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Biomedical subjects

Jun Xu

Publications and source records attributed to Jun Xu.

At least 181 records · Page 10Linked to original sources
PubMed2004

[Correlation between p53 gene mutation and the expression of tumor drug resistance genes in lung cancer and its clinical significance].

OBJECTIVE: To investigate the relationship between p53 mutation and the expression of some drug-resistance genes commonly found in lung cancer. METHODS: Sixty-six of untreated lung cancers and paracancerous tissues were obtained by surgical resection. Immunohistochemical staining was employed for detection of both mutant p53 and drug-resistance associated proteins (MDR1, MRP1, LRP, TOPO II alpha, GST-pi), PCR-SSCP and RT-PCR were used for detection of mutations of p53 exon 5-8 as well as the expression of mRNAs for the genes coding those drug-resistance associated proteins in 31/66 cases. ATP-TCA assay was also performed simultaneously in 12 out of the 31 cases for evaluation of their reaction in response to chemotherapy. RESULTS: Correlations were found between p53 mutation and expression of either Pgp or MRP1 or GST-pi (P < 0.05). There was a significant correlation between p53 mutation with simultaneous expression of Pgp and MRP1 and drug-resistance to either vinorelbine or carboplatin. CONCLUSIONS: The results suggested that p53 mutation in lung cancers was closely correlated with the expression of drug-resistance associated protein which was associated with endogenous resistance to most of chemotherapeutic drugs. It indicated that wild p53 gene therapy might be helpful for treating the endogenous drug resistance of lung cancer in chemotherapeutics.

Adult↗
PubMed2003

TRIP6 enhances lysophosphatidic acid-induced cell migration by interacting with the lysophosphatidic acid 2 receptor.

Lysophosphatidic acid (LPA) induces actin rearrangement, focal adhesion assembly, and cell migration through the activation of small G protein Rho and its downstream effectors. These diverse cellular responses are mediated by its associated G protein-coupled receptors. However, the mechanisms and specificity by which these LPA receptors mediate LPA actions are still poorly understood. Here we show that LPA stimulation promotes the interaction of the LPA(2) receptor with a focal adhesion molecule, TRIP6 (thyroid receptor interacting protein 6)/ZRP-1 (zyxin-related protein 1). TRIP6 directly binds to the carboxyl-terminal tail of the LPA(2) receptor through its LIM domains. LPA-dependent recruitment of TRIP6 to the plasma membrane promotes its targeting to focal adhesions and co-localization with actin stress fibers. In addition, TRIP6 associates with the components of focal complexes including paxillin, focal adhesion kinase, c-Src, and p130(cas) in an agonist-dependent manner. Overexpression of TRIP6 augments LPA-induced cell migration; in contrast, suppression of endogenous TRIP6 expression by a TRIP6-specific small interfering RNA reduces it in SKOV3 ovarian cancer cells. Strikingly, the association with TRIP6 is specific to the LPA(2) receptor but not LPA(1) or LPA(3) receptor, indicating a specific role for TRIP6 in regulating LPA(2) receptor-mediated signaling. Taken together, our results suggest that TRIP6 functions at a point of convergence between the activated LPA(2) receptor and downstream signals involved in cell adhesion and migration.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2003

Peroxisomal proliferator-activated receptor alpha deficiency diminishes insulin-responsiveness of gluconeogenic/glycolytic/pentose gene expression and substrate cycle flux.

Our previous work led to the hypothesis that peroxisomal proliferator-activated receptor alpha (PPAR alpha) modulates insulin action in a compensatory fashion for hepatic glucose balance vs. peripheral glucose disposal. Therefore, we have examined the expression of insulin-dependent gluconeogenic/glycolytic/pentose cycle enzymes and compared these to insulin responsiveness for peripheral vs. hepatic substrate flux and futile cycling in the PPAR alpha knockout mouse. Hepatic gluconeogenic flux, glucose absorption, clearance and recycling, as well as in vivo glucose disposal were evaluated using new mass isotopomer methods. Insulin-dependent gluconeogenic/glycolytic/pentose cycle enzyme expression and glucose futile cycling were diminished; however, glucose disappearance was increased. This supports the hypothesis of hepatic insulin resistance and increased peripheral glucose uptake as compensatory events secondary to the decrease in fatty acid oxidation characteristic of the PPAR alpha knockout. We conclude that 1) the loss of PPAR alpha results in lower expression levels and diminished response to meal regulation for gluconeogenic/glycolytic enzyme expression; and 2) consequently, substrate/futile cycling of glucose is decreased when PPAR alpha is absent despite increased gluconeogenesis. The compensatory changes in liver and peripheral tissue substrate flux and the resultant adaptation for enzyme expression in the liver to have a diminished insulin dependence reflect the loosely linked correlation between phenotype and genotype in hepatic glucose metabolism.

