Search PubMed⌕ Search

Biomedical subjects

H Xu

Publications and source records attributed to H Xu.

At least 127 records · Page 7Linked to original sources
PubMed2001

Multiple effector domains within SNT1 coordinate ERK activation and neuronal differentiation of PC12 cells.

Differentiation of neuronal precursor cells in response to neurotrophic differentiation factors is accompanied by the activation of membrane-anchored SNT signaling adaptor proteins. Two classes of differentiation factors, the neurotrophins and fibroblast growth factors, induce rapid tyrosine phosphorylation of SNT1(FRS2alpha), which in turn enables SNT1 to recruit Shp2 tyrosine phosphatase and Grb2 adaptor protein in complex with the Ras GDP/GTP exchange factor Sos. To determine effector functions of SNT that promote neuronal differentiation of PC12 pheochromocytoma cells, we engineered a chimeric protein, SNT1(IRS)CX, bearing the effector region of SNT1 and the insulin receptor recognition domains of IRS2. Insulin promoted tyrosine phosphorylation of SNT1(IRS)CX in transfected PC12 cells accompanied by sustained activation of ERK1/2 mitogen-activated protein kinases and neuronal differentiation. The SNT1(IRS)CX-mediated response was dependent on endogenous Ras, MEK, and Shp2 activities. Mutagenesis of SNT1(IRS)CX identified three classes of effector motifs within SNT critical for both sustained ERK activation and neuronal differentiation: 1) four phosphotyrosine motifs that mediate recruitment of Grb2, 2) two phosphotyrosine motifs that mediate recruitment of Shp2, and 3) a C-terminal motif that functions by helping to recruit Sos. We discuss possible mechanisms by which three functionally distinct SNT effector motifs collaborate to promote a downstream biochemical and biological response.

3T3 Cells↗
PubMed2001

Opioid peptide receptor studies. 14. Stereochemistry determines agonist efficacy and intrinsic efficacy in the [(35)S]GTP-gamma-S functional binding assay.

Previous data obtained with the cloned rat mu opioid receptor demonstrated that stereochemistry affects the four parameters of the ligand-receptor interaction: potency (ED(50)), efficacy (maximal stimulation), intrinsic efficacy (effect as a function of receptor occupation), and binding affinity. This study evaluated the activities of structurally diverse opioid receptor ligands in the [(35)S]GTP-gamma-S binding assay, comparing the relationship between receptor binding, activation, efficacy, and intrinsic efficacy. The data, obtained with cloned rat mu receptors, demonstrated that an analgetic, (-)-5-m-hydroxyphenyl-2-methylmorphan (NIH8508), and its (+)-isomer (NIH8509), behave as partial agonists, but had different intrinsic efficacy in the [(35)S]GTP-gamma-S binding assay. Replacement of the methyl group with the phenethyl group on the piperidine nitrogen of NIH8508 and NIH8509 [(1R,5S)-AH019 and (1S, 5R)-AH019] increased affinity for the mu receptor and eliminated any agonist effect, supporting the hypothesis that certain structural features make these compounds antagonists. These study also show that all of the fully efficacious mu agonists studied here had high levels of intrinsic efficacy, producing a 50% response at about 10% receptor occupancy. Comparison of the binding K(i) in competitively inhibiting [(125)I]IOXY binding to the functional K(i) for opioid antagonists [K(i)(IOXY)/K(i)(GTP-gamma-S)] provides more detailed evidence that the [(35)S]GTP-gamma-S binding assay can be used to reliably determine apparent functional antagonist K(i) values in addition to agonist ED(50), efficacy and intrinsic efficacy.

Analgesics, Opioid↗
PubMed2001

The role of ICAM-1 molecule in the migration of Langerhans cells in the skin and regional lymph node.

ICAM-1 (CD54) plays an important role in the cell-cell interaction and migration of leukocytes. Previous studies have shown that ICAM-1 is involved in inflammatory reactions and that a defect in ICAM-1 gene inhibits allergic contact hypersensitivity. This study indicates that the migration of hapten presenting Langerhans cells into the regional lymph nodes was significantly reduced in ICAM-1-deficient mice compared to wild-type C57BL/6 mice. The reduced number of dendritic cells in regional lymph nodes did not result from abnormal migration of Langerhans cells into the skin of ICAM-1-deficient mice. The concentration and distribution of Langerhans cells in the naïve skin of ICAM-1-deficient mice was equal to that of wild-type mice. Following hapten sensitization, Langerhans cell migration out of the skin and recruitment of fresh Langerhans cells back to the epidermis was not affected in ICAM-1-deficient mice. Further experiments demonstrated that ICAM-1 deficiency on lymphatic endothelium rather than on dendritic cells was responsible for the reduced migration of Langerhans cells into draining lymph nodes. This study indicates that ICAM-1 regulates the migration of dendritic cells into regional lymph nodes but not into or out of the skin.

