Search PubMed⌕ Search

Biomedical subjects

Hong Zhang

Publications and source records attributed to Hong Zhang.

At least 91 records · Page 5Linked to original sources
PubMed2006

Modification of MyD88 mRNA splicing and inhibition of IL-1beta signaling in cell culture and in mice with a 2'-O-methoxyethyl-modified oligonucleotide.

A number of proinflammatory cytokines, including IL-1beta, signal through the adaptor protein MyD88. This signaling leads to phosphorylation of IL-1R-associated kinase-1 (IRAK-1) and, ultimately, activation of the NF-kappaB transcription factor. A splice variant of MyD88 (MyD88(S)), which lacks the ability to couple IRAK-1 to NF-kappaB, has been described. A chemically modified antisense oligonucleotide (ASO) that alters the splicing ratio of MyD88 to MyD88(S) in both cell culture and in animals has been identified. The ASO (ISIS 337846) binds to exon II donor sites in the MyD88 pre-mRNA. By manipulating levels of MyD88 splicing, proinflammatory signaling through the IL-1R has been shown to be diminished, both in cell culture and in mouse liver. To our knowledge, this represents the first example of modulation of RNA splicing of an endogenous gene target in animals after systemic ASO dosing and suggests that this mechanism may be useful as a novel modulator of inflammatory stimuli.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Effect of low molecular weight organic acids on adsorption and desorption of fluoride on variable charge soils.

The effect of four low molecular weight organic acids on F(-) adsorption by two variable charge soils was investigated using a batch method. The organic acids reduced F(-) adsorption through competition by the acids with F(-) for sorption sites. Oxalic and malonic acids, both of which have simpler chemical structures, were more effective than citric or malic acid. The effect of organic acids on F(-) adsorption was more prominent at higher pH values and with larger amounts of the organic acids. The desorption study showed that the organic acids enhanced the desorption of F(-) adsorbed by the soils. In the control and malic acid systems, desorption increased sharply with decreasing pH, while in the oxalic acid system, desorption rose slightly with decreasing pH. Desorption also increased with increasing amount of organic acid added. There are two possible mechanisms for the effect of the organic acids on F(-) adsorption and desorption: (1) competition of the organic acids with F(-) for adsorption sites and (2) dissolution of the adsorbents, especially dissolution of soil Al.

Adsorption↗
PubMed2006

HO2 ro-vibrational bound-state calculations for large angular momentum: J = 30, 40, and 50.

The Lanczos homogeneous filter diagonalization method and the real Chebyshev filter diagonalization scheme incorporating doubling of the autocorrelation functions have been employed to compute the HO2 ro-vibrational states for high total angular momenta, J = 30, 40, and 50. For such computationally challenging calculations, we have adopted a parallel computing strategy to perform the matrix-vector multiplications. Low-lying bound states and high-lying bound states close to the dissociation threshold are reported. For low-lying bound states, a spectroscopic assignment has been attempted and the widely used approximate J-shifting method has been tested for this deep-well system. For high-lying bound states, the attempted spectroscopic assignments as well as the J-shifting approximation fail because of very strong Coriolis mixing, indicating that the Coriolis couplings are important for this system.

Journal Article↗
PubMed2006

[Characterization of macrolide-resistance mediated by transposable elements Tn1545 and Tn917 in clinical Isolates of Streptococcus pneumoniae].

