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X Xiong

Publications and source records attributed to X Xiong.

At least 73 records · Page 4Linked to original sources

Growth arrest-specific gene 6 (Gas6)/adhesion related kinase (Ark) signaling promotes gonadotropin-releasing hormone neuronal survival via extracellular signal-regulated kinase (ERK) and Akt.

We identified Ark, the mouse homolog of the receptor tyrosine kinase Axl (Ufo, Tyro7), in a screen for novel factors involved in GnRH neuronal migration by using differential-display PCR on cell lines derived at two windows during GnRH neuronal development. Ark is expressed in Gn10 GnRH cells, developed from a tumor in the olfactory area when GnRH neurons are migrating, but not in GT1-7 cells, derived from a tumor in the forebrain when GnRH neurons are postmigratory. Since Ark (Ax1) signaling protects from programmed cell death in fibroblasts, we hypothesized that it may play an antiapoptotic role in GnRH neurons. Gn10 (Ark positive) GnRH cells were more resistant to serum withdrawal-induced apoptosis than GT1-7 (Ark negative) cells, and this effect was augmented with the addition of Gas6, the Ark (Ax1) ligand. Gas6/Ark stimulated the extracellular signal-regulated kinase, ERK, and the serine-threonine kinase, Akt, a downstream component of the phosphoinositide 3-kinase (PI3-K) pathway. To determine whether ERK or Akt activation is required for the antiapoptotic effects of Gas6/Ark in GnRH neurons, cells were serum starved in the absence or presence of Gas6, with or without inhibitors of ERK and PI3-K signaling cascades. Gas6 rescued Gn10 cells from apoptosis, and this effect was blocked by coincubation of the cells with the mitogen-activated protein/ERK kinase (MEK) inhibitor, PD98059, or wortmannin (but not rapamycin). These data support an important role for Gas6/Ark signaling via the ERK and PI3-K (via Akt) pathways in the protection of GnRH neurons from programmed cell death across neuronal migration.

Androstadienes↗

[Observation of the long-term serum insulin level in women with gestational diabetes history].

OBJECTIVE: To determine beta-cell's function by measuring blood glucose level and serum insulin level in women who had history of gestational diabetes mellitus (GDM), but had no long-term diabetes. METHODS: 30 cases in GDM history group, 29 cases in abnormal oral glucose tolerance test(OGTT) history group, and 38 cases in control Group were followed up to undergo fasting blood sugar test and 75 g glucose load test, and to measure their insulin levels. All the cases had no long-term diabetes. RESULT: (1) the blood glucose levels at 2 hour in GDM history group and abnormal OGTT history group were higher than that in control group especially the former, which was very significantly higher (P < 0.001). (2) The insulin at 2 hours in GDM history group was higher than that in control group (P = 0.00067). CONCLUSION: Though women with GDM history do not have long-term diabetes, insulin resistance still exists, postings a possible sign for future diabetes attack.

Adult↗

[A study of interferon alpha-2b as an accessory drug after glaucoma filtration surgery].

OBJECTIVE: To elucidate the inhibitory action of interferon alpha-2b (IFN alpha-2b) on the cicatrization under conjunctiva and the best way to use it after glaucoma filtration surgery. METHODS: Immunohistochemical PAP method and image biological system 2000 (IBAS 2000) were utilized to quantitatively analyze the inhibitory effect of IFN alpha-2b on the expression of epidermal growth factor receptor (EGFR) of cultured calf fibroblasts; the effects of IFN alpha-2b on collagen contents in suture-caused cicatrization under conjunctiva and changes of aqueous humor protein after trabeculectomy performed on rabbits have also been observed. RESULTS: IFN alpha-2b reduced the expression of EGFR of cultured bovine fibroblasts at a dose-dependent manner. The relationship between the EGFR and the dosage of IFN alpha-2b is Y = 2953.8 - 554.5 lgx (r = -0.98, P < 0.01). With 4.67 x 10(-5) micromol/L IFN alpha-2b not only reduced about 50% of the collagen in suture-caused cicatrization, but also significantly decreased the protein concentration of aqueous humour 3 and 72 hours after trabeculectomy. CONCLUSION: It is promising that IFN alpha-2b can be used after glaucoma filtration surgery to reduce excessive cicatrization with many advantages compared with antimetabolites.