Animals↗
PubMed2001

DNA separations in microfabricated devices with automated capillary sample introduction.

A novel method is presented for automated injection of DNA samples into microfabricated separation devices via capillary electrophoresis. A single capillary is used to electrokinetically inject discrete plugs of DNA into an array of separation lanes on a glass chip. A computer-controlled micromanipulator is used to automate this injection process and to repeat injections into five parallel lanes several times over the course of the experiment. After separation, labeled DNA samples are detected by laser-induced fluorescence. Five serial separations of 6-carboxyfluorescein (FAM)-labeled oligonucleotides in five parallel lanes are shown, resulting in the analysis of 25 samples in 25 min. It is estimated that approximately 550 separations of these same oligonucleotides could be performed in one hour by increasing the number of lanes to 37 and optimizing the rate of the manipulator movement. Capillary sample introduction into chips allows parallel separations to be continuously performed in serial, yielding high throughput and minimal need for operator intervention.

Automation↗
PubMed2001

Quantitative determination of nitrendipine and its metabolite dehydronitrendipine in human plasma using liquid chromatography-tandem mass spectrometry.

A sensitive and high-throughput LC-MS-MS method was developed for simultaneous determination of nitrendipine (NIT) and its major metabolite, dehydronitrendipine (DNIT) in human plasma using nifedipine as the internal standard. Plasma samples were prepared based on a simple liquid-liquid extraction. The extracted samples were analyzed on a Zorbax SB C(18) column interfaced with a triple quadrupole tandem mass spectrometer. Positive atmospheric pressure chemical ionization was employed as the ionization source. The analytes were detected by use of selected reaction monitoring mode. Standard curves were linear (r > or = 0.995) over the concentration range of 0.4-40 ng/mL for NIT and 0.2-20 ng/mL for DNIT. The intra- and inter-run precision was measured to be below 8.5% for NIT and DNIT. The inter-run accuracy was less than 4% for the analytes. The overall extraction recoveries of NIT and DNIT were determined to be about 75% and 78% on average, respectively. The chromatographic run time was approximately 3 min. More than 120 samples could be assayed daily with this method, including sample preparation, data acquisition and processing. The method developed was successfully used to investigate plasma concentrations of NIT and DNIT in a pharmacokinetic study of volunteers who received NIT orally.

Antihypertensive Agents↗
PubMed2001

Modulation of the heteromeric Kir4.1-Kir5.1 channels by P(CO(2)) at physiological levels.

Several inward rectifier K(+) (Kir) channels are pH-sensitive, making them potential candidates for CO(2) chemoreception in cells. However, there is no evidence showing that Kir channels change their activity at near physiological level of P(CO(2)), as most previous studies were done using high concentrations of CO(2). It is known that the heteromeric Kir4.1-Kir5.1 channels are highly sensitive to intracellular protons with pKa value right at the physiological pH level. Such a pKa value may allow these channels to regulate membrane potentials with modest changes in P(CO(2)). To test this hypothesis, we studied the Kir4.1-Kir5.1 currents expressed in Xenopus oocytes and membrane potentials in the presence and absence of bicarbonate. Evident inhibition of these currents (by approximately 5%) was seen with P(CO(2)) as low as 8 torr. Higher P(CO(2)) levels (23-60 torr) produced stronger inhibitions (by 30-40%). The inhibitions led to graded depolarizations (5-45 mV with P(CO(2)) 8-60 torr). Similar effects were observed in the presence of 24 mM bicarbonate and 5% CO(2). Indeed, the Kir4.1-Kir5.1 currents were enhanced with 3% CO(2) and suppressed with 8% CO(2) in voltage clamp, resulting in hyper- (-9 mV) and depolarization (16 mV) in current clamp, respectively. With physiological concentration of extracellular K(+), the Kir4.1-Kir5.1 channels conduct substantial outward currents that were similarly inhibited by CO(2) as their inward rectifying currents. These results therefore indicate that the heteromeric Kir4.1-Kir5.1 channels are modulated by a modest change in P(CO(2)) levels. Such a modulation alters cellular excitability, and enables the cell to detect hypercapnia and hypocapnia in the presence of bicarbonate.

