Biomedical subjects

Yang Zhang

Publications and source records attributed to Yang Zhang.

At least 91 records · Page 5Linked to original sources

PubMed2005

[Studies on the chemical constituents in seeds of Atriplex centralasiatica].

OBJECTIVE: To study the chemical constituents in seeds of Atriplex centralasiatica. METHOD: The chemical components were isolated by solvents extractions and column chromatography. The chemical structures were identified on the basis of physicochemical constants and spectral data. RESULT: Six compounds were isolated and identified as isorhamnetin(I), tricin(II), querecetin-7-O-alpha-L-rhamnoside(III), isoorientin(IV), beta-sitosterol(V), beta-daucosterlo(VI). CONCLUSION: Compound I, II, III, IV are isolated from genus Atriplex for the first time.

Atriplex↗

PubMed2005

[Phase II clinical trial on China manufactured recombinant human interleukin-11 derivative in the prevention and treatment of chemotherapy-induced thrombocytopenia].

OBJECTIVE: This phase II clinical trial was designed to evaluate the efficacy and toxicity of recombinant human interleukin-11 (rhIL-11) derivative manufactured in China in the prevention and treatment of chemotherapy-induced thrombocytopenia in cancer patients. METHODS: A total of 100 cancer patients with chemotherapy-induced thrombocytopenia (< or = 75 x 10(9)/L) were studied by self-cross control. Ninty-one of them received 2 cycles of chemotherapy. In the first cycle (control cycle) the patients received chemotherapy only, while in the second cycle (treatment cycle), the patients were given subcutaneous injection of rhIL-11 derivative (40 microg.kg(-1).d(-1)) once daily after chemotherapy for 10 consecutive days or more until platelet count reached > or = 300 x 10(9)/L. RESULTS: 1. The patients with platelet count of < or = 75 x 10(9)/L was 89/89 in the control cycle and 44/89 in the treatment cycle (P = 0.00). The recovery time to the normal platelet count was 1-47 days (median 9 days) in the control cycle, and 1-18 days (median 5.5 days) in treatment cycle (P = 0.00). 2. Patients with platelet count of < or = 50 x 10(9)/L was 56/89 in the control cycle and 20/89 in the treatment cycle (P = 0.00). The recovery time to normal platelet count was 1-31 days (median 9 days) in the control cycle and 3-13 days (median 6 days) in the treatment cycle (P = 0.05). 3. The median nadir platelet count was 44 x 10(9)/L (range: 10 x 10(9)/L-75 x 10(9)/L) in the control cycle, and 83 x 10(9)/L (range: 10 x 10(9)/L-310 x 10(9)/L) in the treatment cycle (P = 0.00). The time of recovery to the normal platelet count was 1-31 days (median 6 days) in the control cycle, and 0-13 days (median 2 days) in the treatment cycle (P = 0.00). 4. Nine of 89 evaluable patients required platelet transfusion in the control cycle versus 1 of 89 patients in treatment cycle (P = 0.01), and the total platelet transfusion was 10 times in the control cycle versus once in the treatment cycle (P = 0.01). 5. The major adverse events associated with rhIL-11 derivative were: headache, fatigue, myalgia/arthralgia, edema and palpitation, etc. CONCLUSION: rhIL-11 derivative can be safely and effectively used for the prevention and treatment for chemotherapy-induced thrombocytopenia.

Adult↗

PubMed2005

[Characterization and identification of Ralstonia solanacearum by ion-exchange chromatography].

Ralstonia solanacearum, a widely distributed and economically important plant pathogen, was characterized by ion-exchange chromatography (IEC). Ralstonia solanacearum was chromatographed on a TOYOPEARL SuperQ-650 C column (200 mm x 4. 6 mm i. d. ) with gradient elution by A (0.02 mol/L piperazidine-chlorhydric acid buffer (pH 8.0) ) and B (A + 1 mol/L NaCl). The pure culture of R. solanacearum was separated into three fractions on a SuperQ-650 C column. They were found all belong to R. solanacearum after the fractions were identified by other biochemical methods. Because of their ability to oxidize 3 disaccharides (lactose, maltose and cellobiose) and 3 hexose alcohols (mannitol, sorbitol and dulcitol), they are classified as biovar III of R. solanacearum. Once the mobility was scaled using microscope and the pathogenetic ability was measured with 2,3 ,4-triphenyltetrazolium chlorid (TTC) medium, the two fractions were in different states. The results are very important to elucidate the multi-states of R. solanacearum and the mechanism of R. solanacearum's pathogenetic mutation.

