Biomedical subjects

W Feng

Publications and source records attributed to W Feng.

At least 37 records · Page 2Linked to original sources

PubMed2001

Variations in prescribing practices for novel antipsychotic medications among Veterans Affairs hospitals.

This study examined prescribing practices for antipsychotic medications at 13 Veterans Affairs (VA) medical centers and whether patients' sociodemographic characteristics were associated with receiving novel agents. Automated pharmacy data were used to identify 599 patients who had been diagnosed as having schizophrenia and who had received a prescription for an antipsychotic medication after their last discharge from a VA medical center in 1997. Novel antipsychotics were found to have been prescribed for almost half of the patients (47 percent). In logistic regression analysis, significant variations in prescription of novel agents were found among the facilities and among ethnic groups. The results of this study suggest that prescribing practices are influenced by both facility and patient characteristics.

Adult↗

PubMed2001

Potentiation of estrogen receptor activation function 1 (AF-1) by Src/JNK through a serine 118-independent pathway.

Estrogen receptor (ER) is activated either by ligand or by signals from tyrosine kinase-linked cell surface receptors. We investigated whether the nonreceptor Src tyrosine kinase could affect ER activity. Expression of constitutively active Src or stimulation of the endogenous Src/JNK pathway enhances transcriptional activation by the estrogen-ER complex and strongly stimulates the otherwise weak activation by the unliganded ER and the tamoxifen-ER complex. Src affects ER activation function 1 (AF-1), and not ER AF-2, and does so through its tyrosine kinase activity. This effect of Src is mediated partly through a Raf/mitogen-activated ERK kinase/extracellular signal-regulated kinase (Raf/MEK/ERK) signaling cascade and partly through a MEKK/JNKK/JNK cascade. Although, as previously shown, Src action through activated ERK stimulates AF-1 by phosphorylation at S118, Src action through activated JNK neither leads to phosphorylation of S118 nor requires S118 for its action. We therefore suggest that the Src/JNK pathway enhances AF-1 activity by modification of ER AF-1-associated proteins. Src potentiates activation functions in CREB-binding protein (CBP) and glucocorticoid receptor interacting protein 1 (GRIP1), and we discuss the possibility that the Src/JNK pathway enhances the activity of these coactivators, which are known to mediate AF-1 action.

CREB-Binding Protein↗

PubMed2001

Elements in erythrocytes of population with different thyroid hormone status.

The contents of elements K, Ca, Fe, Cu, Zn, Se, and Rb in erythrocytes of 78 cases with different thyroid hormone status have been measured by proton-induced X-ray emission and neutron activation analysis. According to the status of thyroid hormones T3, T4, TSH, FT3, and FT4 detected by radioimmunoassay, the experiment subjects were divided into four groups (i.e., hyperthyroid, hypothyroid, critical [one of thyroid hormones was abnormal], and normal). Elements contents and hormones levels of four groups were analyzed by one-way analysis of variance and correlation using an SPSS/PC statistical package. The results showed that the Se contents of four groups were not significantly different (p<0.05). Zn content of hypothyroid group was significantly higher than those of hyperthyroid and critical groups. The Zn content of the normal group was higher than that of the hypothyroid group and lower than that of the hyperthyroid and critical groups. In the hyperthyroid group, there were significant correlations between elements contents and thyroid hormones levels (except TSH), but not between elements contents and levels of thyroid hormones. However, in the hypothyroid group, relatively strong correlations have been found between elements contents and thyroid hormones levels, especially between Zn and the T3/T4 ratio, and between Zn and TSH.

Animals↗

PubMed2000

Transmembrane redox sensor of ryanodine receptor complex.

