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Biomedical subjects

X Hu

Publications and source records attributed to X Hu.

At least 127 records · Page 7Linked to original sources
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

Hybrid technique for dynamic imaging.

A number of data acquisition strategies have been introduced to speed up the image acquisition in dynamic settings. One such technique is the keyhole approach, which is based on reducing k-space coverage, and consequently the spatial resolution, of the dynamic information. Another is based on reducing the field of view of the dynamic information. These two techniques are complementary in that one reduces the field of view in k-space and the other does so in the spatial domain. A hybrid approach which combines the two is described in this study. In numerical simulations and experimental studies, this hybrid approach more accurately depicts the signal changes, outperforming the two techniques from which it is derived. Magn Reson Med 44:51-55, 2000.

Brain↗
PubMed2000

Wavelet transform-based Wiener filtering of event-related fMRI data.

The advent of event-related functional magnetic resonance imaging (fMRI) has resulted in many exciting studies that have exploited its unique capability. However, the utility of event-related fMRI is still limited by several technical difficulties. One significant limitation in event-related fMRI is the low signal-to-noise ratio (SNR). In this work, a method based on Wiener filtering in the wavelet domain is developed and demonstrated for denoising event-related fMRI data. Application of the technique to simulated and experimental data demonstrates that the technique is effective in reducing noise while preserving neuronal activity-induced response.

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

Threshold ion-pair production spectroscopy (TIPPS) of H2 and D2

The threshold ion-pair production spectra at the J" = 0 and J" = 1 thresholds of H2 and J" = 0, 1 and 2 thresholds of D2 obtained with single photon excitation are presented. The ion-pair yield spectra of H2 and D2 over these energy ranges demonstrate strong resonant enhancement, parts of which dominate the TIPPS signals, permitting the assignment of the lower states of these resonances. From those thresholds with weak resonant enhancement (the J" = 0 threshold of H2 and the J" = 1 threshold of D2) a very small direct contribution to ion-pair production can be observed. The behaviour of the TIPPS spectra taken with different applied discrimination fields is understood by modeling the field ionization behaviour of a MATI spectrum of H2, containing both the similarly resonantly enhanced v+ = 8 S(0) ionization threshold and the non-resonantly enhanced S(1) ionization threshold. From the H2 J" = 1 and D2 J" = 0 TIPPS spectra the energetic field-free thresholds of the H2 and D2 ion-pair limits were determined to be 139,714.8 +/- 1.0 cm-1 and 140,370.2 cm-1 +/- 1.0 cm-1, respectively.

Journal Article↗
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

Magnetic resonance studies of brain function and neurochemistry.

In the short time since its introduction, magnetic resonance imaging (MRI) has rapidly evolved to become an indispensable tool for clinical diagnosis and biomedical research. Recently, this methodology has been successfully used for the acquisition of functional, physiological, and biochemical information in intact systems, particularly in the human body. The ability to map areas of altered neuronal activity in the brain, often referred to as functional magnetic resonance imaging (fMRI), is probably one of the most significant recent achievements that rely on this methodology. This development has permitted the examination of functional specialization in human and animal brains with unprecedented spatial resolution, as demonstrated by mapping at the level of orientation and ocular dominance columns in the visual cortex. These functional imaging studies are complemented by the ability to study neurochemistry using magnetic resonance spectroscopy, allowing the determination of metabolic processes that support neurotransmission and neurotransmission rates themselves.

Animals↗
PubMed2000

Starling forces that oppose filtration after tissue oncotic pressure is increased.

We tested the hypothesis that the effective oncotic force that opposes fluid filtration across the microvessel wall is the local oncotic pressure difference across the endothelial surface glycocalyx and not the global difference between the plasma and tissue. In single frog mesenteric microvessels perfused and superfused with solutions containing 50 mg/ml albumin, the effective oncotic pressure exerted across the microvessel wall was not significantly different from that measured when the perfusate alone contained albumin at 50 mg/ml. Measurements were made during transient and steady-state filtration at capillary pressures between 10 and 35 cmH(2)O. A cellular-level model of coupled water and solute flows in the interendothelial cleft showed water flux through small breaks in the junctional strand limited back diffusion of albumin into the protected space on the tissue side of the glycocalyx. Thus oncotic forces opposing filtration are larger than those estimated from blood-to-tissue protein concentration differences, and transcapillary fluid flux is smaller than estimated from global differences in oncotic and hydrostatic pressures.

Animals↗