Biomedical subjects

X Wang

Publications and source records attributed to X Wang.

At least 199 records · Page 11Linked to original sources

PubMed2003

A comparative magnetoencephalographic study of cortical activations evoked by noxious and innocuous somatosensory stimulations.

We recorded somatosensory-evoked magnetic fields and potentials produced by painful intra-epidermal stimulation (ES) and non-painful transcutaneous electrical stimulation (TS) applied to the left hand in 12 healthy volunteers to compare cortical responses to noxious and innocuous somatosensory stimulations. Our results revealed that cortical processing following noxious and innocuous stimulations was strikingly similar except that the former was delayed approximately 60 ms relative to the latter, which was well explained by a difference in peripheral conduction velocity mediating noxious (Adelta fiber) and innocuous (Abeta fiber) inputs. The first cortical activity evoked by both ES and TS was in the primary somatosensory cortex (SI) in the hemisphere contralateral to the stimulated side. The following activities were in the bilateral secondary somatosensory cortex (SII), insular cortex, cingulate cortex, anterior medial temporal area and ipsilateral SI. The source locations did not differ between the two stimulus modalities except that the dipole for insular activity following ES was located more anterior to that following TS. Both ES and TS evoked vertex potentials consisting of a negativity followed by a positivity at a latency of 202 and 304 ms, and 134 and 243 ms, respectively. The time course of the vertex potential corresponded to that of the activity of the medial temporal area. Our results suggested that cortical processing was similar between noxious and innocuous stimulation in SI and SII, but different in insular cortex. Our data also implied that activities in the amygdala/hippocampal formation represented common effects of noxious and tactile stimulations.

Adult↗

PubMed2003

Melanocyte-specific cell mediated immune response in vitiliginous Smyth line chickens.

Smyth line chickens (SL) are an animal model to study human autoimmune vitiligo. Vitiligo in SL chickens is characterized by a post-hatch loss of feather melanocytes (MC) resulting in feather depigmentation. The etiopathology of this disease remains unclear, however, a hypothesis that cell-mediated immunity (CMI) plays an important role in the destruction of melanocytes has been proposed based on previous studies. To support this hypothesis, the delayed wattle response (DWR) to MC lysates was examined in SL chickens and normally pigmented, MHC-matched controls (Brown line, BL; Light Brown Leghorn, LBL) to determine whether vitiliginous SL chickens have MC-specific CMI. Chickens were challenged in one wattle with a lysate of either embryo- or feather-derived cultured MC. Lysates of chick-embryo-fibroblasts (CEF) associated turkey herpesvirus (HVT) vaccine and syngeneic CEF were used as positive and negative control, respectively. Vitiliginous SL chickens exhibited a significantly greater DWR to feather-MC but not to embryo-MC and CEF than nonvitiliginous SL chickens and normally pigmented controls. The DWR to feather-MC peaked at 3 to 5 days post feather-MC lysate injection. Immunohistochemical staining of DWR-positive wattle tissue revealed extensive lymphocyte infiltration at the site of feather-MC injection consisting primarily of T cells (TCR2+, CD4+ or CD8+ T cells). These observations support the presence of MC-specific CMI in SL chickens with vitiligo. The anti-MC CMI activity appears to be specific to MC derived from feathers. SDS-PAGE analysis of different sources of MC lysates revealed a 43 kDa missing band in the lysate of feather-MC established from SL chickens. No other obvious protein pattern differences that could account for the feather MC-specific CMI response in vitiliginous SL chickens were observed among the MC lysates.

Animals↗

PubMed2003

P elements are found in the genomes of nematoceran insects of the genus Anopheles.

We report the identification of genomic sequences in various anopheline mosquitoes (family Culicidae: suborder Nematocera: order Diptera) showing homology to the class II, short inverted-terminal-repeat (ITR) transposable element P from Drosophila melanogaster (family Drosophilidae; suborder Brachycera: order Diptera). Anopheles gambiae appears to have at least six distinct P elements. Other anopheline species, including four additional members of the An. gambiae species complex (An. arabiensis, An. merus, An. melas and An. quadriannulatus), Anopheles stephensi (all subgenus Cellia), An. quadrimaculatus (subgenus Anopheles) and Anopheles albimanus (subgenus Nyssorhynchus) also possess P elements similar to those found in An. gambiae. Ten distinct P element types were identified in the genus Anopheles. At least two of the An. gambiae elements appears to be intact and potentially functional. Phylogenetic analysis of the anopheline P elements reveals them to belong to a distinctly different clade from the brachyceran P elements.

