Biomedical subjects

X Du

Publications and source records attributed to X Du.

At least 109 records · Page 6Linked to original sources

PubMed1998

Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene.

Mutations of the gene Lps selectively impede lipopolysaccharide (LPS) signal transduction in C3H/HeJ and C57BL/10ScCr mice, rendering them resistant to endotoxin yet highly susceptible to Gram-negative infection. The codominant Lpsd allele of C3H/HeJ mice was shown to correspond to a missense mutation in the third exon of the Toll-like receptor-4 gene (Tlr4), predicted to replace proline with histidine at position 712 of the polypeptide chain. C57BL/10ScCr mice are homozygous for a null mutation of Tlr4. Thus, the mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces the LPS signal across the plasma membrane. Destructive mutations of Tlr4 predispose to the development of Gram-negative sepsis, leaving most aspects of immune function intact.

Amino Acid Sequence↗

PubMed1998

FTIR and UV-Vis Spectroscopic Studies of Black Soap Film.

FTIR and UV-vis spectroscopies have been employed to investigate the self-assembly features of a black soap film (BSF) prepared from aqueous solution consisting of 10(-2) M cetyltrimethylammonium bromide (CTAB) and 10(-3) M thiazole yellow (TY) in the liquid-crystalline and gel states, respectively. The construction of two surfactant monolayers of the soap film is independent of the thickness of aqueous core, and the thickness is approximately 1.7 nm at equilibrium. In the liquid-crystalline state, the methylene segments of the hydrocarbon chains are averagely oriented at an angle of 70 degrees with respect to the film normal, and the alkyl chains take a long-range interaction to improve the film elasticity. The TY molecules in the film are horizontally aligned at the monolayer interface in the J-aggregate form. The double-negatively charged TY aggregate greatly enhances the film stability. Dye neutral red is further introduced into the CTAB soap film, the film lifetime is related to the type of the added dyes, in the order of cationic < nonionic < anionic. Copyright 1998 Academic Press.

Journal Article↗

PubMed1998

Regulation of tyrosine hydroxylase gene expression during transdifferentiation of striatal neurons: changes in transcription factors binding the AP-1 site.

We have shown previously that the synergistic interaction of acidic fibroblast growth factor (aFGF) and a coactivator (dopamine, protein kinase A, or protein kinase C activator) will induce the novel expression of tyrosine hydroxylase (TH) in neurons of the developing striatum. In this study we sought to determine whether, concomitant with TH expression, there were unique changes in transcription factors binding the AP-1 regulatory element on the TH gene. Indeed, we found a significant recruitment of proteins into TH-AP-1 complexes as well as a shift from low- to high-affinity binding. Supershift experiments further revealed dramatic changes in the proteins comprising the AP-1 complexes, including recruitment of the transcriptional activators c-Fos, a novel Fos protein, Fos-B, and Jun-D. Concomitantly, there was a decrease in repressor-type factors ATF-2 and CREM-1. aFGF appeared to play a central but insufficient role, requiring the further participation of at least one of the coactivating substances. Experiments examining the signal transduction pathway involved in mediating these nuclear events demonstrated that the presence of only an FGF (1, 2, 4, 9) competent to induce TH caused the phosphorylation of mitogen-activated protein kinase (MAPK). Moreover, the treatment of cells with MEK/ERK inhibitors (apigenin or PD98059) eliminated TH expression and the associated AP-1 changes, suggesting that MAPK was a critical mediator of these events. We conclude that, during transdifferentiation, signals may be transmitted via MAPK to the TH-AP-1 site to increase activators and reduce repressors, helping to shift the balance in favor of TH gene expression at this and possibly other important regulatory sites on the gene.

1-Methyl-3-isobutylxanthine↗

PubMed1998

[Expression of human SRY gene and the DNA-binding property of its product].

