Biomedical subjects

M Xu

Publications and source records attributed to M Xu.

At least 199 records · Page 11Linked to original sources

PubMed1999

[Expression of multidrug resistance-associated protein gene in non-small cell lung cancer].

OBJECTIVE: To study the relationship between expression of multidrug resistance-associated protein (MRP) gene and occurrence of multidrug resistance (MDR) in non-small cell lung cancer (NSCLC). METHODS: Thirty-two NSCLC samples were detected expression of MRP gene and chemosensitivity to 9 antitumor agents by RT-PCR, immunohistochemistry method and in vitro chemosensitivity assay. RESULTS: The positive expression rate of MRP mRNA in NSCLC was 72%, in lung tissue near carcinoma was 10%; the positive expression rate of MRP in NSCLC was 66%, positive staining of MRP located in membrane and cytoplasm of tumor cells, but no positive staining in lung tissue; MRP mRNA and MRP expression of moderate to high differentiation carcinoma was significantly higher than that of low differentiation carcinoma (P < 0.05). There was significant correlation between expression of MRP mRNA and MRP in NSCLC. The expression of MRP in NSCLC, which was resistant to vincristine, etoposide and adriamycin, was higher than that being sensitive to these drugs (P < 0.05). CONCLUSIONS: MRP gene may play an important role of intrinsic drug resistance in NSCLC, overexpression of MRP gene can be achieved through modulation at transcriptional and/or translation level. Overexpression of MRP is a major cause of resistance to vincristine, etoposide and adriamycin.

Antineoplastic Agents↗

PubMed1999

[Dynamic effect of the blood glucose and insulin on serum leptin concentration during oral glucose tolerance test].

OBJECTIVE: To investigate the effects of internal change of plasma glucose and serum insulin levels on serum leptin concentrations during oral glucose tolerance test (OGTT) in normal subjects and type II diabetics (DM). METHODS: Plasma glucose, serum insulin and leptin concentrations were measured simultaneously in 50 age, sex and body mass index matched non-diabetic (non-DM) and 50 DM subjects who were undergoing OGTT. RESULTS: The fast serum leptin concentrations were (3.88 +/- 0.64) microg/L in DM males and (8.30 +/- 1.06) microg/L in DM females. Respectively they were (5.01 +/- 0.64) microg/L and (10.48 +/- 1.30) microg/L in non-DM group. No significant difference was revealed. Comparing with the non-DM group, the glucose curve was elevated and the insulin releasing curve was characterized by a low response and a delayed peak in DM group. As for the leptin releasing curve, both groups showed a decreasing trend, which seemed to be more evident in DM group. CONCLUSION: Leptin concentration does not increase with the release of insulin. On the contrary, it shows a diurnal rhythmic descending trend, suggesting that in vivo, the insulin effect on serum leptin concentration is relatively weak and not able to affect the day-time descending trend of leptin levels.

Blood Glucose↗

PubMed1999

[Re-assessment of indicators for screening lead poisoning].

OBJECTIVE: To determine the accuracy of the indicators for detecting lead poisoning. METHODS: Blood and urine specimens in 157 workers exposed to lead were collected. Their blood levels of lead, free erythrocyte protoporphyrin (FEP), zinc protoporphyrin (ZPP), urine delta-aminolevulinic acid and activity of red cell pyrimidine 5'-nucleotidase were determined, with gold standards of blood lead levels of >or= 1.93 micromol/L and >or= 2.90 micromol/L. Accuracy assessment of the indicators mentioned above for detecting lead poisoning was based on the area under the receiver operative characteristic (AUC(ROC)) curve with a software specially for ROC curve analysis and software of Epi-Info, after determining the optimal cut-off points for the above mentioned indicators in detecting those with blood lead >or= 1.93 micromol/L and >or= 2.90 micromol/L. The sensitivity of screening in parallel for detecting those with blood lead >or= 1.93 micromol/L and >or= 2.90 micromol/L was calculated and compared. RESULTS: For detecting those with blood lead level >or= 1.93 micromol/L, the area under ROC curve (AUC(ROC)) of above indicators was 0.978 for ZPP, 0.973 for red cell P5'N, 0.937 for FEP, 0.890 for urine delta-ALA (significantly different from that for ZPP with P < 0.05), and 0.845 for urine lead level (significantly different from that for ZPP with P < 0.05), respectively. For detecting those with blood lead level >or= 2.90 micromol/L, the area under ROC curve (AUC(ROC)) of above indicators was 0.975 for red cell P5'N, 0.954 for ZPP, 0.906 for FEP (significantly different from that for red cell P5'N with P < 0.05), 0.900 for urine delta-ALA (significantly different from that for red cell P5'N with P < 0.05), and 0.750 for urine lead level (significantly different from that for red cell P5'N with P < 0.05). Sensitivity of screening in parallel with ZPP and P5'N was significantly higher than that with urine levels of lead and delta-ALA. CONCLUSION: Determinations of red cell P5'N and ZPP for detecting those with blood lead >or= 1.93 micromol/L and >or= 2.90 micromol/L are more accurate.

