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Biomedical subjects

X Liu

Publications and source records attributed to X Liu.

At least 289 records · Page 16Linked to original sources

Apatite formed on the surface of plasma-sprayed wollastonite coating immersed in simulated body fluid.

Wollastonite coatings on titanium alloys substrates were prepared by plasma spraying and incubated in simulated body fluids for different periods to investigate the nucleation and growth of apatite on their surface. Surface structural changes of the specimens were analyzed by XRD and IR technologies. SEM and EDS were used to observe surface morphologies and determine the composition of wollastonite coatings before and after immersion in simulated body fluid. The changes in the concentrations of calcium, silicon and phosphorus in the simulated body fluids due to the immersion of the specimens were measured by inductively coupled plasma atomic emission spectroscopy. The results obtained showed that hydroxycarbonate apatite can be formed on the surface of the coating soaked in SBF for 1 day. With longer immersion periods, the coating surface was covered by hydroxycarbonate apatite, which indicated that the wollastonite coating possesses good bioactivity.

Alloys↗

Transitions in functional status among older people in Wuhan, China: socioeconomic differentials.

The vast majority of research on socioeconomic status (SES) and old-age disability is based on data derived from the developed nations. This study evaluates the external validity of current findings by examining old-age disability in China, a developing nation. The direct, indirect, and total effects of SES on disability transitions were ascertained during a 3-year period in a probability sample of 2,943 people aged 60 years or older in Wuhan, China. As SES measures, education and urban residence exert distinct direct and indirect effects on functional transitions with complicated underlying mechanisms. SES has differential effects on functional transitions depending on one's prior functional state. Furthermore, the generally positive effects of SES are partially offset by negative indirect effects

Aged↗

Synaptotagmin VII as a plasma membrane Ca(2+) sensor in exocytosis.

Synaptotagmins I and II are Ca(2+) binding proteins of synaptic vesicles essential for fast Ca(2+)-triggered neurotransmitter release. However, central synapses and neuroendocrine cells lacking these synaptotagmins still exhibit Ca(2+)-evoked exocytosis. We now propose that synaptotagmin VII functions as a plasma membrane Ca(2+) sensor in synaptic exocytosis complementary to vesicular synaptotagmins. We show that alternatively spliced forms of synaptotagmin VII are expressed in a developmentally regulated pattern in brain and are concentrated in presynaptic active zones of central synapses. In neuroendocrine PC12 cells, the C(2)A and C(2)B domains of synaptotagmin VII are potent inhibitors of Ca(2+)-dependent exocytosis, but only when they bind Ca(2+). Our data suggest that in synaptic vesicle exocytosis, distinct synaptotagmins function as independent Ca(2+) sensors on the two fusion partners, the plasma membrane (synaptotagmin VII) versus synaptic vesicles (synaptotagmins I and II).

Aging↗

Association of DDT with spontaneous abortion: a case-control study.

PURPOSE: Spontaneous abortion (SAB), the most common adverse pregnancy outcome, affects approximately 15% of clinically recognized pregnancies. Except for advanced maternal age and smoking, there are not well-established risk factors for SAB. Animal models associate increased fetal resorption or abortion with exposure to the pesticide dichlorodiphenyl trichloroethane (DDT), but epidemiologic investigations of DDT and SAB are inconsistent. We undertook a pilot investigation of the hypothesized association of DDT with SAB. METHODS: Participants in this case-control study were selected from a longitudinal study of reproductive effects of rotating shifts among female Chinese textile workers who were married, ages 22-34, nulliparous without history of SAB or infertility, and planning pregnancy. From 412 pregnancies, 42 of which ended in SAB, 15 SAB cases and 15 full-term controls were randomly selected and phlebotomized. Serum was analyzed for p,p'-DDT, o,p'-DDT, their metabolites (DDE and DDD), and other organochlorines including polychlorinated biphenyls. RESULTS: Cases and controls were nonsmokers and did not differ in age (mean 25 years), body mass index (BMI), passive smoke exposure, or workplace exposures. Cases had significantly (p < 0.05) higher serum levels of p,p'-DDE (22 vs.12 ng/g) and o,p'-DDE (0.09 vs. 0.05 ng/g) than controls. After adjustment for age and BMI, each ng/g serum increase in p,p'-DDE was associated with a 1.13 (CI, 1.02-1.26) increased odds of SAB. With adjustment of serum DDE levels for excretion via breastfeeding, DDE-associated increased odds of SAB remained significant with up to 7% declines in maternal serum DDE levels for each month of breastfeeding. CONCLUSIONS: A potential increased risk of SAB is associated with maternal serum DDE levels.