Inositol 1,4,5-trisphosphate receptors (IP(3)R) and ryanodine receptors (RyR) mediate the release of endoplasmic and sarcoplasmic reticulum (ER/SR) Ca(2+) stores and regulate Ca(2+) entry through voltage-dependent or ligand-gated channels of the plasma membrane. A prominent property of ER/SR Ca(2+) channels is exquisite sensitivity to sulfhydryl-modifying reagents. A plausible role for sulfhydryl chemistry in physiologic regulation of Ca(2+) release channels and the fidelity of Ca(2+) release from ER/SR is lacking. This study reveals the existence of a transmembrane redox sensor within the RyR1 channel complex that confers tight regulation of channel activity in response to changes in transmembrane redox potential produced by cytoplasmic and luminal glutathione. A transporter selective for glutathione is co-localized with RyR1 within the SR membrane to maintain local redox potential gradients consistent with redox regulation of ER/SR Ca(2+) release. Hyperreactive sulfhydryls previously shown to reside within the RyR1 complex (Liu, G., and Pessah, I. N. (1994) J. Biol. Chem. 269, 33028-33034) are an essential biochemical component of a transmembrane redox sensor. Transmembrane redox sensing may represent a fundamental mechanism by which ER/SR Ca(2+) channels respond to localized changes in transmembrane glutathione redox potential produced by physiologic and pathophysiologic modulators of Ca(2+) release from stores.

Animals↗

PubMed2000

Activation of lytic Epstein-Barr virus (EBV) infection by radiation and sodium butyrate in vitro and in vivo: a potential method for treating EBV-positive malignancies.

The consistent presence of the EBV genome in certain tumors offers the potential for novel EBV-directed therapies. Switching the latent form of EBV infection present in most EBV-positive tumor cells into the cytolytic form may be clinically useful because lytic EBV infection leads to host cell destruction, and very few normal cells contain the EBV genome. It would also be therapeutically advantageous to induce expression of EBV-encoded lytic proteins that convert the nucleoside analogues ganciclovir (GCV) and 3'-azido-3'deoxythymidine (AZT) into their active, cytotoxic forms. In this report, we have explored two different approaches for activating the lytic form of EBV infection in tumors. We show that gamma-irradiation at clinically relevant doses induces lytic EBV infection in lymphoblastoid cell lines in vitro as well as in EBV-positive B-cell tumors in SCID mice. In addition, sodium butyrate (given as a single i.p. dose) is effective for activating lytic viral infection in some EBV tumor types in SCID mice. We also examined whether low-dose gamma-irradiation treatment of EBV-positive lymphoblastoid cells in vitro promotes GCV or AZT susceptibility. The combination of radiation with either GCV or AZT induced significantly more cell killing in vitro than either radiation or prodrug treatment alone. Most importantly, we found that the combination of gamma-irradiation and GCV was much more effective in treating EBV-positive lymphoblastoid tumors in SCID mice than either agent alone. Thus, GCV or AZT treatment could potentially enhance the therapeutic efficacy of radiation therapy for EBV-positive lymphomas in patients.

Animals↗

PubMed2000

Arthropod- and host-specific Borrelia burgdorferi bbk32 expression and the inhibition of spirochete transmission.

Antisera to BBK32 (a Borrelia burgdorferi fibronectin-binding protein) and BBK50, two Ags synthesized during infection, protect mice from experimental syringe-borne Lyme borreliosis. Therefore, B. burgdorferi bbk32 and bbk50 expression within Ixodes scapularis ticks and the murine host, and the effect of BBK32 and BBK50 antisera on spirochetes throughout the vector-host life cycle were investigated. bbk32 and bbk50 mRNA and protein were first detected within engorged ticks, demonstrating regulated expression within the vector. Then bbk32 expression increased in mice at the cutaneous site of inoculation. During disseminated murine infection, bbk32 and bbk50 were expressed in several murine tissues, and mRNA levels were greatest in the heart and spleen at 30 days. BBK32 antisera protected mice from tick-borne B. burgdorferi infection and spirochete numbers were reduced by 90% within nymphs that engorged on immunized mice. Moreover, 75% of these ticks did not retain spirochetes upon molting, and subsequent B. burgdorferi transmission by adult ticks was impaired. Larval acquisition of B. burgdorferi by I. scapularis was also inhibited by BBK32 antisera. These data demonstrate that bbk32 and bbk50 are expressed during tick engorgement and that BBK32 antisera can interfere with spirochete transmission at various stages of the vector-host life cycle. These studies provide insight into mechanisms of immunity to Lyme borreliosis and other vector-borne diseases.

