Search PubMed⌕ Search

Biomedical subjects

Z Zhu

Publications and source records attributed to Z Zhu.

At least 37 records · Page 2Linked to original sources
PubMed2003

High-performance liquid chromatographic mass spectrometric method for the determination of ursodeoxycholic acid and its glycine and taurine conjugates in human plasma.

A novel sensitive high-performance liquid chromatography-electrospray mass spectrometry method has been developed for the determination of ursodeoxycholic acid (UDCA) and its glycine and taurine conjugates, glycoursodeoxycholic acid (GDCA) and tauroursodeoxycholic acid (TDCA). The procedure involved a solid phase extraction of UDCA, GDCA, TDCA and the internal standard, 23-nordeoxycholic acid from human plasma on a C18 Bond Elut cartridge. Chromatography was performed by isocratic reverse phase separation with methanol/25 mM ammonium acetate (40/60, v/v) containing 0.05% acetic acid on a C18 column with embedded polar functional group. Detection was achieved using an LC-MS/MS system. The standard curve was linear over a working range of 10-3000 ng/ml for all analytes and gave an average correlation coefficient of 0.9992 or better during validation. The absolute recovery for UDCA, GDCA, TDCA and the internal standard was 87.3, 83.7, 79.5 and 95.8%, respectively. This method is simple, sensitive and suitable for pharmacokinetics, bioequivalence or clinical studies.

Chromatography, High Pressure Liquid↗
PubMed2003

White adipose tissue contributes to UCP1-independent thermogenesis.

Beta3-adrenergic receptors (AR) are nearly exclusively expressed in brown and white adipose tissues, and chronic activation of these receptors by selective agonists has profound anti-diabetes and anti-obesity effects. This study examined metabolic responses to acute and chronic beta3-AR activation in wild-type C57Bl/6 mice and congenic mice lacking functional uncoupling protein (UCP)1, the molecular effector of brown adipose tissue (BAT) thermogenesis. Acute activation of beta3-AR doubled metabolic rate in wild-type mice and sharply elevated body temperature and BAT blood flow, as determined by laser Doppler flowmetry. In contrast, beta3-AR activation did not increase BAT blood flow in mice lacking UCP1 (UCP1 KO). Nonetheless, beta3-AR activation significantly increased metabolic rate and body temperature in UCP1 KO mice, demonstrating the presence of UCP1-independent thermogenesis. Daily treatment with the beta3-AR agonist CL-316243 (CL) for 6 days increased basal and CL-induced thermogenesis compared with naive mice. This expansion of basal and CL-induced metabolic rate did not require UCP1 expression. Chronic CL treatment of UCP1 KO mice increased basal and CL-stimulated metabolic rate of epididymal white adipose tissue (EWAT) fourfold but did not alter BAT thermogenesis. After chronic CL treatment, CL-stimulated thermogenesis of EWAT equaled that of interscapular BAT per tissue mass. The elevation of EWAT metabolism was accompanied by mitochondrial biogenesis and the induction of genes involved in lipid oxidation. These observations indicate that chronic beta3-AR activation induces metabolic adaptation in WAT that contributes to beta3-AR-mediated thermogenesis. This adaptation involves lipid oxidation in situ and does not require UCP1 expression.

Adipose Tissue↗
PubMed2003

Chiral separation and determination of R-(-)- and S-(+)-baclofen in human plasma by high-performance liquid chromatography.

The method presented here is a high-performance liquid chromatography (HPLC)-UV detection method for the determination of baclofen R-(-)- and S-(+)-enantiomers in human plasma using a chiral separation technique. Baclofen enantiomers were extracted from human plasma with a reversed-phase solid-phase extraction (SPE) cartridge. The extract was then injected onto a HPLC system with a UV detection system set at 220 nm. The separation was achieved by using a 150x4.6 mm, 5 microm Phenomenex chirex 3216 chiral column with a mobile phase consisting of 0.4 mM CuSO(4) in acetonitrile-20 mM sodium acetate (17:83). The calibration curves were linear for both R-(-)- and S-(+)-enantiomers of baclofen in the concentration range of 20-5000 ng/ml. The average regressions were 0.9980 and 0.9991 for R-(-)- and S-(+)-baclofen, respectively. Inter-day precision was 3.3-5.2% for R-(-)-baclofen and 3.5-3.9% for S-(+)-baclofen at a concentration range of 60-4000 ng/ml. Intra-day precisions were 0.6-4.4 and 0.5-3.5% for R-(-)-baclofen and S-(+)-baclofen, respectively. The average extraction recovery was 81.6% for R-(-)-baclofen, 83.0% for S-(+)-baclofen and 94.0% for the internal standard (p-aminobenzoic acid). The limit of quantitation for both R-(-)- and S-(+)-baclofen in human plasma was 20 ng/ml. The method is simple and easy to operate with accuracy and reproducibility and it is suitable for pharmacokinetic studies.