OBJECTIVE: To investigate the role which human SRY gene plays in the regulation of the downstream gene. METHODS: The fragment of SRY (sex determinating region on the Y chromosome) HMG domain was cloned into the expressing vector pET-15b. The hSRY gene recombinant plasmid-pETSY was transformed and expressed in E.coliBL21. The target protein was purified by pET His. Tag system. The DNA-binding retardation test and its competitive reaction were conducted between SRY protein and the fragment of Mullerian inhibiting substance (MIS) promoter. RESULTS: The molecular weight of the expressed hSRY protein was shown to be approximately 21kD. The specific DNA binding property of SRY protein to the fragment of MIS was confirmed in the retardation test and its competitive reaction. CONCLUSION: The results suggest that the product of SRY gene can bind the MIS promoter region and may initiate the transcription of MIS.

DNA-Binding Proteins↗

PubMed1998

Cleavage of the cytoplasmic domain of the integrin beta3 subunit during endothelial cell apoptosis.

In this study, we report that the cytoplasmic domain of the integrin beta3 subunit is a target for limited proteolysis during apoptosis of human umbilical vein endothelial cells. Calpain inhibitors inhibited the cleavage of the beta3 cytoplasmic domain, indicating that calpain is required. Calpain-mediated proteolysis of fodrin was also detected, indicating that calpain is activated during endothelial cell apoptosis. A phosphatase inhibitor, sodium orthovanadate, inhibited endothelial cell apoptosis and cleavage beta3, suggesting that protein dephosphorylation preceded integrin cleavage in the apoptosis signaling pathway. beta3 cleavage was observed in cells that were viable, suggesting that it is an early event and not the consequence of post-death proteolysis. The extent of beta3 cleavage correlated with a loss in the capacity of cells to reattach to matrix proteins. Loss of reattachment capacity during apoptosis was significantly retarded by a calpain inhibitor. As the beta3 cytoplasmic domain is required for integrin signaling and interaction with the cytoskeleton, our results suggest that cleavage in the beta3 cytoplasmic domain by calpain or a calpain-like protease negatively regulates integrin-mediated adhesion, signaling, and cytoskeleton association.

Antigens, CD↗

PubMed1998

Identification of two regions in apolipoprotein B100 that are exposed on the cytosolic side of the endoplasmic reticulum membrane.

Protease protection assays of apolipoprotein B100 (apoB) in digitonin-permeabilized HepG2 cells indicated that multiple domains of apoB are exposed to the cytosol through an extensive portion of the secretory pathway. The intracellular orientation of apoB in the secretory pathway was confirmed by immunocytochemistry using antibodies recognizing specific domains of apoB in streptolysin-O (STP-O)- and saponin-permeabilized HepG2 cells. Lumenal epitopes on marker proteins in secretory pathway compartments (p63, p53, and galactosyltransferase) were not stained by antibodies in STP-O-treated cells, but were brightly stained in saponin-treated cells, confirming that internal membranes were not perforated in STP-O-treated cells. An anti-apoB peptide antibody (B4) recognizing amino acids 3221-3240 caused intense staining in close proximity to the nuclear membrane, and less intensely throughout the secretory pathway in STP-O-permeabilized cells. Staining with this antibody was similar in STP-O- and saponin-treated cells, indicating that this epitope in apoB is exposed to the cytosol at the site of apoB synthesis and throughout most of the remaining secretory pathway. Similar results indicating a cytosolic orientation were obtained with monoclonal antibody CC3.4, which recognizes amino acids 690-797 (79-91 kD) in apoB. Two polyclonal antibodies made to human LDL and two monoclonal antibodies recognizing amino acids 1878-2148 (D7.2) and 3214-3506 (B1B6) in apoB did not produce a strong reticular signal for apoB in STP-O-treated cells. The anti-LDL and B1B6 antibodies produced almost identical punctate patterns in STP-O-treated cells that overlapped with LAMP-1, a membrane marker for lysosomes. These observations suggest that the B1B6 epitope of apoB is exposed on the surface of the lysosome. The results identify two specific regions in apoB that are exposed to the cytosol in the secretory pathway.

