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Biomedical subjects

Y Chen

Publications and source records attributed to Y Chen.

At least 829 records · Page 46Linked to original sources

Occurrence of chronic obstructive pulmonary disease among Canadians and sex-related risk factors.

The etiology of chronic obstructive pulmonary disease (COPD) has not been fully understood. This analysis assessed the prevalence of COPD and its risk factors among Canadian men and women. The analysis was based on the data from 7210 subjects aged 35 to 64 years who participated in the first cycle of National Population Health Survey in 1994-1995. COPD was considered present if an affirmative response was given to the question: "Do you have chronic bronchitis or emphysema diagnosed by a health professional?" In order to take the complex survey design into account, analytic weights incorporating a design effect were used in all statistical analyses. The prevalence of COPD was 2.1% in nonsmokers, 2.7% in ex-smokers, and 8.2% in smokers in women. In men, the corresponding prevalence was 0.8%, 2.9%, and 3.5%, respectively. The adjusted odds ratio for current smoking men and women who started smoking before age of 18 years was 3.0 and 5.9 compared with their nonsmoking counterparts. Overweight women demonstrated a 2.4-fold increase in the prevalence of COPD compared with women with normal weight. Men from low-income families had an odds ratio of 3.7 compared with those from high-income families. A history of allergy was significantly related to COPD in both men and women. COPD was common among Canadian women. Early initiation of smoking and being overweight had stronger relationships to the prevalence of COPD in women than in men. On the contrary, household income was more strongly related to COPD for men than for women.

Adult↗

Structure and expression of Xenopus karyopherin-beta3: definition of a novel synexpression group related to ribosome biogenesis.

Karyopherin-beta3 is a nuclear transport receptor that appears to be involved in nuclear import of ribosomal proteins. Here we report on sequence and expression of karyopherin-beta3 in Xenopus. The differential distribution of karyopherin-beta3 mRNA during Xenopus embryogenesis is similar to that of several other protein import factors and of ribosomal proteins. These genes thus define a novel synexpression group in the context of ribosome biogenesis.

Amino Acid Sequence↗

Transgenically ectopic expression of Bmp4 to the Msx1 mutant dental mesenchyme restores downstream gene expression but represses Shh and Bmp2 in the enamel knot of wild type tooth germ.

Bmp4 is a downstream gene of Msx1 in early mouse tooth development. In this study, we introduced the Msx1-Bmp4 transgenic allele to the Msx1 mutants in which tooth development is arrested at the bud stage in an effort of rescuing Msx1 mutant tooth phenotype in vivo. Ectopic expression of a Bmp4 transgene driven by the mouse Msx1promoter in the dental mesenchyme restored the expression of Lef-1 and Dlx2 but neither Fgf3 nor syndecan-1 in the Msx1 mutant molar tooth germ. The mutant phenotype of molar but not incisor could be partially rescued to progress to the cap stage. The Msx1-Bmp4 transgene was also able to rescue the alveolar processes and the neonatal lethality of the Msx1 mutants. In contrast, overexpression of Bmp4 in the wild type molar mesenchyme down-regulated Shh and Bmp2 expression in the enamel knot, the putative signaling center for tooth patterning, but did not produce a tooth phenotype. These results indicate that Bmp4 can bypass Msx1 function to partially rescue molar tooth development in vivo, and to support alveolar process formation. Expression of Shh and Bmp2 in the enamel knot may not represent critical signals for tooth patterning.

Alleles↗

Planar signalling is not sufficient to generate a specific anterior/posterior neural pattern in pseudoexogastrula explants from Xenopus and Triturus.

Early observations on the morphology of total exogastrulae from urodeles (Axolotl) had provided evidence for essential vertical signalling mechanisms in the process of neural induction. Conversely, more recent studies with anurans (Xenopus laevis) making use of molecular markers for neural-specific gene expression appear to support the idea of planar signalling as providing sufficient information for neural differentiation along the anterior-posterior axis. In an attempt to resolve this apparent contradiction, we report on the comparative analysis of morphology and gene expression characteristics with explants prepared from both urodeles (Triturus alpestris) and anurans (Xenopus laevis). For this purpose, we have made use of a refined experimental protocol for the preparation of exogastrulae that is intended to combine the advantages of the Holtfreter type exogastrula and the Keller sandwich techniques, and which we refer to as pseudoexogastrula explants. Analysis of histology and expression of several neural and ectodermal marker genes in such explants suggests that neural differentiation is induced in both species, but only within the intermediate zone between ectoderm and endomesoderm. Therefore, experiments with Xenopus and Triturus explants described in this communication argue against planar signalling events as being sufficient to generate a specific anterior/posterior neural pattern.

