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Biomedical subjects

Z Qiu

Publications and source records attributed to Z Qiu.

At least 19 recordsLinked to original sources
PubMed2001

A disulfide bond is required for functional assembly of NCX1 from complementary fragments.

The cardiac Na(+)-Ca(2+) exchanger consists of a single polypeptide with two transmembrane segment (TMS) clusters separated by a large intracellular loop between TMS5 and TMS6 (Nicoll et al. (1999) J. Biol. Chem. 274, 910-917; Iwamoto et al. (1999) FEBS Lett. 446, 264-268). A "split" exchanger can be expressed by dividing the exchanger cDNA into two fragments so that the NH(2)- and CO(2)H-terminal portions of the protein are expressed as separate polypeptides in HEK293 cells. Expression of partial exchanger molecules did not result in detectable exchanger activity. Cells coexpressing both portions of the exchanger, however, displayed between 30 and 50% of the activity of the intact wild-type exchanger. The full-length exchanger contains a disulfide bond between residues 14 or 20 and 792. We examined the role of this disulfide bond in the split exchanger by mutagenesis and expression studies. Our results indicate that the function of the exchanger requires both TMS clusters and that the C(14 or 20)/C792 disulfide bond is essential for expression of active exchangers from half molecules.

Animals↗
PubMed2001

Structure-activity relationship studies of a bisbenzimidazole-based, Zn(2+)-dependent inhibitor of HCV NS3 serine protease.

A survey of isosteric replacements of the phosphonoalanine side chain coupled with a process of conformational constraint of a bisbenzimidazole-based, Zn(2+)-dependent inhibitor of hepatitis C virus (HCV) NS3 serine protease resulted in the identification of novel series of active compounds with extended side chains. However, Zn(2+)-dependent HCV NS3 inhibition was relatively insensitive to the structural variations examined but dependent on the presence of negatively charged functionality. This result was interpreted in the context of an initial electrostatic interaction between protease and inhibitor that is subsequently consolidated by Zn(2+), with binding facilitated by the featureless active site and proximal regions of the HCV NS3 protein.

Antiviral Agents↗
PubMed2001

Co-transfer of human wild-type p53 and granulocyte-macrophage colony-stimulating factor genes via recombinant adenovirus induces apoptosis and enhances immunogenicity in laryngeal cancer cells.

Co-transfer of immunomodulatory and anti-proliferative genes may be the basis for new strategies to enhance tumor regression. The purpose of this study was to develop a combination gene therapy strategy for the treatment of laryngeal cancer. Human wild-type p53 and granulocyte-macrophage colony-stimulating factor (GM-CSF) genes were transferred into human laryngeal cancer cells mediated by adenovirus type 5 vector co-expressing human wild-type p53 and GM-CSF (Ad-p53/GM-CSF). By the introduction of the wild-type p53 gene, the growth of human laryngeal cancer Hep-2 cells was inhibited and their apoptosis was induced. By the introduction of the GM-CSF gene, the immunogenicity of cancer cells was enhanced. Significant proliferation of tumor infiltrating lymphocytes and tumor-specific cytotoxicity of cytotoxic T lymphocytes were induced by Ad-p53/GM-CSF-infected cancer cells in vitro. The results suggest that the co-transfer of human wild-type p53 and GM-CSF genes into tumor cells via recombinant adenovirus may be further developed into an effective and practical combination gene therapy strategy for laryngeal cancer.

Adenoviridae↗
PubMed2001

Split Na+-Ca2+ exchangers. Implications for function and expression.

The Na(+)-Ca(2+) exchanger has nine transmembrane segments, with a large cytoplasmic loop between the fifth and sixth transmembrane segments. The protein was split within the cytoplasmic loop into two domains consisting of the first five transmembrane segments and the last four transmembrane segments, respectively. The two domains were either expressed individually or coexpressed. Each of the two domains with different lengths of the cytoplasmic loop was fused to green fluorescent protein. We show that coexpression of both domains is required for proper membrane targeting and for expression of functional exchange activity. Fusion to green fluorescent protein does not alter biophysical properties of the exchange process. In addition, truncation of a large portion of the cytoplasmic loop does not alter important properties of the exchanger such as Na(+)-dependent inactivation, activation by chymotrypsin, or exchanger inhibitory peptide (XIP) sensitivity.