Animals↗

[Rat retinal ganglion cells in culture].

OBJECTIVE: To establish a culture system for retinal ganglion cells (RGCs) in order to lay a foundation for the experimental research in vitro. METHODS: The retinae of 16 postnatal 2 - 3 day Sprague-Dawley rats were dissected into cell suspension with trypsin digestion. The cell suspension was implanted in 24 well culture plates with a cover slide 1 cm(2) in size and covered with murine tail collagen preplaced in each well (4 x 10(5) cells/well) and cultured under 37 degree C in an incubator with 5% CO(2). The cells were identified by immunocytochemical method with anti-rat Thy -1.1 monoclonal antibody after culture for 1, 3, 5 days, respectively, and the number of RGCs and its axon-growth percentage were counted in each 10-field high power (HP, 200 x) view under light microscope. RESULTS: The RGCs cultured in murine tail collagen tissue grew very well. Some cells possessed axons and some axons connected in networks. The RGC number and its axon-growth percentage were (401 +/- 9) cells/10 HP and (25.34 +/- 0.72)% in 1-day-culture, (351 +/- 6) cells/10 HP and (35.16 +/- 2.22)% in 3-day-culture, (109 +/- 8) cells/10 HP and (69.84 +/- 0.97)% in 5-day-culture, respectively. CONCLUSION: RGCs can be cultured successfully and the murine tail collagen tissue is a good substratum for RGC survival in vitro.

Animals↗

[Relationship of age, sex, body weight, smoking, blood lipids and fibrinolytic activities in healthy subjects].

Relationship of plasma activities of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1(PAI-1) with age, sex, body weight, smoking, blood lipids were studied in 131 healthy subjects. The results demonstrated that plasma PAI-1 activity increased with age and body weight. PAI-1/t-PA ratio was higher in smoking than in non-smoking subjects. With multivariate analyses, plasma PAI-1 activity was positively correlated with age, body weight index(BMI) in males, and positively correlated with low-density-lipoprotein-cholesterol(LDL) in females, and negatively correlated with plasma tPA activity. Plasma triglyceride, high-density-lipoprotein-cholesterol did not show a correlation to PAI-1 or tPA activity. It is indicated that age, BMI, blood lipids may contribute to moderate fibrinolytic activities and that smoking may affect fibrinolytic function.

Adult↗

[Plasma Lp (a) levels and correlation of Lp (a) with fibrinolysis activation in chronic renal failure].

Plasma Lp (a) concentration and activation of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1(PAI-1) were determined in 50 patients with chronic renal failure (CRF) and in 50 healthy subjects. The results demonstrated that plasma concentration of Lp(a) was significantly higher and plasma t-PA activation was significantly lower in CRF patients than in healthy subjects. With multivariate analyses, plasma Lp(a) concentration was positively correlated with the total amount of 24 h uric protein, plasma BUN and uric protein concentration. Moreover, a negative significant correlation between plasma Lp(a) levels and t-PA activation was observed. Plasma Lp(a) levels did not show a correlation to PAI-1 activation. It is indicated that renal function may contribute to moderate plasma Lp(a) concentration and elevated Lp(a) levels may be related with fibrinolytic impairment.

Adult↗

[Study on the separation of Co2+ from Cu2+, Cd2+, Mn2+, Zn2+ and Fe3+ by extraction chromatography].

In this paper, extraction chromatography by which Co2+ can be separated from Cu2+, Cd2+, Mn2+, Zn2+, Fe3+ is developed. The chromatographic column was 17 mm i.d. x 520 mm, containing polymers synthesized by styrene, divinylbenzene and P204 (volume fraction was 40%), with particle size of 100-200 mesh. The effects of transformation of P204 from the H(+)-form to the Na(+)-form by NaAc solution, the eluent acidity, and eluent composition were investigated. The results indicated that this extraction chromatographic method is good to separate Co2+ from Cu2+, Cd2+, Mn2+, Zn2+ and Fe3+, and the condition of separation is simple and convenient. When the P204 is transformed from the H(+)-form to the Na(+)-form by pH 4.0 NaAc (0.5 mol/L), and the column is eluted with pH 2.5 ClCHCOOH-ClCHCOONa (0.1 mol/L), the separation can be completed effectively.