Chromatography, Ion Exchange↗

PubMed2005

[Effects on the shear bond strength of orthodontic brackets with different concentration of fluorided etching fluid].

OBJECTIVE: This study was to find out the most suitable concentration of added NaF to enough bonding strength of brackets. METHODS: Sixty-four teeth were randomly divided into A, B, C and the control group. NaF of four different concentrations (1.23%, 2%, 3% and 0%) was added into 35% phosphoric acid. The four group teeth were etched with four kinds of fluoride etching fluid respectively and were bonded with brackets. Four specimens in each group were selected by turns after 1, 4, 12 and 24 weeks of bonding. The shear bond strength of the teeth were tested, and the adhesive residual index (ARI) of bonding interface were recorded. RESULTS: The shear bond strength at four test time in each group was no significant (P > 0.05). There was statistical difference of the shear bond strength between four groups (P < 0.05), and group C was lower than the other groups. The ARI was no statistical difference between four groups. CONCLUSION: The effects of etching and bonding had no significant changes when the concentration of added NaF was no more than 2%. The shear bond strength decreased while the concentration of NaF was higher than 3%.

Acid Etching, Dental↗

PubMed2005

[Phase II randomized clinical trail of zoledronic acid in treating metastatic bone pain of malignancy].

BACKGROUND & OBJECTIVE: Bone metastases are the prevailing reason for pain in patients with malignancies, which seriously affect their life quality. Zoledronic acid, the third generation of bisphosphonates, can inhibit the activity of osteoclasts and relieve pain. This study was to evaluate the efficacy and safety of zoledronic acid in treating metastatic bone pain for patients with malignancies. METHODS: A multi-center, randomized, double-blind, and prospective trail was conducted. Patients with metastatic bone pain were randomized to receive zoledromic acid plus monnitol, or pamidronate plus monnitol as positive control. RESULTS: From Oct. 2003 to Oct. 2004, 216 patients with metastatic bone pain were randomized into 2 groups: 109 in zoledromic acid group, and 107 in pamidronate group. There was no significant difference in pain intensity (PI) between zoledromic acid group and pamidronate group before treatment (6.0+/-1.1 vs. 6.0+/-1.3, P=0.938), 7 days after treatment (3.7+/-1.99 vs. 4.1+/-2.0, P=0.119), and 14 days after treatment (3.2+/-2.0 vs. 3.7+/-2.4, P=0.129). The differences in complete response (CR) rate, partial response (PR) rate, and total response rate between the 2 groups were not significant (10.4% vs. 9.5%, 69.8% vs. 69.5%, 88.7% vs. 85.7%, P>0.05). Time to CR was significantly shorter in zoledromic acid group than in pamidronate group [(7.0+/-2.2) days vs. (9.5+/-2.6) days, P=0.033]; the differences in time to PR, duration of CR, and duration of PR between the 2 groups were not significant [(4.9+/-2.6) days vs. (5.0+/-2.5) days, P=0.908; (13.2+/-1.80) days vs. (14.0+/-0.0) days, P=0.155; and (13.4+/-1.9) days vs. (12.8+/-2.8) days, P=0.127]. The main adverse events were fever, nausea, vomiting, and general malaise. The occurrence and severity of adverse events were similar between the 2 groups. CONCLUSION: Zoledromic acid is effective and safe in treating metastatic bone pain of patients with malignancy, which is similar to pamidranate.

Adult↗

PubMed2005

[Glutathione S-transferase M1 polymorphism and the risk on colorectal cancer: a multilevel meta regression].