Amino Acid Sequence↗

PubMed2003

Older people in China and the United Kingdom differ in the relationships among parathyroid hormone, vitamin D, and bone mineral status.

To explore whether there are ethnic differences in relationships among parathyroid hormone (PTH), vitamin D, and bone mineral status, 352 healthy volunteers, 60-83 years old, were studied in Shenyang, Peoples' Republic of China (108 men, 110 women), and in Cambridge, UK (67 men, 67 women), in late winter. Early morning fasting blood and 2-h fasting urine were analyzed for 25-hydroxyvitamin D (25OH-D), PTH, and free deoxypyridinoline (DPD). Hip bone mineral status was measured using dual-energy X-ray absorptiometry (Lunar). There were significant differences (P < 0.001) in plasma 25OH-D and PTH concentrations between Shenyang and Cambridge [25OH-D nmol/L: Shenyang = 29.0 (SD 12.7), Cambridge = 35.7 (12.9)]; PTH ng/L: Shenyang = 34.3 (13.4), Cambridge = 25.2 (11.0)]. PTH was negatively related to 25OH-D in both populations. The relationship was exponential, best described by an inverse log-log equation with no break point (P < 0.001), indicating that the exponential curve did not tend toward a low plateau. PTH was higher for a given 25OH-D and decreased less with increasing 25OH-D in Shenyang than in Cambridge (country-ln25OH-D interaction, P = 0.0005). After adjusting for bone area, weight, height, age, and sex, hip bone mineral content (BMC) was significantly related to PTH concentration in Cambridge but not in Shenyang [femoral neck coefficient: Cambridge = -0.064 (SE 0.027), P = 0.02; Shenyang = -0.027 (0.028), P = 0.3; trochanter: Cambridge = -0.116 (0.034), P = 0.001; Shenyang = -0.019 (0.027), P = 0.5]. There was a significant country-lnPTH interaction at the trochanter (P = 0.02), but not at the femoral neck (P = 0.7). A weak positive association between BMC at the femoral neck and 25OH-D concentration was found in Cambridge [coefficient: 0.054 (0.028), P = 0.05] but not in Shenyang (coefficient: -0.013, P = 0.5; country-ln25OH-D interaction, P = 0.07). Urinary DPD concentration was also positively related to plasma PTH concentration in Cambridge subjects only [coefficient: 0.2 (0.08), P = 0.02]. These data suggest that although PTH increases when 25OH-D decreases, and Chinese people have a higher PTH for a given 25OH-D, older Chinese adults may be more resistant than Britons to the effects of PTH on bone.

Aged↗

PubMed2003

D-2-Hydroxyglutaric aciduria with absence of corpus callosum and neonatal intracranial haemorrhage.

We report D-2-hydroxyglutaric aciduria in a neonate with intracranial haemorrhage and absence of the corpus callosum. D-2-hydroxyglutaric acid was confirmed by specific chiral derivatization gas chromatography-mass spectrometry. Absence of the corpus callosum and spontaneous neonatal intracranial haemorrhage should raise the suspicion for metabolic disease, and especially organic acidurias.

Abnormalities, Multiple↗

PubMed2003

Specificity and functional characteristics of anti-HLA-A mAbs LGIII-147.4.1 and LGIII-220.6.2.

Only three anti-HLA-A monoclonal antibodies (mAbs) have been described in the literature. Two of them recognize determinants shared by only a few HLA-A allospecificities. The third one, mAb 3G11, recognizes a determinant shared by most HLA-A allospecificities. Being an IgM, the latter mAb is not likely to be a useful probe in immunohistochemical reactions and in functional assays. Therefore, in the present study we have characterized the specificity of the mAbs LGIII-147.4.1 and LGIII-220.6.2. The two mAbs that do not share idiotypic determinants recognize distinct but spatially close antigenic determinants expressed on most of the gene products of the HLA-A locus. Specifically, the determinant recognized by mAb LGIII-220.6.2 is expressed on HLA-A1, -A2, -A3, -A26, -A28, -A29, -A30, -A33, -A36, -A74 and -A80 allospecificities. The determinant recognized by mAb LGIII-147.4.1, which appears to be located on the amino-acid residues 79-83 of the heavy chain, is expressed on all HLA-A allospecificities but HLA-A23, -A24, -A25 and -A32. Because of its broad reactivity, the mAb LGIII-147.4.1 was characterized in a number of assays. It was found to be a useful probe to measure the HLA-A antigen level in serum, to assess the HLA-A restriction of cytotoxic T lymphocytes (CTL) and to monitor HLA-A antigen expression in normal and malignant lesions.

