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Biomedical subjects

W Xue

Publications and source records attributed to W Xue.

At least 19 recordsLinked to original sources

trans-3,4-dihydroxy-anti-1,2-epoxy-1,2,3,4-tetrahydrodi- benz[a,j]acridine involvement in dibenz[a,j]acridine DNA adduct formation in mouse skin consistent with Ha-ras mutation patterns in tumors.

Dibenz[a,j]acridine (DBA), is a N-heteropolycyclic aromatic environmental carcinogen found in complex combustion mixtures. The major route of DBA metabolic activation is reportedly through the trans-3,4-dihydroxy-3,4-dihydroDBA (DBA-3,4-DHD). The present studies were undertaken to determine the role of trans-3,4-dihydroxy-anti-1,2-epoxy-1,2,3,4-tetrahydroDBA (DBADE) in DBA activation pathway(s), the DNA bases involved in the binding of DBA to DNA, and whether the adducts produced are consistent with the mutation pattern in the Ha-ras gene. DBA (300 microg) or 50 microg synthesized (+/-)-DBADE was applied to the back of female Hsd:ICR(Br) mice. The mice were sacrificed 48 h later, and skin DNA was isolated, hydrolyzed, and analyzed with (32)P-postlabeling. Of the four adducts produced in vivo, adduct 1 was the major adduct for DBA (>50%) and adduct 2 was the major adduct for DBADE (89%). After the reaction of (+/-)-DBADE with purine nucleotides or calf thymus (CT) DNA in vitro, 100% of the DBADE-2'-dAMP adducts and 94% of DBADE-CT DNA adducts were chromatographically identical on TLC with adduct 2 and 86% of the DBADE-2'-dGMP adducts were chromatographically consistent with adduct 1 by (32)P-postlabeling. Papillomas were induced on the backs of mice by a single application of 0.2 micromol of DBA followed by twice-weekly application of 12-o-tetra-decanoylphorbol-13-acetate (TPA, 2 microg) for 24-26 weeks. Skin carcinomas were induced by twice weekly applications of DBA (0.1 micromol) on the backs of mice. A to T and G to T transversions were found in codons 12, 13, and 61 of the Ha-ras gene in the treated mouse skin carcinoma and papilloma DNA. The mutational spectra in the Ha-ras gene are consistent with the DNA binding of DBA to dG or dA in vivo. Thus, this research has indicated that DBADE plays an important role in DBA metabolic activation and DNA binding in mouse skin, and an alternative pathway through a bis-dihydrodiol-epoxide of DBA may also be involved.

Acridines↗

[The computer-aided measurement of medullary canal in proximal femur].

This study was conducted to search the law of the parameters of medullary canal section shape in proximal femur. The methods of image-processing and taper-curve-fit mathematics were adopted in the acquisition of data and parameters. Computer-aided method and manual method were employed to measure 10 samples of section shape in proximal femur. The results showed that no significant difference was seen between the computer-aided method and manual method(P> 0.05). This approach could reduce man-made errors and process mass samples automatically by computer.

Adult↗

The therapeutic effects of Sheng Jing Zhong Zi Tang in treating male infertility.

Eight-seven cases of male infertility due to spermatopathy were treated with Sheng Jing Zhong Zi Tang (SJZZT [symbol: see text]) for 1-3 courses. The total effective rate was 95.40% (83/87). 56.32% (49/87) of their spouses got pregnant and the semen quality was markedly improved (P < 0.01). The results showed that the decoction could dual-directionally regulate the levels of follicle-stimulating hormone (FSH), prolan B luteinizing hormone (LH), testosterone (T), and cortisol (C).

Adult↗

[The development and application of computer-aided bone histomorphometry system].

The aim of this study is to develop a Computer-aided Bone Histomorphometry System. The method is based on the Micro-graphical Digital System composed of microscope, digital camera, computer and related programs. The methodology was developed to measure the basic data on each image of visual field of hard bone tissue with computer-assistance. Following this, the parameters of bone volume, bone structure and bone metabolism were calculated based on the standardization of bone histomorphometry. Such method has been used in the experimental and clinical studies of osteoporosis to predict the fracture risk and evaluate the drug effect.

Bone Density↗

In vivo genotoxicity of 2-amino-3,8-dimethylimidazo[4, 5-f]quinoxaline in lacI transgenic (Big Blue) mice.

