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Biomedical subjects

Q Zeng

Publications and source records attributed to Q Zeng.

At least 91 records · Page 5Linked to original sources
PubMed1999

[Evaluation of therapeutic efficacy by detection of specific IgG and IgG4 against KLH in schistosomiasis japonica].

The specific IgG and IgG4 antibodies in the sera of patients with Schistosoma japonicum were determined by KLH-ELISA and SEA-ELISA. The results showed that KLH-ELISA was as sensitive and specific as SEA-ELISA. The negative conversion rates of IgG and IgG4 12 months after treatment detected by KLH-ELISA were significantly higher than those by SEA-ELISA. The negative conversion rate of IgG was 92.9%, and that of IgG4 was 97.6% 24 months after treatment. Therefore, it is regarded that detecting specific IgG and IgG4 by KLH has high value in both diagnosing schistosomiasis japonica and assessing its therapeutic efficacy. Particularly the specific IgG4 may be a short-duration antibody which can indicate successful chemotherapy of patients with chronic Schistosoma japonicum infection.

Animals↗
PubMed1998

The core metal-recognition domain of MerR.

MerR, the metalloregulatory protein of the mercury-resistance operon (mer) has unusually high affinity and specificity for ionic mercury, Hg(II). Prior genetic and biochemical evidence suggested that the protein has a structure consisting of an N-terminal DNA binding domain, a C-terminal Hg(II)-binding domain, and an intervening region involved with communication between these two domains. We have characterized a series of MerR deletion mutants and found that as little as 30% of the protein (residues 80-128) forms a stable dimer and retains high affinity for Hg(II). Biophysical measures indicate that this minimal Hg(II)-binding domain assumes the structural characteristics of the wild-type full-length protein both in the Hg(II) center itself and in an immediately adjacent helical protein domain. Our observations are consistent with the core Hg(II)-binding domain of the MerR dimer being constituted by a pair of antiparallel helices (possibly in a coiled-coil conformation) comprised of residues cysteine 82 through cysteine 117 from each monomer followed by a flexible loop through residue cysteine 126. These antiparallel helices would have a potential Hg(II)-binding site at each end. However, just as in the full-length protein, only one of these potential binding sites in the deleted proteins actually binds Hg(II).

Amino Acid Sequence↗
PubMed1998

Topoisomerase II-mediated site-directed alkylation of DNA by psorospermin and its use in mapping other topoisomerase II poison binding sites.

Psorospermin is a plant natural product that shows significant in vivo activity against P388 mouse leukemia. The molecular basis for this selectivity is unknown, although psorospermin has been demonstrated to intercalate into DNA and alkylate N7 of guanine. Significantly, the alkylation reactivity of psorospermin at specific sites on DNA increased 25-fold in the presence of topoisomerase II. In addition, psorospermin trapped the topoisomerase II-cleaved complex formation at the same site. These results imply that the efficacy of psorospermin is related to its interaction with the topoisomerase II-DNA complex. Because thermal treatment of (N7 guanine)-DNA adducts leads to DNA strand breakage, we were able to determine the site of alkylation of psorospermin within the topoisomerase II gate site and infer that intercalation takes place at the gate site between base pairs at the +1 and +2 positions. These results provide not only additional mechanistic information on the mode of action of the anticancer agent psorospermin but also structural insights into the design of an additional class of topoisomerase II poisons. Because the alkylation site for psorospermin in the presence of topoisomerase II can be assigned unambiguously and the intercalation site inferred, this drug is a useful probe for other topoisomerase poisons where the sites for interaction are less well defined.

Alkylation↗
PubMed1998

Design of new topoisomerase II inhibitors based upon a quinobenzoxazine self-assembly model.

A new class of pyridobenzophenoxazine compounds has been developed as topoisomerase II inhibitors for anticancer chemotherapy. These compounds were designed based on a proposed model of a quinobenzoxazine self-assembly complex on DNA. They showed excellent inhibitory effects on several tumor cell lines with nanomolar IC50 values. Their cytotoxic potency correlates with their ability to unwind DNA and inhibit topoisomerase II.

Antineoplastic Agents↗
PubMed1998

Requirement of Stat3 but not Stat1 activation for epidermal growth factor receptor- mediated cell growth In vitro.

Stimulation of epidermal growth factor receptor (EGFR) by ligand(s) leads to activation of signaling molecules including Stat1 and Stat3, two members of the signal transducers and activators of transcription (STAT) protein family. Activation of Stat1 and Stat3 was constitutive in transformed squamous epithelial cells, which produce elevated levels of TGF-alpha, and was enhanced by the addition of exogenous TGF-alpha. Targeting of Stat3 using antisense oligonucleotides directed against the translation initiation site, resulted in significant growth inhibition. In addition, cells stably transfected with dominant negative mutant Stat3 constructs failed to proliferate in vitro. In contrast, targeting of Stat1 using either antisense or dominant-negative strategies had no effect on cell growth. Thus, TGF-alpha/EGFR-mediated autocrine growth of transformed epithelial cells is dependent on activation of Stat3 but not Stat1.

