Search PubMed⌕ Search

Biomedical subjects

W Xu

Publications and source records attributed to W Xu.

At least 307 records · Page 17Linked to original sources
PubMed1998

Direct Observation of Polymer Network Structure in Macroporous N-Isopropylacrylamide Gel by Raman Microscopy.

The Raman microscopy technique is used to characterize the temperature-induced evolution of the pore structures of a macroporous N-isopropylacrylamide (NIPA). The gel is synthesized using a suspension of 45 wt % toluene and 55 wt % pregel NIPA solution. The intensity of the band due to the CH2 bending vibration, centered at 1445 cm-1, is used to monitor the distribution of the polymer chain density in the lateral plane. It is found that the macroporous gel consists of water-rich areas, which can be interpreted as the pores, and polymer-rich areas. At room temperature, the average sizes of the pores and the width of polymer-rich areas are 75 µm and 20 µm, respectively. Both the pores and their surrounding polymer-rich areas have random geometry, as demonstrated by the Raman microimaging. With increased temperature the size of the pores decreases. This process is accompanied by a narrowing of the polymer-rich areas. At higher temperatures polymer chains bunch together and this process accelerates rapidly near the volume phase transition temperature (34 degreesC). Above 36 degreesC, the pore sizes become too small to be resolved using Raman microscopy.

Journal Article↗
PubMed1998

Isolation and characterization of the mouse beta 2/neuroD gene promoter.

Beta2/neuroD is a basic helix-loop-helix protein involved in differentiation of the endocrine pancreas and the central nervous system. A 2-kb fragment containing the 5' upstream region of the mouse beta2/neuroD gene was cloned and sequenced. The cloned fragment was tested for promoter activity in six cell lines. Strong promoter activity was apparent in the three pancreatic beta cell lines, beta-HC3, beta-HC9, and NIT-1, whereas weak activity was seen in NIH 3T3, Rat-1, and MCF-7 cell lines. Analysis of promoter activity of deletion mutants in beta-HC3 cells indicated that while basal promoter activity was observed with a fragment which extended -109 bp upstream of the transcription start site, maximal activity required the fragment -2091 to -297 bp.

Animals↗
PubMed1998

Neuronal expression of the glutamate transporter GLT-1 in hippocampal microcultures.

To address the question of the relative contributions of glial and neuronal glutamate transport in the vertebrate CNS, we studied the distribution of forebrain glutamate transporters in rat hippocampal microcultures, a preparation in which physiological functions of glutamate transporters have been well characterized. Two of the three transporters, GLAST (EAAT1) and EAAC1 (EAAT3), are localized to microculture glia and neurons, respectively, as expected. However, we find strong immunoreactivity for the third glutamate transporter GLT-1 (EAAT2), a putatively glial transporter, in microculture neurons and in a small subset of microculture glia. Indistinguishable immunohistochemical staining patterns for GLT-1 were obtained with antibodies directed against both the N terminal and C terminal of the GLT-1 protein. Double-labeling experiments suggest that neuronal GLT-1 protein is primarily localized to the dendrites of excitatory neurons. Neuronal electrogenic transport currents in response to D-aspartate applications were occluded by the selective GLT-1 inhibitor dihydrokainate. In contrast, glia exhibited a larger transporter current density than did neurons, and the glial transport current was less sensitive to dihydrokainate. Neuronal transport currents were potentiated less than were glial currents when the chaotropic anion thiocyanate was substituted for gluconate in the whole-cell recording pipette, consistent with the previously reported lower anion permeability of EAAC1 and GLT-1 compared with that of GLAST. After microculture glia were rendered nonviable, excitatory autaptic currents (EACs) were prolonged in the presence of dihydrokainate, suggesting that neuronal GLT-1 is capable of participating in the clearance of synaptically released glutamate. Our results suggest that the initially proposed characterization of GLT-1 as a purely glial transporter is too simplistic and that under certain conditions functional GLT-1 protein can be expressed in brain neurons. The study suggests that changes in GLT-1 levels that occur with pathology or experimental manipulations cannot be assumed to be glial.

