Search PubMed⌕ Search

Biomedical subjects

H Xu

Publications and source records attributed to H Xu.

At least 361 records · Page 20Linked to original sources
PubMed1999

FOG-2, a heart- and brain-enriched cofactor for GATA transcription factors.

Members of the GATA family of zinc finger transcription factors have been shown to play important roles in the control of gene expression in a variety of cell types. GATA-1, -2, and -3 are expressed primarily in hematopoietic cell lineages and are required for proliferation and differentiation of multiple hematopoietic cell types, whereas GATA-4, -5, and -6 are expressed in the heart, where they activate cardiac muscle structural genes. Friend of GATA-1 (FOG) is a multitype zinc finger protein that interacts with GATA-1 and serves as a cofactor for GATA-1-mediated transcription. FOG is coexpressed with GATA-1 in developing erythroid and megakaryocyte cell lineages and cooperates with GATA-1 to control erythropoiesis. We describe a novel FOG-related factor, FOG-2, that is expressed predominantly in the developing and adult heart, brain, and testis. FOG-2 interacts with GATA factors, and interaction of GATA-4 and FOG-2 results in either synergistic activation or repression of GATA-dependent cardiac promoters, depending on the specific promoter and the cell type in which they are tested. The properties of FOG-2 suggest its involvement in the control of cardiac and neural gene expression by GATA transcription factors.

Amino Acid Sequence↗
PubMed1999

Differential regulation of renal sodium-phosphate transporter by glucocorticoids during rat ontogeny.

The effects of chronic administration of methylprednisolone (MP) were studied on the ontogeny of the renal type II Na-P(i) transporter (NaPi-2). Immunoblot analysis showed that MP did not alter the expression of NaPi-2 protein levels in suckling and weanling rats; however, there was an approximately 50% decrease in adolescent and adult rats. There was no change in Na-dependent P(i) uptake in brush-border membrane vesicles in suckling rats, but there was an almost twofold decrease in adolescent rats induced by MP treatment. MP administration did not alter mRNA levels in suckling or adolescent rats. Dual injections with the glucocorticoid receptor blocker RU-486 (mifepristone) and MP did not reverse the downregulation of NaPi-2 immunoreactive protein levels in adolescent rats. To control for RU-486 antagonism efficiency, Na/H exchanger isoform 3 (NHE3) protein levels were also assayed after injection with RU-486 and MP. As expected, NHE3 protein levels increased after MP injection; however, the increase was blocked in adolescent rats by RU-486. We conclude that there is an age-dependent responsiveness to glucocorticoids and that the marked decrease in NaPi-2 immunoreactive protein levels and activity in adolescent rats is due to posttranscriptional mechanisms.

Actins↗
PubMed1999

Enhanced beta-receptor-mediated vasorelaxation in hypoxic porcine coronary artery.

To investigate the beta-adrenoceptor-mediated responses in hypoxic coronary arteries, we studied the effect of isoproterenol (Iso) on isolated porcine coronary arteries contracted with endothelin-1 in media aerated with 0, 5, 7.5, and 95% O(2). The concentration-response curve of Iso was significantly shifted to the left by hypoxia (0 and 5% O(2)). In oxygenated and hypoxic arteries, 3 x 10(-8), 10(-6), and 10(-5) M Iso significantly increased the contents of cAMP. However, there was no difference in the increases of cAMP content induced by 3 x 10(-8) M Iso between oxygenated and hypoxic arteries. The content of cAMP induced by high concentrations of Iso (10(-6) and 10(-5) M) was significantly larger in hypoxic than in oxygenated arteries. Furthermore, the potentiation by hypoxia of the Iso-induced vasorelaxation was inhibited by glibenclamide and depolarization by KCl, but not by removal of endothelium and indomethacin. The vasodilatory response to forskolin and dibutyryl cAMP was unaffected by hypoxia. We conclude that activation of the ATP-sensitive K(+) channel may account for the potentiation of the response to Iso in hypoxic coronary arteries.

Animals↗
PubMed1999

Characterization of cis-elements required for osmotic response of rat Na(+)/H(+) exchanger-2 (NHE-2) gene.

