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Hong Zhang

Publications and source records attributed to Hong Zhang.

At least 271 records · Page 15Linked to original sources
PubMed2004

A therapeutic HIV vaccine: how good is good enough?

The goal of a therapeutic HIV vaccine is to attenuate HIV disease progression in those already infected. Our objective was to establish comparative efficacy and cost-effectiveness thresholds at which a therapeutic vaccine would make a valuable contribution to HIV care. Using an HIV computer simulation model, we compared therapeutic vaccination with HIV standard of care without vaccination. Input data were obtained from the literature. Base case and sensitivity analyses related to vaccine magnitude, penetrance, durability, and cost. In the base case (0.5 log magnitude, 25% penetrance, 3-year durability, and US$ 4000 per series), vaccination increased quality-adjusted life expectancy (QALE) by 0.50 months compared to no vaccination (cost-effectiveness ratio US$ 89,900 per quality-adjusted life year (QALY)). Increasing vaccine penetrance to 50% increased the projected QALE benefit to 0.91 months (cost-effectiveness ratio US$ 45,500/QALY). Even modestly effective therapeutic HIV vaccines may produce small but meaningful increases in life expectancy and compare favorably to alternative uses of scarce HIV care resources.

AIDS Vaccines↗
PubMed2004

Enhancement to the RANKPEP resource for the prediction of peptide binding to MHC molecules using profiles.

We introduced previously an on-line resource, RANKPEP that uses position specific scoring matrices (PSSMs) or profiles for the prediction of peptide-MHC class I (MHCI) binding as a basis for CD8 T-cell epitope identification. Here, using PSSMs that are structurally consistent with the binding mode of MHC class II (MHCII) ligands, we have extended RANKPEP to prediction of peptide-MHCII binding and anticipation of CD4 T-cell epitopes. Currently, 88 and 50 different MHCI and MHCII molecules, respectively, can be targeted for peptide binding predictions in RANKPEP. Because appropriate processing of antigenic peptides must occur prior to major histocompatibility complex (MHC) binding, cleavage site prediction methods are important adjuncts for T-cell epitope discovery. Given that the C-terminus of most MHCI-restricted epitopes results from proteasomal cleavage, we have modeled the cleavage site from known MHCI-restricted epitopes using statistical language models. The RANKPEP server now determines whether the C-terminus of any predicted MHCI ligand may result from such proteasomal cleavage. Also implemented is a variability masking function. This feature focuses prediction on conserved rather than highly variable protein segments encoded by infectious genomes, thereby offering identification of invariant T-cell epitopes to thwart mutation as an immune evasion mechanism.

Algorithms↗
PubMed2004

Adrenergic receptor antagonist prevents the left ventricle with chronic pressure-overload from electrical remodeling.

Experiments were performed to investigate the effects of long-term treatment with adrenergic receptor antagonist on electrical remodeling of the left ventricle with chronic pressure-overload. New Zealand rabbits underwent subtotal banding of superrenal abdominal aorta. At 10 weeks after surgery, echocardiography examination was performed, then action potential (AP), inward rectifier potassium current (I(Ki)), delayed rectifier potassium current (I(K)) and Na(+)/Ca(2+) exchanger current (I(Na(+)/Ca(2+))) were recorded in midmyocardial cells isolated from left ventricle of abdominal aorta banded group (banded group), abdominal aorta banding plus Carvedilol intervention group (Carvedilol group), and normal control group rabbits by using the whole-cell patch-clamp techniques. The results showed that left ventricular mass index in control, banded, and Carvedilol groups were 1.78+/-0.06 (n=7), 2.33+/-0.11 (n=7), and 1.87+/-0.08 (n=7), respectively (banded vs control and Carvedilol, P<0.01). At basic cycle length of 2 s, AP duration (measured at 90% repolarization, APD(90), ms) in control, banded, and Carvedilol groups were 522.0+/-19.5 (n=6), 664.7+/-46.2 (n=7), 567.8+/-14.3 (n=8) respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). At test potential of -100 mV, inward I(Ki) density (pA/pF) in control, banded, and Carvedilol groups were -11.8+/-0.50 (n=8), -8.07+/-0.28 (n=8), -10.69+/-0.35 (n=8) respectively (banded vs control and Carvedilol, P<0.01). At test potential of +50 mV, I(K) tail current density (pA/pF) in control, banded, and Carvedilol groups were 0.59+/-0.04 (n=8), 0.40+/-0.02 (n=9), 0.51+/-0.02 (n=8) respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). At test potential of +60 mV, outward I(Na(+)/Ca(2+)) density (pA/pF) in control, banded, and Carvedilol groups were 1.06+/-0.11 (n=8), 1.54+/-0.10 (n=9), 1.24+/-0.07 (n=8), respectively (banded vs control and Carvedilol, P<0.01). At test potential of -120 mV, inward I(Na(+)/Ca(2+)) density (pA/pF) in control, banded, and Carvedilol groups were -0.54+/-0.06 (n =8), -0.75+/-0.04 (n=9), -0.60+/-0.03 (n=8), respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). It is shown that long-term treatment with Carvedilol not only prevents development of cardiac hypertrophy, but also improves the electrophysiological alterations in rabbit hearts with chronic pressure-overload. This finding may add new electrophysiological evidence for the treatment of heart failure and hypertension with adrenergic receptor antagonist.

