Biomedical subjects

X Chen

Publications and source records attributed to X Chen.

At least 1,081 records · Page 60Linked to original sources

PubMed1997

Effect of once weekly administration of mifepristone on ovarian function in normal women.

The effects of mifepristone on ovarian function during a once weekly oral administration regimen were studied in nine healthy women. Each received 25 mg mifepristone on cycle days 3, 10, 17, and 24. Ovulation, as documented by hormonal measurements and ultrasonography, was inhibited during treatment in five subjects, with a midcycle surge of luteinizing hormone and ovulation occurring 6-18 days after the last pill was administered in four of the five subjects. These five treatment cycles were prolonged 9-26 days. The other four subjects had normal cycles as judged by serum hormone levels, ultrasonography, and cycle length. All nine subjects had delayed endometrial growth as indicated by ultrasonography. There was a significant correlation between concentrations of serum mifepristone (10 h and 58 h) and alpha 1-acid glycoprotein, the protein to which mifepristone binds in circulation. Response to mifepristone did not depend on its circulating levels. We conclude that once weekly administration of 25 mg mifepristone can interfere with normal follicular development and function, but the inhibition of ovulation was inconsistent.

Adult↗

PubMed1997

In vitro effects of prostaglandin E2 or indomethacin on the proliferation of lymphokine-activated killer cells and their cytotoxicity against bladder tumor cells in patients with bladder cancer.

PURPOSE: To investigate the combined effects of interleukin-2 (IL-2) with either prostaglandin E2 (PGE2) or indomethacin (IM) on the proliferation and cytolysis of bladder tumor cells by lymphokine-activated killer (LAK) cells in patients with bladder cancer. METHODS: LAK cell proliferation was assayed in the presence of various concentrations of either PGE2 or IM by cell counting. Bladder cancer cell lines BIU-87, EJ and bladder tumor cells (BTC) from the patients were cultured as target cells, and the cytotoxicity of LAK cells was determined by 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, PGE2 in samples of conditioned medium from bladder cancer cells or peripheral blood mononuclear cells (PBMC) as well as plasma from 21 patients with bladder cancer and 20 healthy donors were determined by radioimmunoassay (RIA). RESULTS: The proliferation of LAK cells induced by IL-2 was inhibited by PGE2 (0.05 to 5 ng/mL) in concentration-dependent manner. The enhanced growth of LAK cells was observed at certain concentrations of IM (100-400 ng/mL) from 48 to 96 h. Pretreatment of LAK cells with IM (200 ng/mL) significantly enhanced cytotoxicity against BIU-87, EJ cells, or BTC. More PGE2 was present in conditioned medium from BIU-87 cells than in the conditioned medium from PBMC. CONCLUSIONS: These studies indicate that LAK cell proliferation induced by IL-2 in patients with bladder cancer is inhibited by PGE2 produced by PBMC and bladder cancer cells. This inhibition can be overcome by IM, which may be of use in immunotherapy of bladder cancer.

Carcinoma, Transitional Cell↗

PubMed1997

Elevated neuropeptide Y gene expression and release during hypoglycemic stress.

Our previous studies show that neuropeptide Y (NPY) is involved in mediating sympathetic nerve stimulation-induced vasoconstriction. Insulin hypoglycemia is known to produce increased sympathetic output and elevated arterial pressure. The present study examined the role of NPY in the hypertensive response to insulin by examining the effects of insulin on NPY gene expression, tissue content and release. Subcutaneous injection of insulin produced an immediate increase in plasma NPY immunoreactivity (NPYir) and delayed increases in adrenal and neuronal NPY mRNA and adrenal NPYir in rats. These results suggest that NPY may play a role in insulin-induced hypertension.

Adrenal Medulla↗

PubMed1997

Carotid plaque typing by multiple-parameter ultrasonic tissue characterization.

We evaluated the ability of ultrasonic tissue characterization (UTC), based on backscattered echo signals, to distinguish among the components of advanced carotid plaques. We performed spectral analysis of echo signals acquired from human carotid endarterectomy specimens in vitro to calculate three parameters of the calibrated power spectrum: slope, intercept and total power for fibrous, lipid pool and thrombus constituents of plaque. Plaque constituents were identified histologically. We evaluated classification efficacy by discriminant function analysis. Slope and intercept parameters alone provided correct classification in 92.5%, 57.6% and 72.4% of fibrous, lipid pool and thrombus plaque components, respectively. Slope, intercept and total power used in combination improved classification of the three tissue types to 93.0%, 69.7% and 81.0%. The overall proportion of correctly classified tissue regions increased from 84.5% to 88.0% by the combined use of the three parameters. The improvement in classification that occurred when we included total power as a third parameter suggests that ultrasound plaque components may not consist solely of small, randomly distributed isotropic scatterers. Our ability to identify plaque thrombi provides motivation for future studies of parameter-based imaging methods for identifying such plaque that presents an increased risk of embolic neurologic ischemic events.

