Biomedical subjects

X Zeng

Publications and source records attributed to X Zeng.

At least 37 records · Page 2Linked to original sources

PubMed2001

Atrial L-type Ca2+-channel, beta-adrenorecptor, and 5-hydroxytryptamine type 4 receptor mRNAs in human atrial fibrillation.

Molecular and electrical remodeling of ion channels determining action potential duration has been proposed as a major mechanism in chronic atrial fibrillation. We investigated the mRNA expression of the cardiac L-type Ca2+-channel subunits alpha1c, alpha2/delta1, beta1a, and beta1b/c in atrial tissue of patients with chronic atrial fibrillation compared to patients in sinus rhythm. In addition, the mRNA expression of the 5-hydroxytryptamine type 4-, beta1-, and beta2-adrenergic receptors, which are known to stimulate the L-type Ca2+-current in human atrium, was analyzed and the effect of chronic beta-blocker treatment on the mRNA expression of these receptors and of the L-type Ca2+-channel subunits was assessed. Total RNA was isolated from right atrial appendages of patients in sinus rhythm and of patients with chronic atrial fibrillation. Then, semiquantitative RT-PCR using 18S RNA as the "housekeeping gene" was performed. In patients with chronic atrial fibrillation, there were only mild reductions in mRNA expression of the alpha1c-subunit (-15.5 %, p = 0.13), and of the beta1-subunit isoforms a and c (-13.3 %, p = 0.14 and -16.6%, p = 0.18, respectively). However, mRNA expression of the alpha2/delta1-subunit (-31.5 %, p < 0.01) and of the beta1-subunit isoform b (-39.9 %, p < 0.0005) was significantly reduced in patients with chronic AF. Taken together, the mRNA expression of the beta1-subunit isoforms b and c, which are splice variants, was significantly down-regulated by 26.5 % (p < 0.05) in these patients. The analysis of the beta1c/beta1b ratio resulted in a significant shift by 39.2 % (p < 0.0001) in favor of beta1c in patients with chronic atrial fibrillation. In the AF patients, the abundance of the 5-HT4-receptor transcript was significantly reduced by 36 % (p < 0.05). The beta-adrenoreceptor transcription was unchanged. In both SR and AF patients, chronic beta-blocker treatment did neither significantly effect the mRNA expression of the L-type Ca2+-channel subunits, the beta-adrenoreceptor subtypes 1 and 2, nor that of the 5-HT4-receptor. Our data show that chronic AF is associated with a decrease in the atrial mRNA amount of auxiliary subunits of the L-type Ca2+-channel and of the 5-HT4-receptor. This supports the hypothesis that the observed alterations in mRNA transcription in AF patients may lead to a decrease in the availability of functional L-type Ca2+-channels and 5-HT4-receptors and/or reduce L-type Ca2+-current amplitude and density, thus, promoting and stabilizing the arrhythmia.

Adrenergic beta-Antagonists↗

PubMed2001

Effects of homocysteine on murine splenic B lymphocyte proliferation and its signal transduction mechanism.

OBJECTIVE: Elevated plasma homocysteine (Hcy) levels have been defined as an increased risk of atherosclerosis. However, the mechanisms that Hcy induces the development of atherosclerosis are not fully understood. Therefore, effect of Hcy on B lymphocyte proliferation and its cellular mechanism were examined in normal and hyperhomocysteinemia ApoE-knockout mice. METHODS: Mouse B lymphocytes were incubated with Hcy, related compounds and/or antioxidants and/or inhibitors of PKC, p38 MAPK, NF-kappaB in the presence or absence of lipopolysaccharide. DNA synthesis, production of reactive oxygen species was measured. RESULTS: Hcy (0.1-3.0 mM) and other compounds with thiol (-SH), such as cysteine and glutathione significantly increased resting and lipopolysaccharide-induced B lymphocyte proliferation. ApoE-knockout mice with hypercysteinemia (plasma Hcy levels were 20.3+/-2.9 vs. 2.6+/-0.6 microM in control, P<0.05) had a significant promotion of B cell proliferation in response to lipopolysaccharide. Hcy also increased intracellular reactive oxygen species production. Radical scavengers reduced Hcy-induced B lymphocyte proliferation. The promotion of Hcy was significantly inhibited by inhibitors of PKC (calphostin C and RO-31-8220), p38 MAPK (SB 202190 and PD 169316) and NF-kappaB (pyrrolidine dithiocarbamate). CONCLUSIONS: The reactive oxygen species generated by thiol (-SH) auto-oxidation of Hcy are essential, and PKC, p38 MAPK and NF-kappaB are involved in the Hcy-induced B lymphocyte proliferation. Hyperhomocysteinemia may increase B lymphocyte susceptibility to inflammatory progression of atherosclerotic lesions.