Animals↗

PubMed2000

Effects of CTx and 8-bromo-cAMP on LPS-induced gene expression of cytokines in murine peritoneal macrophages.

LPS, an endotoxin isolated from gram-negative bacterial, has been shown to be a potent cytokine initiator in murine peritoneal macrophages. CAMP-dependent pathway is generally considered to play a suppressive role in immune response. This study investigated the effect of cAMP on LPS-induced gene expression of cytokines in murine macrophages. Our data clearly demonstrated that in LPS-treated macrophages, cAMP elevator (CTx and 8-bromo-cAMP) could increase IL-1Ra and IL-10 gene expression, while mRNAs of IL-1alpha, IL-12, IL-6, and MIF were decreased and other cytokines like IL-1beta, and IFN-gamma did not give a definite tendency. This is the first report that CTx and 8-bromo-cAMP positively regulate IL-1Ra gene expression in LPS-stimulated macrophages. Our data also suggest that a cAMP-dependent pathway may play a regulatory role in Toll-receptor system.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2000

Photochemistry of hydrolytic iron (III) species and photoinduced degradation of organic compounds. A minireview.

On the basis of the research literature of the last fifty years, we have reviewed the photochemical properties of different hydrolytic Fe(III) species and the photodegradation of organic compounds in aqueous solutions initiated by them (mainly including low-molecular-weight Fe(III)-OH complexes, Fe(III) oxides (Fe2O3) and Fe(III) hydroxides (FeOOH)). Furthermore, the feasibility and prospects of the novel photochemical methods of using Fe(III) salts and oxides in wastewater treatments are being discussed in this paper.

Hydrolysis↗

PubMed2000

Degradation mechanism of azo dye C. I. reactive red 2 by iron powder reduction and photooxidation in aqueous solutions.

We have made a comparison of the UV-VIS spectra of three azo dyes, C. I. reactive red 2, orange II and C. I. reactive black 8, in aqueous solutions during treatment with iron powder reduction and photooxidation. From this, we propose their mechanisms for reduction photooxidation. GC/MS analyses of the degradation products of the dye C. I. reactive red 2 demonstrated some important steps producing hydrogenated azo structure, substituted benzene and substituted naphthalene.

Azo Compounds↗

PubMed2000

Functional role of hyperreactive sulfhydryl moieties within the ryanodine receptor complex.

Several laboratories using chemically heterogeneous sulfhydryl modifying agents have shown that sarcoplasmic reticulum (SR) Ca2+ channels known as ryanodine receptors (RyRs) are especially sensitive to modification of functionally important cysteine residues. The functional consequence of sulfhydryl modification of RyRs can include phases of activation and inhibition that are very much dependent on the concentration of the reagent used, the length of exposure, and the nature of the chemical reaction the reagent undertakes with sulfhydryl groups. Most challenging is understanding the relationship for how specific sulfhydryl moieties ascribe specific aspects of RyR function. Considering the structural complexity of the RyR complex with its associated proteins, this task is likely to be a formidable one. A small number of hyperreactive thiols have been shown to exist within the RyR complex. Their functional role does not appear to impact directly on channel gating. Rather hyperreactive cysteine (Cys) moieties may represent biochemical components of a redox sensor that conveys information about localized changes in redox potential produced by physiologic (e.g., glutathione, nitric oxide) and pathophysiologic (quinones, reactive oxygen species) channel modulators to the Ca2+ release process. The molecular and functional details of such a redox sensor remains to be elucidated.

Animals↗

PubMed2000

Effect of endurance training on lipid metabolism in women: a potential role for PPARalpha in the metabolic response to training.

