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Biomedical subjects

X Xiong

Publications and source records attributed to X Xiong.

At least 91 records · Page 5Linked to original sources
PubMed1997

ESX: a structurally unique Ets overexpressed early during human breast tumorigenesis.

The >30 known members of the Ets multigene family of transcriptional regulators are increasingly being recognized for their involvement in early embryonic development and late tissue maturation, directing stage-specific and tissue-restricted programs of target gene expression. Identifiable primarily by their 85 amino acid ETS DNA-binding domain and dispersed across all metazoan lineages into distinct subfamilies, Ets genes also produce malignancies in humans and other vertebrates when overexpressed or rearranged into chimeras retaining the ETS domain, suggesting that their oncogenic potential is determined by the program of target genes they regulate. Searching for Ets factors that regulate expression of the HER2/neu (c-erbB2) oncogene in human breast cancer, we identified a new epithelium-restricted Ets encoding an ETS domain homologous to the Drosophila E74/human Elf-1 subfamily, an amino-terminal region (A-region or Pointed domain) homologous to the distantly related Ets-1 subfamily, and a serine-rich box homologous to the transactivating domain of the lymphocyte-restricted High Mobility Group (HMG) protein, SOX4. Recombinant protein encoded by ESX (for epithelial-restricted with serine box) exhibits Ets-like DNA binding specificity in electrophoretic mobility shift assays and, in transient transfection assays, transactivates Ets-responsive promoter elements including that found in the HER2/neu oncogene. ESX is located at chromosome 1q32 in a region known to be amplified in 50% of early breast cancers, is heregulin-inducible and overexpressed in HER2/neu activated breast cancer cells. Tissue hybridization suggests that ESX becomes overexpressed at an early stage of human breast cancer development known as ductal carcinoma in situ (DCIS).

Amino Acid Sequence↗
PubMed1997

In vitro characterization of the anti-human cytomegalovirus activity of PMEA (Adefovir).

PMEA [9-[2-(phosphonomethoxy)ethyl]adenine; adefovir] has shown anti-cytomegalovirus activity in animal models and in preliminary human trials. PMEA diphosphate (PMEApp), the active antiviral metabolite of PMEA, is a potent inhibitor of human cytomegalovirus (HCMV) DNA polymerase. PMEA is efficiently taken up and phosphorylated to PMEApp in numerous human cell lines. In vitro replication of wild type and drug resistant HCMV clinical isolates is effectively inhibited by PMEA. PMEA in combination with other anti-HCMV agents shows additive inhibition of HCMV replication.

Adenine↗
PubMed1997

Inhibition of growth of Dictyostelium discoideum amoebae by bisphosphonate drugs is dependent on cellular uptake.

PURPOSE: The aim of the study was to determine whether bisphosphonates are internalised by Dictyostelium amoebae and whether cellular uptake is required for their growth-inhibitory effects. Bisphosphonates inhibit growth of amoebae of the slime mould Dictyostelium discoideum, by mechanisms that appear to be similar to those that cause inhibition of osteoclastic bone resorption. METHODS: Cell-free extracts prepared from amoebae that had been incubated with bisphosphonates were analysed by 31P-n.m.r, spectroscopy or ion-exchange f.p.l.c., to identify the presence of bisphosphonates or bisphosphonate metabolites respectively. The growth-inhibitory effect of bisphosphonates towards Dictyostelium amoebae was also examined under conditions in which pinocytosis was inhibited. RESULTS: All of the bisphosphonates studied were internalised by Dictyostelium amoebae, probably by fluid-phase pinocytosis, and could be detected in cell-free extracts. Amoebae that were prevented from internalising bisphosphonates by pinocytosis were markedly resistant to the growth-inhibitory effects of these compounds. In addition, bisphosphonates encapsulated within liposomes were more potent growth inhibitors of Dictyostelium owing to enhanced intracellular delivery of bisphosphonates. CONCLUSIONS: All bisphosphonates inhibit Dictyostelium growth by intracellular mechanisms following internalisation of bisphosphonates by fluid-phase pinocytosis. It is therefore likely that bisphosphonates also affect osteoclasts by interacting with intracellular, rather than extracellular, processes.

