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Biomedical subjects

L Zhu

Publications and source records attributed to L Zhu.

At least 19 recordsLinked to original sources
PubMed2003

Estrogen levels and estrogen receptors in patients with stress urinary incontinence and pelvic organ prolapse.

OBJECTIVES: To investigate the histologic characteristics of tissues presumed to be the cause of urinary stress incontinence and pelvic organ prolapse. METHODS: Cardinal ligament and uterosacral ligament samples were obtained from 73 women undergoing hysterectomy. The evaluation of estrogen receptors (ERs) by immunohistochemical staining was semi-quantitative. Serum estrogen was determined by ELISA. Statistical analyses were performed by the independent-sample t-test and one-way ANOVA. RESULTS: Serum estradiol levels and ER values in the premenopausal women with pelvic organ prolapse were significantly lower than in the control group (P<0.01). A positive correlation was found between ERs and the number of postmenopausal years (P<0.01). ER values were similar in the cardinal and uterosacral ligaments. CONCLUSIONS: Serum estrogen levels and ER values are significantly lower in the uterine ligaments of premenopausal women with pelvic organ prolapse, and there was a positive correlation between ER values in the uterine ligaments and the duration of postmenopausal years. Serum estrogen levels and ER values were similar in the cardinal ligament and the uterosacral ligament.

Adult↗
PubMed2002

Measurement of analyzing power for proton-carbon elastic scattering in the coulomb-nuclear interference region with a 22-GeV/c polarized proton beam.

The analyzing power for proton-carbon elastic scattering in the Coulomb-nuclear interference region of momentum transfer, 9.0x10(-3)<-t<4.1x10(-2) (GeV/c)(2), was measured with a 21.7 GeV/c polarized proton beam at the Alternating Gradient Synchrotron of Brookhaven National Laboratory. The ratio of hadronic spin-flip to nonflip amplitude, r(5), was obtained from the analyzing power to be Rer(5)=0.088+/-0.058 and Imr(5)=-0.161+/-0.226.

Journal Article↗
PubMed2002

Measurement of G(E(p))/G(M(p)) in e(-->)p---> e(-->)p to Q(2) = 5.6 GeV(2).

The ratio of the electric and magnetic form factors of the proton G(E(p))/G(M(p)), which is an image of its charge and magnetization distributions, was measured at the Thomas Jefferson National Accelerator Facility (JLab) using the recoil polarization technique. The ratio of the form factors is directly proportional to the ratio of the transverse to longitudinal components of the polarization of the recoil proton in the elastic e(-->)p---> e(-->)p reaction. The new data presented span the range 3.5< Q(2)< 5.6 GeV(2) and are well described by a linear Q(2) fit. Also, the ratio sqrt[Q(2)] F(2(p))/F(1(p)) reaches a constant value above Q(2) = 2 GeV(2).

Journal Article↗
PubMed2002

Decay of ethanol-induced suppression of glycine-activated current of ventral tegmental area neurons.

We demonstrated previously that ethanol depresses glycine-induced currents in 45% of neurons freshly isolated from the ventral tegmental area (VTA) of rats (), and that protein kinase C (PKC) modulates this action of ethanol (). In the present study, we investigated the time course of this effect of ethanol on VTA neurons from young rats. For 70% of the neurons in which ethanol reduced glycine-evoked currents, this depressant effect gradually diminished during continuous superfusion with ethanol. Its action decayed faster when ethanol was applied in several brief pulses than by continuous superfusion. On the other hand, the decay was especially slower when ethanol was applied in pulses at longer intervals or by preincubation. Phorbol ester 12,13-dibutyrate (PDBu, 1 microM), an activator of PKC, also depressed glycine-induced currents. In approximately 40% (6/15) of the neurons, the effect of PDBu diminished with time and was antagonized by the specific PKC inhibitor, chelerythrine (7 microM). Chelerythrine also attenuated the ethanol-induced depression of glycine-induced currents and its time-dependent decay, thus confirming our previous evidence that PKC mediates, at least in part, the decay of the depressant effect of ethanol on glycine-induced currents of VTA neurons.

Animals↗
PubMed2002

G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion: an excellent alternative for high-risk leukemia.

