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Biomedical subjects

X Hu

Publications and source records attributed to X Hu.

At least 19 recordsLinked to original sources
PubMed2000

Catalytic efficiencies of allelic variants of human glutathione S-transferase Pi in the glutathione conjugation of alpha, beta-unsaturated aldehydes.

The catalytic efficiencies of the allelic variants of human glutathione (GSH) S-transferase Pi (hGSTP1-1), which differ in their primary structures by the amino acids in positions 104 (isoleucine or valine) and/or 113 (alanine or valine), in the GSH conjugation (detoxification) of acrolein and crotonaldehyde have been determined. The k(cat)/K(m) values for hGSTP1-1 isoforms I104,A113 (IA), I104, V113 (IV), V104,A113 (VA) and V104,V113 (VV) toward acrolein were 129+/-3, 116+/-3, 128+/-4 and 92+/-3 mM(-1) s(-1), respectively. The catalytic efficiencies of the hGSTP1-1 variants IA, IV, and VA in the GSH conjugation of acrolein were statistically significantly higher (at P=0.05) compared with the VV isoform. On the other hand, the catalytic efficiencies of the hGSTP1-1 isoforms IA, IV, VA and VV toward crotonaldehyde (16+/-2, 12+/-1, 17+/-2, and 12+/-2 mM(-1)s(-1), respectively) were not statistically significantly different from each other. Our results suggest that hGSTP1-1 polymorphism may be an important factor in differential susceptibility of individuals to the toxic effects of acrolein, which is a widely spread environmental pollutant and generated endogenously during metabolic activation of anticancer drug cyclophosphamide.

Acrolein↗
PubMed2000

Potentiation of benzo[a]pyrene-induced pulmonary and forestomach tumorigenesis in mice by D,L-buthionine-S,R-sulfoximine-mediated tissue glutathione depletion.

In vitro studies have suggested that the glutathione (GSH) S-transferase (GST)-catalyzed GSH conjugation is an important mechanism for the detoxification of (+)-anti-7,8-dihydroxy-9, 10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE], which is the activated form of the widespread environmental pollutant benzo[a]pyrene (BP). However, in vivo experimental evidence for the importance of GSH/GST system in defense against carcinogenic effects of BP is lacking. We hypothesized that if GSH/GST were to play an important role in the detoxification of (+)-anti-BPDE, the tumorigenic activity of BP would be increased by depleting the levels of GSH, which is the required nucleophilic substrate for GST-catalyzed conjugation reactions. In the present study, we have tested the above hypothesis by determining the effect of D, L-buthionine-S,R-sulfoximine (BSO)-mediated tissue GSH depletion on BP-induced tumorigenesis of the lung and forestomach in female A/J mice. Treatment of mice with three i.p. injections of 2.5 mmol BSO/kg (12 h apart) plus 20 mM BSO in drinking water, resulted in a statistically significant reduction in hepatic, pulmonary and forestomach GSH levels. At the same time, BSO-administration caused a statistically significant increase in BP-induced pulmonary and forestomach tumor multiplicity. To the best of our knowledge, the present study is the first report that provides in vivo experimental evidence for the importance of GSH/GST system in cellular protection against carcinogenic effects of BP.

Animals↗
PubMed2000

Comparison of chromosome 3p deletions between cervical precancers synchronous with and without invasive cancer.

Cervical cancers are considered to originate from a series of pre-malignant lesions (cervical intra-epithelial neoplasia, CIN). The mechanisms behind these events are unknown. In addition to HPV infection, deletions of chromosome 3p have been found to be a frequent event in cervical cancer and likely play an important role in the transition of CIN to invasive cancer. To classify the potential role of 3p deletions in early-stage cervical carcinogenesis, we analyzed LOH of 3p in cervical precancers. Thirty cases with single or multiple CIN lesions were selected for the study, including 20 cases without and 10 cases with synchronous invasive cancers. Allelic losses on 1 or more 3p loci were recorded in 33% (3/9) of CIN II and 36% (5/14) of CIN III lesions from 20 cases without co-existing invasive cancer, whereas an increasing percentage of LOH was observed in the 10 precancerous lesions synchronous with invasive cancer, with 71% (5/7) CIN II and 76% (13/17) CIN III lesions. This result implies that 3p deletions have selective roles in early transition of pre-malignancy to invasive cancer. Comparing the LOH patterns between the 2 groups, genetic deletions in cases with invasive cancers involved extensive regions of 3p but were more localized in precancer cases without concomitant invasive cancer. Two interstitial regions, 3p22-21.3 around marker D3S1260 and 3p21.1 around markers D3S1289 and D3S1076, were most frequently deleted in both groups, suggesting that these 2 regions are novel tumor-suppressor loci which may play a role in early transition of cervical precancer to invasive cancer. Identical LOH patterns between multiple CIN lesions and synchronous invasive cancer in the same case suggests that different cervical precancers and invasive cancer are genetically linked and most likely originate from a single precursor cell.