Analysis of Variance↗

PubMed2001

Dissociation and unfolding of GCN4 leucine zipper in the presence of sodium dodecyl sulfate.

The dissociation and unfolding behavior of the GCN4 leucine zipper has been studied using SDS titration. Circular dichroism (CD) spectra showed that the alpha-helix content of the leucine zipper (20 microM) decreased during the sodium dodecyl sulfate (SDS) titration. However, the alpha-helix content of the leucine zipper still remained significant in the presence of 1 mM SDS, with little change detected when the SDS concentration further increased to 2 mM. The dimer dissociation of the leucine zipper is also a co-operative process during SDS titration; with no dimer remaining when SDS concentration reached 1 mM, as shown by electrophoresis and the the theta(222)/theta(208) ratio. Our results indicate that SDS efficiently induces leucine zipper dimer dissociation with the monomers still partially folded. The experimental results provide important evidence for the previous model that partial helix formation precedes dimerization in coiled coil folding.

Circular Dichroism↗

PubMed2001

A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1.

Phosphorylation of the human p53 protein at Ser-392 has been shown to be responsive to UV but not gamma irradiation. Here we describe identification and purification of a mammalian UV-activated protein kinase complex that phosphorylates Ser-392 of p53 in vitro. This kinase complex contains casein kinase 2 (CK2) and the chromatin transcriptional elongation factor FACT (a heterodimer of hSpt16 and SSRP1). In vitro studies show that FACT alters the specificity of CK2 in the complex such that it selectively phosphorylates p53 over other substrates including casein. In addition, phosphorylation by the kinase complex enhances p53 activity. These results thus provide a potential mechanism for p53 activation by UV irradiation.

Amino Acid Sequence↗

PubMed2001

DNA polymerase eta is an A-T mutator in somatic hypermutation of immunoglobulin variable genes.

To determine whether DNA polymerase eta plays a role in the hypermutation of immunoglobulin variable genes, we examined the frequency and pattern of substitutions in variable VH6 genes from the peripheral blood lymphocytes of three patients with xeroderma pigmentosum variant disease, whose polymerase eta had genetic defects. The frequency of mutation was normal but the types of base changes were different: there was a decrease in mutations at A and T and a concomitant rise in mutations at G and C. We propose that more than one polymerase contributes to hypermutation and that if one is absent, others compensate. The data indicate that polymerase eta is involved in generating errors that occur predominantly at A and T and that another polymerase(s) may preferentially generate errors opposite G and C.

Animals↗

PubMed2001

NBP is the p53 homolog p63.

We previously identified a non-p53, p53-responsive DNA element (p53RE)-binding protein named NBP, functionally analogous to p53, from human cervical carcinoma Hela cells. Here we report a biochemical study demonstrating that this activity is the recently cloned p53 analog p63. NBP was purified through conventional and DNA affinity chromatography to apparent homogeneity with a prominent polypeptide migrating in between the 43 and 68 kDa positions on a SDS gel. This polypeptide immunoreacted with monoclonal anti-p63 but not anti-p53 or anti-p73 antibodies. Also, NBP co-purified with p63 through each step of fractionation, as detected with anti-p63 antibodies. DNA-protein complexes formed with purified NBP and p53RE-containing oligomers derived from the p21(waf1) promoter were supershifted by anti-p63 but not anti-p53 antibodies. Thus, these results demonstrate that NBP is encoded by the p53 homolog p63 gene.

