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Hong Xu

Publications and source records attributed to Hong Xu.

At least 55 records · Page 3Linked to original sources

Statistical Viewer: a tool to upload and integrate linkage and association data as plots displayed within the Ensembl genome browser.

BACKGROUND: To facilitate efficient selection and the prioritization of candidate complex disease susceptibility genes for association analysis, increasingly comprehensive annotation tools are essential to integrate, visualize and analyze vast quantities of disparate data generated by genomic screens, public human genome sequence annotation and ancillary biological databases. We have developed a plug-in package for Ensembl called "Statistical Viewer" that facilitates the analysis of genomic features and annotation in the regions of interest defined by linkage analysis. RESULTS: Statistical Viewer is an add-on package to the open-source Ensembl Genome Browser and Annotation System that displays disease study-specific linkage and/or association data as 2 dimensional plots in new panels in the context of Ensembl's Contig View and Cyto View pages. An enhanced upload server facilitates the upload of statistical data, as well as additional feature annotation to be displayed in DAS tracts, in the form of Excel Files. The Statistical View panel, drawn directly under the ideogram, illustrates lod score values for markers from a study of interest that are plotted against their position in base pairs. A module called "Get Map" easily converts the genetic locations of markers to genomic coordinates. The graph is placed under the corresponding ideogram features a synchronized vertical sliding selection box that is seamlessly integrated into Ensembl's Contig- and Cyto- View pages to choose the region to be displayed in Ensembl's "Overview" and "Detailed View" panels. To resolve Association and Fine mapping data plots, a "Detailed Statistic View" plot corresponding to the "Detailed View" may be displayed underneath. CONCLUSION: Features mapping to regions of linkage are accentuated when Statistic View is used in conjunction with the Distributed Annotation System (DAS) to display supplemental laboratory information such as differentially expressed disease genes in private data tracks. Statistic View is a novel and powerful visual feature that enhances Ensembl's utility as valuable resource for integrative genomic-based approaches to the identification of candidate disease susceptibility genes. At present there are no other tools that provide for the visualization of 2-dimensional plots of quantitative data scores against genomic coordinates in the context of a primary public genome annotation browser.

Chromosome Mapping↗

Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment.

Bone marrow transplantation offers great promise for treating a number of disease states. However, the widespread application of this approach is dependent upon the development of less toxic methods to establish chimerism and avoid graft-versus-host disease (GVHD). CD8+/TCR- facilitating cells (FCs) have been shown to enhance engraftment of hematopoietic stem cells (HSCs) in allogeneic recipients without causing GVHD. In the present studies, we have identified the main subpopulation of FCs as plasmacytoid precursor dendritic cells (p-preDCs). FCs and p-preDCs share many phenotypic, morphological, and functional features: both produce IFN-alpha and TNF-alpha, both are activated by toll-like receptor (TLR)-9 ligand (CpG ODN) stimulation, and both expand and mature after Flt3 ligand (FL) treatment. FL-mobilized FCs, most of which express a preDC phenotype, significantly enhance engraftment of HSCs and induce donor-specific tolerance to skin allografts. However, p-preDCs alone or p-preDCs from the FC population facilitate HSC engraftment less efficiently than total FCs. Moreover, FCs depleted of preDCs completely fail to facilitate HSC engraftment. These results are the first to define a direct functional role for p-preDCs in HSC engraftment, and also suggest that p-preDCs need to be in a certain state of maturation/activation to be fully functional.

Animals↗

Light activation, adaptation, and cell survival functions of the Na+/Ca2+ exchanger CalX.

In sensory neurons, Ca(2+) entry is crucial for both activation and subsequent attenuation of signaling. Influx of Ca(2+) is counterbalanced by Ca(2+) extrusion, and Na(+)/Ca(2+) exchange is the primary mode for rapid Ca(2+) removal during and after sensory stimulation. However, the consequences on sensory signaling resulting from mutations in Na(+)/Ca(2+) exchangers have not been described. Here, we report that mutations in the Drosophila Na(+)/Ca(2+) exchanger calx have a profound effect on activity-dependent survival of photoreceptor cells. Loss of CalX activity resulted in a transient response to light, a dramatic decrease in signal amplification, and unusually rapid adaptation. Conversely, overexpression of CalX had reciprocal effects and greatly suppressed the retinal degeneration caused by constitutive activity of the TRP channel. These results illustrate the critical role of Ca(2+) for proper signaling and provide genetic evidence that Ca(2+) overload is responsible for a form of retinal degeneration resulting from defects in the TRP channel.

