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Biomedical subjects

Jing Li

Publications and source records attributed to Jing Li.

464 records · Page 26Linked to original sources
PubMed1998

Cloning of 3H11 mAb variable region gene and expression of 3H11 human-mouse chimeric light Chain.

AIM:To clone mouse anti-human gastric cancer mAb(3H11) variable genes and to construct 3H11 human-mouse chimeric antibody.METHODS: The entire VH and VL genes of anti-gastric cancer mAb 3H11 were cloned by RT-PCR method from 3H11 hybridoma cells, using 5' primers for leader sequences. The 3H11 VL gene was then inserted into human-mouse chimeric light chain expression vector and transfected into murine Sp2/0 myeloma cells.RESULTS: DNA sequence analysis indicated that the cloned genes included the whole leader sequences and the mature Ig variable region encoding sequences. After gene transfection, transient expression of chimeric light chain protein was detected.CONCLUSION: DNA sequences and transient expression indicated that the cloned gene was functional. This work laid basis for constructing 3H11 human mouse chimeric antibody in the future.

Journal Article↗
PubMed1998

High-level Expression and Characterization of the Fusion Protein Consisting of Diphtheria Toxin and Human Interleukin 6.

Diphtheria toxin is a single chain exotoxin of 535 amino acids, secreted from beta Corynebacteriophage diphtheriae. Eukaryotic cells, especially tumor cells are very sensitive to DT. Just one or two molecules of DT can kill a cell. On the surface of some tumor cells, such as human myeloma, heptoma, etc, IL-6 receptor has been demonstrated to be expressed at a very-high level. Selective cytotoxicity mediated by IL-6 receptor could be useful in the targeting therapy of these tumors. Based on this strategy, a hybrid protein consisting of DT and IL-6 was constructed, expressed and characterized. IL-6 cDNA was first modified for constructing the fusion protein of DT/IL-6 and the receptor binding domain of DTDNA was replaced by IL-6 cDNA to obtain the expression vector pdeltaDT/TL-6. After induction by IPTG, the fusion protein was expressed successfully, accounting for 20% of the total bacterial protein. The results of SDS-PAGE and Western blot showed that there was a band of about 64 kD. After preliminary purification, the IL-6 receptor competitive binding test and the cytotoxic activity assay of the deltaDT/TL-6 showed that the fusion protein possessed significant cytotoxic activity to U266 cells; while the cells expressing IL-6 receptors at a medium-level was resistant it to a certain degree.

Journal Article↗
PubMed1997

New Type of Polymeric Indium Tellurides: Low-Temperature Synthesis and Structure Characterization of [M(en)(3)]In(2)Te(6) (M = Fe, Zn) and alpha- and beta-[Mo(3)(en)(3)(&mgr;(2)-Te(2))(3)(&mgr;(3)-Te)(&mgr;(3)-O)]In(2)Te(6).

Crystal growth of metal tellurides and tellurometalates employing solvothermal reactions at temperatures below 200 degrees C have resulted in four new indium tellurium phases, [Fe(en)(3)](In(2)Te(6)) (I), [Zn(en)(3)](In(2)Te(6)) (II), and alpha- and beta-[Mo(3)(en)(3)(&mgr;(2)-Te(2))(3)(&mgr;(3)-Te)(&mgr;(3)-O)]In(2)Te(6) (III-alpha and III-beta). Single crystal X-ray diffraction analyses show that I and II are isostructural and belong to the orthorhombic crystal system, space group P2(1)()2(1)()2(1)() (No. 19). Compound I: a = 11.654 (1) Å, b = 12.968(2) Å, c = 16.273(2) Å, Z = 4. Compound II: a = 11.662(2) Å, b = 12.948(2) Å, c = 16.285(1) Å, Z = 4. The two polymorphs III-alpha and III-beta crystallize in the monoclinic system. Compound III-alpha: a = 11.815(2) Å, b = 21.769(3)Å, c = 14.498(4) Å, beta = 95.43(2) degrees, Z = 4, space group P2(1)()/c (No. 14). Compound III-beta: a = 22.154(3) Å, b = 11.550(2)Å, c = 14.230(2) Å, beta = 99.05(1) degrees, Z = 4, space group P2(1)()/a (No. 14). All four are Zintl compounds containing novel one-dimensional polymeric chains of [(In(2)Te(6))(2)(-)] that can be described as alternating fused five-membered rings [(In(3+))(2)(Te(2)(2)(-))(Te(2)(-))], joined at the In atoms.