Adenine Nucleotides↗
PubMed1997

Effect of incorporation of cidofovir into DNA by human cytomegalovirus DNA polymerase on DNA elongation.

Cidofovir (CDV) (HPMPC) has potent in vitro and in vivo activity against human cytomegalovirus (HCMV), CDV diphosphate (CDVpp), the putative antiviral metabolite of CDV, is an inhibitor and an alternate substrate of HCMV DNA polymerase. CDV is incorporated with the correct complementation to dGMP in the template, and the incorporated CDV at the primer end is not excised by the 3'-to-5' exonuclease activity of HCMV DNA polymerase. The incorporation of a CDV molecule causes a decrease in the rate of DNA elongation for the addition of the second natural nucleotide from the singly incorporated CDV molecule. The reduction in the rate of DNA (36-mer) synthesis from an 18-mer by one incorporated CDV is 31% that of the control. However, the fidelity of HCMV DNA polymerase is maintained for the addition of the nucleotides following a single incorporated CDV molecule. The rate of DNA synthesis by HCMV DNA polymerase is drastically decreased after the incorporation of two consecutive CDV molecules; the incorporation of a third consecutive CDV molecule is not detectable. Incorporation of two CDV molecules separated by either one or two deoxynucleoside monophosphates (dAMP, dGMP, or dTMP) also drastically decreases the rate of DNA chain elongation by HCMV DNA polymerase. The rate of DNA synthesis decreases by 90% when a template which contains one internally incorporated CDV molecule is used. The inhibition by CDVpp of DNA synthesis by HCMV DNA polymerase and the inability of HCMV DNA polymerase to excise incorporated CDV from DNA may account for the potent and long-lasting anti-CMV activity of CDV.

Antiviral Agents↗
PubMed1997

Repression of gonadotropin-releasing hormone promoter activity by the POU homeodomain transcription factor SCIP/Oct-6/Tst-1: a regulatory mechanism of phenotype expression?

POU domain transcription factors are required for neuropeptide expression in selected subsets of hypothalamic neuroendocrine neurons. We now report that expression of the gonadotropin-releasing hormone (GnRH) gene, which controls sexual development, is regulated by the POU protein SCIP/Oct-6/Tst-1. Reverse transcriptase PCR cloning and RNase protection assays demonstrated the presence of SCIP/Oct-6/Tst-1 mRNA in the GnRH-producing neuronal cell line GT1-7. The physiological relevance of this regulatory activity was suggested by the detection of SCIP/Oct-6/Tst-1 mRNA in a subset of GnRH neurons in the hypothalamus of prepubertal female rats. Coexpression of SCIP/Oct-6/Tst-1 in neuronal cells inhibited rat GnRH (rGnRH) promoter activity via three regions of the proximal rGnRH promoter containing SCIP/Oct-6/Tst-1 binding sites. DNase I footprinting, gel shift assays, and DNA and protein mutagenesis studies indicated that both direct DNA binding and protein-protein interactions are required for SCIP/Oct-6/Tst-1 modulation of GnRH gene expression. Activation of SCIP/Oct-6/Tst-1 expression in terminally differentiated GnRH neurons may be a factor determining the ratio of phenotypically "inactive" versus "active" GnRH neurons during postnatal life.

Animals↗
PubMed1997

[A short-term clinical study on a new aqueous humor drainage implant for refractory glaucoma].

