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Biomedical subjects

Jie Li

Publications and source records attributed to Jie Li.

At least 199 records · Page 11Linked to original sources
PubMed2004

[Dendritic cells present particulate E7 protein of human papillomavirus and induce strong immunity].

OBJECTIVE: To investigate the feasibility of using dendritic cell (DC)-beads-antigen (Ag) as novel cancer vaccine form with E7 as the target antigen. METHODS: C57BL/6 mouse was killed and the femora were taken out. Marrow cells were isolated and cultured with IL-3 and granulocyte-macrophage growth stimulating factor (GM-CSF) so as to prepare DCs. Flow cytometry was conducted to analyze the phenotype. FITC-labeled polystyrene beads-ovalbumin (OVA) or polystyrene beads-human papillomavirus (HPV) E7 protein were added into the culture fluid to be co-cultured with the DCs for 3 hours. Flow cytometry was conducted to analyze the up-taking rates of polystyrene beads-OVA and of polystyrene beads-HPV E7 protein by the DCs and B3Z T cell hybridoma cells were co-cultured and then beads-OVA or beads-SIIFEKL polypeptide was added into the culture fluid. The absorbance was read. Twelve mice were injected with DC-beads-OVA, DC-beads-E7, DC-OVA antigen epitope (SIIFEKL), or DC-E7 epitope (RAHYNIVTF) into the plantae and killed in 36 hours to take out the iliac lymph nodes. Flow cytometry was conducted to analyze the phenotypes of the bead-positive cells. Mice were killed 10 days after immunization and their heart blood was collected. Enzyme linked immunosorbent assay was used to detect the levels of antibodies. Immunized and non-immunized mice were killed and their spleens were taken out. ELISPOT was used to detect the number of cells secreting interferon (IFN)gamma. RESULTS: DCs were seen in the culture fluid of mice marrow cells 5 days after culture with IL-3 and GM-CSF. The bead-positive rates of bead-E7 and bead-OVA were 64% +/- 18% and 58% +/- 16% respectively (P > 0.05) in the IL-3DCs. The CD40 expression rate in the bead-positive cells in the graining iliac lymph nodes was significantly higher after feeding by beads-E7 in comparison with that before the feeding (P < 0.05), the NLDC145, and MHC-II expression rates were increased to a certain degree, however the F4/80 expression rate was decreased. The DCs fed with bead-OVA or with OVA antigen epitope SIIFEKL, especially the former, significantly activated the B3Z cells. The serum IgG level in the mice immunized by beads-E7 was significantly increases, the IgM level was increased slightly, however, the IgA level almost remained unchanged. The numbers of IFNgamma SFU in the splenic cells of the mice immunized by DC-bead-OVA and DC-bead-E7 were significantly higher than that in the unimmunized mice, especially those immunized by DC-bead-OVA. CONCLUSION: DCs fed with beads-E7 can migrate to the draining lymph nodes and induce high level humeral and cellular immunity. DC-beads-Ag seems better than DC-epitope according to the strength of induced immunity. DC-beads-Ag may be an ideal vaccine form and can be used to develop other cancer vaccine.

Animals↗
PubMed2004

Type-B response regulators display overlapping expression patterns in Arabidopsis.

Two-component signaling systems, involving His kinases, His-containing phosphotransfer proteins, and response regulators, have been implicated in plant responses to hormones and environmental factors. Genomic analysis of Arabidopsis supports the existence of 22 response regulators (ARRs) that can be divided into at least two distinct groups designated type-A and type-B. Phylogenetic analysis indicates that the type-B family is composed of one major and two minor subfamilies. The expression of the type-B ARRs was examined by using both reverse transcription-PCR and beta-glucuronidase fusion constructs. The major subfamily of type-B ARRs showed particularly high expression in regions where cytokinins play a significant role, including cells in the apical meristem region and in young leaves that would be undergoing cell division. Multiple members within this same subfamily of type-B ARRs were expressed near the root tip with highest expression in the root elongation zone. beta-Glucuronidase-fusions to full-length ARR2, ARR12, and ARR19 were nuclear localized, consistent with a role in transcriptional regulation. These data suggest that differing expression levels of the type-B ARRs may play a role in modulating the cellular responses to cytokinin.

