PubMed Health⌕ Search

Biomedical subjects

Weiping Zhang

Publications and source records attributed to Weiping Zhang.

At least 37 records · Page 2Linked to original sources

Novel heat shock protein Hsp70L1 activates dendritic cells and acts as a Th1 polarizing adjuvant.

Heat shock proteins (HSPs) are reported to act as effective adjuvants to elicit anti-tumor and anti-infection immunity. Here, we report that Hsp70-like protein 1 (Hsp70L1), a novel HSP derived from human dendritic cells (DCs), has potent adjuvant effects that polarize responses toward Th1. With a calculated molecular weight of 54.8 kDa, Hsp70L1 is smaller in size than Hsp70 but resembles it both structurally and functionally. Hsp70L1 shares common receptors on DCs with Hsp70 and can interact with DCs, promoting DC maturation and stimulating secretion of the proinflammatory cytokines interleukin 12p70 (IL-12p70), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), and the chemokines IP-10, macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and normal T cell expressed and secreted (RANTES). The induction of interferon-gamma-inducible protein 10 (IP-10) secretion by Hsp70L1 is not shared by Hsp70, and other functional differences include more potent stimulation of DC IL-12p70, CC-chemokine, and CCR7 and CXCR4 expression by Hsp70L1. Immunization of mice with the hybrid peptide Hsp70L1-ovalbumin(OVA)(257-264) induces an OVA(257-264)-specific Th1 response and cytotoxic T lymphocyte (CTL) that results in significant inhibition of E.G7-OVA tumor growth. The ability of Hsp70L1 to activate DCs indicates its potential as a novel adjuvant for use with peptide immunizations; the Hsp70L1 antigen peptide hybrid may serve as a more effective vaccine for the control of cancer and infectious diseases.

Adjuvants, Immunologic↗

Wave mixing of optical pulses and bose-einstein condensates.

We investigate theoretically the four-wave mixing of optical and matter waves resulting from the scattering of a short light pulse off an atomic Bose-Einstein condensate, as recently demonstrated by D. Schneble et al. [Science 300, 475 (2003)]]. We show that atomic "pair production" from the condensate results in the generation of both forward- and backward-propagating matter waves. These waves are characterized by different phase-matching conditions, resulting in different angular distributions and temporal evolutions.

Journal Article↗

Effective induction of therapeutic antitumor immunity by dendritic cells coexpressing interleukin-18 and tumor antigen.

Dendritic cell (DC) based cancer vaccine can induce potent antitumor immunity in murine models; however, objective clinical responses have been observed only in a minority of cancer patients. To improve the antitumor effect of DC vaccine, Th1-biasing cytokine interleukin (IL) 18 and melanoma-associated antigen gp100 were cotransfected into bone marrow-derived DC (IL-18/gp100-DC), which were used as vaccine to induce the protective and therapeutic immunity in a B16 melanoma model. Immunization with IL-18/gp100-DC resulted in tumor resistance in 87.5% of the mice challenged with B16 cells; however, 12.5% and 25% of mice immunized with gp100 gene-modified DC (gp100-DC) or IL-18 gene-modified DC (IL-18-DC) were tumor free, respectively. Most importantly, IL-18/gp100-DC immunization led to the generation of potent therapeutic immunity that significantly inhibited the tumor growth and improved the survival period of mice bearing established melanoma. Immune cell depletion experiments identified that CD4(+) T cells also played an important role in the priming phase of antitumor immunity and CD8(+) T lymphocytes were the primary effectors. gp100-specific CTL response were induced most markedly in the tumor-bearing mice immunized with IL-18/gp100-DC. Administration with such vaccine also significantly increased the production of Th1 cytokine (IL-2 and interferon-gamma) and induced infiltration of inflammatory cells inside and around the tumors. In addition, natural killer cell activity was also augmented. These results indicate that immunization with DC vaccine coexpressing Th1 cytokine IL-18 and tumor antigen gene may be an effective strategy for a successful therapeutic vaccination.

Animals↗

Cloning and functional characterization of human septin 10, a novel member of septin family cloned from dendritic cells.

Septins are a family of cytoskeletal proteins with GTPase activity involved in various cellular biological processes. Here, we describe the identification of septin 10, a novel septin family member from human dendritic cells. The 3018-bp full-length cDNA potentially encodes a 517-residue peptide, sharing closest homology to human septin 8 and septin 6. With a conserved GTP-binding motif at its N-terminus, septin 10 protein can bind to GTP and exert GTPase activity. Human septin 10 gene is electronically mapped to 8q11.2-12. It is ubiquitously expressed in normal tissues, with the abundant expression in heart and kidney, placenta, skeletal muscles, liver and lung, as well as various tumor cell lines. Interestingly, dendritic cells express upregulated septin 10 upon LPS-induced maturation. Based on its GFP-fusion protein, septin 10 is found to localize in cytoplasm and nucleus, with a subcellular pattern independent of the filamentous state of actin.