Adaptation, Ocular↗

Expression profiling of substantia nigra in Parkinson disease, progressive supranuclear palsy, and frontotemporal dementia with parkinsonism.

BACKGROUND: Parkinson disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra. Genes contributing to rare mendelian forms of PD have been identified, but the genes involved in the more common idiopathic PD are not well understood. OBJECTIVES: To identify genes important to PD pathogenesis using microarrays and to investigate their potential to aid in diagnosing parkinsonism. DESIGN: Microarray expression analysis of postmortem substantia nigra tissue. PATIENTS: Substantia nigra samples from 14 unrelated individuals were analyzed, including 6 with PD, 2 with progressive supranuclear palsy, 1 with frontotemporal dementia with parkinsonism, and 5 control subjects. MAIN OUTCOME MEASURES: Identification of genes significantly differentially expressed (P<.05) using Affymetrix U133A microarrays. RESULTS: There were 142 genes that were significantly differentially expressed between PD cases and controls and 96 genes that were significantly differentially expressed between the combined progressive supranuclear palsy and frontotemporal dementia with parkinsonism cases and controls. The 12 genes common to all 3 disorders may be related to secondary effects. Hierarchical cluster analysis after exclusion of these 12 genes differentiated 4 of the 6 PD cases from progressive supranuclear palsy and frontotemporal dementia with parkinsonism. CONCLUSIONS: Four main molecular pathways are altered in PD substantia nigra: chaperones, ubiquitination, vesicle trafficking, and nuclear-encoded mitochondrial genes. These results correlate well with expression analyses performed in several PD animal models. Expression analyses have promising potential to aid in postmortem diagnostic evaluation of parkinsonism.

Aged↗

Genomic convergence to identify candidate genes for Parkinson disease: SAGE analysis of the substantia nigra.

Genomic convergence is a multistep approach that combines gene expression with genomic linkage to identify and prioritize susceptibility genes for complex disease. As a first step, we previously performed linkage analysis on 174 multiplex Parkinson's disease (PD) families, identifying five peaks for PD risk and two for genes affecting age at onset (AAO) in PD [Hauser et al., Hum Mol Genet 2003;12:671-677]. We report here the next step: serial analysis of gene expression [SAGE; Scott et al., JAMA 2001;286:2239-2242] to analyze substantia nigra tissue from three PD patients and two age-matched controls. We find 933 differentially expressed genes (P<0.05) between PD and controls, but of these, only 50 genes represented by unique SAGE tags map within our previously described PD linkage regions. Furthermore, genes encoded by mitochondrial DNA are expressed 1.5-fold higher in PD patients versus controls, without an increase in the corresponding nuclear-encoded mitochondrial components, suggesting an increase in mtDNA genomes in PD or a disjunction with nuclear expression. The next step in the genomic convergence process will be to screen these 50 high-quality candidate genes for association with PD risk susceptibility and genetic effects on AAO.

Aged↗

Facile synthesis of bis(hydroxamamide)-based tetradentate ligands for 99mTc-radiopharmaceutical.

A facile, two-step synthesis of the bis(hydroxamamide)-based tetradentate ligands for 99mTc-radiopharmaceuticals is described. Firstly, the hydroxamamide was converted to hydroximic acid chloride by reaction with sodium nitrite in hydrochloric acid at 0 degrees C. Secondly, treating the halide with the ethylenediamine or 1,3-propylenediamine in absolute ethanol formed the desired products, N,N'-ethylene bis(1-(4-nitroimidazole-1-yl)-propan-hydroxyiminoamide) (I) and N,N'-propylene bis(1-(4-nitroimidazole-1-yl)-propanhydroxyiminoamide) (II). The corresponding 99mTc complexes showed high yields and were found by paper electrophoresis to be electrically neutral under physiological conditions. The partition coefficients indicated a distinct difference between the two complexes.

Electrophoresis, Paper↗

Cytokine-induced myeloid differentiation is dependent on activation of the MEK/ERK pathway.