Journal Article↗
PubMed1996

Synthesis and Characterization of a Boronated Metallophthalocyanine for Boron Neutron Capture Therapy.

Synthesis of the first fully characterized, water-soluble boronated phthalocyanine is reported. Reaction of 4-nitrophthalonitrile with dimethyl malonate in the presence of base yielded dimethyl (3,4-dicyanophenyl)malonate which was converted into dimethyl (3,4-dicyanophenyl)propargylmalonate by sequential treatment with potassium hydroxide and propargyl bromide. Formation of the o-carborane cage was accomplished by reaction of the alkyne with decaborane in acetonitrile at reflux. High-temperature solid state condensation of the resulting o-carboranylphthalonitrile with cobalt(II) chloride followed by ester deprotection and cation exchange provided the water-soluble closo-carbonylphthalocyanine product. The product contains 40 boron atoms (27% boron by weight) and may be useful as a tumor-seeking boron delivery agent for boron neutron capture therapy of cancer.

Journal Article↗
PubMedDate not supplied

Semiconductor dopant profiling by off-axis electron holography.

Silicon wafers with a complex but known dopant profile were used to explore possible methods for improving the reliability of off-axis electron holography for quantitative determination of electrostatic potential profiles in doped semiconductor devices. The variability of results from nominally identical structures was attributed to local charging and associated external fields, forcing the development of a more robust approach to hologram analysis that incorporated an additional phase correction factor rather than rely on vacuum for phase flattening. Consistent results in close agreement with simulated profiles based on measured dopant distributions could then be obtained. Carbon coating was shown to be effective in reducing accumulation of charge caused by emission of secondary electrons. Overall, this work demonstrates that reliable potential profiles from unbiased samples should be obtainable on a routine basis provided that regions suitable for flattening of the phase profile can be identified.

Journal Article↗
PubMedDate not supplied

Synthesis of polyethylene glycol (PEG) derivatives and PEGylated-peptide biopolymer conjugates.

We synthesized a library of 50 poly(ethylene glycol) (PEG) derivatives to expand the extent of conjugation with biologically active molecules (biopolymers, peptides, drugs, etc.) and biomaterial substrates. The formation of PEG derivatives was confirmed with HPLC, (1)H and (13)C NMR. PEG derivatives were polymerized into networks in order to study the role of PEG and terminal functional groups in modulating the hydrophilicity of biomaterials and cell-biomaterial interaction. The resulting surface hydrophilicity and the number of adhered fibroblasts were primarily dependent on the PEG concentration with the molecular weight and the terminal functional group of PEG derivatives being less important. One of PEG derivatives, PEG-bis-glutarate, was utilized to link peptide sequences to gelatin backbone in the formation of novel biomedical hydrogels. PEG-peptide conjugates were characterized by mass spectroscopy. PEG-peptide modified gelatins were characterized by gel permeation chromatography.

Biopolymers↗
PubMedDate not supplied

Parallel approach for solution-phase synthesis of 2-quinoxalinol analogues and their inhibition of LPS-induced TNF-alpha release on mouse macrophages in vitro.

A parallel solution-phase synthesis of 2-quinoxalinol analogues is described. The key step-simultaneous reductions of m-Ar(NO2)2 to m-Ar(NH2)2 was investigated extensively. We obtained preliminary pharmacological activity of those analogues for the inhibition of LPS-induced TNF-alpha release on mouse macrophage in vitro. Two compounds revealed inhibitory activity, with IC50 values of 0.40 microM (7-amino-6-[(3-methoxypropyl)amino]-3-methyl-2-quinoxalinol) and 2.2 microM (7-amino-6-[(3-butoxypropyl)amino]-3-methyl-2-quinoxalinol), respectively.

Animals↗
PubMedDate not supplied

Novel statistical approach for primary high-throughput screening hit selection.

The standard activity threshold-based method (the "top X" approach), currently widely used in the high-throughput screening (HTS) data analysis, is ineffective at identifying good-quality hits. We have proposed a novel knowledge-based statistical approach, driven by the hidden structure-activity relationship (SAR) within a screening library, for primary hit selection. Application to an in-house ultrahigh-throughput screening (uHTS) campaign has demonstrated it can directly identify active scaffolds containing valuable SAR information with a greatly improved confirmation rate compared to the standard "top X" method (from 55% to 85%). This approach may help produce high-quality leads and expedite the hit-to-lead process in drug discovery.

Algorithms↗
PubMedDate not supplied

Computing the minimum recombinant haplotype configuration from incomplete genotype data on a pedigree by integer linear programming.

