Biomedical subjects

Xia Li

Publications and source records attributed to Xia Li.

At least 127 records · Page 7Linked to original sources

PubMed2004

Plasticity in eucaryotic 20S proteasome ring assembly revealed by a subunit deletion in yeast.

The 20S proteasome is made up of four stacked heptameric rings, which in eucaryotes assemble from 14 different but related subunits. The rules governing subunit assembly and placement are not understood. We show that a different kind of proteasome forms in yeast when the Pre9/alpha3 subunit is deleted. Purified pre9Delta proteasomes show a two-fold enrichment for the Pre6/alpha4 subunit, consistent with the presence of an extra copy of Pre6 in each outer ring. Based on disulfide engineering and structure-guided suppressor analyses, Pre6 takes the position normally occupied by Pre9, a substitution that depends on a network of intersubunit salt bridges. When Arabidopsis PAD1/alpha4 is expressed in yeast, it complements not only pre6Delta but also pre6Delta pre9Delta mutants; therefore, the plant alpha4 subunit also can occupy multiple positions in a functional yeast proteasome. Importantly, biogenesis of proteasomes is delayed at an early stage in pre9Delta cells, suggesting an advantage for Pre9 over Pre6 incorporation at the alpha3 position that facilitates correct assembly.

Arabidopsis↗

PubMed2004

Centrally administered oxytocin elicits exaggerated grooming in oxytocin null mice.

Experiments were conducted to determine if the chronic absence of the neurotransmitter oxytocin (OT) in null mice resulted in alterations in the responsiveness and abundance of central OT receptors. Self-grooming elicited by intracerebroventricularly administered OT was studied as an indicator of the activation of central OT receptors and autoradiography was used to map the distribution and density of OT receptors in OT null and wild type mice. The intracerebroventricular administration of OT, but not vehicle, artificial cerebrospinal fluid (aCSF), produced a robust increase in grooming behavior in both OT null and wild type animals, P<.001. However, OT-induced grooming was significantly greater in OT null than wild type mice, P<.005. The enhanced grooming was selective to OT as indicated by the finding that grooming to intracerebroventricular arginine vasopressin (AVP) was of the same magnitude in both OT null and wild type mice. OT-induced grooming appears to be mediated through the activation of OT receptors because pretreatment of animals with an OT antagonist, Atosiban, abolished OT-induced grooming, but not AVP-induced grooming. OT receptor distribution and binding in brains of OT null and wild type mice were examined by autoradiography and were not significantly different. The results indicate that the chronic absence of OT in null mice leads to an increase in OT receptor responsiveness that contributes to the augmented grooming activity elicited by centrally administered OT.

Animals↗

PubMed2004

Learnability-based further prediction of gene functions in Gene Ontology.

Currently the functional annotations of many genes are not specific enough, limiting their further application in biology and medicine. It is necessary to push the gene functional annotations deeper in Gene Ontology (GO), or to predict further annotated genes with more specific GO terms. A framework of learnability-based further prediction of gene functions in GO is proposed in this paper. Local classifiers are constructed in local classification spaces rooted at qualified parent nodes in GO, and their classification performances are evaluated with the averaged Tanimoto index (ATI). Classification spaces with higher ATIs are selected out, and genes annotated only to the parent classes are predicted to child classes. Through learnability-based further predicting, the functional annotations of annotated genes are made more specific. Experiments on the fibroblast serum response dataset reported further functional predictions for several human genes and also gave interesting clues to the varied learnability between classes of different GO ontologies, different levels, and different numbers of child classes.

Computational Biology↗

PubMed2004

Nitrite generates an oxidant stress and increases nitric oxide in EA.hy926 endothelial cells.