Baclofen↗
PubMed2003

Inhibition of human leukemia in an animal model with human antibodies directed against vascular endothelial growth factor receptor 2. Correlation between antibody affinity and biological activity.

Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) have been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis. We recently showed that certain 'liquid' tumors such as leukemia not only produce VEGF, but also express functional VEGFR, resulting in an autocrine loop for tumor growth and propagation. A chimeric anti-VEGFR2 (or kinase insert domain-containing receptor, KDR) antibody, IMC-1C11, was shown to be able to inhibit VEGF-induced proliferation of human leukemia cells in vitro, and to prolong survival of nonobese diabetic-severe combined immune deficient (NOD-SCID) mice inoculated with human leukemia cells. Here we produced two fully human anti-KDR antibodies (IgG1), IMC-2C6 and IMC-1121, from Fab fragments originally isolated from a large antibody phage display library. These antibodies bind specifically to KDR with high affinities: 50 and 200 pM for IMC-1121 and IMC-2C6, respectively, as compared to 270 pM for IMC-1C11. Like IMC-1C11, both human antibodies block VEGF/KDR interaction with an IC(50) of approximately 1 nM, but IMC-1121 is a more potent inhibitor to VEGF-stimulated proliferation of human endothelial cells. These anti-KDR antibodies strongly inhibited VEGF-induced migration of human leukemia cells in vitro, and when administered in vivo, significantly prolonged survival of NOD-SCID mice inoculated with human leukemia cells. It is noteworthy that the mice treated with antibody of the highest affinity, IMC-1121, survived the longest period of time, followed by mice treated with IMC-2C6 and IMC-1C11. Taken together, our data suggest that anti-KDR antibodies may have broad applications in the treatment of both solid tumors and leukemia. It further underscores the efforts to identify antibodies of high affinity for enhanced antiangiogenic and antitumor activities.

Animals↗
PubMed2003

Upregulation of Fas and FasL expression in testosterone-induced apoptosis of macrophages.

To the best of the authors' knowledge, there have been few reports on the effect of testosterone on the apoptosis of macrophages. In this report, we studied the effect of testosterone on the apoptosis of bone marrow-derived macrophages (BMMs) and the function of the Fas/Fas ligand (FasL) system in the process. Results showed that testosterone treatment in vitro at the physiological concentration of 10 nM did not induce the apoptosis of BMMs. However, BMMs underwent apoptosis when treated at higher concentrations of testosterone (100, 200 and 400 nM). Testosterone-induced apoptosis was associated with the enhanced expression of Fas, FasL, and caspase-8. These data suggest that the Fas/FasL system may play an important role in the testosterone-induced apoptosis of macrophages.

Animals↗
PubMed2002

High-performance liquid chromatographic method for the determination of gabapentin in human plasma.

A sensitive high-performance liquid chromatography (HPLC) method using UV detection for the determination of gabapentin in human plasma has been developed. In this method, gabapentin was extracted from human plasma with a reversed-phase solid-phase extraction (SPE) cartridge followed by derivatization with phenylisothiocyanate. Analysis was achieved by using a HPLC system that was equipped with a UV detector. The quantitation limit of gabapentin in human plasma was 0.03 microg/ml. The method is sensitive with excellent selectivity and reproducibility and it has been applied to a bioequivalence clinical study with great success.

Acetates↗
PubMed2002

Mechanical properties of the periosteum in the pig, Sus scrofa.

