in somatic cells are normal, the chromosomes in anomalous sperms may be abnormal.

Adult↗

[Genetic polymorphism of eight STR loci in the Han population in Henan province].

OBJECTIVE: To investigate the allele frequencies of eight short tandem repeats(STR) loci: TH01, FES, D19S400, D7S820, D16S539, D20S161, D3S1545 and D5S818 in Han population in Henan province. METHODS: DNA was extracted with phenol-chloroform from EDTA-blood samples of the unrelated individuals in Henan province and amplified with PCR technique. The PCR product was analyzed with the undenatured PAGE vertical electrophoresis and silver-stain. RESULTS: The authors got the frequencies of the eight loci. The heterozygosities of the eight loci are 0.66, 0.67, 0.80, 0.76, 0.79, 0.79, 0.78 and 0.78; the discrimination powers are 0.83, 0.83, 0.94, 0.91, 0.93, 0.93, 0.92 and 0.92. CONCLUSION: The heterozygosities of the eight loci are high and the frequencies are in good agreement with Hardy-Weinberg equilibrium, so the eight loci can be used in individual identification testing.

Alleles↗