Nitrite is a breakdown product of nitric oxide that in turn is oxidized to nitrate in cells. In this work, we investigated whether reactive oxidant species mightbe generated during nitrite metabolism in cultured EA.hy926 endothelial cells. Nitrite was taken up by the cells in a time- and concentration-dependent manner and oxidized to nitrate, which accumulated in cells to concentrations almost 10-fold those of nitrite. Conversion of low millimolar concentrations of nitrite to nitrate was associated with increased oxidant stress in the cells. This manifested as increased oxidation of dihydrofluorescein in tandem with depletion of both GSH and ascorbate. Further, loading cells with ascorbate or treatment with desferrioxamine prevented nitrite-induced dihydrofluorescein oxidation. Nitrite within cells also increased the fluorescence of 4-amino-5-methylamino-2',7'-difluorofluorescein and inhibited the activity of cellular glyceraldehyde 3-phosphate dehydrogenase, which are markers of intracellular nitrosation reactions. Intracellular ascorbate partially prevented both of these effects of nitrite. Although ascorbate can reduce nitrite to nitric oxide at low pH, in endothelial cells loaded with ascorbate, its predominant effect at high nitrite concentrations is to prevent potentially damaging nitrosation reactions.

Cell Line↗

PubMed2004

The influence of dexamethasone on the proliferation and apoptosis of pulmonary inflammatory cells in bleomycin-induced pulmonary fibrosis in rats.

OBJECTIVE: The aim of this study was to investigate the inhibitory effect of dexamethasone on the state of proliferation/apoptosis of the pulmonary inflammatory cells in a rat pulmonary fibrosis model induced by bleomycin. METHODOLOGY: Seventy-five pathogen-free Sprague-Dawley (SD) rats were randomly divided into three groups: control, bleomycin (BLM) and dexamethasone (DXM) groups with 25 rats in each group. Each group was then divided into five subgroups based on time of study (1-, 3-, 7-, 14- and 28-days). BAL fluid was obtained, the cells were counted and a differential was performed. A lower DNA content in apoptotic cells was detected and quantitated by flow cytometry. Haematoxylin and eosin staining was performed to observe the extent of alveolitis and fibrosis of lung tissue; the morphological changes in apoptotic cells were discerned by transmission electron-microscopy and a semi-quantitative assessment of apoptotic cells in lung tissue was performed using in situ TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling). RESULTS: The total number of inflammatory cells and the percentage of neutrophils in BAL fluid in almost every subgroup of the DXM group were significantly lower than those in corresponding subgroups of the BLM group (P < 0.01). The percentages of apoptotic cells in BAL fluid in the 14-day and 28-day subgroups of the DXM group were higher than those in corresponding subgroups of the BLM group (P < 0.05). The peak of alveolitis in the DXM group shifted backward and the extent of fibrosis was less than that in the BLM group. The apoptosis index (AI) of inflammatory cells in each of the DXM subgroups was higher than that in corresponding BLM subgroups except for day 14. CONCLUSION: Dexamethasone can induce apoptosis of pulmonary inflammatory cells and reduce the extent of alveolitis and fibrosis in bleomycin-induced pulmonary fibrosis of rats.

Animals↗

PubMed2004

Expression profiling of murine acute promyelocytic leukemia cells reveals multiple model-dependent progression signatures.

Leukemia results from the expansion of self-renewing hematopoietic cells that are thought to contain mutations that contribute to disease initiation and progression. Studies of the gene expression profiles of human acute myeloid leukemia samples has allowed their classification based on the presence of translocations and French-American-British subtypes, but it is not yet clear whether their molecular signatures reflect the initiating mutations or mutations acquired during progression. To begin to address this question, we examined the expression profiles of normal murine promyelocyte-enriched samples, nontransformed murine promyelocytes expressing human promyelocytic leukemia-retinoic acid receptor alpha (PML-RARalpha) fusion gene, and primary acute promyelocytic leukemia cells. The expression profile of nontransformed cells expressing PML-RARalpha was remarkably similar to that of wild-type promyelocytes. In contrast, the expression profiles of fully transformed cells from three acute promyelocytic leukemia model systems were all different, suggesting that the expression signature of acute promyelocytic leukemia cells reflects the genetic changes that contributed to progression. To further evaluate these progression events, we compared two high-penetrance acute promyelocytic leukemia models that both commonly acquire an interstitial deletion of chromosome 2 during progression. The two models exhibited distinct gene expression profiles, suggesting that the dominant molecular signatures of murine acute promyelocytic leukemia can be influenced by several independent progression events.