OBJECTIVE: In order to investigate the relationship between Glutathione S-transferase M1 (GSTM1) status and the risk on colorectal cancer as well as to detect the related factors to this association. METHODS: A pooled analysis of multilevel Meta-regression was performed to estimate GSTM1 deficiency associated with the risks of colorectal cancer. Then subgroup Meta-regression was undertaken to evaluate the possible relationship between heterogeneity and the related characteristics. RESULTS: The overall pooled odds ratios of colorectal cancer risk associated with GSTM1 deficiency was 1.17 (95% CI: 1.08-1.26). Ethnicity, percent of GSTM1 deficiency in population had significant relationships with heterogeneity across the studies (P < 0.05). Results of subgroup Meta-regression showed that GSTM1 deficiency was significantly associated with colorectal cancer risk in ethnic subgroups of Asians, Caucasians and in low level (lower than 50%) of GSTM1 deficiency population (P < 0.05). The respective pooled ORs were 1.14, 1.25 and 1.29. CONCLUSION: GSTM1 deficiency seemed to be a risk factor for colorectal cancer, while interactions on the characteristics of ethnicity, percentage of GSTM1 deficiency in the studied population were related to this association.

Asian People↗

PubMed2004

Scoring function for automated assessment of protein structure template quality.

We have developed a new scoring function, the template modeling score (TM-score), to assess the quality of protein structure templates and predicted full-length models by extending the approaches used in Global Distance Test (GDT)1 and MaxSub.2 First, a protein size-dependent scale is exploited to eliminate the inherent protein size dependence of the previous scores and appropriately account for random protein structure pairs. Second, rather than setting specific distance cutoffs and calculating only the fractions with errors below the cutoff, all residue pairs in alignment/modeling are evaluated in the proposed score. For comparison of various scoring functions, we have constructed a large-scale benchmark set of structure templates for 1489 small to medium size proteins using the threading program PROSPECTOR_3 and built the full-length models using MODELLER and TASSER. The TM-score of the initial threading alignments, compared to the GDT and MaxSub scoring functions, shows a much stronger correlation to the quality of the final full-length models. The TM-score is further exploited as an assessment of all 'new fold' targets in the recent CASP5 experiment and shows a close coincidence with the results of human-expert visual assessment. These data suggest that the TM-score is a useful complement to the fully automated assessment of protein structure predictions. The executable program of TM-score is freely downloadable at http://bioinformatics.buffalo.edu/TM-score.

Automation↗

PubMed2004

Glucagon stimulates exocytosis in mouse and rat pancreatic alpha-cells by binding to glucagon receptors.

Glucagon, secreted by the pancreatic alpha-cells, stimulates insulin secretion from neighboring beta-cells by cAMP- and protein kinase A (PKA)-dependent mechanisms, but it is not known whether glucagon also modulates its own secretion. We have addressed this issue by combining recordings of membrane capacitance (to monitor exocytosis) in individual alpha-cells with biochemical assays of glucagon secretion and cAMP content in intact pancreatic islets, as well as analyses of glucagon receptor expression in pure alpha-cell fractions by RT-PCR. Glucagon stimulated cAMP generation and exocytosis dose dependently with an EC50 of 1.6-1.7 nm. The stimulation of both parameters plateaued at concentrations beyond 10 nm of glucagon where a more than 3-fold enhancement was observed. The actions of glucagon were unaffected by the GLP-1 receptor antagonist exendin-(9-39) but abolished by des-His1-[Glu9]-glucagon-amide, a specific blocker of the glucagon receptor. The effects of glucagon on alpha-cell exocytosis were mimicked by forskolin and the stimulatory actions of glucagon and forskolin on exocytosis were both reproduced by intracellular application of 0.1 mm cAMP. cAMP-potentiated exocytosis involved both PKA-dependent and -independent (resistant to Rp-cAMPS, an Rp-isomer of cAMP) mechanisms. The presence of the cAMP-binding protein cAMP-guanidine nucleotide exchange factor II in alpha-cells was documented by a combination of immunocytochemistry and RT-PCR and 8-(4-chloro-phenylthio)-2'-O-methyl-cAMP, a cAMP-guanidine nucleotide exchange factor II-selective agonist, mimicked the effect of cAMP and augmented rapid exocytosis in a PKA-independent manner. We conclude that glucagon released from the alpha-cells, in addition to its well-documented systemic effects and paracrine actions within the islet, also represents an autocrine regulator of alpha-cell function.