Animals↗
PubMed2003

Minireview: Sex chromosomes and brain sexual differentiation.

The brains of males and females differ, not only in regions specialized for reproduction, but also in other regions (controlling cognition, for example) where sex differences are not necessarily expected. Moreover, males and females are differentially susceptible to neurological and psychiatric disease. What are the origins of these sex differences? Two major sources of sexually dimorphic information could lead to sex differences in brain function. Male and female brain cells carry a different complement of sex chromosome genes and are influenced throughout life by a different mix of gonadal hormones. Until recently all sex differences in the brain have been attributed to the differential action of gonadal hormones. Recent findings, however, suggest that brain cells that differ in their genetic sex are not equivalent, and that difference may contribute to sex differences in brain function. Here we discuss evidence for sex chromosome effects on both neural and nonneural systems, which together provide support for the idea that XX and XY cells differentiate even before they are influenced by gonadal hormones, and even if they are exposed to similar levels of gonadal steroids. Fortunately, new model systems for studying sex chromosome effects have recently been developed, and they should help in testing further the role of sex chromosome genes.

Animals↗
PubMed2003

Neonatal mice possessing an Sry transgene show a masculinized pattern of progesterone receptor expression in the brain independent of sex chromosome status.

To assess the relative roles of sex chromosome genes and gonadal steroid hormones in producing sex differences in progesterone receptor (PR) expression in the forebrain of neonatal mice, we used mice in which the Sry gene had been deleted from the Y-chromosome and inserted as a transgene on an autosome in both XX and XY genotypes. Levels of PR immunoreactivity (PRir) in the anteroventral periventricular nucleus, the medial preoptic nucleus, and the ventromedial nucleus were significantly higher in mice that possessed an Sry transgene compared with mice that lacked an Sry transgene, regardless of their complement of sex chromosomes (XX vs. XY). This result suggests that sexual differentiation of PR expression in these regions is likely controlled mainly by gonadal hormones, not by the genetic sex of the brain cells. No differences in PRir were detected between wild-type XY mice with the Sry gene on the Y-chromosome and XY mice with the Sry transgene, suggesting that testicular hormones produced in these two genotypes have comparable effects on neural tissue.

Animals↗
PubMed2003

Size dependence of second-order optical nonlinearity of CdS nanoparticles studied by hyper-Rayleigh scattering.

The second-order optical nonlinearity of CdS nanoparticles with different mean diameters of 28.0, 30.0, 31.5, 50.0, and 91.0 A was studied by the incoherent hyper-Rayleigh scattering technique. Results show that the first-order hyperpolarizability beta value per CdS particle decreases with decreasing size from 91.0 to 31.5 A; however, as CdS particle size further decreases, this trend is reversed and the beta value increases. Substantially, the normalized value of the first-order hyperpolarizability per CdS formula unit, beta(0), exhibits systematic enhancement with decreasing size. This is interpreted in terms of a so-called surface contribution mechanism. The two aspects of quantum size effects, the size dependence of optical band-gap and oscillator strength, cannot be adopted to explain the size dependence of the second-order optical nonlinearity of CdS nanoparticles.

Journal Article↗
PubMed2003

High-throughput nuclear magnetic resonance analysis using a multiple coil flow probe.

An automated method for high-throughput nuclear magnetic resonance (NMR) spectroscopy has been developed using a four-coil Multiplex NMR probe. The probe is constructed with solenoidal microcoils optimized for detection of small volume, mass-limited samples and a flow-through design. Four samples can be simultaneously injected into the Multiplex probe with a robotics liquid handler and then analyzed in rapid succession using a selective excitation experiment. Due to the simultaneous injection of four samples and the reduced analysis time with rapid selective excitation, the analysis rate achieved thus far is as low as 1 sample/34 s for 1D 1H NMR.