Arabidopsis↗
PubMed2004

Cancer chemopreventive activity of a mixture of Chinese herbs (antitumor B) in mouse lung tumor models.

Antitumor B (ATB), also known as Zeng Sheng Ping, is a Chinese herbal mixture composed of six plants. Previously, clinical studies have shown a significant chemopreventive efficacy of ATB against human esophageal and lung cancers. In the present study, A/J mice harboring a dominant-negative p53 and/or heterozygous deletion of Ink4a/Arf and treated with benzo[a]pyrene were used to investigate the chemopreventive effects of ATB on chemically induced lung tumorigenesis. Mice with various genotypes treated with ATB displayed a significant reduction in lung tumor multiplicity and tumor load. Treatment with ATB resulted in an approximately 40% decrease in tumor multiplicity and a 70% decrease in tumor load in both wild-type mice and in mice with a loss of the Ink4a/Arf tumor suppressor genes. Interestingly, ATB decreased tumor multiplicity and volume by 50 and 90%, respectively, in mice with a dominant-negative p53 and in mice with both a p53 mutation and deletion of Ink4a/Arf. Kras2 mutation analysis of the lung tumors revealed that tumors harbored mutations in the 12th codon of Kras2. There were no differences in either the incidence or types of mutations between tumors treated with or without ATB. Oligonucleotide array analysis revealed 284 genes that were differentially expressed in mouse lung tumors as compared to the normal lung, and it was found that 114 out of these 284 genes changed their expression toward the normal levels in tumors treated with ATB. Most of the genes modulated by ATB belong to several cellular signaling pathways, including Notch (Notch homolog 2, manic fringe homolog), growth factor (FGF intracellular-binding protein, PDGFalpha), G protein-Ras-MAPK (MAPK3, MAP3K4, rab3A, Rap1, RSG5, PKCtheta), ubiquitin-proteasome (CDC34, Cullin1, 26S proteasome), and apoptosis (BAD promoter, caspase 3). These results suggest that ATB is an effective chemopreventive against mouse lung tumorigenesis. Furthermore, ATB exhibited an enhanced inhibitory effect in animals harboring genetic alterations (Kras2, p53, and Ink4a/Arf), which are often seen in human lung adenocarcinomas.

Animals↗
PubMed2004

Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome.

Complete DiGeorge syndrome is a fatal congenital disorder characterized by athymia, hypoparathyroidism, and heart defects. Less than half of patients are 22q11 hemizygous. The goal of this study was to assess if immune suppression followed by postnatal thymus transplantation would lead to T-cell function in 6 infant patients who had host T cells at the time of transplantation. All infants had fewer than 50 recent thymic emigrants (CD3(+)CD45RA(+)CD62L(+)) per cubic millimeter (mm(3)) and all had some proliferative response to the mitogen phytohemagglutinin. Four infants had rash, lymphadenopathy, and oligoclonal populations of T cells in the periphery. Five of 6 patients are alive at the follow-up interval of 15 months to 30 months. The 5 surviving patients developed a mean of 983 host CD3(+) T cells/mm(3) (range, 536/mm(3)-1574/mm(3)), a mean of 437 recent thymic emigrants/mm(3) (range, 196/mm(3)-785/mm(3)), and normal proliferative responses to phytohemaglutinin (follow-up from day 376 to day 873). The TCR repertoire became polyclonal in patients who presented with oligoclonal T cells. All patients had thymopoiesis on allograft biopsy. Postnatal thymus transplantation after treatment with Thymoglobulin shows promise as therapy for infants with complete DiGeorge syndrome who have significant proliferative responses to mitogens or who develop rash, lymphadenopathy, and oligoclonal T cells.