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), a heterocyclic amine found in cooked meat, is a strong mutagen in the Salmonella/microsome assay and was proven to be a hepatocarcinogen in rodents. We used the lacI transgenic (Big Blue(R)) mouse to investigate MeIQx genotoxicity in vivo. lacI mutant frequencies were examined in liver and colon after single intragastric administration of MeIQx (males) or 12 weeks of feeding in the diet (males and females). Micronucleus induction was monitored in the peripheral blood and cell proliferating activity was monitored by proliferating cell nuclear antigen (PCNA) immunostaining, but only after the intragastric administration. Intragastric treatment with MeIQx (100 mg/kg) did not increase mutant frequency (MF) in liver or colon but it did induce a slight but statistically significant increase in the incidence of micronucleated reticulocytes 48 h after the treatment. No apparent increase in PCNA-positive foci was observed in any of tissues analyzed 14 days after the treatment. Administration of MeIQx (300 ppm) in diet for 12 weeks, however, caused MF increases in liver and colon in male and female mice, with greater increases in the females. An increase was also obvious after 4 weeks, but only in females. The sex difference in MF is consistent with the fact that female mice are more susceptible to MeIQx carcinogenesis. These results demonstrated that in the transgenic mouse mutation assay, long-term feeding of MeIQx was more effective than single gastric exposures in revealing the compound's mutagenicity in the target organs of carcinogenicity and that sex differences in susceptibility can also be observed.

Administration, Oral↗

Susceptibility to prostate cancer: interaction between genotypes at the androgen receptor and prostate-specific antigen loci.

The androgen receptor (AR) regulates gene transcription by binding to androgen response elements in target gene promoters. The prostate-specific antigen (PSA) gene has a polymorphic androgen response element sequence with two alleles, A and G. We hypothesize that allelic differences in AR-driven PSA expression may influence prostate cancer risk. To test this hypothesis, we assayed PSA genotype for 57 prostate cancer cases and 156 controls from our previous pilot study in which prostate cancer risk was associated with the AR "CAG-short" genotype. Odds ratios (ORs) were estimated relating prostate cancer risk to AR and PSA genotypes, singly and in combination. Subjects with the PSA GG genotype were at significantly increased risk for advanced, but not for localized, prostate cancer (OR, 2.90; 95% confidence interval, 1.24-6.78). When cross-classifying subjects by AR and PSA genotypes, subjects with either a CAG-short allele (and not PSA GG) or with the PSA GG genotype (and not CAG-short) had a modest, statistically insignificant increase in prostate cancer risk overall. However, subjects with both a short CAG allele and PSA genotype GG had a more than 5-fold increase in prostate cancer risk (OR, 5.08; 95% confidence interval, 1.59-16.25). All of the ORs were substantially greater for advanced prostate cancer. Studies with larger numbers of advanced cases will be needed to confirm these results. These results indicate that polymorphism in the PSA gene promoter influences prostate cancer risk, and that the allelic variation in promoter activity may be androgen-dependent. Furthermore, these results support a multigenic etiology for prostate cancer.

Aged↗

One-electron oxidation is not a major route of metabolic activation and DNA binding for the carcinogen 7H-dibenzo[c,g]carbazole in vitro and in mouse liver and lung.

7H-Dibenzo[c,g]carbazole (DBC) is a potent multi-site, multi-species carcinogen present in a variety of complex mixtures derived from the incomplete combustion of organic matter. Like many carcinogens, DBC requires metabolic activation to an electrophilic species to exert its mutagenic and carcinogenic effects. One-electron oxidation, leading to the formation of radical cation intermediates, has been proposed as a mechanism of metabolic activation for DBC in vitro resulting in unstable DNA adducts. The purpose of this research was to determine whether one-electron oxidation is a mechanism of activation and DNA binding for DBC in vivo. Specific depurinating DBC-DNA adducts formed by one-electron oxidation were analyzed in mouse liver at 4 h following a single i.p. dose of 40 mg/kg of 11 microCi [(14)C]DBC. In addition to five previously published adduct standards, two newly identified adduct standards were characterized by mass spectrometry and NMR, namely DBC-6-N7-Ade and DBC-6-N1-Ade; however, neither was observed in mouse liver. Only the DBC-5-N7-Gua adduct was observed in mouse liver extracts at a level of 6.5 +/- 1. 8 adducts/10(6) nucleotides. In addition, the formation of AP sites and stable DBC-DNA adducts was analyzed in mouse liver and lung at 4, 12 and 24 h following a single i.p. dose of 0.4, 4 or 40 mg/kg DBC (n = 3/group). There was a distinct time- and dose-response of stable DBC-DNA adducts detected by (32)P-post-labeling. There was not a clear dose-response for formation of AP sites; however, a significant increase over control levels was observed at the 4 and 40 mg/kg dose groups at 4 and 12 h post dosing, respectively. Quantitative comparisons indicate that the depurinating DBC-5-N7-Gua adduct constitutes approximately 0.4% of total adducts measured whereas the stable adducts detected by (32)P-post-labeling constitute 99.6% of total adducts measured following a 40 mg/kg dose and a 4 h time-point. The data indicate that one-electron oxidation does occur in mouse liver in vivo. However, one-electron oxidation is a minor mechanism of activation in that the percentage of total adducts formed through this route constitutes a minor percentage of the total adducts formed.