Animals↗
PubMed2001

Deregulated expression of DP1 induces epidermal proliferation and enhances skin carcinogenesis.

E2F transcription factors have been implicated in several cellular processes, including proliferation, apoptosis, and oncogenic transformation. A functional E2F factor consists of a heterodimer containing an E2F polypeptide (E2F1-E2F6) and a DRTF1-polypeptide (DRTF1-polypeptide-1 (DP1) or DRTF1-polypeptide-2). It is the E2F subunit that supplies the transcriptional activation domain and the motif involved in binding to members of the retinoblastoma tumor suppressor family. The role of the DP subunit in regulating E2F-dependent activities is not completely understood. To examine the properties of DP1 in vivo, we generated transgenic mouse lines expressing DP1 under the control of a keratin 5 (K5) promoter. Overexpression of DP1 in basal layer keratinocytes caused mild hyperplasia and hyperproliferation of the epidermis but did not result in increased apoptosis or spontaneous tumor development. Coexpression of DP1 with E2F1 or E2F4 in the epidermis of bigenic mice modestly enhanced proliferation and apoptosis over the levels induced by E2F1 or E2F4 expression alone. In a two-stage chemical carcinogenesis assay, more and larger skin tumors developed in K5 DP1 transgenic mice than in nontransgenic mice. These findings show that in this in vivo model, deregulated expression of DP1 on its own induced proliferation and enhanced carcinogenesis.

Animals↗
PubMed2001

Cloning and characterization of human erythroid membrane-associated protein, human ERMAP.

We describe here the cloning and characterization of the human gene ERMAP, identified by subtractive hybridization using early and late gestation human fetal liver. By in situ hybridization, we found human ERMAP to be expressed not only in erythoid cells in fetal liver and adult bone marrow, but also in reticulocytes and circulating erythroblasts in 8-12-week fetal cord blood. The human ERMAP protein is predicted to contain a transmembrane segment and one extracellular immunoglobulin fold (IgV). The cytoplasmic region contains a highly conserved B30.2 motif, multiple consensus sequences for kinases, and post-Golgi sorting signals. The protein was localized to the cell surface as shown by an antibody specific for a peptide predicted from the IgV fold. The amino acid sequence of human ERMAP is highly homologous with that of mouse ERMAP, but differs in the number of extracellular immunoglobulin folds. Human ERMAP represents a new unique member of the rapidly growing B30.2 domain proteins.

Amino Acid Sequence↗
PubMed2001

IL-12 enhances lymphoaccumulation by suppressing cell death of T cells in MRL- lpr/lpr mice.

Lymphoaccumulation occurs in MRL- lpr/lpr mice, because double-negative T cells (DNT cells) cannot be deleted due to their Fas mutation, i.e., lpr. We show here that IL-12 enhances in lymphoaccumulation by suppressing cell death of DNT cells in [corrected] MRL- lpr/lpr mice. It has been reported that viable DNT cells from MRL- lpr/lpr mice undergo rapid apoptosis in ordinary cell culture without additional stimulation, suggesting that unknown in vivo factors other than lpr suppress the apoptosis. In the present study, we found that plasma IL-12p40 monomer and/or homodimer level increased with age in MRL- lpr/lpr but not in MRL-+/+ mice, and the increase in IL-12 correlated well with lymphoaccumulation. Requirement of IL-12 in lymphoaccumulation and in suppressed cell death of DNT cells of MRL- lpr/lpr mice was assessed. When an antibody neutralizing IL-12 was injected into old MRL- lpr/lpr mice with high plasma IL-12 level, lymphoaccumulation was diminished. When IL-12p40- or IL-12p70-encoding plasmid was administered to young MRL- lpr/lpr mice before the plasma IL-12 level increases, lymphoaccumulation was enhanced. The ordinary cell culture-induced cell death of DNT cells from MRL- lpr/lpr mice was suppressed in the presence of IL-12. Since DNT cells produce IFN-gamma, a potent inducer of IL-12, the INF-gamma induced-IL-12 may enhance lymphoaccumulation in MRL- lpr/lpr mice.

Age Factors↗
PubMed2001

Environmental regionalization for the management of township and village enterprises in China.

