Biomedical subjects

Hu Chen

Publications and source records attributed to Hu Chen.

33 records · Page 2Linked to original sources

PubMed2004

A novel method for protein secondary structure prediction using dual-layer SVM and profiles.

A high-performance method was developed for protein secondary structure prediction based on the dual-layer support vector machine (SVM) and position-specific scoring matrices (PSSMs). SVM is a new machine learning technology that has been successfully applied in solving problems in the field of bioinformatics. The SVM's performance is usually better than that of traditional machine learning approaches. The performance was further improved by combining PSSM profiles with the SVM analysis. The PSSMs were generated from PSI-BLAST profiles, which contain important evolution information. The final prediction results were generated from the second SVM layer output. On the CB513 data set, the three-state overall per-residue accuracy, Q3, reached 75.2%, while segment overlap (SOV) accuracy increased to 80.0%. On the CB396 data set, the Q3 of our method reached 74.0% and the SOV reached 78.1%. A web server utilizing the method has been constructed and is available at http://www.bioinfo.tsinghua.edu.cn/pmsvm.

Computational Biology↗

PubMed2004

Orientational order in binary mixtures of hard Gaussian overlap molecules.

Based on a standard constant-pressure Monte Carlo molecular simulation, we have studied liquid crystal phases of binary mixtures of nonspherical molecules. The components of the mixtures are two types of hard Gaussian overlap (HGO) molecules. The first type of molecule has a small molecularelongation parameter (short HGO molecules) and cannot form stable liquid crystal phase in the bulk by themselves. The second type of molecule has a large elongation parameter (long HGO molecules) and can form a liquid crystal phase easily. In the mixtures, the short HGO molecules can form an orientationally ordered phase because the long HGO molecules form confining surfaces to induce the alignment of the short molecules. We also study the isotropic-nematic phase transition in different mixtures composed of short and long HGO molecules with different elongations and concentrations. The obtained result implies that small anisotropic molecules can show liquid crystal behavior.

Journal Article↗

PubMed2004

[Characteristic analysis of acute leukemia immunophenotyping in 180 cases by flow cytometry].

To study the acute Leukemia immunophenotype and its diagnosis value, three color direct immunofluorescece staining methods of flow cytometry and immunophenotype of antibody integration system were used for detection of 180 cases of acute leukemia. The results showed that patients with ALL expressed lymphocyte antigen, and 49.4% patients with ALL accompanied myeloid antigen; all patients with AML expressed myeloid antigen, and 43.2% patients with AML accompanied lymphocyte antigen. In conclusion, leukemia immunophenotyping by three-color direct immunofluore staining methods could define some particular types of leukemia with an important value in diagnosis, treatment and predicting prognosis of acute leukemia.

Adolescent↗

PubMed2004

[Preparation of dendritic cell tumor-vaccine with dendritic cells and problems in its clinical uses--review].

Dendritic cell (DC), the most powerful antigen presenting cell, has been paid close attention to tumor immunotherapy. The tumor antigens were extracted by different ways to pulse DC, and then the mature DC were infused to patients to accelerate anti-tumor immuno responses. Its clinical use would provide a new therapeutic pathway other than surgical operation, irradiation, chemotherapy. In this paper, biological characteristics of DC, tumor-vaccine preparation and its clinical use were reviewed.

Cancer Vaccines↗

PubMed2003

[Selected CD34+ cell autologous transplantation for advanced malignant tumors].

OBJECTIVE: To determine the clinical results of selected CD34(+) cell autologous transplantation in advanced malignant tumors. METHODS: After pretreatment, fifteen patients aged 12 - 70 (49.5) years with various Stage III or IV malignant tumors were given the sorted CD34(+) cells collected by magnetic-activated cell sorting (Clini MACS, Milteny Biotech, Germany). RESULTS: Peripheral blood progenitor cells (PBPC) from the patients were mobilized by chemotherapy and G-CSF 5 micro g/kg per day. CD34(+) cells gave 2.0 - 5 log depletion after cell sorting, with a median yield of CD34(+) selected cells of 2.4 (0.15 - 12.03) x 10(6)/kg. It gave a median recovery of 64 (52 - 81.4)% and median purity of 98.2 (83.2 - 99.7)%. The median time of neutrophil recovery > 1.0 x 10(9)/L and platelet recovery > 20 x 10(9)/L post-transplantation were 14 (8 - 26) days and 13 (11 - 35) days, respectively. On follow-up of 2 - 33 (11) months, the event-free survival rate was 53.3% (8/15) and the overall survival rate was 66.7% (10/15). CONCLUSION: Transplantation of autologous selected PBPC CD34(+) cells gives prompt and stable engraftment. Selected CD34(+) cell transplantation, being a safe approach, may improve the clinical outcome even in patients with advanced malignant tumors.