Chromosome Deletion↗
PubMed2000

Constitutive activation of retinoic acid receptor beta2 promoter by orphan nuclear receptor TR2.

The orphan nuclear receptor TR2 functions as a constitutive activator for the endogenous retinoic acid receptor beta2 (RAR(beta2)) gene expression in P19 embryonal carcinoma cells and for reporters driven by the RAR(beta2) promoter in COS-1 cells. The activation of RAR(beta2) by TR2 is mediated by the direct repeat-5 (DR5) element located in the RAR(beta2) promoter. Furthermore, cAMP exerts an enhancing effect on the activation of RAR(beta2) by TR2, which is mediated by the cAMP response element located in the 5'-flanking region of the DR5. The constitutive activation function-1 (AF-1) of TR2 is mapped to amino acid residues 10-30 in its N-terminal A segment. A direct molecular interaction occurs between CREMtau and TR2, detected by co-immunoprecipitation, which is mediated by the N-terminal AB segment of TR2. In gel mobility shift assays, TR2 competes with P19 nuclear factor binding to the RAR(beta2) promoter, and TR2 and CREMtau bind simultaneously to this DNA fragment. The role of TR2 in the early events of RA signaling process is discussed.

Animals↗
PubMed2000

Identification of hepatitis B virus indigenous to chimpanzees.

Hepatitis B viruses (HBV) and related viruses, classified in the Hepadnaviridae family, are found in a wide variety of mammals and birds. Although the chimpanzee has been the primary experimental model of HBV infection, this species has not been considered a natural host for the virus. Retrospective analysis of 13 predominantly wild-caught chimpanzees with chronic HBV infection identified a unique chimpanzee HBV strain in 11 animals. Nucleotide and derived amino acid analysis of the complete HBV genome and the gene coding for the hepatitis B surface antigen (S gene) identified sequence patterns that could be used to reliably identify chimpanzee HBV. This analysis indicated that chimpanzee HBV is distinct from known human HBV genotypes and is closely related to HBVs previously isolated from a chimpanzee, gibbons, gorillas, and orangutans.

Amino Acid Sequence↗
PubMed2000

A multiscale approach for analyzing in vivo spectroscopic imaging data.

A multiscale approach for analyzing in vivo magnetic resonance spectroscopic imaging (SI) data is described in this paper. With this method, fitting is performed at multiple spatial scales in a coarse-to-fine order. Results obtained at one scale are used as prior knowledge in fitting spectra at the next scale. The multiscale approach was validated with simulated data and demonstrated with proton SI datasets of the human brains. The results showed that this method improved the robustness and efficiency of the fitting and facilitated the automatic analysis of in vivo SI data.

Algorithms↗
PubMed2000

Temporal filtering of event-related fMRI data using cross-validation.

To circumvent the problem of low signal-to-noise ratio (SNR) in event-related fMRI data, the fMRI experiment is typically designed to consist of repeated presentations of the stimulus and measurements of the response, allowing for subsequent averaging of the resulting data. Due to factors such as time limitation, subject motion, habituation, and fatigue, practical constraints on the number of repetitions exist. Thus, filtering is commonly applied to further improve the SNR of the averaged data. Here, a time-varying filter based on theoretical work by Nowak is employed. This filter operates under the stationary wavelet transform framework and is demonstrated to lead to good estimates of the true signals in simulated data. The utility of the filter is also shown using experimental data obtained with a visual-motor paradigm.

Artifacts↗
PubMed2000

Risk factors for severe injuries associated with falls from playground equipment.