5'-Nucleotidase↗

PubMed1999

[Studies on chemical constituents of Forsythia suspensa (Thunb) Vahl].

OBJECTIVE: To study the chemical constituents of Forsythia suspensa. METHOD: Basedon silicacolumn chromatography, of which six compounds were obtained from the alcohol extract of F. suspensa, three identified by physicochemical and spectroscopic analyses. RESULT: The three compounds were identified as stearic acid, palmitic acid and beta-sitosterol. CONCLUSION: The three compounds were separated from F. suspensa fruits for the first time.

Forsythia↗

PubMed1999

[Plasma HDL subfractions in endogenous hypertriglyceridemia].

Our previous studies indicated that while the plasma triglycerides (TG) levels were significantly increased, HDL-C and apo A I levels were significantly decreased and abnormal HDL compositions were found in hypertriglyceridemic (HTG) patients. Whether the particle sizes of plasma HDL in HTG undergo a change has not yet been reported. This study was designed to observe the changes of plasma HDL subfractions in HTG patients. The plasma TG, total cholesterol (TC), HDL-C, apo A I, A II, B100, C II, C III, and E, HDL compositions and HDL subfractions--HDL2a, HDL2b, HDL3a, HDL3b and HDL3c were measured in 25 HTG patients (plasma TG > 2.26 mmol/L, TC < 6.72 mol/L) and 25 age-sex matched healthy subjects (plasma TG < 1.69 mmol/L, TC < 5.17 mmol/L). Plasma HDL was isolated by one step density gradient ultracentrifugation. Plasma and HDL TC, TC were determined by enzymatic methods; apo A I, A II, B100, C II, C III and E were measured by RID kits developed by ourselves. HDL subfractions were analyzed by a gradient gel electrophoresis method (GGE). The variation coefficients in one gel were 2.3% to 8.3% and the variation coefficients among gels were 3.5% to 9.3%. The results indicated that in the HTG group, the fasting plasma TG, apo B100, C II, C III and E levels were significantly higher (P < 0.001) and HDL-C, apo A I levels were lower (P < 0.05) as compared with those in the control group. TC in HDL in the HTG group were significantly increased (P < 0.05), while TG, apo A I, C II, C III and E were significantly decreased (P < 0.05, P < 0.01). Among HDL subfractions in the HTG group, HDL2b was significantly decreased (P < 0.02); HDL2a and HDL3a were increased (P < 0.05, P < 0.02). With the increase of plasma TG levels in the HTG group, the HDL particle sized tended to become smaller. According to the results, it is suggested that the changes of plasma HDL subfractions in HTG are related to the changes of the apolipoprotein compositions of HDL, which lead to the increase of HDL catabolism, therefore the plasma HDL2b content decreases and HDL2a, HDL3a contents increase.

Adult↗

PubMed1999

[Chemical composition of Fordia cauliflora Hemsl].

OBJECTIVE: To study chemical constituents of the root of Fordia cauliflora. METHOD: Three compounds were obtained from the ethanolic extract of the roots of F. cauliflora by silica column chromatography, and identified by physico-chemical and spectroscopic analysis. RESULT: The compounds were identified as stearic acid, palmitic acid and beta-sitosterol. CONCLUSION: These compounds were obtained from this plant for the first time.

Fabaceae↗

PubMed1999

[Field application of oral artesunate for preventing Schistosoma japonicum infection].

AIM: To assess the preventive effect of oral artesunate against S. japonicum infection. METHODS: Residents in two pilots in the schistosomiasis endemic regions, 562 cases in Yanghe pilot, Wangjiang County and 218 cases in Shashan pilot, Guichi City, Anhui Province, were selected for this study. The residents were divided into two groups. Group I received artesunate 6 mg/kg once every 2 weeks for 4 times 2 wk after contacting with infested water from July to September in 1997. Group II received the same dosage of placebo at the corresponding times. Four weeks after the last administration, stool examination using hatching method and Kato's method was conducted to evaluate the effect. RESULTS: In Yanghe pilot, 2 cases were hatching positive in the artesunate-treated group with an infection rate of 0.7% (2/273), while 11 cases were stool positive in placebo group with an infection rate of 3.8% (11/289) and a mean EPG of 26.40 +/- 1.49. In Shashan pilot, all cases in artesunate-treated group were stool negative, while 7 cases were stool positive in the placebo group with an infection rate of 6.3% (7/111), and a mean EPG of 14.23 +/- 2.14. The protection rate of artesunate was 80.9% and 100%, respectively, in the two pilots. CONCLUSION: Artesunate can protect the residents from S. japonicum infection effectively.