DiGeorge Syndrome↗
PubMed2004

Thermodynamic stability and kinetic foldability of a lattice protein model.

By using serial mutations, i.e., a residue replaced by 19 kinds of naturally occurring residues, the stability of native conformation and folding behavior of mutated sequences are studied. The 3 x 3 x 3 lattice protein model with two kinds of interaction potentials between the residues, namely the original Miyazawa and Jernigan (MJ) potentials and the modified MJ potentials (MMJ), is used. Effects of various sites in the mutated sequences on the stability and foldability are characterized through the Z-score and the folding time. It is found that the sites can be divided into three types, namely the hydrophobic-type (H-type), the hydrophilic-type (P-type) and the neutral-type (N-type). These three types of sites relate to the hydrophobic core, the hydrophilic surface and the parts between them. The stability of the native conformation for the serial mutated sequences increases (or decreases) as the increasing in the hydrophobicity of the mutated residues for the H-type sites (or the P-type sites), while varies randomly for the N-type sites. However, the foldability of the mutated sequences is not always consistent with the thermodynamic stability, and their relationship depends on the site types. Since the hydrophobic tendency of the MJ potentials is strong, the ratio between the number of the H-type sites and the number of the P-type sites is found to be 1:2. Differently, for the MJJ potentials it is found that such a ratio is about 1:1 which is relevant to that of real proteins. This suggests that the modification of the MJ potentials is rational in the aspect of thermodynamic stability. The folding of model proteins with the MMJ potentials is fast. However, the relationship between the foldability and the thermodynamic stability of the mutated sequences is complex.

Hydrophobic and Hydrophilic Interactions↗
PubMed2004

Dopamine and L-dopa disaggregate amyloid fibrils: implications for Parkinson's and Alzheimer's disease.

Protein deposition diseases involve the aggregation of normally soluble proteins, leading to both fibrillar and amorphous deposits. The aggregation of alpha-synuclein is associated with Parkinson's disease, and the aggregation of the Abeta peptide is associated with Alzheimer's disease. Here we show that L-dopa, dopamine, and other catecholamines dissolve fibrils of alpha-synuclein and Abeta peptide generated in vitro. The catecholamines also inhibited the fibrillation of these proteins. In addition, intraneuronal alpha-synuclein deposits formed in a mouse model were dissolved by incubation of tissue slices with L-dopa. These catecholamines are susceptible to oxidative breakdown, and we show that oxidation products are more effective than the parent compounds in inhibition. The ability to dissolve fibrils provides a new approach for studying mechanisms and consequences (e.g., the relationship between fibril formation and neurodegeneration) of protein aggregation. It is also likely to help in the development of strategies for the prevention and treatment of protein deposition diseases.

Alzheimer Disease↗
PubMed2004

Application of the synthetic aminosugars for glycodiversification: synthesis and antimicrobial studies of pyranmycin.

A divergent approach was employed for the synthesis of aminosugars, from which a novel library of aminoglycoside antibiotics (pyranmycins) was synthesized. Pyranmycins have comparable antibacterial activity as neomycin, a clinically used aminoglycoside antibiotic, against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Mycobacterium smegmatis. In addition, pyranmycins, like streptomycin, are bacteriocidal while isoniazid (INH) is bacteriostatic. Therefore, pyranmycins may provide new therapeutic options in the treatment against tuberculosis. Several members of pyranmycins also manifest modest anti-Tat and anti-Rev activities, which may aid in the development of new anti-HIV agents. Although the antibacterial activity of pyranmycins against aminoglycoside resistant bacteria is less than expected, the synthetic methodologies of utilizing a library of aminosugars can be a model for future studies of glycodiversification or glycorandomization.

Amino Sugars↗
PubMed2004

[Classification and clinical study of plasma cell mastitis under breast duct endoscope].