The intracellular signaling pathways that mediate cytokine-induced granulocytic and monocytic differentiation are incompletely understood. In this study, we examined the importance of the MEK/ERK signal transduction pathway in granulocyte-colony stimulating factor (G-CSF)-induced granulocytic differentiation of murine 32 Dc l3 cells, and in interleukin-6 (IL-6)-induced monocytic differentiation of murine M1 cells. Induction of granulocytic differentiation with G-CSF, or monocytic differentiation with IL-6, led to rapid and sustained activation of the MEK-1/-2 and ERK-1/-2 enzymes. Inhibition of the MEK/ERK pathway by pretreatment with the MEK inhibitor U 0126 dramatically attenuated G-CSF-induced granulocytic differentiation and IL-6-induced monocytic differentiation. Inhibition of MEK/ERK signaling also significantly reduced cytokine-induced DNA binding activities of STAT 3 and PU.1, transcription factors that have been implicated in myeloid differentiation. Additionally, interleukin-3, which inhibits G-CSF-induced differentiation of 32 Dc l3 cells, also inhibited the ability of G-CSF to stimulate prolonged MEK/ERK activation. Thus, the opposing actions of different hematopoietic cytokines on myeloid progenitors may be mediated at the level of MEK/ERK activation. Taken together, these studies demonstrate an important requirement for MEK/ERK activation during cytokine-induced granulocytic and monocytic differentiation.

Animals↗

Resonance Rayleigh scattering study of interaction of heparin with some cationic surfactants and their analytical application.

Binding of heparin with a cationic surfactant such as cetyldimethyl benzylammonium chloride (CDBAC), tetradecyldimethyl benzylammonium chloride (Zeph), cetylpyridinium bromide (CPB), tetradecane pyridinium bromide (TPB) and cetyltrimethylammonium bromide (CTAB) in a near-neutral medium can result in a significant enhancement of resonance Rayleigh scattering (RRS) intensities. The results showed that the reaction conditions and RRS spectral characteristics of these reactions are similar, but their sensitivities are obviously different. Among them, the sensitivity of CDBAC with an aryl and large molecular weight is the highest, while that of CTAB without aryl and with small molecular weight is the lowest. The detection limit for heparin of the former is 11 ng ml(-1) while that of the latter is 33 ng ml(-1). The method has better selectivity and was applied to the determination of trace amounts of heparin in sodium heparin injection samples with satisfactory results. Furthermore, it is discovered that the RRS intensity is related to the structure and molecular weight of the cationic surfactant.

Heparin↗

Association between VDR ApaI polymorphism and hip bone mineral density can be modified by body mass index: a study on postmenopausal Chinese women.

Osteoporosis is a major public health problem for old people. Genetic factors are considered to be major contributors to the pathogenesis of postmenopausal osteoporosis. The vitamin D receptor (VDR) gene is a prominent candidate gene for the regulation of postmenopausal bone mass; however, despite extensive studies, controversy remains regarding its association with postmenopausal body mineral density (BMD) variation. In this study, a total of 260 healthy postmenopausal Chinese women were genotyped at the VDR ApaI locus using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Raw hip BMD was significantly associated with VDR ApaI polymorphism with and without adjusting for age (P=0.015 and 0.040, respectively). This genetic effect can explain 3.32% of hip BMD variation. However, the significant association vanished after correcting for both age and body mass index (BMI) (P=0.169). In addition, we observed a significant association between VDR ApaI polymorphism with unadjusted BMI (P=0.042) or BMI adjusted for age (P=0.049). The raw hip BMD was also found to be significantly correlated with BMI (r=0.517, P=0.0001), with BMI explaining 26.35% of the variation of hip BMD. All of these facts prompt us to conclude that the significant association between the VDR ApaI genotype and hip BMD may be modified by BMI in postmenopausal Chinese women. Our findings may partially explain the earlier inconsistent association results concerning the VDR gene and BMD, and highlight the importance of incorporating covariates such as BMI into osteoporosis association studies.

Aged↗

Peritoneal fluid concentrations of interleukin-17 correlate with the severity of endometriosis and infertility of this disorder.

This prospective study aimed to determine whether patients with endometriosis are having different level of interlukin-17 (IL-17) in peritoneal fluid when compared with patients without endometriosis. The patients with minimal/mild endometriosis had a significantly higher level of IL-17 in peritoneal fluid compared with those with moderate/severe endometriosis or without endometriosis. The concentration of IL-17 in peritoneal fluid was significantly higher when endometriosis and infertility coexist. However, the concentration of IL-17 in peritoneal fluid did not correlate with the phase of the menstrual cycle in the patients with or without endometriosis. Our study suggested that IL-17 might play an important role in the pathogenesis of early endometriosis and endometriosis-associated infertility.