Environmental regionalization (ER) is the basis of environmental assessment, prediction, planning and decision-making. ER techniques were applied to the management of Township and Village Enterprises (TVEs) in China. TVEs are generally middle and small-scale enterprises widely distributed in rural areas with rapid development and high discharge rates of pollutants, which impact heavily on the environment. A set of 13 indicators was chosen to evaluate TVEs in China: (1) runoff depth (P = 75%); (2) rainfall; (3) atmospheric pollution coefficient; (4) percent of forest coverage; (5) national income per capita; (6) economic density of TVEs; (7) population density; (8) environmental management staff at county level; (9) cultivated area per capita; (10) technical advancement of TVEs; (11) environmental impact of TVE industrial structure; (12) ratio of waste water to runoff; and (13) coal consumption density. Fuzzy cluster analysis was employed to conduct quantitative classification. Four zones and seven subzones were obtained. The classification system was adapted to the requirements of environmental management for TVEs at national level.

China↗
PubMed2001

Protective effects of flavonoids in the roots of Scutellaria baicalensis Georgi against hydrogen peroxide-induced oxidative stress in HS-SY5Y cells.

Oxidative stress plays an important role in the pathological process of neurodegenerative diseases. The effects of four major flavonoids present in Scutellaria baicalensis Georgi on hydrogen peroxide-induced neuronal cell damage are studied in this paper. When human neuroblastoma SH-SY5Y cells were incubated in Hanks' solution with the addition of 400 microM hydrogen peroxide for 2 h, the viability of cells was decreased remarkably, while the cell lipid peroxidation and the percentage of lactose dehydrogenase released into the culture medium was significantly increased. Addition of 10 microM of baicalein and baicalin significantly attenuated the cellular injury induced by hydrogen peroxide, while the effect of wogonin was marginal and wogonoside showed no effect at the tested concentration. In a separate experiment, 10 microM of baicalein and baicalin also antagonized the intracellular free-calcium concentration ([Ca2+]i) increase caused by 1 mM hydrogen peroxide. The effects of baicalein in both experiments were similar to those of quercetin, a well-studied antioxidant flavonoid. These results demonstrated the protective effects of flavonoids originating from Scutellaria baicalensis Georgi on the oxidative injury of neuronal cells.

Cell Survival↗
PubMed2001

A study on the prevention and treatment of myopia with nacre on chicks.

The contents of mineral elements and amino acids in the hydrolysate of the traditional Chinese mineral medicine nacre have been determined. It has long since been proved by the practice of doctors of traditional Chinese medicine that pearl can be used to treat eye diseases. Based on such an understanding, a study is made of the influence of the said medicine on the incidence of myopia. First a form-sense-deprived model (FDM) for chicks is developed and the effect of the said medicine on the elongation of axis oculi is determined with an Abbe's comparator and an A-mode ultrasound instrument. The activity of superoxide dismutase (SOD), nitric oxide synthetase (NOS), and the content of nitric oxide (NO) in the retino-pigmental epithelium choroid homogenate are also analysed. The role of the said traditional Chinese mineral medicine in preventing and treating myopia is explained with respect to the above findings. The results obtained will provide a basis for using nacre, a traditional Chinese mineral medicine, to prevent and treat myopia.

Amino Acids↗
PubMed2001

Size effects of realgar particles on apoptosis in a human umbilical vein endothelial cell line: ECV-304.

Regulation of endothelial cell apoptosis is a critical modulator of normal and pathological angiogenesis. Inorganic arsenic, especially arsenic trioxide, has been demonstrated to induce clinical remission in patients with acute promyelocytic leukemia as well as those with several solid cancers. So, in this study, we examined the in vitro effect of realgar(As2S2), used to treat human diseases for centuries in traditional Chinese medicine, on cell survival and apoptosis in a human umbilical vein endothelial cell (HUVEC) line: ECV-304. Four different suspensions of realgar particles with diameters from 100-500 nm containing equivalent doses were investigated to determine their size effects. After 2, 4, 6 and 8 h, realgar particles of diameters 100 nm and 150 nm obviously reduced ECV-304 cell survival, which was evidenced by a reduction of cell viability in the MTT assay, whereas cells exhibited slight viability reduction in response to treatment with realgar particles of diameters 200 nm and 500 nm. Significant apoptosis was identified by morphological observation, flow cytometry assay and DNA gel electrophoresis in the ECV-304 cells by the presence of realgar particles of diameters 100 nm and 150 nm. It is demonstrated that particles of realgar with average diameters from 100 nm to 150 nm can induce ECV-304 cell apoptosis. These results suggest that particles of realgar smaller than 150 nm may provide a less toxic agent for anti-neoplasia by suppressing angiogenesis.

