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Biomedical subjects

Z Wu

Publications and source records attributed to Z Wu.

At least 73 records · Page 4Linked to original sources
PubMed2001

Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1.

Blood glucose levels are maintained by the balance between glucose uptake by peripheral tissues and glucose secretion by the liver. Gluconeogenesis is strongly stimulated during fasting and is aberrantly activated in diabetes mellitus. Here we show that the transcriptional coactivator PGC-1 is strongly induced in liver in fasting mice and in three mouse models of insulin action deficiency: streptozotocin-induced diabetes, ob/ob genotype and liver insulin-receptor knockout. PGC-1 is induced synergistically in primary liver cultures by cyclic AMP and glucocorticoids. Adenoviral-mediated expression of PGC-1 in hepatocytes in culture or in vivo strongly activates an entire programme of key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, leading to increased glucose output. Full transcriptional activation of the PEPCK promoter requires coactivation of the glucocorticoid receptor and the liver-enriched transcription factor HNF-4alpha (hepatic nuclear factor-4alpha) by PGC-1. These results implicate PGC-1 as a key modulator of hepatic gluconeogenesis and as a central target of the insulin-cAMP axis in liver.

3T3 Cells↗
PubMed2001

Reactions of tetrakis(dimethylamide)-titanium, -zirconium and -hafnium with silanes: synthesis of unusual amide hydride complexes and mechanistic studies of titanium-silicon-nitride (Ti-Si-N) formation.

M(NMe(2))(4) (M = Ti, Zr, Hf) were found to react with H(2)SiR'Ph (R' = H, Me, Ph) to yield H(2), aminosilanes, and black solids. Unusual amide hydride complexes [(Me(2)N)(3)M(mu-H)(mu-NMe(2))(2)](2)M (M = Zr, 1; Hf, 2) were observed to be intermediates and characterized by single-crystal X-ray diffraction. [(Me(2)N)(3)M(mu-D)(mu-NMe(2))(2)](2)M (1-d(2), 2-d(2)) were prepared through reactions of M(NMe(2))(4) with D(2)SiPh(2). Reactions of (Me(2)N)(3)ZrSi(SiMe(3))(3) (5) with H(2)SiR'Ph were found to give aminosilanes and (Me(2)N)(2)Zr(H)Si(SiMe(3))(3) (6). These reactions are reversible through unusual equilibria such as (Me(2)N)(3)ZrSi(SiMe(3))(3) (5) + H(2)SiPh(2) right arrow over left arrow (Me(2)N)(2)Zr(H)Si(SiMe(3))(3) (6) + HSi(NMe(2))Ph(2). The deuteride ligand in (Me(2)N)(2)Zr(D)Si(SiMe(3))(3) (6-d(1)) undergoes H-D exchange with H(2)SiR'Ph (R' = Me, H) to give 6 and HDSiR'Ph. The reaction of Ti(NMe(2))(4) with SiH(4) in chemical vapor deposition at 450 degrees C yielded thin Ti-Si-N ternary films containing TiN and Si(3)N(4). Ti(NMe(2))(4) reacts with SiH(4) at 23 degrees C to give H(2), HSi(NMe(2))(3), and a black solid. HNMe(2) was not detected in this reaction. The reaction mixture, upon heating, gave TiN and Si(3)N(4) powders. Analyses and reactivities of the black solid revealed that it contained -H and unreacted -NMe(2) ligands but no silicon-containing ligand. Ab initio quantum chemical calculations of the reactions of Ti(NR(2))(4) (R = Me, H) with SiH(4) indicated that the formation of aminosilanes and HTi(NR(2))(3) was favored. These calculations also showed that HTi(NH(2))(3) (3b) reacted with SiH(4) or H(3)Si-NH(2) in the following step to give H(2)Ti(NH(2))(2) (4b) and aminosilanes. The results in the current studies indicated that the role of SiH(4) in its reaction with Ti(NMe(2))(4) was mainly to remove amide ligands as HSi(NMe(2))(3). The removal of amide ligands is incomplete, and the reaction thus yielded "=Ti(H)(NMe(2))" as the black solid. Subsequent heating of the black solid and HSi(NMe(2))(3) may then yield TiN and Si(3)N(4), respectively, as the Ti-Si-N materials.