Magnetic Resonance Spectroscopy↗
PubMed2003

Pulsed-ionization miniature ion mobility spectrometer.

We have demonstrated a miniature ion mobility spectrometer (IMS) that employs single pulses of corona discharge ionization. IMS spectra of both positive and negative ions generated from ambient air were measured as a function of drift field under various ionization conditions. Ion mobility spectra were studied with various pulse widths for both positive and negative ions, giving insights into mechanisms and kinetics of corona discharge ionization used in the miniature IMS. A combination of a pulsed potential with a steady dc bias was used to generate ions in the miniature IMS. There was a threshold dc potential for ion generation for a given pulse height. The dc ionization threshold was found to decrease linearly with increasing pulse height.

Journal Article↗
PubMed2003

Determination of a glucose-dependent futile recycling rate constant from an intraperitoneal glucose tolerance test.

Increased glucose cycling between glucose and glucose-6-phosphate is characteristic of insulin resistance and hyperglycemia seen with Type II diabetes. Traditionally, glucose cycling is determined by the difference between hepatic glucose output measured with separate [2-3H]glucose and [6-3H]glucose infusions. We demonstrate a novel method for determining hepatic glucose recycling from an intraperitoneal glucose tolerance test (IPGTT). A single tracer, [1, 2-13C(2)]glucose (a M2 glucose isotopomer), was administered at 1mg/g body weight to 4-month-old C57BL/6 mice. Hepatic glucose recycling was monitored by the appearance of a plasma M1 isotopomer of glucose, which is produced by the action of the pentose cycle on the M2 glucose isotopomer in the liver. The initial M2 enrichment was 56% and decreased to 13% at the end of 3 h, and the M1 enrichment peaked at 2 h. The ratio of plasma M1/M2 glucose increased linearly with time to approximately 25%, and the regression of the M1/M2 ratio against time gives a slope, termed the in vivo glucose-dependent futile recycling rate constant k(HR). k(HR) estimates glucose/glucose-6-phosphate futile cycling, along with glucose recycling through the pentose cycle. These observations demonstrate complex substrate cycling during an IPGTT using a single stable isotope tracer.

Animals↗
PubMed2003

Isolation and characterization of 27-O-demethylrifamycin SV methyltransferase provides new insights into the post-PKS modification steps during the biosynthesis of the antitubercular drug rifamycin B by Amycolatopsis mediterranei S699.

The gene rif orf14 in the rifamycin biosynthetic gene cluster of Amycolatopsis mediterranei S699, producer of the antitubercular drug rifamycin B, encodes a protein of 272 amino acids identified as an AdoMet: 27-O-demethylrifamycin SV methyltransferase. Frameshift inactivation of rif orf14 generated a mutant of A. mediterranei S699 that produces no rifamycin B, but accumulates 27-O-demethylrifamycin SV (DMRSV) as the major new metabolite, together with a small quantity of 27-O-demethyl-25-O-desacetylrifamycin SV (DMDARSV). Heterologous expression of rif orf14 in Escherichia coli yielded a 33.8-kDa polyhistidine-tagged polypeptide, which efficiently catalyzes the methylation of DMRSV to rifamycin SV, but not that of DMDARSV or rifamycin W. 27-O-Demethylrifamycin S was methylated poorly, if at all, by the enzyme to produce rifamycin S. The purified enzyme does not require a divalent cation for catalytic activity. While Ca(2+) or Mg(2+) inhibits the enzyme activity slightly, Zn(2+), Ni(2+), and Co(2+) are strongly inhibitory. The K(m) values for DMRSV and S-adenosyl-L-methionine (AdoMet) are 18.0 and 19.3 microM, respectively, and the K(cat) is 87s(-1). The results indicate that DMRSV is a direct precursor of rifamycin SV and that acetylation of the C-25 hydroxyl group must precede the methylation reaction. They also suggest that rifamycin S is not the precursor of rifamycin SV in rifamycin B biosynthesis, but rather an oxidative shunt-product.

Actinomycetales↗
PubMed2003

Mediation of cadmium-induced oxidative damage and glucose-6-phosphate dehydrogenase expression through glutathione depletion.