OBJECTIVE: To investigate the therapeutic effect of a new aqueous humor drainage implant made in China for treatment of refractory glaucoma. METHODS: The implant was designed by ourselves and manufactured by Beijing Rubber Products Design & Research Institute. From July 1993 to September 1995, we observed 40 cases (41 eyes) with refractory glaucoma treated with the implantation surgery, including neovascular glaucoma (NVG) 16 eyes, non-neovascular glaucoma (NNVG) 25 eyes. RESULTS: The mean period of postoperative follow-up was 9.2 (range 3-27 months) months, the IOP was lowered from preoperative 7.20 +/- 1.51 kPa to postoperative 2.40 +/- 1.33 kPa in NVG group and from preoperative 6.27 +/- 1.07 kPa to postoperative 2.00 +/- 2.93 kPa in NNVG group. The success rate was 81% in NVG group and 84% in NNVG group. The common postoperative complications were flat anterior chamber, hyphema, choroidal detachment and so on. CONCLUSIONS: Our newly designed aqueous humordrainage implant provides an economic implant in China. The method of implantation is simple, is one of the effective methods for treatment of refractory glaucoma and can be widely used in clinics.

Adult↗
PubMed1997

[The study and primary application of multimedia teaching and learning system for diseases of temporomandibular joint].

A multimedia computer-assistant teaching and learning system for diseases of temporomandibular joint was reported in this paper. It was designed and implemented in Windows (Chinese) on PC 486. It was emphasized that interactive teaching and learning was an available, funny method and student was the focus of teaching and learning in this system. A satisfied result was obtained by utilizing of this multimedia teaching and learning system for primary application.

Computer-Assisted Instruction↗
PubMed1997

Establishment of doxorubicin-resistant human bladder cancer cell line (BUI-87/ADMR) and its mechanism of multidrug resistance.

OBJECTIVE: To establish a doxorubicin-resistant human bladder cancer cell line, BIU-87/ADMR, and to study its biological characteristics and mechanism of drug resistance. METHODS: A human bladder cancer cell line resistant to doxorubicin, BIU-87/ADMR, has been established in vitro by exposing BIU-87 parent cells to progressively increasing concentrations of the drug over a period of 8 months. The cell line has been characterized in terms of growth kinetics, morphology, cross-resistance to other anticancerous agents, pharmacokinetics of daunorubicin and expression of P-glycoprotein (P-gp) which is closely related to the MDR phenotype. RESULTS: The BIU-87/ADMR cell line was 6.3 times more resistant to doxorubicin than the parent BIU-87. It exhibited cross-resistance to doxorubicin derivatives (epirubicin, daunorubicin), vincristine and etoposide, but not to cisplatin and mitomycin C. Compared to the parent cells, the resistant cells have a slower growth rate and lower confluent density. Unlike the parent BIU-87, about 75% of the BIU-87/ADMR cells showed a positive reaction with monoclonal antibody against P-gp, JSB-1. Intracellular drug accumulation studies with fluorescence spectrometry indicated that the resistance exhibited by the BIU-87/ ADMR line was mainly caused by an increased active efflux. CONCLUSIONS: The results suggest that MDR is an important phenomenon in bladder cancer and that more than one pathway of MDR may be present in human bladder cancer cell lines. BIU-87/ADMR may be a useful model for the development of new chemotherapeutic strategies in overcoming drug-resistance in the treatment of bladder cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Detection of chlamydia trachomatis by polymerase chain reaction assay in nonbacterial prostatitis.

OBJECTIVE: To evaluate the sensitivity and specificity of polymerase chain reaction (PCR) technique in comparison with diethylaminoethyl-dextran (DEAE-dextran)-treated HeLa cell culture method for detection of chlamydia trachomatis in nonbacterial prostatitis. METHODS: Thirty patients had symptoms of prostatitis for at least three months. None of them had evidence of urethritis on urethral Gram stain or recurrent bacteria. Routine localization of bacteria was negative. White blood cell count in expressed prostatic secretion (EPS) was more than 10 per high-power field (10/HPF). None of these patients had received antibiotics during the six weeks before the study, although all had received multiple courses of antibiotics for treatment of prostatitis syndrome. The EPS specimens from these patients were placed in 0.5-ml Eppendorf tubes and stored at -70 degrees C until they were processed for PCR and DEAE-dextran-treated HeLa cell culture. RESULTS: Six specimens were positive for C. trachomatis by both PCR and culture, and 21 were negative by both tests. There were three specimens with discrepant results, including two that were positive by PCR and negative by culture, and one that was positive by culture and negative by PCR. Comparing PCR technique with culture method, the sensitivity, specificity, positive predictive value and negative predictive value of the former were 85.7%, 91.3%, 75.0% and 95.5% respectively. CONCLUSIONS: PCR analysis of EPS is a highly sensitive and specific noninvasive technique for detection of chlamydia trachomatis. It provides a unique opportunity for early identification of or rapid screening for chlamydia trachomatis infection in patients with nonbacterial prostatitis. The reliability of PCR assay offers clinicians a clear indication for the initiation of treatment of chlamydia trachomatis infection.