Arteriosclerosis↗

PubMed1997

Capsaicin and carbon dioxide act by distinct mechanisms on sensory nerve terminals in the cat cornea.

The discharge of single afferent units recorded from filaments of the mixed ciliary nerve of anaesthetised cats was used to study the effects of CO2, capsaicin and the capsaicin antagonist, capsazepine, on sensory nerve terminals in the cornea. Units were selected on the basis of their sensitivity to CO2 (98.5% applied to the cornea for 30 s in a moist gas stream). Of these units, about 50% (18/38) also responded to capsaicin (0.1 microM applied as droplet and washed off after 20 s), with a discharge of similar magnitude to that produced by CO2. The other CO2-sensitive units (20/38) did not respond to capsaicin. Capsaicin-sensitive units responded more rapidly to CO2 (mean latency to first spike 0.7 +/- 0.2 s) than capsaicin-insensitive units (mean latency to first spike 5.1 +/- 1.2 s). On the basis of their conduction velocity, both the capsaicin-sensitive and the capsaicin-insensitive groups included both A- and C-fibres. Application of capsazepine (10 microM for 5-20 min) to the cornea reversibly blocked the response of the units to capsaicin without affecting responses to CO2. Units that were acutely desensitised by exposure to capsaicin (0.1 microM) for 30 s, during which time the discharge evoked by capsaicin declined to zero, still responded to CO2, though the response was reduced by 44% compared with controls. It is concluded that activation of sensory afferents in the cat cornea by capsaicin and by CO2 appear to involve distinct mechanisms, since: (a) many CO2- sensitive units are not excited by capsaicin; (b) capsazepine selectively blocks excitation by capsaicin without affecting responses to CO2; and (c) desensitisation to capsaicin impairs only partially the responsiveness to CO2.

Animals↗

PubMed1997

Ibogaine and a total alkaloidal extract of Voacanga africana modulate neuronal excitability and synaptic transmission in the rat parabrachial nucleus in vitro.

Ibogaine is a natural alkaloid of Voacanga africana that is effective in the treatment of withdrawal symptoms and craving in drug addicts. As the synaptic and cellular basis of ibogaine's actions are not well understood, this study tested the hypothesis that ibogaine and Voacanga africana extract modulate neuronal excitability and synaptic transmission in the parabrachial nucleus using the nystatin perforated patch-recording technique. Ibogaine and Voacanga africana extract dose dependently, reversibly, and consistently attenuate evoked excitatory synaptic currents recorded in parabrachial neurons. The ED50 of ibogaine's effect is 5 microM, while that of Voacanga africana extract is 170 micrograms/ml. At higher concentrations, ibogaine and Voacanga africana extract induce inward currents or depolarization that are accompanied by increases in evoked and spontaneous firing rate. The depolarization or inward current is also accompanied by an increase in input resistance and reverses polarity around 0 mV. The depolarization and synaptic depression were blocked by the dopamine receptor antagonist haloperidol. These results indicate that ibogaine and Voacanga africana extract 1) depolarize parabrachial neurons with increased excitability and firing rate; 2) depress non-NMDA receptor-mediated fast synaptic transmission; 3) involve dopamine receptor activation in their actions. These results further reveal that the Voacanga africana extract has one-hundredth the activity of ibogaine in depressing synaptic responses. Thus, ibogaine and Voacanga africana extract may produce their central effects by altering dopaminergic and glutamatergic processes.

Animals↗

PubMed1997

Nkx2.6 expression is transiently and specifically restricted to the branchial region of pharyngeal-stage mouse embryos.

The Nkx2.6 gene belongs to the NK superfamily of homeobox genes (Harvey, 1996). We report here the expression pattern of the murine Nkx2.6 gene during early mouse development, which is unique among the NK family of homeobox genes in that its expression is restricted to the very narrow development period between stages E8.5 and E10.5 of embryogenesis. The distribution of Nkx2.6 transcripts is also quite restricted spatially, with expression detected uniquely within the caudal branchial arches. Nkx2.6 is expressed in all three layers comprising the caudal branchial arches (ectoderm, mesectoderm and endoderm) with the strongest expression being detected in the surface ectoderm.