Abortion, Spontaneous↗

Uncoupling protein1 mRNA, mitochondrial GTP-binding, and T4 5'-deiodinase of brown adipose tissue in euthermic Daurian ground squirrel during cold exposure.

Regulation of thermogenic activity and uncoupling protein1 (UCP1) expression in brown adipose tissue (BAT) were studied in euthermic Daurian ground squirrel after acute and chronic cold exposure at 4 degrees C. The UCP1 concentration was indirectly determined by titration with its specific ligand [3H]-labeled GTP, and Ucp1 mRNA was detected by using a [32P]-labeled antisense oligonucleotide probe. Both acute and chronic cold exposure stimulated up-regulation of Ucp1 mRNA. Although UCP1 concentration is not significantly increased after 24 h of cold exposure, it is markedly elevated by 75% in squirrels after 4-week cold adaptation compared with controls raised at 22 degrees C. Changes in T4 5'-deiodinase activity were closely associated with variations of Ucp1 mRNA level. Ucp1 gene expression is significantly affected by cold exposure in BAT from euthermic Daurian ground squirrels. In addition, the activation of T4 5'-deiodinase may be an important regulatory factor in cold-induced Ucp1 expression.

Adaptation, Physiological↗

Cold adaptive thermogenesis in small mammals from different geographical zones of China.

The mechanisms of thermogenesis and thermoregulation were studied in the tree shrew (Tupaia belangeri) and greater vole (Eothenomys miletus) of the subtropical region, and Brandt's vole (Microtus brandti), Mongolian gerbil (Meriones unguiculatus), Daurian ground squirrel (Spermophilus dauricus) and plateau pika (Ochotona curzoniae) of the northern temperate zone. Resting metabolic rate (RMR) and non-shivering thermogenesis (NST) increased significantly in T. belangeri, E. miletus, M. brandti and M. unguiculatus after cold acclimation (4 degrees C) for 4 weeks. In T. belangeri, the increase in RMR and thermogenesis at liver cellular level were responsible for enhancing the capacity of enduring cold stress, and homeothermia was simultaneously extended. Stable body temperature in M. brandti, E. miletus, M. unguiculatus and O. curzoniae was maintained mainly through increase in NST, brown adipose tissue (BAT) mass and its mitochondrial protein content, and the upregulation of uncoupling protein (UCP1) mRNA, as well as enhancement of the activity of cytochrome C oxidase, alpha-glycerophosphate oxidase and T(4) 5'-deiodinase in BAT mitochondria. The RMR in O. curzoniae and euthermic S. dauricus was not changed, while NST significantly increased during cold exposure; the former maintained their stable body temperature and mass, while body temperature in the latter declined by 4.8 degrees C. The serum T(3) concentration or ratio of T(3)/T(4) in all the species was enhanced after cold acclimation. Results indicated that: (1) the adaptive mechanisms of T. belangeri residing in the subtropical region to cold are primarily by increasing RMR and secondly by increasing NST, and the mechanisms of thermogenesis are similar to those in tropical mammals; (2) in small mammals residing in northern regions, the adaptation to cold is chiefly to increase NST; (3) the mechanism of cold-induced thermogenesis in E. miletus residing in subtropical and high mountain regions is similar to that in the north; (4) a low RMR in warm environments and peak RMR and NST in cold environments enabled M. unguiculatus to tolerate a semi-desert climate; (5) O. curzoniae has unusually high RMR and high NST, acting mainly via increasing NST to adapt to extreme cold of the Qinghai-Tibet Plateau; (6) the adaptation of euthermic S. dauricus to cold is due to an increase in NST and a relaxed homeothermia; and lastly (7) the thyroid hormone is involved in the regulation of cold adaptive thermogenesis in all the species studied.

Adaptation, Physiological↗

The anaphase-promoting complex mediates TGF-beta signaling by targeting SnoN for destruction.

Degradation of SnoN is thought to play an important role in the transactivation of TGF-beta responsive genes. We demonstrate that the anaphase-promoting complex (APC) is a ubiquitin ligase required for the destruction of SnoN and that the APC pathway is regulated by TGF-beta. The destruction box of SnoN is required for its degradation in response to TGF-beta signaling. Furthermore, the APC activator CDH1 and Smad3 synergistically regulate SnoN degradation. Under these circumstances, CDH1 forms a quaternary complex with SnoN, Smad3, and APC. These results suggest that APC(CDH1) and SnoN play central roles in regulating growth through the TGF-beta signaling system.

Amino Acid Sequence↗

Ski/Sno and TGF-beta signaling.