ATP-Binding Cassette Transporters↗
PubMed1998

osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.

Osteoprotegerin (OPG) is a secreted protein that inhibits osteoclast formation. In this study the physiological role of OPG is investigated by generating OPG-deficient mice. Adolescent and adult OPG-/- mice exhibit a decrease in total bone density characterized by severe trabecular and cortical bone porosity, marked thinning of the parietal bones of the skull, and a high incidence of fractures. These findings demonstrate that OPG is a critical regulator of postnatal bone mass. Unexpectedly, OPG-deficient mice also exhibit medial calcification of the aorta and renal arteries, suggesting that regulation of OPG, its signaling pathway, or its ligand(s) may play a role in the long observed association between osteoporosis and vascular calcification.

Animals↗
PubMed1998

Differences in elasticity of vinculin-deficient F9 cells measured by magnetometry and atomic force microscopy.

We have investigated a mouse F9 embryonic carcinoma cell line, in which both vinculin genes were inactivated by homologous recombination, that exhibits defective adhesion and spreading [Coll et al. (1995) Proc. Natl. Acad. Sci. USA 92, 9161-9165]. Using a magnetometer and RGD-coated magnetic microbeads, we measured the local effect of loss and replacement of vinculin on mechanical force transfer across integrins. Vinculin-deficient F9Vin(-/-) cells showed a 21% difference in relative stiffness compared to wild-type cells. This was restored to near wild-type levels after transfection and constitutive expression of increasing amounts of vinculin into F9Vin(-/-) cells. In contrast, the transfection of vinculin constructs deficient in amino acids 1-288 (containing the talin- and alpha-actinin-binding site) or substituting tyrosine for phenylalanine (phosphorylation site, amino acid 822) in F9Vin(-/-) cells resulted in partial restoration of stiffness. Using atomic force microscopy to map the relative elasticity of entire F9 cells by 128 x 128 (n = 16,384) force scans, we observed a correlation with magnetometer measurements. These findings suggest that vinculin may promote cell adhesions and spreading by stabilizing focal adhesions and transferring mechanical stresses that drive cytoskeletal remodeling, thereby affecting the elastic properties of the cell.

Animals↗
PubMed1998

Peptide and protein phosphorylation by protein tyrosine kinase Csk: insights into specificity and mechanism.

Csk (C-terminal Src kinase) is a protein tyrosine kinase that phosphorylates Src family member C-terminal tails, resulting in down-regulation of Src family members. The molecular basis of Csk's substrate specificity and catalytic mechanism with a protein substrate was investigated. Using a peptide library approach, preferential amino acids which are unrelated to the conserved Src C-terminal sequence were identified. The validity of these preferences was confirmed by synthesizing a short consensus peptide and demonstrating its high catalytic efficiency with Csk. These results underscore the difficulties of relying on amino acids neighboring tyrosine in protein sequences as predictors of protein kinase substrate specificity for in vivo analysis. In addition, a catalytically inactive version of the Src family member, Lck (lymphoid cell kinase), was expressed, purified, and evaluated as a Csk substrate. It was proven to be the most catalytically efficient substrate yet identified for Csk. The high efficiency of purified Csk phosphorylating a pure, unphosphorylated Src family member argues against the importance of an SH2-phosphotyrosine docking interaction or the involvement of extra recruitment proteins in facilitating Csk phosphorylation of Src family members. Kinetic studies revealed that the chemical step is at least partially rate-determining in Csk-mediated phosphoryl transfer to the Lck protein. Other properties including preferences for Mn over Mg, thio effects, and Km's for ATP also correlate fairly well between protein and peptide phosphorylation. The lack of a significant impact of increased salt on the Km for Lck phosphorylation differs from Csk-mediated poly(Glu,Tyr) phosphorylation, and argues against the importance of electrostatic effects in the Csk-Lck binding interaction. The failure of the Lck phosphorylation product (phosphotyrosine-505) to significantly inhibit Csk phosphorylation of Lck is consistent with a catalytic model involving multidomain structural interactions between substrate and enzyme.