Endurance training increases fatty acid oxidation (FAO) and skeletal muscle oxidative capacity. However, the source of the additional fat and the mechanisms for increasing FAO capacity in muscle are not clear. We measured whole body and regional lipolytic activity and whole body and plasma FAO in six lean women during 90 min of bicycling exercise (50% pretraining peak O(2) consumption) before and after 12 wk of endurance training. We also assessed skeletal muscle content of peroxisome proliferator-activated receptor-alpha (PPARalpha) and its target proteins that regulate FAO [medium-chain and very long chain acyl-CoA dehydrogenase (MCAD and VLCAD)]. Despite a 25% increase in whole body FAO during exercise after training (P < 0.05), training did not alter regional adipose tissue lipolysis (abdominal: 0.56 +/- 0.26 and 0.57 +/- 0.10 micromol x 100 g(-1) x min(-1); femoral: 0.13 +/- 0.07 and 0.09 +/- 0.02 micromol x 100 g(-1) x min(-1)), whole body palmitate rate of appearance in plasma (168 +/- 18 and 150 +/- 25 micromol/min), and plasma FAO (554 +/- 61 and 601 +/- 45 micromol/min). However, training doubled the levels of muscle PPARalpha, MCAD, and VLCAD. We conclude that training increases the use of nonplasma fatty acids and may enhance skeletal muscle oxidative capacity by PPARalpha regulation of gene expression.

Acyl-CoA Dehydrogenase↗

PubMed2000

[Advances in diagnosis and treatment of ectopic pregnancy during the past ten years].

OBJECTIVE: To investigate the changes of diagnosis and treatment of ectopic pregnancy (EP) during the past ten years. METHODS: Medical records of 1,970 cases with EP seen in our hospital from Jan. 1987 to Dec. 1996 were collected and analyzed retrospectively. RESULTS: (1) The incidence of EP increases from 1.0 per 42.4 labours during 1987-1988 to 1.0 per 6.6 labours in 1995-1996. (2) Diagnosis was confirmed more by television laparoscopy, transvaginal ultrasonography and sensitive human chorionic gonadotropin-beta subunit assay rather than loparotomy and with a shorter period, (6.5 +/- 0.7) days in 1987-1988 versus (3.7 +/- 0.2) days in 1995-1996. (3) The choice of treatment was more conservative or through laparoscopic surgery than abdominal salpingectomy. (4) The success rate of conservative surgery expectant management reached 100.0% and medical treatment with a variety of choices around 80.0%-85.%. CONCLUSIONS: Although the incidence of EP increased, with the improvement of diagnostic approaches, patients were detected at an earlier stage and possible to be treated more conservatively.

Female↗

PubMed1999

Modification of ryanodine receptor/Ca2+ release channel with dinitrofluorobenzene.

Modification of the ryanodine receptor (RyR)/Ca(2+) release channel with 2,4-dinitrofluorobenzene (DNFB) indicated that two classes of amino group interact with the reagent, as can be distinguished on the basis of their reactivity/accessibility and the effects on ryanodine binding and single channel activities. One group interacted very rapidly (t(1/2)<30 s) at 25 degrees C with low concentrations of DNFB [C(50) (concentration of DNFB required for 50% inhibition or stimulation of ryanodine binding)=5 microM], and at pH values of 6.2 and higher. This interaction resulted in the marked stimulation of ryanodine binding and the complete inhibition of a single Ca(2+) release channel incorporated into planar lipid bilayer. The second group is accessible at higher temperatures (37 degrees C); at pH values higher than 7.4 it reacted slowly (t(1/2)=20 min) with high concentrations of DNFB (C(50)=70 microM). This interaction led to the inhibition of ryanodine binding and single channel activity. Modification of RyR with DNFB under the stimulatory conditions resulted in 3.6-fold and 6-fold increases in ryanodine-binding and Ca(2+)-binding affinities respectively. Modification with DNFB under the inhibitory conditions resulted in a decrease in the total ryanodine-binding sites. The exposure of the RyR single channel to DNFB under both inhibitory and stimulatory conditions led to the complete closure of the channel. However, when modified under the stimulatory conditions, but not under the inhibitory ones, the DNFB-modified closed channel could be re-activated by sub-micromolar concentrations of ryanodine, in the presence of nanomolar concentrations of Ca(2+). The DNFB-modified ryanodine-activated RyR channel showed fast transitions between open, closed and several sub-conductance states, and was completely closed by Ruthenium Red. ATP re-activated the DNFB-modified closed channel or, if present during modification, prevented the inhibition of RyR channel activity by DNFB. Neither the stimulation nor the inhibition of ryanodine binding by modification with DNFB was affected by the presence of ATP. By using the photoreactive ATP analogue 3'-O-(4-benzoyl)benzoyl-[alpha-(32)P]ATP we found that DNFB modification had no effect on the ATP-binding site of RyR. The results are discussed with regard to the involvement of amino group residues in channel gating, ryanodine association/dissociation and occlusion, and the relationship between the open/closed state of the RyR and its capacity to bind ryanodine.

