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Biomedical subjects

W Zhang

Publications and source records attributed to W Zhang.

At least 109 records · Page 6Linked to original sources
PubMed2004

Relative risk of knee chondrocalcinosis in siblings of index cases with pyrophosphate arthropathy.

OBJECTIVES: To examine the genetic contribution to common, apparently sporadic, radiographic knee chondrocalcinosis (CC) and pyrophosphate arthropathy (PA). METHOD: (1). DESIGN: radiographic sibling study. Comparison of the prevalences of knee CC and PA in siblings of index cases with PA with those in the community. (2). SUBJECTS: 80 index cases with PA listed for total knee replacement; 122 of their siblings aged >or=40 years; and 1729 participants from community knee pain surveys who had undergone knee radiographs. (3). MAIN OUTCOME MEASURE: odds ratios of knee CC and PA in siblings versus community participants. RESULTS: The prevalence of knee CC was 13% (15/116) in the siblings and 6.9% (119/1727) in the community participants. The adjusted odds ratio (aOR) was 1.2, 95% confidence interval (CI) 0.6 to 2.3. The main risk factors for knee CC were age, knee pain, and knee OA. The prevalence of knee PA was 7% (9/122) in the siblings and 3.4% (59/1729) among the community participants (aOR = 1.1, 95% CI 0.4 to 2.7). The main risk factors for PA were age and knee pain. The age, sex, and knee pain standardised prevalence of PA in the Nottingham community aged >or=40 was 2.40%. CONCLUSION: The risk of knee CC and PA in siblings of index cases with PA is no higher than that in the general population. Although rare familial CC is recognised, this study suggests that no major genetic predisposition to CC occurs in common symptomatic knee OA.

Adult↗
PubMed2004

Distribution and shifting trends of bacterial keratitis in north China (1989-98).

AIMS: To study the distribution and shifting trends of bacterial keratitis. METHODS: The data of 2220 corneal isolates from 1 January 1989 to 31 December 1998 were reviewed retrospectively. RESULTS: Positive culture was recovered in 490 isolates. Gram positive cocci and Gram negative bacilli represented 51% and 39.4%, respectively. Pseudomonas aeruginosa was the most common pathogen (32.2%). A gradual increase in the percentage of Gram positive cocci coupled with a decrease of Gram negative bacilli. CONCLUSION: Pseudomonas aeruginosa and coaculase negative Staphylococcus were the most common pathogens in bacterial keratitis in north China.

China↗
PubMed2004

Design of a high-throughput assay for alternative splicing using polymerase colonies.

We propose an assay to detect and quantify alternative splicing simultaneously for numerous genes in a pool of cellular mRNA. The assay exploits polymerase colonies, a recently developed method for sampling and amplifying large numbers of individual transcript molecules into discrete spots on a gel. The proposed assay combines the advantages of microarrays for transcript quantitation with the sensitivity and precision of methods based on counting single transcript molecules. Given a collection of spots s(i), each containing an unknown splice variant of some known gene G(i), we design a series of hybridizations to short oligonucleotide probes to determine in parallel which exons of G(i) are present in every spot s(i). We give algorithms to minimize the cost of such designs.

Alternative Splicing↗
PubMed2004

Effect of high-level natural radiation on chromosomes of residents in southern China.

To study the effect of low-dose (rate) radiation on human health, we analyzed chromosomes of peripheral lymphocytes of residents in a high background radiation area (HBRA) and compared the results with those obtained from residents in a control area (CA) in Guangdong Province, China. Unstable types of chromosome aberrations (dicentrics and rings) were studied in 22 members of eight families in HBRA and 17 members of five families in CA. Each family consists of three generations. On average 2,600 cells per subject were analyzed. 27 adults and six children in HBRA and 25 adults and eight children in CA were studied with respect to translocations. On average 4,741 cells per subject were examined. We found an increase of the frequency of dicentrics and rings in HBRA, where the natural radiation level is three to five times higher than in the control area. But the increase of translocations in HBRA was within the range of individual variation in the controls.