Amino Acid Sequence↗

PubMed1998

Design, synthesis, and evaluation of the multidrug resistance-reversing activity of D-glucose mimetics of hapalosin.

When five substituents of hapalosin were placed on D-glucose, molecular modeling revealed that the substituents on mimetics 2 and 3 occupy similar spatial positions as the corresponding substituents on hapalosin. Mimetic 3 and all the glucopyranoside intermediates generated in its synthesis were assessed for their ability to reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) or the multidrug resistance-associated protein (MRP). None of the sugar compounds were as effective as hapalosin in inhibiting P-gp in cytotoxicity and drug accumulation assays using MCF-7/ADR cells. By contrast, four D-glucose compounds exhibited similar efficacy as hapalosin in antagonizing MRP in cytotoxicity assays with HL-60/ADR cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Cytotoxic effect of 7alpha-hydroxy-4-cholesten-3-one on HepG2 cells: hypothetical role of acetaldehyde-modified delta4-3-ketosteroid-5beta-reductase (the 37-kd-liver protein) in the pathogenesis of alcoholic liver injury in the rat.

We recently identified delta4-3-ketosteroid-5beta-reductase as the 37 kd liver protein which is highly susceptible to acetaldehyde modification in rats continuously fed alcohol. The 5beta-reductase is a key enzyme involved in bile acid synthesis. We report here that the ability to degrade 7alpha-hydroxy-4-cholesten-3-one (HCO) was lower in the liver cytosol of alcohol-fed rats than in control animals, suggesting an inhibition of the 5beta-reductase enzyme activity by acetaldehyde modification. We also showed that HCO exhibited a time- and concentration-dependent cytotoxicity to HepG2 cells. HCO cytotoxicity was noticeable at a concentration of 2.5 microg/mL. When 10 microg/mL of HCO was added to confluent cell monolayers, 57% and 37% of cells remained viable after 24 and 48 hours of treatment. The decrease in cell viability was accompanied by an increased lactic dehydrogenase activity in the culture medium. DNA extracted from HCO-treated cells showed no evidence of DNA fragmentation when analyzed by agarose gel electrophoresis. Staining with propidium iodide showed no nuclear condensation in cells. Thus, cell death by HCO treatment was caused by necrosis and not by apoptosis. Various agents, including, serum proteins, hormones, bile acids, antioxidants, Ca++-chelators, Fe++-chelator, CYP450 inhibitor, adenylate cyclase inhibitor, protease inhibitors, and nitric oxide synthase inhibitor, did not protect against HCO cytotoxicity. We speculate that HCO concentrations may be elevated around the pericentral area in the liver after chronic alcohol ingestion, causing local cell necrosis. The release of cellular contents and protein-acetaldehyde adducts (PAAs) may activate nonparenchymal cells and provoke autoimmune reaction. Thus, the formation of the 37 kd-PAA may play an important role in the initiation of alcoholic liver injury.

Acetaldehyde↗

PubMed1998

Genetic and physical mapping of the Lps locus: identification of the toll-4 receptor as a candidate gene in the critical region.

On the basis of 2093 meioses analyzed in two separate intraspecific backcrosses, the location of the mouse Lpsd mutation was circumscribed to a genetic interval 0.9 cM in size. A total of 19 genetic markers that lie in close proximity to the mutation were examined in mapping. Most of these were previously unpublished polymorphic microsatellites, identified by fragmentation of YAC and BAC clones spanning the region of interest. Lpsd was found to be inseparable from the microsatellite marker D4MIT178, and from three novel polymorphic microsatellites identified near D4MIT178. The mutation was confined between two novel microsatellite markers, herein designated "B" and "83.3." B lies centromeric to the mutation, and was separated by four crossovers in a panel of 1600 mice; 83.3 lies distal to the mutation and was separated by three crossovers in a panel of 493 mice. 66 BAC clones and one YAC clone were assembled to cover > 95% of the critical region. Estimates based on pulsed field gel electrophoresis and fluorescence in situ hybridization indicate that the The B-->83.3 interval is about 3.2 Mb in length. A minimal area of zero recombinational distance from Lpsd was also assigned, and found to occupy approximately 1.2 Mb of physical size. To identify gene candidates, nearly 40,000 sequencing runs were performed across the critical region. Selective hybridization and exon trapping were also employed to identify genes throughout the "zero" region. Only a single intact gene was identified within the entire critical region. This gene encodes the Toll-4 receptor, a member of the IL-1 receptor family.