Transforming growth factor-beta is a potent inhibitor of epithelial cell proliferation. Proteins involved in TGF-beta signaling are bona fide tumor suppressors and many tumor cells acquire the ability to escape TGF-beta growth inhibition through the loss of key signaling transducers in the pathway or through the activation of oncogenes. Recent studies indicate that there is a specific connection between the TGF-beta signaling pathway and the Ski/SnoN family of oncoproteins. We summarize evidence that Ski and SnoN directly associate with Smad proteins and block the ability of the Smads to activate expression of many if not all TGF-beta-responsive genes. This appears to cause abrogation of TGF-beta growth inhibition in epithelial cells.

Animals↗

High-resolution quantitative trait locus mapping for body weight in mice by recombinant progeny testing.

A major obstacle to the positional cloning of quantitative trait loci (QTLs) lies in resolving genetic factors whose allelic effects are blurred by environmental and background genetic variation. We investigate a fine-mapping approach that combines the use of an interval-specific congenic strain with progeny testing of recombinants for markers flanking a QTL. We apply the approach to map a murine QTL with an approximately 20% effect on growth rate by progeny testing 39 recombinants in a 12 cM region of the X chromosome. We use a likelihood analysis in an attempt to maximize the information on QTL map location and effect. The major X-linked effect is mapped to an approximately 2 cM region flanked by markers about 5 cM apart, outside which LOD support for the QTL drops extremely steeply by about 80. Nearly unambiguous assignment of the QTL genotypic state is obtained for each recombinant. The resolution of individual recombinants in the region is therefore sufficiently high to facilitate the positional cloning of the locus, although progress has been hampered because the genomic region containing the QTL shows an exceptionally low level of polymorphism in comparison with recent studies.

Alleles↗

Advanced technique for three-dimensional visualization of compound distributions in a rice kernel.

A three-dimensional (3D) visualization technique for the compound distribution in a rice kernel was developed. This technique is a combination of sectioning, staining, and digital image postprocessing. By using a special microtome system with adhesive tapes, a set of sequential sections of a rice kernel, which can be preserved with their own set of relative position data, was obtained. A single set of sequential sections was stained by various chemical techniques for the visualization of protein, starch, or lipid content. Each stained section was digitally captured using a CCD imaging device. As the stained areas represent areas containing dye-target complex, the distribution of each compound in the section was visualized in two dimensions. The digitally captured images of a single set of sequential sections were reconstructed to produce a 3D plotting image. As a result, the distributions of various compounds in a rice kernel could be visualized in a new 3D model.

Coloring Agents↗

Antisweet saponins from Gymnema sylvestre.

Three new oleanane-type triterpene glycosides (1-3), along with the sodium salt of alternoside II (4), were isolated from an ethanol extract of the leaves of Gymnema sylvestre. The structures of these new saponins were identified as 21 beta-O-benzoylsitakisogenin 3-O-beta-D-glucopyranosyl(1-->3)-beta-D-glucuronopyranoside (1), the potassium salt of longispinogenin 3-O-beta-D-glucopyranosyl(1-->3)-beta-D-glucuronopyranoside (2), and the potassium salt of 29-hydroxylongispinogenin 3-O-beta-D-glucopyranosyl(1-->3)-beta-D-glucuronopyranoside (3). The aglycon of 3, gymnemagenol (3a), was characterized as 3 beta,16 beta,28, 29-tetrahydroxyolean-12-ene. Structure elucidation was accomplished by interpretation of NMR (DQF-COSY, HMQC, and HMBC) results, FABMS, and hydrolysis. Saponin 1 and the sodium salt of alternoside II (4) exhibited antisweet activity.

Adult↗

Metabolism of equilenin in MCF-7 and MDA-MB-231 human breast cancer cells.