Administration, Oral↗

PubMed1999

[In vivo anti-fecundity effect of recombinant Sjc26 GST against Schistosoma japonicum in immunized mice].

AIM: To observe the anti-fecundity effect of recombinant Sjc26 GST against Schistosoma japonicum and its mechanism. METHODS: Male ICR mice were immunized with rSjc26 GST. Five days after final injection, mice of the immunization and control groups were challenged with 40 +/- 1 S. japonicum cercariae. All mice were sacrified at 6 weeks after challenge. RESULTS: The worm reduction rate was 30.0%, and the egg reduction rates in the liver and in the spleen were 57.1% and 79.9%, respectively. Inhibition of the vitelline gland and testis was also observed by transmission electron microscopy. The number of vitelline globes, vitelline droplets and lipid droplets in the cytoplasm of vitelline cell and the number of lipid droplets in the supporting cells and the number of spermatids in the testis were apparently reduced. CONCLUSION: The damage of the main reproductive organs of Schistosoma japonicum was one of the factors responsible for rSjc26 GST-bound anti-fecundity action.

Animals↗

PubMed1999

[Effects of anion ions on the structures of lanthanum glycine amino acid complex compounds].

Two lanthanum-glycine amino acid complexes, La(Gly)3 (ClO4)3 x H2O and La(Gly)3Cl3 x 3H2O, were synthesized with different anion ions. The infrared spectra of two complexes were characterized. The results show that the two complexes have different structures with different anion ions and the water molecules exit with different status in the two complexes. The results also indicate that one of the perchlorate ions is involved in the coordination in La(Gly)a(ClO4)3 x H2O.

Anions↗

PubMed1998

Resistance to DNA fragmentation and chromatin condensation in mice lacking the DNA fragmentation factor 45.

The DNA fragmentation factor 45 (DFF45) is a subunit of a heterodimeric nuclease complex critical for the induction of DNA fragmentation in vitro. To understand the in vivo role of DFF45 in programmed cell death, we generated DFF45 mutant mice. DNA fragmentation activity is completely abolished in cell extracts from DFF45 mutant tissues. In response to apoptotic stimuli, splenocytes, thymocytes, and granulocytes from DFF45 mutant mice are resistant to DNA fragmentation, and splenocytes and thymocytes are also resistant to chromatin condensation. Nevertheless, development of the immune system in the DFF45 mutant mice is normal. These results demonstrate that DFF45 is critical for the induction of DNA fragmentation and chromatin condensation in vivo, but is not required for normal immune system development.

Animals↗

PubMed1998

Induction of microglial reaction and expression of nitric oxide synthase I in the nucleus dorsalis and red nucleus following lower thoracic spinal cord hemisection.

In the present study, immunohistochemical stainings for OX-6, OX-42, nitric oxide synthase I and II as well as nitrotyrosine were used to investigate possible correlation among microglial reactivity, nitric oxide synthase upregulation, peroxynitrite involvement and neuronal death in the nucleus dorsalis and red nucleus following lower thoracic spinal cord hemisection. Significant neuronal loss was found in the ipsilateral nucleus dorsalis and contralateral red nucleus after cord hemisection. A distinctive microglial reaction for OX-42 could be observed from one to four weeks post axotomy in the ipsilateral nucleus dorsalis; by contrast, it was observed on both sides of the red nucleus from one to three weeks following cord hemisection. The activated microglial cells showed some degree of hypertrophy. From the microglial immunoreactivity as well as their appearance, it was speculated that microglial activation might be beneficial or protective to the axotomized neurons. In normal and sham-operated rats, neurons of the nucleus dorsalis were not nitric oxide synthase I reactive. Three weeks after cord hemisection, neurons in the ipsilateral nucleus dorsalis below the lesion showed strong immunoreactivity. Neurons in the red nucleus that normally displayed weak nitric oxide synthase I immunoreactivity showed an increase on both sides of the nucleus. These results suggested that nitric oxide synthase I expression in the nucleus dorsalis following axotomy was synthesized de novo and might act as a neurotoxic agent. However, the bilateral increase in expression of nitric oxide synthase I in the red nucleus after lower thoracic cord hemisection was due to up-regulation of the constitutive enzyme and might have some neuroprotective function. Our results also suggested that peroxynitrite played no or little role in the neurodegeneration in the nucleus dorsalis and red nucleus following axotomy.