Carcinoma, Hepatocellular↗
PubMed1998

Inhibition of human squamous cell carcinoma growth in vivo by epidermal growth factor receptor antisense RNA transcribed from the U6 promoter.

BACKGROUND: Squamous cell carcinomas of the head and neck (SCCHN), unlike normal mucosal squamous epithelial cells, overexpress epidermal growth factor receptor (EGFR) messenger RNA and protein. EGFR protein is required to sustain the proliferation of SCCHN cells in vitro. To determine whether EGFR expression contributes to tumor growth, we investigated the effect of suppressing EGFR expression in tumor xenografts through in situ expression of antisense oligonucleotides. METHODS: Intratumoral cationic liposome-mediated gene transfer was used to deliver plasmids capable of expressing sense or antisense EGFR sequences into human head and neck tumors, which were grown as subcutaneous xenografts in nude mice. The oligonucleotides were expressed under the control of the U6 RNA promoter. RESULTS: Direct inoculation of the EGFR antisense (but not the corresponding sense) plasmid construct into established SCCHN xenografts resulted in inhibition of tumor growth, suppression of EGFR protein expression, and an increased rate of apoptosis (programmed cell death). Sustained antitumor effects were observed for up to 2 weeks after the treatments were discontinued. CONCLUSION: These results suggest that interference with EGFR expression, using an antisense-based gene therapy approach, may be an effective means of treating EGFR-overexpressing tumors, including SCCHN.

Animals↗
PubMed1998

A single plasmid vector (pSTAR) mediating efficient tetracycline-induced gene expression.

A plasmid vector (pSTAR) has been constructed which confers neomycin resistance for selecting stably transfected cells, possesses a cloning cassette for placing a gene of interest under the control of the tetO DNA motif, and expresses rtTAnls which, upon association with tetracycline, binds to and drives gene expression from the tetO DNA motif. The plasmid pSTAR/LacZ, which has the gene for beta-galactosidase inserted into the cloning cassette, was transfected into Chinese hamster ovary (CHO) cells and selected for stably transfected cells. In pooled transfectants of CHO, tetracycline induced the expression of beta-galactosidase in 10-30% of cells. Using clonal transfectants, beta-galactosidase expression was induced by tetracycline in essentially every cell. Furthermore, induction of beta-galactosidase expression by tetracycline was both dose- and time-dependent. Similar tetracycline-induced beta-galactosidase expression is also observed in other cell types. The pSTAR vector is thus suited to facilitate the application of tetracycline-induced gene expression in diverse research areas.

Animals↗
PubMed1998

Downmodulation of TGF-alpha protein expression with antisense oligonucleotides inhibits proliferation of head and neck squamous carcinoma but not normal mucosal epithelial cells.

Interruption of an autocrine growth pathway involving TGF-alpha and EGFR may inhibit tumor growth and improve survival in head and neck cancer patients. We previously demonstrated that biopsy specimens and established cell lines from patients with squamous cell carcinoma of the head and neck (SCCHN) overexpress TGF-alpha and its receptor, epidermal growth factor receptor (EGFR) at both the mRNA and protein levels. Protein localization studies showed that TGF-alpha and EGFR are produced by the same epithelial cells in tissues from head and neck cancer patients further supporting a role for this ligand-receptor pair in an autocrine growth pathway. To confirm that TGF-alpha contributes to autocrine growth, we examined the effect of down regulation of TGF-alpha protein on SCCHN cell proliferation. Treatment of 6 SCCHN cell lines with antisense oligodeoxynucleotides targeting the translation start site of human TGF-alpha mRNA decreased TGF-alpha protein production by up to 93% and reduced cell proliferation by a mean of 76.2% compared to a 9.7% reduction with sense oligonucleotide (range P = 0.036-0.0001). TGF-alpha antisense oligonucleotide exposure also decreased TGF-alpha protein levels in normal oropharyngeal mucosal epithelial cells, however their growth rate was not affected. These findings indicate that TGF-alpha is participating in an autocrine signaling pathway in transformed, but not in normal mucosal epithelial cells, that promotes proliferation.

Base Sequence↗
PubMed1998

Mouse PRL-2 and PRL-3, two potentially prenylated protein tyrosine phosphatases homologous to PRL-1.