Journal Article↗
PubMed2001

Fractal and chaotic behavior of circular cellular automata.

A new type of circular cellular automata (CCA) has been introduced. The evolutions of the CCA obtained by the clockwise, anticlockwise, and scanning line-by-line site sequence in the successively growing rings divided from a square lattice are studied. The evolution seems to form a twisty fishnet when the CCA are grown by the first two sequences. Sierpinski triangle gasket or the modulated ones are formed in the fourth quadrant of the CCA grown by the line scanning sequence. Fractal analysis is used to characterize the relationships between the pattern formed and the initial position of the growing ring and it is found that the pattern is very sensitive to the initial growth condition, showing the chaotic behavior.

Journal Article↗
PubMed2001

Normal faulting in central Tibet since at least 13.5 Myr ago.

Tectonic models for the evolution of the Tibetan plateau interpret observed east-west thinning of the upper crust to be the result of either increased potential energy of elevated crust or geodynamic processes that may be unrelated to plateau formation. A key piece of information needed to evaluate these models is the timing of deformation within the plateau. The onset of normal faulting has been estimated to have commenced in southern Tibet between about 14 Myr ago and about 8 Myr ago and, in central Tibet, about 4 Myr ago. Here, however, we report a minimum age of approximately 13.5 Myr for the onset of graben formation in central Tibet, based on mineralization ages determined with Rb-Sr and 40Ar-39Ar data that post-date a major graben-bounding normal fault. These data, along with evidence for prolonged activity of normal faulting in this and other Tibetan grabens, support models that relate normal faulting to processes occurring beneath the plateau. Thinning of the upper crust is most plausibly the result of potential-energy increases resulting from spatially and temporally heterogeneous changes in thermal structure and density distribution within the crust and upper mantle beneath Tibet. This is supported by recent geophysical and geological data, which indicate that spatial heterogeneity exists in both the Tibetan crust and lithospheric mantle.

Journal Article↗
PubMed2001

Functional imaging of brain activity in conscious monkeys responding to sexually arousing cues.

Olfactory cues can elicit intense emotional responses. This study used fMRI in male common marmoset monkeys to identify brain areas associated with sexual arousal in response to odors of ovulating female monkeys. Under light anesthesia, monkeys were secured in a specially designed restrainer and positioned in a 9.4 T magnetic resonance spectrometer. When fully conscious, they were presented with the scents of both ovariectomized and ovulating monkeys. The sexually arousing odors of the ovulating monkeys enhanced signal intensity in the preoptic area and anterior hypothalamus compared to the odors of ovariectomized monkeys. These data corroborate previous findings in monkeys based on invasive electrical lesion and stimulation techniques and demonstrate the feasibility of using non-invasive functional imaging on fully conscious common marmosets to study cue-elicited emotional responses.

Animals↗
PubMed2001

Transcriptional regulation of human oxysterol 7 alpha-hydroxylase gene (CYP7B1) by Sp1.

Oxysterol 7 alpha-hydroxylase catalyzes hydroxylation of oxysterols and neurosterols and plays a role in the alternative bile acid synthesis pathway. This gene is widely expressed in many organs and peripheral tissues and may protect tissues from the toxicity of oxysterols. Mutation in CYP7B1 caused neonatal cholestasis. To examine the regulatory mechanisms governing CYP7B1 expression, the 5' flanking sequence of the CYP7B1 was analyzed and revealed a CpG island of about 1.2 kb. Transient transfection assays of deletion mutants of the CYP7B1 promoter-luciferase reporter gene in human liver-derived HepG2, fibroblast NT1088, and human embryonic kidney 293 cell lines revealed that the region from -291 to +189 was critical for gene transcription. Three GC box sequences located between -25 and +10 were essential for basal transcription because mutations of these sequences markedly reduced promoter activity. Sp1 and Sp3 bound to these sequences as demonstrated by DNase I footprinting assays and electrophoretic mobility shift assay. Thus, regulation of CYP7B1 transcription by Sp1 may play a pivotal role in regulating oxysterol levels, which regulate cholesterol metabolism.

