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S Wu

Publications and source records attributed to S Wu.

At least 217 records · Page 12Linked to original sources
PubMed1999

Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer's disease.

The epsilon4 allele of apolipoprotein E (apo E) is associated with an increased risk for developing Alzheimer's disease (AD). This may be due to interactions between apo E and the amyloid-beta protein (Abeta). To assess the effects of human apo E isoforms on Abeta deposition in vivo, we bred apo E3 and apo E4 hemizygous (+/-) transgenic mice expressing apo E by astrocytes to mice homozygous (+/+) for a mutant amyloid precursor protein (APPV717F) transgene that develop age-dependent AD neuropathology. All mice were on a mouse apo E null (-/-) background. By nine months of age, APPV717F+/-, apo E-/- mice had developed Abeta deposition, and, as reported previously, the quantity of Abeta deposits was significantly less than that seen in APPV717F+/- mice expressing mouse apo E. In contrast to effects of mouse apo E, similar levels of human apo E3 and apo E4 markedly suppressed early Abeta deposition at nine months of age in APPV717F+/- transgenic mice, even when compared with mice lacking apo E. These findings suggest that human apo E isoforms decrease Abeta aggregation or increase Abeta clearance relative to an environment in which mouse apo E or no apo E is present. The results may have important implications for understanding mechanisms underlying the link between apo E and AD.

Alzheimer Disease↗
PubMed1999

Multiple androgen response elements and a Myc consensus site in the androgen receptor (AR) coding region are involved in androgen-mediated up-regulation of AR messenger RNA.

The androgen receptor (AR) gene is transcriptionally regulated by AR (autoregulation); however, the androgen response elements (AREs) required for this process have not been found in the AR promoter or in the 5'-flanking region. We previously showed that the AR cDNA contains AREs involved in AR mRNA autoregulation and that auto(up)regulation is reproduced in PC3 cells (a human prostate cancer cell line) expressing the human AR cDNA driven by a heterologous promoter. A 350-bp fragment of the AR cDNA contains the requisite AREs (ARE-1 and ARE-2) and, when linked upstream of a reporter gene, confers androgen inducibility in a cell-specific manner. Here we report that, although an AR cDNA harboring silent mutations of ARE-1 and ARE-2 produces a transcriptionally active AR, AR mRNA encoded by this mutant cDNA is not up-regulated in androgen-treated PC3 cells. Thus, ARE-1 and ARE-2 are essential for androgen-mediated up-regulation of AR mRNA in this model. Since ARE-1 and ARE-2 are located on separate exons (exons D and E) in the AR gene, we evaluated these AREs in their native context, a 6.5-kb AR genomic fragment. Androgen regulated the 6.5-kb AR genomic fragment and the 350-bp region of the AR cDNA at comparable levels, suggesting that sequences in exons D and E are likely to be involved in androgen-mediated up-regulation of the native AR gene. Furthermore, androgen regulated both responsive regions in U2OS cells, a human osteoblastic cell line that exhibits androgen-mediated up-regulation of native AR mRNA. DNAse I footprinting of the 350-bp region with recombinant AR (DNA- and ligand-binding domains) suggested the presence of additional AREs. Gel shift analyses and mutational studies showed that maximal androgen regulation and AR binding were dependent on the integrity of four AREs (ARE-1, ARE-1A, IVSARE, and ARE-2). While the presence of multiple, nonconsensus AREs is common among other androgen-regulated enhancers, the androgen-responsive region of the AR gene is unique because it contains exonic AREs. DNA binding studies with nuclear extracts were performed to determine whether non-AR transcription factors contribute to androgen regulation of the 350-bp region. These studies, in conjunction with mutational analysis and reporter gene assays with dominant negative Myc and Max expression vectors, showed that Myc and Max interaction with a Myc consensus site is required for androgen regulation of the 350-bp fragment. These results represent a novel interaction between AR and the Myc family of proteins and support a model of androgenic control of AR mRNA via AR and Myc family interaction with a unique internal androgen-responsive region harboring multiple exonic regulatory sequences.

Androgens↗
PubMed1999

Neoplastic conversion of human urothelial cells in vitro by overexpression of H2O2-generating peroxisomal fatty acyl CoA oxidase.