Animals↗

PubMed2003

Endoplasmic reticulum chaperone-specific monoclonal antibodies for flow cytometry and immunohistochemical staining.

Endoplasmic reticulum (ER) chaperones of the antigen processing machinery play a crucial role in HLA class I antigen complex assembly and antigen presentation. The characterization of the expression of these chaperones in normal tissues and malignant lesions has been hampered by the lack or limited availability of ER chaperone-specific monoclonal antibodies (mAb) that are suitable for immunohistochemical staining. To overcome this limitation, we have generated human calnexin, ERp57, calreticulin and tapasin-specific mAb-secreting hybridomas from BALB/c mice immunized with peptides and recombinant proteins. The mAb TO-5, TO-2, TO-11 and TO-3 were shown to be specific for calnexin, ERp57, calreticulin and tapasin, respectively, as they react specifically with the corresponding immunizing peptides in ELISA and with the corresponding proteins when tested with human lymphoid cell lysates in Western blotting. Furthermore, the reactivity of the four mAb with the corresponding intracellular antigens yielded intracellular staining when the mAb were tested with formalin-fixed, microwave-treated and saponin-permeabilized cells in indirect immunofluorescence and with formalin-fixed, paraffin-embedded tissue sections in the immunoperoxidase reaction. These results suggest that the ER chaperone-specific mAb we have developed are useful probes for characterizing the expression of ER chaperones of the antigen processing machinery in normal and pathological cells. This information will contribute to defining the effects of abnormalities in their expression on HLA class I antigen expression and function and on the interactions of target cells with the host's immune system.

Animals↗

PubMed2003

Nitric oxide promotes p53 nuclear retention and sensitizes neuroblastoma cells to apoptosis by ionizing radiation.

Nitric oxide (NO) is a potent activator of the p53 tumor suppressor protein. However, the mechanisms underlying p53 activation by NO have not been fully elucidated. We previously reported that a rapid downregulation of Mdm2 by NO may contribute to the early phase of p53 activation. Here we show that NO promotes p53 nuclear retention and inhibits Mdm2-mediated p53 nuclear export. NO induces phosphorylation of p53 on serine 15, which does not require ATM but rather appears to depend on the ATM-related ATR kinase. An ATR-kinase dead mutant or caffeine, which blocks the kinase activity of ATR, effectively abolishes the ability of NO to cause p53 nuclear retention, concomitant with its inhibition of p53 serine 15 phosphorylation. Of note, NO enhances markedly the ability of low-dose ionizing radiation to elicit apoptotic killing of neuroblastoma cells expressing cytoplasmic wild-type p53. These findings imply that, through augmenting p53 nuclear retention, NO can sensitize tumor cells to p53-dependent apoptosis. Thus, NO donors may potentially increase the efficacy of radiotherapy for treatment of certain types of cancer.

Active Transport, Cell Nucleus↗

PubMed2003

NRADD, a novel membrane protein with a death domain involved in mediating apoptosis in response to ER stress.

NRADD (neurotrophin receptor alike death domain protein) is a novel protein with transmembrane and cytoplasmic regions highly homologous to death receptors, particularly p75(NTR). However, the short N-terminal domain is unique. Expression of NRADD induced apoptosis in a number of cell lines. The apoptotic mechanism involved the activation of caspase-8 and execution of apoptosis without requiring mitochondrial components. The activation of this death receptor-like mechanism required the N-terminal domain, which is N-glycosylated and needed for subcellular targeting. Deletion of the N-terminal domain produced a dominant-negative form of NRADD that protected neurons and Schwann cells from a variety of endoplasmic reticulum (ER) stressors. NRADD may therefore be a necessary component for generating an ER-induced proapoptotic signal.