Abdominal Pain↗

Interaction effects between estrogen receptor alpha and vitamin D receptor genes on age at menarche in Chinese women.

AIM: To evaluate whether estrogen receptor alpha (ER-alpha) and vitamin D receptor (VDR) genes are associated with the age at menarche in Chinese women. METHODS: A total of 390 pre-menopausal Chinese women were genotyped at the ER-alpha PvuII, XbaI, and VDR ApaI loci using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). RESULTS: Neither the ER-alpha gene nor the VDR gene individually had significant effects on the age at menarche in our subjects (P>0.10). However, evidence of interaction effects between the two genes were observed: with the aa genotype at the VDR ApaI locus, subjects with haplotype PX at the ER-alpha gene had, on average, 6 months later onset of menarche than the non-carriers (P=0.01). CONCLUSION: We found that neither the ER-alpha gene or the VDR gene had a significant association with the age at menarche individually. However, potential interaction effects between the two genes were observed in Chinese women.

Adult↗

Measuring blood flow velocities based on three image processing techniques.

The classification of microcirculation can be based on the size of the capillary and the velocity of the blood flow. For each type of microcirculation, the ad hoc method is required to measure the blood flow velocity. In this paper, the correlation method is used to measure blood flow velocity in the small-size capillary. The large-size capillaries are classified into three types based on the blood velocities, say low-speed, high-speed, and unstable one. The template-matching algorithm, the Fast Fourier Transform algorithm and a high-speed video camera measurement are used to measure the blood velocities corresponding to those three types of large-size capillary. It was shown by several experiments that fairly good results for different types of capillary may be obtained by using the proposed three image processing algorithms.

Algorithms↗

The use of preventive strategies for bone loss.

Osteoporosis is a worldwide problem that is increasing significantly as the global population both increases and ages. While osteoporosis has been extensively studied in recent years, the utilization of traditional Chinese medicine (TCM) for the diagnosis, prevention and treatment of this condition has seldom been examined. This paper examines the theories and the literature that relate to diagnosis, prevention and treatment of bone loss at the time of menopause according to the principles of TCM. It also considers practical developments in these areas as illustrated by the authors' research findings in recent studies. TCM diagnosis attributes a number of different underlying patterns to menopausal bone loss. A very common pattern in this situation is a Kidney qi and yin deficiency pattern. TCM analysis can be used as an early determinant of those persons who are potentially at risk of bone loss. Acupuncture, herbal medicine and Tai Ji exercise can then be applied to prevent and treat osteoporosis. These treatments can be effective, if they are applied correctly. The therapies may also be used in the treatment and prevention of osteoporosis, as well as the general maintenance of women's health during menopause.

Acupuncture Therapy↗

Strain and age-related changes in the localization of intestinal CD161+ natural killer cells and CD8+ intraepithelial lymphocytes along the longitudinal crypt axis in inbred rats.

Using a cell position approach, this study indicates that the frequency of CD161(+) natural killer (NK) cells in the epithelia of DA rats was greater than that of WKAH and F344 rats. We further divided the epithelia into proliferating and differentiated regions according to the localization of BrdU-incorporated cells. Comparison between the different regions indicates that a majority of CD161(+) NK cells were located in the proliferating region. With age, a decline in the number of CD161(+) NK cells and CD8(+) intraepithelial lymphocytes (IELs) was observed in the distal colon, especially in the proliferating region of all three strains. Taken together with our previous report that DA rats have far stronger resistance in the colon to preneoplastic lesion than do other strains, these results indicate that CD161(+) NK cells play an important role in immune-surveillance at the bottom of the crypt.

Age Factors↗

[Spectrum of gene expression of a multi-drug resistant leukemia cell line with high tumorigenicity in nude mice].