Sulfate conjugates of the B-ring unsaturated estrogens, equilin, equilenin, and 8-dehydroestrone, and their 17alpha- and 17beta-dihydro analogues, constitute about 54% of Premarin (Wyeth-Ayerst), the most commonly prescribed estrogen formulation in estrogen replacement therapy. Despite the wide clinical use of Premarin, there have been very few studies on the metabolism of the B-ring unsaturated estrogens in humans and there is no information regarding the fate of these compounds in breast tissue or tumors. In this study, we investigated the metabolism of equilenin in two lines of human breast-cancer cells, MCF-7 and MDA-MB-231. MCF-7 cells respond to treatment with Ah-receptor agonists with induction of cytochromes P450 1A1 and 1B1, whereas in MDA-MB-231 cells P450 1B1 is predominantly induced. Metabolites of equilenin were identified and quantified by GC/MS utilizing a series of synthetic metabolite standards and deuterium-labeled analogues as internal standards. In the two cell lines, the same pathways of equilenin metabolism were observed. Equilenin was reduced at C-17 to the 17beta-dihydro form, with minimal production of the 17alpha-dihydro isomer. Both equilenin and 17beta-dihydroequilenin were hydroxylated at the C-4 position, and the resultant catechol metabolites were methylated to form 4-methoxyequilenin and 4-methoxy-17beta-dihydroequilenin. Rates of equilenin metabolism were markedly elevated in cultures exposed to the Ah-receptor agonists, 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3,4,4',5-tetrachlorobiphenyl, implicating the activities of P450s 1A1 and 1B1 in the metabolism. The 2-hydroxylation pathways of equilenin and 17beta-dihydroequilenin metabolism were not observed. In microsomal reactions with cDNA-expressed human enzymes, both P450s 1A1 and 1B1 catalyzed the 4-hydroxylation of 17beta-dihydroequilenin, whereas with 17beta-estradiol as substrate P450 1A1 catalyzes predominantly 2-hydroxylation and P450 1B1 predominantly 4-hydroxylation. Since P450 1B1 is constitutively expressed and both P450s 1A1 and 1B1 are inducible in many extrahepatic tissues including the mammary epithelium, these results indicate the potential for 4-hydroxylation of equilenin and 17beta-dihydroequilenin in extrahepatic, estrogen-responsive tissues.

Aryl Hydrocarbon Hydroxylases↗

Equine estrogen metabolite 4-hydroxyequilenin induces DNA damage in the rat mammary tissues: formation of single-strand breaks, apurinic sites, stable adducts, and oxidized bases.

Epidemiological data strongly suggest that a woman's risk of developing breast cancer is directly related to her lifetime estrogen exposure. Estrogen replacement therapy in particular has been correlated with an increased cancer risk. Previously we showed that the equine estrogens equilin and equilenin, which are major components of the estrogen replacement formulation Premarin (Wyeth-Ayerst), are metabolized to the catechol, 4-hydroxyequilenin which autoxidizes to an o-quinone causing oxidation and alkylation of DNA in vitro [Bolton, J. L., Pisha, E., Zhang, F., and Qiu, S. (1998) Chem. Res. Toxicol. 11, 1113-1227]. In the present study, we injected 4-hydroxyequilenin into the mammary fat pads of Sprague-Dawley rats. Analysis of cells isolated from the mammary tissue for DNA single-strand breaks and oxidized bases using the comet assay showed a dose-dependent increase in both types of lesions. In addition, LC-MS-MS analysis of extracted mammary tissue showed the formation of an alkylated depurinating guanine adduct. Finally, extraction of mammary tissue DNA, hydrolysis to deoxynucleosides, and analysis by LC-MS-MS showed the formation of stable cyclic deoxyguanosine and deoxyadenosine adducts as well as oxidized bases. This is the first report showing that 4-hydroxyequilenin is capable of causing DNA damage in vivo. In addition, the data showed that 4-hydroxyequilenin induced four different types of DNA damage that must be repaired by different mechanisms. This is in contrast to the endogenous estrogen 4-hydroxyestrone where only depurinating guanine adducts have been detected in vivo. These results suggest that 4-hydroxyequilenin has the potential to be a potent carcinogen through the formation of variety of DNA lesions in vivo.

Animals↗

Mammography utilization among california women age 40-49 in a managed care environment.

OBJECTIVE: To examine the utilization of screening mammography and the relationship between risk factors and mammography use in women age 40-49 in a managed care environment. DESIGN: Retrospective observational study based on a mailed survey. SETTING: A large HMO in California. PATIENTS/PARTICIPANTS: The study population included respondents age 40-49 who completed a breast health assessment questionnaire mailed to all women age 34-49 and enrolled in a California HMO in early 1997. MAIN RESULTS: About 67.6% of the 20,391 women age 40-49 had at least one mammogram during 1995 and 1996. Logistic regression revealed that women age 40-44 were less likely (odds ratio: 0.83-0.90) than women age 45-49 to obtain mammography. Family history of breast cancer (odds ratio: 1.12-1.16), breast biopsy (odds ratio: 1.14-1.18), and a mammogram in the previous three years (odds ratio: 1.15-1.18) were associated with an increased likelihood of taking a mammogram. However, monthly breast self-exams (odds ratio: 0.996-1.04), having a child at or after age 30 (odds ratio: 0.97-1.02), and having menarche at age 12 or younger (odds ratio: 0.96-1.01) had no significant effect on the screening mammography rates. CONCLUSION: A relatively higher percentage of younger HMO members receive screening mammography than that of general population. However, some higher-risk groups, especially women whose first pregnancies were late in life, do not show a higher rate of using mammography.