The fibrous periosteum forms an intermediary between muscle and ligament forces and the underlying osteoblastic tissue, thus the mechanical properties of the periosteum are critical to understanding osteogenic stimuli. Regional and directional variation in periosteal properties may contribute to the biomechanical regulation of growth in some bones. Periostea of the pig mandibular body, zygomatic arch and metacarpal were loaded to failure under continuous tension. Each tissue type was tested in both the long-axis and transverse orientation. Stiffness, peak stress and peak strain were compared between orientations and among regions. Within the zygomatic periosteum there was little indication of regional difference, and neither zygomatic nor mandibular periosteum showed directional differences. The metacarpal periosteum showed a directional effect only in peak strain, which was greater longitudinally than transversely. There were striking differences, however, among the periostea of the three bones. The zygomatic arch periosteum was the stiffest tissue (91.7+/-30.5 MPa) and showed the highest strength (12.3+/-4.6 MPa). The metacarpal periosteum demonstrated slightly lower stiffness and strength (84.7+/-35.1 and 11.3+/-5.3 MPa), and peak strains in zygomatic and metacarpal periostea were similarly high (17.7+/-3.7 and 17.9+/-3.7 MPa, respectively). The periosteum of the mandibular body was the most deformable tissue (63.0+/-25.4 MPa), with the lowest-peak strain (15.6+/-3.0 MPa) and the least strength (8.2+/-4.1 MPa). These results correspond with those of previous work in long bones, in that periosteum interfacing with ligament or muscle (e.g. zygomatic, metacarpal) demonstrates greater stiffness and strength than periosteum adjacent to loose connective tissue (e.g. mandibular body). Therefore, the degree to which the periosteal tissue serves as a functional interface between bone and muscle is reflected in the different failure properties of periostea from different bones. The structural fortification of the zygomatic arch periosteum relative to other periosteal tissues suggests a role for the periosteum in stabilizing the zygomatic arch-muscle functional complex. On the other hand, the similar failure properties of zygomatic and squamosal periostea from the zygomatic arch mean that the differential growth of these bones cannot be attributed to mechanical stimuli intrinsic to the periosteal tissue.

Animals↗
PubMed2001

Determinants of the broad recognition of exocytic Rab GTPases by Mss4.

Rab GTPases function as essential regulators of vesicle transport between subcellular compartments of eukaryotic cells. Mss4, an evolutionarily conserved Rab accessory factor, facilitates nucleotide release and binds tightly to the nucleotide-free form of exocytic but not endocytic Rab GTPases. A structure-based mutational analysis of residues that are conserved only in exocytic Rab GTPases reveals three residues that are critical determinants of the broad specificity recognition of exocytic Rab GTPases by Mss4. One of these residues is located at the N-terminus of the switch I region near the nucleotide binding site whereas the other two flank an exposed hydrophobic triad previously implicated in effector recognition. The spatial disposition of these residues with respect to the structure of Rab3A correlates with the dimensions of the elongated Rab interaction epitope in Mss4 and supports a mode of interaction similar to that of other exchange factor-GTPase complexes. The complementarity of the corresponding interaction surfaces suggests a hypothetical structural model for the complex between Mss4 and Rab GTPases.

Amino Acid Sequence↗
PubMed2001

Optimizing nitrogen management in food and energy production and environmental protection: summary statement from the Second International Nitrogen Conference.

Human efforts to produce food and energy are changing the nitrogen (N) cycle of the Earth. Many of these changes are highly beneficial for humans, while others are detrimental to people and the environment. These changes transcend scientific disciplines, geographical boundaries, and political structures. They challenge the creative minds of natural and social scientists, economists, engineers, business leaders, and decision makers. The Second International Nitrogen Conference was designed to facilitate communications among all stakeholders in the "nitrogen community" of the world. The Conference participants" goal in the years and decades ahead is to encourage every country to make optimal choices about N management in food production and consumption, energy production and use, and environmental protection. Scientific findings and recommendations for decision makers that emerged from the Conference are presented.

Agriculture↗
PubMed2001

Synthesis and ring-expanding oligomerization of an extremely strained macrocyclic aromatic ether-sulfone.

[reaction: see text] An extremely strained, 5-ring, macrocyclic aromatic ether-sulfone, [-1,4-C(6)H(4)SO(2)-1,4-C(6)H(4)O-1,3-C(6)H(4)O-1,4-C(6)H(4)SO(2)-1,4-C(6)H(4)-], synthesized by nickel-catalyzed intramolecular coupling of a bis-chlorophenylene-terminated precursor, undergoes fluoride-promoted ring expansion in dilute solution, giving a series of higher macrocyclic oligomers including cyclic dimer, trimer, and tetramer. The latter contains 20 aromatic residues in a 92-atom ring and is one of the largest synthetic organic macrocycles to be crystallographically characterized. The synthesis, structure, and ring expansion of a related macrocyclic ether-ketone are also reported.

Journal Article↗
PubMed2001

Airway inflammation and remodeling in asthma. Lessons from interleukin 11 and interleukin 13 transgenic mice.