OBJECTIVE: To evaluate the clinical significance of breast duct endoscope for plasma cell mastitis. METHODS: Breast duct endoscope was performed on 250 patients with nipple discharge. The characters of 95 cases of plasma cell mastitis under the breast duct endoscope were analyzed and studied. RESULTS: Among the 95 cases with plasma cell mastitis, 21 were in type I, 43 in type II, 18 in type III and 13 in type IV. Eighty-three cases were treated with no-operation treatment, and 45 completely released, 38 partly released. There were 5 cases with middle to serious atypical hyperplasia in 12 cases treated with operation, that were all confirmed by pathological examination. CONCLUSION: In patients with plasma cell mastitis, clear diagnosis can be made through breast duct endoscope, and the breast duct with lesions could be positioned. It is a necessary assistant method for patients to avoid biopsy or decrease the biopsy range.

Adolescent↗
PubMed2004

OH radicals generated by DC corona discharge for improving the pulsed discharge desulfuration efficiency.

Positive DC corona discharge is formed with needle-plate electrode configuration, in which the water vapor is ejected though the needle points. The purpose is to increase the numbers of the water-based radicals, ionize the water molecule and improve the desulfuration efficiency of pulsed corona reactor. The water ions were determined by four stages molecular beam mass spectrometer and diagnose the water-based radicals by emission spectrograph. A conclusion on formation of ions and radicals with DC corona discharges can be drawn.

Electrodes↗
PubMed2004

Rifampicin inhibits alpha-synuclein fibrillation and disaggregates fibrils.

The aggregation of alpha-synuclein in dopaminergic neurons of the substantia nigra is a critical step in the pathogenesis of Parkinson's disease. We show that the antibiotic rifampicin inhibited alpha-synuclein fibrillation and disaggregated existing fibrils in a concentration-dependent manner. Size-exclusion chromatography data indicated that rifampicin stabilized alpha-synuclein as both a monomer and soluble oligomers comprised of partially folded alpha-synuclein. Experiments using aged samples of rifampicin indicated that the most active species in inhibiting fibrillation and disaggregating fibrils is an oxidation product of rifampicin, which was confirmed in experiments under anaerobic conditions. These results indicate that rifampicin-mediated inhibition of alpha-synuclein fibrillation and disaggregation of fibrils involves preferential stabilization of monomeric and soluble oligomeric forms, and that rifampicin potentially may have therapeutic application for Parkinson's disease.

Dose-Response Relationship, Drug↗
PubMed2004

A proprietary extract from North American ginseng (Panax quinquefolium) enhances IL-2 and IFN-gamma productions in murine spleen cells induced by Con-A.

A patented aqueous extract from North American ginseng (Panax quinquefolium), containing mainly oligosaccharides and polysaccharides, is commercially available over the counter as COLD-FX (CVT-E002). This proprietary extract is used for the treatment of upper respiratory tract infections. Its in vitro stimulating effects on the immunoglobulin production by B lymphocytes and on natural immune responses by peritoneal exudates macrophages have been previously reported. Using C57 BL/6 mice, an ex vivo study was conducted to examine Con-A-induced splenocytic productions of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) as markers of acquired immune responses. CVT-E002 (10-500 microg/ml) significantly increased Con-A-induced IL-2 and IFN-gamma productions in spleen cells in a dose-dependent manner. Such response was seen by the ginseng extract originated from three different lots, suggesting consistency between the lots.

Adjuvants, Immunologic↗
PubMed2004

Complete DiGeorge syndrome: development of rash, lymphadenopathy, and oligoclonal T cells in 5 cases.