Adult↗

Promoter-specific binding of Rap1 revealed by genome-wide maps of protein-DNA association.

We determined the distribution of repressor-activator protein 1 (Rap1) and the accessory silencing proteins Sir2, Sir3 and Sir4 in vivo on the entire yeast genome, at a resolution of 2 kb. Rap1 is central to the cellular economy during rapid growth, targeting 294 loci, about 5% of yeast genes, and participating in the activation of 37% of all RNA polymerase II initiation events in exponentially growing cells. Although the DNA sequence recognized by Rap1 is found in both coding and intergenic sequences, the binding of Rap1 to the genome was highly specific to intergenic regions with the potential to act as promoters. This global phenomenon, which may be a general characteristic of sequence-specific transcriptional factors, indicates the existence of a genome-wide molecular mechanism for marking promoter regions.

Binding Sites↗

Distinct regulators control the expression of the mid-hindbrain organizer signal FGF8.

Local expression of FGF8 at the mid/hindbrain boundary (MHB) governs the development of multiple neurons and support cells. Here we show that the paired-domain protein Pax2 is necessary and sufficient for the induction of FGF8 in part by regulating the expression of Pax5&8. A network of transcription and secreted factors, including En1, Otx2, Gbx2, Grg4 and Wnt1&4, that is established independently of Pax2, further refines the expression domain and level of FGF8 at the MHB through opposing effects on Pax2 activity. Our results indicate that the expression of local organizing factors is controlled by combinatorial interaction between inductive and modulatory factors.

Animals↗

Influence of sibutramine on energy expenditure in African American women.

OBJECTIVE: African American women have a high prevalence of obesity, which partially may be explained by their lower rates of resting energy expenditure (REE). The aim of this study was to examine the influence of acute sibutramine administration on REE and post-exercise energy expenditure in African American women. RESEARCH METHODS AND PROCEDURES: A total of 15 premenopausal, African American women (age, 29 +/- 5 years; body fat, 38 +/- 7%) completed a randomized, double-blind cross-over design with a 30-mg ingestion of sibutramine or a placebo. Each trial was completed a month apart in the follicular phase and included a 30-minute measurement of REE 2.5 hours after sibutramine or placebo administration. This was followed by 40 minutes of cycling at approximately 70% of peak aerobic capacity and a subsequent 2-hour measurement of post-cycling energy expenditure. RESULTS: There was no difference (p > 0.05) in REE (23.70 +/- 2.81 vs. 23.69 +/- 2.95 kcal/30 min), exercise oxygen consumption (1.22 +/- 0.15 vs. 1.25 +/- 0.15 liter/min), and post-cycling energy expenditure (104.2 +/- 12.7 vs. 104.9 +/- 11.4 kcal/120 min) between the sibutramine and placebo trials, respectively. Cycling heart rate was significantly higher (p = 0.01) during the sibutramine (158 +/- 14 beats/min) vs. placebo (150 +/- 12 beats/min) trials. DISCUSSION: These data demonstrate that acute sibutramine ingestion does not increase REE or post-exercise energy expenditures but does increase exercising heart rate in overweight African American women. Sibutramine may, therefore, impact weight loss through energy intake and not energy expenditure mechanisms.

Adult↗

Improving the quality of care of patients with asthma: the example of patients with severely symptomatic disease.

The increasing economic burden of asthma care is incurred partly by patients with more severe symptoms. However, little is known about the characteristics of these severe asthma patients. This study examined sociodemographic, disease-specific characteristics and health care utilization that are related to asthma disease severity, for the purpose of identifying areas for treatment improvement. A total of 2927 asthma patients (12 years or older), who were continuously enrolled in one of three participating health plans for a 6-month study period and who responded to an asthma survey, were included in the study. Univariate and multivariate analyses were performed to examine the sociodemographic, disease-specific characteristics and health care utilization by asthma severity. About 25% of the patients reported experiencing severe asthma symptoms. They were more likely to be African-Americans, Hispanics, women, patients with less than a college education, residents in the south-west, current smokers, and those receiving care from non-specialists. Severe asthmatics reported having less of an understanding of the clinical manifestation of asthma and the means to manage asthma exacerbation. Outpatient contacts did not differ significantly between severe and other patients, although their utilization of emergency room and inpatient care was significantly greater. This study suggests that a significant proportion of asthma patients is experiencing severe symptoms and barriers other than access to care prevent appropriate control of asthma. Poor control appears to be related to smoking, deficits in knowledge about self-care, not receiving medical care from a specialist, and inadequate use of medications.

Adolescent↗