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Biomedical subjects

G Sun

Publications and source records attributed to G Sun.

At least 163 records · Page 9Linked to original sources

Eotaxin expression and eosinophilic inflammation in asthma.

Asthma is a chronic inflammatory disease of the airways characterized by a marked infiltration of eosinophils in the bronchial mucosa, and the mechanisms that cause the selective recruitment of these cells are areas of active investigation. In this study, we found increased expression of the eosinophil chemoattractant eotaxin in bronchial mucosa of asthmatic patients. The increase in number of cells expressing eotaxin mRNA correlated with the number of eosinophils in the bronchial tissue and with two major clinical and functional indices of disease severity, suggesting that eotaxin is involved in the recruitment of eosinophils and in eosinophil-induced tissue damage in asthma. Cell sources of eotaxin were bronchial epithelial cells, T lymphocytes, macrophages and eosinophils themselves. The use of drugs that interfere with eotaxin synthesis and function may represent a more specific approach in asthma treatment.

Asthma↗

The allergen Der p1 induces NF-kappaB activation through interference with IkappaB alpha function in asthmatic bronchial epithelial cells.

Asthma is an inflammatory disease of the airways due to an interaction between genetic and environmental factors, and allergy represents the most important predisposing trait. Here, we investigated why and how the allergen most often implicated in the pathogenesis of asthma and other allergic diseases causes the expression of the genes for proinflammatory cytokines in airway epithelium. We found that Der p1 promotes activation of transcriptional factor NF-kappaB by interference with the function of its cytoplasmic inhibitor IkappaB alpha. This is the first report on the effect of an allergen on transcriptional factors. Our results improve the understanding of the mechanisms involved in allergic diseases and suggest potential therapeutic utility of NF-kappaB blockers.

Adult↗

Csk phosphorylation and inactivation in vitro by the cAMP-dependent protein kinase.

Csk is a protein tyrosine kinase that phosphorylates other protein tyrosine kinases of the Src family and down-regulates their activities. It is not known how Csk is regulated. We investigated the possibility that Csk is regulated through phosphorylation by examining if Csk can serve as an in vitro substrate for a panel of protein kinases. We found that Csk was phosphorylated by the cAMP-dependent protein kinase (PKA), but not by protein kinase C, Src, or the fibroblast growth factor receptor kinase. Csk phosphorylation in vitro by PKA is on a serine residue(s) and can reach a stoichiometry of approximately 0.6 mol phosphate per mole of enzyme. Furthermore, incubation with PKA in the presence of ATP and magnesium ion results in a time-dependent decrease in Csk kinase activity. A six-fold decrease in Csk activity (expressed as Vmax/Km ratio) was achieved due to a threefold increase in its Km and a twofold decrease in its Vmax value within 1 h of incubation with the catalytic subunit of PKA and ATP-Mg. Both phosphorylation and inactivation by PKA were blocked by a PKA-specific inhibitor. Csk mutants with a deleted SH2 or SH3 domain retained their ability to be phosphorylated and inactivated by PKA, indicating that the phosphorylation site is located within the catalytic domain. These studies suggest that the cAMP-dependent protein kinase can regulate Csk activity.

Amino Acid Sequence↗

Requirement for an additional divalent metal cation to activate protein tyrosine kinases.

In addition to the magnesium ion needed to form the true phosphate-donating substrate (ATP-Mg complex), we have determined that at least one additional Mg2+ ion is essential for the activation of protein tyrosine kinases. This activation was investigated in detail using purified Csk, Src, and the fibroblast growth factor receptor kinase, which led to the following conclusions. (1) The catalytic activity of these kinases is dependent on the Mg2+ concentration present in the assay, approaching saturation at 5-8 mM MgCl2, while ATP was saturated at approximately 1 mM MgCl2. (2) Extrapolation to zero free Mg2+ at a constant ATP-Mg concentration predicts zero activity, suggesting that free magnesium ion in excess of that needed to bind to ATP is essential for the activation of these enzymes. (3) The free magnesium ion activates Csk and Src kinase activity by increasing the Vmax but does not change their apparent Km(ATP-Mg). In contrast, the free magnesium ion activates the fibroblast growth factor receptor kinase activity by increasing its Vmax and decreasing its apparent Km(ATP-Mg). These and previous studies with the insulin receptor tyrosine kinase suggest that receptor-type protein tyrosine kinases respond to the concentration of free Mg2+ differently than soluble protein tyrosine kinases. (4) With the phosphate-accepting substrate as the variable ligand, increases in the concentration of free Mg2+ resulted in increases in the apparent Vmax for all tyrosine kinases examined, but the apparent Km response is dependent on the enzyme and the substrate used. While these studies do not pinpoint a single kinetic mechanism, they do suggest that additional magnesium ion(s) is(are) an essential activator for protein tyrosine kinases in addition to being a part of the ATP-Mg complex. The difference among protein tyrosine kinases in their kinetic response to the additional divalent metal cation and the potential biological significance of such are discussed.