OBJECTIVE: To investigate the characterization of ermB gene expression and dissemination in macrolide-resistant Streptococcus pneumoniae (Sp) in Shanghai. METHODS: Eighty-six erythromycin-resistant isolates of Sp were isolated from 3 hospitals in Shanghai. E-test or K-B disk diffusion test were used to determine the susceptibility to 12 antibiotics according to the National Committee for Clinical Laboratory Standards. Macrolide resistant genes ermB and mefE, and transposable elements Tn1545 and Tn917 were amplified by PCR. The isolates were divided into Tn1545 and Tn917 groups according to the transposable elements thereof. Double disc test with erythromycin and clindamycin discs divided the isolates into 2 macrolide resistant phenotypes: cMLS(B) (inducible) phenotype and M phenotype (resistant to erythromycin and sensitive to clindamycin). BOX-PCR was used to analyze the homology of the S. pneumoniae. RESULTS: (1) Of the 86 erythromycin-resistant isolates, the positive rates of ermB, mefE, Tn1545, and Tn917 were 94%, 46%, 87% and 7% respectively. Tn1545 and Tn917 were not detected in 5 ermB-mdfE + strains. (2) Most strains in the Tn1545 and Tn917 groups were highly resistant to erythromycin with a MIC50 of 256 microg/ml. The Tn917 group had a lower MIC to beta-lactam antibiotics and lower resistance to tetracycline, levofloxacin, and compound sulfonamide in comparison with the Tn1545 group. (3) The most common macrolide resistance phenotype of the Tn1545 group was cMLS(B) phenotype. Three strains in the Tn917 group had a 194 bp deletion in the promoter region of ermB and an insertion of TAAA motif in the N end of leader peptide, resulting in the change of the ermB gene from inducible to constitutive expression. (4) BOX-PCR showed that Tn1545 and Tn917 might spread horizontally. CONCLUSION: In Shanghai ermB-mediated cMLS(B) is the most prevalent phenotype in macrolide-resistant Streptococcus pneumoniae isolates. Primarily, the ermB gene was carried and spread horizontally by Tn1545.

Anti-Bacterial Agents↗
PubMed2006

Leukocyte-platelet aggregate adhesion and vascular permeability in intact microvessels: role of activated endothelial cells.

Leukocyte-platelet aggregation and aggregate adhesion have been indicated as biomarkers of the severity of tissue injury during inflammation or ischemic reperfusion. The objective of this study is to investigate the mechanisms of the aggregate adhesion and quantitatively evaluate its relationship with microvessel permeability. A combined autologous blood perfusion with single microvessel perfusion technique was employed in rat mesenteric venular microvessels. The aggregate adhesion was induced by systemic application of TNF-alpha plus local application of platelet-activating factor (PAF). Changes in permeability were determined by measurements of hydraulic conductivity (Lp) before and after aggregate adhesion in the same individually perfused microvessels. The compositions of the adherent aggregates were identified with fluorescent labeling and confocal imaging. In contrast to leukocyte adhesion as single cells resulting in no increase in microvessel permeability, aggregate adhesion induced prolonged increases in microvessel Lp (6.1 +/- 0.9 times the control, n = 9) indicated by the initial Lp measurements after 3 h of blood perfusion, which is distinct from the transient Lp increase caused by PAF-induced endothelial activation in the absence of blood. Isoproteronol (Iso) attenuated aggregate adhesion-mediated Lp increases if applied after autologous blood perfusion and prevented the aggregate adhesion if the initial endothelial activation is inhibited by applying Iso before PAF administration but showed less effect on single leukocyte adhesion. This study demonstrated that leukocyte-platelet aggregate adhesion via a mechanism different from that of single leukocyte adhesion caused a prolonged increase in microvessel permeability. Our results also indicate that the initial activation of endothelial cells by PAF plays a crucial role in the initiation of leukocyte-platelet aggregate adhesion.

Adrenergic beta-Agonists↗
PubMed2006

p53 plays a central role in UVA and UVB induced cell damage and apoptosis in melanoma cells.

We investigated whether p53 plays a role in UV induced apoptosis in melanoma. UVA and UVB induced apoptosis in dose dependent and wild type p53 melanoma cells were much more vulnerable than the mutant cells, indicating that p53 played a role in UV-induced apoptosis in melanoma. No difference in p53 expression pattern between the primary and matched metastatic melanomas was noticed in tumour tissue or cell lines from the same patients. Our findings indicate that expression of p53 plays a role in UV-induced apoptosis in melanoma cells, but not important in melanoma progression from primary to metastasis.

Apoptosis↗
PubMed2006

Tandem repeats polymorphism of MUC20 is an independent factor for the progression of immunoglobulin A nephropathy.