Blotting, Western↗

PubMed2001

Transient transgenic expression of gamma interferon promotes Legionella pneumophila clearance in immunocompetent hosts.

Gamma interferon (IFN-gamma) and T1-phenotype immune responses are important components of host defense against a variety of intracellular pathogens, including Legionella pneumophila. The benefit of intrapulmonary adenovirus-mediated IFN-gamma gene therapy was investigated in a nonlethal murine model of experimental L. pneumophila pneumonia. Intratracheal (i.t.) administration of 10(6) CFU of L. pneumophila induced the expression of T1 phenotype cytokines, such as IFN-gamma and interleukin-12 (IL-12). Natural killer cells were identified as the major cellular source of IFN-gamma. To determine if enhanced expression of IFN-gamma in the lung could promote pulmonary clearance of L. pneumophila, we i.t. administered 5 x 10(8) PFU of a recombinant adenovirus vector containing the murine IFN-gamma cDNA (AdmIFN-gamma) concomitant with L. pneumophila. We observed a 10-fold decrease in lung bacterial CFU at day 2 in the AdmIFN-gamma-treated group compared to controls (P < 0.01). Alveolar macrophages isolated from AdmIFN-gamma-treated animals displayed enhanced killing of intracellular L. pneumophila organisms ex vivo. Similar improvements in bacterial clearance were observed with i.t. recombinant IFN-gamma treatment. The transient transgenic expression of IL-12, a known inducer of IFN-gamma and promoter of T1-type immune responses, resulted in more modest improvement in bacterial clearance (sixfold reduction; P < 0.05). These results demonstrate that, even in immunocompetent hosts, exogenous administration or transient transgenic expression of IFN-gamma, and to a lesser extent IL-12, may be of potential therapeutic benefit in the treatment of patients with Legionella pneumonia.

Animals↗

PubMed2001

Alveolar macrophage deactivation in murine septic peritonitis: role of interleukin 10.

Sepsis predisposes the host to a number of infectious sequelae, particularly the development of nosocomial pneumonia. Mechanisms by which sepsis results in impairment of lung antibacterial host defense have not been well defined. Alveolar macrophages (AM) represent important immune effector cells of the lung airspace. In this study, we examined the effects of cecal ligation and puncture (CLP) on murine AM function ex vivo, including the expression of proinflammatory cytokines and AM phagocytic activity. AM were harvested from mice subjected to a sham operation and CLP 24 h after laparotomy, adherence purified, and challenged with lipopolysaccharide (LPS) or left unstimulated. Both unstimulated and LPS-stimulated AM from mice subjected to CLP (CLP mice) produced significantly smaller amounts of proinflammatory cytokines tumor necrosis factor alpha and interleukin (IL-12) and C-X-C chemokines KC and macrophage inflammatory protein 2 than similarly treated AM from animals subjected to a sham operation. Furthermore, AM isolated from CLP mice displayed a marked impairment in phagocytic activity, as determined by flow cytometry, with this defect persisting to 48 h post-CLP. Induction of peritoneal sepsis syndrome resulted in a time-dependent increase in IL-10 in plasma and peritoneal fluid. Interestingly, the impairment in AM proinflammatory-cytokine production and phagocytic activity observed in AM from CLP mice was partially reversed by the in vivo neutralization of IL-10 prior to AM harvest. These observations suggest that abdominal sepsis syndrome results in significant impairment in AM effector cell function, which is mediated, in part, by sepsis-induced expression of IL-10.

Animals↗

PubMed2001

Chemokine-dependent neutrophil recruitment in a murine model of Legionella pneumonia: potential role of neutrophils as immunoregulatory cells.