Adult↗
PubMed2004

Gastrointestinal stromal tumors: overview of pathologic features, molecular biology, and therapy with imatinib mesylate.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. These tumors develop at any site but are most commonly reported in the stomach. They originate from the neoplastic transformation of the intestinal pacemaker cell, the interstitial cell of Cajal. GISTs strongly express the receptor tyrosine kinase KIT and have mutations in the KIT gene, most frequently in exon 11 encoding the intracellular juxtamembranous region. Expression of KIT is seen in almost all GISTs, regardless of the site of origin, histologic appearance, or biologic behavior, and is therefore regarded as one of the key diagnostic markers. Distinction from smooth muscle tumors, such as leiomyosarcomas, and other mesenchymal tumors is very important because of prognostic differences and therapeutic strategies. Predicting the biologic behavior of GISTs is often difficult by conventional pathologic examination; tumor size and mitotic rate are the most important prognostic indicators. The prognostic significance of KIT mutations is controversial and thus far has not been clearly linked with biologic behavior. KIT mutations are associated with tumor development, and cytogenetic aberrations are associated with tumor progression. The pathogenesis of GISTs involves a gain-of-function mutation in the KIT proto-oncogene, leading to ligand-independent constitutive activation of the KIT receptor. KIT-wild-type GISTs have shown mutually exclusive platelet-derived growth factor receptor (PDGFR) mutation and activation. The use of imatinib mesylate (also known as Gleevec or STI-571) has greatly increased the therapeutic efficacy for this otherwise chemotherapy-resistant tumor. GISTs with very low levels of KIT expression may respond to imatinib mesylate therapy if the receptors are activated by specific mechanisms. KIT-activating mutations fall into two groups: the regulatory type and the enzymatic site type. The regulatory type of mutation is conserved at the imatinib binding site, whereas the enzymatic site mutation has a structurally changed drug-binding site, resulting in drug resistance. Resistance to the drug is the major cause of treatment failure in cancer therapy, emphasizing the need for researchers to understand KIT signaling pathways so as to identify new therapeutic targets. This review summarizes the pathologic features of GISTs, recent advances in understanding their molecular and biologic features, and therapy with imatinib mesylate.

Antineoplastic Agents↗
PubMed2003

Optically tunable fiber grating transmission filters.

We propose and demonstrate single- and multiple-passband fiber grating transmission filters that are remotely tunable by exploitation of the optical pump-induced thermal effects in Er/Yb-codoped fiber sections. A repeatable, wavelength-independent induced phase shift of 0.1 pi/mW is obtained without hysteresis and anisotropic effects. A transmission extinction ratio of >23 dB with a 3-mW change in pump power is achieved.

Journal Article↗
PubMed2003

Cre/lox-mediated marker gene excision in transgenic maize (Zea mays L.) plants.

After the initial transformation and tissue culture process is complete, selectable marker genes, which are used in virtually all transformation approaches, are not required for the expression of the gene of interest in the transgenic plants. There are several advantages to removing the selectable marker gene after it is no longer needed, such as enabling the reuse of selectable markers and simplifying transgene arrays. We have tested the Cre/ lox system from bacteriophage P1 for its ability to precisely excise stably integrated marker genes from chromosomes in transgenic maize plants. Two strategies, crossing and autoexcision, have been tested and demonstrated. In the crossing strategy, plants expressing the Cre recombinase are crossed with plants bearing a transgene construct in which the selectable marker gene is flanked by directly repeated lox sites. Unlike previous reports in which incomplete somatic and germline excision were common, in our experiments complete somatic and germline marker gene excision occurred in the F(1) plants from most crosses with multiple independent Cre and lox lines. In the autoexcision strategy, the cre gene, under the control of a heat shock-inducible promoter, is excised along with the nptII marker gene. Our results show that a transient heat shock treatment of primary transgenic callus is sufficient for inducing cre and excising the cre and nptII genes. Genetic segregation and molecular analysis confirmed that marker gene removal is precise, complete and stable. The autoexcision strategy provides a way of removing the selectable marker gene from callus or other tissues such as embryos and kernels.