Animals↗
PubMed2001

Gene expression profile changes in initiation and progression of squamous cell carcinoma of esophagus.

Tumorigenesis is a complex process involving multiple genes. As a step toward understanding the complicated changes between normal and malignant cells, this report focused on gene expression profile variations among normal and abnormal esophageal epithelium tissues. The cDNA microarray approach was used to investigate gene expression profiles of 5 different stages during initiation and progression of esophageal cancer. According to pathological characteristics, these 5 stages were normal, dysplasia I (mild dysplasia), dysplasia II (moderate dysplasia), carcinoma in situ (CIS) and squamous cell carcinoma of esophagus (SCC). Comparing and analyzing those gene expression profiles, we observed that the expression levels of many genes changed in dysplasia I and some known tumor-related genes were over-expressed or under-expressed in all 4 abnormal stages. Using principle component analysis we identified a set of genes that may play an important role in tumor development. Hybridization data were confirmed by semi-quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. These results suggest that cDNA microarray technology is a useful tool to discover genes frequently involved in esophageal neoplasia and provides novel clues to diagnosis, early detection and intervention of SCC.

Carcinoma in Situ↗
PubMed2001

DNA synthesis and mitotic clonal expansion is not a required step for 3T3-L1 preadipocyte differentiation into adipocytes.

Upon differentiation induction of 3T3-L1 preadipocytes by a hormone mixture containing 1-isobutyl-3-methylxanthine, dexamethasone, and insulin, the preadipocytes undergo approximately 2 rounds of mitotic clonal expansion, which just precedes the adipogenic gene expression program and has been thought to be an essential early step for differentiation initiation. By inducing 3T3-L1 preadipocytes with each individual hormone, it was determined that the mitotic clonal expansion was induced only by insulin and not by 1-isobutyl-3-methylxanthine or dexamethasone. Cell number counting and fluorescence-activated cell-sorting analysis indicated that a significant fraction of 3T3-L1 preadipocytes differentiated into adipocytes without mitotic clonal expansion when induced with the combination of 1-isobutyl-3-methylxanthine and dexamethasone. Furthermore, when normally induced 3T3-L1 preadipocytes were treated with PD98059 (an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1) to block the activation of extracellular signal-regulated kinase (Erk) 1 and Erk2, the mitotic clonal expansion was blocked, but adipocyte differentiation was not affected. These observations were confirmed by bromodeoxyuridine labeling. The differentiated adipocytes induced with 1-isobutyl-3-methylxanthine and dexamethasone or standard hormone mixture plus PD98059 were not labeled by bromodeoxyuridine. Thus, it is evident that 3T3-L1 preadipocytes could differentiate into adipocytes without DNA synthesis and mitotic clonal expansion. Our results also suggested that activation of Erk1 and Erk2 is essential to but not sufficient for induction of mitotic clonal expansion.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Helix packing of functionally important regions of the cardiac Na(+)-Ca(2+) exchanger.

In a revised topological model of the cardiac Na(+)-Ca(2+) exchanger, there are nine transmembrane segments (TMSs) and two possible re-entrant loops (Nicoll, D. A., Ottolia, M., Lu, Y., Lu, L., and Philipson, K. D. (1999) J. Biol. Chem. 274, 910-917; Iwamoto, T., Nakamura, T. Y., Pan, Y., Uehara, A., Imanaga, I., and Shigekawa, M. (1999) FEBS Lett. 446, 264-268). The TMSs form two clusters separated by a large intracellular loop between TMS5 and TMS6. We have combined cysteine mutagenesis and oxidative cross-linking to study proximity relationships of TMSs in the exchanger. Pairs of cysteines were reintroduced into a cysteine-less exchanger, one in a TMS in the NH(2)-terminal cluster (TMSs 1-5) and the other in a TMS in the COOH-terminal cluster (TMSs 6-9). The mutant exchanger proteins were expressed in HEK293 cells, and disulfide bond formation between introduced cysteines was analyzed by gel mobility shifts. Western blots showed that S117C/V804C, A122C/Y892C, A151C/T815C, and A151C/A821C mutant proteins migrated at 120 kDa under reducing conditions and displayed a partial mobility shift to 160 kDa under nonreducing conditions. This shift indicates the formation of a disulfide bond between these paired cysteine residues. Copper phenanthroline and the cross-linker N', N'-o-phenylenedimaleimide enhanced the mobility shift to 160 kDa. Our data suggest that TMS7 is close to TMS3 near the intracellular side of the membrane and is in the vicinity of TMS2 near the extracellular surface. Also, TMS2 must adjoin TMS8. This initial packing model of the exchanger brings two functionally important domains in the exchanger, the alpha 1 and alpha 2 repeats, close to each other.