Amino Acid Sequence↗

PubMed2003

A novel tetracycline-controlled transactivator-transrepressor system enables external control of oncolytic adenovirus replication.

The use of restricted replication-competent adenoviruses (RRCAs) inducing tumor cell-specific lysis is a promising approach in cancer gene therapy. However, the use of RRCAs in humans carries considerable risk, since after injection into the patient, further regulation or inhibition of virus replication from the outside is impossible. Therefore, we have developed a novel system allowing external pharmacological control of RRCA replication. We show here that a tumor-selective E1B-deleted RRCA can be tightly regulated by use of doxycycline (dox)-controlled adenoviral E1A gene expression, which in turn determines vector replication. RRCA replication is switched on by addition and switched off by withdrawal of dox. The system results in efficient tumor cell killing after induction by dox, whereas cells are unaffected by the uninduced system. It was also employed for efficient external control of transgene expression from cotransfected replication-deficient adenovectors. Furthermore, the use of a liver cell-specific human alpha1-antitrypsin (hAAT)-promoter driving a tetracycline-controlled transcriptional silencer allowed specific protection of cells with hAAT-promoter activity in the absence of dox in vitro and in vivo, delineating a new principle of 'tissue protective' gene therapy. The concept of external control of RRCAs may help to improve the safety of cancer gene therapy.

Adenoviridae↗

PubMed2003

Insulin resistance but not visceral adipose tissue is associated with plasminogen activator inhibitor type 1 levels in overweight and obese premenopausal African-American women.

OBJECTIVE: To compare plasma plasminogen activator inhibitor type 1 (PAI-1) levels and to examine the association of PAI-1 with visceral adiposity and other components of the metabolic syndrome in overweight and obese premenopausal African-American (AA) and Caucasian (CC) women. DESIGN: Cross-sectional study. SUBJECTS: 33 CC and 23 AA healthy, overweight and obese, premenopausal women (age 19-53 y, body mass index 28.1-48.9 kg/m(2)). MEASUREMENTS: Body mass index, sagittal diameter, waist circumference, percentage body fat, visceral and subcutaneous adipose tissue (by anthropometry, magnetic resonance imaging (MRI), and bioelectric impedance techniques), PAI-1, leptin, lipids, glucose, insulin, and insulin resistance (by HOMA IR). RESULTS: AA women had lower triglyceride levels and less visceral adipose tissue (VAT) volume than CC despite similar BMI. PAI-1 levels were not significantly different in the two groups. Insulin resistance was associated with PAI-1 in both groups but only in CC women were VAT, triglyceride, HDL cholesterol and blood pressure related to plasma PAI-1 levels. Multiple regression analysis showed that VAT in CC and insulin resistance in AA were independent predictors of PAI-1. CONCLUSION: VAT is significantly associated with circulating PAI-1 levels in overweight and obese CC but not AA premenopausal women.

Adipose Tissue↗

PubMed2003

Type I coagulation factor V deficiency caused by compound heterozygous mutation of F5 gene.

A 16-year-old Chinese female with prolonged bleeding after surgery has been studied. Routine clotting tests revealed a prolonged activated partial thromboplastin time (APTT; 126.6 s) and prothrombin time (PT; 42.8 s). The coagulation factors activities were normal except for factor V, which was only 0.3% of normal. DNA analysis of the FV gene revealed five nucleotide substitutions in exons, including two silent mutations (G327A and A5112G), one polymorphism (G1628A), a G1348T missense mutation and 4887 approximately 8delG. These abnormalities were associated with her FV deficiency, perhaps by causing a Gly392Cys substitution in FV amino acid sequence or by introducing a premature stop codon at amino acid position 1390. This is the third case in which FV deficiency is caused by compound heterozygous mutation of F5 gene, and is the first report from a Chinese family.

Adolescent↗

PubMed2003

Molecular characterization of the microbial species that colonize human ileal and colonic mucosa by using 16S rDNA sequence analysis.