Adolescent↗

PubMed2003

[Changes in peripheral lymphocyte subfraction in cytomegalovirus infections during the early stage of allogenic peripheral blood stem cell transplantation].

OBJECTIVE: To study the alterations and the clinical significance of peripheral lymphocyte subsets in patients with active cytomegalovirus (CMV) infection during the early stage of allogeneic peripheral blood stem cell transplantation (PBSCT) and to investigate the influence of active CMV infection on immunity. METHODS: K(3)-EDTA anticoagulated peripheral blood samples were collected weekly from 27 allogeneic PBSCT recipients in the first 3 months after PBSCT. CMV pp65 antigen in peripheral white blood cells were tested by indirect immunofluorescence assay, and lymphocyte subsets were detected by flow cytometry with specific fluorescent monoclonal antibodies. In the meantime lymphocyte subsets of 51 samples from healthy blood donors were tested as normal control values. RESULTS: CD(4)(+) T cell count for all recipients was significantly low throughout the first 3 months after PBSCT as compared with normal donors (P < 0.01). Of the 27 allogeneic PBSCT recipients, 5 had no active CMV infection, 10 had asymptomatic CMV active infection, 12 had symptomatic CMV infection. The average CD(4)(+) T cell counts (x 10(6)/L) for the different groups of patients were 328 +/- 203, 239 +/- 218 and 199 +/- 92; The average CD(8)(+) T cell counts (x 10(6)/L) were 400 +/- 380, 267 +/- 206 and 603 +/- 461, respectively. The average percentage of CD(4)(+) CD(28)(+) T cell subsets were (89.2 +/- 8.9)%, (84.2 +/- 10.1)% and (63.5 +/- 11.4)%, respectively. The recipients with asymptomatic CMV active infection were likely to have more natural killer (NK) cells as compared with those without active CMV infection (P < 0.01). The patients with symptomatic CMV infection had significantly lower CD(4)(+) cell count and higher CD(8)(+) cell count than those with asymptomatic CMV infection (P < 0.01). The percentage of CD(4)(+) CD(28)(+) cells was decreased significantly in the CMV active infection group (P < 0.01). CONCLUSIONS: CMV active infection could induce dramatic alterations in lymphocyte subsets lymphocyte subsets and host immunity for allogeneic PBSCT recipients. Therefore, the changes of lymphocyte subsets might serve as auxiliary parameters to predict active CMV infections in this kind of immunocompromised patients.

Adolescent↗

PubMed2003

Interventional therapy of malignant obstructive jaundice.

OBJECTIVE: To assess the short-term results of interventional therapy for malignant obstructive jaundice. METHODS: In 82 patients with malignant obstructive jaundice, hepatocellular carcinoma was detected in 10 patients, carcinoma of gallbladder in 14, hilar biliary carcinoma in 22, pancreatic carcinoma in 20, and hilar metastatic carcinoma in 16. Percutaneous transhepatic biliary internal and/or external drainage (PTBIED) was performed in 61 patients and percutaneous transhepatic insertion of biliary stent (PTIBS) in 21. RESULTS: The level of total serum bilirubin (TSB) was reduced in 71 patients and less markedly in others. The level of TSB of the 61 patients was reduced from 450.12+/-113.51 micromol/L before operation to 240.25+/-107.81 micromol/L and 90.91+/-101.72 micromol/L 1 and 2 weeks after operation respectively. The TSB level of the 21 patients was reduced from 410.53+/-98.13 micromol/L to 270.23+/-115.64 micromol/L and 105.43+/-97.85 micromol/L 1 and 2 weeks after operation, respectively. No significant difference was found in the effect between PTBIED and PTIBS. Short-term complications developed in 33 patients. Seven patients died 30 days after operation. CONCLUSION: Interventional therapy may be simple, safe and effective in the treatment of malignant obstructive jaundice.