Adenosine Triphosphate↗

PubMed1999

Affinity chromatography of human estrogen receptor-alpha expressed in Saccharomyces cerevisiae. Combination of heparin- and 17beta-estradiol-affinity chromatography.

Estrogen receptor-alpha is a member of the nuclear hormone receptor superfamily and is considered as a very important regulatory protein. Human estrogen receptor-alpha has been cloned into Saccharomyces cerevisiae as a fusion to ubiquitin and expression is controlled by a metallothionin promotor. Pilot scale quantities of receptor have been produced by a yeast strain transformed with expression plasmid YEpE13 [Graumann et al., J. Steroid Biochem. Mol. Biol. 57 (1996) 293] in a 14 l stirred tank reactor. The yeast extract contained 2-4 pmol of receptor protein per mg total protein. A purification scheme has been developed using heparin-affinity chromatography combined with affinity chromatography with immobilized 17beta-estradiol 17-hemisuccinate. Heparin-affinity chromatography was very efficient to remove host cell protein. Accompanying proteins that stabilize unoccupied receptor have not been dissociated during elution. The receptor could be purified 5-10-fold in ligand-free state. In contrast to previous reports, we did not find a difference of the binding affinity of liganded and unliganded receptor for heparin immobilized onto Sepharose. The unoccupied receptor could be further purified 100-fold with ligand-affinity chromatography using 17beta-estradiol 17-hemisuccinate-bovine serum albumin-Sepharose. The receptor could be kept in its native state, although saturated with 17beta-estradiol. The purification sequence allows an efficient production of receptor. Further improvement of productivity can be only accomplished by increasing the expression level.

Base Sequence↗

PubMed1999

Effects of dextran on tracheal mucociliary velocity in dogs in vivo.

We have previously shown that dextran (molecular weight 4kDa) is a potential mucolytic agent, reducing the viscoelasticity and spinnability of cystic fibrosis (CF) sputum and improving its mucociliary clearability during in vitro testing. We wished to see whether low molecular weight (LMW) dextran had similar effects on mucus rheology when administered by aerosol to living dogs, and whether the administration of dextran increased the rate of mucociliary clearance. Healthy mongrel dogs were anesthetized with pentobarbital and intubated. After a 30-min Ringer aerosol delivery during spontaneous breathing, tracheal mucociliary velocity (TMV by charcoal marker particle transport) was measured under bronchoscopic control, and mucus for viscoelasticity analysis (magnetic rheometer) was collected by the endotracheal tube method. Then LMW dextran in Ringer vehicle was delivered by aerosol via the endotracheal tube, followed by the same procedures. We performed eight experiments in eight dogs, involving 30 min administrations of dextran aerosol; all dogs received inhalations of 20 mg/ml, 65 mg/ml, and 200 mg/ml dextran. Compared with Ringer control, TMV increased to 145% of control (P=0.0417) at 65 mg/ml dextran. Mucus viscoelasticity (G*) significantly decreased to 19% of control (P=0.0426) at 65 mg/ml. This in vivo study supports our previous in vitro testing, that LMW dextran decreases the mucus viscoelasticity and increases the rate of mucociliary clearance. We estimate the dosage received by aerosol at 65 mg/ml to be within the effective concentration range studied in vitro, i.e. 10-15 mg/ml final concentration. The results are consistent with the proposed mechanism that the saccharide moieties in LMW dextran compete for hydrogen bonding sites with other mucous glycoproteins. These new hydrogen bonds are structurally and rheologically ineffective, thus reducing the overall cross-link density, and making the mucus more easily cleared by ciliary and cough mechanisms.

Administration, Inhalation↗

PubMed1999

Comparison of the chromium distribution in organs and subcellular fractions of normal and diabetic rats by using enriched stable isotope Cr-50 tracer technique.