Noninflammatory structural alterations, variously referred to as airway remodeling, are well documented in the asthmatic airway. However, the pathogenesis of these alterations, the importance of airway remodeling in generating the asthma phenotype, and the natural history of airway remodeling responses have not been adequately defined. Because exaggerated cytokine production is a characteristic feature of the asthmatic airway, we used constitutive and inducible overexpression transgenic systems to investigate the contributions that interleukin 11 (IL-11) and IL-13 might make to airway remodeling responses. These studies demonstrated that both cytokines produce responses in the murine airway with features similar to those in human asthmatic tissues. IL-11 caused airway fibrosis with the enhanced accumulation of interstitial collagens, myocytes, and myofibroblasts. IL-13 caused mucous metaplasia, enhanced mucin gene expression, enhanced tissue hyaluronic acid accumulation, and subepithelial fibrosis. Importantly, IL-11 was detected most readily in tissues from asthmatic subjects with severe airway remodeling that was similar to that seen in the IL-11 transgenic mice. In addition, IL-11 was shown to inhibit asthma-like inflammation while stimulating airway fibrosis. This suggests that IL-11 elaboration is, in part, an attempt at airway healing. Last, a novel triple transgenic system is described that allows transgene expression to be regulated in a true "on/off" manner. This system may be useful in defining the reversibility of transgene-induced airway remodeling responses.

Animals↗
PubMed2001

IL-13 transgene state impairs mycobacterial (type-1) and schistosomal (type-2) antigen-elicited responses.

Transgenic technology provides one approach for examining cytokine properties in vivo. This study directly tested the effect of a lung-targeted IL-13 transgene on the induction and elicitation of Th1 and Th2 cell-mediated immuno-inflammatory responses. Induction of Th1 (type 1) and Th2 (type 2) responses were tested by sensitization of IL-13 transgenics and littermates with purified protein derivative (PPD) of Mycobacterium bovis or Schistosoma mansoni eggs. Secondary elicitation of pulmonary granulomas was examined in adoptively sensitized transgenics and littermates challenged with bead-bound PPD or S. mansoni egg antigens. Parameters included lymphoid tissue cytokine profiles and granuloma sizes. Results showed that induction and elicitation of both type 1 and type 2 cytokines and granulomas were significantly abrogated in transgenics. Systemic effects were possible, as transgenic serum contained high levels of circulating IL-13. These findings support the concept that IL-13 impairs effector functions and provide novel information regarding its role in regulating Th2 cytokines.

Adoptive Transfer↗
PubMed2001

Conjugated polymers containing 2,3-dialkoxybenzene and iptycene building blocks.

[structure: see text]. New poly(phenylene ethynylene)s (PPEs) and poly(phenylene vinylene)s (PPVs) that are highly emissive in solution and thin films were prepared utilizing palladium-catalyzed cross-coupling between new 1,4-diiodo-2,3-dialkoxybenzene- and iptycene-containing monomers. The absorption and emission spectra of the resulting polymers consistently showed a significant blue shift relative to the corresponding polymer analogues containing 2,5-dialkoxyphenylenes.

Journal Article↗
PubMed2001

Dynamics of spiral waves under the modulation of noise pulses.

This work aims at investigating the dynamics of spiral waves under the modulation of noise pulses. Both rigid rotating and meandering spirals are considered. The numerical simulations show that for meandering spirals there exists a minimal external radius of the tip trajectory at an optimal intensity when keeping the duration constant, or for an optimal duration when keeping the intensity constant. For rigid rotating spirals an interesting phenomenon is that the clockwise-counterclockwise transition of the trajectory occurs when we raise the duration of the noise pulse for a fixed intensity.

Journal Article↗
PubMed2001

Complete inhibition of vascular endothelial growth factor (VEGF) activities with a bifunctional diabody directed against both VEGF kinase receptors, fms-like tyrosine kinase receptor and kinase insert domain-containing receptor.

Vascular endothelial growth factor (VEGF) binds to and mediates its activity mainly through two tyrosine kinase receptors, VEGF receptor 1 [or fms-like tyrosine kinase receptor (Flt-1)] and VEGF receptor 2 [or kinase insert domain-containing receptor (KDR)]. Numerous studies have shown that overexpression of VEGF and its receptor plays an important role in tumor-associated angiogenesis and hence in both tumor growth and metastasis. We demonstrated previously that antagonistic antibodies to KDR specifically inhibited VEGF-stimulated receptor activation, cell migration, and endothelial cell mitogenesis. Here we constructed a recombinant bifunctional diabody that is capable of blocking both Flt-1 and KDR from binding to their ligands, including VEGF and placenta growth factor (PlGF). The diabody was expressed in Escherichia coli and purified by single-step affinity chromatography. The diabody retained the capacity to bind both KDR and Flt-1 and effectively blocked interaction between KDR and VEGF, Flt-1 and VEGF, and Flt-1 and PlGF. Furthermore, the diabody is a stronger inhibitor than its parent antibodies to VEGF-stimulated mitogenesis of human endothelial cells, as well as both VEGF- and PlGF-induced migration of human leukemia cells. Taken together, our results suggest that dual receptor blockade with the bifunctional diabody may prove to be a more efficient approach in inhibiting VEGF-stimulated angiogenesis.

3T3 Cells↗