Adult↗

PubMed2002

Nonunique steady states in the disordered harmonic chain.

The heat transport in disordered harmonic chains (DHCs) with arbitrary heat baths is studied, based on a general formulation developed by Dhar [Phys. Rev. Lett. 86, 5882 (2001)]. The obtained temperature profile of a steady state is very unusual for any heat bath: (i) it is not unique, but dependent on the initial condition; (ii) it may be highly nonlinear, even though the temperature difference of the two ends of the system is in zero limit, and the temperature gradient inverted Delta T is not inversely proportional to the system size; and (iii) when a DHC is coupled to two thermostats with the same temperature, the temperature of the system is still not uniform. The localized higher frequency normal modes induced by the mass disorders are responsible for these strange properties.

Journal Article↗

PubMed2002

Classification of amino acids based on statistical results of known structures and cooperativity of protein folding.

It has been found that the 20 kinds of amino acids have different frequencies of occurrence in alpha,beta, and coil structures [P. Y. Chou and G. D. Fasman, Biochemistry 13, 211 (1974)]. Based on more known structures of proteins, frequencies for each amino acid in alpha and beta secondary structures are recalculated. Next step, under the approximation ignoring the chain connectivity of proteins, energy parameters to form alpha and beta secondary structures for each amino acid are obtained. According to the hydrophobicity and energies in alpha and beta secondary structures, 20 kinds of amino acids are classified. The results suggest that dividing amino acids to five or nine groups is desirable. At last, a protein model considering both two-body hydrophobic interaction and one-body energy to form secondary structures, hydrophobic-polar alphabeta model, is introduced. It is shown that the consistency among various energy terms makes the cooperativity of protein folding closer to the experiments.

Amino Acid Sequence↗

PubMed2002

[Mesenchymal stem cells suppress allogeneic T cell responses by secretion of TGF-beta1].

To investigate the mechanisms underlying the issue that bone marrow mesenchymal stem cells (MSC) could trigger low responsiveness of allogeneic T lymphocytes against alloantigens, phenotypes of T cells were analysed with flow cytometry before and after coculture of allogeneic T lymphocytes with MSC. Further, expression of cytokines including IL-4, IFN-gamma and TGF-beta1 was evaluated by RT-PCR and ELISA as well. The results showed that CD8(+) subpopulation was increased and CD25(+) subset was decreased in proportion after coculture of allogeneic T lymphocytes with MSC for 2 weeks. RT-PCR assay showed that MSC expressed TGF-beta1 but not IL-4 and IFN-gamma, and the result was further proved by ELISA assay showing that the secretion of TGF-beta1 reached to 1 ng/ml in 72 hours. It was concluded that allogeneic MSC suppressed T cells activation by alteration of T cell subpopulations. The suppressive effect was at least in part due to the secretion of TGF-beta1. The results indicate that MSC pretreatment might be useful in the prevention of GVHD in HLA-mismatched bone marrow transplantation and further donors for hematopoietic stem cells could be selected from greater potentials.

Bone Marrow Cells↗

PubMed2000

In Vitro Amidating Processing of Products Expressed by Gene Engineering.

To set up an in vitro amidating system, a recombinant human calcitonin with a glycine at C termial (mhCT-Gly) was used as the amidating substrate of recombinant rat peptidylglycine alpha-amidating monooxygenase (rPAM). First, the mhCT-Gly gene was synthesized and cloned into a fusion expression vector to get an expression plasmid pGEXCT. The GST-fused mhCT-Gly was highly expressed in E.coli BL21(DE3) harboring the pGEXCT, and was purified rapidly by affinity chromatography. Second, using the method of ultrafiltration, the rPAM was prepared from the supernatant of cultured transfectant CHO cells which express rPAM stably. Finally, the in vitro amidating experiments were carried out using GST-mhCT-Gly as substrate and the prepared rPAM. The results of dot blot with the specific antibody and of mass spectrum assay indicated that amidating product GST-hCT-NH(2) could be easily detected. This study provides a useful method for the amidation of recombinant products in vitro.