A case control study design was used to determine the risk factors for severe injuries associated with falls from playground equipment. Children presenting to the Hospital for Sick Children in Toronto because of falls from playground equipment (1995-1996) were identified through daily review of admissions and emergency department visits. Cases were defined as children with a severe injury (AIS > or = 2), whereas, controls were children with a minor injury (AIS < 2). Data on age, sex, socioeconomic status, prior experience on the equipment, previous playground injury, type of equipment, height of fall, undersurface, nature of injury, body part involved, and disposition were collected via telephone interview, field trip measurement, and mailed questionnaire. A total of 126 children were studied--67 cases and 59 controls. There were no differences between the two groups on age, sex, socioeconomic status, prior exposure to the equipment, or previous playground injury. Extremity fractures predominated in the case group, while, facial lacerations predominated in the control group. The median height of fall for cases was 199 cm, compared with 160 cm for controls (P = 0.021). Cases were also more likely to have fallen from a height of > 150 cm (73%), compared with controls (54%), P = 0.027. The majority of cases (82%) and controls (86%) fell onto an impact absorbing undersurface (P = 0.540). The median depth of impact absorbing undersurface, however, for both case and control injuries was 3 cm--well below the recommended safety standards. Height of fall was an important risk factor for severe injury associated with falls from playground equipment. Above 150 cm, the risk of severe injury was increased 2-fold.

Accidental Falls↗
PubMed2000

Oligomerization of RAR and AML1 transcription factors as a novel mechanism of oncogenic activation.

RAR and AML1 transcription factors are found in leukemias as fusion proteins with PML and ETO, respectively. Association of PML-RAR and AML1-ETO with the nuclear corepressor (N-CoR)/histone deacetylase (HDAC) complex is required to block hematopoietic differentiation. We show that PML-RAR and AML1-ETO exist in vivo within high molecular weight (HMW) nuclear complexes, reflecting their oligomeric state. Oligomerization requires PML or ETO coiled-coil regions and is responsible for abnormal recruitment of N-CoR, transcriptional repression, and impaired differentiation of primary hematopoietic precursors. Fusion of RAR to a heterologous oligomerization domain recapitulated the properties of PML-RAR, indicating that oligomerization per se is sufficient to achieve transforming potential. These results show that oligomerization of a transcription factor, imposing an altered interaction with transcriptional coregulators, represents a novel mechanism of oncogenic activation.

Cell Transformation, Neoplastic↗
PubMed2000

Trends in bicycling-related head injuries in children after implementation of a community-based bike helmet campaign.

BACKGROUND/PURPOSE: The aim of this study was to determine the effect of a community-based bike helmet promotion campaign on bike helmet use and related head injuries in children (0 to 14 years of age) in a large North American city. METHODS: The authors established a multifaceted, multidisciplined, community-based campaign to promote bike helmet use by children in 1989. The goals were to increase helmet use by 100% per year, to reduce fatal bike-related head injuries by 50% overall, and to explore the feasibility of legislation mandating helmet use. Helmet use was measured by standardized field observations repeated annually in a single borough within the metropolitan area. To estimate head injury incidence, the number of admissions to hospital for the treatment of bike-related head injuries in a regional trauma registry, which included all residents in the target population was used. The authors were unable to control for changes in exposure to bicycling or in the criteria for admissions to hospital for the treatment of head injuries during the study period. RESULTS: The bike helmet use rate rose from 4% in 1990 to 67% in 1996. The number of head injury admissions fell from 46 in 1990 to 24 in 1996. Legislation requiring helmet use by all children went into effect in October 1995. CONCLUSIONS: Bike helmet use increased significantly during the first 4 years of the campaign and again after the helmet law was implemented. The total number of bike-related head injury admissions declined by more than 50%. The campaign achieved all of its goals except for a 50% reduction in fatal head injuries, which were too infrequent for analysis.

Adolescent↗
PubMed2000

Intestinal absorption of beta-carotene ingested with a meal rich in sunflower oil or beef tallow: postprandial appearance in triacylglycerol-rich lipoproteins in women.

BACKGROUND: Evidence indicates that different types of fat have different effects on the postprandial plasma triacylglycerol response. Therefore, the type of fat may influence the appearance of beta-carotene in postprandial triacylglycerol-rich lipoproteins, which is used as an indicator of intestinal beta-carotene absorption. OBJECTIVE: We compared in female subjects the appearance of beta-carotene in plasma triacylglycerol-rich lipoproteins after beta-carotene was ingested with a meal containing sunflower oil or beef tallow. DESIGN: Women (n = 11) each ingested 2 different vitamin A-free, fat-rich meals that were supplemented with beta-carotene (47 micromol) and contained equivalent amounts (60 g) of sunflower oil or beef tallow. Blood samples were collected hourly from 0 to 10 h; additional samples were collected at selected intervals until 528 h. In a subgroup of the women (n = 7), plasma chylomicrons and 3 subfractions of VLDLs were separated by cumulative rate ultracentrifugation. RESULTS: The appearance of beta-carotene in chylomicrons and in each VLDL subfraction was lower after ingestion with the meal containing sunflower oil than after ingestion with the meal containing beef tallow (P < 0.03). In chylomicrons, the area under the concentration-versus-time curve (AUC) for beta-carotene was 38.1 +/- 13.6% lower (P < 0.03); in contrast, the AUC for triacylglycerol was higher (P < 0.05) after the sunflower-oil-rich meal than after the beef-tallow-rich meal. CONCLUSIONS: Ingestion of beta-carotene with a meal rich in sunflower oil as compared with a meal rich in beef tallow results in lower appearance of beta-carotene and greater appearance of triacylglycerol in triacylglycerol-rich lipoproteins.