Animals↗

PubMed2004

An ensemble method for gene discovery based on DNA microarray data.

The advent of DNA microarray technology has offered the promise of casting new insights onto deciphering secrets of life by monitoring activities of thousands of genes simultaneously. Current analyses of microarray data focus on precise classification of biological types, for example, tumor versus normal tissues. A further scientific challenging task is to extract disease-relevant genes from the bewildering amounts of raw data, which is one of the most critical themes in the post-genomic era, but it is generally ignored due to lack of an efficient approach. In this paper, we present a novel ensemble method for gene extraction that can be tailored to fulfill multiple biological tasks including (i) precise classification of biological types; (ii) disease gene mining; and (iii) target-driven gene networking. We also give a numerical application for (i) and (ii) using a public microarrary data set and set aside a separate paper to address (iii).

Algorithms↗

PubMed2004

Effect of estrogen deprivation on follicle/oocyte maturation and embryo development in mice.

BACKGROUND: It is believed that estrogen plays pivotal roles in the regulation of follicle/oocyte maturation and oocyte fertilizability. It is also involved in the functional preparation of the fallopian tubes for subsequent gamete interaction, in early embryonic development occurring in the tubal microenvironment, and in the preparation of the uterus for implantation. This study was designed to determine whether estrogen is required for follicular and embryonic development. METHODS: The biosynthesis of estrogen was blocked by a daily injection of the aromatase inhibitor, Arimidex, at a dose of 100 micro g/d, using 3 - 4 week old C57B6 F1 female mice. Injections were continued for 3 days in experiment 1 (n = 10) and for 5 days in experiment 2 (n = 23). Mice in the control group (n = 27) were given the same amount of saline. Exogenous gonadotrophin [7.5 IU pregnant mare serum gonadotrophin (PMSG)] was administered to induce follicular growth and development on the second day. In experiment 1, we tested estrogen and progesterone levels and examined ovary morphology two days later. In experiment 2, 47 hours after PMSG injection, 5 IU human chorionic gonadotropin (hCG) was given and two female mice were then caged with a male mouse overnight. Two days later, we measured estrogen and progesterone levels. We then removed the embryos, cultured them, and examined embryonic development every 24 hours for 3 days. RESULTS: Before hCG injection, estrogen levels in mice from the Arimidex group were suppressed by 94%, and progesterone levels were suppressed by 75%. There was no difference between the two groups in mean number of total follicles found per animal (30.4 follicles/animal in the control group and 27 follicles/animal in the Arimidex group). Two days after hCG injection, estrogen levels in the Arimidex group were significantly lower than that in the control group (P < 0.01), while progesterone levels were not significantly lower (P > 0.05). The rate of development of embryos, morulae, blastocysts, and hatching blastocysts was not significantly different between the two groups (P = 0.20, 0.10, 0.44, and 0.38, respectively). CONCLUSIONS: In the present study, by depriving mice of normal estrogen support, we have been able to rule out the absolute need for rising levels of estrogen for the completion of the follicular maturation process and the development of embryos in vitro.

Anastrozole↗

PubMed2004

[Clinicopathologic features of usual interstitial pneumonia and its differential diagnosis from idiopathic nonspecific interstitial pneumonia].