Journal Article↗

PubMed2000

[Expression of GATA-2 Gene and Immunoglobulin Heavy Chain Germline Gene C( micro ) in Leukemia Cells and Its Significance]

To investigate the significance of GATA-2 and immunoglobulin heavy chain germline gene C( micro ) (IgH germline gene C( micro )) expression and coexpression in various leukemia cells, GATA-2 and IgH germline gene C( micro ) mRNA in bone marrow and peripheral blood cells from 63 leukemia patients were detected by reverse transcription-polymerase chain reaction (RT-PCR). No GATA-2 or IgH germline gene C( micro ) mRNA were detected in normal bone marrow and peripheral blood. GATA-2 mRNA were be detected in 91.3% patients with acute myeloid leukemia (AML), 75% patients with acute lymphoblastic leukemia (ALL) as well as 83.3% patients with chronic myeloid leukemia (CML-CP); IgH germline gene C( micro ) mRNA were be identified in 47.8% AML, 41.6% ALL, as well as 5.6% CML-CP. All patients with CML-AP and CML-BC expressed GATA-2 mRNA and partly expressed IgH germline gene C( micro ) mRNA. 47.8% AML and 41.6% ALL patients coexpressed GATA-2 and IgH germline gene C( micro ) mRNA. GATA-2(+) IgH germline gene C( micro )(+) cells of AML and ALL were mainly HLA-DR positive. As aberration of the transcription factors, GATA-2 and germline IgH germline gene C( micro ) gene might been linked to leukemogenesis. Various expression of GATA-2 and germline IgH germline gene C( micro ) gene in leukemia might correlated with the heterogeneous differentiation level of leukemia cells. The fact that leukemia with GATA-2(+) IgH germline gene C( micro )(+) coexpression indicated multilineage impairment of hematopoietic cells.

Journal Article↗

PubMed1999

Expression Purification and Activity ofhuman Myristoyl-CoA:N-myristoyltransferase.

A gene encodinghuman myristoyl-CoA: protein N-myristoyltransferase (hNMT) from a brain cDNA libraryhas been obtained by PCR amplification and DNA sequencing. Then the mature-type and His(6)-fusion-type expression plasmids (pMF-hNMT(3) and pMFHT-hNMT(2)) containing the hNMT gene under control of T7 promoter have been constructed and transformed into E. coli BL21(DE3). SDS-PAGE analysis showed that the recombinant hNMT products expressed at 37 degrees were almost unsoluble but most of the His(6)-hNMT product expressed at lower temperature (22 degrees ) was soluble and its yield was about 7% of the total soluble cellular proteins. By immobilized metal (Ni(2+)) chelation affinity chromatography up to 80% His(6)-hNMT was purified by one step from bacterial lysate. The labelling experiment in vitro domonstrated that the expressed and purified His(6)-hNMT had an obvious catalytic activity to transferring myristoyl group.

Journal Article↗

PubMed1998

Studies on Structure and Function of the Myristoyltransferase Inhibitor Peptide Displayed on Phage Surface.

Site-directed mutagenesis was used to identify the critical residues and functional sequences of a potent NMT inhibitor peptide displayed on phage surface. W2A, H6N and H6R largely lowered the inhibitory activities of the mutated phages, and the activity of P3A and V4V5 right curved arrow A4A5 was also slightly reduced. However, V4V5 right curved arrow W4W5, H12N, H14N, C9S, C15S, deltaC15, deltaH14C15 and deltaC9--C15 had no obvious effect on the inhibition. These results suggest that W2, P3 and H6 are important in the peptide structure and/or the interaction with NMT, that amino acids with larger side chain are the more favorable residues between P3 and H6, and also that the sequences between C9 and C15 have no clear contribution to the inhibitory activity. In summary, the functional prptide directly related to the role of inhibition has been located between the N terminal T1 and A8 of the inhibitor peptide.

Journal Article↗

PubMed1998

Selection of Myristoyltransferase Inhibitor Phages from Phage Display Random Peptide Library.

Through screening library with either immobilized or coated enzymes, we selected disease-related myristoyltransferase inhibitor phages from phage display random peptide library. After high-affinity bound phages were obtained, they were subjected to in vitro NMT inhibition assay to identify inhibitor phages. The results of DNA sequencing, peptide sequence deducing and sequence aligning of the 16 inhibitor phages suggested that the sequences of inhibitor peptides obtained by the two separate screening methods appeared overlapping, and included a consensus motif PX(0-3)H/R or H/RX(0-3)R, in which X represented a non-specific amino acid.

Journal Article↗