Action Potentials↗
PubMed2004

Disparate effects of telomere attrition on gene expression during replicative senescence of human mammary epithelial cells cultured under different conditions.

Telomere shortening in populations of human mammary epithelial cells (HMECs) that survive early replicative arrest (M0) by the inactivation of p16(INK4A) during cell culture on plastic dishes leads to a state of permanent replicative arrest termed senescence. While culture of HMECs on feeder layers abrogates M0 and p16(INK4A) inactivation, progressive telomere attrition in these cells also eventually results in permanent replicative arrest. Expression of telomerase prevents both senescence on plastic (S-P) and senescence on feeder layers (S-FL) in HMECs, as it does also in cultured primary human fibroblasts. We report here that the gene expression profiles of senescence in HMECs of the same lineage maintained under different culture conditions showed surprisingly little commonality. Moreover, neither of these senescence-associated profiles in HMECs resembles the profile for senescence in human fibroblasts. These results indicate that senescence-associated alterations in gene expression resulting from telomere attrition are affected by culture conditions as well as by cell origins, and argue that replicative senescence at the molecular level is a diverse rather than unique cellular process.

Adult↗
PubMed2004

[Surveillance of antimicrobial susceptibility of Haemophilus influenzae isolates from children in Beijing, Shanghai, and Guangzhou 2000 - 2002].

OBJECTIVE: To investigate the situation of antibiotic resistance of Haemophilus influenzae isolates from Chinese children. METHODS: Eight hundred and ninety-eight strains of H. influenzae isolated from randomly selected pediatric out-patients in Beijing, Shanghai and Guangzhou 2000 approximately 2002 underwent determination of antibiotic susceptibility by E test MIC method for beta-lactam antibiotics (ampicillin, amoxicillin/clavulanic acid, ceftriaxone, cefuroxime, and cefaclor) and KB disc diffusion method for chloramphenicol, tetracycline, sulfamethoxazole/trimethoprim (SMZ/TMP), azithromycin, and ciprofloxacin. RESULTS: The average rate of beta-lactamase production among these isolates was 12%. The MIC50 and MIC90 of ampicillin were 0.25 microg/ml and 4 microg/ml respectively for the 898 isolates, 88% of the isolates were susceptible to ampicillin and 10.6% was resistant. There was no beta-lactamase negative strains among the ampicillin intermediately-susceptible and resistant strains. All the isolates were susceptible to amoxicillin/clavulanic acid, ceftriaxone, cefuroxime and azithromycin. 96.1% of the H. influenzae isolates generally remained susceptible to cefaclor with a MIC50 of 1.5 microg/ml and a MIC90 of 3 microg/ml, and 99% of the isolates were susceptible to ciprofloxacin. The susceptibility rate to tetracycline of the isolates from Beijing and Shanghai areas were 57% and 61% respectively, both lower than the susceptibility rates of the isolates from Guangzhou (81%), while the resistant rate to SMZ/TMP of the isolates from Beijing was 35%, lower than those of the isolates from Guangzhou (47%) and Shanghai (54%). The resistant rate to ampicillin was 7.7% in 2000 and was increased to 14.5% in 2002. 34.5% of all the isolates were susceptible to 8 antimicrobial agents while 12.8% was multi-drug resistant. 58.5% of the isolates were distributed in five major antimicrobial resistance profiles in which SMZ/TMP resistance (29.8%) was the most prevalent, followed by SMZ/TMP and tetracycline combined resistance (12.5%) and tetracycline resistance (9.4). The ampicillin non-susceptible isolates had higher resistant rates to cefaclor (23.5%), tetracycline (63.3%), SMZ/TMP (74.5%) and chloramphenicol (63.3%) than the ampicillin susceptible strains (1.6%, 51.4%, 11.1% and 4.9% respectively). CONCLUSION: Beta-lactamase production and ampicillin resistance among the isolates from Chinese children are increasing generally during the period 2000 approximately 2002. There is variation of resistance among different regions. There are strong correlations between ampicillin resistance and resistance to cefaclor, chloramphenicol, and tetracycline among the H. Influenzae isolates.