Animals↗

Increased levels of intracellular iron in the brains of ApoE-deficient mice with closed head injury.

Previous studies have revealed that apolipoprotein E (apoE)-deficient mice have distinct memory deficits and neurochemical derangements and are oxidatively stressed prior to and following closed head injury. The objective of this study was to evaluate the possibility that the enhanced susceptibility of apoE-deficient mice to closed head injury is related to impairments in their antioxidative iron-chelating mechanisms. ApoE-deficient and control mice were subjected to closed had injury, after which the extent of brain-damage and the level of iron-containing cells were assessed. Examination of the brain-damaged areas in the injured mice revealed that, by Day 3 post injury, animals of both groups were maximally and similarly affected. While the size of the damaged area of the injured control mice diminished significantly by Day 7, however recovery was not observed in injured apoE-deficient mice up to at least 14 days post-injury. Histopathologically, the decrease in the damaged areas in the control mice was interpreted as related to decreased edema. Numbers of iron-containing cells at Days 3 and 7 after injury were greater in the brains of control mice than in the apoE-deficient mice. Whereas the number of iron-containing cells in injured control mice decreased at days 9 and 14-post injury, that of the injured apoE-deficient mice plateaued by Day 9 at a level more than two-fold higher than the maximal level seen for controls. The size of the damaged areas and the number of iron-containing cells were correlated (P < 0.03) for both mouse groups at days 9 and 14 after injury. The data suggest that the increased susceptibility of apoE-deficient mice to closed head injury may be due, at least in part, to impaired iron scavenging and sustained oxidative stress.

Animals↗

The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues.

Proapoptotic Bcl-2 family members have been proposed to play a central role in regulating apoptosis. However, mice lacking bax display limited phenotypic abnormalities. As presented here, bak(-/-) mice were found to be developmentally normal and reproductively fit and failed to develop any age-related disorders. However, when Bak-deficient mice were mated to Bax-deficient mice to create mice lacking both genes, the majority of bax(-/-)bak(-/-) animals died perinatally with fewer than 10% surviving into adulthood. bax(-/-)bak(-/-) mice displayed multiple developmental defects, including persistence of interdigital webs, an imperforate vaginal canal, and accumulation of excess cells within both the central nervous and hematopoietic systems. Thus, Bax and Bak have overlapping roles in the regulation of apoptosis during mammalian development and tissue homeostasis.

Abnormalities, Multiple↗

Study of infrared and mass spectra of N-2-(3'-phthalide-yl)phthalazin-1-one.

The infrared and mass spectra of N-2-(3'-phthalide-yl)phthalazin-1-one were studied. The loss of one or two natural CO residues was observed from the title compound and its partial fragment ions. Using the MIKE spectrum of ion m/z 250, its most possible structure was confirmed. Two possible paths of the formation of the title compound were also proposed.

Mass Spectrometry↗

Effect of 3' terminal adenylic acid residue on the uridylation of human small RNAs in vitro and in frog oocytes.