Chromosome Segregation↗
PubMed2003

Preautonomic neurons in the paraventricular nucleus of the hypothalamus contain estrogen receptor beta.

Central actions of estrogen (E2) include, among others, modulation of autonomic and cardiovascular function. Despite the well-known influence of sex steroid hormones on the incidence of cardiovascular disorders, little is known about the neural substrates and receptors mediating central E2 actions on autonomic function. The paraventricular nucleus of the hypothalamus (PVN) is an important site for the integration of neuroendocrine and autonomic function. Interestingly, while this region was originally found to lack the classical ERalpha receptor, recent studies demonstrated a high degree of expression of the ERbeta subtype. To determine specifically whether autonomic-related neurons in the PVN express ERbeta, thus constituting a neuronal substrate for central E2 actions on autonomic function, we carried out an immunohistochemical study of ERbeta expression in a subpopulation of PVN neurons that innervate the rostroventrolateral medulla (RVLM). ERbeta immunostained neurons were found in medial and caudal aspects of the PVN, overlapping with the distribution of RVLM-projecting neurons. Overall, approximately 50% of RVLM-projecting PVN neurons expressed ERbeta immunoreactivity. Interestingly, the degree of colocalization was found to be sex-dependent (higher expression in males), and varied according to the topographical distribution of neurons within the PVN. ERbeta immunoreactivity was also observed in magnocellular compartments of the PVN, although this appeared to be consistently weaker than that observed in autonomic-related subnuclei. These studies demonstrate for the first time ERbeta expression in identified autonomic-related neurons in the PVN, and suggest that these neurons constitute an important neuronal substrate mediating E2 actions on autonomic and cardiovascular control.

Animals↗
PubMed2003

Protein interaction for an interferon-inducible systemic lupus associated gene, IFIT1.

OBJECTIVE: To identify disease-related genes and immune-regulatory pathways in the pathogenesis of systemic lupus erythematosus (SLE) by using gene expression profiling and protein-protein interaction analysis. METHODS: Peripheral white blood cell gene expression profiles of 10 SLE patients were determined by oligonucleotide microarray analysis. Clustering of the gene expression profile was compared with the clinical immune phenotype. SLE-induced genes that were over- or under-expressed were determined and independently validated using a real-time polymerase chain reaction (PCR) method. To study their potential function and the possible pathways involved, a candidate gene was cloned and a GST (glutathione S-transferase) fusion protein was expressed in Escherichia coli. The fusion protein was further purified using the glutathione Sepharose 4B system, and was treated as bait to capture prey from SLE peripheral white blood cell lysate. MALDI-TOF (matrix-assisted laser desorption/ionization-time-of-flight) mass spectrometry was then performed to determine the prey protein. RESULTS: Similarity was found between the gene expression profile and the immune phenotype clusters of the SLE patients. More than 20 disease-associated genes were identified, some of which have not been related to SLE previously. Of these genes, a cluster of interferon-induced genes were highly correlated. IFIT1 (interferon-induced with tetratricopeptide repeats 1) was one of these genes, and overexpression of its mRNA was confirmed independently by real-time PCR in a larger population (40 SLE patients and 29 normal controls). An IFIT1 protein- protein interaction study showed that IFIT1 may interact with Rho/Rac guanine nucleotide exchange factor. CONCLUSION: The gene expression profile seems to be the molecular basis of the diverse immune phenotype of SLE. On the basis of the SLE-related genes found in this study, we suggest that the interferon-related immune pathway is important in the pathogenesis of SLE. IFIT1 is the first gene described as a candidate gene for SLE, and may function by activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor. IFIT1 and the interferon-related pathway may provide potential targets for novel interventions in the treatment of SLE.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Identification of SNPs and development of allele-specific PCR markers for gamma-gliadin alleles in Triticum aestivum.