Animals↗

PubMed1998

Comparison of interleukin-11 and epidermal growth factor on residual small intestine after massive small bowel resection.

BACKGROUND/PURPOSE: Interleukin-11 (IL-11) is a multifunctional cytokine derived from bone marrow, which has a trophic effect on small bowel epithelium. This study compares the effects of IL-11 with epidermal growth factor (EGF), a growth factor known to enhance small bowel adaptation. METHODS: Forty Sprague-Dawley rats (90 to 100 g) underwent an 85% mid-small bowel resection with primary anastomosis on day 0. Rats were divided into four treatment groups: controls (group I) received bovine serum albumin (BSA), group II received IL-11, 125 microg/kg subcutaneously (SC) twice daily, group III received EGF, 0.10 microg/g SC bid, and group IV received EGF and IL-11 in the above doses. Half of the animals (five per group) were killed on day 4 of therapy, and the rest were killed on day 8. Animals were evaluated for weight, mucosal length, and bowel wall muscle thickness on days 4 and 8, and expression of proliferating cell nuclear antigen (PCNA) in intestinal crypt and smooth muscle cells on day 8. RESULTS: There were two deaths; both were 8-day controls. Body weight was similar at day 4 and day 8. Mucosal thickness in groups II (IL-11) and group IV (IL-11 and EGF) was significantly increased at day 4 and 8 when compared with controls (group I) and EGF (group III, P < .001). Muscle thickness was significantly increased in the EGF and combined group IV compared with the BSA controls and IL-11 groups (P < .001). Thirty-two percent of the mucosal crypt cells in Group I stained positive for PCNA, whereas 51%, 53%, and 60% stained positive in groups II (IL-11), III (EGF), and IV (IL-11 and EGF), respectively. In groups I and II, 2% and 1.7% of the myocytes stained positive for PCNA, whereas 11.2% and 5.2% of the myocytes in group III and IV stained positive. CONCLUSIONS: These data suggest that IL-11 has a trophic effect on small intestinal enterocytes, causing cell proliferation and increased mucosal thickness. EGF has a more generalized effect on intestine causing proliferation of both enterocytes and myocytes. IL-11, with or without EGF, may be a useful adjunct in instances of short bowel syndrome.

Adaptation, Physiological↗

PubMed1998

The influence of apoptosis on intestinal barrier integrity in rats.

BACKGROUND: Apoptosis is a critical step responsible for maintaining the cellular balance between proliferation and death and for controlling tumorigenesis. Although an increase in intestinal apoptotic cells has been considered to be associated with the pathogenesis of gastrointestinal injury, little is understood concerning the role of apoptosis in the development of intestinal barrier dysfunction. METHODS: Apoptosis induced by intraperitoneal injection of doxorubicin in rats was evaluated by transmission electron microscopy and the TUNEL histochemistry method. Treatment with deoxy-D-glucose (a glycolytic pathway inhibitor) or cycloheximide (a protein synthesis inhibitor) was performed after doxorubicin challenge. Passage of human serum albumin from blood to the intestinal interstitium and the intestinal lumen or from the intestine to the intestinal interstitium and blood was evaluated by means of albumin clearance. RESULTS: A significant increase in gut water content, albumin flux, and bidirectional clearance of albumin accompanied by apoptotic epithelial cell increase was noted in doxorubicin-challenged rats treated with saline. The increase in endothelial and epithelial permeability and the increase of apoptosis could partly be prevented by treatment with deoxy-D-glucose or cycloheximide. CONCLUSION: Doxorubicin-increased epithelial apoptosis within the intestine occurs simultaneously with increased bidirectional permeability of the intestinal barrier, probably associated with both glycolytic and protein synthesis pathways. Apoptosis may thus play a role in the pathogenesis of intestinal barrier dysfunction.