It is known that several small RNAs including human and Xenopus signal recognition particle (SRP) RNA, U2 small nuclear RNA (snRNA) and 7SK RNAs are posttranscriptionally adenylated, whereas U6 snRNA and ribosomal 5S RNA are posttranscriptionally uridylated on their 3' ends. In this study, we provide evidence that a small fraction of U6 snRNA and 5S ribosomal RNA molecules from human as well as Xenopus oocytes contain a single posttranscriptionally added adenylic acid residue on their 3' ends. These data show that U6 snRNA and 5S rRNAs are posttranscriptionally modified on their 3' ends by both uridylation and adenylation. Although the SRP RNA, 7SK RNA, 5S RNA, and U6 snRNA with the uridylic acid residue on their 3' ends were readily uridylated, all these RNAs with posttranscriptionally added adenylic acid residue on their 3' ends were not uridylated in vitro, or when U6 snRNA with 3' A(OH) was injected into Xenopus oocytes. These results show that the presence of a single posttranscriptionally added adenylic acid residue on the 3' end of SRP RNA, U6 snRNA, 5S rRNA, or 7SK RNA prevents 3' uridylation. These data also show that adenylation and uridylation are two competing processes that add nucleotides on the 3' end of some small RNAs and suggest that one of the functions of the 3' adenylation may be to negatively affect the 3' uridylation of small RNAs.

Adenosine Monophosphate↗

The role of mineral in the storage of elastic energy in turkey tendons.

Mammals elastically store energy in leg and foot tendons during locomotion. In the turkey, much of the force generated by the gastrocnemius muscle is stored as elastic energy during tendon deformation and not within the muscle. During growth, avian tendons mineralize in the portions distal to the muscle and show increased tensile strength and modulus as a result. The purpose of this study was to evaluate the viscoelastic behavior of turkey tendons and self-assembled collagen fiber models to determine the molecular basis for tendon deformation. The stress-strain behavior of tendons and self-assembled collagen fibers was broken into elastic and viscous components. The elastic component was found to be to a first approximation independent of source of the collagen and to depend only on the extent of cross-linking. In the absence of cross-links the elastic component of the stress was found to be negligible for self-assembled type I collagen fibers. In the presence of cross-links the behavior approached that found for mineralized turkey tendons. The elastic constant for turkey tendon was shown to be between 5 and 7.75 GPa while it was about 6.43 GPa for self-assembled collagen fibers aged for 6 months at 22 degrees C. The viscous component for mineralized turkey tendons was about the same as that of self-assembled collagen fibers aged for 6 months, a result suggesting that addition of mineral does not alter the viscous properties of tendon. It is concluded that elastic energy storage in tendons involves direct stretching of the collagen triple-helix, nonhelical ends, and cross-links between the molecules and is unaffected by mineralization. Furthermore, it is hypothesized that mineralization of turkey tendons is an efficient means of preserving elastic energy storage while providing for increased load-bearing ability required for locomotion of adult birds.

Animals↗

Isolation and identification of stilbenes in two varieties of Polygonum cuspidatum.

The roots of two varieties of Polygonum cuspidatum (Hu Zhang and Mexican Bamboo) were analyzed for resveratrol and analogues. The roots of each variety were dried and ground into a powder. The powdered roots were then extracted with methanol and ethyl acetate. The ethyl acetate fraction of the Mexican Bamboo was then subjected to fractionation and purification using silica gel column chromatography and semipreparative HPLC. In addition to resveratrol (3,5,4'-trihydroxystilbene), three stilbene glucosides were identified by (1)H NMR, (13)C NMR, and MS. The stilbene glucosides were shown to be a piceatannol glucoside (3,5,3', 4'-tetrahydroxystilbene 4'-O-beta-D-glucopyranoside), resveratroloside (3,5,4'-trihydroxystilbene 4'-O-beta-D-glucopyranoside), and piceid (3,5,4'-trihydroxystilbene 3-O-beta-D-glucopyranoside). The levels of the piceatannol glucoside and piceid were twice as high in the Mexican Bamboo as compared to the Hu Zhang.

Chromatography, High Pressure Liquid↗

Effect of urea on volatile generation from Maillard reaction of cysteine and ribose.

Urea occurs naturally in many food products, and its presence affects food quality. However, little is known about its impact on flavor generation in food production. In this study, the urea contents in beef, pork, and chicken were determined. The effects of urea and pH on thermal flavor generation were investigated using the model system of cysteine with ribose, which was heated to the roasting temperature of 180 degrees C for 2 h at pH 5 and pH 8.5. The results revealed relatively large amounts of urea in these meats and demonstrated that pH affects aroma generation. Volatiles identified from the reaction system of ribose and cysteine showed that sulfur-containing compounds such as thiophenes, thiazoles, and thiophenethiols were the most abundant compounds. The addition of urea into the reaction mixture caused the disappearance or reduction in content of some sulfur-containing compounds but resulted in the generation of several important nitrogen-containing volatiles, like pyrazine, methylpyrazine, 2,5- (and 2,6-)dimethylpyrazine and other alkylpyrazines, which are known to elicit roasty, nutty flavor notes. A plausible explanation for this phenomenon is that ammonia can be released from urea upon heating and the formed ammonia competes with hydrogen sulfide to react with Maillard reaction precursors to produce nitrogen-containing compounds such as alkylpyrazines.