English Abstract↗

Co- and posttranslational translocation mechanisms direct cystic fibrosis transmembrane conductance regulator N terminus transmembrane assembly.

Transmembrane topology of most eukaryotic polytopic proteins is established cotranslationally at the endoplasmic reticulum membrane through the action of alternating signal and stop transfer sequences. Here we demonstrate that the cystic fibrosis transmembrane conductance regulator (CFTR) achieves its N terminus topology through a variation of this mechanism that involves both co- and posttranslational translocation events. Using a series of defined chimeric and truncated proteins expressed in a reticulocyte lysate system, we have identified two topogenic determinants encoded within the first (TM1) and second (TM2) membrane-spanning segments of CFTR. Each sequence independently (i) directed endoplasmic reticulum targeting, (ii) translocated appropriate flanking residues, and (iii) achieved its proper membrane-spanning orientation. Signal sequence activity of TM1, however, was inefficient due to the presence of two charged residues, Glu92 and Lys95, located within its hydrophobic core. As a result, TM1 was able to direct correct topology for less than half of nascent CFTR chains. In contrast to TM1, TM2 signal sequence activity was both efficient and specific. Even in the absence of a functional TM1 signal sequence, TM2 was able to direct CFTR N terminus topology through a ribosome-dependent posttranslational mechanism. Mutating charged residues Glu92 and Lys95 to alanine improved TM1 signal sequence activity as well as the ability of TM1 to independently direct CFTR N terminus topology. Thus, a single functional signal sequence in either the first or second TM segment was sufficient for directing proper CFTR topology. These results identify two distinct and redundant translocation pathways for CFTR N terminus transmembrane assembly and support a model in which TM2 functions to ensure correct topology of CFTR chains that fail to translocate via TM1. This novel arrangement of topogenic information provides an alternative to conventional cotranslational pathways of polytopic protein biogenesis.

Amino Acid Sequence↗

Dual UV-absorbing background electrolytes for simultaneous separation and detection of small cations and anions by capillary zone electrophoresis.

The simultaneous separation and detection of small cations and anions by capillary zone electrophoresis (CZE) with indirect ultraviolet (UV) detection was successfully demonstrated in a background electrolyte (BGE) containing two UV-absorbing components. Benzylamine, imidazole, benzenesulfonic acid, sulfosalicylic acid, and pyromellitic acid were tested as the components of the BGE. The success of the simultaneous separation of the cations and anions is dependent upon the proper selection of the electrolyte components and control of the migration of the ions towards the detector. High pH is beneficial to the detection of anionic analytes but not to the separation of cationic analytes because of large electroosmotic flow produced under this condition. The upper pH limit of the working pH range is confined by the pKa value of the cationic component of the BGE. The influence of pH and total electrolyte concentration on the electroosmatic flow (EOF) counteracted each other. This counteraction effect imposes an upper limit on the change of total electrolyte concentration at certain pH. It was found that the EOF should be larger by at least 10 x 10(-5) cm2V(-1)s(-1) than the electrophoretic mobilities of the anions so that the anions could be detected on the cathodic side within reasonable times and with good peak shapes. In the imidazole-sulfosalicylic acid BGE, the detection limits (signal to noise, S/N = 3) for the cations and anions ranged from 100 to 900 ppb. In the benzylamine-pyromellitic acid BGE, K+, Na+, Li+, CH3 COO-, HPO4(2-), F-, ClO3-, ClO4-, NO3-, NO2-, Cl- and SO4(2-) were separated within twelve minutes. The strategies for selection of the electrolyte components of the binary BGE were also discussed.

Acetic Acid↗

Mutations in hepatitis B DNA polymerase associated with resistance to lamivudine do not confer resistance to adefovir in vitro.

To determine whether adefovir is active against lamivudine-resistant hepatitis B virus (HBV), the inhibition constants of adefovir diphosphate and lamivudine triphosphate for wild-type and mutant human HBV DNA polymerases, which contain amino acid substitutions associated with lamivudine resistance, were compared. Recombinant wild-type and mutant human HBV DNA polymerases were expressed and substantially purified using a baculovirus expression system and immunoaffinity chromatography. HBV DNA polymerase mutants M552I, M552V, and L528M/M552V showed resistance to lamivudine triphosphate with inhibition constants (Ki) increased by 8.0-fold, 19.6-fold, and 25.2-fold compared with that of wild-type HBV DNA polymerase. However, these mutants remained sensitive to adefovir diphosphate with the inhibition constants increasing by 1.3-fold and 2.2-fold or decreasing by 0.79-fold. The L528M single mutation, identified in patients with increasing HBV DNA levels during therapy with famciclovir, also remained sensitive to adefovir diphosphate with the inhibition constant increased by only 2.3-fold.