MUC20, an upregulated novel gene in the renal tissues of patients with IgA nephropathy (IgAN), was recently identified. The variable number of tandem repeats (VNTR) polymorphism of the MUC20 gene was detected in several cell lines. In the present study, we investigated a possible association of MUC20 VNTR polymorphism with the clinical manifestations and progression in patients with IgAN. A total of 1,147 Chinese subjects, including 657 patients with IgAN and 490 geographically matched healthy controls, were involved in this investigation. One hundred and thirty-seven patients had been followed up for 60.6 +/- 22.4 months. MUC20 VNTR polymorphism was genotyped by polymerase chain reaction amplification and confirmed by sequencing. The alleles were divided into two groups according to the repeat times of MUC20 VNTR, i.e. small alleles (VNTR repeat times < or = 3) and large alleles (VNTR repeat times >3), and the genotypes of subjects were classified into SS, SL and LL groups. The frequencies of the alleles and genotypes of MUC20 VNTR polymorphisms did not differ between patients with IgAN and healthy controls. Additionally, there was no significant difference in the clinical features. Furthermore, IgAN patients with SL/LL genotypes had a higher risk of decline in renal function (odds ratio 20.9; 95% confidence interval 2.6-168.1; p = 0.004) than those with SS genotypes. The present study revealed that there is no association between the VNTR polymorphism of the MUC20 gene and the clinical manifestations in IgAN patients at the time of renal biopsy. However, IgAN patients with SL/LL genotypes had a higher risk of the progression to end-stage renal disease.

Adolescent↗
PubMed2006

The L561A substitution in the nascent base-pair binding pocket of RB69 DNA polymerase reduces base discrimination.

Several variants of RB69 DNA polymerase (RB69 pol) with single-site replacements in the nascent base-pair binding pocket are less discriminating with respect to noncomplementary dNMP incorporation than the wild-type enzyme. To quantify the loss in base selectivity, we determined the transient-state kinetic parameters for incorporation of correct and all combinations of incorrect dNMPs by the exonuclease-deficient form of one of these RB69 pol variants, L561A, using rapid chemical quench assays. The L561A variant did not significantly alter the k(pol) and K(D) values for incorporation of correct dNMPs, but it showed increased incorporation efficiency (k(pol)/K(D)) for mispaired bases relative to the wild-type enzyme. The incorporation efficiency for mispaired bases by the L561A variant ranged from 1.5 x 10(-)(5) microM(-)(1) s(-)(1) for dCMP opposite templating C to 2 x 10(-)(3) microM(-)(1) s(-)(1) for dAMP opposite templating C. These k(pol)/K(D) values are 3-60-fold greater than those observed with the wild-type enzyme. The effect of the L561A replacement on the mutation frequency in vivo was determined by infecting Escherichia coli harboring a plasmid encoding the L561A variant of RB69 pol with T4 phage bearing a mutant rII locus, and the rates of reversions to rII(+) were scored. The exonuclease-proficient RB69 pol L561A displayed a weak mutator phenotype. In contrast, no progeny phage were produced after infection of E. coli, expressing an exonuclease-deficient RB69 pol L561A, with either mutant or wild-type T4 phage. This dominant-lethal phenotype was attributed to error catastrophe caused by the high rate of mutation expected from combining the pol L561A and exo(-) mutator activities.

Alanine↗
PubMed2006

Use of a chemically modified antisense oligonucleotide library to identify and validate Eg5 (kinesin-like 1) as a target for antineoplastic drug development.

A library of 2'-methoxyethyl-modified antisense oligonucleotides (2'MOE ASO) targeting 1,510 different genes has been developed, validated, and used to identify cell cycle regulatory genes. The most effective molecular target identified was Eg5 (kinesin-like-1), which when inhibited gave the largest increase in 4N DNA in various tumor cells. The Eg5 ASO reduced Eg5 levels, inhibited proliferation, increased apoptosis, and altered the expression of other cell cycle proteins, including survivin and Aurora-A. To examine the therapeutic utility of the Eg5 ASO, the compound was also evaluated in xenograft models. Treatment with Eg5 ASO produced a statistically significant reduction of tumor growth, reduction in Eg5 expression in the tumors, and changes in histone phosphorylation, consistent with a loss of Eg5 protein expression. These data show, for the first time, the utility of a 2'MOE ASO library for high-throughput cell culture-based functional assays and suggest that an Eg5 ASO also has potential in a therapeutic strategy.