Base Sequence↗
PubMed2001

Partial degradation of phenol by advanced electrochemical oxidation process.

The partial electrocatalytic degradation of phenol to organic acids has been investigated using an undivided electrolytic reactor with a beta-PbO2 anode containing fluorine resin. It was found that the decrease of benzoquinone (BQ) formed during phenol degradation and the acceleration of the process from phenol to organic acids are possible under an optimized operating condition. A possible pathway for phenol degradation was proposed, and a mathematical model for phenol and BQ evolution was developed. Operating parameters such as initial pH, current density, and temperature of the reaction were found to greatly impact the degradation rate of the phenol and even the pathway. Higher removal rate of phenol and BQ can be achieved at an appropriate temperature and higher current density in acidic medium preferably at pH 4. Under these conditions, phenol would be more likely degraded in the pathway from phenol to organic acids rather than through the BQ. When phenol is completely removed, the toxicity of the wastewater would be lessened suitable for biological process treatment. Accounting for the decrease of instantaneous current efficiency (ICE) during degradation, partial degradation would be highly economical for wastewater treatment, which would be an alternative process in practical application.

Disinfectants↗
PubMed2001

Novel alkylpolyamine analogues that possess both antitrypanosomal and antimicrosporidial activity.

A novel series of alkyl- or aralkyl-substituted polyamine analogues was synthesized containing a 3-7-3 polyamine backbone. These analogues were evaluated in vitro, and in one case in vivo, for activity as antitrypanosomal agents, and for activity against opportunistic infection caused by Microsporidia. Compound 21 inhibits trypanosomal growth with an IC(50) as low as 31nM, while compound 24 shows promising activity in vitro against trypanosomes, and against Microsporidia in vitro and in vivo.

Animals↗
PubMed2001

Insights into long-range structural effects on the stereochemistry of aldol condensations: a practical total synthesis of desoxyepothilone F.

A processable total synthesis of a potent antitumor agent, desoxyepothilone F (dEpoF, 21-hydroxy-12,13-desoxyepothilone B, 21-hydroxyepothilone D), has been accomplished. The route is highly convergent. The new technology has also been applied to a total synthesis of 12,13-desoxyepothilone (dEpoB). The crucial point of departure from previous syntheses of dEpoB and dEpoF involves presentation of the C1-C11 sector for Suzuki coupling with C3 in reduced form. Hitherto, the required S stereochemistry at C3 had been implemented via reduction of a keto function after Suzuki coupling. Whereas that chemistry worked quite well in a synthesis of dEpoB, it was not transferable to a high-yielding synthesis of dEpoF. The reduction of the keto group at C3 via a Noyori protocol after Suzuki coupling had proved to be very difficult. In our current approach, two consecutive aldol reactions are used to fashion the acyl sector. In the first aldol condensation, C6 becomes attached to C7. Following protection at C7, a two-carbon acetate equivalent is used to join C2 and C3 with very high asymmetric induction at C3. Only after this center has been implemented is the Suzuki reaction conducted. This major advance allowed us to synthesize dEpoF in a straightforward fashion. These findings found ready application in the total synthesis of dEpoB. Another part of the study involved analysis of the factors associated with aldol condensations joining C6 to C7. In the work described herein, the consequences of the status of C3 in promoting the C6-C7 aldol coupling are probed in detail. Dramatic stereochemical long-range effects uncovered during the study are described, and a working model to explain these effects has emerged.

Antineoplastic Agents↗
PubMed2001

Monoclonal anti-acid-labile subunit oligopeptide antibodies and their use in a two-site immunoassay for ALS measurement in humans.