Animals↗

PubMed1998

Hydroxyl group of insulin A19Tyr is essential for receptor binding: studies on (A19Phe)insulin.

One mutant proinsulin gene was constructed through PCR with the code of A19Tyr changed into that of Phe. The mutant proinsulin, (A19Phe)-lysproinsulin (F19KPI) was expressed in E. coli and purified. After trypsin and carboxypeptidase B cleavage and Resource Q separation, (A19Phe)-human insulin (F19HI) was obtained. With native insulin as standard, activity assay and structural analysis were carried out. It was found that the conformation of F19HI is very similar to that of native insulin according to the data from native PAGE, reverse-phase FPLC and circular dichroism spectrum, which are also in agreement with the result of radioimmune assay. F19HI retains almost full immune activity, but displays only 13.3% of receptor binding activity. These results suggest that the hydroxyl group of insulin A19Tyr is essential for receptor binding.

Circular Dichroism↗

PubMed1998

[A clinicopathological analysis of 15 cases with congenital tumors in fetus and newborn].

OBJECTIVE: The incidence rate of congenital tumors in fetuses and neonates and its influence on fetal outcome including development and death were analysed. METHODS: Both clinical manifestations and pathological data of 15 cases with congenital tumor were analysed retrospectively. RESULTS: The incidence rate of congenital tumors in fetuses and neonates was 7.7/100,000 with a rate of 0.7% in total perinatal autopsies. The most common tumor was teratoma (46.7%), the next was hemangioma (26.7%). Among 15 cases with congenital tumor, 9 cases (60.0%) were complicated with polyhydroamnios; 11 perinates (73.3%) were born with body weight appropriate for gestational age, 6 perinates (40.0%) were associated with various anomalies which were commonly secondary to the tumors. The common causes responsible for death were malformation, placental impairment due to tumor invasion or tumor grown at a special site. CONCLUSION: The incidence rate of congenital tumors in fetuses and neonates was very low. Because the tumor usually exhibited a local effect, under carefully evaluating the development of neonates, it is promising to get complete cure.

Adult↗

PubMed1998

[Cytokines release related to cardiopulmonary bypass in patients with prosthetic valve replacement].

To examine cytokines release related to cardiopulmonary bypass(CPB), the anthers investigated the possible differences in cytokines responses between patients undergoing prosthetic valve replacement (study group, n = 10) and those receiving closure of patent ductus arteriosus or pericardiectomy(control group, n = 9). Venous levels of interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-10 (IL-10) were measured at multiple time points before, during and after operation. As compared with pre-operative values, IL-2 levels in both groups decreased significantly (P < 0.05), and the levels of sIL-2R, IL-6, TNF-alpha, and IL-10 in both groups increased significantly at multiple time points post-operative (P < 0.01). All the values of cytokines returned to pre-operative levels at 7th post-operative day. Although there were no pre-operative differences in these cytokines between the two groups (P > 0.05), the post-operative changes of cytokines in study group was more obvious than that in control group (P < 0.01). In study group IL-10 rose to a peak value of around 620 pg/ml at the end of CPB while IL-6 and TNF-alpha levels reached their peak values of around 88 pg/ml and 52 pg/ml respectively at 1st post-operative day. IL-10 has been reported as an antiinflammatory cytokine. The preceding IL-10 peak value, as compared with the peak values of IL-6 and TNF-alpha, could be associated with the interplay and regulation of cytokine network. On the other hand, in control group the levels of IL-6, TNF-alpha, and IL-10 reached their peak values at 1st post-operative day simultaneously. The values were 34 pg/ml, 36 pg/ml, and 162 pg/ml respectively. This result suggests that besides surgical stress mediated cytokines production or suppression, CPB itself also results in obvious changes of cytokine metabolism. However further studies are needed to elucidate the underlying mechanisms and clinical value of post-operative cytokines production or suppression related to CPB in patients with prosthetic valve replacement.