Acridine Orange↗
PubMed2001

Effect of ligustrazine on hematopoiesis in bone marrow transplantation mice.

The effect of Ligustrazine on the hematopoiesis after bone marrow transplantation (BMT) in allogenic BMT mice was investigated. After the typical mice model of allogenic BMT had been established, the mice were randomly divided into three groups: BMT group, Ligustrazine group and normal group. The BMT group was given normal saline (0.2 ml, twice a day) through gastric tube, while the Ligustrazine group was given Ligustrazine through gastric tube (0.2 ml, twice a day). At the 1st, 7th and 14th day after BMT, we observed the peripheral blood cells and bone marrow nuclear cells (BMNC), as well as the expression level of Heparan Sulfate (HS) and stromal cell derived factor-1 (SDF-1) on bone marrow sections by using immunohistochemistry (SABC-AP), the expression of CXCR4 on the BMNC. The results showed that on the 7th and 14th day, the peripheral blood white cells, platelets, BMNC and the expression levels of CXCR4, HS and SDF-1 were significantly higher in Ligustrazine group than in the BMT group (P < 0.05). It was concluded that Ligustrazine could promote hematopoiesis at the early stage of hematopoietic reconstitution after BMT.

Animals↗
PubMed2001

A preliminary clinical study of three-dimensional ultrasonography in prenatal diagnosis.

To evaluate the clinical value of three-dimensional ultrasonography (3DUS) in prenatal diagnosis, 134 pregnant women with high-risk factors in second and third trimester were examined by 3DUS. The results showed that 3DUS could provide more diagnostic information, exclude the abnormalities and enhance the confidence level of physician in 102 normal pregnant women. 3DUS was helpful in the diagnosis in 17 (60.7%) of 28 cases of fetal anomalies. However, 3DUS was not useful in evaluating intrauterine growth retardation in 4 cases. It is concluded that 3DUS is helpful in prenatal diagnosis.

Adult↗
PubMed2001

Pulmonary sequestration: three dimensional dynamic contrast-enhanced MR angiography and MRI.

In order to evaluate the diagnostic value of three-dimensional contrast-enhanced MR angiography and MRI for pulmonary sequestration, 5 patients with pulmonary sequestration underwent 3D fast imaging by steady state precession (FISP) with a contrast medium and breath holding following chest radiography, CT and MR scans. The reconstructed MR angiography was performed using maximum intensity projection (MIP) and multiplanar reconstruction (MPR) techniques. It was found that the chest radiography showed pulmonary sequestration as a persistent area of opacity in the posterior basal segment of the left lower lobe, which was close to mediastinum in 2 cases and close to diaphragma in 3 cases. CT revealed a soft issue mass beyond descending aorta and lobar emphysema around the pulmonary sequestration. And the supplying vessel was documented in 2 cases on enhanced CT. MRI demonstrated a hyperintensity mass with respect to normal lung parenchyma on T1WI and T2WI, and the origin of the supplying vessel in 3 cases. The reconstructed CE MRA using MIP or MRP techniques clearly showed the supplying vessel and its course, branches as well as draining vessels. It was concluded that 3D CE MRA of demonstrating the supplying and draining vessels to pulmonary sequestration, together with plain MRI, can provide a diagnosis and aid in surgical planning without the need for DSA.

Adolescent↗
PubMed2001

Three-dimensional ultrasonography in obstetrics: the clinical value.

To investigate the clinical value of three-dimensional ultrasonography (3DUS) in obstetrics, various 3DUS rendering methods including surface mode, transparent mode and multiplanar mode were employed to scan 30 fetuses in second and third trimester by using the transabdominal volume transducer. The results showed that surface mode could vividly demonstrate the surface morphologic features of the fetuses, as well as the stereo-shape and the spatial relationship among the surface structures. The face, limbs, umbilical cord and outer genitalia of the fetus could be well displayed by surface mode. Transparent mode could reveal the bony structures under the surface, such as ribs, vertebrae, crania, etc. The result was not affected by the sophisticated curvature of these bony structures and the success rate was up to 100%. When rendered by multiplanar mode, the region of interest (ROI) could be viewed from different directions. It should be concluded that 3DUS could serve as a supplement to two-dimensional ultrasonography (2DUS). 3DUS might play an important role in prenatal diagnosis and enhance the diagnostic confidence level of the physicians.

Female↗