We study the problem of reconstructing haplotype configurations from genotypes on pedigree data with missing alleles under the Mendelian law of inheritance and the minimum-recombination principle, which is important for the construction of haplotype maps and genetic linkage/association analyses. Our previous results show that the problem of finding a minimum-recombinant haplotype configuration (MRHC) is in general NP-hard. This paper presents an effective integer linear programming (ILP) formulation of the MRHC problem with missing data and a branch-and-bound strategy that utilizes a partial order relationship and some other special relationships among variables to decide the branching order. Nontrivial lower and upper bounds on the optimal number of recombinants are introduced at each branching node to effectively prune the search tree. When multiple solutions exist, a best haplotype configuration is selected based on a maximum likelihood approach. The paper also shows for the first time how to incorporate marker interval distance into a rule-based haplotyping algorithm. Our results on simulated data show that the algorithm could recover haplotypes with 50 loci from a pedigree of size 29 in seconds on a Pentium IV computer. Its accuracy is more than 99.8% for data with no missing alleles and 98.3% for data with 20% missing alleles in terms of correctly recovered phase information at each marker locus. A comparison with a statistical approach SimWalk2 on simulated data shows that the ILP algorithm runs much faster than SimWalk2 and reports better or comparable haplotypes on average than the first and second runs of SimWalk2. As an application of the algorithm to real data, we present some test results on reconstructing haplotypes from a genome-scale SNP dataset consisting of 12 pedigrees that have 0.8% to 14.5% missing alleles.

Algorithms↗
PubMedDate not supplied

The Epstein-Barr virus-associated gastric carcinoma in Southern and Northern China.

In the present study, we examined the proportions of Epstein-Barr virus-associated gastric carcinomas (EBV-GCs) in Guangzhou, southern China and Shenyang, northern China, two areas differing markedly in nasopharyngeal carcinoma (NPC) incidence. Using in situ hybridization assay, the presence of EBV-encoded small RNA (EBER) was examined in 198, and 180 gastric cancer cases in Guangzhou and Shenyang, respectively. The proportion of EBV-GC in Guangzhou (9%) was significantly higher than that in Shenyang (6%), and the odds ratio (OR) for Guangzhou, after adjusting for the effects of age, sex, and tumor subsite, was 2.7 (95% CI = 1.1-6.2) when Shenyang was taken as reference. There was a male predominance of EBV-GC, and the OR for male was 3.0 (95% CI = 1.2-7.3) when female was taken as reference. We observed a weak and negative age dependence in the proportion of EBV-GC (p-values for trend = 0.077). The EBV-GC was most commonly observed in the middle part of stomach in both series. The frequency of EBV-GCs was higher in cases with p53 overexpression than in cases without p53 expression (OR = 2.4, 95% CI = 1.0-5.8). Among p53-positive cases, the frequency of EBV-GC decreased as the proportion of p53-positive carcinoma cells increased (p for trend = 0.021). In conclusion, the present study suggested that the frequency of EBV-GC in Guangzhou, southern China, where NPC is the most common in the world, may be higher than that in other parts of China.

Adult↗
PubMedDate not supplied

Genetic incorporation of a herpes simplex virus type 1 thymidine kinase and firefly luciferase fusion into the adenovirus protein IX for functional display on the virion.

An advantage of the adenoviral vector is its molecular flexibility, which allows for vector tropism modifications for the purpose of cell targeting. In addition to targeting ligands, the capacity to incorporate heterologous peptides has allowed capsid incorporation of other functionalities. We have defined the minor capsid protein IX (pIX) as a locus capable of presenting incorporated ligands on the virion surface. Thus, we sought to exploit the possibility of incorporating functional proteins at pIX. In our current study, we sought to expand the potential utility of our capsid labeling strategy by developing simultaneous imaging capacity for dedicated small animal positron emission tomography and bioluminescence imaging on a single adenoviral vector. Therefore, we constructed an adenovirus that incorporates a fusion protein of herpes simplex virus type 1 thymidine kinase and firefly luciferase (Luc) (TK-Luc) into adenovirus capsid pIX. Our study herein clearly demonstrates our ability to rescue viable adenoviral particles that display functional TK-Luc as a component of their capsid surface. Most importantly, Ad-pIX-TK-Luc retained dual enzymatic functions in vitro and in vivo. This dual-modality approach will allow dynamic or real-time imaging analysis of adenovirus-based interventions with maximized analytic flexibility and enhanced resolution potential.

Adenoviridae↗