ATP-Binding Cassette Transporters↗

PubMed2004

Solvent-dependent chemoselectivities in additions of beta-carbonyl imines to allyltrimethylsilane with CTAN.

The oxidative coupling of beta-carbonyl imines and allyltrimethylsilane with CTAN were investigated in CH(3)CN and CH(2)Cl(2). In CH(3)CN allylation products were obtained predominantly, while in CH(2)Cl(2), dihydropyrrole products were obtained exclusively. Solvent-assisted nucleophilic cleavage of the intermediate beta-silyl cation is proposed to play a role in the solvent-dependent chemoselectivity.

Journal Article↗

PubMed2004

Development and large scale benchmark testing of the PROSPECTOR_3 threading algorithm.

This article describes the PROSPECTOR_3 threading algorithm, which combines various scoring functions designed to match structurally related target/template pairs. Each variant described was found to have a Z-score above which most identified templates have good structural (threading) alignments, Z(struct) (Z(good)). 'Easy' targets with accurate threading alignments are identified as single templates with Z > Z(good) or two templates, each with Z > Z(struct), having a good consensus structure in mutually aligned regions. 'Medium' targets have a pair of templates lacking a consensus structure, or a single template for which Z(struct) < Z < Z(good). PROSPECTOR_3 was applied to a comprehensive Protein Data Bank (PDB) benchmark composed of 1491 single domain proteins, 41-200 residues long and no more than 30% identical to any threading template. Of the proteins, 878 were found to be easy targets, with 761 having a root mean square deviation (RMSD) from native of less than 6.5 A. The average contact prediction accuracy was 46%, and on average 17.6 residue continuous fragments were predicted with RMSD values of 2.0 A. There were 606 medium targets identified, 87% (31%) of which had good structural (threading) alignments. On average, 9.1 residue, continuous fragments with RMSD of 2.5 A were predicted. Combining easy and medium sets, 63% (91%) of the targets had good threading (structural) alignments compared to native; the average target/template sequence identity was 22%. Only nine targets lacked matched templates. Moreover, PROSPECTOR_3 consistently outperforms PSIBLAST. Similar results were predicted for open reading frames (ORFS) < or =200 residues in the M. genitalium, E. coli and S. cerevisiae genomes. Thus, progress has been made in identification of weakly homologous/analogous proteins, with very high alignment coverage, both in a comprehensive PDB benchmark as well as in genomes.

Algorithms↗

PubMed2004

14-3-3sigma mediation of cell cycle progression is p53-independent in response to insulin-like growth factor-I receptor activation.

We investigated the role of 14-3-3sigma protein in insulin-like growth factor-I (IGF-I) receptor signaling. It has been previously shown that 14-3-3sigma negatively regulates cell cycle especially in response to p53-sensitive DNA damage. In this study we demonstrated that 14-3-3sigma is a positive mediator of IGF-I receptor-induced cell proliferation. Treatment with IGF-I increased 14-3-3sigma mRNA and protein levels about 4-fold, in a time-dependent manner in MCF-7 breast cancer cells. Preincubation with the phosphoinositide 3'-kinase inhibitor LY294002 significantly reduced the effects of IGF-I on 14-3-3sigma gene expression in these cells, suggesting that this effect of IGF-I occurs via the phosphoinositide 3'-kinase pathway. 14-3-3sigma is induced by IGF-I in MCF-7 cells, which express wild-type p53, as well as in MCF-7 cells transfected with a small interference RNA targeting duplex that reduced p53 expression levels. These results suggest that IGF-I induces 14-3-3sigma expression in a manner that is independent of p53. Using the small interference RNA strategy, we demonstrated that a 70-75% reduction of 14-3-3sigma mRNA levels resulted in a similar decrease in the effects of IGF-I on cell cycle progression and proliferation in MCF-7 cells. This effect was also associated with a reduction in IGF-I-induced cyclin D1 expression. Taken together, these results suggest that 14-3-3sigma positively mediates IGF-I-induced cell cycle progression.