The Na(+)/H(+) exchanger (NHE-2) has been implicated in osmoregulation in the kidney, because it transports Na(+) across the cell membrane and efficiently alters intracellular osmolarity. On hyperosmotic stress, NHE-2 mRNA increases in abundance in mouse inner medullary collecting duct (mIMCD-3) cells, suggesting possible transcriptional regulation. To investigate the molecular mechanism of potential transcriptional regulation of NHE-2 by hyperosmolarity, we have functionally characterized the 5'-flanking region of the gene in mIMCD-3 cells. Transient transfection of luciferase reporter gene constructs revealed a novel cis-acting element, which we call OsmoE (osmotic-responsive element, bp -808 to -791, GGGCCAGTTGGCGCTGGG), and a TonE-like element (tonicity-responsive element, bp -1201 to -1189, GCTGGAAAACCGA), which together are shown to be responsible for hyperosmotic induction of the NHE-2 gene. Electrophoretic mobility shift assays suggest that different DNA-protein interactions occur between these two osmotic response elements. However, both DNA sequences were shown to specifically bind nuclear proteins that dramatically increase in abundance under hyperosmotic conditions. Isolation of trans-acting factors and characterization of their specific interaction with these osmotic response elements will further elucidate the transcriptional mechanisms controlling NHE-2 gene expression under hyperosmolar conditions.

Animals↗
PubMed1999

Protective effect of the type IV phosphodiesterase inhibitor rolipram in EAU: protection is independent of IL-10-inducing activity.

PURPOSE: Experimental autoimmune uveoretinitis (EAU) is a cell-mediated model of retinal autoimmunity that is negatively regulated by interleukin (IL)-10. The antidepressant drug rolipram, a type IV phosphodiesterase inhibitor, enhances IL-10 production by monocyte/macrophages. The effect of rolipram on induction of EAU and its associated immunologic responses was investigated. METHODS: Mice were challenged for EAU induction by immunization with the retinal antigen interphotoreceptor retinoid-binding protein (IRBP) or by adoptive transfer of uveitogenic T cells and were treated with rolipram. EAU severity and immunologic responses to IRBP were analyzed. In addition, the effect of rolipram added to the culture on antigen-driven responses of primed lymph node cells was tested. RESULTS: Rolipram treatment from days -1 to 7 after immunization (afferent phase) was not protective, but severity of EAU was reduced to 50% by treatment from days 8 to 16 after immunization or when EAU was induced by adoptive transfer (efferent phase). Antigen-specific proliferation and interferon (IFN)-gamma production ex vivo by lymph node cells of protected mice were not reduced. However, the addition of rolipram directly to the culture suppressed IRBP-driven proliferation and IFN-gamma production by primed lymph node cells. Freshly explanted lymph node cells of treated mice showed inhibition of IFN-gamma mRNA but no parallel enhancement of IL-10 mRNA by quantitative polymerase chain reaction. Rolipram inhibited EAU in IL-10 knockout mice equally well compared with controls and suppressed their primed lymph node cells in culture. CONCLUSIONS: Rolipram appears to inhibit the expansion and effector function of uveitogenic T cells, raising the possibility that it may be useful for treatment of established disease. Contrary to expectations based on in vitro studies, the protective effects in vivo appear to be independent of IL-10. The observation that suppression of antigen-specific responses is demonstrable only in the physical presence of the drug suggests that, in a clinical setting, continuous administration of rolipram might be needed to sustain its therapeutic effect.

Adoptive Transfer↗
PubMed1999

Immunosuppressive effects of silicon phthalocyanine photodynamic therapy.

The purpose of this study was to determine if silicon phthalocyanine 4 (Pc 4), a second-generation photosensitizer being evaluated for the photodynamic therapy (PDT) of solid tumors, was immunosuppressive. Mice treated with Pc 4 PDT 3 days before dinitrofluorobenzene sensitization showed significant suppression of their cell-mediated immune response when compared to mice that were not exposed to PDT. The response was dose dependent, required both Pc 4 and light and occurred at a skin site remote from that exposed to the laser. The immunosuppression could not be reversed by in vivo pre-treatment of mice with antibodies to tumor necrosis factor-alpha or interleukin-10. These results provide evidence that induction of cell-mediated immunity is suppressed after Pc 4 PDT. Strategies that prevent PDT-mediated immunosuppression may therefore enhance the efficacy of this therapeutic modality.

Animals↗
PubMed1999

[Linkage analysis of chromosome 5 and asthma in a Chinese population].

