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Biomedical subjects

Q Zhang

Publications and source records attributed to Q Zhang.

At least 181 records · Page 10Linked to original sources
PubMed2001

Involvement of Erks activation in cadmium-induced AP-1 transactivation in vitro and in vivo.

Cadmium is a potent and effective carcinogen in rodents and has recently been accepted by IARC (International Agency for Research on Cancer) as a category I carcinogen. Cadmium-induced up-regulation of intracellular signaling pathways leading to increased mitogenesis is thought to be a major mechanism for the carcinogenic activity following chronic cadmium exposure. In the present study, we found that exposure of cells to cadmium induced significant activation of AP-1 and all three members of the MAP kinase family in mouse epidermal JB6 cells. The induction of AP-1 activity by cadmium appears to involve activation of Erks, since the induction of AP-1 activity by cadmium was blocked by pretreatment of cells with PD98058. Interestingly, the induction of AP-1 by cadmium was greatly enhanced by the chemical tumor promoter, TPA and the growth factor EGF, but not by ultraviolet C radiation. In vivo studies demonstrated that cadmium could also induce transactivation of AP-1 in AP-1-luciferase report transgenic mice. Considering the role of AP-1 activation in tumor promotion, the results presented in this study provide a possible molecular mechanism for cadmium-induced carcinogenesis.

Animals↗
PubMed2001

Rac1 orientates epithelial apical polarity through effects on basolateral laminin assembly.

Cellular polarization involves the generation of asymmetry along an intracellular axis. In a multicellular tissue, the asymmetry of individual cells must conform to the overlying architecture of the tissue. However, the mechanisms that couple cellular polarization to tissue morphogenesis are poorly understood. Here, we report that orientation of apical polarity in developing Madin-Darby canine kidney (MDCK) epithelial cysts requires the small GTPase Rac1 and the basement membrane component laminin. Dominant-negative Rac1 alters the supramolecular assembly of endogenous MDCK laminin and causes a striking inversion of apical polarity. Exogenous laminin is recruited to the surface of these cysts and rescues apical polarity. These findings implicate Rac1-mediated laminin assembly in apical pole orientation. By linking apical orientation to generation of the basement membrane, epithelial cells ensure the coordination of polarity with tissue architecture.

Actins↗
PubMed2001

Gene therapy restores vision in a canine model of childhood blindness.

The relationship between the neurosensory photoreceptors and the adjacent retinal pigment epithelium (RPE) controls not only normal retinal function, but also the pathogenesis of hereditary retinal degenerations. The molecular bases for both primary photoreceptor and RPE diseases that cause blindness have been identified. Gene therapy has been used successfully to slow degeneration in rodent models of primary photoreceptor diseases, but efficacy of gene therapy directed at photoreceptors and RPE in a large-animal model of human disease has not been reported. Here we study one of the most clinically severe retinal degenerations, Leber congenital amaurosis (LCA). LCA causes near total blindness in infancy and can result from mutations in RPE65 (LCA, type II; MIM 180069 and 204100). A naturally occurring animal model, the RPE65-/- dog, suffers from early and severe visual impairment similar to that seen in human LCA. We used a recombinant adeno-associated virus (AAV) carrying wild-type RPE65 (AAV-RPE65) to test the efficacy of gene therapy in this model. Our results indicate that visual function was restored in this large animal model of childhood blindness.

Animals↗
PubMed2001

HAL1 mediate salt adaptation in Arabidopsis thaliana.

The yeast HAL1 gene was introduced into Arabidopsis thaliana by Agrobacterium tumefaciens-mediated transformation with vacuum infiltration under the control of CaMV 35S promoter. Thirty-three individual kanamycin resistant plants were obtained from 75,000 seeds. Southern blotting analysis indicated that HAL1 gene had been integrated into all of the transgenic plants' genomes. The copy number of HAL1 gene in transgenic plants was mostly 1 to 3 by Southern analysis. Phenotypes of transgenic plants have no differences with wild type plants. Several samples of transformants were self-pollinated, and progenies from transformed and non-transformed plants (controls) were evaluated for salt tolerance and gene expression. Measurement of concentrations of intracellular K+ and Na+ showed that transgenic lines were able to retain less Na+ than that of the control under salt stress. Results from different tests indicated the expression of HAL1 gene promotes a higher level of salt tolerance in vivo in the transgenic Arabidopsis plants.