The enriched stable isotope 50Cr(III) tracer technique combined with neutron activation analysis was used to examine the intracellular distribution of Cr(III) in the liver, pancreas, testes, and kidney homogenates of both normal and diabetic rats. Our new results showed that the nucleic fraction has the highest Cr concentration in the liver cell of both normal and diabetic rats. The diabetic rats retain more Cr in the mitochondrial and lysosomal fractions of liver homogenate than the normal. This is likely an indication of chromium participating in the glucose or lipid metabolism to compensate the low level of insulin in the body of diabetic rats. The concentrations of Cr in the subcellular fractions of pancreas, testes, and kidney in the normal rats are higher than those in the diabetic rats, which favor the hypothesis that Cr(III) plays its biological function via interaction with the insulin-sensitive tissues or enhancement of the sensitivity of the insulin receptor.

Animals↗

PubMed1999

Borrelia burgdorferi erpT expression in the arthropod vector and murine host.

The expression of a Borrelia burgdorferi gene, erpT, was investigated throughout the spirochaete life cycle in the arthropod vector and the murine host. Three phage clones from a B. burgdorferi DNA expression library synthesized a 30 kDa antigen that was recognized by antibodies in the sera of B. burgdorferi-infected mice but not mice hyperimmunized with B. burgdorferi lysates. Differential antibody binding suggested that this protein was preferentially expressed in vivo. This antigen was designated ErpT, based upon 99.6% homology with the BBF01 sequence in the B. burgdorferi genome. ErpT was not detected on spirochaetes cultured in BSK II medium by indirect immunofluorescence or in B. burgdorferi lysates by immunoblotting, implying that ErpT is not readily produced in vitro. erpT mRNA was not discernible by Northern blot but was identified by RNA polymerase chain reaction in vitro, indicating that erpT is expressed at low levels by cultured spirochaetes. erpT expression was then investigated in the vector and mice because B. burgdorferi do not normally reside in culture medium. RNA polymerase chain reaction and immunofluorescence studies demonstrated that erpT was expressed by a small minority of B. burgdorferi (11/500, 2.2%) within unfed ticks and then repressed during engorgement. erpT mRNA or ErpT antibodies were first detected in B. burgdorferi-infected mice at 4 weeks, suggesting that erpT was not expressed in the early stages of murine infection. Then, during persistent infection, RNA polymerase chain reaction showed that erpT was expressed by B. burgdorferi within the joints, heart and spleen, but not by spirochaetes in the skin. Immunization of mice with ErpT was antigenic but was not protective. These studies demonstrate that B. burgdorferi erpT is differentially expressed throughout the B. burgdorferi life cycle, in both the vector and the mammalian host, and is primarily expressed in extracutaneous sites during murine infection.

Animals↗

PubMed1999

Antagonistic effects of NES and NLS motifs determine S. cerevisiae Rna1p subcellular distribution.

Nucleus/cytosol exchange requires a GTPase, Ran. In yeast Rna1p is the GTPase activating protein for Ran (RanGAP) and Prp20p is the Ran GDP/GTP exchange factor (GEF). RanGAP is primarily cytosolic and GEF is nuclear. Their subcellular distributions led to the prediction that Ran-GTP hydrolysis takes place solely in the cytosol and GDP/GTP exchange solely in the nucleus. Current models propose that the Ran-GTP/Ran-GDP gradient across the nuclear membrane determines the direction of exchange. We provide three lines of evidence that Rna1p enters and leaves the nuclear interior. (1) Rna1p possesses leucine-rich nuclear export sequences (NES) that are able to relocate a passenger karyophilic protein to the cytosol; alterations of consensus residues re-establish nuclear location. (2) Rna1p possesses other sequences that function as a novel nuclear localization sequence able to deliver a passenger cytosolic protein to the nucleus. (3) Endogenous Rna1p location is dependent upon Xpo1p/Crm1p, the yeast exportin for leucine-rich NES-containing proteins. The data support the hypothesis that Rna1p exists on both sides of the nuclear membrane, perhaps regulating the Ran-GTP/Ran-GDP gradient, participating in a complete RanGTPase nuclear cycle or serving a novel function.

Amino Acid Sequence↗