Quantification of the acid-labile subunit (ALS) has to date been restricted to immunoassays utilizing polyclonal antibodies. By immunization with N-terminal and C-terminal specific ALS oligopeptides, we generated monoclonal antibodies (mAbs) that target ALS-specific sequences outside the nonspecific leucine-rich repeats in the ALS molecule. For mAb selection, a special screening method was developed. Monoclonal antibody 5C9, which targets the N-terminus of ALS, is immobilized and the anti-ALS mAb 7H3, directed against the C-terminus, is biotinylated and used as tracer Ab. Due to the extreme pH-lability of ALS, changes in immunorecognition of ALS were investigated after acidification for protein unfolding in different pH ranges and in a time-dependent manner. It was determined that acidification of the serum samples to pH 2.7 for 30 min, followed by neutralization and dilution to 1:100 was the optimal acid-neutralization method. For standardization purposes, a serum pool derived from healthy volunteers was assigned the value 1 U/ml ALS. The sandwich assay has a working range with a linear dose-response curve in a log/log system between 0.005 and 10 U/ml. ALS levels in seven acromegalic patients ranged from 2.0 to 4.2 U/ml, and in 12 untreated growth hormone deficient patients from 0.036 to 0.986 U/ml (mean=0.45 U/ml). After 12 months of growth hormone therapy, ALS levels increased significantly to 1.18+/-0.45 U/ml (mean+/-SD; p<0.0006). The increase ranged from 0.48 to 1.4 U/ml. The change in ALS with growth hormone (GH) therapy correlated closer with the change in IGF-I (r=0.798, p=0.0057; Spearman rank correlation) than with the change in insulin-like growth factor binding protein (IGFBP3; r=0.549, p=0.057). This specific sandwich assay for the measurement of ALS provides a potentially valuable indicator of growth hormone secretory status. With this mAb-based immunofluorometric assay, the nonspecific detection of other proteins containing leucine-rich repeat sequences can be excluded.

Acromegaly↗
PubMed2001

[Diagnosis and treatment of brain tumors in jugular foramen region].

OBJECTIVE: To analyze the diagnosis and treatment of brain tumors in jugular foramen region. METHODS: 22 patients with brain tumor in jugular foramen region who had been diagnosed and treated from 1996 to 2000. Considerable literature was reviewed. RESULTS: Tumor imaging technique showed masses of different shapes in unilateral jugular foramen region. All of the 22 patients underwent operation via different approaches. Total removal of the tumor was achieved in 20 patients and subtotal removal in 2. Pathological examination confirmed the diagnosis of neurinoma in 13 patients, tumor of glomus jugulare in 4, meningioma in 3, chordoma in 1, and metastatic tumor in 1. Only one patient died after operation. The mortality rate was as low as 4.5%. CONCLUSION: The most common tumors in jugular foramen region are neurinoma, tumor of glomus jugulare, and meningioma. Surgery is effective in treatment of brain tumor in jugular foramen region.

Adolescent↗
PubMed2001

Synthesis, electrochemistry, and spectroscopic characterization of bis-dirhodium complexes linked by axial ligands.