Adult↗

PubMed1998

[The parapharyngeal space tumour of children: reports of 4 cases].

In 1986-1996, four childish patients with parapharyngeal space tumour were treated in our hospital. In the beginning, we ought to define the size and range by CT scanning. The second, we excized it from neck-flank. The patients had a satisfying effect after surgical operation. Meantimes, it's necessary to protect the important vessel and nerve in surgical operation.

Child↗

PubMed1998

[Clinical study on tripterygium wilfordii complex ester tablet in treating rheumatoid arthritis].

OBJECTIVE: To observe the curative effect, toxic and side effect of Tripterygium Wilfordii Complex Ester Tablet (TWT, a preparation of Folium Tripterygium wilfordii) in treating rheumatoid arthritis. METHODS: Two hundred and seventy seven patients were observed with prospective, multicentric and random double-blind control method. One hundred and forty cases of TWT group were treated with TWT 2 tablets each time, 3 times a day orally, and the other 137 cases treated with Tripterygium Wilfordii Polycoside Tablet (TPT, a preparation of Radix Tripterygium Wilfordii) 2 tablets each time were taken as control, 3 times a day orally. The therapeutic course for both groups was 6 weeks. RESULTS: The markedly controlled rate of the TWT group was 26.71% and the total effective rate was 86.43%, while those in the control group were 26.28% and 83.94% respectively, the difference between the two groups was insignificant (P > 0.05). The occurrence of side-effect in the two groups was 20.00% and 23.35% respectively, also showed no significant difference (P > 0.05). CONCLUSION: The Folium Tripterygium Wilfordii preparation is similar in efficacy and security to the Radix Tripterygium Wilfordii preparation.

Adolescent↗

PubMed1998

[The value of cephalometric analysis in diagnosis and treatment of obstructive sleep apnea syndrome].

OBJECTIVES: To study the value of cephalometric analysis in the diagnosis, treatment option and evaluation of prognosis. METHODS: A detailed cephalometric analysis was performed using lateral X-ray films from 50 cases with obstructive sleep apnea syndrome (OSAS) and 30 age- and sex-matched controls. RESULTS: Statistical results showed that OSAS patients were different from controls in the following aspects: 1. Their uvula, soft palate and tongue were significantly enlarged. 2. The hyoid bone was displaced inferiorly and posteriorly. 3. The posterior airway space (palatopharyngeal plane) was narrow. 4. The hard palate was elongated. 5. The mandibular body was retropositioned. Fifty unselected consecutive OSAS patients(mean AHI 51.42 +/- 3.96, Medilog SAC 847, Oxford UK) underwent LAUPP using CO2 laser. Twenty-five cases were followed-up for 4-8 months. 10/25 had obtained a reduction in AHI > 50%, 15/25 had AI < 20 times. The success rate was compared with cephalomentric findings. CONCLUSION: Cephalometry has an important diagnostic and predictive value in the clinical investigation of patients suspected of having OSAS.

Adult↗

PubMed1998

[A histochemical study on baicalin].

Baicalin in the root of Scutellaria baicalensis was analysed histochemically by means of TLC and HPLC. It was determined that the content of baicalin in phloem was 11.08%, in xylem 7.86%, in phellem 2.19% and in centric decayed part 0.815%. Thus the quality of root of Scutellaria baicalensis is believed to consist in thin phellem, high ratio of phloem to xylem and absence of centric decayed part.

Drugs, Chinese Herbal↗