An in vitro study was conducted to determine if malignant transformation can be induced in human urothelial cells immortalized with human papillomavirus E6/E7 genes. A clone designated 1T1 was isolated and then stably transfected with an acyl CoA oxidase (ACOX)-expression construct. The cells generated H2O2 in a large quantity from the substrate linoleic acid (LA). After 56 days of LA treatment, cells persistently formed an epithelial cyst in athymic nude mice with an occasional intracystic epithelial nodule. Our results indicate that human urothelial cells can be transformed to low grade neoplastic cells by H2O2 and suggest that H2O2 may be involved in the development of bladder cancer.

Acyl-CoA Oxidase↗
PubMed1999

BUBR1 phosphorylation is regulated during mitotic checkpoint activation.

Eukaryotic cells have evolved a mechanism that delays the progression of mitosis until condensed chromosomes are properly positioned on the mitotic spindle. To understand the molecular basis of such monitoring mechanism in human cells, we have been studying genes that regulate the mitotic checkpoint. Our early studies have led to the cloning of a full-length cDNA encoding MAD3-like protein (also termed BUBR1/MAD3/SSK1). Dot blot analyses show that BUBR1 mRNA is expressed in tissues with a high mitotic index but not in differentiated tissues. Western blot analyses show that in asynchronous cells, BUBR1 protein primarily exhibits a molecular mass of 120 kDa, and its expression is detected in most cell lines examined. In addition, BUBR1 is present during various stages of the cell cycle. As cells enter later S and G2, BUBR1 levels are increased significantly. Nocodazole-arrested mitotic cells obtained by mechanical shake-off contain BUBR1 antigen with a slower mobility on denaturing SDS gels. Phosphatase treatment restores the slowly migrating band to the interphase state, indicating that the slow mobility of the BUBR1 antigen is attributable to phosphorylation. Furthermore, purified recombinant His6-BUBR1 is capable of autophosphorylation. Our studies indicate that BUBR1 phosphorylation status is regulated during spindle disruption. Considering its strong homology to BUB1 protein kinase, BUBR1 may also play an important role in mitotic checkpoint control by phosphorylation of a critical cellular component(s) of the mitotic checkpoint pathway.

Cell Cycle Proteins↗
PubMed1999

[Effect of mifepristone on cell-cycle kinetics of human placental chorio-trophoblastic and decidual cell].

OBJECTIVE: To study the effects of mifepristone on cell-cycle kinetics of human placental chorio-trophoblastic and decidual cells. METHODS: Flow-cytometry was introduced in the study of the mechanism of early pregnancy terminating drug, mifepristone. Twenty-three samples were obtained from normal pregnant women by surgical aspiration. Another 24 samples were obtained in women pretreated with 150 mg mifepristone 48 hours before operation. RESULTS: The percentage of the cytotrophoblastic cells in G0 + G1 phases was much higher in the treatment group (P < 0.01), whereas it was much lower (P < 0.01) in G2 + M phases, and the proliferating index of cells was significantly decreased. Apart from the increasing of decidual cells in G2 + M phases (P < 0.05), there was no change in other phases. CONCLUSIONS: Mifepristone may block the transformation of the cytotrophoblastic cells from G0, G1 phases to S phase, thus leading to the block of the proliferation of cells. Mifepristone has much more significant effects on the chorionic villi than on the decidua.

Abortifacient Agents, Steroidal↗
PubMed1999

[A randomized, double-blind, multicentre study on comparing levonorgestrel and mifepristone for emergency contraception].

OBJECTIVE: To compare the efficacy, side effects and the effect on next menstruation of levonorgestrel(LNG) to low dose mifepristone in emergency contraception. METHODS: The study is a randomized double-blind multicenter comparative trial. The clients who have unprotected intercourse within 72 hours were allocated to one of the two study groups. In LNG group, 0.75 mg LNG was taken twice with 12 hours apart. In mifepristone (Mife-) group, single dose of 10 mg mifepristone was taken and a placebo 12 hours after. Follow-up visit was paid on the seventh day of the expected next menstruation to evaluate the contraceptive efficacy and to record side effects and menstruation. Contraceptive efficacy was calculated by Dixon's method. RESULTS: The total valid subjects in LNG and Mife- group were 643 and 633, respectively. There were 20 and 9 pregnancies occurred respectively in each group. The failure rate was 3.1% and 1.4%. Contraceptive efficacy rate of preventing pregnancy was 59.2% and 79.7%, the difference was statistically significant (P < 0.05). The incidence of various side effects was less than 10.0% which were mild. There was no statistically difference between the two groups. The percentage of subjects who had their next menstruation before or after their expected menstruation 3 days in LNG group and Mife- group was 77.7% and 78.5% respectively. The menstrual period less than 7 days was 95.0% and 93.3%. CONCLUSION: Use of levonorgestrel or low dose mifepristone for emergency contraception is effective and safe.