The coding regions of 28 entries of hexaploid wheat gamma-gliadin genes, gene fragments or pseudogenes in GenBank were used for nucleotide alignment. These sequences could be divided into nine subgroups based on nucleotide variation. The chromosomal locations of five of the seven unassigned subgroups were identified through subgroup-specific polymerase chain reactions (PCR) using Chinese Spring group-1 nulli-tetrasomic lines. Multiple single nucleotide polymorphisms (SNPs) and small insertions/deletions were identified in each subgroup. With further mining from wheat expressed sequence tag databases and targeted DNA sequencing, two SNPs were confirmed and one SNP was discovered for genes at the Gli-A1, Gli-B1 and Gli-D1 loci. A modified allele-specific PCR procedure for assaying SNPs was used to generate dominant DNA markers based on these three SNPs. For each of these three SNPs, two allele-specific primer sets were used to test Chinese Spring and 52 commercial Australian wheat varieties representing a range of low-molecular-weight (LMW) alleles. PCR results indicated that all were positive with one of the primer sets and negative with the other, with the exception of three varieties containing the 1BL/1RS chromosomal translocation that were negative for both. Furthermore, markers GliA1.1, GliB1.1 and GliD1.1 were found to be correlated with Glu-A3 a, b or c, Glu-B3 b, c, d or e and Glu-D3 a, b or e LMW glutenin alleles, respectively. Markers GliA1.2, GliB1.2 and GliD1.2 were found to be correlated with the Glu-A3 d or e, Glu-B3 a, g or h and Glu-D3 c alleles, respectively. These results indicated that the gamma-gliadin SNP markers could be used for detecting linked LMW glutenin subunit alleles that are important in determining the quality attributes of wheat products.

Alleles↗
PubMed2003

Possible involvement of oxidative stress in cisplatin-induced apoptosis in LLC-PK1 cells.

Use of cisplatin, a chemotherapeutic agent, is associated with toxicity as a significant number of patients develop a decline in renal function. The mechanisms by which cisplatin produces renal injury are not well understood. It has been suggested that free radical-catalyzed lipid peroxidation can induce apoptosis or necrosis leading to renal injury. This study examined whether low concentrations of cisplatin induce apoptosis in LLC-PK1 cells and whether caspases 1, 2, 3, 8, and 9 are activated during this event. Our results show a dose- and time-dependent induction of apoptosis by micromolar concentrations of cisplatin. Expression of oncogenes c-myc and p53 was induced, and except for caspase 1, all the other caspases tested were activated. Z-VAD, the broad-spectrum inhibitor of caspases, prevented caspase activation and apoptosis, but not c-myc and p53 induction. On the other hand, N-acetylcysteine prevented cisplatin-induced apoptosis as well as c-myc induction but not p53 induction. The antioxidant trolox also prevented cisplatin-induced apoptosis. The results suggest that antioxidants and caspase inhibitors may alleviate cisplatin-associated nephrotoxicity.

Animals↗
PubMed2003

Evaluation of the 1992-1999 World Bank Schistosomiasis Control Project in China.

The 1992-1999 World Bank Schistosomiasis Control Project in China contributed significantly to the disease control with its specific strategy and approach. An evaluation was made in this paper based on project control and surveillance data collected from all project provinces systematically year by year. Several indicators were computed, comparison was made using the 1989 survey data as the baseline, and correlation analysis was carried out on prevalence in humans, prevalence in cattle and buffaloes and infection rate of snails. From 1992 to 1998, the overall prevalence in human population, prevalence in children aged 7-14 and prevalence in cattle and buffaloes decreased by 5.74, 59.55 and 62.30%, respectively. Snail areas increased by 14.85% throughout the project period, while snail infection rate and density of infected snails decreased by 68.75 and 44.95%. Hubei province was among all eight provinces the most impressive in schistosomiasis control during the project. Results show that coverage of chemotherapy was among other factors the most directly-related to the prevalence in humans. The drug for chemotherapy-praziquantel was effective for new cases rather than reinfection. As to the overall achievement, most of the objectives set for the project had been achieved, especially the decrease in prevalence, in both human population and cattle and buffaloes. However, the achievement of snail control was not so ideal, which calls for rectification for a more applicable and practical strategy of snail control in China.