Animals↗

Biodegradation of carbazole by Ralstonia sp. RJGII.123 isolated from a hydrocarbon contaminated soil.

The use of microorganisms for bioremediation of contaminated soils may be enhanced with an understanding of the pathways involved in their degradation of hazardous compounds. Ralstonia sp. strain RJGII.123 was isolated from soil located at a former coal gasification plant, based on its ability to mineralize carbazole, a three-ring N-heterocyclic pollutant. Experiments were carried out with strain RJGHII.123 and 14C-carbazole (2 mg/L and 500 mg/L) as the sole organic carbon source. At 15 days, 80% of the 2 mg/L carbazole was recovered as CO2, and <1% remained as undegraded carbazole, while 24% of the 500 mg/L carbazole was recovered as CO2 and approximately 70% remained as undegraded carbazole. Several stable intermediates were formed during this time. These intermediates were separated by high performance liquid chromatography (HPLC) and were characterized using high resolution mass spectroscopy (HR-MS) and gas chromatography - mass spectroscopy (GC-MS). At least 10 ring cleavage products of carbazole degradation were identified; four of these were confirmed as anthranilic acid, indole-2-carboxylic acid, indole-3-carboxylic acid, and (1H)-4-quinolinone by comparison with standards. These data indicate that strain RJGII.123 shares aspects of carbazole degradation with previously described Pseudomonas spp., and may be useful in facilitating the bioremediation of NHA from contaminated soils.

Betaproteobacteria↗

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↗

[Pressure influence on mRNA expression and protein synthesis of inducible nitric oxide synthetase in bovine trabecular meshwork cell].

OBJECTIVE: To investigate the inducible nitric oxide synthetase (iNOS) mRNA expression and protein synthesis in bovine trabecular meshwork cell and discuss the possible effects of nitric oxide (NO) in the development of glaucoma. METHODS: 20 mm Hg, 40 mm Hg, 60 mm Hg and 80 mm Hg pressure were respectively added on cultured trabecular cells of new born bovine. No pressure group was set as the control. The changes of iNOS mRNA and protein in trabecular meshwork cells under different pressures were demonstrated qualitatively and quantitatively by in situ hybridization and nicotinamide-adenine dinucleotide phosphate diaphorase (NADPH-d) histochemical assay. RESULTS: The expression of iNOS mRNA and its protein synthesis became higher and higher as the pressure was increased. There was weak iNOS mRNA expression in the control and 20 mm Hg groups, and no significant difference between them. 40 mm Hg and 60 mm Hg groups had a statistical difference from the control group. And 80 mm Hg group had a very significant difference from the control group. There was no difference between 40 mm Hg and 60 mm Hg groups, but they had significant difference from 80 mm Hg group. NADPH-d histochemical assay showed almost the same results except that there was significant difference between 40 mm Hg and 60 mm Hg groups. CONCLUSIONS: Pressure can evoke the expression of iNOS mRNA, and the nitric oxide thus produced can be one of the causes of trabecular meshwork destruction, that may induce or aggravate glaucoma.

Animals↗

Formation of a ribonucleoprotein complex of mouse hepatitis virus involving heterogeneous nuclear ribonucleoprotein A1 and transcription-regulatory elements of viral RNA.