Animals↗
PubMed2001

A novel approach for studying endogenous abeta processing using cultured primary neurons isolated from APP transgenic mice.

The central component of senile amyloid plaques in Alzheimer's disease (AD) is the beta-amyloid peptide (Abeta), derived from proteolytic processing of the amyloid precursor protein (APP). In this study, we developed an in vitro model to measure and identify soluble Abeta from primary cortical neurons. Neurons were isolated from mice transgenic for human APP695 containing the K670N, M671L double mutation. We characterized soluble Abeta using Western blot and ELISA assays. We found that the Abeta levels in conditioned media from these neurons were readily detectable and almost five times higher than in CSF. The majority of Abeta in the media was Abeta1-40; however, Abeta1-42 was also detectable. When the neurons were exposed to Phorbol 12-myristate 13-acetate (PMA), alpha1-antichymotrypsin, or alpha1-antitrypsin, the alterations of soluble Abeta levels were consistent with other models reported. Most importantly, the soluble Abeta in our model was remarkably stable, and aliquots were unchanged after prolonged incubations or repeated freeze/thaw cycles. The Abeta appeared to be monomeric by Western blot analysis. Soluble Abeta coimmunoprecipitated with endogenous mouse apolipoprotein E from the primary cultures. Taken together, our data demonstrated that using a Western blot assay to detect soluble Abeta from transgenic mouse overexpressing APP695 is sensitive, specific, and reliable and provides an accessible model for examining the neuronal metabolism of APP and Abeta.

Amyloid beta-Peptides↗
PubMed2001

Elevation of LDL receptor-related protein levels via ligand interactions in Alzheimer disease and in vitro.

The low-density lipoprotein (LDL) receptor-related protein (LRP) is a multifunctional receptor in the CNS that binds both apolipoprotein E (apoE) and activated alpha2-macroglobulin (alpha2M*); all 3 proteins are genetically associated with Alzheimer disease (AD). In this study we found an 85% increase in LRP levels in human AD brain frontal cortex, along with an increased level of the LRP ligands, apoE, and alpha2M. We speculated that LRP levels might be increased in response to the increased levels of its ligands, apoE, and alpha2M*. To test this hypothesis we examined the effects of alpha2M* on LRP in primary cultures. Treatment of neurons with alpha2M* significantly increased LRP levels (by 92%). This increase was prevented by coculture with receptor-associated protein (RAP), which blocks binding of LRP ligands to LRP Native alpha2M or RAP alone did not change LRP levels in vitro. We also found that alpha2M* stimulated activation of astrocytes in vitro and promoted the levels of LRP by 65%. These data indicate 1) the LRP ligand alpha2M* increases levels of LRP in primary neuronal and astrocytic cultures, 2) alpha2M*-induction of LRP levels in vitro depends on binding to LRP, and 3) LRP levels are increased in AD brain, perhaps in response to the increased levels of alpha2M.

Aged↗
PubMed2001

[Single particle source apportionment of atmospheric aerosol based on proton microprobe].

A proton microprobe with high resolution and high sensitivity was applied to analyze atmospheric aerosol in the people's park in Shanghai urban for single particle source apportionment. The results showed that the sum of the average contribution rates from the sources of soil dust, building construction dust, vehicle exhaust and metallurgical industry, which are the main pollution sources of atmospheric aerosol in Shanghai urban and surpasses 80%. Besides, about 13% of the particles could not be identified. On the basis of cluster analysis of these particles, they are preliminary known belonging to two different individual sub-pollution sources and a new unidentified pollution source.

Aerosols↗
PubMed2001

[Adenovirus-mediated transfer of human wild-type p53, GM-CSF, and B7-1 genes efficiently produces growth suppression and apoptosis of hepatocellular cells in vitro].