The effect of cadmium (Cd), a significant environmental contaminant, on the expression of glucose-6-phosphate dehydrogenase (G6PDH), has been investigated. G6PDH is the key rate-limiting enzyme in the pentose pathway and the expression of its gene has been shown to be redox-sensitive. We show that incubation of primary rat hepatocytes with Cd induces oxidative stress in a time- and concentration-dependent manner as measured by increases in the cytotoxic parameters, lactate dehydrogenase (LDH) and lipid peroxidation (LPO). Significant increases in LDH leakage and LPO can be measured after 12 and 24 h, respectively, in the presence of 4 microM cadmium chloride. However, prior to significant increases in cytotoxic parameters, and within only 6 h of Cd treatment, significant decreases in reduced glutathione and increases in the expression of G6PDH as measured by mRNA levels and enzyme activity are observed. The signal protein MAP kinase (MAPK) is also induced by Cd within 6 h. Blocking the Cd induction of MAPK using the antioxidant N-acetyl cysteine (10 mM) or Trolox (0.5 mM) or the MEK specific inhibitor PD098059 (20 microM) also blocks the Cd induction of G6PDH suggesting that MAPK is a signal protein involved in the redox regulation of this gene.

Acetylcysteine↗
PubMed2003

Role of NF-kappa B in liver ischemia reperfusion injury of rats.

To determine the role of NF-kappa B in ischemia reperfusion (I/R) injury of the rat liver, rats underwent partial hepatic ischemia and reperfusion. The left and median lobes of the liver were subjected to ischemia for 90 min followed by reperfusion for defined times. NF-kappa B activity was analyzed by electrophoretic mobility shift assay (EMSA). Semiquantitative reverse-transcriptase polymerase chain reaction was used to analyze TNF-alpha and ICAM-1 mRNA levels. Results showed during liver I/R injury, NF-kappa B activation was induced in a time dependent manner. NF-kappa B was activated within 1 h and 2 h after the initiation of reperfusion and decreased after 4 h. Messenger RNA expression of TNF-alpha and ICAM-1 were increased after the reperfusion of 2 h. It was concluded that during hepatic I/R injury, NF-kappa B was activated and could bind to special sequence in the promoters of budget genes, which can up-regulate the expression of TNF-alpha and ICAM-1 mRNA to result in ischemia reperfusion injury of the rat liver.

Animals↗
PubMed2003

Intron requirement for AFP gene expression in Trichoderma viride.

The 430 bp ORF of the Aspergillus giganteus antifungal protein (AFP) gene, containing two small introns, was fused between the promoter and the terminator of the Aspergillus nidulans trpC gene. The AFP gene in this vector produced detectable levels of spliced mRNA in Trichoderma viride. In contrast, in the same vector configuration, its 285 bp intronless derivative showed no accumulation of mRNA when transformed into T. viride. Such expression results were confirmed at the protein level. This fact demonstrated that the introns were required for AFP gene expression in T. viride. This is thought to be a novel phenomenon found in filamentous fungi. Although the mechanism of splicing in filamentous fungi might be similar to that in other eukaryotes, little is known of how it affects expression. This study suggests that the small introns in filamentous fungal genes may not only act as intervening elements, but may also play crucial roles in gene expression by affecting mRNA accumulation. Furthermore, it may provide new evidence for intron-dependent evolution.

Fungal Proteins↗
PubMed2003

Innovative approach for improvement of an antibiotic-overproducing industrial strain of Streptomyces albus.

Working with a Streptomyces albus strain that had previously been bred to produce industrial amounts (10 mg/ml) of salinomycin, we demonstrated the efficacy of introducing drug resistance-producing mutations for further strain improvement. Mutants with enhanced salinomycin production were detected at a high incidence (7 to 12%) among spontaneous isolates resistant to streptomycin (Str(r)), gentamicin, or rifampin (Rif(r)). Finally, we successfully demonstrated improvement of the salinomycin productivity of the industrial strain by 2.3-fold by introducing a triple mutation. The Str(r) mutant was shown to have a point mutation within the rpsL gene (encoding ribosomal protein S12). Likewise, the Rif(r) mutant possessed a mutation in the rpoB gene (encoding the RNA polymerase beta subunit). Increased productivity of salinomycin in the Str(r) mutant (containing the K88R mutation in the S12 protein) may be a result of an aberrant protein synthesis mechanism. This aberration may manifest itself as enhanced translation activity in stationary-phase cells, as we have observed with the poly(U)-directed cell-free translation system. The K88R mutant ribosome was characterized by increased 70S complex stability in low Mg(2+) concentrations. We conclude that this aberrant protein synthesis ability in the Str(r) mutant, which is a result of increased stability of the 70S complex, is responsible for the remarkable salinomycin production enhancement obtained.