The roles of CXC chemokine-mediated host responses were examined with an A/J mouse model of Legionella pneumophila pneumonia. After intratracheal inoculation of 10(6) CFU of L. pneumophila, the bacterial numbers in the lungs increased 10-fold by day 2; this increase was accompanied by the massive accumulation of neutrophils. Reverse transcription-PCR data demonstrated the up-regulation of CXC chemokines, such as keratinocyte-derived chemokine, macrophage inflammatory protein 2 (MIP-2), and lipopolysaccharide-induced CXC chemokine (LIX). Consistent with these data, increased levels of KC, MIP-2, and LIX proteins were observed in the lungs and peaked at days 1, 2, and 2, respectively. Although the administration of anti-KC or anti-MIP-2 antibody resulted in an approximately 20% decrease in neutrophil recruitment on day 2, no increase in mortality was observed. In contrast, the blockade of CXC chemokine receptor 2 (CXCR2), a receptor for CXC chemokines, including KC and MIP-2, strikingly enhanced mortality; this effect coincided with a 67% decrease in neutrophil recruitment. Interestingly, anti-CXCR2 antibody did not affect bacterial burden by day 2, even in the presence of a lethal challenge of bacteria. Moreover, a significant decrease in interleukin-12 (IL-12) levels, in contrast to the increases in KC, MIP-2, and LIX levels, was demonstrated for CXCR2-blocked mice. These data indicated that CXCR2-mediated neutrophil accumulation may play a crucial role in host defense against L. pneumophila pneumonia in mice. The increase in lethality without a change in early bacterial clearance suggested that neutrophils may exert their protective effect not through direct killing but through more immunomodulatory actions in L. pneumophila pneumonia. We speculate that a decrease in the levels of the protective cytokine IL-12 may explain, at least in part, the high mortality in the setting of reduced neutrophil recruitment.

Animals↗

PubMed2001

TspO as a modulator of the repressor/antirepressor (PpsR/AppA) regulatory system in Rhodobacter sphaeroides 2.4.1.

The TspO outer membrane protein of Rhodobacter sphaeroides has been shown to be involved in controlling the transcription of a number of genes which encode enzymes involved in photopigment biosynthesis and the puc operon. The display of regulated genes appears identical to those genes encompassing the PpsR/AppA repressor/antirepressor regulon, although the effect of TspO is modest relative to that of PpsR/AppA. To directly address the hypothesis that TspO is effective through the PpsR/AppA system, we constructed mutant strains with mutations in both tspO and appA. In all cases, the phenotypes examined resembled those of the appA lesion by itself, leading us to conclude that TspO works through or modulates the PpsR/AppA system and acts upstream of the site of action of these regulatory proteins. In earlier publications, we had suggested that TspO is involved in the efflux of a certain intermediate(s) of the porphyrin biosynthesis pathway and that transcriptional regulation of target gene expression could be explained by the accumulation of a coactivator of AppA function. Although the data reported here do not precisely identify this coactivator, they lend support to this hypothesis. We discuss the importance of this form of gene control as the result of the recent extension of the TspO system to Sinorhizobium meliloti, as described by Davey and de Bruijn (M. E. Davey and F. J. de Bruijn, Appl. Environ. Microbiol. 66:5353-5359, 2000). It is therefore possible that this system constitutes a more widely, although not universally, demonstrated form of gene regulation.

Bacterial Proteins↗

PubMed2001

Development of a fluorescence based high throughput assay for antagonists of the human chorionic gonadotropin receptor extracellular domain: analysis of peptide inhibitors.