Adenosine Triphosphate↗

Antiestrogenic activities of alternate-substituted polychlorinated dibenzofurans in MCF-7 human breast cancer cells.

PURPOSE: 1,3,6,8-Substituted alkyl polychlorinated dibenzofurans (PCDFs), typified by 6-methyl-1,3,8-triCDF (MCDF), inhibit 17 beta-estradiol (E2)-induced responses in the rodent uterus and human breast cancer cells. The major purpose of the experiments reported here was to determine the structure-dependent antiestrogenic activities of several alternate-substituted (1,3,6,8- and 2,4,6,8-) PCDFs. METHODS: The antiestrogenic activities were determined in MCF-7 human breast cancer cells using two assays, that is E2-induced cell proliferation and induction of chloramphenicol acetyl transferase (CAT) activity in cells transiently transfected with the E2-responsive Vit-CAT plasmid. RESULTS: MCDF (10(-5) M), 6-isopropyl-1,3,8-triCDF, 6-ethyl-1,3,8-triCDF, 3-isopropyl-6-methyl-1,8-diCDF, and 6-methyl-2,4,8-triCDF, inhibited both E2-induced cell proliferation and CAT activity in MCF-7 cells. All of the remaining ten congeners inhibited either E2-induced cell proliferation or CAT activity, but not both responses. CONCLUSIONS: The antiestrogenic activity of the alternate-substituted PCDFs involves interactions between the aryl hydrocarbon and estrogen receptor signaling pathways. Although these compounds exhibited antiestrogenic activity in MCF-7 cells, the effects of individual congeners were response-specific, and there were no apparent structure-activity relationships.

Benzofurans↗

Inactivation of rotavirus by new polymeric water disinfectants.

Two new insoluble polymeric materials were evaluated for their efficacies in inactivating rotavirus in flowing water in a biocidal filter application. The two polymers are N-chloro and N-bromo derivatives of a poly-styrene hydantoin prepared from commercial poly-styrene. The studies were conducted for rotavirus in halogen demand-free water at pH 7.0, 25 degrees C and Environmental Protection Agency (EPA) Test Water no. 2 at pH 9.0, 4 degrees C which contained heavy halogen demand. The range of flow rates studied was 0.16-1.22 ml s-1 corresponding to contact times in the range of 4-24 s. Both of the polymers were effective in inactivating rotavirus, the N-bromo derivative providing a 4-6 log reduction under the test conditions. The materials may be useful as supplemental filters for hand-held water purification units.

Disinfectants↗

Endothelin-1 induces bronchial myofibroblast differentiation.

Endothelin-1 may contribute to bronchial smooth muscle constriction and airway remodelling in asthma, where bronchial epithelial cells represent an important source of this peptide. We report here that asthmatic bronchial epithelial cells exposed to allergens in vitro induce the differentiation of airway fibroblasts into myofibroblasts, and that they do so through a granulocyte/macrophage colony-stimulating factor-mediated upregulation of endothelin-1 production. By this mechanism bronchial epithelial cells may participate in the genesis of bronchial subepithelial fibrosis, a process which contributes to airway narrowing in asthma.

Actins↗

[Treatment of congenital eyelid syndrome (CES)].

According to our observation and treatment on 21 CES cases, they could be divided into two types, and the distinction was the developing condition of palpebral tissues. Beside the two stage technique to treat 13 CES cases, the one stage technique was also used to treat 8 CES cases by modification of the management of medial canthal ligament, e.g. partially shortening the lateral part of the superficial head of medial canthal ligament. The key is the amount of the horizontal tension of upper eyelid subsequent to medial canthoplasty. The follow-up time was 7 years. Comparing the pre- and post-operative examination results of both one stage and two stage techniques, it was shown that both of them could achieve the goals of enlarging the eyelid fissure and completely elevating the upper eyelid.