Adenine↗

The inhibitory effects of IFN alpha-2b on EGFR expression and growth of cultured subconjunctival fibroblasts.

To investigate to what extent the growth of cultured subconjunctival fibroblasts was regulated by epidermal growth factor receptor (EGFR), we observed the expression of EGFR inhibited by interferon alpha-2b (IFN alpha-2b) and determined the growth of cultured subconjunctival fibroblasts by immunohistochemical and MTT methods. The linear relationships between the concentration of IFN alpha-2b and EGFR expression or growth were y = 1252.7-554.61 lgx (r = -0.98, P < 0.01), y = 0.523-0.0421 lgx (r = -0.93, P < 0.05) respectively. The concentration of IFN alpha-2b at doubled IC50 to EGFR (6.55 x 10(3) IU/ml) only inhibited the cell growth by 25.13%. The results suggested that the growth of subconjunctival fibroblasts may be controlled by many other growth factors because it was only partially inhibited by decreasing EGFR expression.

Animals↗

Hodgkin disease: use of Tl-201 to monitor mediastinal involvement after treatment.

PURPOSE: To compare thallium-201 scintigraphy with gallium-67 scintigraphy in the detection of residual or recurrent mediastinal Hodgkin disease after treatment. MATERIALS AND METHODS: The authors performed planar Ga-67 and Tl-201 scintigraphy in 39 patients aged 7-18 years (27 with mediastinal primary disease) after primary treatment. These scans and those in a control group of 14 patients with newly diagnosed known mediastinal Hodgkin disease were evaluated independently by two radiologists for abnormal mediastinal activity. Results were compared with chest computed tomographic (CT) findings and with the clinical criteria of disease status. Interobserver agreement and consensus agreement on gallium and thallium scan findings were evaluated with the kappa statistic, and the specificity of the two imaging methods was analyzed. RESULTS: All study patients were judged to be free of mediastinal disease with CT and the clinical criteria. Interobserver agreement on findings in the treated and control patients was stronger with gallium scintigraphy (kappa +/- SD = 0.956 +/- 0.044) than with thallium scintigraphy (kappa = 0.638 +/- 0.110). Specificity of ratings based on thallium (85% +/- 6) and gallium (90% +/- 5) scintigraphic findings of mediastinal disease did not differ significantly (P = .48). Specificity improved when the results of the two examinations were combined (97% +/- 2). CONCLUSION: Thallium scintigraphy can help to predict the absence of mediastinal Hodgkin disease after treatment.

Adolescent↗

Identification of novel factors that regulate GnRH gene expression and neuronal migration.

We used differential display PCR on two GnRH producing cell lines to identify genes involved in GnRH gene expression and neuronal migration. RNA from Gn10 cells (derived from a tumor in the olfactory area when GnRH neurons are migrating and make low levels of GnRH) and from GT1-7 cells (derived from a tumor in forebrain when GnRH neurons are postmigratory and make high levels of GnRH) was reverse transcribed into cDNA. The cDNA was amplified using three anchored primers and eight random primers from each cell line and products from duplicate reactions electrophoresed in parallel in a denaturing acrylamide gel. Differentially expressed cDNAs were excised, reamplified and used as probes in Northern analysis of total RNA from each cell line to confirm differentially expressed RNA. The cDNAs were sequenced and compared to the Genbank database. Four of five clones isolated from GT1-7 GnRH neurons are novel, while four of five clones isolated from Gn10 cells have homology to known DNA sequences. One clone, Gn8-01 encodes adhesion related kinase (Ark), a molecule that has an N-terminal domain characteristic of cell adhesion molecules and whose kinase domain may play a role in protection from apoptosis. Together these data support the usefulness of the technique to identify novel genes that play a role in the control of GnRH expression and neuronal migration.

Apoptosis↗

[Relationship of lipoprotein(a) to fibrinolytic activities in healthy subjects].