Chlamydia Infections↗
PubMed1997

Short-term clinical study on a new aqueous humor drainage implant for refractory glaucoma.

OBJECTIVE: To investigate the therapeutic effect of a new aqueous humor drainage (HAD) implant made in China for the treatment of refractory glaucoma. METHODS: The implant was designed by ourselves and manufactured by Beijing Rubber Products Design and Research Institute. From July, 1993 to September, 1995, we observed 40 patients (41 eyes) with refractory glaucoma treated by implantation surgery, including 16 eyes with neovascular glaucoma (NVG) and 25 eyes with non-neovascular glaucoma (NNVG). RESULTS: The mean period of postoperative follow-up was 9.2 (range, from 3-27) months, the intraocular pressure (IOP) was lowered from preoperative 7.20 +/- 1.51 kPa to postoperative 2.40 +/- 1.33 kPa in NVG group and from preoperative 6.27 +/- 1.07 kPa to postoperative 2.00 +/- 2.93 kPa in NNVG group. The success rate was 81% in NVG group and 84% in NNVG group. The common postoperative complications were flat anterior chamber, hyphema and choroidal detachment. CONCLUSIONS: Our newly designed aqueous humor drainage implant is an economical implant in China and one of the alternative and effective methods for the treatment of refractory glaucoma. It can be widely used in clinics.

Adult↗
PubMed1996

Continuous and group sequential conditional probability ratio tests for phase II clinical trials.

We present continuous and group sequential designs for phase II clinical trials based on the sequential conditional probability ratio test (SCPRT). The SCPRT is derived from a conditional likelihood ratio, where the conditioning is on what the corresponding (reference) fixed sample size test (RFSST) would achieve. In other words, we obtain the sequential design by controlling the maximum probability that the SCPRT does not agree with the RFSST. We shall discuss the difference between SCPRT and stochastic curtailment which also uses the concept of conditional distribution. We show that the power function of the SCPRT is virtually the same as that of the RFSST and its average sample numbers (ASNs) are close to those of Wald's sequential probability ratio test (SPRT), whereas its maximum sample size is no greater than that of the RFSST. Thus the SCPRT has all the desirable properties, such as allowing the use of the RFSST at the last analysis, of the Fleming procedure for phase II trials. The SCPRT, however, preserves the power function of the RFSST better and gives us the option for continuous monitoring. Our recommendation, therefore, is to use a group SCPRT boundary (for interim analyses performed as scheduled) embedded in a continuous SCPRT boundary (for unplanned interim analyses and analyses at times based on data trends). We provide as well a bias-adjusted estimator of the success rate after sequential stopping. We illustrate the method with several examples. The method applies to any single-arm clinical trial with binary endpoints, such as the classic paired design.

Clinical Trials, Phase II as Topic↗
PubMed1996

Structure of the distal human gonadotropin releasing hormone (hGnrh) gene promoter and functional analysis in Gt1-7 neuronal cells.