Adult↗

[Applied anatomy of the submental vessels and submental flaps].

To search ideal flaps for facial defect repair, the authors performed dissection in the submental region of 20 cadavers. Different methods were used in the anatomic study. It is concluded that 1. there is a submental artery and two concomitant veins on each side of the submental region; 2. four types of flaps can be formed; 3. the flap can be transferred as a free or pedicled flap; 4. while creating the flap, the anterior belly of the bigastric muscle should be included and the branches of the facial nerve and inferior alveolar nerve must be protected. With the well-matched color and texture, the flap of the submental region is suitable for facial defect repair.

Arteries↗

[Treatment of atrial fibrillation using maze procedure by radiofrequency ablation].

From May 1994 to May 1996, 20 cases of atrial fibrillation were treated by means of Maze procedure by radiofrequenncy ablation, at the same time 19 cases of these patients were complicated with rheumatic heart valve disease and valve replacement operations were perfomned, in the other case atrial septal defect was repaired. Yoshio Kosakai's operation route was adopted in radiofrequency ablation procedure. After operation 16 patients of atrial fibrillation resumed sinus rhythm (80%), in 4 casess of atrial fibrillation sinus rhythm was unsuccessfully restored, two patients remained atrial fibrillation, one patient was of atrial flutter, the other was of nodal rhythm. Short time was needed in radiofrequency ablation Maze procedure, average time increase of aortic clamping was 20.5 minutes, and there was no danger of hemorrhage related to this kinds of Maze procedure. During 7-10 days after operation, there appeared superventricular arrhythmia which might be related to ill-distribution of radiofrequency ablation, and interference of atrial electric activity.

Adult↗

[Application of Apo B 3' DNA polymorphisms in forensic science Practice].

Amp-FLP analyses of Apo B 3' VNTR locus in human blood stain, saliva (stain), semen, mixed stain and hair have been carried out. The genotypings have been achieved. The genotypes of Apo B 3' locus can be detected accurately in blood stains kept at room temperature within 15 weeks and at -20 degrees C within two years. In a series of paternity testing on 34 cases, 8 false alleged fathers were excluded; of them, 6 were excluded by Apo B 3' locus alone or by Apo B 3' locus combined with other genetic markers. 3 rape cases were investigated; 2 suspects were excluded.

Apolipoproteins B↗

[The application of D1S80 locus analysis to forensic problems by using Amp-FLP technique].

This is a paper on paternity testing in 85 test cases and the identification of individuals from mixed stains of semen and vaginal secretion in two rape cases. We used primers flanking the hypervariable region of the D1S80 gene to amplify DNA extracted from fresh blood, blood stain, saliva stain, semen stain, mixed stain in vaginal swab, and from fetal tissues. The results revealed that 35 out of 85 alleged fathers in 85 paternity testing cases were excluded. In 30 of the 35 excluded cases, the alleged fathers were excluded by D1S80 locus analysis. The exclusion rate was 35.29%. In 2 of the excluded cases, the alleged fathers were excluded by D1S80 locus analysis only. In 50 nonexcluded paternity testing cases, the paternity index(PI) of D1S80 locus was 2. 0576-111.1111. It indicates that D1S80 locus analysis plays an important role in elevation the relative chance of paternity (RCP) value. In 41 of the 50 nonexcluded cases, RCP was higher that 99.75%. RCP reached 99.300%-99.649% in 9 of cases. In one rape and homicide case, the genotype of D1S80 locus of sperm on the vaginal swab was detected. It gave a clue to investigation. In the other rape case, the genotype of D1S80 of sperm on the vaginal swab was consistent with the blood stain from the suspect. So the suspect was not excluded. Since the D1S80 locus has a high discrimination power it is very useful for forensic individual identification and parentage testing. Some problems have been discussed in this paper.

Blood Stains↗

Mutations identified in exon 7 of phenylalanine hydroxylase gene in Chinese.

Exon 7 of the phenylalanine hydroxylase (PAH) gene was analyzed in 45 children affected with classic phenylketonuria (PKU) from northern China by using PCR-single strand conformation polymorphism (PCR-SSCP) technique and DNA direct sequencing. Six missense mutations(i.e. R243Q, R241H, G247V, L249H, F2541 and G257V) and one silent mutation (V245v) were identified. The latter three missense mutations were demonstrated as novel mutations in comparison with the PAH mutation database. One missense mutation (R241H) was first documented in Chinese. Our results showed population and region differences in the PAH mutation distribution, and suggest that there is more than one founding population for PKU in China. The finding of novel mutations will enhence the molecular diagnosis of PKU.