14-3-3 Proteins↗

PubMed2004

Evidence for hypothalamic K+(ATP) channels in the modulation of glucose homeostasis.

Several lines of evidence support the hypothesis that ATP-sensitive K+ channels (K+(ATP)) participate in the brain's regulation of peripheral glucose homeostasis. In testing this hypothesis we conducted a series of in vivo experiments using albino rats and bilateral intrahypothalamic injections of K+(ATP) channel blockers, glibenclamide and repaglinide. The results show that 0.2 and 2.0 nM injections of glibenclamide lowered blood glucose in a dose-dependent manner. During mild insulin-induced hypoglycemia, hypothalamic glibenclamide delayed recovery to normoglycemia. The impaired recovery was associated with a reduction in plasma norepinephrine (P<0.001), though circulating epinephrine and glucagon were not reduced. In a separate experiment, 2-deoxy-D-glucose (200 mg/kg) was intraperitoneally administered to produce neuroglucopenia. Hypothalamic injections of either glibenclamide or repaglinide significantly blunted compensatory hyperglycemic responses (P<0.01). In a feeding study, 2.0, but not 0.2 nM of hypothalamic glibenclamide, reduced chow intake over a 2-h period (P<0.01). The results support the hypothesis that hypothalamic K+(ATP) channels participate in central glucose-sensing and glucose regulation.

Animals↗

PubMed2004

Automated structure prediction of weakly homologous proteins on a genomic scale.

We have developed TASSER, a hierarchical approach to protein structure prediction that consists of template identification by threading, followed by tertiary structure assembly via the rearrangement of continuous template fragments guided by an optimized C(alpha) and side-chain-based potential driven by threading-based, predicted tertiary restraints. TASSER was applied to a comprehensive benchmark set of 1,489 medium-sized proteins in the Protein Data Bank. With homologues excluded, in 927 cases, the templates identified by our threading algorithm PROSPECTOR_3 have a rms deviation from native <6.5 A with approximately 80% alignment coverage. After template reassembly, this number increases to 1,172. This shows significant and systematic improvement of the final models with respect to the initial template alignments. Furthermore, significant improvements in loop modeling are demonstrated. We then apply TASSER to the 1,360 medium-sized ORFs in the Escherichia coli genome; approximately 920 can be predicted with high accuracy based on confidence criteria established in the Protein Data Bank benchmark. These results from our unprecedented comprehensive folding benchmark on all protein categories provide a reliable basis for the application of TASSER to structural genomics, especially to proteins of low sequence identity to solved protein structures.

Algorithms↗

PubMed2004

SPICKER: a clustering approach to identify near-native protein folds.

We have developed SPICKER, a simple and efficient strategy to identify near-native folds by clustering protein structures generated during computer simulations. In general, the most populated clusters tend to be closer to the native conformation than the lowest energy structures. To assess the generality of the approach, we applied SPICKER to 1489 representative benchmark proteins </=200 residues that cover the PDB at the level of 35% sequence identity; each contains up to 280,000 structure decoys generated using the recently developed TASSER (Threading ASSembly Refinement) algorithm. The best of the top five identified folds has a root-mean-square deviation from native (RMSD) in the top 1.4% of all decoys. For 78% of the proteins, the difference in RMSD from native to the identified models and RMSD from native to the absolutely best individual decoy is below 1 A; the majority belong to the targets with converged conformational distributions. Although native fold identification from divergent decoy structures remains a challenge, our overall results show significant improvement over our previous clustering algorithms.

Algorithms↗

PubMed2004

Large-scale assessment of the utility of low-resolution protein structures for biochemical function assignment.