OBJECTIVE: To investigate the linkage between asthma and 5q31-33 in a Chinese population. METHODS: The linkage between microsatellite markers in 5q and asthma and allergy was tested by lod score analysis. RESULTS: The linkage between asthma and 5q31-33 was not confirmed. CONCLUSION: The genes at 5q31-33 are not likely to contribute to inheritance of asthma in this Chinese population.

Asthma↗
PubMed1999

Activation of the lama2 gene in muscle regeneration: abortive regeneration in laminin alpha2-deficiency.

Mutations in laminin alpha2, a subunit of the basement membrane protein laminin-2/merosin, cause merosin-deficient congenital muscular dystrophy. To gain insight into the molecular mechanism of disease, we generated and used a mutant mouse, dyW, in which the lacZ gene was inserted into the lama2 gene so that beta-galactosidase would be expressed in place of laminin alpha2. Heterozygous and homozygous mutant mice are normal at birth, but homozygous mice develop muscular dystrophy at 2 to 3 weeks of age. The lama2/lacZ gene was highly expressed in muscle in the early stages of embryonic myogenesis, but was down-regulated at later stages in both heterozygous and homozygous mice. No beta-galactosidase activity was detected in skeletal muscle after birth in adult heterozygous mice. In contrast, high beta-galactosidase activity was detected in postnatal homozygous mice. Induction of injury in heterozygous mice resulted in intense reexpression of beta-galactosidase in the injured muscle early in regeneration, with a decline in enzyme activity as repair of the tissue progressed. Although the initial response to injury was similar in heterozygous and homozygous mice with abundant beta-galactosidase-positive, mononucleated cells in the injured area, repair was rarely completed in the homozygous mice, evidently caused by excessive death of cells associated with immature myofibers. The defect in muscle repair was very efficiently corrected in homozygous dyW mice expressing a human LAMA2 transgene in skeletal muscle. The data show the importance of laminin alpha2 in muscle regeneration and suggest that a major contributor to disease in muscular dystrophy is abortive regeneration.

Animals↗
PubMed1999

[Protein kinase a mediated excitatory adrenergic effect on chronically compressed dorsal root ganglion neurons in rats].

With a model of chronically compressed dorsal root ganglion (CCD), the present study was undertaken to test how the plasticity of sympathetic-sensory coupling is and whether the coupling is mediated by intracellular messenger PKA by analysing extracellularly recorded spontaneous activity of single A-fibers originating from the CCD neurons in vitro. Eighty-five out of 95 neurons from injured DRGs during application of norepinephrine (NE) were adrenosensitive. Among the 85 neurons, 44 exhibited excitation, 21 showing excitation followed by suppression, 6 displaying alternated excitation and suppression, and 14 suppression. In addition, adrenosensitivity was observed in 15 silent injured DRGs. The excitatory effect of NE was blocked by alpha 1 and alpha 2 adrenoceptor antagonists yohimbine (10 mumol/L) or prazosin (5 mumol/L). Rp-cAMPS (50-250 mumol/L, n = 6), a specific inhibitor of PKA, and H-89 (10 mumol/L, n = 6), an inhibitor of PKA catalytic subunit, obviously suppressed the NE-evoked excitation. Furthermore, the excitatory effect of NE was attenuated by SQ 22, 536 (1 mmol/L), an adenylate cyclase inhibitor (n = 6). The above results demonstrate that injury to DRG neuron body triggered the adrenosensitivity, which was mediated by alpha 1, alpha 2 adrenoceptors and PKA.

Adrenergic Fibers↗
PubMed1999

[Pattern and dynamic changes of integer multiples in spontaneous discharge of injured dorsal root ganglion neurons].

For the purpose of the present investigation, spontaneous discharges of dorsal root ganglion (DRG) neurons of the rats, which had undergone 3-10 days' chronic compression, were studied. It was found that the interspike interval (ISI) of 17 out of 156 fibers had integer multiples temporal rhythm pattern, in which all the ISI were integer multiples of a basic ISI and a return map of their ISI could be constructed as a crystal grid structure. This temporal pattern could be modified by Na+ channel and K+ channel on their membranes. These data indicated the presence of some irregular discharge trains with their intrinsic regularity.

Action Potentials↗
PubMed1999

[Preventive effect of endothelin-1 mRNA antisense oligonucleotide on acute myocardial ischemic arrhythmia in rats].