OBJECTIVE: To investigate the mechanism of multi-drug resistance of K562-n/VCR cell line with both bcr-abl and mdr-1 expressions by clustering analysis of differential gene expression profiles. METHODS: By DNA microarray technique, genes differentially expressed by K562-n/VCR and K562-n cell lines were identified and analyzed. RESULTS: DNA microarray analysis of K562-n/VCR and K562-n cells was repeated three times and revealed 58 genes significantly differentially expressed among 12,800 genes arrayed. All but one was up-regulated in K562-n/VCR cells. The only gene down-regulated was a-myb. The up-regulated genes were MDR-associated genes, oncogenes, cytoskeleton, protein kinases and phosphatases, apoptotic and antiapoptotic factors, metabolism, transcriptional regulators associated with stress response, cell cycle checkpoint control, and genes for signal transduction proteins. CONCLUSION: These results indicate that, besides MDR-associated genes, other known and unknown genes may also be involved in the mechanism of multi-drug resistance.

Animals↗

[Risk factors and prognosis of contrast-induced nephropathy with renal dysfunction].

OBJECTIVE: To investigate the risk factors, clinical characteristics, and prognosis of contrast-induced nephropathy (CIN) in patients with renal dysfunction. METHODS: We retrospectively analyzed 44 patients with renal dysfunction who received coronary angiography in our hospital. CIN was found in 23 patients, after angiography. We compared the clinical characteristics, medication during angiography day, volume of contrast-medium, as well as renal function changes before and after angiography in patients with (23 cases) and without (21 cases) CIN. The CIN patients were further divided into two groups according to their serum creatinine (Scr) levels: renal function recovery group (12 cases) and renal function non-recovery group (11 cases), and difference between these two groups was analyzed. RESULTS: CIN incidence was 52.3% (23/44) in all 44 patients with renal dysfunction. CIN incidence was 42% (8/19) in patients whose Scr was between 132.6 - 168 micromol/L, was 60% (15/25) in those whose Scr was more than 176.8 micromol/L. In all 23 CIN patients, the average volume of contrast-medium was (144.79 +/- 71.8) ml, while 43.5% of the CIN patients whose dosage was over the maximum threshold of contrast-medium; the average risk factors were 5.14 +/- 1.3. Compared with the group without CIN, the difference was statistically significant (P < 0.05). Multiple stepwise regression analysis showed the volume of radio-contrast-medium was correlated with CIN in patients with renal dysfunction (F=10.4, P=0.003). Patients in the CIN group showed a significant rise of Scr level 24, 48, and 72 hours after angiography. However, the urine volume had no change before and after angiography. Renal function was improved in 12 of 23 patients (52.2%), and deteriorated in 11 patients (47.8%). Four patients (17.4%) received dialysis. Compared with the non-reavery group, Scr levels [(194.5 +/- 70.7) micromol/L, (443.8 +/- 282.9) micromol/L, respectively] of pre-angiography in renal function recovery group and the patients whose dosage was over maximum threshold of contrast-medium (2/12, 8/11) had significant difference (P < 0.05). CONCLUSIONS: Higher volume of contrast-medium is a risk factor of CIN in patients with renal dysfunction. Pre-angiography Scr level and the contrast-medium volume are correlated with the prognosis of CIN in such patients.

Aged↗

[Determination of interleukin-17 concentrations in peritoneal fluid of women with endometriosis].

OBJECTIVE: To investigate the role of interleukin-17 (IL-17) in the pathogenesis of endometriosis. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of IL-17 in peritoneal fluid of 36 patients with different stage endometriosis and 26 patients without endometriosis. RESULTS: The concentrations of IL-17 in peritoneal fluid of the patients with and without endometriosis were (5.7 +/- 1.9) ng/L and (5.3 +/- 1.4) ng/L, respectively, without significant difference between the two groups (P > 0.05). According to staging criteria of r-AFS, the concentrations of peritoneal IL-17 in the patients with stage I-II endometriosis (6.4 +/- 1.7) ng/L were significantly higher than those in the patients with stage III-IV endometriosis (5.1 +/- 1.8) ng/L and in the patients without endometriosis (P < 0.05). There was no difference with regard to peritoneal IL-17 concentrations between proliferative and secretory phases in the patients with or without endometriosis (P > 0.05). The levels of peritoneal IL-17 were significantly higher in the endometriosis patients with infertility (6.4 +/- 1.8) ng/L than in the endometriosis patients without infertility (5.1 +/- 1.8) ng/L (P < 0.05). CONCLUSION: IL-17 may play an important role in the pathogenesis of early endometriosis and pathophysiology of endometriosis-associated infertility.

Adult↗