OBJECTIVE: To investigate the tumor suppressor activity of recombinant adenovirus vector expressing the human wild-type p53, GM-CSF, and B7-1 proteins (designated as BB-102) in human hepatocellular carcinoma cells (HCC) in vitro. METHODS: The wild-type p53 BEL-7402, mutant p53 HLE, and HuH-7 HCC cell lines were infected with BB-102 at MOI of 50 in vitro. Immunohistochemical assay was used to determine p53 expressed by BB-102. Tumor suppressor activity of the expressed p53 was identified by terminal deoxynucleotidy I transferase (TdT) assay in BB-102-infected HCC cell lines. RESULTS: p53 protein was found to express in a dose-dependent manner in BB-102-infected HCC cell lines. The proliferation of HCC cell lines were suppressed significantly at the average rates of 58.5%, 81.5%, and 71.1% for BEL-7402, HLE, and HuH-7 respectively from 4 to 10 days, accompanying inducing apoptosis in BB-102-infected HCC cell lines. CONCLUSIONS: Besides the expression of B7-1 and GM-CSF, BB-102 is able to express p53 protein in independent manner and exerts its anti-tumor activity, which suggests that BB-102 may be useful for gene therapy against HCC in vivo.

Adenoviridae↗
PubMed2000

c-Crk, a substrate of the insulin-like growth factor-1 receptor tyrosine kinase, functions as an early signal mediator in the adipocyte differentiation process.

Differentiation of 3T3-L1 preadipocytes into adipocytes is induced by a combination of inducers, including a glucocorticoid, an agent that elevates cellular cAMP, and a ligand of the insulin-like growth factor-1 receptor. Previous studies have implicated protein-tyrosine phosphatase (PTPase) HA2, a homologue of PTPase 1B, in the signaling cascade initiated by the differentiation inducers. Vanadate, a potent PTPase inhibitor, blocks adipocyte differentiation at an early stage in the program, but has no effect on the mitotic clonal expansion required for differentiation. Exposure of preadipocytes to vanadate along with the inducing agents led to the accumulation of pp35, a phosphotyrosyl protein that is a substrate for PTPase HA2. pp35 was purified to homogeneity and shown by amino acid sequence and mass analyses of tryptic peptides to be c-Crk, a known cytoplasmic target of the insulin-like growth factor-1 receptor tyrosine kinase. Transfection of 3T3-L1 preadipocytes with a c-Crk antisense RNA expression vector markedly reduced c-Crk levels and prevented differentiation into adipocytes. Studies with C3G, a protein that binds to the SH3 domain in c-Crk, showed that phosphorylation of c-Crk rendered the SH3 domain inaccessible to C3G. Taken together, these findings indicate that locking c-Crk in the phosphorylated state with vanadate prevents its participation in the signaling system that initiates adipocyte differentiation.

3T3 Cells↗
PubMed2000

Dynamic process of information transmission complexity in human brains.

Based on a complexity analysis of mutual information transmission of EEG developed by us [Xu J, Liu Z, Liu R, Yang Q (1997) Physica D 106: 363-374], dynamic processes of the complexity of mutual information transmission in human brains were studied. To diminish possible problems due to coarse graining preprocessing, some new measures of complexity were used. The results show that, just before and after generalized seizures, the complexities of almost all information transmission between different brain areas drop significantly; there is also a temporary decrease of complexity when subjects shift their attention. The above facts suggest that there is a transient decrease of information transmission complexity when brain state changes occur suddenly. Mental arithmetic tasks activate the left temporal lobe to exchange more information with other brain areas. The results hint that the methods used here might be an approach to observe quick processes in the living brain.

Adult↗
PubMed2000

Modified Aloe barbadensis polysaccharide with immunoregulatory activity.

Aloe barbadensis polysaccharide was partially digested with cellulase and further purified by dialysis, stepwise ethanol precipitation, and size exclusion chromatography. Crude modified Aloe polysaccharide (MAP) activated macrophage cells and stimulated fibroblast growth. Under the same conditions, native Aloe barbadensis gel had no effect on macrophage activation. MAP prevented ultraviolet B (UVB) irradiation-induced immune suppression as determined by contact hypersensitivity (CHS) response in C3H/HeN mice. This in vivo activity was correlated with the activity of MAP to inhibit UVB irradiation-induced tumor necrosis factor alpha (TNF-alpha) release from human epidermoid carcinoma cells (KB cells). MAP with an average molecular weight of 80,000 Dalton (Da) contained mannose, galactose, and glucose in a ratio of 40:1.4:1.0. MAP was likely a linear, highly acetylated molecule.