Animals↗

PubMed1997

Non-glycosaminoglycan bearing domains of perlecan and aggrecan influence the utilization of sites for heparan and chondroitin sulfate synthesis.

Perlecan and aggrecan are proteoglycans that receive primarily heparan sulfate and chondroitin sulfate side chains, respectively. Their large multidomained core proteins have little or no homology to each other and their glycosaminoglycan (GAG) attachment sites are restricted to certain domains only. We examined the involvement of the non-GAG bearing domains in designating the GAG type added to the GAG attachment domain by preparing cDNA constructs that expressed perlecan/aggrecan chimeras as recombinant products in COS-7 cells and then determining the size and GAG composition of the recombinant products. The results showed that domain I of perlecan receives primarily (73-81%) heparan sulfate when coupled with domain II and III of perlecan, but when coupled with the G3 domain of aggrecan, it receives primarily (59-63%) chondroitin sulfate. Furthermore, the chondroitin sulfate attachment region of aggrecan received GAG side chains more readily when coupled to the G3 domain of aggrecan than when coupled to domains II and III of perlecan. The GAG side chains on all these recombinant products were small and similar in size. These findings indicate that the utilization of attachment sites for heparan and chondroitin sulfate or the sulfation of these GAGs can be influenced, in part, by non-GAG bearing domains.

Aggrecans↗

PubMed1997

Meeting review: the Second meeting on the Critical Assessment of Techniques for Protein Structure Prediction (CASP2), Asilomar, California, December 13-16, 1996.

In most fields of scientific endeavor, the outcomes of important experiments are not always known before the experiments are performed. But in protein structure prediction, algorithms are usually developed and tested in situations where the answers are known. In December 1996, the Second Meeting on the Critical Assessment of Techniques for Protein Structure Prediction (CASP2) was held in Asilomar, California to rectify this situation: protein sequences were provided in advance for which the experimental structure had not yet been published. Over 70 research groups provided bona fide predictions on 42 targets in four categories: comparative or 'homology' modeling, fold recognition or 'threading', ab initio structure predictions, and docking predictions. Since the previous CASP meeting in 1994, the role of fold recognition in structure prediction has increased enormously with the largest number of groups participating in this category. In this review, we highlight some of the important developments and give at least a qualitative sense of what kind of methods produced some of the better predictions.

Computer Simulation↗

PubMed1997

Analysis of the ecdysteroid UDP-glucosyltransferase gene of Heliothis armigera single-nucleocapsid baculovirus.

An ecdysteroid UDP-glucosyltransferase (egt) gene was identified from the single (S) nucleocapsid nucleopolyhedrovirus of Heliothis armigera (HearNPV). In baculovirus-infected insects the viral enzyme (EGT) plays a pivotal role in abrogating the insect molting process. The open reading frame of the egt gene is 1545 nucleotides long, encoding a putative protein of 515 amino acids with a Mr of 59.1. The 5'-noncoding region contains a putative early (CAGT) and late (TAAG) motif for transcription initiation, a transcription enhancer sequence (CGTCGC) and two TATA boxes. A putative polyA signal, AATAAA, was found downstream of the translation stop codon. A putative signal peptide of 21 residues was present at the N-terminus of the EGT. The HearNPV egt gene has a high degree of nucleotide and amino acid sequence homology to the egt genes of Buzura suppressaria SNPV and Spodoptera exigua MNPV. The HearNPV EGT shares ten conserved motifs with other EGTs. A phylogenetic tree of twelve baculovirus EGTs was constructed by using maximum parsimony analysis, suggesting that SNPVs do not form a separate clade within the baculovirus family.

Amino Acid Sequence↗

PubMed1997

Relation between academic achievement and social adjustment: evidence from Chinese children.

A sample of children in Shanghai, P.R. China, initially aged 10 and 12 years, participated in this 2-year longitudinal project. Information on academic achievement and indexes of social adjustment, including social competence, aggression, social inhibition, leadership, and peer acceptance, was collected from multiple sources. It was found that academic achievement predicted children's social competence and peer acceptance. In turn, children's social functioning and adjustment, including social competence, aggression-disruption, leadership, and peer acceptance, uniquely contributed to academic achievement. These results generally supported the "reciprocal effects" model concerning the relations between academic achievement and social adjustment (S. P. Hinshaw, 1992).

Achievement↗

PubMed1997

Cloning of a Ca(2+)-ATPase gene and the role of cytosolic Ca2+ in the gibberellin-dependent signaling pathway in aleurone cells.