Acute myocardial ischemia was induced by occlusion of the anterior descending of left coronary artery (LAD) in rats; the resultant arrhythmia in 1 h after LAD occlusion was evaluated. In order to prevent expression of endothelin-1 mRNA, human endothelin-1 mRNA antisense oligonucleotide (ET-1 AS-ODN) was intravenously injected 2 h before LAD occlusion. The effect of AS-ODN on plasma ET-1 concentration and the acute ischemic arrhythmia were observed. The results showed that plasma ET-1 was significantly decreased in rats pretreated with AS-ODN, and both the incidence and severity of the acute ischemic arrhythmia were decreased dose-dependently as compared with normal saline control and sense oligonucleotide control, indicating that ET-1 AS-ODN could prevent acute myocardial ischemic arrhythmia and that endogenous endothelin-1 may play an important role in the development of acute ischemic arrhythmia in rats.

Animals↗
PubMed1999

Assessment of serial changes of bone mineral density at lumbar spine and femoral neck before and after liver transplantation.

OBJECTIVE: To assess serial changes of bone mass before and after orthotopic liver transplantation (OLT). METHODS: Consecutive bone mineral density (BMD) of lumbar spine (L2-L4) and femoral neck in 38 patients with chronic liver failure within 2 months before OLT, 6, 12 and 24 months after OLT was determined using dual energy X-ray absorptiometry. RESULTS: 29% of 38 patients before OLT had osteoporosis (BMD below 2 standard deviate). BMD levels at L2-L4 and femoral neck decreased and incidence of osteoporosis increased in the first 6 months after OLT. Over beyond 6 months post-OLT BMD levels at L2-L4 increased to just slightly above the pretransplant level and incidence of osteoporosis decreased from 36.8% (6 months after OLT) to 7.9% (24 months after OLT). Although BMD levels at femoral neck by 12 and 24 months after OLT gradually increased, BMD levels at femoral neck were still lower than those before OLT. CONCLUSIONS: There was already a low bone mass in patients with chronic liver disease before OLT and liver transplantation induced a marked and rapid bone loss.

Adult↗
PubMed1999

[Genetic polymorphisms of homocysteine metabolism related enzymes in patients with coronary heart disease].

OBJECTIVE: To study genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and cystathionine beta-synthase(CBS) T833C related to homocysteine metabolism in patients with coronary heart disease (CHD). METHODS: 209 patients with CHD and 101 controls were selected. MTHFR genetic C677T polymorphism was determined by PCR-RFLP, and CBS T833C polymorphism by ARMS method. Plasma homocysteine levels were detected with HPLC. RESULTS: The frequencies of MTHFR T homogenetic type and heterogenetic type (27.8% and 45.4%) in case group were higher than those in normal group(22.8% and 34.6%). There were significant differences in the frequencies of genotypes and alleles between two groups (P < 0.05). C homogenotype of CBS gene was found in 21 patients, and 2 in the normal group. There were evident differences in the frequencies of genotypes and alleles of the two groups (P < 0.001). Moreover, plama homocysteine levels were markedly higher in patients with MTHFR or CBS genetic mutation than those in patients without mutation (P < 0.05). CONCLUSIONS: Hyperhomocysteinemia is an independent risk factor of CHD. MTHFR and CBS are the main enzymes related to homocysteine metabolism. Their genetic mutations are possibly important mechanism of hyperhomocysteinemia and coronary heart disease.

Adult↗
PubMed1999

[Changes of calcitonin gene-related peptide content in induced sputum from patients with COPD and asthma].

OBJECTIVE: To explore the role of sensory neuropeptide calcitonin gene-related peptide (CGRP) in the pathogenesis of chronic airway inflammatory diseases COPD and bronchial asthma. METHODS: Patients with COPD (n = 19), bronchial asthma (n = 14), all were in stable stage and 10 normal volunteers were examined. After hypertonic saline inhalation challenge in all subjects, CGRP-LI concentration in the induced sputum was measured by radioimmunoassay. Cellular content was assayed by microscopic analysis, the relation between CGRP-LI level and FEV1 value was calculated by linear regression. RESULTS: The sputum CGRP concentrations in patients with COPD and patients with asthma were (15.97 +/- 2.15) ng/L, (18.79 +/- 3.91) ng/L, respectively, both were significantly higher than those in normal volunteers (2.36 +/- 0.35) ng/L. Moreover, CGRP concentrations in induced sputum in each disease group were correlated with the degree of airflow obstruction, r = -0.50 and -0.61, respectively (P < 0.05). The percentage of neutrophil cell count (64.9 +/- 2.9)% was significantly higher in patients with COPD (P < 0.01), while the percentage of eosinophil cell count (5.8 +/- 0.5)% was increased in patients with asthma (P < 0.01). CONCLUSIONS: The data suggested that CGRP release may participate in the chronic inflammation of patients with COPD and bronchial asthma.