OBJECTIVE: To investigate the clinicopathologic features of usual interstitial pneumonia (UIP) and its differential diagnosis from idiopathic nonspecific interstitial pneumonia (INSIP). METHODS: The clinical and pathological features of 15 UIP and 11 cases of INSIP, having received open or video-assisted thoracoscopic lung biopsies and having follow-up information were reviewed. RESULTS: UIP occurred more often in males over 50 years of age. Clinical findings included progressive shortness of breath, cough, sputum and crackles over both lung fields. High resolution computerized tomography (HRCT) showed patchy attenuation, especially over both lower lobes. Honeycombing was found in 8 cases. Histologically, UIP was characterized by scattered fibrotic foci, fibrosis (often associated with honeycombing) and pulmonary architectural destruction. It had a heterogeneous appearance, with alternating areas of normal lung, interstitial inflammation, fibrosis and honeycomb changes. The frequencies of fibroblastic foci, muscle sclerosis, honeycomb changes, diffuse fibrosis and pulmonary architectural destruction in UIP and INSIP were 100% and 27.3% (P<0.001), 80.0% and 36.4% (P<0.05), 86.7% and 27.3% (P<0.001), 100% and 54.5% (P<0.01) and 100% and 45.5% (P<0.05), respectively. The response rate to glucocorticoid was 26.7% and 72.7% (P<0.05) in UIP and INSIP respectively. CONCLUSIONS: The distinction between UIP and INSIP is difficult if based on clinical examination alone. HRCT is helpful for differential diagnosis in some difficult cases. Definite diagnosis depends mainly on open lung biopsies. Key histologic features of UIP include heterogeneous appearance with interstitial inflammation, fibroblastic foci, scar formation and honeycomb changes.

Adult↗

PubMed2004

[Analysis of the mRNA expression similarity of genes in the same gene expression regulatory pathway].

In this work we analysed the relationship of gene expression from the point of view of gene expression regulatory pathway. Using seven sets of Saccharomyces cerevisiae gene chip expression profile data, and information from two pathway database (KEGG and CYGD), we analysed the mRNA expression similarity of genes in the same gene expression regulatory pathway by Genehub software, that involved totally 16 pathways with more than 495 genes. From the calculation of two different similarity measures-Pearson correlation coefficient and Spearman correlation coefficient, we found that about 94 percent of gene expression regulatory pathways are correlatively expressed in more than 4(including 4) sets of expression profile data, and it presents additional evidence for the correlation between gene function and its expression in the view of gene expression regulatory pathways.

Algorithms↗

PubMed2004

[Theoretical study of contactless conductivity detector for electrophoresis chip].

Currently most electrophoresis chips use optical detection methods, which brings some difficulties in micromation and integration of electrophoresis chips. In order to solve this problem, a new high-frequency contactless conductivity detector for electrophoresis chip is designed. At the same time, theoretical study and analysis of this new detector are carried out, based on the construction of an equivalent circuit mode of high-frequency conductivity detector and the design of the structure. With the consideration of many factors including band broadening, the dimensions of the structure were designed and optimized. In summary, the detector has many advantages such as wide application range, simple structure and easy integration.

Conductometry↗

PubMed2004

[Synthesis and characterization of mixed ligand complexes rare earth with 2,3-dimethoxylbenzoic acid and 1,10-phenanthroline].

The quaternary mixed anion of rare earth with 2,3-dimethoxylbenzoic acid and 1,10-phenanthroline has been synthesized from the water-ethanol solution. Elemental analysis shows that the complexes general formula is RE(2,3-DMOBA)2NO3Phen (RE = La, Nd, Eu, Dy). The complexes are characterized by IR, UV, TG-DTA analysis. Nu2 + nu5, nu2 + nu6 of NO3- are observed in 1772 and 1737 cm(-1) in IR spectra of complexes, it shows that NO3- group is in a bridging-chelating mode in which two O atoms chelate to RE3+ ions. UV spectra of ligand and complexes are different, it shows that ligand 2,3-dimethoxylbenzoate and 1,10-phenanthroline coordinate to RE3+ ions. Visible absorption spectra of Nd(2,3-DMOBA)2NO3Phen show that hypersensitive transition of neodymium.

Benzoic Acid↗

PubMed2004

[Spectra of complexes Eu(III)-furoic acid].