Cysteine↗

A metabolite of equine estrogens, 4-hydroxyequilenin, induces DNA damage and apoptosis in breast cancer cell lines.

Estrogen replacement therapy has been correlated with an increased risk of developing breast or endometrial cancer. 4-Hydroxyequilenin (4-OHEN) is a catechol metabolite of equilenin which is a minor component of the estrogen replacement formulation marketed under the name of Premarin (Wyeth-Ayerst). Previously, we showed that 4-OHEN autoxidizes to quinoids which can consume reducing equivalents and molecular oxygen, are potent cytotoxins, and cause a variety of damage to DNA, including formation of bulky stable adducts, apurinic sites, and oxidation of the phosphate-sugar backbone and purine/pyrimidine bases [Bolton, J. L., Pisha, E., Zhang, F., and Qiu, S. (1998) Chem. Res. Toxicol. 11, 1113-1127]. All of these deleterious effects could contribute to the cytotoxic and genotoxic effects of equilenin in vivo. In the study presented here, we examined the relative toxicity of 4-OHEN in estrogen receptor (ER) positive cells (MCF-7 and S30) compared to that in breast cancer cells without the estrogen receptor (MDA-MB-231). The data showed that 4-OHEN was 4-fold more toxic to MCF-7 cells (LC(50) = 6.0 +/- 0. 2 microM) and 6-fold more toxic to S30 cells (LC(50) = 4.0 +/- 0.1 microM) than to MDA-MB-231 cells (LC(50) = 24 +/- 0.3 microM). Using the single-cell gel electrophoresis assay (comet assay) to assess DNA damage, we found that 4-OHEN causes concentration-dependent DNA single-strand cleavage in all three cell lines, and this effect could be enhanced by agents which catalyze redox cycling (NADH) or deplete cellular GSH (diethyl maleate). In addition, the ER(+) cell lines (MCF-7 and S30) were considerably more sensitive to induction of DNA damage by 4-OHEN than the ER(-) cells (MDA-MB-231). 4-OHEN also caused a concentration-dependent increase in the amount of mutagenic lesion 8-oxo-dG in the S30 cells as determined by LC/MS-MS. Cell morphology assays showed that 4-OHEN induces apoptosis in these cell lines. As observed with the toxicity assay and the comet assay, the ER(+) cells were more sensitive to induction of apoptosis by 4-OHEN than MDA-MB-231 cells. Finally, the endogenous catechol estrogen metabolite 4-hydroxyestrone (4-OHE) was considerably less effective at inducing DNA damage and apoptosis in breast cancer cell lines than 4-OHEN. Our data suggest that the cytotoxic effects of 4-OHEN may be related to its ability to induce DNA damage and apoptosis in hormone sensitive cells in vivo, and these effects may be potentiated by the estrogen receptor.

Apoptosis↗

Dysregulated expression of bcl-2 and bax in oral carcinomas: evidence of post-transcriptional control.

A study was conducted to investigate the gene expression of bcl-2 and bax in oral squamous cell carcinomas. We used reverse-transcriptase-polymerase chain reaction (RT-PCR) to evaluate the expression of bcl-2 and bax mRNAs and the ratio of bcl-2/bax mRNA, and employed immunohistochemistry to investigate the bcl-2- and bax-encoded proteins. It was observed that the expression level of bcl-2 mRNA or bax mRNA was not consistent with their protein level in some cases. Higher expression of bcl-2 mRNA and stronger immunostaining of bcl-2 protein were found in oral squamous cell carcinomas than in the adjacent histologically normal oral epithelium. These findings were more prominent in poorly differentiated carcinomas. No significant differences in bax mRNA and protein were observed between carcinomas and the adjacent histologically normal oral epithelium. However, poorly differentiated carcinomas showed very weak immunostaining for bax. The ratio of bcl-2/bax mRNA was higher in carcinomas than in the adjacent histologically normal oral epithelium, and higher ratios were seen in most of poorly differentiated carcinomas. This study supplies indirect evidence of post-transcriptional control of bcl-2 and bax expression, and suggests that dysregulated expression of bcl-2 and bax may be related to the differentiation of oral squamous cell carcinomas.