To assess potential species-specific expression of gonadotropin releasing hormone (GnRH), the distal human (h) GnRH promoter was cloned, characterized and tested in gene transfer studies. The nucleotide sequence of approximately 3.8 kb of 5'-flanking region was determined. Homology to the rat (r) GnRH sequence was observed in the proximal promoter region between -551 h (-424 r) and the transcriptional start site and within multiple distal promoter regions. In contrast, there was little similarity in the sequences between -1131/-551 h and -1031/-424 r. A deletion panel of 5'-flanking hGnRH promoter constructs was made and tested in transient transfection assays in GnRH-producing mouse GT1-7 neuronal cells. The largest hGnRH promoter construct (-3832/+5 h) exhibited high levels of reporter activity, similar to that observed with the largest rGnRH construct (-3026/+116 r). However, in contrast to the rat gene, deletion of distal promoter sequences of the hGnRH promoter to -1971, -1131 or -551 did not result in a decrease in luciferase reporter activity. Further truncation to -350 resulted in a 3-fold decrease in luciferase activity. There was no preferential use of the putative upstream hGnRH start site in neuronal cells. DNase I protection assays showed unique protection patterns with nuclear extracts from GT1-7 and Gn10 neuronal cells and the hGnRH and rGnRH promoter fragments. These data suggest the presence of different cis-acting elements and transacting factors that mediate species-specific neuronal GnRH expression.

Animals↗
PubMed1996

Kinetic analysis of the interaction of cidofovir diphosphate with human cytomegalovirus DNA polymerase.

Cidofovir [CDV,(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, HPMPC] is an acyclic cytosine nucleoside phosphonate analog with potent in vitro and in vivo activity against a broad spectrum of herpesviruses. CDV diphosphate (CDVpp), the putative antiviral metabolite of CDV, is a competitive inhibitor of dCTP and an alternate substrate for human cytomegalovirus (HCMV) DNA polymerase. HCMV DNA polymerase used a synthetic DNA primer-template with a Km value of 90 +/- 8 nM and incorporated dCTP approximately 42 times more efficiently than CDVpp. HCMV DNA polymerase also utilized a synthetic DNA primer containing a single molecule of CDV at the 3'-terminus. The Km value for this DNA primer-template was 165 +/- 42 nM and incorporation of dCTP was approximately 17 times more efficient than that of CDVpp. The slower rate of incorporation of CDVpp was due mostly to the higher Km value of CDVpp toward the enzyme-primer-template complexes. These data demonstrate that incorporation of a single CDV into DNA by HCMV DNA polymerase does not lead to chain termination.

Animals↗
PubMed1996

The effects of radiofrequency catheter ablation on the metabolic enzymes and Ca(++)-ATPase of myocytes.

Using histochemical technique, the effects of radiofrequency catheter ablation (RFCA) on the activities of LDH, SDH, CCO, and Ca++-ATPase of guinea-pig ventricular myocytes were examined. The histological changes were observed for comparison. Radiofrequency energy (500 kHz) delivered was 20 W x 10 s. The results were as follows: RFCA resulted in significant impairments in all the four kinds of enzymes but without statistical differences in the areas involved in this energy level. No statistically significant difference was found between the ranges of enzymatic damages and areas of pathological lesions. These findings showed a consistency in areas of the histological and histochemical lesions resulted from RFCA.

Animals↗
PubMed1996

Assembly-defective OmpC mutants of Escherichia coli K-12.

Novel ompC(Dex) alleles were utilized to isolate mutants defective in OmpC biogenesis. These ompC(Dex) alleles also conferred sensitivity to sodium dodecyl sulfate (SDS), which permitted the isolation of SDS-resistant and OmpC-specific phage-resistant mutants that remained Dex+. Many mutants acquired resistance against these lethal agents by lowering the OmpC level present in the outer membrane. In the majority of these mutants, a defect in the assembly (metastable to stable trimer formation) was responsible for lowering OmpC levels. The assembly defects in various mutant OmpC proteins were caused by single-amino-acid substitutions involving the G-39, G-42, G-223, G-224, Q-240, G-251, and G-282 residues of the mature protein. This assembly defect was correctable by an assembly suppressor allele, asmA3. In addition, we investigated one novel OmpC mutant in which an assembly defect was caused by a disulfide bond formation between two nonnative cysteine residues. The assembly defect was fully corrected in a genetic background in which the cell's ability to form disulfide bonds was compromised. The assembly defect of the two-cysteine OmpC protein was also mended by asmA3, whose suppressive effect was not achieved by preventing disulfide bond formation in the mutant OmpC protein.