Amino Acid Sequence↗

Rab39, a novel Golgi-associated Rab GTPase from human dendritic cells involved in cellular endocytosis.

Rab GTPases are Ras-like small molecular weight GTP binding proteins that are involved in various steps along the exocytic and endocytic pathways. Here we report that Rab39, a novel Rab protein, is a Golgi-associated protein involved in endocytosis of HeLa cells. Full-length cDNA of Rab39 contains 1251bp with an open reading frame (ORF) of 636bp, which is predicted to encode a 211 aa protein. By blast analysis of Rab39 cDNA and protein sequence with homologues, we find that Rab39 may be a short variant of Rab34. Rab39 contains conserved motifs involved in phosphate/guanosine binding and a microbody C-terminal targeting signal. RT-PCR analysis indicates that Rab39 is mainly detected in epithelial cell lines, and Northern blot analysis shows that Rab39 is expressed ubiquitously in human tissues. By using FITC-BSA as an endocytic tracer, we show that Rab39 can facilitate endocytosis in HeLa cells when expressed either transiently or stably. Confocal microscopy examination of Rab39 subcellular localization suggests that Rab39 is associated with Golgi-associated organelles. Our findings demonstrate that Rab39 is a novel Rab GTPase involved in cellular endocytosis.

3T3 Cells↗

Feshbach-resonance-induced atomic filamentation and quantum pair correlation in atom-laser-beam propagation.

We study the propagation of an atom laser beam through a spatial region with a magnetic field tuned around a Feshbach resonance. Magnetic fields below the resonance produce an effective focusing Kerr medium that causes a modulational instability of the atomic beam. Under appropriate circumstances, this results in beam breakup and filamentation seeded by quasiparticle fluctuations and in the generation of correlated atomic pairs.

Journal Article↗

Cloning and identification of a novel ubiquitin-like protein, BMSC-UbP, from human bone marrow stromal cells.

Ubiquitin is one of phylogenetically well-conserved proteins in all eukaryotes. Ubiquitin-dependent modification of protein contributes to fine regulation of cellular biological processes. Using large-scale screening of human bone marrow stromal cell (BMSC) cDNA library, we isolated a full-length cDNA of 1352 bp encoding 380 amino acids with a ubiquitin domain (UBQ), which was designed as bone marrow stromal cell-derived ubiquitin-like protein (BMSC-UbP). In addition to UBQ domain at its N-terminus, BMSC-UbP also possesses a ubiquitin-associated domain at its C-terminus, sharing moderate homology to some ubiquitin-like proteins such as UBIN, Chap1, and ubiquilin. BMSC-UbP localizes at chromosome 15q22.3-q23 as confirmed by blast search in human genome. BMSC-UbP mRNA is widely expressed in human multiple tissues and various tumor cell lines. Moreover, BMSC-UbP mRNA decreased in BMSC stimulated with PMA and increased in HL60 cells stimulated with LPS, suggesting that BMSC-UbP might play roles in regulation of BMSC function or cell differentiation through an evocator- and cell-specific pattern.

Amino Acid Sequence↗

Cloning and functional characterization of GNPI2, a novel human homolog of glucosamine-6-phosphate isomerase/oscillin.

The enzyme, glucosamine-6-phosphate isomerase (GNPI) or deaminase (GNPDA) (EC 5.3.1.10), catalyzes the conversion of GNP to fructose-6-phosphate and ammonia, with an aldo/keto isomerization and an amination/deamination. A hamster sperm-derived protein (Oscillin) with high similarity to bacterial GNPI has been proved to be capable of inducing calcium oscillation in eggs at fertilization. GNPI/Oscillin was supposed to be an important factor in starting embryonic development. From the cDNA library of human dendritic cells (DC), we isolated a novel full-length cDNA encoding a 276-amino acid-residue protein that shares high homology with human GNPI/Oscillin. So, the novel molecule is named as GNPI2. The GNPI2 gene consists of seven exons and six introns. It is mapped to chromosome 4. Northern blot analysis indicated that the tissue distribution of GNPI2 mRNA is different from that of human GNPI or Oscillin mRNA. GNPI2 is ubiquitously expressed in most of human tissues with high expression in testis, ovary, placenta, and heart. Like GNPI, the recombinant GNPI2 has been proved to have the enzymatic activity to catalyze the conversion of GNP to fructose-6-phosphate. Our results indicated that GNPI2 is a novel protein with definite function as a GNPI.