Aged↗
PubMed1999

[The study on COPD rat model produced by bacterial infection].

OBJECTIVE: To observe the role of bacterial infection in pathogenesis of COPD. METHODS: The COPD animal model was developed by intranasal repeated injecting Klebsiella pneumoniae(K) or pneumococcal pneumoniae(P) into rat respiratory tract. Histomorphyological changes were observed, PaO2, PaCO2 and right ventricular systolic pressure (RVSP) were analysed. RESULTS: 1 week after injecting K and 4 week after injecting P, the epithelia of bronchioles showed obvious injury. From the 4th week there was severe chronic inflammatory process of bronchioles in 2 experimental groups including thickened wall, narrowed lumen and developed emphysema. In addition, the walls of arterioles accompanying bronchioles were also thickened obviously. Right ventricular systolic pressure raised in 2 experimental groups (P < 0.01). From the 16th week, PaO2 dropped and PaCO2 raised in K group. CONCLUSIONS: Repeated injecting intranasally of the proper amount of klebsiella pneumoniae or pneumococcal pneumoniae into rats' lungs can induce rat small airway inflammation and emphysema. Combining with PaO2, PaCO2 and RVSP analysis, we suggest the model established shows main features of COPD.

Animals↗
PubMed1999

[Changes in [Ca2+]i and IP3 levels in the process of cisplatin-induced apoptosis of gastric carcinoma].

OBJECTIVE: To study the change and significance of intracellular-free calcium levels ([Ca2+]i) and inositol 1, 4, 5-trisphosphate (IP3) levels in the process of gastric carcinoma cell apoptosis induced by cisplatin. METHODS: Apoptosis induced by cisplatin in gastric carcinoma BGC823 cell was investigated by light and electronmicroscopy, agarose gel electrophoresis and flow cytometry. [Ca2+]i was determined by Fura-2 fluorescin load technic, IP3 was determined by competitive protein binding method. RESULTS: When BGC823 cells were treated with cisplatin (2 micrograms/ml) for 24 hours changes appeared typical of apoptosis. [Ca2+]i and IP3 were significantly increased, especially at the initial stage of apoptosis. However, from 2 to 24 hours after cisplatin treatment, IP3 levels progressively decreased, being significantly lower than those of the untreated controls. CONCLUSION: In the process of cisplatin induced apoptosis of gastric carcinoma cells, [Ca2+]i and IP3 levels are up-regulated at the very initial stage but down-regulated from 2 hours afterwards.

Antineoplastic Agents↗
PubMed1999

[Immunohistochemistry and DNA content of gastro-intestinal carcinoid].

OBJECTIVE: To study the relationship between clinical pathology and antigen expression and DNA content of gastrointestinal carcinoid tumors. METHODS: Fifty-two cases of paraffin-embedded gastrointestinal carcinoid specimens were collected. According to Gould's criteria, there were 20 cases of typical carcinoid, 20 cases of atypical carcinoid and 12 cases of undifferentiated carcinoid. Ten different kinds of antigen were examined by immunohistochemical staining and DNA contents by flow cytometry. RESULTS: Calcitonin (CT), carcinoembryonic antigen (CEA) and vasoactive intestinal peptide (VIP) expression was significantly reduced in typical carcionoid compared to that in other two types of carcionoid. Their expression was more marked in progression than in early stage of the disease. VIP expression was significantly higher in patients with than without lymph node metastases. Cellular DNA analysis showed significant difference between the typical and the other two types of carcinoid. Tumors with expression of VIP and CEA were mostly aneuploid. CONCLUSION: To study expression of relevant antigens in gastrointestinal carcinoid in relation to histological type and cellular DNA content helps determine its biologic behavior and prognosis.

Adult↗