Animals↗
PubMed2006

[Relationship between polymorphism of parathyroid hormone and bone mineral density and relevant biochemical indicators in women].

OBJECTIVE: To investigate the distribution of parathyroid hormone (PTH) gene polymorphisms and the relationships of PTH gene polymorphisms with bone mass and serum bone relative biochemical markers. METHODS: Blood samples of 314 normal female volunteers, aged 20 - 80, were collected. Serum PTH, bone alkaline phosphatase (sBAP), cross-linked N-telopeptide of collagen type I (sNTX), cross-linked C-telopeptide of collagen type I (sCTX), osteoprotegerin (OPG) and leptin were determined by ELISA. Polymorphisms of PTH gene were detected by polymerase chain reaction fragment length polymorphisms (PCR-RFLP) of restriction enzyme BstBI. BMD (QDR4500A) of the anteroposterior spine (AP), supine lateral spine (Lat), and femoral neck (FN) were measured. RESULTS: (1) The genotype frequency of BB, Bb, and bb were 75.8%, 23.3% and 0.9% respectively in normal females volunteers. The frequencies of RFLP alleles B and b were 87.5% and 12.5% respectively. There was no difference in the polymorphism frequency of PTH gene between the post- and pre menopausal women. (2) There were no significant differences in the BMD of the AP, Lat, and FN and the serum biochemical markers between the BB and Bb genotypes. (3) Multiple stepwise regression analysis showed that PTH did not influence the BMD values. CONCLUSION: PTH gene polymorphism has no relationship with bone mass and serum bone biochemical markers in normal females.

Adult↗
PubMed2006

Design and synthesis of dipeptidyl glutaminyl fluoromethyl ketones as potent severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors.

This paper describes the design and synthesis of dipeptidyl N,N-dimethyl glutaminyl fluoromethyl ketones (fmk) as severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors. The compounds were tested against SARS-CoV-induced cell death in Vero or CaCo2 cells as a measurement of the inhibiting effects of the compounds on the replication of the virus. Z-Leu-Gln(NMe(2))-fmk (6a) was found to be a potent inhibitor with low toxicity in cells, protecting cells with an EC(50) value of 2.5 microM and exhibiting a selectivity index of >40.

Animals↗
PubMed2006

Fabrication of electroactive layer-by-layer films of myoglobin with gold nanoparticles of different sizes.

Alternate adsorption of oppositely charged myoglobin (Mb) and gold nanoparticles with different sizes were used to assemble {Au/Mb}n layer-by-layer films on solid surfaces by electrostatic interaction between them. The direct electrochemistry of Mb was realized in {Au/Mb}n films at pyrolytic graphite (PG) electrodes, showing a pair of well-defined, nearly reversible cyclic voltammetry (CV) peaks for the Mb heme FeIII/FeII redox couple. Quartz crystal microbalance (QCM), electrochemical impedance spectroscopy (EIS), and CV were used to monitor or confirm the growth of the films. Compared with other Mb layer-by-layer films with nonconductive nanoparticles or polyions, {Au/Mb}n films showed much improved properties, such as smaller electron-transfer resistance (Rct) measured by EIS with Fe(CN)3-/4- redox probe, higher maximum surface concentration of electroactive Mb (Gamma*max), and better electrocatalytic activity toward reduction of O2 and H2O2, mainly because of the good conductivity of Au nanoparticles. Because of the high biocompatibility of Au nanoparticles, adsorbed Mb in the films retained its near native structure and biocatalytic activity. The size effect of Au nanoparticles on the electrochemical and electrocatalytic activity of Mb in {Au/Mb}n films was investigated, demonstrating that the {Au/Mb}n films assembled with smaller-sized Au nanoparticles have smaller Rct, higher Gamma*max, and better biocatalytic reactivity than those with larger size.

Adsorption↗
PubMed2006

SUMO modification through rapamycin-mediated heterodimerization reveals a dual role for Ubc9 in targeting RanGAP1 to nuclear pore complexes.