Aldose-Ketose Isomerases↗

Cloning and functional characterization of GMPR2, a novel human guanosine monophosphate reductase, which promotes the monocytic differentiation of HL-60 leukemia cells.

PURPOSE: To identify the biological function of a novel molecule which shows high homology with human guanosine monophosphate reductase (GMPR) and is named GMPR2. METHODS: GMPR2 cDNA was cloned from the cDNA library of human dendritic cells and was characterized by Bioinformatics. The expression pattern of GMPR2 was analyzed by Northern blotting. The enzymatic activity of the purified recombinant GMPR2 protein was determined using a spectrophotometric assay. HL-60 leukemia cells were transfected with GMPR2 and the expression of CD14 and myeloperoxidase (MPO) in HL-60 cells with and without 12- o-tetra-decanoyl-phorbol-13-acetate (TPA) induction was monitored by FACS analysis. RESULTS: The novel gene contained ten exons and nine introns and was mapped to 14q11-21. Northern blotting indicated a ubiquitous expression of GMPR2 mRNA in most of the human tissues and cancer cell lines investigated. The recombinant GMPR2 protein was able to reduce GMP. The expression of CD14 and MPO in HL-60 leukemia cells overexpressing GMPR2 clearly increased after induction by TPA. CONCLUSIONS: GMPR2 is a novel human GMP reductase, and overexpression of GMPR2 can promote the monocytic differentiation of HL-60 leukemia cells.

Amino Acid Sequence↗

DC-CLM, a cadherin-like molecule cloned from human dendritic cells, inhibits growth of breast cancer cells.

PURPOSE: To identify the characteristics and function of a cadherin-like molecule, cloned from a human dendritic cell (DC) cDNA library and designated DC-derived cadherin-like molecule (DC-CLM). METHODS: The mRNA expression of DC-CLM in tissues and cells was analyzed by Northern blot and RT-PCR, respectively. In order to express DC-CLM in target cells, we constructed a pcDNA3.1/DC-CLM expression vector and transfected it into MCF-7 human breast cancer cells. Tumor growth was demonstrated by cell proliferation and colony formation. RESULTS: DC-CLM cDNA encoded a protein of 260 amino acids and the gene was localized to chromosome 5q31. The predicted protein possessed a definitive cadherin-specific sequence motif and shared homology with classical cadherin. However, no transmembrane segment was observed in DC-CLM. Northern blot revealed the ubiquitous nature of DC-CLM transcripts in human tissues, with high expression in heart, brain, prostate, testis and ovary. RT-PCR demonstrated that DC-CLM was widely expressed in hematopoietic and epithelial tumor cell lines, but was not expressed in MCF-7. Interestingly, DC-CLM expression was upregulated in DC activated by lipopolysaccharides. DC-CLM expression in the stable transfectant (MCF-7/DC-CLM) was confirmed by RT-PCR and Western blot. DC-CLM protein was found to be secreted by MCF-7/DC-CLM but not expressed on the membrane of MCF-7/DC-CLM. DC-CLM transfection resulted in significant inhibition of in vitro growth and colony formation of MCF-7 cells. CONCLUSIONS: A cadherin-like molecule DC-CLM was cloned from human DC and it may be a soluble cadherin-like molecule for tumor suppression. DC-CLM was upregulated in activated DC and may be involved in the effector function of activated DC.

Amino Acid Sequence↗

Analysis of aging of piezoelectric crystal resonators.

Aging of piezoelectric (quartz crystal) resonator has been identified as one of the most important quality control problems of quartz crystal products. Aging is defined as frequency change with time. Aging in quartz resonators can be due to several sources: mass transfer due to contamination inside the resonator enclosure, stress-strain in the resonator blank, quartz defect, etc. In this study, the stress-strain effect, which has been believed as a dominant factor contributing to aging, is studied. The stress-strain effect is caused mainly by the long-term viscoelastic properties of bonding adhesive that attach quartz crystal plate to the ceramic base package. With the available accelerating testing method under elevated temperatures, the stress-strain induced aging in the quartz crystal resonators can be investigated. Because of the miniaturized size of the resonator, a digital image analysis method called image intensity matching technique (IIMT) is applied to obtain deformation patterns in the quartz blank due to thermal load. Our preliminary results showed that the unsymmetric thermal deformations may be a dominant contributing factor to aging. For simulation purposes, finite-element analysis is used to investigate the deformation patterns (i.e., stress-strain distributions) and corresponding natural frequency shift in the piezoelectric resonators. The viscoelastic behavior of mounting adhesives is incorporated into the analysis to show the dominant effect of long-term behavior of stress-strain developed in the crystal resonators. Also, some geometrical aspects-such as uneven mounting supports due to distances, volumes and heights of the adhesives-are simulated in the model.