AIM: The aim of this study was to characterize the bacterial community adhering to the mucosa of the terminal ileum, and proximal and distal colon of the human digestive tract. METHODS AND RESULTS: Pinch samples of the terminal ileum, proximal and distal colon were taken from a healthy 35-year-old, and a 68-year-old subject with mild diverticulosis. The 16S rDNA genes were amplified using a low number of PCR cycles, cloned, and sequenced. In total, 361 sequences were obtained comprising 70 operational taxonomic units (OTU), with a calculated coverage of 82.6%. Twenty-three per cent of OTU were common to the terminal ileum, proximal colon and distal colon, but 14% OTU were only found in the terminal ileum, and 43% were only associated with the proximal or distal colon. The most frequently represented clones were from the Clostridium group XIVa (24.7%), and the Bacteroidetes (Cytophaga-Flavobacteria-Bacteroides) cluster (27.7%). CONCLUSION: Comparison of 16S rDNA clone libraries of the hindgut across mammalian species confirms that the distribution of phylogenetic groups is similar irrespective of the host species. Lesser site-related differences within groups or clusters of organisms, are probable. SIGNIFICANCE AND IMPACT: This study provides further evidence of the distribution of the bacteria on the mucosal surfaces of the human hindgut. Data contribute to the benchmarking of the microbial composition of the human digestive tract.

Adult↗

PubMed2003

Nutritional regulation of white adipocyte vascular endothelial growth factor (VEGF).

White adipose tissue has distinctive angiogenic properties. White adipocytes are capable of producing vascular endothelial growth factor (VEGF) in response to insulin and catecholamines. Recognizing the dual functions of adipose tissue as an endocrine/metabolic organ and fuel storage depot with an inimitable ability to adjust its organ mass, our aim was to determine whether fasting would affect adipocyte VEGF 165 production. Rats were fed ad libitum, then fasted for 24 hours, and then refed after the 24-hour fast. The isolated white adipocytes from each group and blood endocrine/metabolic profiles were examined at each stage, yielding three sets of results. Using cultured adipocytes, fasting caused a two-fold increase in VEGF 165 formation compared to fed rats that normalized after refeeding. Likewise, freshly prepared adipocytes manifested a three-fold augmentation in adipocyte VEGF 165 mRNA expression and a 60 % increase the transcriptional regulator hypoxia-inducible factor 1 (HIF-1alpha) that normalized after refeeding. Blood studies revealed the expected fasting-related alterations in glucose, beta-hydroxybutyrate and corticosterone. Plasma VEGF concentrations were attenuated by 26 % with fasting, and did not normalize with refeeding. Multiple linear regression analyses uncovered statistically significant inverse correlations between plasma VEGF and blood beta-hydroxybutyrate or serum corticosterone. Blood glucose, in contrast, correlated directly with plasma VEGF. We will discuss the potential role of enhanced adipocyte VEGF formation during starvation in light of the known actions of this factor on vascular endothelial mitogenesis and permeability.

3-Hydroxybutyric Acid↗

PubMed2003

[Gap junctions in the human urinary bladder].

PURPOSE: Gap junctions are intercellular contacts important for the synchronization of muscle cell activity through electrical coupling. Since the role of gap junctions for the function of smooth bladder muscle is still a matter of debate, we investigated the occurrence of gap junctions and the gap junctional protein connexin (Cx) 45 in the detrusor of the nonobstructed stable human bladder. MATERIALS AND METHODS: Detrusor biopsies from 6 patients aged 64 (55-72) years with stable nonobstructed bladders were investigated for the occurrence of gap junctions by electron microscopy, molecular biological techniques and immunohistochemistry. RESULTS: Transmission electron microscopy and freeze fracture showed the presence of gap junction at plasma membranes of detrusor smooth muscle cells. By reverse transcriptase (RT) polymerase chain reaction (PCR) and in situ hybridization, we found an expression of Cx45 in the detrusor. These data were confirmed by immunolocalization of Cx45 on smooth muscle cells. CONCLUSIONS: This study provides morphological as well as molecular biological and immunohistochemical evidence that bladder smooth muscle cells are electrically coupled.

Aged↗

PubMed2003

Acute phase response in acute pancreatitis: a comparison with abdominal sepsis.