Based on our encouraging results of G-CSF-primed HLA-matched related marrow transplants for high-risk leukemia, we extended the study from matched related to haploidentical transplants using G-CSF primed marrow and sequential immunosuppressants to prevent both graft-versus-host disease (GVHD) and host-versus-graft rejection (HVGR). Fifteen high-risk leukemia patients, who needed urgent transplantation but lacked an HLA-matched donor, underwent G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion. Donors were given G-CSF (Lenograstim) at 3-4 microg/kg/day for 7 days prior to marrow harvest. GVHD and HVGR prophylaxis were combined in the sequential usage of cyclosporin A, methotrexate, anti-thymocyte globulin and mycophenolate mofetil. All patients established sustained trilineage engraftment at a median of 19 days and 21 days for neutrophil and platelets respectively. G-CSF priming significantly increased CD34(+) and CFU-GM cells, reduced total lymphocytes and reversed the CD4(+)/CD8(+) ratio in the donor marrow. The incidence of grade II-IV acute GVHD was 33.3%. Nine patients survived more than a year with a Karnofsky performance status of 100%. Estimated overall disease-free survival at 2 years was 60 +/- 7%. In conclusion, using G-CSF priming marrow grafts along with sequential immunosuppressants provided an excellent alternative for the treatment of high-risk hematological malignancy in patients who lack matched donors.

Adolescent↗
PubMed2002

IGF-I regulates osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand in vitro and OPG in vivo.

IGF-I, a ubiquitous polypeptide, plays a key role in longitudinal bone growth and acquisition. The most predominant effect of skeletal IGF-I is acceleration of the differentiation program for osteoblasts. However, in vivo studies using recombinant human (rh) IGF-I and/or rhGH have demonstrated stimulation of both bone formation and resorption, thereby potentially limiting the usefulness of these peptides in the treatment of osteoporosis. In this study, we hypothesized that IGF-I modulates bone resorption by regulating expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL) in bone cells. Using Northern analysis in ST2 cells, we found that human IGF-I suppressed OPG mRNA in a time- and dose-dependent manner: 100 micro g/LIGF-I (13 nM) decreased OPG expression by 37.0 +/- 1.8% (P < 0.002). The half maximal inhibitory dose of IGF-I was reached at 50 micro g/liter ( approximately 6.5 nM) with no effect of IGF-I on OPG message stability. Conditioned media from ST2 cells confirmed that IGF-I decreased secreted OPG, reducing levels by 42%, from 12.1-7 ng/ml at 48 h (P < 0.05). Similarly, IGF-I at 100 micro g/liter (13 nM) increased RANKL mRNA expression to 353 +/- 74% above untreated cells as assessed by real-time PCR. In vivo, low doses of rhGH when administered to elderly postmenopausal women only modestly raised serum IGF-I (to concentrations of 18-26 nM) and did not affect circulating OPG concentrations; however, administration of rhIGF-I (30 micro g/kg.d) for 1 yr to older women resulted in a significant increase in serum IGF-I (to concentrations of 39-45 nM) and a 20% reduction in serum OPG (P < 0.05). In summary, we conclude that IGF-I in a dose- and time-dependent manner regulates OPG and RANKL in vitro and in vivo. These data suggest IGF-I may act as a coupling factor in bone remodeling by activating both bone formation and bone resorption; the latter effect appears to be mediated through the OPG/RANKL system in bone.

Animals↗
PubMed2001

Construction of a square-planar molecular box: self-assembly of palladium(II) complexes of 3,6,9,16,19,22-hexaazatricyclo[22.2.2.2(11,14)]triacon-11,13,24,26(1),27,29-hexaene through hydrogen-bonding interactions.

Binuclear palladium(II) complexes of the macrocyclic polyamine 3,6,9,16,19,22-hexaazatricyclo[22.2.2.2(11,14)]triacon-11,13,24,26(1),2 7,29-hexaene (L) are used to construct molecules having special shapes. In this study two binuclear palladium(II) complexes [Pd(2)LI(2)]I(2)and [Pd(2)LCl(2)](NO(3))(2).H(2)O are synthesized and structurally characterized. X-ray crystallography shows that both complexes exist as one-dimensional chains formed via intermolecular hydrogen-bonding N(3)-H(3C)---X in which X is I and Cl. Moreover, the ligands in both complexes adopt a boatlike conformation that may facilitate the formation of the tetranuclear complex. The cationic aqua complex [Pd(2)L(H(2)O)(m)(NO(3))(n)]((4-n)+, obtained by the treatment of [Pd(2)LI(2)]I(2)and [Pd(2)LCl(2)]Cl(2) with AgNO(3), is used as a building block for the construction of a tetranuclear palladium(II) complex [Pd(4)L(2)(C(2)O(4))(2)](NO(3))(4).6H(2)O. X-ray crystallography shows that the tetranuclear complex forms an open, hydrophobic box. These molecular boxes are connected via the hydrogen bond N(3)-H(3C)---O(4B) (symmetry code B: x, 1 + y, z) into a one-dimensional chain. A two-dimensional structure is formed via pi-pi stacking of the plane defined by C6 to C11 in the one chain and its symmetry-related plane (symmetry code C: -x, -1 - y, 2 - z) in another chain. This study exemplifies a new method for the assembly of molecular boxes using a macrocyclic ligand.

Journal Article↗
PubMed2001

Identification of dipeptidyl nitriles as potent and selective inhibitors of cathepsin B through structure-based drug design.