Protein tyrosine phosphatases (PTPs) play a fundamental role in regulating diverse cellular processes. PRL-1 is a unique nuclear PTP that is induced in mitogen-stimulated cells and regenerating liver. Database searches using the PRL-1 sequence led to the identification of mouse PRL-2 and PRL-3 which exhibit 87% and 76% identity to mouse PRL-1 in their amino acid sequences. All three mouse PRL proteins contain a C-terminal consensus sequence for prenylation. All PRL proteins bear significant sequence homology to Cdc14p and the recently identified tumor suppressor PTEN/MMAC1, in regions other than the conserved PTP signature motif. The nucleotide sequences of the coding regions of mouse PRL-2 and PRL-3 are, respectively, 71% and 62%, identical to mouse PRL-1, while the 5' un-translated regions of mouse PRL-1, PRL-2, and PRL-3 are much more divergent. Northern blot analysis revealed that PRL-2 is preferentially expressed in skeletal muscle, while PRL-3 is preferentially expressed in both skeletal muscle and heart, although both PRL-2 and PRL-3 are expressed at lower levels in other tissues.

Amino Acid Sequence↗
PubMed1998

A novel synaptobrevin/VAMP homologous protein (VAMP5) is increased during in vitro myogenesis and present in the plasma membrane.

cDNA clones encoding a novel protein (VAMP5) homologous to synaptobrevins/VAMPs are detected during database searches. The predicted 102-amino acid VAMP5 harbors a 23-residue hydrophobic region near the carboxyl terminus and exhibits an overall amino acid identity of 33% with synaptobrevin/VAMP1 and 2 and cellubrevin. Northern blot analysis reveals that the mRNA for VAMP5 is preferentially expressed in the skeletal muscle and heart, whereas significantly lower levels are detected in several other tissues but not in the brain. During in vitro differentiation (myogenesis) of C2C12 myoblasts into myotubes, the mRNA level for VAMP5 is increased approximately 8- to 10-fold. Immunoblot analysis using antibodies specific for VAMP5 shows that the protein levels are also elevated approximately 6-fold during in vitro myogenesis of C2C12 cells. Indirect immunofluorescence microscopy and immunoelectron microscopy reveal that VAMP5 is associated with the plasma membrane as well as intracellular perinuclear and peripheral vesicular structures of myotubes. Epitope-tagged versions of VAMP5 are similarly targeted to the plasma membrane.

Amino Acid Sequence↗
PubMed1998

Immunoreactive endothelin-1 and its receptors in human adrenal tissues.

To elucidate the pathophysiologic significance of endothelin-1 (ET-1) in adrenal and the mechanism for reduced responsiveness to exogenous ET-1 in aldosterone-producing adenoma (APA), we have investigated ET-1 receptors by radioligand binding assay (RBA) in human normal adrenal (NA), APA, idiopathic hyperaldosteronism (IHA), and pheochromocytoma (PHEO), immunoreactive (ir-) ET-1 content in NA, APA and PHEO by radioimmunoassay (RIA), and immunohistochemical staining of ET-1 with the peroxidase-anti-peroxidase (PAP) method in NA, APA, and PHEO. A single class of high-affinity binding sites for ET-1 was found in human NA and tumor tissues. Dissociation constant (Kd) values of ET-1 receptors were similar in NA, APA, and IHA, but maximal binding capacity (Bmax) of ET-1 receptors was lower in APA than in NA and IHA. Both Kd and Bmax in PHEO were higher than those in NA, APA, and IHA. Ir-ET-1 content in tumors of APA and PHEO were higher than in NA. Immunohistochemical staining was more intense in the tumor cells of APA and PHEO than in NA. These results suggest that the reduced response to exogenous ET-1 in APA could be related to downregulation of ET-1 receptors in the tumor. Increased ET-1 content and receptors may lead to hypersecretion of catecholamine in PHEO. ET-1 produced in normal and tumor adrenal tissues may regulate aldosterone and catecholamine secretion from adrenals in a paracrine/autocrine fashion.

Adrenal Gland Neoplasms↗
PubMed1998

Normalization of EGFR mRNA levels following restoration of wild-type p53 in a head and neck squamous cell carcinoma cell line.

Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by mutation of the p53 tumor suppressor gene and increased expression of the epidermal growth factor receptor (EGFR). To determine the potential link between p53 and EGFR expression, we examined the effect of overexpressing wild-type p53 on EGFR mRNA levels in HNSCC. In these studies, a temperature-sensitive (ts) p53 mutant was transfected into an HNSCC line which contained a deletion of one allele of the p53 gene and a mutation of the remaining allele. Following selection, six clones were isolated, characterized by Southern blot analysis, and stable expression of mutant p53 protein was confirmed by immunoblotting of clones grown at the mutant temperature. Total RNA was isolated from transfectants grown at both wild-type or mutant temperatures followed by Northern blot analysis to determine levels of EGFR mRNA expression at the two p53 conformations. Clones grown at the wild-type temperature (32.5 degreesC) demonstrated a 69% 13% decrease in EGFR mRNA compared with the same cells grown at the mutant temperature (39.5 degreesC; p=0.006) indicating that restoration of wild-type p53 reduces EGFR mRNA levels in this HNSCC cell line. These findings suggest that abnormalities in p53 may contribute to activation of EGFR gene transcription.