Adult↗

Unwanted thought: age differences in the correction of social judgements.

This study use a false information paradigm to study age differences in the correction of social judgments. Younger and older adults read 2 criminal reports, with true information printed in black and false information in red. Following the reports, all participants were asked to recommend prison terms among other ratings. Age differences in baseline measures were also assessed by corresponding control groups who read only true information. Compared with younger adults under full attention, older adults under full attention and younger adults under divided attention were reliably influenced by the nature of the false statements (either extenuating or exacerbating the severity of the crimes). When contrasted with their relevant control groups, older adults under full attention and younger adults under divided attention failed to correct their social judgments. This study lends support to a processing resource explanation for age differences in the correction process for social judgments.

Adolescent↗

Genotype-based screen for ENU-induced mutations in mouse embryonic stem cells.

The ability to generate mutations is a prerequisite to functional genetic analysis. Despite a long history of using mice as a model system for genetic analysis, the scientific community has not generated a comprehensive collection of multiple alleles for most mouse genes. The chemical mutagen of choice for mouse has been N-ethyl-N-nitrosourea (ENU), an alkylating agent that mainly causes base substitutions in DNA, and therefore allows for recovery of complete and partial loss-, as well as gain-, of-function alleles . Specific locus tests designed to detect recessive mutations showed that ENU is the most efficient mutagen in mouse with an approximate mutation rate of 1 in 1,000 gametes. In fact, several genome-wide and region-specific screens based on phenotypes have been carried out. The anticipation of the completion of the human and mouse genome projects, however, now emphasizes genotype-driven genetics--from sequence to mutants. To take advantage of the mutagenicity of ENU and its ability to create allelic series of mutations, we have developed a complementary approach to generating mutations using mouse embryonic stem (ES) cells. We show that a high mutation frequency can be achieved and that modulating DNA-repair activities can enhance this frequency. The treated cells retain germline competency, thereby rendering this approach applicable for efficient generation of an allelic series of mutations pivotal to a fine-tuned dissection of biological pathways.

Amino Acid Substitution↗

Combinational immunotherapy for established tumors with engineered tumor vaccines and adenovirus-mediated gene transfer.

There are currently extensive studies relating to cancer vaccines using tumor cells engineered to express immunogenes and cancer gene therapy using adenovirus (AdV)-mediated gene transfer. In this study, a mouse tumor cell line, VKCK, was cotransfected with genes coding for tumor necrosis factor-alpha (TNF-alpha) and costimulatory B7-1 molecule to enhance immunogenicity. The transfectant cell line VKCK-TNF-alpha/B7-1 showed reduced tumorigenicity and tumor regression. Its inoculation further induced protective immunity; both CD4+ and CD8+ T cells were involved in the induction phase, whereas only CD8+ T cells mediated the effector phase. Susceptible mice bearing VKCK tumors developed a T helper type 2-dominant response, whereas resistant mice with VKCK-TNF-alpha/B7-1 tumor regression developed a T helper type 1-dominant response to VKCK, indicating that the tumor regression was related to a shift in the cytokine profile of the host from type 2 to type 1. Vaccination of VKCK-TNF-alpha/B7-1 cells inhibited tumor formation derived from a single dose of 3 x 10(6) VKCK cells and eradicated 3-day tumors but not 10-day tumors. AdV-mediated TNF-alpha gene transfer by intratumoral injection of AdV-TNF-alpha significantly inhibited tumor growth but failed to eradicate any well-established tumors. However, combinational immunotherapy with vaccination of VKCK-TNF-alpha/B7-1 cells and AdV-mediated TNF-alpha gene transfer not only significantly inhibited tumor growth but also eradicated 10-day VKCK tumors in three of eight mice. Therefore, the present study may be useful not only in understanding the mechanisms responsible for an efficient antitumoral immunity, but also in establishing a more effective immunotherapeutic approach for cancer patients.