Journal Article↗

Cloning and functional characterization of ACAD-9, a novel member of human acyl-CoA dehydrogenase family.

Acyl-CoA dehydrogenases (ACADs) are a family of mitochondrial enzymes catalyzing the initial rate-limiting step in the beta-oxidation of fatty acyl-CoA. The reaction provides main source of energy for human heart and skeletal muscle. Eight human ACADs have been described. Deficiency of these enzymes, especially very long-chain acyl-CoA dehydrogenase (VLCAD), usually leads to severe human organic diseases, such as sudden death in infancy, infantile cardiomyopathy (CM), hypoketotic hypoglycemia, or hepatic dysfunction. By large-scale random sequencing, we identified a novel homolog of ACADs from human dendritic cell (DC) cDNA library. It contains an open reading frame (ORF) of 1866bp, which encodes a 621 amino acid protein. It shares approximately 47% amino acid identity and 65% similarity with human VLCAD. So, the novel molecule is named as acyl-CoA dehydrogenase-9 (ACAD-9), the ninth member of ACADs. The new gene consists of 18 exons and 17 introns, and is mapped to chromosome 3q26. It contains the two signatures shared by all members of the ACADs. ACAD-9 mRNA is ubiquitously expressed in most normal human tissues and cancer cell lines with high level of expression in heart, skeletal muscles, brain, kidney, and liver. Enzymatic assay proved that the recombinant ACAD-9 protein has the dehydrogenase activity on palmitoyl-coenzyme A (C16:0) and stearoyl-coenzyme A (C18:0). Our results indicate that ACAD-9 is a novel member of ACADs.

Acyl-CoA Dehydrogenase↗

Macroscopic spin tunneling and quantum critical behavior of a condensate in a double-well potential.

In a previous work [H. Pu, W. Zhang, and P. Meystre, Phys. Rev. Lett. 87, 140405 (2001)]], we have shown that a spinor condensate confined in a periodic or double-well potential exhibits ferromagnetic behavior due to the magnetic dipole-dipole interactions between different wells, and in the absence of external magnetic field, the ground state has a twofold degeneracy. In this work, we demonstrate the possibility of observing macroscopic quantum spin tunneling between these two degenerate states and show how the tunneling rate critically depends on the strength of the transverse field.

Journal Article↗

Adenovirus-mediated intratumoral lymphotactin gene transfer potentiates the antibody-targeted superantigen therapy of cancer.

Bacterial superantigens are extremely potent activators of murine and human T lymphocytes. To engineer superantigens for cancer immunotherapy, staphylococcal enterotoxin A (SEA) was genetically fused to the Fab region of the human colon carcinoma-reactive monoclonal antibody (mAb) C215. Fusion protein C215Fab-SEA can trigger cytotoxic T cells against C215 antigen positive tumor cells and induce tumor-suppressive cytokines. However, the antitumor effect of C215Fab-SEA is often not satisfactory because of T cell deletion after activation and failure to induce potent CTL activity after repeated administration. Lymphotactin (Lptn) is a potent chemoattractant for T cells and NK cells. To improve the therapeutic efficacy of fusion protein C215Fab-SEA we investigated in this study the antitumor responses elicited by combination of C215Fab-SEA and adenovirus-mediated intratumoral Lptn gene transfer in the preestablished C215 antigen expressing B16 melanoma murine model. More significant inhibition of tumor growth and prolonged survival time were observed in tumor-bearing mice that received combined therapy of C215Fab-SEA and Ad-Lptn than those of mice treated with C215Fab-SEA or Ad-Lptn alone. The highest CTL activity of tumor-bearing mice was induced after combined therapy. Intratumoral coadministration of C215Fab-SEA and Ad-Lptn augmented splenic NK activity of tumor-bearing mice most markedly. Our data demonstrate that the in vivo antitumor effect of C215Fab-SEA immunotherapy is potentiated significantly by combination with intratumoral Lptn gene transfer through more efficient induction of specific and nonspecific antitumor immune responses.

Adenoviridae↗

[Combination of mycophenolate mofetil with cyclosporine A and methotrexate for the prophylaxes of acute graft versus host disease in allogeneic peripheral stem cell transplantation].