Adaptation, Physiological↗
PubMed2001

Constitutive STAT3-activation in Sezary syndrome: tyrphostin AG490 inhibits STAT3-activation, interleukin-2 receptor expression and growth of leukemic Sezary cells.

Interleukin-2 (IL-2) is a growth factor which upon binding to high-affinity receptors (IL-2Ralphabetagamma) triggers mitogenesis in T cells. IL-2Ralpha expression is restricted to T cells which have recently encountered antigen, and in healthy individuals the majority (>95%) of peripheral T cells are IL-2Ralpha negative. An aberrant expression of IL-2Ralpha has recently been described in cutaneous T-cell lymphoma (CTCL). Here, we study the regulation of IL-2Ralpha expression and STATs in a tumor cell line obtained from peripheral blood from a patient with Sezary syndrome (SS), a leukemic variant of CTCL. We show that (1) STAT3 (a transcription factor known to regulate IL-2Ralpha transcription) is constitutively tyrosine-phosphorylated in SS tumor cells, but not in non-malignant T cells; (2) STAT3 binds constitutively to a STAT-binding sequence in the promotor of the IL-2Ralpha gene; (3) the Janus kinase inhibitor, tyrphostine AG490, inhibits STAT3 activation, STAT3 DNA binding, and IL-2Ralpha mRNA and protein expression in parallel; and (4) tyrphostine AG490 inhibits IL-2 driven mitogenesis and triggers apoptosis in SS tumor cells. In conclusion, we provide the first example of a constitutive STAT3 activation in SS tumor cells. Moreover, our findings suggest that STAT3 activation might play an important role in the constitutive IL-2Ralpha expression, survival, and growth of malignant SS cells.

Antineoplastic Agents↗
PubMed2001

Wolbachia infection shared among planthoppers (Homoptera: Delphacidae) and their endoparasite (Strepsiptera: Elenchidae): a probable case of interspecies transmission.

Wolbachia, a group of parasitic bacteria of arthropods, are believed to be horizontally transmitted among arthropod taxa. We present a new probable example of interspecies horizontal transmission of Wolbachia by way of an endoparasite based on the conformity of Wolbachia gene sequences. Field samples of two rice planthoppers, Laodelphax striatellus and Sogatella furcifera possessed identical Wolbachia. Among three major endoparasites of planthoppers, a strepsipteran, Elenchus japonicus, harboured the identical Wolbachia strain, suggesting strepsipteran transmission of Wolbachia from one planthopper to the other. No Wolbachia was detected in a mermithid nematode Agamermis unka, and dryinid wasps possessed different types of Wolbachia.

Animals↗
PubMed2001

Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus.

BACKGROUND & AIMS: The aim of this study was to assess the potential of 3 spectroscopic techniques (fluorescence, reflectance, and light-scattering spectroscopy) individually and in combination, for evaluating low- and high-grade dysplasia in patients with Barrett's esophagus (BE). METHODS: Fluorescence spectra at 11 excitation wavelengths and a reflectance spectrum were acquired in approximately 1 second from each site before biopsy using an optical fiber probe. The measured fluorescence spectra were combined with the reflectance spectra to extract the intrinsic tissue fluorescence. The reflectance spectra provided morphologic information about the bulk tissue, whereas light-scattering spectroscopy was used to determine cell nuclear crowding and enlargement in Barrett's epithelium. RESULTS: Significant differences were observed between dysplastic and nondysplastic BE in terms of intrinsic fluorescence, bulk scattering properties, and levels of epithelial cell nuclear crowding and enlargement. The combination of all 3 techniques resulted in superior sensitivity and specificity for separating high-grade from non-high-grade and dysplastic from nondysplastic epithelium. CONCLUSIONS: Intrinsic fluorescence, reflectance, and light-scattering spectroscopies provide complementary information about biochemical and morphologic changes that occur during the development of dysplasia. The combination of these techniques (Tri-Modal Spectroscopy) can serve as an excellent tool for the evaluation of dysplasia in BE.