Ampicillin↗
PubMed2004

Determination of the structures of four new isomeric cyclitols.

A series of impurities, which were all of the same molecular formula, C17H33NO7, were obtained in the process of voglibose synthesis. After isolation and purification, four isomeric cyclitols were completely assigned by 2D NMR experiments. One of the compounds was established by single-crystal X-ray diffraction analysis as 5,6-dideoxy-5-{[2-hydroxy-1-(hydroxymethyl)ethyl]amino}-1-C-(methoxycyclohexylmethyl)-D-epi-inositol.

Carbohydrate Conformation↗
PubMed2004

Neutralizing antibodies in patients with severe acute respiratory syndrome-associated coronavirus infection.

BACKGROUND: Severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) is the principal etiologic agent of SARS. We analyzed serum samples obtained from 623 patients with SARS in Beijing, to determine whether infection with SARS-CoV can elicit neutralizing antibodies (NAbs). METHODS: We developed a highly sensitive and safe neutralization assay using the SARS-CoV pseudotyped virus and used this assay to determine the titers of the NAbs in serum samples from patients with SARS. RESULTS: We found that 85.9% of serum samples contained NAbs against SARS-CoV and that most of the NAb activities could be attributed to immunoglobulin G. The NAbs became detectable first at 5-10 days after the onset of symptoms, and their levels peaked at 20-30 days and then were sustained for >150 days. The serum samples could neutralize the pseudotype particles bearing the spike glycoproteins from different SARS-CoV strains, suggesting that the NAbs to SARS-CoV were broadly reactive. CONCLUSIONS: NAbs to SARS-CoV are broadly elicited in patients with SARS and, according to their kinetics, may correlate with viral load during the early stages of the disease. These results suggest that it is possible to develop effective vaccines against SARS and that NAbs provide a potential strategy for treating patients with SARS.

Antibodies, Viral↗
PubMed2004

Carbon-11-methionine positron emission tomography imaging of chordoma.

OBJECTIVE: Chordoma is a rare malignant bone tumor that arises from notochord remnants. This is the first trial to investigate the utility of (11)C-methionine (MET) positron emission tomography (PET) in the imaging of chordoma before and after carbon-ion radiotherapy (CIRT). DESIGN AND PATIENTS: Fifteen patients with chordoma were investigated with MET-PET before and after CIRT and the findings analyzed visually and quantitatively. Tumor MET uptake was evaluated by tumor-to-nontumor ratio (T/N ratio). RESULTS: In 12 (80%) patients chordoma was clearly visible in the baseline MET-PET study with a mean T/N ratio of 3.3+/-1.7. The MET uptake decreased significantly to 2.3+/-1.4 after CIRT ( P<0.05). A significant reduction in tumor MET uptake of 24% was observed after CIRT. Fourteen (93%) patients showed no local recurrence after CIRT with a median follow-up time of 20 months. CONCLUSION: This study has demonstrated that MET-PET is feasible for imaging of chordoma. MET-PET could provide important tumor metabolic information for the therapeutic monitoring of chordoma after CIRT.

Aged↗
PubMed2004

Spiral breakup due to mechanical deformation in excitable media.

To address the problem of how cardiac muscle contraction affects the dynamics of rotating spiral waves, spiral breakup induced by mechanical deformation in excitable media is studied in two partial-differential-equation models. It is shown that spirals begin to break up at omega=0.5 omega(0) when we increase the amplitude of the mechanical deformation gradually. Our numerical results point to a new mechanism of transition from spirals to spatiotemporal chaos, in which the anisotropic time-dependent diffusion coefficient is essential.

Journal Article↗
PubMed2004

Adenosine acts through A2 receptors to inhibit IL-2-induced tyrosine phosphorylation of STAT5 in T lymphocytes: role of cyclic adenosine 3',5'-monophosphate and phosphatases.