Animals↗

PubMed1998

Selection at a P-glycoprotein gene in ivermectin- and moxidectin-selected strains of Haemonchus contortus.

Resistance to anthelmintics that are used to control parasite populations in domestic animals has become a serious problem worldwide. The development of resistance is an evolutionary process that leads to genetic changes in parasite populations in response to drug exposure. The anthelmintic ivermectin is known to bind to the human membrane transport protein, P-glycoprotein, and P-glycoprotein-deficient mice treated with ivermectin have shown signs of neurotoxicity. P-glycoprotein is believed to be involved in the multidrug resistance phenotype seen in some human cancers and for drug resistance in some protists. We have examined the genetic variation of a P-glycoprotein homologue from the nematode Haemonchus contortus to see if an association exists between specific alleles of this gene and survival to exposure to ivermectin or moxidectin. Two parasite strains passaged without drug treatment and three strains, subjected to anthelmintic selection and derived from the unselected strains, were examined. Allelic variation in the unselected strains showed this locus to be highly polymorphic. chi 2 analyses of allele frequencies showed significant differences between the unselected and the drug-selected derived strains. In all three drug-selected strains, an apparent selection for the same allele was observed. These findings suggest that P-glycoprotein may be involved in resistance to both ivermectin and moxidectin in H. contortus.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Cloning, characterization and expression of the gene coding for a cytosine-5-DNA methyltransferase recognizing GpC.

A novel gene encoding a cytosine-5-DNA methyltransferase recognizing the dinucleotide GpC was cloned from Chlorella virus NYs-1 and expressed in both Escherichia coli and Saccharomyces cerevisiae . The gene was sequenced and a predicted polypeptide of 362 amino acids with a molecular weight of 41.903 kDa was identified. The protein contains several amino acid motifs with high similarity to those of other known 5-methylcytosine-forming methyltransferases. In addition, this enzyme, named M. Cvi PI, shares 66% identity and 76% similarity with M. Cvi JI, the only other cytosine-5-DNA methyltransferase cloned from a Chlorella virus. The short, frequently occurring recognition sequence of the new methyltransferase will be very useful for in vivo chromatin structure studies in both yeast and higher organisms.

Amino Acid Sequence↗

PubMed1998

Biochemical characterization of MIP-1 alpha nuclear protein.

A family of hematopoietic specific transcription factors, MIP-1 alpha nuclear protein (MNP) family, has recently been identified. They are intimately involved in regulating the transcription of the huMIP-1 alpha gene in monocytes, T-cells, and transformed B-cells. One member of the family (MNP-1) is essential for promoter activity in monocytes and B-cells, while another (MNP-2) is required for full promotor activity in T-cells. A third member of the family (MNP-3) is expressed in PMA induced HL60 cells and probably has a role in monocyte differentiation. In this communication we demonstrate by two techniques that MNP-1 and MNP-2 are distinct but related factors, and we present further evidence to show that MNP-1 acts as a heterodimer.

Base Sequence↗

PubMed1998

Antimutagenic activity of tea towards 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline: effect of tea concentration and brew time on electrophile scavenging.

Green tea and black tea inhibit colon carcinogenesis in rats exposed to the cooked meat-derived mutagen 2-amino-3-methylimidazo[4, 5-f]quinoline (IQ). The present study compared the inhibitory activities of green tea and black tea towards a direct-acting mutagenic metabolite of IQ, namely 2-hydroxyamino-3-methylimidazo[4, 5-f]quinoline (N-hydroxy-IQ), under various brewing conditions. The following observations were made: (a) green tea (Sencha midoriiro) and black tea (English Breakfast tea) brewed at concentrations of 1. 25%, 2.5% or 5.0% (w/v) dose-relatedly inhibited the mutagenic activity of N-hydroxy-IQ in the Salmonella assay, (b) most of the antimutagenic components were released from the teas within 1-2 min of brewing, (c) under identical brewing conditions, green tea was significantly more effective than black tea, and (d) fractionation of green tea by HPLC revealed that most of the antimutagenic activity co-eluted with the compounds epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG), both of which are known for their anti-oxidant properties. These results suggest that catechins in tea might protect against such diverse reactive intermediates as free radicals and electrophiles formed during the metabolic activation of carcinogens and mutagens.

Animals↗

PubMed1998

Unraveling dopamine D3 receptor function in response to psychostimulants using a genetic approach.