SUMOs (small ubiquitin-related modifiers) are eukaryotic proteins that are covalently conjugated to other proteins and thereby regulate a wide range of important cellular processes. The molecular mechanisms by which SUMO modification influences the functions of most target proteins and cellular processes, however, remain poorly defined. A major obstacle to investigating the effects of SUMO modification is the availability of a system for selectively inducing the modification or demodification of an individual protein. To address this problem, we have developed a procedure using the rapamycin heterodimerizer system. This procedure involves co-expression of rapamycin-binding domain fusion proteins of SUMO and candidate SUMO substrates in living cells. Treating cells with rapamycin induces a tight association between SUMO and a single SUMO substrate, thereby allowing specific downstream effects to be analyzed. Using RanGAP1 as a model SUMO substrate, the heterodimerizer system was used to investigate the molecular mechanism by which SUMO modification targets RanGAP1 from the cytoplasm to nuclear pore complexes (NPCs). Our results revealed a dual role for Ubc9 in targeting RanGAP1 to NPCs: In addition to conjugating SUMO-1 to RanGAP1, Ubc9 is also required to form a stable ternary complex with SUMO-1 modified RanGAP1 and Nup358. As illustrated by our studies, the rapamycin heterodimerizer system represents a novel tool for studying the molecular effects of SUMO modification.

Dimerization↗
PubMed2006

Aryl hydrocarbon receptor modulation of tumor necrosis factor-alpha-induced apoptosis and lysosomal disruption in a hepatoma model that is caspase-8-independent.

Recent studies suggest that the aryl hydrocarbon receptor (AhR) modulates susceptibilities to some pro-apoptotic agents. AhR-containing murine hepatoma 1c1c7 cultures underwent apoptosis following exposure to tumor necrosis factor-alpha (TNFalpha) + cycloheximide (CHX). In contrast, Tao cells, an AhR-deficient variant of the 1c1c7 line, were refractory to this treatment. AhR sense/antisense transfection studies demonstrated that AhR contents influenced susceptibility to the pro-apoptotic effects of TNFalpha + CHX. 1c1c7 cells and all variants expressed comparable amounts of TNF receptor-1 and TRADD. However, no cell line expressed FADD, and consequently pro-caspase-8 was not activated. AhR content did not influence JNK and NF-kappaB activation. However, Bid and pro-caspase-9, -3, and -12 processing occurred only in AhR-containing cells. Analyses of cathepsin B and D activities in digitonin-permeabilized cultures and the monitoring of cathepsin B/D co-localization with Lamp-1 indicated that TNFalpha + CHX disrupted late endosomes/lysosomes in only AhR-containing cells. Stabilization of acidic organelles with 3-O-methylsphingomyelin inhibited TNFalpha + CHX-induced apoptosis. The cathepsin D inhibitor pepstatin A suppressed in vitro cleavage of Bid by 1c1c7 lysosomal extracts. It also delayed the induction of apoptosis and partially prevented Bid cleavage and the activation of pro-caspases-3/7 in cultures treated with TNFalpha + CHX. Similar suppressive effects occurred in cultures transfected with murine Bid antisense oligonucleotides. These studies showed that in cells where pro-caspase-8 is not activated, TNFalpha + CHX can initiate apoptosis through lysosomal disruption. Released proteases such as cathepsin D trigger the apoptotic program by activating Bid. Furthermore, in the absence of exogenous ligand, the AhR modulates lysosomal disruption/permeability.

Animals↗
PubMed2006

Degradation of porphyran from Porphyra haitanensis and the antioxidant activities of the degraded porphyrans with different molecular weight.

In the present paper, ascorbate and hydrogen peroxide (H2O2) were used to degrade porphyran. It was found that porphyran could be degraded by free radical that was generated by ascorbate and H2O2 in combination. It was possible to prepare desired porphyran products with different molecular weight by adjusting ascorbate to H2O2 proportions and their concentrations. The molar ratio of 1 was demonstrated more effective than in other ratios. Higher concentrations accelerated the degradation. Moreover, results of chemical analysis and FT-IR spectra suggested that the main structure of degraded products still remained although some changes happened. The degraded and natural porphyrans possessed scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH)-radical activity and reducing power. Higher antioxidant activities were found in both systems when the molecular weight was reduced. The results indicated that the antioxidant activities were closely related to the molecular weight. The degraded porphyrans are potential antioxidant in vitro.