Anti-Bacterial Agents↗
PubMed2003

Factors predisposing to severe acute pancreatitis: evaluation and prevention.

AIM: To analyze factors predisposing to the infections associated with severe acute pancreatitis (SAP) and to work out ways for its prevention. METHODS: Total 208 cases of SAP treated in this hospital from Jan. 1980 to Dec. 2001 were retrospectively analyzed. RESULTS: Statistical difference in the incidence of the aforementioned infections was found between the following pairs: between the groups of bloody or non-bloody ascites, paralytic ileus lasting shorter or longer than 5 days, Ranson scores lower or higher than 5, hematocrit lower or higher than 45 %, CT Balthazar scores lower or higher than 7 and between 1980.1-1992.6 or 1992.7-2001.12 admissions (chi(2)>3.84, P<0.05), while no statistical difference was established between the groups of biliogenic and non - biliogenic pancreatitis, serum amylase <200 U/L and > or =200 U/L, serum calcium <2 mmol /L and > or =2 mmol/L or groups of total parenteral nutrition shorter or longer than 7 days (chi(2)<3.84, P>0.05). CONCLUSION: Occurrence of infection in patients with SAP is closely related with bloody ascites, paralytic ileus > or =5 days, Ranson scores > or =5, hematocrit > or =45 % and CT Balthazar Scores > or =7, but not with pathogens, serum calcium and total parenteral nutrition (TPN). Comprehensive prevention of pancreatic infection and practice of individualized therapy contribute to reducing the incidence of infection.

Acute Disease↗
PubMed2003

[Relationship between the genotypes of hepatitis B virus and the severity of liver diseases].

OBJECTIVE: To investigate the relationship between different genotypes of hepatitis B virus (HBV) and the severity of liver diseases. METHODS: The S nucleotide sequences of HBV strains isolated from plasma samples of 284 patients were detected and compared. Among them, 87 patients were HBV asymptomatic carriers (ASC), 157 chronic hepatitis B (CHB), 22 liver cirrhosis (LC), and 18 hepatocellular carcinoma (HCC). RESULTS: Genotypes B and C were predominant, with a 26.1% proportion and a 63.2% proportion respectively. The percentage of genotypes B and C in patients with ASC, CHB, LC, and HCC were significantly different (x(2)=15.09, P<0.001). Compared with genotype B, genotype C was more common in patients with CHB and HCC (59.6% vs 43.2%, chi(2)=10.87, P<0.001; 7.7% vs 1.4%, x(2)=7.41, P<0.001), but in patients with LC there was no different (7.7% vs 8.1%, chi(2)=1.29, P>0.05). CONCLUSION: This study suggests that genotype B and C are predominant. And genotype C may induce more severe the liver inflammation than genotype B may do.

Adult↗
PubMed2003

[Study on retention and stability of linear occlusal complete dentures].

OBJECTIVE: To learn retention and stability of linear occlusal complete dentures by investigating the subjective feelings of patient and the value of retention force. METHODS: Static retention forces of maxillary and mandibular dentures were measured for 25 patients wearing linear occlusal dentures by using Hz-1 retention dynamometer. The subjective feelings of patients in functional state were gained simultaneously through questionnaire. RESULTS: Linear occlusal dentures demonstrate good retention in static and dynamic state. Among patients with severe resorption of residual ridge (RRR), mandibular linear occlusal dentures (shown good retentive subjective feelings) demonstrate significantly smaller retention force than those with slight or medium degree of RRR. There is no correlation between the subjective feelings and the values of retention forces of mandibular dentures. The subjective feelings of patients wearing new linear occlusal dentures are much better than that of old anatomic occlusal dentures. CONCLUSION: Linear occlusal dentures improve the performances of dentures by enhancing their stability during mastication movement.

Aged↗