Adult↗
PubMed1999

Study on vertical transmission of Chlamydia trachomatis using PCR and DNA sequencing.

OBJECTIVE: To investigate the vertical transmission rate of Chlamydia trachomatis (CT) in Chongqing, China. METHODS: Specimens taken from 278 women and from their 79 infants were examined by cell culture, polymerase chain reaction (PCR) and DNA sequence analysis. Chlamydia trachomatis was isolated in McCoy cell culture. CT DNA was extracted with a modified Nal method. After cloning, recombinant plasmids were used for sequence analysis with the dideoxy chain termination method. RESULTS: 10.8% (30/278) of the cervical cultures of pregnant women were positive for Chlamydia trachomatis, while the positive rate tested by PCR was 14.0% (39/278). The vertical transmission rate of Chlamydia trachomatis was 55.0% (11/20). The incidences of conjunctivitis and pneumonia in infants with Chlamydia trachomatis positive mothers were 27.3% and 18.2%, respectively. DNA sequences of Chlamydia trachomatis isolated from the cervix of a mother and the nasopharynx of her baby were identical. CONCLUSION: Chlamydia trachomatis infection is quite common in Chongqing, China. Our report is the first report of CT vertical transmission proved by DNA sequence analysis.

Adult↗
PubMed1999

[Expression of C-erbB-2 oncogene mRNA in salivary gland tumors].

OBJECTIVE: To study relationship of C-erb-2 oncogene mRNA expression and histotype, tumorigenesis and biological behavior of salivary gland neoplasms. METHODS: Using 32P labeled oligonucleotide as probe, the dot blot technique was used to study the expression of C-erbB-2 oncogene mRNA in salivary gland neoplasm with normal salivary gland as control. RESULTS: With the expression in normal salivary gland as a standard, low C-erbB-2 mRNA expression was seen in adenolymphoma, basal cell adenoma. However, various degrees of over-expression of C-erbB-2 oncogene mRNA were detected in pleomorphic adenoma, mucoepidermoid carcinoma, acinic cell carcinoma, adenoid cystic carcinoma, papillary cystic carcinoma, and myoethelial cell carcinoma. CONCLUSION: C-erbB-2 oncogene mRNA over-expression in salivary gland neoplasm is related to biological behavior of salivary gland carcinoma.

Adenolymphoma↗
PubMed1999

[P-selectin and tachykinins in bronchial hyperresponsiveness of asthma].

OBJECTIVE: The characteristic feature of asthma is bronchial hyperresponsiveness (BHR). It is due predominately to inflammation of airways. Pathologically, there are inflammatory infiltration, epithelial sloughing and mucosal edema in the bronchi. The objective of this study is to investigate the relationship between BHR and airway inflammation. METHODS: 57 cases of asthma and 22 normal subjects were tested with bronchial reactivity examination and P-selectin, substance P (SP) and vasoactive intestinal peptide (VIP) in plasma. RESULTS: It was found that the bronchial reactivity to inhaled methacholine was positive in 53 of the 57 asthmatic patients (92.98%), while the remaining four were negative (7.02%). Twenty-two normal subjects were all negative with the test of bronchial reactivity. The levels of P-selectin and SP in asthmatics with corticosteroids treatment (n = 27) were higher than those in the control group (P < 0.05), but lower than those in asthmatics treated with aminophylline and salbutamol sulfate (n = 30), (P < 0.01). The concentration of VIP in asthmatics with corticosteroids treatment was significantly higher than that of asthmatics with out corticosteroids treatment (P < 0.01) but lower than that in the control group (P < 0.01). There was positive relationship between bronchial reactivity and P-selectin (r = 0.328, P < 0.05), as well as SP (r = 0.529, P < 0.01) in asthmatics, but negative relationship between bronchial reactivity and VIP (r = -0.419, P < 0.05). CONCLUSION: The increase of P-selectin and SP and decrease of VIP can induce BHR, corticosteroids can reduce levels of P-selectin, SP and enhance the level of VIP, therefore it can improve the reactivity of airway and relieve symptoms.