The synthesis and electrochemical and spectroscopic properties of bis-dirhodium complexes containing ap or dpf bridging ligands, (ap)(4)Rh(2)(C triple bond C)(2)Rh(2)(ap)(4) (2) and (dpf)(4)Rh(2)(CNC(6)H(4)NC)Rh(2)(dpf)(4) (4), were investigated (where ap and dpf are the 2-anilinopyridinate and N,N'-diphenylformamidinate ions, respectively). The related "simple" dirhodium species, (ap)(4)Rh(2)(C triple bond C)(2)Si(CH(3))(3) (1) and (dpf)(4)Rh(2)(CNC(6)H(5)) (3), with the same set of bridging ligands were also synthesized and their properties compared to those of the analogous bis-dirhodium complexes. Compound 1 was obtained by mixing (ap)(4)Rh(2)Cl and Li(C triple bond C)(2)Si(CH(3))(3) in refluxing THF for 16 h under vacuum while compound 2 was prepared by a reaction between (ap)(4)Rh(2)(C triple bond C)(2)Li and (ap)(4)Rh(2)Cl under similar conditions. The reaction between (CF(3)COO)(4)Rh(2) and molten Hdpf under vacuum for 24 h leads to the generation of compound 3 with a yield of 65%. The red-orange compound 4 was obtained upon addition of 0.5 equiv of CNC(6)H(4)NC at room temperature to a CH(2)Cl(2) solution containing (dpf)(4)Rh(2) which was synthesized according to a method described previously in the literature. Compound 1 crystallizes in the triclinic space group P1, with a = 10.164(3) A, b = 13.881(3) A, c = 18.805(4) A, alpha = 73.55(2) degrees, beta = 77.89(2) degrees, gamma = 84.85(2) degrees, and Z = 2. Crystals of 2 were not good enough to collect adequate data for X-ray analysis, but the identity of this compound was confirmed, along with its P1; space group. Crystals of 3 and 4 belong to the monoclinic, P2(1)/c space group and the triclinic, P1; space group, respectively, with a = 13.5254(5) A, b = 13.7387(4) A, c = 27.2011(12) A, beta = 102.637(2) degrees, and Z = 4 for 3 and a = 13.866(8) A, b = 14.756(7) A, c = 15.008(6) A, alpha = 79.91(3) degrees, beta = 87.72(4) degrees, gamma = 89.19(4) degrees, and Z = 1 for 4. Compound 1 exhibits a single reversible oxidation at E(1/2) = 0.66 V and a single reversible reduction at E(1/2) = -0.44 V vs SCE in THF, 0.2 M TBAP. Both processes involve a one-electron transfer. Compound 2 undergoes a reversible oxidation at E(1/2) = 0.60 V and two separate one-electron-transfer reductions at E(1/2) = -0.52 and -0.65 V in THF, 0.2 M TBAP. The oxidation involves two overlapped one-electron-transfer processes. Compounds 3 and 4 undergo two reversible oxidations in CH(2)Cl(2), 0.1 M TBAP located at E(1/2) = 0.23 and 1.22 V (3) or 0.22 and 1.20 V (4). Each redox reaction of 3 involves a one-electron-transfer step while each redox reaction of 4 involves two overlapping one-electron transfers. Compound 2 shows interaction between the two dirhodium cores upon reduction, while 4 gives no evidence of electronic interaction between the two dirhodium units during either reduction or oxidation. An ESR signal with axial symmetry was obtained for the neutral compounds 1 and 2, and a similar spectrum was obtained for the singly oxidized products of compounds 3 and 4, thus suggesting the electronic configuration of (sigma)(2)(pi)(4)(delta)(2)(pi)(4)(delta)(1) for the neutral compounds 1 and 2 as well as for the oxidized compounds 3 and 4. The four compounds were also characterized by FTIR and UV-visible spectroscopy as well as by mass spectrometry.

Journal Article↗
PubMed2001

Multi-residue analysis of avermectins in swine liver by immunoaffinity extraction and liquid chromatography-mass spectrometry.

A multi-residue LC-MS method was developed to determine avermectin residues in swine liver. Abamectin and ivermectin (22,23-dihydroabamectin) were extracted, and cleaned up by immunoaffinty columns with immobilized anti-avermectin polyclonal antibodies. The cleaned samples were separated by high-performance liquid chromatography (HPLC) with a C8 column and determined by negative-ion atmospheric pressure chemical ionization (APCI) mass spectrometry (MS) using selective ion monitoring (SIM) of [M-H]-. Recoveries of abamectin and ivermectin from fortified samples at 5-100 microg kg(-1) levels ranged from 74 to 94% and from 65 to 87%, respectively. The limits of detection were 5 microg of abamectin or ivermectin in 1 kg sample.

Animals↗
PubMed2001

Differential NF-kappaB and IkappaB gene expression during development of cardiac allograft rejection versus CD154 monoclonal antibody-induced tolerance.

BACKGROUND: The Rel/NF-kappaB transcription factor pathway, regulated by IkappaB proteins, is considered central to immune responses, although there are surprisingly few in vivo data concerning alloresponses. METHODS: We undertook analysis of NF-kappaB and IkappaB mRNA intracardiac allograft expression, and NF-kappaB nuclear translocation, during acute rejection versus CD154 monoclonal antibody (mAb)-induced tolerance induction in fully MHC-disparate mice. RESULTS: Intragraft expression of all nine NF-kappaB and IkappaB genes increased during development of rejection, and nuclear translocation of p50, p52, and p65 was detected. CD154 mAb therapy decreased mRNA levels of all nine NF-kappaB and IkappaB genes, and impaired nuclear translocation of p50, p52, and p65 NF-kappaB proteins. However, prolonged survival could not be induced by CD154 mAb in p50- or p52-deficient allograft recipients, indicating an absolute requirement for expression of these genes in CD154 mAb-induced tolerance. CONCLUSIONS: We conclude that, whereas blanket approaches to NF-kappaB suppression are unlikely to be effective strategies for tolerance induction, a better understanding of the roles of individual NF-kappaB and IkappaB genes may allow development of more precise and effective therapies.