Adenosine Triphosphate↗
PubMed1998

The Effect of Many-Body Interactions on the Sedimentation of Monodisperse Particle Dispersions

An experimental investigation was made of the sedimentation rate of low-charged monodisperse silica and polystyrene latex particle dispersions as a function of the particle volume fraction. It was found that the normalized sedimentation velocity U/U0, corrected for the effect of the two-body hydrodynamic interaction, increases with the particle volume fraction, which indicates that the degree of particle aggregation inside the dispersions increases with the particle volume fraction. This phenomenon results from attractive many-body hydrodynamic interactions between colloidal particles. It is reported for the first time that the many-body hydrodynamic interaction becomes important at the particle concentration of 6.5 vol% in monodisperse dispersions, and the many-body thermodynamic interaction is negligible at a low particle concentration, i.e., less than 15 vol%. The effect of many-body hydrodynamic interaction on the particle microstructure was also experimentally examined by using a nondestructive Kossel diffraction technique based on the principle of back-light scattering. It was found that the particle packing structure inside the dispersion initially becomes more ordered with the increase of the particle volume fraction. However, there is less increase in the particle ordering structure after 6 vol%. Furthermore, after the particle concentration reaches 10 vol%, the particle packing structure decreases to a value lower than that of 6 vol% due to the increased particle aggregation, as found in the sedimentation experiments. Predictions of a statistical thermodynamic model were compared with the experimental data on structure factors. It is found that particle dimerization occurs around 10 vol%, which agrees with the sedimentation results. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗
PubMed1998

Does participation in psychosocial treatment augment the benefit of clozapine? Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.

BACKGROUND: This study examines the role of participation in psychosocial treatment as a mediator of the clinical effectiveness of clozapine. METHODS: Subjects participated in a 12-month double-blind random-assignment trial comparing clozapine and haloperidol in patients hospitalized 30 to 364 days for refractory schizophrenia at 15 Department of Veterans Affairs medical centers. A broker-advocate case management intervention was used to facilitate participation in psychosocial treatments and to document such participation. RESULTS: Between those who continued receiving clozapine (n=122) or a conventional antipsychotic drug (n=169) for 12 months, those receiving clozapine were more likely to participate in psychosocial rehabilitation treatment. Although they were no more likely to receive clinical recommendations for such treatments, they were more likely to both verbally accept recommendations and to act on them. Structural equation modeling shows that participation in psychosocial treatment did not play a mediating role in clozapine's effect on outcomes at 6 months, but was associated with both reduced symptoms and improved quality of life at 12 months. CONCLUSIONS: Clozapine facilitates participation in psychosocial treatment, and such enhanced participation is associated with improved quality-of-life and symptom outcomes. Psychosocial rehabilitation should be offered concomitantly with clozapine.

Adult↗
PubMed1998

Jak-STAT pathway is involved in the induction of TNF-beta gene during stimulation by IL-2.

IL-2 is the major regulatory cytokine of the immune system. It plays a key role in T cell survival, growth and activation. IL-2 may induce the expression of multiple genes including some cytokine genes. The induction of these genes is triggered by different signal pathways, one of them being the Jak-STAT signal pathway. The genes regulated by this pathway remain to be determined. By studying IL-2-inducible genes, we have confirmed that the TNF-beta gene is one of the immediate early genes activated by IL-2. By analysis of the DNA sequences around 180-300 bases upstream of the transcription initiation point of the mouse TNF-beta gene, we demonstrate that there is a STAT5 binding site which is essential to the inducibility of the TNF-beta gene. Furthermore, in BA/F3 cells co-transfected with the STAT5A gene and IL-2R beta gene, the activation of the TNF-beta gene promoter by IL-2 was greatly promoted, whereas the TNF-beta gene promoter became IL-2-non-inducible if the STAT5A gene was substituted with a dominant negative STAT5A, i.e. a C-terminally truncated mutant. Taken together, our results show that the Jak-STAT signal pathway is involved in induction of the TNF-beta gene in cells stimulated by IL-2.