Adult↗
PubMed1999

[Surveillance of bacterial resistance in Shanghai in 1998].

OBJECTIVE: To investigate the resistance of clinical bacterial isolates as a reference for rational use of antibiotics. METHODS: Using Kirby-Bauer method for bacterial susceptibility testing and NCCLS 1997 as assessment criteria. RESULTS: The number of Gram positive organisms was increasing in clinical isolates. Among the Staphylococci aureus (SA) and coagulase negative Staphylococci (CNS), methicillin resistant SA (MRSA) and methicillin resistant CNS (MRCNS) accounted for 70.7% and 54.9% respectively, but no vancomycin resistant strain was found. Vancomycin-resistant Enterococci was about 5%. Resistant rates of Klebsiella spp, Serratia spp, Enterobacter spp and Acinetobacter spp against third generation cephalosporins and fluoroquinolones increased markedly. The resistant rates of most Enterobacteriaceae species against imipenem were increasing gradually, while the resistant rates of Pseudomonas aeruginosa against ceftazidime, cefoperazone and imipenem were significantly higher as compared with the data in 1994. CONCLUSION: The urgent need of restricting the misuse of antibiotics.

Anti-Bacterial Agents↗
PubMed1999

[A study on relationship between blood lead level and physical growth and development of babies and young children in Shanghai].

OBJECTIVE: To study the effects of low level lead exposure on physical growth and development in young children. METHODS: Blood lead level and indicators for physical growth and development, such as body height and weight, and head and chest circumferences were measured in randomly sampled 1,969 children aged 1 - 6 years in Shanghai. Z scores for these indicators were calculated for each of them based on their age and sex-specific norms for children in urban and suburban Shanghai. And, regression analysis of blood lead level was conducted on them. RESULTS: Geometric mean of blood lead level was 0.400 micromol/L in young children of Shanghai, and 744 (37.8%) of 1,969 children were equal to or higher than 0.483 micromol/L. Geometric mean of blood lead level correlated in reverse to the Z scores for their body height, weight and head circumference, even if adjusted for the potential confounding factors. CONCLUSION: Low level lead exposure could cause adverse effects on their physical growth and development in young children of Shanghai.

Body Height↗
PubMed1999

[A preliminary report on two distinct tumor-suppressor regions on chromosome 1p36.2-p36.3 in human hepatocellular carcinomas].

OBJECTIVE: Both cytogenetic and molecular genetic analyses have unveiled non-random genomic alterations in the distal short arm of human chromosome 1 associated with a number of human malignancies including heptatocellular carcinoma (HCC). The aim of this investigation is to determine the precise region of deletion that may harbor the putative tumor suppressor genes in HCC. METHODS: For the study of the loss of heterozygosity (LOH), 38 cases of hepatitis B virus (HBV) associated HCC and their corresponding non-tumor liver tissues were detected with 43 microsatellite polymorphic markers particularly focusing on 1p. RESULTS: Twenty-eight of the 38 (74%) tumors showed LOH on at least one locus on 1p36.2-p36.3. Two distinct smallest common deleted regions (SCDRs) with different patterns of deletion were identified. The first SCDR is located on locus D1S2795 at 1p36.3, between loci D1S2145 and D1S2893. The second SCDR is located at 1p36.2, between loci D1S244 and D1S489. Both of the SCDRs have not been previously described in HCC. In addition, a region of possible homozygous deletion (HD) was also detected within the second SCDR between loci D1S1597 and D1S489 by comparative multiplex PCR. This is the first observation of a possible homozygous deletion on the distal short arm of chromosome 1 in HCC as well as in human tumors. CONCLUSIONS: The high-resolution deletion mapping of 1p36.2-p36.3 in HCC in this study confirmed the presence of two distinct regions of deletion. Our data strongly suggest the presence of at least two tumor suppressor regions on 1p36.2-p36.3 and play an important role in the pathogenesis of HBV associated HCC. These results also provide a basis for further studies directed at cloning potential tumor suppressor genes in these regions.