Adult↗
PubMed2000

Effects of glucosinolates and flavonoids on colonization of the roots of Brassica napus by Azorhizobium caulinodans ORS571.

Plants of Brassica napus were assessed quantitatively for their susceptibility to lateral root crack colonization by Azorhizobium caulinodans ORS571(pXLGD4) (a rhizobial strain carrying the lacZ reporter gene) and for the concentration of glucosinolates in their roots by high-pressure liquid chromatography (HPLC). High- and low-glucosinolate-seed (HGS and LGS) varieties exhibited a relatively low and high percentage of colonized lateral roots, respectively. HPLC showed that roots of HGS plants contained a higher concentration of glucosinolates than roots of LGS plants. One LGS variety showing fewer colonized lateral roots than other LGS varieties contained a higher concentration of glucosinolates than other LGS plants. Inoculated HGS plants treated with the flavonoid naringenin showed significantly more colonization than untreated HGS plants. This increase was not mediated by a naringenin-induced lowering of the glucosinolate content of HGS plant roots, nor did naringenin induce bacterial resistance to glucosinolates or increase the growth of bacteria. The erucic acid content of seed did not appear to influence colonization by azorhizobia. Frequently, leaf assays are used to study glucosinolates and plant defense; this study provides data on glucosinolates and bacterial colonization in roots and describes a bacterial reporter gene assay tailored easily to the study of ecologically important phytochemicals that influence bacterial colonization. These data also form a basis for future assessments of the benefits to oilseed rape plants of interaction with plant growth-promoting bacteria, especially diazotrophic bacteria potentially able to extend the benefits of nitrogen fixation to nonlegumes.

Azorhizobium caulinodans↗
PubMed2000

Cell cycle and transcriptional control of human myeloid leukemic cells by transforming growth factor beta.

TGFbeta1 is a potent growth inhibitor of both primitive and more differentiated human myeloid leukemic cells. The extent of the growth inhibitory response to TGFbeta varies with cell type, and is not linked to stages of differentiation of cell lines. Downregulation of multiple cell cycle-regulatory molecules is a dominant event in TGFbeta1-mediated growth inhibition of human MV4-11 myeloid leukemia cells. Both G1-phase and G2-phase cyclins and cdks participate in the regulation of TGFbeta1-mediated growth inhibition of MV4-11 cells. By both depressing cdk2 synthesis and up-regulating cyclin E-associated p27, TGFbeta1 may magnify its inhibitory efficiency. TGFbeta1 also rapidly inhibits phosphorylation of pRb at several serine and threonine residues. The underphosphorylated pRb associates with E2F-4 in G1 phase, whereas the phosphorylated pRb mainly binds to E2F-1 and E2F-3 in proliferating MV4-11 cells. Since TGFbeta1 upregulates p130/E2F-4 complex formation and downregulates p107/E2F-4 complex formation, with E2F-4 levels remaining constant, our results suggest that E2F-4 is switched from p107 to pRb and p130 when cells exit from the cell cycle and arrest in G1 by TGFbeta1. In summary, TGFbeta1 inhibits growth of human myeloid leukemic cells through multiple pathways, whereas the "cdk inhibitor" p27 is both a positive and negative regulator.

CDC2-CDC28 Kinases↗
PubMed2000

Post-transcriptional regulation of mouse kappa-opioid receptor expression.

Three mRNA variants are generated from the mouse kappa-opioid receptor (KOR) gene. The expression patterns of these KOR mRNA variants in adult animal tissues and during developmental stages are examined. Furthermore, the biological significance of generating these variants is demonstrated with respect to two post-transcriptional mechanisms, i.e., mRNA stability and translation efficiency. Variants A and B are both transcribed from promoter 1 of the KOR gene and expressed from early developmental stages through adult life. Although their sequences differ only at a 30-nucleotide insertion for variant B, these two variants are distinct with regard to their expression patterns, mRNA stability, and translation efficiency. Variant A is expressed ubiquitously in all the tissues examined and has a longer t(1/2) (12 h), whereas variant B is more specific to the central nervous system both pre- and postnatally and has a t(1/2) of approximately 8 h. Variant C is transcribed from promoter 2 of the KOR gene and is most specifically expressed, being detected only in the brain stem, spinal cord, and thalamic/hypothalamic areas of postnatal animals. With regard to protein translation, variants B and C are significantly more efficient than variant A. This study provides the evidence for multiple levels of KOR regulation. The biological implication of the generation of KOR mRNA variants is discussed.