The dopamine D3 receptor is expressed mostly in the limbic regions of the brain that influence reward-related behaviors, including responses to psychostimulants. However, the lack of ligands with sufficient D3 receptor specificity has hampered our understanding of its possible involvement in mediating psychostimulant actions. To unravel dopamine D3 receptor function and underlying mechanisms in response to psychostimulants, we used a genetic approach and generated D3 receptor gene mutant mice. Our analysis indicates that the D3 mutant mice exhibit enhanced behavioral sensitivity to cocaine, amphetamine and combined injections of D1-and D2-class receptor agonists. By contrast, the combined electrophysiological effects of the same D1-and D2-class agonists on single neurons within the nucleus accumbens were not changed in the D3 mutant mice. We propose that the D3 receptor modulates responses to psychostimulants by inhibiting the cooperative effects of postsynaptic D1-and other D2-class receptors at systems level. The continuous use of the gene targeting approach will provide essential information regarding the molecular and cellular basis of psychostimulant actions and allow the development of new strategies in the prevention and cure of drug abuse.

Amphetamine↗

PubMed1998

Binding of hsp90 to the glucocorticoid receptor requires a specific 7-amino acid sequence at the amino terminus of the hormone-binding domain.

The glucocorticoid receptor (GR) HBD must be bound to the protein chaperone hsp90 in order to acquire the high affinity steroid binding conformation. Despite this crucial role of hsp90, its binding site in GR remains poorly defined. Large portions of the GR HBD have been implicated and no similarity has been established between steroid receptor HBDs and the catalytic domains of the protein kinases (e.g. pp60(src), Raf) that also form stable heterocomplexes with hsp90. Thus, it has been thought that some general property of the proteins, such as exposure of hydrophobic residues in partially denatured regions, determines the assembly of stable hsp90 heterocomplexes. In this work, we have studied fusion proteins containing glutathione S-transferase (GST) and very short amino-terminal truncations just before and at the beginning of the rat GR HBD that are otherwise intact to the carboxyl terminus. Overexpression in COS cells of the chimeras GST537C and GST547C was found to yield receptors that were bound to hsp90 and had wild-type steroid binding affinity. However, removal of 7 more amino acids to form GST554C resulted in a fusion protein that did not bind either hsp90 or steroid. Additional mutations revealed that the role of these 7 amino acids was neither to provide a spacer between protein domains nor to expose a protein surface by introducing a bend in the conserved alpha-helix. Instead, these observations support a model in which the sequence of the 7 amino acids directly or indirectly affects hsp90 binding to the GR HBD. Thus, a region of GR that has not been thought to be relevant for hsp90 binding is now seen to be of critical importance, and these data argue strongly against the commonly accepted model of receptor-hsp90 heterocomplex assembly in which the chaperone initially interacts nonspecifically with hydrophobic regions of the partially denatured HBD and subsequently assists its folding to the steroid binding confirmation.

Amino Acid Sequence↗

PubMed1998

Ivermectin resistance in nematodes may be caused by alteration of P-glycoprotein homolog.

Resistance to ivermectin and related drugs is an increasing problem for parasite control. The mechanism of ivermectin resistance in nematode parasites is currently unknown. Some P-glycoproteins and multidrug resistance proteins have been found to act as membrane transporters which pump drugs from the cell. A disruption of the mdrla gene, which encodes a P-glycoprotein in mice, results in hypersensitivity to ivermectin. Genes encoding members of the P-glycoprotein family are known to exist in nematodes but the involvement of P-glycoprotein in nematode ivermectin-resistance has not been described. Our data suggest that a P-glycoprotein may play a role in ivermectin resistance in the sheep nematode parasite Haemonchus contortus. A full length P-glycoprotein cDNA from H. contortus has been cloned and sequenced. Analysis of the sequence showed 61-65% homology to other P-glycoprotein/multidrug resistant protein sequences, such as mice, human and Caenorhabditis elegans. Expression of P-glycoprotein mRNA was higher in ivermectin-selected than unselected strains of H. contortus. An alteration in the restriction pattern was also found for the genomic locus of P-glycoprotein derived from ivermectin-selected strains of H. contortus compared with unselected strains. P-glycoprotein gene structure and/or its transcription are altered in ivermectin-selected H. contortus. The multidrug resistance reversing agent, verapamil, increased the efficacy of ivermectin and moxidectin against a moxidectin-selected strain of this nematode in jirds (Meriones unguiculatus). These data indicate that a P-glycoprotein may be involved in resistance to ivermectin and other macrocyclic lactones in H. contortus.

ATP Binding Cassette Transporter, Subfamily B, Mem↗