Cathepsin B is a member of the papain superfamily of cysteine proteases and has been implicated in the pathology of numerous diseases, including arthritis and cancer. As part of an effort to identify potent, reversible inhibitors of this protease, we examined a series of dipeptidyl nitriles, starting with the previously reported Cbz-Phe-NH-CH(2)CN (19, IC(50) = 62 microM). High-resolution X-ray crystallographic data and molecular modeling were used to optimize the P(1), P(2), and P(3) substituents of this template. Cathepsin B is unique in its class in that it contains a carboxylate recognition site in the S(2)' pocket of the active site. Inhibitor potency and selectivity were enhanced by tethering a carboxylate functionality from the carbon alpha to the nitrile to interact with this region of the enzyme. This resulted in the identification of compound 10, a 7 nM inhibitor of cathepsin B, with excellent selectivity over other cysteine cathepsins.

Animals↗
PubMed2001

The role of the third beta strand in gp120 conformation and neutralization sensitivity of the HIV-1 primary isolate DH012.

Neutralization of HIV-1 primary isolates has been a tremendous challenge for AIDS vaccine development. Here, we identify a single amino acid change (T198P) in gp120 that alters the neutralization sensitivity of the primary isolate DH012 to antibodies against multiple neutralization epitopes that include the V3, CD4-induced, and CD4 binding sites in gp120. This mutation is located in the V1/V2 stem region that forms the third beta strand (beta3) of the bridging sheet of gp120. The conformation of variable loops, especially V1/V2 and V3, was proposed to regulate the accessibility of these neutralization epitopes. The results of this study indicate a direct association between the V1/V2 and V3 loops of DH012 gp120. The single amino acid mutation T198P in the beta3 severely compromises the interaction between the V1/V2 and V3 loops. These results suggest that interaction of V1/V2 and V3 can mask the neutralization epitopes and that the beta3 plays a critical role in determining the neutralization sensitivity by modulating the interaction. This study provides an insight into why primary isolates are relatively resistant to antibody neutralization and might facilitate the development of anti-HIV strategies against HIV-1 infection.

Base Sequence↗
PubMed2001

Liquid-phase microextraction of phenolic compounds combined with on-line preconcentration by field-amplified sample injection at low pH in micellar electrokinetic chromatography.

This paper describes a novel method that applies field-amplified sample injection (FASI) in micellar electrokinetic chromatography (MEKC) with a low pH background electrolyte (BGE). Six phenolic compounds prepared in water or NaOH solution were used as the test analytes. Sample was injected electrokinetically after the introduction of a plug of water. During the injection, the water plug was pumped out of the capillary inlet by the electroosmotic flow, and the phenolic anions migrated very quickly in the direction of the outlet. When the anions reached the boundary between the water plug and BGE, they were neutralized and ceased moving. Thereafter, MEKC was initiated for the separation. This on-line preconcentration method could be conveniently coupled with a liquid-liquid-liquid microextraction procedure, in which a hollow fiber was used as an extraction solvent support to extract the analytes from the water sample. The acceptor phase consisted of 8 mM NaOH. After extraction, the extract was analyzed directly by MEKC, as described.

Journal Article↗
PubMed2001

Anti-apoptotic protein survivin plays a significant role in tubular morphogenesis of human coronary arteriolar endothelial cells by hypoxic preconditioning.

Brief exposure of endothelial cells to oxidative stress induced by hypoxia followed by reoxygenation enhances tube formation. Our study provides evidence that hypoxic preconditioning accelerates tubular morphogenesis along with the activation of reactive oxygen species-inducible nuclear transcription factor-kappaB (NF-kappaB), phosphatidylinositol 3-kinase (PI3-kinase) and broad-spectrum anti-apoptotic protein survivin in human coronary arteriolar endothelial cells (HCAEC). The formation of tubular morphogenesis was inhibited by using the PI3-kinase and NF-kappaB antagonists LY294002 and SN50 respectively. The activation of survivin by hypoxic preconditioning was also inhibited by LY294002 and SN50 along with increased apoptosis in HCAEC. These data demonstrate a crucial role of PI3-kinase/Akt/NF-kappaB/survivin signaling in tubular morphogenesis of HCAEC triggered by hypoxic preconditioning.

Apoptosis↗
PubMed2001

Direct extraction of specific pharmacophoric flavonoids from gingko leaves using a molecularly imprinted polymer for quercetin.

A new straightforward approach to extract active components from Chinese traditional herb was reported by using a molecularly imprinted polymer (MIP) as the sorbent material. The MIP was prepared using quercetin, a typical active compound of the flavonoid family in gingko leaves as the template. Acrylamide was used as the functional monomer and two polar solvent tetrahydrofuran was used as the porogen. Afterwards, the polymer was evaluated by chromatographic analysis. It exhibited high selectivity for quercetin and good affinity to its structural analogues. Specific binding amount of quercetin on the MIP in the solvent methanol was 12 microg/g polymer by the cartridge test. The MIP cartridge could directly trap a specific class of compounds including quercetin and kaempferol from the hydrolyzate of gingko leaves. The result demonstrated the possibility of direct extraction of certain pharmacophoric constituents from herb by MIP technology. The compounds extracted were confirmed by time-of-flight mass spectrometry.