The ultimate goal of this investigation was to identify intermediary steps in the gibberellin (GA)-dependent signaling pathway in rice aleurone cells. By using a differential display approach, a number of putative GA-responsive genes were isolated. One of them, a GA-responsive Ca(2+)-ATPase gene, was identified and partially characterized. A genomic clone and a cDNA clone were isolated and sequenced. The deduced amino acid sequence showed that this protein resembles an endoplasmic reticulum membrane Ca(2+)-ATPase. In a transient assay in rice aleurone cells, expression of the introduced Ca(2+)-ATPase cDNA bypassed the GA requirement for stimulating the expression of a major target gene, the alpha-amylase c gene (Osamy-c). This result suggests that GA-dependent expression of this Ca(2+)-ATPase gene (OsCa-atpase) plays an important role in the GA-dependent signal-transduction pathway. To investigate the possible involvement of other proteins and genes that may affect the intracellular Ca2+ level, compounds which can block different putative steps in the signal-transduction pathway were introduced into rice aleurone cells, and then the level of the OsCa-atpase transcript or the Osamy-c transcript was monitored. In the presence of GA, the rice Ca(2+)-ATPase and the Ca2+ channels appeared to co-regulate the local concentration of cytosolic Ca2+. The release of Ca2+ from the internal stores to the cytoplasm was presumably initiated by inositol-1,4,5-triphosphate which reached a peak level within 25 min after GA induction. As a second messenger, Ca2+ binds to calmodulin (CaM), and the Ca2+/CaM complex regulates the cytosolic Ca2+ by affecting expression of the OsCa-atpase. Finally, a working model is proposed for the GA-dependent signaling pathway in aleurone cells.

Amino Acid Sequence↗

PubMed1997

The in vitro effect of vitamin D3 analogue EB-1089 on a human prostate cancer cell line (PC-3).

OBJECTIVE: To determine the effect of vitamin D3 analogue (EB-1089) on the growth and proliferation of a prostate cancer cell line (PC-3). MATERIALS AND METHODS: PC-3 cells (10(4) cells per well) were plated into 24-well tissue culture plates. After 24 h, the culture medium was replaced with one containing the vitamin D3 analogue EB-1089; a control treatment using only replacement medium was conducted in parallel. Cell proliferation was measured by the incorporation of 3H-thymidine 7 and 12 days after the addition of the vitamin D3 analogue. Cells were precipitated with 5% trichloroacetic acid and the radioactivity determined using a scintillation counter. Each experiment was performed at least five times. RESULTS: There was a significant dose-dependent inhibition of cell growth after 7 and 12 days of treatment with EB-1089, varying from 40 to 70% of the 3H-thymidine incorporation by controls, respectively. The maximum inhibition occurred with 0.1 micromol/L EB-1089 on day 7 and day 12 (both P < 0.01). Longer incubation times appeared to have a greater effect when higher concentrations of EB-1089 were used. CONCLUSION: These in vitro studies have shown that the vitamin D3 analogue EB-1089 can significantly reduce the growth rate of the prostate cancer cell line PC-3. This would support the hypothesis that deficiency of vitamin D increases the risk of prostate cancer and further in vivo testing of vitamin D is warranted for its potential role in active therapy.

Antineoplastic Agents↗

PubMed1997

Effects of chronic ethanol treatment on the expression of calcium transport carriers and NMDA/glutamate receptor proteins in brain synaptic membranes.

Acute exposure to ethanol inhibits both the NMDA receptors and the Na/Ca-exchange carriers in neuronal membranes. This alters intraneuronal signaling pathways activated by Ca2+. Neurons exposed chronically to ethanol exhibit enhanced density and activity of NMDA receptors and increased maximal activity of the exchangers. In the present study, the expression of brain synaptic membrane proteins with ligand binding sites characteristic of NMDA receptors and of exchange carriers were determined after chronic ethanol administration (15 days) to rats. Such treatment caused an increase in the expression of the NMDAR1 receptor subunit, 15% above the levels in the pair-fed controls, as well as of three subunits of a complex that has properties characteristic of NMDA receptors, the glutamate, carboxypiperazinylphosphonate, and glycine binding proteins. Increases for the three binding proteins were 49, 50, and 62%, respectively. The expression of the 120-kDa exchanger proteins was increased by 14% and that of a 36-kDa exchanger-associated protein by 33%. Both the binding proteins and the exchangers returned to basal levels within 36-72 h after withdrawal from ethanol. No changes were detected in synaptic membrane Ca2+, Mg2+-ATPases. The enhanced expression of receptor and exchanger-associated proteins may explain the increases in the density and activity of NMDA receptors and exchange carriers after chronic ethanol treatment.