Blotting, Northern↗
PubMed1998

[Identification of antigens shared between Schistosoma japonicum and Trichinella spiralis].

Cross-reactivity was analysed between the antigen of T. spiralis muscular larvae and antigens of cercariae, liver stage schistosomula, 30 day male and female adult worms of S. japonicum by means of EITB technique. The result showed that the antigens of cercariae schistosomula, female worms except male worms, were recognized by sera from rabbits immunized with T. spiralis antigens or by sera from T. spiralis infected rabbits. The molecular weight of recognized antigens ranges from 15 to 100 kD, mainly from 50 to 70 kD. The immunized rabbit sera and the infected rabbit sera reacted with the same cross-antigens of S. japonicum. Among these schistosome stages, the cercariae showed the most cross-reactive bands, the second were the liver stage schistosomula, and 30 day female worms only showed a weak band which located at 97 kD position. Meanwhile, the anti-S. japonicum sera recognized several T. spiralis antigens which located at 34 kD and above, especially 35-38 kD. The results suggest that there are many antigens shared between T. spiralis and S. japonicum and the main cross-reactive antigens are found in the larva stages of S. japonicum and T. spiralis muscular larva. The cross-reactive antigens are different between various stages of S. japonicum and muscular larva of T. spiralis.

Animals↗
PubMed1998

[An ultrastructural observation of peripheral blood neutrophils in patients with hepatitis B].

The abnormal changes of peripheral blood neutrophils in 13 patients with hepatitis B were observed under electron microscope. The morphological and structural changes of neutrophils included irregularity of shape, a large number of pseudopodia and phagocytic vacuoles, less electron dense granules, increased nuclear holes and vacuoles, etc. The present study provides the ultrastructural evidence of impaired neutrophil morphology and functions in such patients.

Adult↗
PubMed1998

[Morphometric analysis of gap junctions of the cell membrane in human uterine smooth muscle at term].

OBJECTIVE: To study the changes of the gap junctions (GJS) in the uterine smooth muscle cells at various stages of labor, and its relationship with the onset of labor. METHODS: 18 women (38 to 41 gestational weeks) were divided into three groups: not-in-labor, pre-labor, active in labor and six cases in each group. The uterine myometrium tissues were observed by transmission electron microscopy (TEM) and lanthanum tracing method. RESULTS: The lengths and areas of GJS in uterine corpus and lower segment in the active in labor group were significantly larger than that of the other 2 groups, but there was no significant difference between the not-in-labor and pre-labor groups. The area but not the lengths of GJS in corpus was significant larger than that in the lower segment in the active in labor group. CONCLUSION: The great increase of length and areas of GJS in all parts of the uterine smooth muscle was closely correlated with onset of labor.

Adult↗
PubMed1998

[Schistosoma japonicum: purification and diagnostic application of recombinant 32 kD antigen].

Separation and purification of rSj32 were carried out with SDS-PAGE and electroelution technique. The purified rSj32, AWA and SEA were used to examine sera of patients with schistosomiasis, healthy individuals and patients with other parasitic diseases by ELISA. The results showed that the molecule weight of rSj32 was 37 kD. The sensitivity and specificity of rSj32 as a coating antigen in ELISA were as good as those of AWA and SEA. It is suggested that rSj32 antigen is a potential antigen for immunodiagnosis of schistosomiasis japonica.

Animals↗
PubMed1998

[Distribution of transforming growth factor-beta and its receptor in bronchiolo-alveolar cell hyperplasia and bronchiolo-alveolar carcinoma].

The distribution of the three isoforms of transforming growth factor (TGF)-beta (TGF-beta 1, -beta 2, and -beta 3) as well as their signaling receptor, TGF-beta type I receptor (T beta R-I), in bronchiolo-alveolar cell hyperplasia (BAH) and bronchiolo-alveolar carcinoma (BAC) was examined by immunohistochemistry using specific antibodies. The results showed that the expression of one or more TGF-beta subtypes occurred in a large proportion of BAC and BAH tissues. The expression of TGF-beta 1 and TGF-beta 3 was increased in tumor cells compared with hyperplastic cells. BAC with expression of two or three ligands was associated with a higher incidence of lymph node metastasis. These results suggest that hyperplastic cells and cancer cells derived from bronchiolo-alveolar cell can synthesize and secrete TGF-beta isoforms and its receptor T beta R-I which may contribute to the progression of BAC in part.

Adenocarcinoma, Bronchiolo-Alveolar↗