Alleles↗
PubMed1995

IUD use and the risk of ectopic pregnancy: a meta-analysis of case-control studies.

Because of inconsistent findings among case-control studies on the relationship between IUD use and the risk of ectopic pregnancy, a meta-analysis of published literature was conducted. From 1977 through 1994, 19 publications regarding 16 studies of ectopic pregnancy and IUD use were found by MEDLINE and manual search. The odds ratio (ORs) of ectopic pregnancy with current and past IUD use in each study were pooled. A quality score system was developed to assess each study. Funnel plot was used to assess potential publication biases. For current IUD use, when cases were compared to pregnant controls, there was an increased risk of ectopic pregnancy (pooled OR: 10.63, 95% confidence interval (CI): 7.66-14.74); when cases were compared to non-pregnant controls, there was no risk of ectopic pregnancy (pooled OR: 1.06, 95% CI: 0.91-1.24). Past IUD use could mildly increase the risk of ectopic pregnancy (pooled OR: 1.40, 95% CI: 1.23-1.59). Selecting pregnant or non-pregnant women as controls, however, did not affect the OR estimates of past IUD use. Current IUD use does not increase the risk of the ectopic pregnancy. However, a pregnancy with an IUD in situ is more often an ectopic one than a pregnancy with no IUD. Past IUD use could mildly elevate the risk of ectopic pregnancy.

Adolescent↗
PubMed1995

Ten-year experience with abdominal aortic aneurysm repair in octogenarians: early results and late outcome.

PURPOSE: This study was undertaken to determine the mortality and morbidity rates associated with abdominal aortic aneurysm (AAA) repair in octogenarians and to identify factors that may influence survival in this age group. METHODS: One hundred fourteen patients (mean age 83 years) were admitted consecutively with 106 infrarenal and eight juxtarenal AAAs from 1984 through 1993. Ninety-four AAAs were asymptomatic, whereas 20 patients with symptoms had 11 intact and nine ruptured AAAs. The mean AAA diameter was 6.7 cm. Repair consisted of aortic bifurcation grafts in 77 patients (67%), tube grafts in 35 (31%), and extraanatomic procedures in 2 (2%). A total of 29 patients (25%) had undergone previous coronary artery bypass (24 patients) or transluminal coronary angioplasty (five patients) either incidentally or as a preliminary procedure before resection of their AAAs. RESULTS: The 30-day mortality rate for the entire series was 14%, but it declined from 23% (11/48) during the first 5 years to 8% (5/66) during the second 5 years of the study period (p = 0.028). Fatal complications occurred in nine (9.6%) of the 94 patients with asymptomatic AAAs and in seven (35%) of the 20 patients who had symptomatic AAAs (p = 0.008). Considering only patients with asymptomatic AAAs, the early mortality rate in the second 5 years (4%) improved significantly (p = 0.038) in comparison to that (17%) for the first 5 years of the study period. The cumulative 5-year survival rate of 48% for 97 available operative survivors was not quite so good as that (59%) for the normal male population of the United States at the age of 80 years (p < 0.0001). Nevertheless, the 5-year survival rate was 80% for 27 operative survivors who received previous myocardial revascularization compared with 38% for 70 others who did not (p = 0.0077). Multiple Cox-regression analysis identified the perioperative homologous blood requirement (p = 0.03) and a history of previous myocardial revascularization (p = 0.03) as significant independent factors influencing late survival. CONCLUSIONS: Repair of AAAs in properly selected octogenarians is safe and durable. When otherwise indicated, it should not be withheld on the basis of advanced age alone. Prior treatment of severe coronary artery disease is associated with enhanced late survival, but patient selection probably is an important consideration in this respect.

Aged↗