Adolescent↗
PubMed2003

Autoantibodies to IL-12 in myasthenia gravis patients with thymoma; effects on the IFN-gamma responses of healthy CD4+ T cells.

In humans, interleukin-12 (IL-12) and interferon-alpha (IFN-alpha) normally favor IFN-gamma-producing "Th1" T cell responses. Myasthenia gravis (MG) patients with thymomas frequently have high-titer neutralizing autoantibodies against these cytokines, but not against IFN-gamma. Because they occasionally develop intractable (even fatal) infections, we have tested effects of their sera on the generation of IFN-gamma responses by healthy adult T cells to autologous lipopolysaccharide (LPS)-treated dendritic cells (DC). Anti-IL-12(+) sera consistently reduced IFN-gamma responses substantially, whether assessed by intracellular staining or ELISA. Therefore, thymoma patients with intractable infections might benefit from cautious IFN-gamma therapy. We discuss wider implications of the surprising rarity of clear clinical hazards-or benefits-of these autoantibodies.

Adult↗
PubMed2003

Nitric oxide inhibits the firing activity of hypothalamic paraventricular neurons that innervate the medulla oblongata: role of GABA.

Nitric oxide (NO) has been shown to modulate autonomic function by acting both peripherally and centrally. A growing body of evidence indicates that the paraventricular nucleus of the hypothalamus (PVN), an important site for autonomic and endocrine homeostasis, constitutes an important locus mediating central NO actions. However, the cellular targets and mechanisms mediating NO actions within the PVN are not completely understood. Here, we examined whether NO influences the firing activity of identified PVN neurons that innervate two functionally different autonomic centers, the dorsal vagal complex (DVC) and the rostral ventrolateral medulla (RVLM). Perforated patch-clamp recordings were performed in hypothalamic slices containing retrogradely labeled PVN neurons innervating the DVC or the RVLM. Application of the NO donors dyethylamine- or 1-propanamine, 3-(2-hydroxy-2-nitroso-1-propylhydrazino) NONOate inhibited the firing activity of both DVC- and RVLM-projecting PVN neurons. Furthermore, application of 2-(4-carboxypheny)-4,4,5,5,-tetramethilimidazoline-1-oxyl-3-oxide (carboxy-PTIO), or the relatively selective neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole alone, increased their basal firing activity, suggesting the presence of an endogenous NO inhibitory tone. GABAergic synaptic activity in PVN neurons was potentiated by NO donors, an action that involved a presynaptic mechanism. Furthermore, the NO-mediated inhibition of firing activity was blocked by the GABA(A) receptor antagonist bicuculline, suggesting that NO-inhibitory actions involved potentiation of local GABAergic synaptic activity. Immunohistochemical studies showed that approximately 25% of DVC- and RVLM-projecting PVN neurons express nNOS, suggesting that a proportion of these medullary-projecting PVN neurons contribute to the cellular source of NO within the PVN. In summary, NO has been identified as an important molecule controlling autonomic function under physiological and pathological conditions. Here, we provide information on the cellular mechanisms mediating central NO actions. Our results demonstrate for the first time that NO modulates the activity of identified populations of PVN neurons that innervate the medulla oblongata, an action that is likely mediated by enhancing synaptic GABAergic function. This work suggests that NO-GABA interaction in PVN neurons that innervate the medulla constitutes an efficient cellular mechanism mediating NO central regulation of autonomic function.

Action Potentials↗
PubMed2003

Evolution of microstructures in materials induced by electropulsing.