Three europium complexes [Eu(FA)3 x 2H2O] x NO3 (4,4'-Hbpy), [Eu(FA)3 x phen]H2O and Eu(FA)2 x NO3 x phen have been synthesized (FA = alpha-furoate, phen = 1,10-phenanthroline, 4,4'-Hbpy = 4,4'-bipyridine). The compositions and structures of these complexes were determined with elemental analysis, IR, UV and luminescence spectra. The luminescence spectra of the Eu complexes in solution show that the intensity of the ternary complex [Eu(FA)3 x phen]H2O is higher than that of the quaternary complex Eu(FA)2 x NO3 x phen, and much higher than that of [Eu(FA)3 x 2H2O] x NO3 (4,4'-Hbpy). The measured lifetime is 0.46 ms for complex [Eu(FA)3 x 2H2O] x NO3 (4,4'-Hbpy). These measured lifetimes are 1.13 and 1.20 ms for complexes [Eu(FA)3 x phen]H2O and Eu(FA)2 x NO3 x phen, respectively. This phenomenon correlates with antenna effect of phen and luminescence quenching of coordinated water.

Electrochemistry↗

PubMed2004

[A study on europium sensitized chemiluminescence of pipemidic acid].

A flow injection chemiluminescence method for the determination of Pipemidic acid (PPA) was developed. It is based on luminescence produced with KMnO4-Na2S2O4 CL system sensitized by Eu3+-PPA. The familar excipients such as starch and dextrine do not cause interference. The several kinds of affect on chemiluminescence were studied. The linear range and detection limit for PPA are 7.00 x 10(-9)-9.00 x 10(-7) mol x L(-1) and 4.09 x 10(-9) mol x L(-1), respectively. This method have successfully been applied to the determination of PPA in tablet and urine. And the mechanism of chemiluminescence is proposed.

Cerium↗

PubMed2004

[Improved radioligand assay of insulin autoantibody].

OBJECTIVE: To establish an improved radioligand assay of insulin autoantibody (IAA) and to investigate the diagnostic role of IAA in type 1 diabetes (T1DM). METHODS: 125I-insulin antigens were mixed with sera samples in the Eppendorf tubes. The immunocomplexes were precipitated with protein A-agarose, then washed with TBST buffer and counted the cpm value using liquid scintillation counter. The assay results were expressed by IAA index and compared with those of an international standardized laboratory and a domestic anti-insulin antibody kit. Sera of 32 recent-onset type 1 diabetic patients and 120 healthy controls were screened for IAA and the consistency, sensitivity, specificity and the diagnostic value of IAA were evaluated. RESULTS: (1) The intra-assay coefficient of variation (CV) was 5.8% - 8.3%, and the inter-assay CV 7.0% - 11.0%. The IAA indices of 41 samples tested in our laboratory and in an international standardized laboratory were strongly positively related (r = 0. 783, P < 0. 01) (100.0% concordance). Arrayed according to their antibody titers, the IAA indices of 82 samples measured in our laboratory and in a domestic anti-insulin antibody kit were also strongly positively related (r = 0.982, P < 0.0001) (89.0% concordance, Kappa value 0.813), but 9 samples were positive with low titer (index 0.05 - 1.00) by the radioligand assay or negative by the kit. 2) The IAA index cut-off point was determined according to the upper limit of 99.5% percentile of 120 healthy controls. The index of 0.051 or higher was defined as positive. The IAA positivity prevalence was 18.8% (6/32) in type I diabetes and 0.8% (1/120) in the healthy controls (P < 0.001). The positivity frequency of IAA was 28.6% (4/14) in patients younger than 15 years of age and the duration less than half a year, while 11.1% (2/ 18) in those older than 15. CONCLUSION: The improved radioligand assay for IAA has a high sensitivity and specificity and can be used in clinical practice, especially for the low-titer positive subjects.

Adolescent↗

PubMed2004

[Replacement of insulin by fasting C-peptide in modified homeostasis model assessment to evaluate insulin resistance and islet beta cell function].