Barrett Esophagus↗
PubMed2001

Changes in asthma drug therapy costs for patients receiving chronic montelukast therapy in the U.K.

The aim of this study was to assess changes in the costs of asthma drug therapy before and during the use of chronic montelukast treatment in the U.K. A retrospective cohort analysis of a primary care database in the U.K. was carried out. Patients with chronic montelukast use (> or = 140 once-daily doses) were selected for analysis. Benchmarking data were obtained for matched patients with chronic inhaled corticosteroid (ICS) use and patients with chronic salmeterol therapy with concomitant ICS use. The main outcome measures were changes in utilization and monthly cost of asthma therapies costs. Asthma patients experienced significant (P<0.05) reductions in the monthly costs of ICS, short-acting beta-agonists and antibiotics following chronic montelukast therapy. Monthly concomitant drug costs were reduced by Pound Sterling 7.49 per month, which offset 27.5% of the additional cost of montelukast, yielding an increase in total drug costs of Pound Sterling 19.78 per month. Meanwhile, increased total drug costs for matched patients with chronic ICS use, and matched patients with chronic salmeterol therapy and concomitant ICS use, increased by Pound Sterling 5.37 per month and Pound Sterling 44.55 per month respectively. Additionally, patients using chronic montelukast therapy experienced a statistically significant (P<0.05) reduction in the use of short acting beta-agonists, and antibiotics, suggesting improvement in asthma control. Chronic use of montelukast therapy is associated with a reduction of concomitant drug therapy costs.

Acetates↗
PubMed2001

High rates of loss of heterozygosity on chromosome 19p13 in human breast cancer.

We have recently discovered that the nuclear matrix protein SAFB is an oestrogen receptor corepressor. Since it has become clear that many steroid receptor cofactors play important roles in breast tumorigenesis, we investigated whether SAFB could also be involved in breast cancer. To address this question, the gene locus was examined for structural alterations in breast cancer tissue. Laser capture microdissection was used for isolating DNA from paired primary breast tumour and normal tissue specimens, and the loss of heterozygosity (LOH) at chromosome 19p13.2-3 was determined by use of microsatellite markers. LOH was detected at the marker D19S216, which colocalizes with the SAFB locus, in specimens from 29 (78.4%) of 37 informative patients. The peak LOH rate occurred at D19S216 near the SAFB locus, with LOH frequencies ranging from 21.6% to 47.2% at other markers. The finding of a very high LOH rate at the marker D19S216 strongly indicates the presence of a breast tumour-suppressor gene locus. While preliminary findings of mutations in SAFB suggest that this indeed may be a promising candidate, other potential candidate genes are located at this locus.

Antigens, Nuclear↗
PubMed2001

Two unusual oleanane saponins from Anemone anhuiensis.

From the rhizomes of Anemone anhuiensis (Ranunculaceae), two new triterpene saponins, anhuienosides A (1) and B (2), were isolated. These compounds are glycosylated at C-23 and their structures were elucidated as hederagenin 23-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside (1) and 23-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl ester (2) on the basis of chemical and spectral evidence.

Carbohydrate Sequence↗
PubMed2001

Screening for CRX gene mutations in Chinese patients with Leber congenital amaurosis and mutational phenotype.

PURPOSE: To screen for possible disease-causing mutations in the CRX gene in Chinese patients with Leber congenital amaurosis (LCA) and to enrich the understanding of its mutational phenotype. METHODS: Genomic DNA was collected from 27 patients with LCA. The coding sequences of the CRX gene were analyzed using the PCR-heteroduplex-SSCP method. Mutations were confirmed by DNA sequencing. RESULTS: We identified two heterozygous variations in the CRX gene in two patients with LCA. One was a deletion (GCC-->-CC, A181D1bp) leading to a frameshift and protein truncation. This mutation was present in a patient with LCA, but not in his healthy parents. The ocular manifestations of this A181Delta1bp mutation are described. An intronic variation (IVS1-13G-->C) was found in a patient with LCA as well as in his healthy father. CONCLUSION: A heterozygous A181D1bp mutation in the CRX gene caused an LCA phenotype in a Chinese patient.