Asian People↗

[Experimental comparison of two coxsackievirus B3 variants in murine myocardial cells].

There is lack of direct evidence whether the myocarditis can be induced by CVB3o. The two coxsackievirus B3 variants were used to infected murine myocardial cells. The results showed that: (1) In culture medium of murine myocardial cells infected with two variants, it did not show much differences in titers at 12 and 24 hours between CVB3o and CVB3m. (2) The two variants could all induce the death of myocardium, but with the elapse of time, the cell death rate of CVB3m infected cells was much higher than CVB3o. (3) CVB3o could not block the myocardial cells from infection by CVB3m. It is concluded that myocardial cells can be infected by CVB3o, but the degree of infection is lower than CVB3m.

Animals↗

[Serum G-CSF levels in patients with chronic aplastic anemia].

OBJECTIVE: To explore the pathogenesis of aplastic anemia. METHODS: The spleen cells of BALB/c miceimmunized with rhG-CSF were fused with myeloma cell line SP2/0. Three murine hybridomas producing monoclonal antibody (McAb) against rhG-CSF were obtained. Serum levels of G-CSF in 54 cases of chronic aplastic anemia (CAA) were detected by ELISA method. RESULTS: Serum G-CSF levels in 70.4% (38 of 54 cases) of the CAA patients were increased (272.76 +/- 58.39ng/L). There was a negative correlation between blood neutrophil counts and serum G-CSF levels (r = -0.535, P<0.01). CFU-GM were detected in 12 cases of CAA, and all was decreased (17.92 +/- 10.28/2 x 10(5) nucleated cell). Serum G-CSF levels in almost 30% (12 of 54 cases) of the CAA patients were not increased. CONCLUSION: The hematopoietic progenitor cells of CAA patients were impaired, and some CAA could be treated with rhG-CSF and immunosuppressive agents.

Adult↗

[In vitro study on the effects of the novel retinoids on the proliferation and differentiation of normal and leukemic cells].

OBJECTIVE: To evaluate the prospect for clinical use of four novel retinoid compounds (retinoid 1, retinoid 2, retinoid 3 and retinoid 4), which were different structurally from all-trans retinoic acid. METHODS: The effects of the four retinoids on the differentiation and clonal proliferation of NB4 cells and fresh acute promyelocytic leukemia (APL) cells and on the proliferation of normal hematopoietic cells were studied. Cell morphological examination,nitro tetrazolium blue reduction test, cell cycle dynamics, and colony formation assay were used in the study. RESULTS: Novel retinoids induced differentiation of NB4 and fresh APL cells, and markedly inhibited CFU-L growth of NB4 and fresh APL cells. The activity related to their chemical structures and retinoid 2 was more active. The novel retinoids enhanced the growth of CFU-GM, CFU-E and CFU--Meg of normal bone marrow cells. CONCLUSION: These novel retinoids, especially retinoid 2, may regulate the proliferation and differentiation of normal hematopoiesis, induce APL cell differentiation and maturation, and are worthy of further study for clinical use.

Cell Differentiation↗

[Reversal of drug resistance in multidrug resistant tumor cells by an oligomer complementary to the MDR1 gene].

OBJECTIVE: To overcome the multidrug resistance (MDR) in tumor cells. METHODS: Human drug resistant cell line KB-8-5 was transfected with a synthetic oligodeoxynucleotide complementary to the 5' end region of MDR1 gene (ODN). In vitro drug sensitivity was measured by MTT assay. Intracellular drug concentration was assessed by flow cytometric analysis and expression of P-glycoprotein (Pgp) was determined by immunohistochemistry method. RESULTS: The administration of ODN for 72 hours increased daunorubicin (DNR) accumulation and decreased Pgp expression in KB-8-5 cells. Incomplete reversal of MDR in the KB-8-5 cells was observed when lipofectin was used to deliver ODN to the cells. Lipofectin enhanced the reversing activity, and approximately 74.43% of the cells lost their resistance to DNR. CONCLUSION: ODN circumvents resistance in the KB-8-5 cells may be ascribed to the reduced expression of Pgp in the cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