OBJECTIVE: To evaluate the efficacy of combination of mycophenolate mofetil (MMF) with cyclosporine (CsA) and methotrexate (MTX) on prophylaxes of acute graft-versus-host disease (GVHD) in HLA-matched allogeneic peripheral blood stem cell transplantation (allo-PBSCT). METHODS: Thirty-nine patients with acute leukemia (n = 21) and chronic myeloid leukemia (n = 17) and severe aplastic anemia (n = 1) were treated with allo-PBSCT from HLA matched siblings (n = 36) or unrelated donors (n = 3). Twenty-six patients were in CsA + MTX group. CsA was given at a dosage of 2 mg.kg(-1).d(-1) by continuous intravenous injection for 24 h, since on day(-1) and injection of CsA was changed to oral administration of CsA around day 18. CsA was tapered by 10% per week after day + 90. MTX was given at the dosage of 15 mg at day + 1, and 10 mg at day + 3, + 6 and + 11, respectively. Thirteen patients were included in MMF + CsA + MTX group with the same dosage of CsA and MTX as above but omitted at day + 11. MMF of 2 g/day was added orally from day + 1 to day + 28 post transplantation. RESULTS: All patients in both groups were successfully engrafted. The days of recovery of neutrophils and platelets were not significantly different between two groups (P > 0.05). The incidence of acute GVHD in MMF + CsA + MTX group (7.6%) was significantly lower than that in CsA/MTX group (46.2%, P < 0.05). Incidence of grade II approximately IV GVHD in MMF group was 0 while that in control group was 23.0%. The incidence of severe mucositis was lower in MMF group (15.4%) than in the control group (30.8%) (P < 0.05). CONCLUSION: The regimen of MMF + CsA + MTX for prevention of acute GVHD in allo-PBSCT is more efficient than that of CsA + MTX, without adversely affecting the engraftment and relapse rate.

Acute Disease↗

Role of sterol regulatory element-binding protein 1 in regulation of renal lipid metabolism and glomerulosclerosis in diabetes mellitus.

Diabetic renal disease is associated with lipid deposits in the kidney. The purpose of our study was to determine whether there is altered regulation of the sterol regulatory element-binding proteins (SREBPs) in the diabetic kidney and whether SREBPs mediate the abnormal renal lipid metabolism and diabetic renal disease. In streptozotocin-induced diabetes in the rat, there were marked increases in SREBP-1 and fatty acid synthase (FAS) expression, resulting in increased triglyceride (TG) accumulation. Treatment of diabetic rats with insulin prevented the increased renal expression of SREBP-1 and the accumulation of TG. The role of hyperglycemia in the up-regulation of SREBP-1 was confirmed in renal cells cultured in a high glucose media. High glucose induced increased expression of SREBP-1a and -1c mRNA, SREBP-1 protein, and FAS, resulting in increased TG content. To determine a direct role for SREBP in mediating the increase in renal lipids and glomerulosclerosis, we studied SREBP-1a transgenic mice with increased renal expression of SREBP-1. The increase in SREBP-1 was associated with increased expression of FAS and acetyl CoA carboxylase, resulting in increased TG content, increased expression of transforming growth factor beta1 and vascular endothelial growth factor, mesangial expansion, glomerulosclerosis, and proteinuria. Our study therefore indicates that renal SREBP-1 expression is increased in diabetes and that SREBP-1 plays an important role in the increased lipid synthesis, TG accumulation, mesangial expansion, glomerulosclerosis, and proteinuria by increasing the expression of transforming growth factor beta and vascular endothelial growth factor.

Animals↗

Phonon spectrum and dynamical stability of a dilute quantum degenerate Bose-Fermi mixture.

We calculate the phonon excitation spectrum in a zero-temperature dilute boson-fermion gaseous mixture. We show how the sound velocity changes due to the boson-fermion interaction, and we determine the dynamical stability regime of a homogeneous mixture. We identify a resonant phonon-exchange interaction between the fermions as the physical mechanism leading to the instability.

Journal Article↗

Spin waves in a Bose-Einstein--condensed atomic spin chain.

The spin dynamics of atomic Bose-Einstein condensates confined in a one-dimensional optical lattice is studied. The condensates at each lattice site behave like spin magnets that can interact with each other through both the light-induced dipole-dipole interaction and the static magnetic dipole-dipole interaction. We show how these site-to-site dipolar interactions can distort the ground-state spin orientations and lead to the excitation of spin waves. The dispersion relation of the spin waves is studied and possible detection schemes are proposed.

Journal Article↗