Animals↗
PubMed2001

Tyr199 in transmembrane domain 5 of the beta2-adrenergic receptor interacts directly with the pharmacophore of a unique fluorenone-based antagonist.

Mutagenesis of the beta2-adrenergic receptor (beta2AR) has suggested that amino acids in transmembrane domain 5 (TMD 5) play an important role in the interaction of the receptor with the catechol end of adrenergic agonists. However, little direct biochemical evidence for the interaction of any beta2AR agonist or antagonist with TMD 5 has been reported. To identify receptor amino acids that contribute to the beta2AR antagonist binding site, we identified the precise amino acid photoinsertion site of a novel carazolol-like fluorenone antagonist photoaffinity label, [125I]iodoaminoflisopolol ([125I]IAmF). A unique property of this photolabel is that the photoreactive centre is also the binding pharmacophore, which corresponds to the catechol end of related beta2AR agonists. [125I]IAmF specifically photolabels membrane-bound and purified beta2AR from a baculovirus/Spodoptera frugiperda (fall armyworm) ('Sf9') expression system. When the photolabelled beta2AR was cleaved by trypsin or Factor Xa, 30 kDa labelled peptides were generated. On the basis of concanavalin A binding and amino acid sequencing, these contain the N-terminus of the beta2AR, including TMDs 1-5. Further cleavage of the 30 kDa peptides with endoproteinase Lys-C generated a 4 kDa labelled peptide with an N-terminal amino acid sequence between TMDs 4 and 5. Radiosequencing of this peptide demonstrated that the precise [125I]IAmF photoinsertion site was Tyr(199) in TMD 5. Since the photoreactive centre and the binding pharmacophore of IAmF are the same, these data demonstrate that Tyr(199) interacts with the planar fluorenone moiety of a carazolol-like beta2AR antagonist, and contributes significant new information regarding the binding site for beta2AR antagonists.

Adrenergic beta-2 Receptor Antagonists↗
PubMed2001

Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1.

Muscle tissue is the major site for insulin-stimulated glucose uptake in vivo, due primarily to the recruitment of the insulin-sensitive glucose transporter (GLUT4) to the plasma membrane. Surprisingly, virtually all cultured muscle cells express little or no GLUT4. We show here that adenovirus-mediated expression of the transcriptional coactivator PGC-1, which is expressed in muscle in vivo but is also deficient in cultured muscle cells, causes the total restoration of GLUT4 mRNA levels to those observed in vivo. This increased GLUT4 expression correlates with a 3-fold increase in glucose transport, although much of this protein is transported to the plasma membrane even in the absence of insulin. PGC-1 mediates this increased GLUT4 expression, in large part, by binding to and coactivating the muscle-selective transcription factor MEF2C. These data indicate that PGC-1 is a coactivator of MEF2C and can control the level of endogenous GLUT4 gene expression in muscle.

Animals↗
PubMed2001

XANES study on the valence transitions in cerium oxide nanoparticles.

The aim of this work is the determination of Ce environment and valence state in Cerium oxide nanoparticles prepared by the microemulsion method. X-ray absorption near-edge structure measurements at Ce L3 edge were performed on the nanoparticles as a function of annealing temperature, ranging from 298K to 873K under air condition. The experimental results support the conclusion that Ce ion, in the investigated systems, is in trivalence state when the annealing temperature is below 473K. As the temperature increases up to 623K, the XANES spectrum shows the coexistence of Ce3+ and Ce4+ states. When the temperature is higher than 623K, the spectra become identical to that of CeO2 with a distinct double-peak structure, corresponding to the Ce4+ state.

Journal Article↗