Chromatography, High Pressure Liquid↗
PubMed2001

Observation of a (6)(LambdaLambda)He double hypernucleus.

A double-hyperfragment event has been found in a hybrid-emulsion experiment. It is identified uniquely as the sequential decay of ( 6)(LambdaLambda)He emitted from a Xi(-) hyperon nuclear capture at rest. The mass of ( 6)(LambdaLambda)He and the Lambda-Lambda interaction energy DeltaB(LambdaLambda) have been measured for the first time devoid of the ambiguities due to the possibilities of excited states. The value of DeltaB(LambdaLambda) is 1.01+/-0.20(+0.18)(-0.11) MeV. This demonstrates that the Lambda-Lambda interaction is weakly attractive.

Journal Article↗
PubMed2001

Hydrogen peroxide generated during cellular insulin stimulation is integral to activation of the distal insulin signaling cascade in 3T3-L1 adipocytes.

In a variety of cell types, insulin stimulation elicits the rapid production of H(2)O(2), which causes the oxidative inhibition of protein-tyrosine phosphatases and enhances the tyrosine phosphorylation of proteins in the early insulin action cascade (Mahadev, K., Zilbering, A., Zhu, L., and Goldstein, B. J. (2001) J. Biol. Chem. 276, 21938-21942). In the present work, we explored the potential role of insulin-induced H(2)O(2) generation on downstream insulin signaling using diphenyleneiodonium (DPI), an inhibitor of cellular NADPH oxidase that blocks insulin-stimulated cellular H(2)O(2) production. DPI completely inhibited the activation of phosphatidylinositol (PI) 3'-kinase activity by insulin and reduced the insulin-induced activation of the serine kinase Akt by up to 49%; these activities were restored when H(2)O(2) was added back to cells that had been pretreated with DPI. Interestingly, the H(2)O(2)-induced activation of Akt was entirely mediated by upstream stimulation of PI 3'-kinase activity, since treatment of 3T3-L1 adipocytes with the PI 3'-kinase inhibitors wortmannin or LY294002 completely blocked the subsequent activation of Akt by exogenous H(2)O(2). Preventing oxidant generation with DPI also blocked insulin-stimulated glucose uptake and GLUT4 translocation to the plasma membrane, providing further evidence for an oxidant signal in the regulation of the distal insulin-signaling cascade. Finally, in contrast to the cellular mechanism of H(2)O(2) generation by other growth factors, such as platelet-derived growth factor, we also found that insulin-stimulated cellular production of H(2)O(2) may occur through a unique pathway, independent of cellular PI 3'-kinase activity. Overall, these data provide insight into the physiological role of insulin-dependent H(2)O(2) generation, which is not only involved in the regulation of tyrosine phosphorylation events in the early insulin signaling cascade but also has important effects on the regulation of downstream insulin signaling, involving the activation of PI 3'-kinase, Akt, and ultimately cellular glucose transport in response to insulin.

3T3 Cells↗
PubMed2001

Experimental observation of generalized time-lagged chaotic synchronization.

We investigate, experimentally, synchronization in coupled chaotic oscillators in the presence of large parameter mismatches and identify a different phenomenon: generalized time-lagged synchronization. Specifically, we find that there can be a functional relation between time-lagged dynamical variables of the coupled oscillators in wide parameter regimes.

Journal Article↗
PubMed2001

Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals.

BH3-only proteins function at a proximal point in a conserved cell death pathway by binding, through their BH3 domains, to other Bcl-2 family members and triggering mitochondrial events associated with apoptosis. Here, we describe a strongly pro-apoptotic BH3-only protein, designated Bbc3, whose expression increases in response to diverse apoptotic stimuli. bbc3 mRNA levels were induced by exposure to DNA-damaging agents and by wild-type p53, which mediates DNA damage-induced apoptosis. p53 transactivated bbc3 through consensus p53 binding sites within the bbc3 promoter region, indicating that bbc3 is a direct target of p53. Additionally, bbc3 mRNA was induced by p53-independent apoptotic stimuli, including dexamethasone treatment of thymocytes, and serum deprivation of tumor cells. Insulin-like growth factor-1 and epidermal growth factor, growth factors with broad anti-apoptotic activity, were each sufficient to suppress Bbc3 expression in serum-starved tumor cells. These results suggest that the transcriptional regulation of bbc3 contributes to the transduction of diverse cell death and survival signals.

Amino Acid Sequence↗