A simple method for prompt fluorescent detection of inhibitors of human chorionic gonadotropin (hCG) binding to the extracellular domain of the human luteinizing hormone/chorionic gonadotropin (hLH/CG) receptor was developed for high throughput screening (HTS). Construction and analysis of a recombinant phage that displays the extracellular binding domain of the hLH/CG receptor on its surface and specifically binds hCG was previously described. To facilitate the identification of molecules that disrupt the interaction of hCG with its receptor, a method for prompt fluorescent detection of these phage bound to hCG was developed. This technique is extremely sensitive and employs fluorescent labels (PBXL dyes) that are derived from red and blue-green algae. Antibodies labeled with PBXL dye were able to specifically detect phage that display the extracellular domain of the hLH/CG receptor when bound to hCG immobilized in 96-well microplates. Decreases in fluorescence correlate with the concentration of exogenous hCG or hCG antagonists in the assay. This prompt fluorescence detection assay was optimized in a 96-well format as a model system for HTS applications that target the receptors for the group of hormones known as the gonadotropins. Low-affinity molecules that disrupt binding of the phage-displayed receptor extracellular domain to hCG can be rapidly identified in this high throughput screen.

Automation↗

PubMed2001

Detection of novel ALAD gene polymorphisms using denaturing high-performance liquid chromatography.

Denaturing high-performance liquid chromatography (DH-PLC), which is based on the separation of mismatched DNA heteroduplexes, is one of the most promising techniques for detecting nucleotide polymorphisms. Lead is an important environmental toxicant that can impair the cardiovascular, central nervous, renal, reproductive, and hematologic systems. Here we compare the sensitivity and efficiency of DNA polymorphism detection in the delta-aminolevulinate dehydratase (ALAD) gene encoding the principal lead-binding protein in humans by means of DHPLC and direct DNA sequencing of polymerase chain reaction amplicons. In a sample of 48 unrelated Chinese women, five novel mutations were discovered in intron 6 (G13298C). exon 7 (C13348T), intron 8 (C13847T), intron 12 (C15096T), and the 3' untranslated region of exon 13 (A15762C). The allele frequencies of C13298, T13348, T13847, T15096, and C15762 alleles were 21.3%, 2.3%. 82.1%, 62.5%, and 1.1%, respectively. All five mutations were detected by both DHPLC and direct DNA sequencing. No previously reported missense ALAD mutations were found in this Chinese population. Our study confirms that DHPLC provides an accurate method for the rapid identification of single nucleotide polymorphisms.

Adult↗

PubMed2001

[Influence of elevated atmospheric CO2 concentration on photosynthesis and leaf nitrogen partition in process of photosynthetic carbon cycle in Musa paradisiaca].

The photosynthetic rate (Pn) in leaves of Musa paradisiaca grown under elevated CO2 concentration (700 +/- 56 microliters.L-1) for one week was 5.14 +/- 0.32 mumol.m-2.s-1, 22.1% higher than that under ambient CO2 concentration, while under elevated CO2 concentration for 8 week, the Pn decreased by 18.1%. It can be inferred that the photosynthetic acclimation to elevated CO2 concentration and the Pn inhibition occurred in leaves of M. paradisiaca. The respiration rate in light (Rd) was lower in leaves under higher CO2 concentration, compared with that under ambient CO2 concentration. If the respiration in light was not included, the difference in CO2 compensation point for the leaves of both plants was not significant. Under higher CO2 concentration for 8 weeks, the maximum carboxylation rate(Vcmax) and electron transportation rate (J) in leaves decreased respectively by 30.5% and 14.8%, compared with that under ambient CO2 concentration. The calculated apparent quantum yield (alpha) in leaves under elevated CO2 concentration according to the initial slope of Pn/PAR was reduced to 0.014 +/- 0.010 molCO2.mol-1 quanta, compared with the value of 0.025 +/- 0.005 molCO2.mol-1 quanta in the control. The efficiency of light energy conversion also decreased from 0.203 to 0.136 electrons.quanta-1 in plants under elevated CO2 concentration. A lower partitioning coefficient for leaf nitrogen in Rubisco, bioenergetics and thylakoid light-harvesting components was observed in plants under higher CO2 concentration. The results indicated that the multi-process of photosynthesis was suppressed significantly by a long-term (8 weeks) higher CO2 concentration incubation.

Carbon Dioxide↗

PubMed2001

[Adsorption of weak deep blue GR on hydroxy-aluminum montmorillonite].