Adenosine is a purine nucleoside with immunosuppressive activity that acts through cell surface receptors (A(1), A(2a), A(2b), A(3)) on responsive cells such as T lymphocytes. IL-2 is a major T cell growth and survival factor that is responsible for inducing Jak1, Jak3, and STAT5 phosphorylation, as well as causing STAT5 to translocate to the nucleus and bind regulatory elements in the genome. In this study, we show that adenosine suppressed IL-2-dependent proliferation of CTLL-2 T cells by inhibiting STAT5a/b tyrosine phosphorylation that is associated with IL-2R signaling without affecting IL-2-induced phosphorylation of Jak1 or Jak3. The inhibitory effect of adenosine on IL-2-induced STAT5a/b tyrosine phosphorylation was reversed by the protein tyrosine phosphatase inhibitors sodium orthovanadate and bpV(phen). Adenosine dramatically increased Src homology region 2 domain-containing phosphatase-2 (SHP-2) tyrosine phosphorylation and its association with STAT5 in IL-2-stimulated CTLL-2 T cells, implicating SHP-2 in adenosine-induced STAT5a/b dephosphorylation. The inhibitory effect of adenosine on IL-2-induced STAT5a/b tyrosine phosphorylation was reproduced by A(2) receptor agonists and was blocked by selective A(2a) and A(2b) receptor antagonists, indicating that adenosine was mediating its effect through A(2) receptors. Inhibition of STAT5a/b phosphorylation was reproduced with cell-permeable 8-bromo-cAMP or forskolin-induced activation of adenylyl cyclase, and blocked by the cAMP/protein kinase A inhibitor Rp-cAMP. Forskolin and 8-bromo-cAMP also induced SHP-2 tyrosine phosphorylation. Collectively, these findings suggest that adenosine acts through A(2) receptors and associated cAMP/protein kinase A-dependent signaling pathways to activate SHP-2 and cause STAT5 dephosphorylation that results in reduced IL-2R signaling in T cells.

Adenosine↗
PubMed2004

Effects of degree of enzymatic interesterification on the physical properties of margarine fats: solid fat content, crystallization behavior, crystal morphology, and crystal network.

In this study enzymatic-interesterified margarine fats with different conversion degrees were produced in a packed-bed reactor. The effects of conversion degree on the formation of free fatty acids and diacyglycerols, solid fat content, crystallization behavior, microstructure, and crystal network were investigated, and the enzymatically interesterified products were compared with a chemically interesterified product. Formation of free fatty acids and diacyglycerols increased slightly with increasing conversion degree. The solid fat content was higher at 10 and 20 degrees C and lower at 30, 35, and 40 degrees C with increasing conversion degree. Increased conversion degree from the blend to products, measured by X-ray with addition of 50% of rapeseed oil for dilution, caused the content of beta to decrease from 100% to 33%, and 30% and eventually to pure beta' crystal. However, double chain packing was observed for both the blend and products. Isothermal crystallization kinetics was characterized by the Fisher-Turnbull model. The highest free energy was observed for the blend. A small deformation with oscillation tests shows a significant difference between the blend and interesterified products. The differences of microstructure between the blend, different conversion degree, and chemical randomized product were observed.

Chemical Phenomena↗
PubMed2004

The C. elegans Polycomb gene SOP-2 encodes an RNA binding protein.

Epigenetic silencing of Hox cluster genes by Polycomb group (PcG) proteins is thought to involve the formation of a stably inherited repressive chromatin structure. Here we show that the C. elegans-specific PcG protein SOP-2 directly binds to RNA through three nonoverlapping regions, each of which is essential for its localization to characteristic nuclear bodies and for its in vivo function in the repression of Hox genes. Functional studies indicate that the RNA involved in SOP-2 binding is distinct from either siRNA or microRNA. Remarkably, the vertebrate PcG protein Rae28, which is functionally and structurally related to SOP-2, also binds to RNA through an FCS finger domain. Substitution of the Rae28 FCS finger for the essential RNA binding region of SOP-2 partially restores localization to nuclear bodies. These observations suggest that direct binding to RNA is an evolutionarily conserved and potentially important property of PcG proteins.

Animals↗
PubMed2004

Screening for topoisomerase I binding compounds by high-performance liquid chromatography-mass spectrometry.

A new rapid compound screening approach for topoisomerase I binding activity is presented. DNA topoisomerase I is used as a target protein to capture binding compounds from a mixture of combinatorial compounds by bioaffinity ultrafiltration. Using high-performance liquid chromatography combined with electrospray ionization mass spectrometry, small-molecule active compounds were identified. We also have successfully applied this method to identifying compounds from cells grown in culture.

Chemistry Techniques, Analytical↗
PubMed2004

Epidemiological investigation of esophageal carcinoma.