BACKGROUND: Five patients with DiGeorge syndrome presented with infections, skin rashes, and lymphadenopathy after the newborn period. T-cell counts and function varied greatly in each patient. Initial laboratory testing did not suggest athymia in these patients. OBJECTIVE: The purpose of this study was to determine whether the patients had significant immunodeficiency. METHODS: Research testing of peripheral blood included immunoscope evaluation of T-cell receptor beta variable gene segment repertoire diversity, quantification of T-cell receptor rearrangement excision circles, and detection of naive T cells (expressing CD45RA and CD62L). RESULTS: The patients were classified as having DiGeorge syndrome on the basis of syndromic associations and heart, parathyroid, and immune abnormalities. Immunoscope evaluation revealed that the T-cell repertoires were strikingly oligoclonal in all patients. There were few recent thymic emigrants, as indicated by the very low numbers of naive T cells (<50/mm(3)) and the absence of T-cell receptor rearrangement excision circles. These studies showed that all 5 patients were athymic. Two patients died, one from infection. No thymus was found during the complete autopsy performed on one patient. CONCLUSION: Patients with DiGeorge syndrome, skin rash, and lymphadenopathy should undergo analysis of naive T-cell numbers and of T-cell receptor beta variability segment repertoire to determine whether they are athymic, even if they have T cells with mitogen responsiveness. It is important for physicians to realize that patients with complete DiGeorge syndrome remain profoundly immunodeficient after development of these atypical features (rash, lymphadenopathy, and oligoclonal T cells). Prompt diagnosis is necessary for appropriate management.

Child, Preschool↗
PubMed2004

Mutations affecting thymus organogenesis in Medaka, Oryzias latipes.

The thymus is an organ for T lymphocyte maturation and is indispensable for the establishment of a highly developed immune system in vertebrates. In order to genetically dissect thymus organogenesis, we carried out a large-scale mutagenesis screening for Medaka mutations affecting recombination activating gene 1 (rag1) expression in the developing thymus. We identified 24 mutations, defining at least 13 genes, which led to a marked reduction of rag1 expression in the thymus. As thymus development depends on pharyngeal arches, we classified those mutations into three classes according to the defects in the pharyngeal arches. Class 1 mutants had no or slight morphological abnormalities in the pharyngeal arches, implying that the mutations may include defects in such thymus-specific events as lymphocyte development and thymic epithelial cell maturation. Class 2 mutants had abnormally shaped pharyngeal arches. Class 3 mutants showed severely attenuated pharyngeal arch development. In Class 2 and Class 3 mutants, the defects in thymus development may be due to abnormal pharyngeal arch development. Those mutations are expected to be useful for identifying the molecular mechanisms underlying thymus organogenesis.

Animals↗
PubMed2004

Transcriptional inactivation of STAT3 by PPARgamma suppresses IL-6-responsive multiple myeloma cells.

Multiple myeloma (MM) remains largely incurable despite conventional and high-dose therapies. Therefore, novel biologically based treatment approaches are urgently required. Here we demonstrate that expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in MM cells and its agonists 15-d-PGJ2 and troglitazone completely abolished IL-6-inducible MM cell proliferation and induced apoptosis through affecting expression of multiple cell cycle or apoptosis genes, whereas PPARgamma antagonist GW9662 and PPARalpha agonist WY14643 did not display this inhibitory effect. These PPARgamma agonists significantly inhibited DNA binding and transactivation of STAT3 bound to the promoter of target genes in chromatin, but did not affect the expression of IL-6 receptor and phosphorylation of JAK/STAT3, MAPK, and PI3K/Akt. Interestingly, although inactivation of STAT3 by PPARgamma agonists is in a PPARgamma-dependent manner, the molecular mechanism by which two structurally distinct PPARgamma agonists suppress IL-6-activated STAT3 shows the divergent interactions between PPARgamma and STAT3 including direct or SMRT-mediated association.

Anilides↗
PubMed2004

Cloning and functional analysis of a novel DREB1/CBF transcription factor involved in cold-responsive gene expression in Zea mays L.