The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) specifically binds to two transcription-regulatory elements, i.e., the leader and intergenic sequence, of the negative-strand (template-strand) RNA of mouse hepatitis virus (MHV) and may play a role in viral RNA transcription. Previous studies based on the defective-interfering RNAs of MHV suggested that these two RNA elements may interact with each other during transcription, although they do not have complementary sequences. In this study, we showed by an in vitro reconstitution assay that hnRNP A1 could mediate the formation of an RNP complex involving these two RNA elements. Both the RNA-binding domains and protein-interacting domain of hnRNP A1 contributed to the efficient formation of the RNP complex; however, the presence of the two RNA-binding domains alone, without the protein-interacting domain, also resulted in some RNP formation. Omission of hnRNP A1 in the reconstitution reaction abolished the RNP formation, and mutations of the IG sequences significantly inhibited the RNP formation. These findings suggest that the two cis-acting transcription-regulatory sequences of MHV RNA can interact with each other through the formation of an RNP complex involving a cellular protein hnRNP A1. This RNP complex may participate in MHV RNA transcription.

Animals↗

Expression of the IL-12 receptor beta 1 and beta 2 subunits in human tuberculosis.

To determine whether the Th1 response in tuberculosis correlated with IL-12R expression, we measured expression of the IL-12R beta 1 and IL-12R beta 2 subunits, as well as IL-12R beta 2 mRNA expression in tuberculosis patients and healthy tuberculin reactors. In tuberculosis patients, IFN-gamma production by Mycobacterium tuberculosis-stimulated PBMC was reduced, the percentages of T cells expressing IL-12R beta 1 and IL-12R beta 2 were significantly decreased, and IL-12R beta 2 mRNA expression was also markedly reduced. In contrast, in pleural fluid and lymph nodes at the site of disease in tuberculosis patients, in which IFN-gamma production is enhanced, IL-12R beta 2 mRNA expression was also increased. In M. tuberculosis-stimulated peripheral blood T cells from tuberculosis patients, anti-IL-10 and anti-TGF-beta enhanced IL-12R beta 1 and IL-12R beta 2 expression, and IFN-gamma production. In M. tuberculosis-stimulated peripheral blood T cells from healthy tuberculin reactors, recombinant IL-10 and TGF-beta reduced IL-12R beta 1 and IL-12R beta 2 expression, as well as IFN-gamma production. In combination with prior studies showing increased production of TGF-beta by blood monocytes from tuberculosis patients, this suggests that increased TGF-beta production is the underlying abnormality that reduces IL-12R beta 1 and IL-12R beta 2 expression in tuberculosis. Our findings provide evidence that IL-12R expression correlates well with IFN-gamma production in human tuberculosis, and that expression of IL-12R beta 1 and IL-12R beta 2 may play a central role in mediating a protective Th1 response.

Cells, Cultured↗

Ionization potentials and metabolic activations of carbazole and acridine derivatives.

7H-Dibenzo[c,g]carbazole (DBC) and dibenz[a,j]acridine (DBA) representing environmental nitrogen-heterocyclic aromatic (NHA) genotoxicants undergo differing metabolism and exhibit differing DNA binding patterns and carcinogenic activities. Two chemical oxidation-related parameters, anodic peak potentials (E(pa)) and maximum absorption energies (E(CT)) of the charge-transfer complexes, were measured for a series of 18 derivatives of carbazole and acridine. On the basis of the E(pa) and E(CT) values and the ionization potential (IP) data of the parent carbazole and acridine that are available in the literature, with linear regression analyses, IP values of the 18 carbazoles and acridines were reported for the first time. The two sets of IP values determined from either E(pa) or E(CT) agreed with one another for most of the compounds. Carbazoles possessed IP values (ranging from 7.2 to 7.6 eV) that are lower than those of acridines (i.e., 7.8-8.1 eV). These data are consistent with the potential activation of carbazole and/or acridine derivatives. For DBC having an IP of approximately 7.3 eV, both one-electron oxidation and monooxygenation pathways are involved in the metabolic activation. In contrast, DBA with a high IP of approximately 8.0 eV is activated through the monooxygenation pathway only. Therefore, just as it is known for carcinogenic PAHs, IP appears to be an important parameter in predicting the metabolic activation for genotoxic NHA in the environment.

Acridines↗

[Preoperative arterial infusion chemotherapy of colorectal carcinoma pathological and clinical effects].