Antioxidants↗
PubMed2006

Regional differences in anatomical landmarks for placing anterior instrumentation of the thoracic spine in both normal patients and patients with adolescent idiopathic scoliosis.

STUDY DESIGN: A retrospective analysis of patients who had magnetic resonance imaging (MRI) of the thoracic spine, comparing those with a normal straight spine and those with a right thoracic adolescent idiopathic scoliosis (AIS). OBJECTIVE: To analyze the position of the rib head with respect to the spinal canal and vertebral body in normal patients and those with right thoracic AIS using MRI. SUMMARY OF BACKGROUND DATA: When placing anterior vertebral body screws in thoracic AIS, the most cephalad screws are most at risk for loosening because of smaller vertebral body size and the position of the rib heads, which may obscure more of the vertebral bodies. To our knowledge, there are no studies defining the relationship of the rib head to the vertebral anatomy in thoracic AIS. METHODS: Transverse MRIs of the vertebral bodies from the 4th thoracic (T4) vertebra to the 12th thoracic (T12) vertebra in normal patients (n = 21) and patients with AIS (n = 21) group were analyzed regarding the following parameters: (1) percent vertebra obscured by rib head (i.e., the percent of the sagittal plane vertebral body length obscured by the overlapping rib head); (2) posterior safe angle, defined as the most posterior angle a screw can be placed, which avoids the spinal canal; and (3) anterior safe angle, defined as the most anteriorly directed screw trajectory that safely obtained good screw purchase. RESULTS: In both the normal and AIS groups, the percent vertebra obscured by rib head significantly decreased from T4 (30% in normal group and 34.7% in AIS group) to T12 (-0.4% in normal group and 3.5% in AIS group) (P < 0.05). The rib head was positioned more anterior to the vertebral body in the cephalad-thoracic spine when compared to a more posterior position in the caudal thoracic spine. In each group, the posterior safe angle significantly decreased from T4 (23 degrees in normal group and 20.8 degrees in AIS group) to T12 (-0.9 degrees in normal group and 2.1 degrees in AIS group) (P < 0.05), while the anterior safe angle significantly increased from T4 (27.5 degrees in normal group and 26.6 degrees in AIS group) to T12 (38.3 degrees in normal group and 38.5 degrees in AIS group) (P < 0.05). CONCLUSIONS: It is important to understand the relationship of the rib head to the vertebral body to provide-excellent screw purchase within the vertebral body without risking penetration into the spinal canal. In both normal and AIS groups, the relationship of the rib head to the vertebral body and spinal canal changes so that the rib head is positioned more anteriorly in the cephalad-thoracic spine and more posteriorly in the caudal thoracic spine. When placing anterior thoracic screws, at the cephalad- thoracic spine (T4, T5, T6, and T7), removal of rib heads is recommended to allow for good screw purchase. However, at the caudal thoracic spine (T10-T12), staying anterior to the rib head is important to avoid penetration into the spinal canal.

Adolescent↗
PubMed2006

Drift of spiral waves controlled by a polarized electric field.

The drift behavior of spiral waves under the influence of a polarized electric field is investigated in the light that both the polarized electric field and the spiral waves possess rotation symmetry. Numerical simulations of a reaction-diffusion model show that the drift velocity of the spiral tip can be controlled by changing the polarization mode of the polarized electric field and some interesting drift phenomena are observed. When the electric field is circularly polarized and its rotation follows that of the spiral, the drift speed of the spiral tip reaches its maximal value. On the contrary, opposite rotation between the spiral and electric field locks the drift of the spiral tip. Analytical results based on the weak deformation approximation are consistent with the numerical results. We hope that our theoretical results will be observed in experiments, such as the Belousov-Zhabotinsky reaction.

Algorithms↗