AIM: To review the characteristics of esophageal carcinoma in recent 30 years in the epidemiological investigation. METHODS: A total of 1 520 cases of esophageal carcinoma in the First Affiliated Hospital of Zhejiang University Medical College admitted from 1970 until now were reviewed. Their age, gender, position of carcinoma and histological type were analyzed. RESULTS: The morbidity of esophageal carcinoma was increasing during the observation period. Compared with the 1970s (9.5%), the ratio of adenocarcinoma significantly increased after the 1980s (19.1%). The difference was significant (P</=0.05). CONCLUSION: The morbidity of esophageal adenocarcinoma was increasing and advanced clinical study should be strengthened.

Adenocarcinoma↗
PubMed2004

B23/nucleophosmin serine 4 phosphorylation mediates mitotic functions of polo-like kinase 1.

Phosphoprotein profiling by Kinetworks trade mark analysis of M-phase-arrested HeLa cells by nocodazole treatment revealed that a novel mitosis-specific phosphorylation event occurred in the nucleolar protein B23/nucleophosmin at a conserved Ser-4 residue. Consistent with the resemblance of the Ser-4 phosphorylation site to the Polo-like kinase 1 (Plk1) consensus recognition sequence, inhibition of Plk1 by a kinase-defective mutation (K82M) abrogated B23 Ser-4 phosphorylation, whereas activation of Plk1 by a constitutively active mutation (T210D) enhanced its phosphorylation following in vivo transfection and in vitro phosphorylation assays. Depletion of endogenous Plk1 by RNA interference abolished B23 Ser-4 phosphorylation. The physical interaction of Plk1 and B23 was further demonstrated by their co-immunoprecipitation and glutathione S-transferase fusion protein pull-down assays. Interference of Ser-4 phosphorylation of B23 induced multiple mitotic defects in HeLa cells, including aberrant numbers of centrosomes, elongation and fragmentation of nuclei, and incomplete cytokinesis. The phenotypes of B23 mutants are reminiscent of a subset of those described previously in Plk1 mutants. Our findings provide insights into the biochemical mechanism underlying the role of Plk1 in mitosis regulation through the identification of Ser-4 in B23 as a major physiological substrate of Plk1.

Cell Cycle Proteins↗
PubMed2004

Relationship of body surface area with bone density and its risk of osteoporosis at various skeletal regions in women of mainland China.

The aim of this study was to investigate the relationship between body surface area (BS) and bone mineral density (BMD) and the associated osteoporosis risk at various skeletal regions in women from mainland China. BMD was measured at the posteroanterior (PA) spine (L1-L4), supine lateral spine (L2-L4) including volumetric BMD (vBMD), hip including femoral neck, trochanter and total hip, and forearm, including radius + ulna ultradistal (R + UUD), 1/3 site (R + U1/3) and total region (R + UT) using a dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) in 3418 females aged from 18 to 75 years. Data analysis revealed a positive correlation between BS and BMD at the various skeletal regions (r = 0.114-0.373, all P = 0.000), but no correlation with vBMD (r = 0.000, P = 0.934). Using the stepwise regression model, BMDs at various skeletal regions were dependent variables while height, weight, body mass index (BMI), BS and projective bone area (BA) were independent variables; BS was determined to be the most important variable that affected the PA spine, hip and forearm BMDs. Subjects were divided into three groups according to size: large BS group (LBSG), intermediate BS group (IBSG) and small BS group (SBSG). The BMD at different skeletal regions of subjects between groups exhibited a significant gradient difference, with LBSG > IBSG > SBSG, but this was not seen for vBMD. On the fitting curves where BMD varied with age at the PA spine, femoral neck, total hip and R + UUD, BMDs of LBSG were 6.93-9.29% higher than those of IBSG and 12.1-16.9 % higher than those of SBSG, whereas those of SBSG were 6.12-9.59% lower than those of IBSG at various skeletal regions, respectively. The prevalence rates and risks of osteoporosis of LBSG were significantly lower than those of SBSG and IBSG, whereas those of IBSG were obviously lower than those of SBSG at various skeletal regions, respectively, presenting a gradient difference among the three study groups, LBSG < IBSG < SBSG. Our study shows that the relationship between BS and BMD exceeds that between BMD and height or weight in women in mainland China. When areal BMD is employed, those with a larger BS have higher areal BMD and lower risks of osteoporosis while, conversely, those with a smaller BS have lower areal BMD, and therefore higher risk for osteoporosis. However, when vBMD is used, these differences diminish or even disappear.

Adolescent↗