Animals↗
PubMed2000

Prolonged activation of the mitogen-activated protein kinase pathway is required for macrophage-like differentiation of a human myeloid leukemic cell line.

The role of the mitogen-activated protein kinase (MAPK) signal transduction pathway in the proliferation of mammalian cells has been well established. However, there are relatively few reports concerning cell differentiation being mediated by MAPK. The effect of phorbol 12-myristate 13-acetate (PMA) on cell differentiation and signal transduction in a human myeloid leukemia cell line, TF-1a, was investigated. When TF-1a cells were treated with 10(-6), 10(-7), 10(-8), and 10(-9) M PMA for 24 h, they underwent 98, 93, 91, and 51% macrophage-like differentiation, respectively. PMA treatment rapidly (10 min) induced phosphorylation of MAPK kinase (MEK and p44/42 MAPK), which persisted for at least 24 h. p44/42 MAPK immunoprecipitates from lysates of PMA-treated cells had increased ability to phosphorylate the transcription factor Elk-1. This is important because phosphorylated Elk-1 can be considered an "end-product" of the MAPK pathway. In contrast, treatment of TF-1a cells with granulocyte/macrophage-colony stimulating factor induced only transient activation of MEK and p44/42 MAPK (10-20 min) and an increase (approximately 50%) in cell proliferation, without any change in cellular differentiation. These results suggest that macrophage-like differentiation may be dependent on prolonged activation of the MAPK pathway. Additional support for this conclusion was obtained from experiments showing that treatment of TF-1a cells with antisense oligonucleotides for MEK1 coding sequences prior to adding PMA inhibited macrophage-like differentiation. Furthermore, transient transfection with an inactive, dominant-negative MEK mutant also inhibited PMA-induced differentiation, whereas transient transfection with a plasmid coding for constitutively activated MEK led to macrophage-like differentiation in the absence of PMA.

Blotting, Western↗
PubMed1999

A photothrombotic ring stroke model in rats with or without late spontaneous reperfusion in the region at risk.

This study aimed at developing a dual setup of the photothrombotic ring stroke model with or without late spontaneous reperfusion in the region at risk and to explore the morphological consequences. The exposed crania of adult male Wistar rats were subjected to a ring-shaped laser-irradiation beam (o.d. 5.0 mm, 0.35 mm thick) for 2 min simultaneously with intravenous erythrosin B (17 mg/kg) infusion. Transcardial carbon-black perfusion revealed that a laser intensity of 0.90 W/cm(2) resulted in late, that is, starting at 72 h, spontaneous reperfusion, whereas the lowest laser intensity that produced lack of reperfusion at 7 days post-irradiation was 1.84 W/cm(2). Laser-Doppler flowmetry showed prompt cortical cerebral blood flow (cCBF) reduction both in the ring lesion and region at risk (12% and 25% of control values) after high-intensity irradiation; these reduced flow values were more rapid and pronounced than in the low-intensity irradiation setup as previously shown. The high- compared with low-intensity irradiation setup produced more frequent occurrence of thrombi in the ring-lesion region and a larger ischemic cortical lesion with a more rapid pace of ischemic cellular changes in the ring-lesion region and the region at risk. The region at risk transformed into pannecrosis in the high-intensity, but recovered morphologically in the low-intensity irradiation setup. This dual photothrombotic setup with or without spontaneous reperfusion enables the study of events related to ischemic cell survival or death in an anatomically predefined region at risk.

Animals↗
PubMed1999

Development of New Chiral P,N Ligands and Their Application in the Cu-Catalyzed Enantioselective Conjugate Addition of Diethylzinc to Enones.

High enantioselectivity (up to 98 % ee) has been achieved for the conjugate addition of diethylzinc to acyclic enones utilizing Cu(I) complexes of the novel chiral P,N ligands 1. The high enantioselectivities are best achieved using [Cu(OTf)](2) small middle dotC(6)H(6) as the copper catalyst precursor in nonpolar solvents such as toluene or Cl(CH(2))(2)Cl. R=H, CH(3); Tf=F(3)CSO(2).

Journal Article↗