Hydroxy-alumium montmorillonite may serve as potential adsorbents for organic pollutants from wastewater. It was synthesized by titrating Na-montmorillonite with hydroxy-aluminum solution (OH-/Al3+ molar ratio was 2.4). From powder XRD data, it was shown that the interlayer(d001) of montmorillonite was increased greatly from 12.58A to 18.63A. Seven modified montmorillonite samples, including hydroxy-aluminum montmorillonite, were used to remove the dye of weak deep blue GR from water. The results showed that hydroxy-alumium montmorillonite had very high adsorption ability, only 0.0200 g could treat 25 ml weak deep GR with 95% removal. The different adsorption mechanisms of weak deep blue GR on modified montmorillonite: surface adsorption, ion-exchanging and partion, were suggested.

Adsorption↗

PubMed2001

[The change of genioglossus muscle activity of OSAS patients with and without snoreguard].

OBJECTIVE: The effect of snoreguard on the genioglossus (GG) muscle activity of OSAS patients was investigated. METHODS: Fifteen male patients with mild to severe OSAS were diagnosed by overnight polysomnographic and GG EMG studies, and reexamined with snoreguard. GG muscle activities of these patients with and without snoreguard were compared. RESULTS: The results revealed that the overnight GG muscle activity decreased significantly and the fluctuating GG muscle activity was improved effectively by the treatment of snoreguard. CONCLUSION: The treatment mechanisms of mandibular advancing appliance on OSAS are mechanical enlargement of upper airway and the passivity of GG muscle during treatment.

Adult↗

PubMed2001

[A classification of anterior open bite].

OBJECTIVE: It intended to investigate different craniofacial types of anterior open bite. METHODS: 116 patients with anterior open bite were selected randomly. The craniofacial morphology and airway structures were measured and analyzed with multivariate analyses. RESULTS: 4 factors (mandible rotation factor, facial height factor, dental and skeletal saggittal factor and maxillary rotation factor) were extracted from 156 items including age, gender and craniofacial characteristics by data reduction and factor analysis procedure. Anterior open-bite patients were classified into 5 types, which are dental-alveolar type, mandibular clockwise rotation type, long face type, maxillary counter-clockwise rotation type and skeletal Class III type with K-means cluster analysis procedure. A simple cluster method was summarized to facilitate clinical practice. CONCLUSION: It suggested that classification play an important role in diagnosis and decision making procedure.

Adolescent↗

PubMed2001

Modeling the effects of epidemics on routinely collected data.

The use of routinely collected data, such as absenteeism, to provide an early warning of an epidemic will depend on better understanding of the effects of epidemics on such data. We reviewed studies in behavioral medicine and health psychology in order to build a model relating known factors related to human health information and treatment seeking behavior and effects on routinely collected data. This review and modeling effort may be useful to researchers in early detection, simulation, and response policy analysis.

Data Collection↗

PubMed2001

[Changes serum level of tumor specific growth factor and their clinical significance in mechanical trauma patients].

OBJECTIVE: To investigate the post-traumatic changes in the serum level of tumor specific growth factor (TSGF) and their relationship with Injury Severity Score and to inquire into the possible mechanism and clinical significance. METHODS: Fifty patients with mechanical trauma were eligible and included. According to the standard of Injury Severity Score (ISS), the patients were divided into there groups: mild degree group, (ISS < or = 16, n = 31) severe degree group (16 < ISS < 25, n = 13) extreme severe degree group (ISS > or = 25, n = 6). The blood samples of all patients were obtained within 24 hours, and those of 25 dynamically observed patients were obtained on days 3, 5, 7, 9 and 12. RESULTS: The serum level of TSGF was significantly higher in patients with trauma in different groups (P < 0.05). The dynamical observation showed that the index demonstrated curve changes with increase in early stage and decrease later. the climax of TSGF appeared on 7 day in all 3 groups. The TSGF serum levels in extremely severe degree and severe degree groups > mild degree group on days 5, 7, 9 and 12 day (P < 0.05). CONCLUSION: TSGF has relationship with the inflammatory response and recovery of trauma.

Adult↗