Adjuvants, Immunologic↗
PubMed2000

Mutations in the E1 hydrophobic domain of rubella virus impair virus infectivity but not virus assembly.

Rubella virus (RV) virions contain three structural proteins, a capsid protein that interacts with viral genomic RNA to form a nucleocapsid and two membrane glycoproteins, E2 and E1. We found that substitution of either an aspartic acid residue at Gly93 (G93D) or a glycine residue at Pro104 (P104G) in the internal hydrophobic domain of E1 affected virus infectivity but not virus assembly. Viruses carrying G93D and P104G mutations had impaired infectivity, reduced 1,000-fold and 10-fold, respectively. A revertant was isolated from the G93D mutant. Sequencing analysis showed that the substituted aspartic acid residue in G93D mutant had reverted to the original glycine residue, suggesting the involvement of Gly93 in membrane fusion during viral entry.

Amino Acid Substitution↗
PubMed2000

Anti-fecundity immunity in mice immunized with anti-idiotypic monoclonal antibody NP30 of Schistosoma japonicum.

OBJECTIVE: To observe the effects of anti-fecundity and anti-embryonation immunity of anti-idiotypic monoclonal antibody NP30 of Schistosoma japonicum on female adult worm. METHODS: The active immunization of C57BL/6 mice was conducted by means of three intraperitoneal injections of NP30. The control group was injected with SP2/0 ascites intraperitoneally. RESULTS: On the twenty-seventh day after challenge infection, the number of eggs in the liver tissue and in uterus of the group immunized with NP30 decreased by 30.91% and by 38.55%, respectively. On the thirty-ninth day after the challenge infection, the number of mature eggs in the liver tissue of the group immunized with NP30 decreased by 66.63% and the number of dead eggs increased by 60.66%. CONCLUSIONS: NP30, with which mice were actively immunized, possesses double effects of anti-fecundity and anti-embryonation immunity on female adult worm of Schistosoma japonicum, therefore it can be used as a promising candidate of anti-pathologic vaccine molecule against Schistosomiasis japonica.

Animals↗
PubMed2000

Vasoactive effects of adrenotensin and its interactions with adrenomedullin.

OBJECTIVE: To investigate the vasoactive effects of adrenotensin and the interactions between adrenotensin and adrenomedullin (ADM). METHODS: Isolated rat aortic tension, rat mean arterial pressure and 3H-TdR incorporation of rat vascular smooth muscle cells were measured. Isolated rat aortas were incubated in K-H solution containing adrenomedullin or adrenotensin. The released adrenotensin or adrenomedullin (in incubation medium) from rat aortas was measured by radioimmunoassay. RESULTS: 1 x 10(-8) and 1 x 10(-7) mol/L adrenotensin augmented rat aortic tension in a dose-dependent manner (P < 0.01). An intravenous bolus injection of adrenotensin (2.5 nmol/kg, i.v.) increased the mean arterial pressure by 28% in anesthetized rats (P < 0.01). 1 x 10(-7) mol/L adrenotensin increased 3H-TdR incorporation in cultured rat vascular smooth muscle cells by 55% (P < 0.01). Adrenomedullin inhibited these activities of adrenotensin to different extents. 1 x 10(-9), 1 x 10(-8) and 1 x 10(-7) mol/L adrenotensin decreased adrenomedullin release rates by 19%, 35% and 46%, respectively (P < 0.05 or P < 0.01) and 1 x 10(-8) mol/L adrenomedullin also inhibited adrenotensin release by 45% from rat aorta (P < 0.01). CONCLUSION: Adrenotensin is a novel peptide that elicits the activities of vasoconstriction, pressor effects and induces the proliferation of vascular smooth muscle cells. There is antagonism in vascular activities and reciprocal inhibition in the release between adrenotensin and adrenomedullin. These interactions are manifestations of intramolecular regulation of proadrenomedullin (Pro-ADM).

Adrenomedullin↗