OBJECTIVE: To investigate the possibility of using C-peptide to replace insulin in homeostasis model assessment (Homa) to evaluate insulin resistance and islet beta cell function. METHODS: Oral glucose tolerance test (OGTT) was performed in 21 normal subjects, whose venous blood was drawn before taking glucose and 30, 60, 120 minutes after taking glucose. Insulin and C-peptide were determined with radioimmune assay. Homa indices of insulin resistance and islet beta cell function were calculated. Multiple stepwise linear regression model of insulin resistance was measured using C-peptide x blood glucose as independent variables and Homa-IR was used as the dependent variable, while the model of islet beta cell function was determined using C-peptide/(fasting blood glucose - 3.5) as the independent variable and Homaislet as the dependent variable. RESULTS: The modified Homa formula were: Homa-IR (CP) = 1.5 + fasting blood glucose x fasting C-peptide/2800 (F = 5. 511, P = 0.029), Homa-islet (CP-Normal) = 0.27 x fasting C-peptide /(fasting blood glucose - 3.5) + 50, and Homa-islet (CP-DM) = 0.27 x fasting C-Peptide/(fasting blood glucose - 3.5) (F = 212.961, P = 0.000), respectively. The modified Homa-IR (CP) and Homa-IR, Homa-islet (CP) and Homa-islet were highly correlated (r =0.689 and r = 0.788; all P = 0.000). Using Homa and modified Homa formula to evaluate the insulin resistance and islet beta cell function both in the normal and diabetic subjects was similar. CONCLUSION: Fasting C-peptide can substitute insulin in Homa model to assess insulin resistance and islet beta cell function. The modified homeostasis model assessment may be applied in the diabetics using exogenous insulin.

Adult↗

PubMed2004

[Clinical characteristics and classification of 2128 outpatients with diabetes].

OBJECTIVE: To determine the clinical characteristics of diabetic outpatients and their classification,and to provide some suggestions for diagnostics, education and follow-up of outpatients. METHODS: We analyzed the data of 2 128 outpatients recorded in the past year, and studied the clinical characteristics, distribution of types and relation between glutamate decarboxylase antibody (GADA) and age, sex and duration. RESULTS: Of all the patients, 918 (43.1%) were new-onset, and 1883 (88.6%) aged 40 or older. Altogether 782(36.7%) of the patients were done with GADA examination and 4.2% of them were GADA positive. Twelve patients were type 1 diabetes and 764 were type 2 diabetes, respectively with 33.3% and 3.8% GADA positive. The prevalence of GADA positive was 5.1% for men and 3.2% for women (P > 0.05). The frequencies of GADA positive in patients with different duration (1 year, 5 years, 10 years and more) were 4.4%, 4.8%, 1.7% and 4.9% (P >0.05) respectively. CONCLUSION: The new-onset population of the studied patients is dominated by 40-year olds or older. Type 2 diabetes is the main type in the diabetes spectrum. The frequency of GADA positive is irrelevant to sex and duration.

Adolescent↗

PubMed2003

Genetic linkage analysis of longitudinal hypertension phenotypes using three summary measures.

BACKGROUND: Longitudinal data often have multiple (repeated) measures recorded along a time trajectory. For example, the two cohorts from the Framingham Heart Study (GAW13 Problem 1) contain 21 and 5 repeated measures for hypertension phenotypes as well as epidemiological risk factors, respectively. Direct modelling of a large number of serially and biologically correlated traits in the context of linkage analysis can be prohibitively complex. Alternatively, we may consider using univariate transformation for linkage analysis of longitudinal repeated measures. RESULTS: We evaluated the utility of three conventional summary measures (mean, slope, and principal components) for genetic linkage analysis of longitudinal phenotypes by analyzing the chromosome 10 data of the Framingham Heart Study. Except for the temporal slope, all of the summary methods and the multivariate analysis identified the previously reported region, marker GATA64A09, for systolic blood pressure or high blood pressure. Further analysis revealed that this region may harbor gene(s) affecting human blood pressure at multiple stages of life. CONCLUSION: We conclude that mean and principal components are feasible alternatives for genetic linkage analysis of longitudinal phenotypes, but the slope might have a separate genetic basis from that of the original longitudinal phenotypes.

Adult Children↗