Asian People↗
PubMed2001

Novel deletion of the RPGR gene in a Chinese family with X-linked retinitis pigmentosa.

PURPOSE: To characterize a Chinese family with inherited retinitis pigmentosa (RP). METHODS: Linkage studies and haplotype analysis were used for gene mapping, and single-strand conformation polymorphism (SSCP) analysis and direct DNA sequence analysis were used for identifying the responsible mutation. RESULTS: Pedigree analysis suggests that RP in the Chinese family RP002 is inherited either as an autosomal recessive trait or as an X-linked trait. Linkage analysis of RP002 excluded all known autosomal recessive RP loci. Further analysis with 17 polymorphic markers covering the entire X chromosome localized the RP gene in RP002 between markers GATA175D03 and GATA144D04 on Xp11.4, a region where the RP3 gene (RPGR ) is found. Mutation analysis of the RPGR gene in RP002 revealed a novel 28-bp deletion in exon 7. This deletion resulted in an in-frame stop codon that eliminates the C-terminal two-thirds of the RPGR protein. The 28-bp deletion co-segregated with the disease in the family and was not present in 100 normal Chinese individuals. Female carriers of the deletion were affected with myopia and had ERG abnormalities and mild constriction of visual field. CONCLUSIONS: A novel 28-bp deletion in the RPGR gene identified in an X-linked Chinese RP family causes severe RP in male patients as well as myopia and ERG abnormalities in female carriers. The deletion represents the largest microdeletion identified in RPGR to date, and expands the spectrum of RPGR mutations causing XLRP.

Adolescent↗
PubMed2001

Non-invasive and quantitative near-infrared haemoglobin spectrometry in the piglet brain during hypoxic stress, using a frequency-domain multidistance instrument.

The frequency-domain multiple-distance (FDMD) method is capable of measuring the absolute absorption and reduced scattering coefficients of optically turbid media. Absolute measurement of absorption at two near-infrared (NIR) wavelengths makes possible the quantitation of tissue haemoglobin concentration and tissue haemoglobin oxygen-saturation (StO2). However, errors are introduced by the uncertainties of background absorption and the dissimilarities between real tissues and the simplified mathematical model on which these measurements are based. An FDMD-based tissue instrument has been used for the monitoring of tissue haemoglobin concentration and oxygenation in the brain of newborn piglets during periods of hypoxia and hyperoxia. These tissue haemoglobin saturation values were compared with arterial saturation (SaO2) and venous saturation (SvO2) measured by blood gas analyses. A linear correlation was observed between StO2 and the average of SaO2 and SvO2. However, StO2 is not equal to any fixed weighted average of SaO2 and SvO2 unless we introduce an effective background tissue absorption. The magnitude of the background absorption was about 0.08 cm(-1) at 758 nm and 0.06 cm(-1) at 830 nm, and it was nearly consistent between piglets. The origin of this 'effective' background absorption may be real, an artefact caused by the application of a simplified model to a complex sample, or a combination of factors.

Animals↗
PubMed2001

Production of cloned goats from enucleated oocytes injected with cumulus cell nuclei or fused with cumulus cells.

This study was designed to produce cloned goats from cumulus cells. Cloning donor nuclei were from cumulus cells either freshly isolated or cultured in vitro. Enucleated oocytes were either injected with cumulus cell nuclei without piezo-driven manipulator (injection method) or fused with cumulus cells (fusion method). The survival rate of cloned embryos, obtained by injection, was higher than that derived from fusion (62.7 and 45.9%, respectively). Two cloned goats were derived by fusion with in vitro cultured cumulus cells without starvation, but died shortly after natural birth, from respiratory difficulties. Their birth weights (2.23 kg and 2.03 kg) were within the normal range (2.0-2.7 kg) and postmortem analysis revealed no morphological abnormalities. The third cloned goat, derived by injection of nuclei from freshly isolated cumulus cells, weighed 3.3 kg at birth, and was 37% overweight compared with the average weight of the same species. This goat is healthy and well as this paper is being prepared. Nested PCR-RFLP analysis confirmed that all the cloned goats were derived from the donor cells.