Animals↗

PubMed1997

Lysozyme fragmentation induced by gamma-radiolysis.

Irradiation of lysozyme in frozen states in the absence of oxygen induces specific fragmentation at defined sites along the backbone chain. This paper localizes radio-fragmentation sites by two methods. First, N-terminal sequencing of radiolysis fragments after separation by SDS-polyacrylamide gel electrophoresis and estimation of their molecular masses. Secondly, after purification of radiolysis fragments by reverse phase-HPLC and determination of their molecular mass by electro-spray-ionization mass-spectrometric analysis, combined to N-terminal sequencing and total amino acid analysis. Evidence for the breakage of the peptide bond itself (CO-NH) is given, with radio-fragmentation sites mostly found at the surface of irradiated lysozyme in solvent exposed loops and turns.

Chromatography, High Pressure Liquid↗

PubMed1997

A dominant mutation in the Chlamydomonas reinhardtii nuclear gene SIM30 suppresses translational defects caused by initiation codon mutations in chloroplast genes.

A suppressor of a translation initiation defect caused by an AUG to AUU mutation in the Chlamydomonas reinhardtii chloroplast petD gene was isolated, defining a nuclear locus that we have named SIM30. A dominant mutant allele at this locus, sim30-1d, was found to increase the translation initiation rate of the mutant petD mRNA. sim30-1d was also able to suppress the translational defect caused by an AUG to AUC mutation in the petD gene, and an AUG to AUU mutation in the chloroplast petA gene. We therefore suggest that the SIM30 gene may encode a general chloroplast translation factor. The ability of sim30-1d to suppress the petD AUG to AUU mutation is diminished in the presence of one or more antibiotic resistance markers located within the 16S and 23S rRNAs, suggesting that the activity of the sim30-1d gene product in translation initiation may involve interaction with ribosomal subunits.

Animals↗

PubMed1997

Evidence for selection of a population of multi-reactive B cells into the splenic marginal zone.

Antibody reactivity to self-antigens is a normal component of the immune system. To study the mechanism by which self-reactive B cells are generated and maintained, we analyzed B cell development in transgenic mice that express a rearranged VH81X heavy chain from the pre-immune repertoire. In these mice, > 95% of B cells express the transgene in association with a variety of kappa light chains but V kappa 1 C being the dominant light chain. These transgenic B cells with identical V kappa 1C-J kappa 5 joins do not normally secrete IgM in vivo, but antibodies derived from these B cells, through LPS activation in vitro or after hybridoma immortalization, are self-reactive and recognize an ubiquitous epitope(s) on intracytoplasmic proteins from different tissues. They have the phenotype and localization pattern of long-lived marginal zone B cells and their development in vivo is blocked by injection of soluble VH81X-V kappa 1CJ kappa 5 IgM antibody. The observations in this transgenic mouse provide evidence for positive selection of a population of self-reactive B cells. These B cells enter the peripheral pool of B cells where they localize in the marginal zone of the spleen and, in contrast to other transgene-expressing B cells, do not secrete IgM antibody.

Animals↗

PubMed1997

Development of VH81X transgene-bearing B cells in fetus and adult: sites for expansion and deletion in conventional and CD5/B1 cells.

The most D-proximal functional VH gene, VH81X, is preferentially expressed in the mouse fetal B cell repertoire; however, it is expressed in few B cells in the adult. To determine when VH81X gene expression affects size and phenotype of particular stages in B cell differentiation, transgenic mice have been developed expressing a germline fetal liver-derived VH81X-mu rearrangement. Comparative analysis of B lymphopoiesis reveals similarities and differences between fetal liver and adult bone marrow which pinpoint developmental stages in mice during which VH81X-expressing B cell progenitors expand or deplete compartment sizes. These include a similar reduction in c-kitR+ and establishment of a predominant CD43low/HSAhigh phenotype within the B220+ CD43+ compartment which is dependent on the association of the transgene with lambda 5. In contrast, the CD43- pre-B and immature B cell compartments are expanded in the fetus but not in the adult. In addition, there are other factors that later disfavor the survival of VH81X-expressing B1 and B2 cells. Thus the failure to detect VH81X-bearing B cells in the adult is the result of a multistep selection process occurring at all stages during B repertoire expansion.

Aging↗