Animals↗
PubMed1998

Co-expression of immunogenic determinants by the same cellular immunogen is required for the optimum immunotherapeutic benefit in mice with melanoma.

Tumor-associated T cell epitopes are recognized by T cells in the context of determinants specified by class I loci. Since the rejection of foreign histocompatibility antigens is known to enhance tumor immunity, immunization with a cellular vaccine that combined the expression of both syngeneic and allogeneic class I determinants could have important immunological advantages over a vaccine that expressed either syngeneic or allogeneic determinants alone. To investigate this question in a mouse melanoma model system, we tested the immunotherapeutic properties of B16 melanoma x LM fibroblast hybrid cells in C57BL/6J mice with melanoma. Like C57BL/6J mice, B16 cells expressed H-2Kb class I determinants and (antibody-defined) melanoma-associated antigens. LM cells, of C3H mouse origin, formed H-2Kk determinants along with B7.1, a co-stimulatory molecule that can activate T cells. The B16 x LM hybrid cells co-expressed H-2Kb and H-2Kk class I determinants, B7.1 and the melanoma-associated antigens. C57BL/6J mice with melanoma, immunized with the semi-allogeneic hybrid cells, developed CD8-mediated melanoma immunity and survived significantly (P < 0.005) longer than mice with melanoma immunized with a mixture of the parental cell types. The failure of melanoma immunity to develop in mice injected with the mixture of parental cells indicated that co-expression of the immunogenic determinants by the same cellular immunogen was necessary for an optimum immunotherapeutic effect. Augmented immunity to melanoma in mice immunized with the semi-allogeneic hybrid cells points toward an analogous form of therapy for patients with melanoma.

Animals↗
PubMed1998

Institutional influences on the primary cesarean section rate in Utah, 1992 to 1995.

OBJECTIVES: Our purpose was to evaluate institutional and organizational influences on cesarean section rates in Utah and to adjust such rates for differences in patient acuity. STUDY DESIGN: Data on cesarean section rates were derived from the Utah Hospital Discharge Database and adjusted for patient acuity by correcting raw cesarean rates for those patients undergoing cesarean section meeting regional gestational age transport criteria. RESULTS: When analyzed by means of 1-way analysis of variance, the following factors had a significant negative correlation (P < .05) with cesarean section rate: presence of a newborn intensive care unit and maternal-fetal medicine subspecialists, presence on the medical staff of obstetrician-gynecologist(s) as opposed to family physicians only, delivery volume >1500/y, urban location, and 24-hour in-house anesthesiology. When cesarean rates were corrected for acuity, facilities with maternal-fetal medicine specialists and a newborn intensive care unit had significantly lower rates (P < .001) and more uniform rates than otherwise similar institutions. CONCLUSIONS: More medically sophisticated physicians and institutions have lower cesarean rates when patient acuity is taken into account.

Cesarean Section↗
PubMed1998

New genetic group of measles virus isolated in the People's Republic of China.