Animals↗
PubMed2001

Production of secretory leukocyte protease inhibitor by human amniotic membranes and regulation of its concentration in amniotic fluid.

Secretory leukocyte protease inhibitor (SLPI) is a potent inhibitor of human leukocyte elastase. SLPI is a protein found in various human fluids, including parotid secretions, cervical mucus, seminal plasma and ascites. Western blot analysis revealed that SLPI protein is detected as a 12 kDa band in both the amniotic fluid and the amniotic membrane. The amniotic fluid concentrations of SLPI were assayed by enzyme-linked immunosorbent assay. SLPI concentrations in the amniotic fluid of women in the third trimester were higher than those in the second trimester. Immunohistochemistry using an anti-SLPI polyclonal antibody revealed positive staining in epithelial cells in amniotic membranes. Reverse transcription-polymerase chain reaction demonstrated that SLPI transcripts could be detected in the amniotic membranes. To determine the mechanism of SLPI production by amniotic cells, purified amniotic cells were stimulated with various cytokines. Amniotic cells produced SLPI in a dose-dependent manner when stimulated with interleukin (IL)-1alpha, IL-1beta, and tumour necrosis factor-alpha. The present findings show that SLPI is produced by the amniotic membranes in response to cytokine concentrations. The SLPI in the amniotic fluid may contribute to immunodefence mechanisms during pregnancy.

Amniotic Fluid↗
PubMed2001

Surface acoustic wave reflection from diamond-like carbon thin film reflecting arrays on LiNbO3 substrates.

Surface acoustic wave (SAW) reflection from diamond-like carbon (DLC) strip reflecting arrays on Y-Z LiNbO3 is investigated. The reflection from DLC strips with triangular cross section has been observed. Reflection increases in alternating DLC and Al strips in 90 degrees reflecting arrays in comparison with pure Al structures. The values of reflection coefficient per period in the slanted reflecting arrays are estimated to be about 1.0% for pure DLC strips (height to wavelength ratio equal to 0.02), 2% for uniform Al coating on DLC reflecting arrays, and 3.5% for alternating DLC and Al strips. This value is higher than that for pure Al strips by about 0.7%. Reflection properties are briefly discussed, and preparation technique is presented.

Journal Article↗
PubMed2001

Prevalence, antigenic specificity, and bactericidal activity of poultry anti-Campylobacter maternal antibodies.

Poultry are considered the major reservoir for Campylobacter jejuni, a leading bacterial cause of human food-borne diarrhea. To understand the ecology of C. jejuni and develop strategies to control C. jejuni infection in the animal reservoir, we initiated studies to examine the potential role of anti-Campylobacter maternal antibodies in protecting young broiler chickens from infection by C. jejuni. Using an enzyme-linked immunosorbent assay (ELISA), the prevalence of anti-C. jejuni antibodies in breeder chickens, egg yolks, and broilers from multiple flocks of different farms were examined. High levels of antibodies to the organism were detected in serum samples of breeder chickens and in egg yolk contents. To determine the dynamics of anti-Campylobacter maternal antibody transferred from yolks to hatchlings, serum samples collected from five broiler flocks at weekly intervals from 1 to 28 or 42 days of age were also examined by ELISA. Sera from the 1-day and 7-day-old chicks showed high titers of antibodies to C. jejuni. Thereafter, antibody titers decreased substantially and were not detected during the third and fourth weeks of age. The disappearance of anti-Campylobacter maternal antibodies during 3 to 4 weeks of age coincides with the appearance of C. jejuni infections observed in many broiler chicken flocks. As shown by immunoblotting, the maternally derived antibodies recognized multiple membrane proteins of C. jejuni ranging from 19 to 107 kDa. Moreover, in vitro serum bactericidal assays showed that anti-Campylobacter maternal antibodies were active in antibody-dependent complement-mediated killing of C. jejuni. Together, these results highlight the widespread presence of functional anti-Campylobacter antibodies in the poultry production system and provide a strong rationale for further investigation of the potential role of anti-C. jejuni maternal antibodies in protecting young chickens from infection by C. jejuni.

Animals↗