BACKGROUND: Increased knowledge on the underlying pathophysiological mechanisms in acute pancreatitis (AP) and abdominal sepsis (AS) is essential, not least for the development of novel ways of treatment. The present study aims at determining dynamic changes in the systemic inflammatory response in AP and AS. METHODS: AP was induced by the intraductal injection of sodium taurodeoxycholate in the rat, while AS was induced by caecal ligation and puncture. The animals were killed 1, 3, 6 and 9 h after challenge. Plasma exudation of radiolabelled albumin, myeloperoxidase (MPO), TNF-alpha, MCP-1, superoxide and hydrogen peroxide was measured. RESULTS: Leakage index of human serum albumin showed a significant increase early (I h) after induction of AP and later (9h) in AS compared to controls (P < 0.05). Hydrogen peroxide generation by circulating monocytes/macrophages was high early (1 h) in AP and after 3 and 6h in AS. Superoxide generation increased by time after both challenges. MPO activity increased significantly, starting at 3 h in both AP and AS (P < 0.05). TNF-alpha increased significantly at 6 and 9 h in both models. CONCLUSION: Our results indicate differences in the release of systemic inflammatory mediators and cellular response in AP and AS. However, potential similarities in end-effect, such as the development of remote organ injury (lungs), may exist as implied by the MPO results. Further investigations of the mechanisms are crucial.

Abdomen↗

PubMed2003

Predicting toxicity of benzene derivatives by molecular hologram derived quantitative structure-activity relationships (QSARS).

Holographic quantitative structure-activity relationship (HQSAR) is an emerging QSAR technique with the combined application of molecular hologram, which encodes the frequency of occurrence of various molecular fragment types, and the subsequent partial least squares (PLS) regression analysis. Based on molecular hologram, alignment-free QSAR models could be rapidly and easily developed with highly statistical significance and predictive ability. In this paper, the toxicity data for a series of 83 benzene derivatives to the autotrophic Chlorella vulgaris (IGC50, negative logarithmic form of 6-h 50% population growth inhibition concentration in mmol/l) were subjected to HQSAR analysis and this resulted in a model with a high predictive ability. The robustness and predictive ability of the model were validated by "leave-one-out" (LOO) cross-validation procedure and an external testing set. The influence of fragment distinction parameters and fragment size on the quality of the HQSAR model have been also discussed.

Benzene Derivatives↗

PubMed2003

Systems-wide chicken DNA microarrays, gene expression profiling, and discovery of functional genes.

The goal of our current consortium project is to launch a new era--functional genomics of poultry--by providing genomic resources [expressed sequence tags (EST) and DNA microarrays] and by examining global gene expression in target tissues of chickens. DNA microarray analysis has been a fruitful strategy for the identification of functional genes in several model organisms (i.e., human, rodents, fruit fly, etc.). We have constructed and normalized five tissue-specific or multiple-tissue chicken cDNA libraries [liver, fat, breast, and leg muscle/epiphyseal growth plate, pituitary/hypothalamus/pineal, and reproductive tract (oviduct/ovary/testes)] for high-throughput DNA sequencing of EST. DNA sequence clustering was used to build contigs of overlapping sequence and to identify unique, non-redundant EST clones (unigenes), which permitted printing of systems-wide chicken DNA microarrays. One of the most promising genetic resources for gene exploration and functional gene mapping is provided by two sets of experimental lines of broiler-type chickens developed at INRA, France, by divergent selection for extremes in growth traits (fast-growing versus slow-growing; fatness versus leanness at a similar growth rate). We are using DNA microarrays for global gene expression profiling to identify candidate genes and to map growth, metabolic, and regulatory pathways that control important production traits. Candidate genes will be used for functional gene mapping and QTL analysis of F2 progeny from intercrosses made between divergent genetic lines (fat x lean lines; fast-growing x slow-growing lines). Using our first chicken liver microarray, we have already identified several interesting differentially expressed genes in commercial broilers and in divergently selected broiler lines. Many of these candidate genes are involved in the lipogenic pathway and are controlled in part by the thyrotropic axis. Thus, genome-wide transcriptional profiling is a powerful tool used to visualize the cascade of genetic circuits that govern complex biological responses. Global gene expression profiling and QTL scans should enable us to functionally map the genetic pathways that control growth, development, and metabolism of chickens. This emerging technology will have broad applications for poultry breeding programs (i.e., use of molecular markers) and for future production systems (i.e., the health and welfare of birds and the quality of poultry products).

Animal Husbandry↗