OBJECTIVE: To investigate the pathological and clinical effects of preoperative selective intra-arterial infusion chemotherapy on colorectal carcinoma. METHODS: 30 patients with colorectal carcinoma underwent selective regional arterial angiography by Seldinger's method followed by intra-arterial infusion chemotherapy. RESULTS: changes of karyopyknosis, karyorrhexis, coagulation and necrosis of cytoplasm in cancer cells around vascular vessels were found in all cases. Interstitial edema, invasion of inflammatory cells, fibroelastosis around cancer cells, proliferous intima, thrombus and inflammation of vessels were also found at the same sites. CONCLUSIONS: Histological changes are significant after preoperative selective intra-arterial infusion chemotherapy for colorectal carcinoma. This therapy can relieve symptoms.

Adult↗

Cellular protein hnRNP-A1 interacts with the 3'-end and the intergenic sequence of mouse hepatitis virus negative-strand RNA to form a ribonucleoprotein complex.

We previously showed that several cellular proteins specifically bind to the 3'-end and the intergenic sequences of the negative-strand RNA of mouse hepatitis virus (MHV), and proposed that these distant RNA sequences can be brought together by cellular and viral proteins (Furuya and Lai, 1993; Zhang et al., 1994; Zhang and Lai, 1995). The cellular protein p35 has been identified as a heterogeneous nuclear ribonucleoprotein (hnRNP) A1. We have now expressed hnRNP-A1 as a glutathione-S-transferase (GST) fusion protein and demonstrated that the amino terminal two-thirds of hnRNP-A1 interacted with the two MHV regulatory RNA sequences (3'-end and intergenic sequences) through protein-RNA interaction while its carboxy-terminal glycine-rich domain mediated homomeric (protein-protein) interactions. In a partially reconstituted reaction, in which the two MHV RNA fragments and the purified GST-hnRNP-A1 fusion protein were mixed, an RNP complex was formed. Depletion of either hnRNP-A1 or one of the RNA components abolished the complex formation. These results indicate that hnRNP-A1 can mediate the formation of an MHV RNP complex, which includes both the negative-strand leader and intergenic sequences. Site-directed mutagenesis revealed that mutations in the MHV intergenic sequences, which inhibited MHV RNA transcription, also inhibited the RNP complex formation. Deletion analysis showed that the amino terminal RNA-binding domains of hnRNP-A1 is essential for the RNP complex formation while the carboxy-terminal protein-binding domain enhanced the complex formation by 90-fold. These findings provide direct evidence demonstrating that the negative-strand leader RNA and intergenic sequences can form an RNP complex mediated by cellular protein hnRNP-A1.

Animals↗

Functional involvement of urokinase-type plasminogen activator receptor in pemphigus acantholysis.

Urokinase-type plasminogen activator (uPA) has been well documented in the development of pemphigus acantholysis. The function of its receptor (uPA-R) in pemphigus acantholysis has only recently attracted attention. Increased expression of uPA-R has been demonstrated in pemphigus vulgaris. In this study, we have further explored the functional involvement of uPA-R in pemphigus acantholysis. Our results show that uPA-R expression is significantly increased in acantholytic foci of pemphigus vulgaris and pemphigus foliaceus but not in bullous pemphigoid or normal skin specimens; the expression of uPA-R in cultured human keratinocytes is subjected to regulation by pemphigus vulgaris IgG but not by pemphigoid IgG or normal human IgG; furthermore, anti-uPA-R monoclonal antibody effectively inhibits pemphigus vulgaris IgG induced acantholysis in skin organ cultures. These data suggest that uPA-R may play an important role in the pathogenesis of pemphigus acantholysis.

Acantholysis↗

Production of monocyte chemoattractant protein 1 in tuberculosis patients.

To investigate the role of monocyte chemoattractant protein 1 (MCP-1) in the immune response to Mycobacterium tuberculosis, we studied MCP-1 production in tuberculosis patients. CD14+ blood monocytes from tuberculosis patients spontaneously expressed higher levels of MCP-1 mRNA and protein than CD14+ monocytes from healthy tuberculin reactors. MCP-1 production in lymph nodes from tuberculosis patients was also markedly increased. These findings suggest that MCP-1 can contribute to the antimycobacterial inflammatory response by attracting monocytes and T lymphocytes.

Chemokine CCL2↗