MOTIVATION: Several protein function prediction methods employ structural features captured in three-dimensional (3D) descriptors of biologically relevant sites. These methods are successful when applied to high-resolution structures, but their detection ability in lower resolution predicted structures has only been tested for a few cases. RESULTS: A method that automatically generates a library of 3D functional descriptors for the structure-based prediction of enzyme active sites (automated functional templates, 593 in total for 162 different enzymes), based on functional and structural information automatically extracted from public databases, has been developed and evaluated using decoy structures. The applicability to predicted structures was investigated by analyzing decoys of varying quality, derived from enzyme native structures. For 35% of decoy structures, our method identifies the active site in models having 3-4 A coordinate root mean square deviation from the native structure, a quality that is reachable using state of the art protein structure prediction algorithms. AVAILABILITY: See http://www.bioinformatics.buffalo.edu/resources/aft/

Algorithms↗

PubMed2004

Inducible expression of Bcl-XL inhibits sodium butyrate-induced apoptosis in hybridoma, resulting in enhanced antibody production.

Sodium butyrate (NaBu) can increase the specific Mab production rate of hybridomas by enhancing histone hyperacetylation and influencing the cell cycle, but it can also inhibit cell growth and induce apoptosis. Thus, the beneficial effect of NaBu on Mab secretion is compromised by its cytotoxic effect. In the present study, expression of the anti-apoptotic protein human Bcl-XL was made inducible in hybridoma H18 to overcome the cytotoxic effect of NaBu, circumventing the detrimental effects of constitutive high-level expression. We constructed an expression vector in which the promoter of a mammalian metallothionein (MT) gene drove the expression of bcl-XL in response to metal exposure. The vector was then used to exogenously control the expression of bcl-XL in H18 hybridoma cells. Our data showed that stably transfected H18.D4 cells expressed high levels of Bcl-X(L), which was induced within 24 h of addition of ZnSO4. NaBu (0.4 mM) increased antibody production by more than 3-fold in H18.D4. This effect resulted from the suppression of NaBu-induced apoptosis, allowing the H18.D4 cells to grow at higher viability and extending culture longevity by >3 days.

Animals↗

PubMed2004

The localization of occluded matrix proteins in calcareous spicules of sea urchin larvae.

The sea urchin embryo forms calcareous endoskeletal spicules composed of calcite and an occluded protein matrix. Though the latter is approximately 0.1% of of the mass, the composite has substantially altered material properties, e.g., conchoidal fracture planes and increased hardness. Experiments were conducted to examine the localization of matrix proteins occluded in the mineral by use of immunocytochemistry coupled with scanning electron microscopy (SEM). The isolated, unfixed spicules were etched under relatively gentle conditions and exposed to affinity purified antibodies made against two different matrix proteins, as well as an antibody to the entire constellation of matrix proteins. Immunogold tagged secondary antibody was used to observe antibody localization in the back scatter mode of SEM. All proteins examined were very widely distributed throughout the calcite, supporting a model of the structure in which a multiprotein assemblage is woven with fine texture around microcrystalline domains of calcite. Gentle etching revealed a laminar arrangement of calcite solubility, consistent with a stepwise deposition of matrix and mineral to increase girth of the spicule.

Animals↗

PubMed2004

Structure of Escherichia coli AMP nucleosidase reveals similarity to nucleoside phosphorylases.

AMP nucleosidase (AMN) catalyzes the hydrolysis of AMP to form adenine and ribose 5-phosphate. The enzyme is found only in prokaryotes, where it plays a role in purine nucleoside salvage and intracellular AMP level regulation. Enzyme activity is stimulated by ATP and suppressed by phosphate. The structure of unliganded AMN was determined at 2.7 A resolution, and structures of the complexes with either formycin 5'-monophosphate or inorganic phosphate were determined at 2.6 A and 3.0 A resolution, respectively. AMN is a biological homohexamer, and each monomer is composed of two domains: a catalytic domain and a putative regulatory domain. The overall topology of the catalytic domain and some features of the substrate binding site resemble those of the nucleoside phosphorylases, demonstrating that AMN is a new member of the family. The structure of the regulatory domain consists of a long helix and a four-stranded sheet and has a novel topology.

Amino Acid Sequence↗