Genetic and antigenic characterization of 14 wild-type measles viruses isolated from four provinces in the People's Republic of China during 1993 and 1994 was conducted. Sequence analyses of the hemagglutinin (H) and nucleoprotein (N) genes indicated that 13 of the 14 Chinese viruses comprised a previously undescribed genetic group. Viruses from this unique group were the most genetically diverse measles viruses described, so far. The Chinese viruses differed from other wild-type viruses by as much as 6.9% in the H gene and 7.0% in the N gene at the nucleotide level. One of the 14 viruses was a member of the same genetic group that contains the Edmonston strain. Antigenic analysis using monoclonal antibodies to the H protein did not detect significant differences in binding patterns between the Chinese viruses and other wild-type measles viruses. In addition, representative viruses from the unique Chinese group were neutralized by both human post-vaccination antiserum and mouse antiserum against the H protein of the Edmonston vaccine virus. Viruses closely related to these Chinese viruses were also associated with importations of measles into the United States during 1997 from Vietnam and Hong Kong suggesting that viruses from this new genetic group continue to circulate in China and possibly other parts of Asia.

Antigens, Viral↗
PubMed1998

Interactive effects of cocaine and gender on thymocytes: a study of in vivo repeated cocaine exposure.

This study used a mouse model including both sexes to assess the impact of repeat cocaine exposure on the differentiation and function of T cell in thymus. Cocaine hydrochloride in 0.9% saline, 5 mg or 40 mg/kg, was administrated by i.p. injection to C57BL/6 mice for 10 days. Thymocytes were obtained 24 h after the 10th injection. Repeat in vivo cocaine exposure inhibited the proliferation of T lymphocytes in response to Con-A and Con-A plus anti-CD28. The proliferation induced by IL-2 in the Con-A stimulated T blasts was attenuated in cocaine treated mice. These effects were seen at a lower cocaine dose in female mice. The total number of thymocytes was reduced. Although the percentage of mature thymocytes (CD4+ CD8- and CD4- CD8+ cells) was not altered, the absolute cell numbers were attenuated. Both percentage and absolute cell number of immature thymocytes (CD4+ CD8+) decreased and the pre-mature (CD4- CD8-) cells increased. CD28 and CD25 expression were attenuated in Con-A stimulated thymocytes of mice treated with cocaine at 40 mg/kg. Interleukin 2 production was not significantly altered, however, gamma-IFN production was decreased by cocaine exposure at 40 mg/kg. In conclusion, cocaine exerts inhibitory effects on the function of mature thymocytes, and on the differentiation of thymocytes. A gender difference in response to cocaine was noted in that female mice were more sensitive to lower dose of cocaine exposure.

Animals↗
PubMed1998

Highly sensitive and specific ELISA with monoclonal antibody capture to measure Dermatophagoides farinae 1-specific IgE.

BACKGROUND: Dermatophagoides farinae (Der f) is a major allergen in Der f extract. Measurement of Der f I-specific IgE has not been commonly used, because of the difficulty in obtaining large amounts of purified Der f 1. OBJECTIVES: To improve the diagnosis of dust mite allergy, we wanted to develop an ELISA to measure Der f 1-specific IgE in which purified Der f 1 is not required. METHODS: Using a monoclonal antibody (mAb) against Der f 1, a mAb-capture ELISA was developed. Microplates coated with the mAb were sequentially incubated with crude Der f extract, serum samples, goat anti-human IgE, and conjugated rabbit anti-goat IgG. A conventional ELISA using purified Der f 1 as capture (Der f 1-ELISA) was developed to compare it with the mAb-capture ELISA. RESULTS: There was a significant correlation between the two ELISAs (r = 0.89, P < .001) with a sensitivity of 0.8 U/mL. Both the assays were inhibited by the crude Der f extract in a dose-dependent manner. Using the two ELISAs, serum Der f 1-specific IgE was evaluated in 12 allergic patients with positive skin tests to Der f extract, 14 allergic patients with negative skin tests to Der f extract, and 15 healthy subjects. The mean Der f 1-IgE and the positivity rate of Der f I-IgE were higher in the mite-allergic group and lower in the healthy group when the mAb-ELISA was used (P < .01) than when the Der f 1-ELISA was used (P < .05). CONCLUSIONS: Der f 1-specific IgE can be measured by mAb-capture ELISA using crude Der f extract. The mAb-ELISA is more sensitive and specific than the conventional Der f 1-capture ELISA in diagnosing dust mite allergy.