Carcinoma, Hepatocellular↗
PubMed1999

[Influence of triiodothyronine and insulin on liver adenine nucleotide levels in portal triad-clamping rats].

OBJECTIVE: To assess the influence of triiodothyronine(T3) and insulin on liver adenine nucleotide levels in portal triad-clamping rats. METHOD: A rat model of normothermic portal triad clamping was established to observe the influence of T3 and insulin on the contents of liver adenine nucleotides and survival rates. RESULT: The ATP levels and the 72 h-survival rate of T3 group were significantly higher than those of insulin group and saline group(P < 0.05). The blood glucose levels were obviously decreased and all the rats died within 6 hours postoperation in insulin group. CONCLUSIONS: T3 can improve hepatic energy metabolism after portal triad clamping and increase survival rate, whereas such effects were not found in insulin group.

Adenine Nucleotides↗
PubMed1998

[Use of the primed in situ labeling technique for a rapid detection of chromosomes X, 18].

OBJECTIVE: To develop a rapid method for detection of chromosomes. METHODS: Chromosomes X, 18 were detected by the primed in situ labeling(PRINS) in eight samples of female peripheral blood cultures. RESULTS: Specific chromosomes were obtained on both metaphase and interphase nuclei. The efficiency of labeling was 84%-92%(mean=89%) in chromosome 18, and 73%-87%(mean=84%) in chromosome X. The pretreatment of slides by proteinase K markedly raised the efficiency of labeling and increased the intensity of signals. PRINS reaction could be performed automatically with a programmable thermocycler in less than one hour. CONCLUSION: The results suggest that PRINS is a fast and specific method for identifying chromosomes. It may be a reliable technique for detecting aneuploid in prenatal diagnosis.

Chromosomes, Human, Pair 18↗
PubMed1998

Bacteroides fragilis enterotoxin cleaves the zonula adherens protein, E-cadherin.

Strains of Bacteroides fragilis associated with diarrheal disease (enterotoxigenic B. fragilis) produce a 20-kDa zinc-dependent metalloprotease toxin (B. fragilis enterotoxin; BFT) that reversibly stimulates chloride secretion and alters tight junctional function in polarized intestinal epithelial cells. BFT alters cellular morphology and physiology most potently and rapidly when placed on the basolateral membrane of epithelial cells, suggesting that the cellular substrate for BFT may be present on this membrane. Herein, we demonstrate that BFT specifically cleaves within 1 min the extracellular domain of the zonula adherens protein, E-cadherin. Cleavage of E-cadherin by BFT is ATP-independent and essential to the morphologic and physiologic activity of BFT. However, the morphologic changes occurring in response to BFT are dependent on target-cell ATP. E-cadherin is shown here to be a cellular substrate for a bacterial toxin and represents the identification of a mechanism of action, cell-surface proteolytic activity, for a bacterial toxin.

Bacteroides fragilis↗
PubMed1998

Alteration of a single hydrogen bond between class II molecules and peptide results in rapid degradation of class II molecules after invariant chain removal.

To characterize the importance of a highly conserved region of the class II beta chain, we introduced an amino acid substitution that is predicted to eliminate a hydrogen bond formed between the class II molecule and peptide. We expressed the mutated beta chain with a wild-type alpha chain in a murine L cell by gene transfection. The mutant class II molecule (81betaH-) assembles normally in the endoplasmic reticulum and transits the Golgi complex. When invariant chain (Ii) is coexpressed with 81betaH-, the class II-Ii complex is degraded in the endosomes. Expression of 81betaH- in the absence of Ii results in a cell surface expressed molecule that is susceptible to proteolysis, a condition reversed by incubation with a peptide known to associate with 81betaH-. We propose that 81betaH- is protease sensitive because it is unable to productively associate with most peptides, including classII-associated invariant chain peptides. This model is supported by our data demonstrating protease sensitivity of peptide-free wild-type I-Ad molecules. Collectively, our results suggest both that the hydrogen bonds formed between the class II molecule and peptide are important for the integrity and stability of the complex, and that empty class II molecules are protease sensitive and degraded in endosomes. One function of DM may be to insure continuous groove occupancy of the class II molecule.

Amino Acid Substitution↗