The transcription factors DREB1s/CBFs specifically interact with the DRE/CRT cis-acting element (core motif: G/ACCGAC) and control the expression of many stress-inducible genes in Arabidopsis. We isolated a cDNA for a DREB1/CBF homolog, ZmDREB1A in maize using a yeast one-hybrid system. The ZmDREB1A proteins specifically bound to DRE and the highly conserved valine at the 14th residue in the ERF/AP2 DNA binding domain was a key to determining the specific interaction between this protein and the DRE sequence. Expression of ZmDREB1A was induced by cold stress and slightly increased by high-salinity stress. This gene was also transiently expressed by mechanical attack. ZmDREB1A activated the transcription of the GUS reporter gene driven by DRE in rice protoplasts. Overexpression of ZmDREB1A in transgenic Arabidopsis induced overexpression of target stress-inducible genes of Arabidopsis DREB1A resulting in plants with higher tolerance to drought and freezing stresses. This indicated that ZmDREB1A has functional similarity to DREB1s/CBFs in Arabidopsis. The structure of the ERF/AP2 domain of ZmDREB1A in maize is closely related to DREB1-type ERF/AP2 domains in the monocots as compared with that in the dicots. ZmDREB1A is suggested to be potentially useful for producing transgenic plants that is tolerant to drought, high-salinity and/or cold stresses.

Amino Acid Sequence↗
PubMed2004

Regulation of hepatitis B virus core promoter by transcription factors HNF1 and HNF4 and the viral X protein.

Hepatitis B virus (HBV) core promoter contains a binding site for nuclear receptors. A natural double mutation in this binding site, which changes nucleotide (nt) 1765 from A to T and nt 1767 from G to A, selectively abolishes the binding of several nuclear receptors without affecting that of HNF4. This double mutation also creates a binding site for the transcription factor HNF1 and changes two amino acids in the overlapping X protein sequence. In this study, we have examined the roles of HNF1, HNF4, and the X protein in the regulation of the core promoter activities in Huh7 hepatoma cells. Our results indicate that HNF4 could stimulate the expression of the precore RNA and the core RNA from the core promoter of both the wild-type (WT) HBV and the double mutant, although its effect on the former was more prominent. In contrast, HNF1, which did not affect the WT core promoter, suppressed the precore RNA expression of the double mutant. Further analysis using HBV genomic constructs, with and without the ability to express the X protein, indicates that the X protein did not affect the HNF4 activity on the core promoter and affected the HNF1 activity on the core promoter of only the double mutant. Thus, our results indicate that the phenotypic differences of HBV WT and double-mutant core promoters are at least partially due to the differential activities of HNF1, HNF4, and the X protein on these two promoters.

Amino Acid Sequence↗
PubMed2004

Long-term neuroprotection induced by regional brain cooling with saline infusion into ischemic territory in rats: a behavioral analysis.

The neuroprotective effect of hypothermia has long been recognized. Our recent studies have demonstrated the significant therapeutic value of local brain cooling in the ischemic territory prior to reperfusion in stroke, with reduced infarction and inflammatory responses up to 48 hours of reperfusion. The goal of this study was to determine if local brain cooling, produced by infusion of cold saline, could induce long-term functional improvement after stroke. A hollow filament was used to block the middle cerebral artery (MCA) for 3 hours, and then to locally infuse the ischemic territory with 6 ml cold saline (20 degrees C) for 10 minutes prior to reperfusion. This brain cooling infusion induced a significant (p < 0.01) decrease in neurologic deficits and significantly (p < 0.01) improved motor behavior in ischemic rats after 14 days of reperfusion, compared with ischemic rats without local cold saline infusion. This improvement continued for up to 28 days after reperfusion. No significant difference in motor performance was observed between the brain cooling infusion and normal control groups. Significant (p < 0.01) reductions in infarct volume were also evident. In conclusion, a local cerebral hypothermia induced by local saline infusion prior to reperfusion produced a long-term functional recovery after ischemic stroke. A therapeutic procedure, which combines prereperfusion infusion into an ischemic region with coincident cerebral hypothermia and perhaps subsequent recanalization of an occluded intracranial vessel, may improve the outcome for stroke patients.

Animals↗