Adenoviridae↗

Current trend and risk factors for kidney stones in persons with spinal cord injury: a longitudinal study.

STUDY DESIGN: A multi-center longitudinal study. OBJECTIVES: To estimate the current trend in the incidence of first kidney stone among persons with spinal cord injury (SCI) and to delineate the potential contributing factors. SETTING: Twenty-one Model SCI Care Systems throughout the United States. METHODS: A longitudinal cohort of 8314 subjects enrolled in the National SCI Database between 1986 and 1999 was used to estimate and compare the incidence of first kidney stone with a previous report of 5850 SCI patients injured between 1973 and 1982. A Cox regression analysis was performed to identify risk factors for stones, including age, race, gender, severity of injury, and method of urinary drainage. These variables have been routinely collected, on a yearly basis, by the collaborating SCI centers. RESULTS: During the 12 years, 6 months of case ascertainment, 286 incident stone cases were documented. The risk was greatest during the first 3 months after injury (31 cases per 1000 person-years), quickly decreasing and leveling off later (eight cases per 1000 person-years). It was estimated that within 10 years after injury, 7% of persons with SCI would develop their first kidney stone. There was no evidence that the risk has changed over the past 25 years (P=0.96). During the first year post injury only, a significantly increased risk of stones was observed in Caucasians and persons aged 45 years or older. A positive association of the severity of injury and requiring instrumentation for bladder emptying with kidney stones was found after the first year post injury. The type of urinary drainage, including indwelling, intermittent, and condom catheterization, had no significant differential effect on stone formation at either risk period. CONCLUSIONS: The highest risk of kidney stones is within the first few months post injury. Little progress has been made in reducing this risk. Although inability to control bladder function is an important risk factor after the first year post injury, for those who need bladder management, the type of urinary drainage does not appear to be an important factor in determining risk. Spinal Cord (2000) 38, 346 - 353.

Adolescent↗

Does eradication of Helicobacter pylori alone heal duodenal ulcers?

BACKGROUND: Eradication of Helicobacter pylori infection prevents duodenal ulcer (DU) relapse, but it remains uncertain whether eradication of H. pylori alone heals duodenal ulceration. AIM: To test the hypothesis that eradication of H. pylori infection is accompanied by healing of duodenal ulcer. METHODS: A total of 115 consecutive patients with endoscopically confirmed H. pylori-infected duodenal ulcer were randomly assigned to one of two groups. Group BTC patients received a 1-week course of colloidal bismuth subcitrate 220 mg b.d., tinidazole 500 mg b.d., clarithromycin 250 mg b.d. Group OBTC patients received omeprazole 20 mg daily for 4 weeks with the BTC regimen during the first week. Endoscopy with antral biopsies and 13C-urea breath test (UBT) were performed before and 4 weeks after completion of the 7-day triple or quadruple therapy. RESULTS: Eight patients dropped out (four in BTC and four in OBTC). Duodenal ulcer healing rates on an intention-to-treat basis in BTC and OBTC were 86% (95% CI: 77-95%) and 90% (95% CI: 82-98%), respectively. The eradication rates of H. pylori on an intention-to-treat basis in BTC and OBTC were 88% (95% CI: 79-96%) and 91% (95% CI: 84-99%), respectively. There were no statistically significant differences in ulcer healing rates and eradication rates between these two groups (P > 0.05). Epigastric pain resolved more rapidly in patients assigned to OBTC compared with those assigned to BTC. Both of the two regimens were well tolerated with only minor side-effects (3% of the 115 patients) and the compliance was good. CONCLUSIONS: BTC is a very effective H. pylori eradication regimen. Almost all duodenal ulcers heal spontaneously after cure of H. pylori infection using a 1-week low-dose bismuth-based triple therapy. Treating duodenal ulcer with simultaneous administration of omeprazole achieves ulcer pain relief more rapidly.

Adolescent↗