Plasma tissue-type plasminogen activator(tPA) and plasminogen activator inhibitor(PAI-1) and lipoprotein(a) [Lp(a)] in 133 healthy subjects were determined. The results demonstrated that PAI-1 activity was higher in Lp(a) > or = 0.3 g.L-1 group than Lp(a) < 0.3 g.L-1 group (P < 0.05). Univariate statistical analyses showed Lp(a) concentration was positively associated with PAI-1 activity (P < 0.01), but not with age, sex, body mass index, blood lipids or tPA activity.

Adult↗

Clinical trial designs based on sequential conditional probability ratio tests and reverse stochastic curtailing.

We propose a group sequential method based on the sequential conditional probability ratio test and show that it has the conservatism desired in practice. We also propose calculating the discordant probability, that is, the probability that the sequential test concludes differently from a fixed-sample test at the planned end of the trial, recognizing that this probability could be substantial, even if the sequential test has the same size and power as the fixed-sample size test at the planned end of the study. In addition, we show that the proposed method can be used as a stochastic curtailing tool. Thus, the method accommodates unplanned interim analyses as well as those deemed necessary based on data trends, virtually without inflating the type I error, but it is less conservative than the usual stochastic curtailing. The method is implemented through an interactive computer program.

Adrenergic beta-Antagonists↗

HER2/Neu and the Ets transcription activator PEA3 are coordinately upregulated in human breast cancer.

HER2/Neu is overexpressed in 25-30% of all human breast cancers as a result of both gene amplification and enhanced transcription. Transcriptional upregulation of HER2/neu leads to a 6-8-fold increased abundance of its mRNA per gene copy and likely results from the elevated activity of transcription factors acting on the HER2/neu promoter. Here we report that transcripts of PEA3, an ETS transcription factor implicated in oncogenesis, were increased in 93% of HER2/Neu-overexpressing human breast tumor samples. Analyses to uncover the molecular basis for elevated PEA3 transcripts in HER2/Neu-positive breast tumors revealed that the HER2/Neu receptor tyrosine kinase initiated an intracellular signaling cascade resulting in increased PEA3 transcriptional activity; transcriptionally-activated PEA3 stimulated HER2/neu and PEA3 gene transcription by binding to sites in the promoters of these genes. PEA3 also activates transcription of genes encoding matrix-degrading proteinases, enzymes required for tumor cell migration and invasion. These findings implicate PEA3 in the initiation and progression of HER2/Neu positive breast cancer, and suggest that PEA3 and signaling proteins affecting its regulation are appropriate therapeutic targets.

Animals↗

Structural cues involved in endoplasmic reticulum degradation of G85E and G91R mutant cystic fibrosis transmembrane conductance regulator.

Abnormal folding of mutant cystic fibrosis transmembrane conductance regulator (CFTR) and subsequent degradation in the endoplasmic reticulum is the basis for most cases of cystic fibrosis. Structural differences between wild-type (WT) and mutant proteins, however, remain unknown. Here we examine the intracellular trafficking, degradation, and transmembrane topology of two mutant CFTR proteins, G85E and G91R, each of which contains an additional charged residue within the first putative transmembrane helix (TM1). In microinjected Xenopus laevis oocytes, these mutations markedly disrupted CFTR plasma membrane chloride channel activity. G85E and G91R mutants (but not a conservative mutant, G91A) failed to acquire complex N-linked carbohydrates, and were rapidly degraded before reaching the Golgi complex thus exhibiting a trafficking phenotype similar to DeltaF508 CFTR. Topologic analysis revealed that neither G85E nor G91R mutations disrupted CFTR NH2 terminus transmembrane topology. Instead, WT as well as mutant TM1 spanned the membrane in the predicted C-trans (type II) orientation, and residues 85E and 91R were localized within or adjacent to the plane of the lipid bilayer. To understand how these charged residues might provide structural cues for ER degradation, we examined the stability of WT, G85E, and G91R CFTR proteins truncated at codons 188, 393, 589, or 836 (after TM2, TM6, the first nucleotide binding domain, or the R domain, respectively). These results indicated that G85E and G91R mutations affected CFTR folding, not by gross disruption of transmembrane assembly, but rather through insertion of a charged residue within the plane of the bilayer, which in turn influenced higher order tertiary structure.

Animals↗