Adolescent↗
PubMed1998

Formation of isomorphic desolvates: creating a molecular vacuum.

The objective of this work was to investigate a common but poorly understood category of crystalline organic substances: isomorphic desolvates. When solvent is lost from a crystal lattice but the lattice retains its three-dimensional order, a lattice is created which is in a high-energy state relative to the original solvate structure. The desolvated lattice can reduce its internal energy by either resorbing solvent or by relaxation processes which increase the packing efficiency of the solid by reducing the unit cell volume. In the following paper, solid-state properties of isomorphic desolvates of cephalexin, cefaclor, erythromycin A, and spirapril hydrochloride hydrates are investigated. The hygroscopicity of the compounds are evaluated using a vacuum moisture balance, and structural relaxation is measured using a combination of X-ray powder diffraction and isothermal microcalorimetry. The study results are explained in terms of Kitaigorodski's close packing principle.

Absorption↗
PubMed1998

Endogenous orphanin FQ: evidence for a role in the modulation of electroacupuncture analgesia and the development of tolerance to analgesia produced by morphine and electroacupuncture.

1. Our previous work has demonstrated that exogenously administered orphanin FQ (OFQ) antagonizes morphine analgesia and electroacupuncture analgesia (EAA) in the brain and potentiates morphine analgesia and EAA in the spinal cord of the rat. In the present study we evaluated the role of endogenously released OFQ in the development of tolerance to morphine and electroacupuncture (EA) and the analgesia produced by electroacupuncture, by use of the IgG fraction of an anti-OFQ antibody (OFQ-Ab) microinjected into the rat central nervous system (CNS). 2. EAA was produced by stimulating rats at a frequency of 100 Hz. Rats were classified as either high responders (HR) or low responders (LR) based on the analgesic effects of EA. LRs could be converted into HRs by the intracerebroventricular (i.c.v.) microinjection of OFQ-Ab at both 1:1 and 1:10 dilutions but not 1:100. HRs could be changed into LRs by the intrathecal (i.t.) injection of OFQ-Ab at both 1:1 and 1:10 dilutions, but not 1:100. 3. Acute morphine tolerance was induced in rats by repeated subcutaneous (s.c.) injections of morphine (5 mg kg, every 2 h) for 16 h. When injected i.c.v. the OFQ-Ab (1:1 dilution) had no effect on the development of acute morphine tolerance. 4. Chronic morphine tolerance was produced in rats by repeated injection of morphine (5-60 mg kg, s.c., 3 x a day) for 6 days. I.c.v. injection of OFQ-Ab (1:1 dilution) reversed this type of morphine tolerance in rats by 50% (P < 0.01). 5. Acute tolerance to the analgesia produced by EA developed after 6 h of continuous (100 Hz, 3 mA) stimulation. This tolerance was almost completely reversed by the i.c.v. injection of OFQ-Ab (1:1 dilution) (P < 0.05). 6. Chronic tolerance to the analgesic effect of EA was produced by repeatedly administering increasing current (1, 2 and 3 mA, each lasting for 10 min, for a total of 30 min) at a frequency of 100 Hz once a day for 6 days. I.c.v. injection of OFQ-Ab (1:1 dilution) reversed this kind of tolerance by 50% (P < 0.01). 7. Together these results suggest that 100 Hz EA may enhance the release of endogenous OFQ in the CNS of the rat, which in turn may act to antagonize EA-produced analgesia in the brain but potentiate EA produced analgesia in the spinal cord. Therefore, OFQ appears to play an important role in the development of tolerance to the analgesic effects produced by EA. 8. The mechanisms underlying the development of acute morphine tolerance and chronic morphine tolerance appear to be different. Central OFQ may play an important role in the development of tolerance after chronic morphine administration.

Adaptation, Physiological↗