Nanostructures were formed in several conventional materials under single electropulsing, that is nanophases of alpha-Cu(Zn) and beta'-(CuZn) in a cold-worked alpha-Cu(Zn) alloy, nanosized gamma-Fe in a low-carbon steel, nanosized alpha-Al in a superduralumin, and orientated nanosized TiC in a TiC/NiCr cermet. The mechanisms responsible for the above nanostructured transitions can be attributed to the competition of many factors induced by electropulsing, including high-rate heating, thermal stress, reduced thermodynamic energy barrier and high-rate electron impacting. Also, many low-energy dislocation configurations, twins and stacking faults were formed in the copper alloy and cermet under the electropulsing. Such evolution of defects was associated with the electrical, thermal and stress energies induced by the electropulsing.

Journal Article↗
PubMed2003

p53 Immunostaining guided laser capture microdissection (p53-LCM) defines the presence of p53 gene mutations in focal regions of primary prostate cancer positive for p53 protein.

OBJECTIVES: A wide range of p53 mutations (5-65%), detected by various methods, has been reported in primary prostate cancers (CaP). IHC staining of radical prostatectomy specimens shows marked heterogeneity of focally distributed p53-positive cells. However, a significant relationship between the focal staining of p53 and cancer recurrence after radical prostatectomy has been noted. Increased frequency of p53 mutations has been generally observed in advanced stage CaP and metastatic prostate cancer cell lines. The significance of focal p53 immunostaining in primary CaP remains uncertain with respect to the p53 gene mutation or tumor progression. The goal of this study was to evaluate p53 gene mutations in focal regions of primary prostate cancers positive by p53 immunostaining. METHODS: Whole-mount prostates from men with clinically organ-confined prostate cancer were immunostained for p53 protein. Laser capture microdissection (LCM) was used to harvest p53 positive cells from areas of tumor and prostatic intraepithelial neoplasia and benign gland. DNA from microdissected cells were amplified for p53 exons 5-8 by polymerase chain reaction (PCR) and analyzed for mutations by single strand conformation polymorphism and DNA sequencing. Mutation analysis of the p53 gene exons 5-8 was performed in the p53 immunostaining positive focal regions (1+ to 4+) of whole-mount prostate sections from 16 patients. RESULTS: Of 16 patients with p53 IHC positive tumors, 11 (69%) had p53 gene mutations as determined by DNA sequence analysis. However, randomly microdissected tumor cells from 4 of 18 patients (22%) negative for p53 IHC also demonstrated mutations in the p53 gene. A significant fraction of prostate tumors with focally positive immunostaining for p53 have been confirmed to contain mutations in the p53 gene. CONCLUSIONS: p53 immunostaining guided LCM combined with DNA-based analyses emphasizes the presence of focal p53 mutations in primary prostate cancers and underscores the significance of previous observations showing a correlation between focal p53 immunostaining in primary CaP and cancer recurrence after radical prostatectomy.

Base Sequence↗
PubMed2003

Nitric oxide: a local signalling molecule controlling the activity of pre-autonomic neurones in the paraventricular nucleus of the hypothalamus.

AIM: The gas molecule nitric oxide (NO) has been shown to modulate autonomic function by acting both peripherally and centrally. Accumulating evidence indicates that the paraventricular nucleus (PVN) of the hypothalamus is an important locus mediating central NO actions on autonomic function, under both physiological and pathological conditions. However, the cellular targets and mechanisms mediating NO actions within the PVN are still poorly understood. RESULTS: By combining in vitro patch-clamp recordings with neuronal tract tracing techniques, we show that neuronal excitability of autonomic-related neurones in the PVN is tonically inhibited by an endogenous NO input. Furthermore, immunohistochemical studies show that approximately 25% of autonomic-related PVN neurones express neuronal nitric oxide synthase, suggesting that at least a proportion of them contribute to the cellular sources of NO within the PVN. CONCLUSION: In summary, this work suggests that NO modulation of the firing activity of autonomic-related PVN neurones constitutes an efficient mechanism mediated central NO regulation of autonomic function.

Action Potentials↗