Biomedical subjects

Hui Zhang

Publications and source records attributed to Hui Zhang.

At least 253 records · Page 14Linked to original sources

PubMed2004

A six-month, placebo-controlled trial of D-cycloserine co-administered with conventional antipsychotics in schizophrenia patients.

RATIONALE: D-Cycloserine, a partial agonist at the glycine site of the N-methyl-D-aspartate receptor, has demonstrated inconsistent efficacy for negative and cognitive symptoms of schizophrenia. The strongest evidence for efficacy has come from studies using D-cycloserine at a dose of 50 mg/day added to conventional antipsychotics in trials of 8 weeks duration or less. OBJECTIVE: To assess the efficacy for negative symptoms and cognitive impairment of D-cycloserine augmentation of conventional antipsychotics in a 6-month trial. METHODS: Fifty-five schizophrenia patients with prominent negative symptoms, treated with conventional antipsychotics, were randomly assigned to treatment with D-cycloserine 50 mg/day or placebo for 6 months in a double-blind, parallel group design. RESULTS: Twenty-six subjects completed the 6-month trial; drop-out rates did not differ between treatment groups. D-Cycloserine treatment did not differ from placebo treatment on any primary outcome measure at 8 or 24 weeks, including response of negative symptoms and performance on a cognitive battery. Serum D-cycloserine concentrations did not correlate with response of negative symptoms. CONCLUSION: D-Cycloserine did not exhibit therapeutic effects in this trial, possibly reflecting the high drop-out rate, a narrow range of therapeutic serum concentrations, a modest magnitude of therapeutic effect for the selected outcome measures, or loss of efficacy over time. Because D-cycloserine is a partial agonist with relatively low affinity for the glycine site, the magnitude of potential therapeutic effect may be smaller than that achieved by the higher-affinity full agonists, glycine and D-serine.

Adult↗

PubMed2004

Levels of plasma des-gamma-carboxy protein C and prothrombin in patients with liver diseases.

AIM: To study the plasma des-gamma-carboxy protein C activity, antigen and prothrombin levels in patients with liver diseases and their clinical significance. METHODS: Plasma protein C activity (PC:C) was detected by chromogenic assay and antigen (PC:Ag) and des-gamma-carboxy protein C (DCPC) were detected by ELISA. Total prothrombin and unabsorbed prothrombin in plasma were detected by ecarin chromogenic assay. RESULTS: Compared with the control, the levels of PC:C and PC:Ag in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC) were lower (PC:C: 104.65+/-23.0%, 62.50+/-24.89%, 56.75+/-20.14%, PC:Ag: 5.31+/-1.63 microg/mL, 2.28+/-1.15 microg/mL, 2.43+/-0.79 microg/mL, P<0.05). The levels of PC:Ag in patients with acute viral hepatitis (AVH) also was lower (2.98+/-0.91 microg/mL, P<0.01), but PC:C was close to the control (93.76+/-30.49%, P>0.05). The levels of DCPC in patients with HCC were remarkably higher (0.69+/-0.29 microg/mL, 1.18+/-0.63 microg/mL, 0.45+/-0.21 microg/mL, P<0.05) and its average was up to 50% of total PC:Ag. But those of DCPC in patients with AVH were not significantly different from the control. The levels of total prothrombin were lower in patients with LC, but higher in patients with HCC. The levels of unabsorbed prothrombin were predominantly higher than those of other groups. CONCLUSION: PC:C and PC:Ag in patients with liver diseases (except PC:C in AVH) were lower. The total prothrombin was lower in patients with LC. The higher level of unabsorbed prothrombin may be used as a scanning marker for HCC. DCPC may be used as a complementary marker in the diagnosis of HCC.

Adult↗

PubMed2004

Blocking programmed death-1 ligand-PD-1 interactions by local gene therapy results in enhancement of antitumor effect of secondary lymphoid tissue chemokine.

The negative signal provided by interactions of programmed death-1 (PD-1) and its ligands, costimulatory molecules PD-L1 (also B7-H1) and PD-L2 (also B7-DC), is involved in the mechanisms of tumor immune evasion. In this study, we found that this negative signal was also involved in immune evasion in tumor immunotherapy. When we used different doses of a constructed eukaryotic expression plasmid, pSLC, which expresses functional murine secondary lymphoid tissue chemokine (SLC, CCL21), to treat BALB/c mice inoculated with H22 murine hepatoma cells, the inhibitory effect was enhanced along with the increase of pSLC dosage. Unexpectedly, however, the best complete inhibition rate of tumor was reached when pSLC was used at the dosage of 50 microg but not 100 or 200 microg. RT-PCR and real-time PCR revealed that both PD-L1 and PD-L2 genes were expressed in tumor and vicinal muscle tissues of tumor-bearing mice and the expression level was significantly increased if a higher dosage of pSLC was administered. We then constructed a eukaryotic expression plasmid (pPD-1A) that expresses the extracellular domain of murine PD-1 (sPD-1). sPD-1 could bind PD-1 ligands, block PD-Ls-PD-1 interactions, and enhance the cytotoxicity of tumor-specific CTL. Local gene transfer by injection of pPD-1A mediated antitumor effect and improved SLC-mediated antitumor immunity. The combined gene therapy with SLC plus sPD-1 did not induce remarkable autoimmune manifestations. Our findings provide a potent method of improving the antitumor effects of SLC and possibly other immunotherapeutic methods by local blockade of negative costimulatory molecules.

Animals↗

PubMed2004

Bimodal role of conventional protein kinase C in insulin secretion from rat pancreatic beta cells.

The present study was conducted to evaluate the role of conventional protein kinase C (PKC) in calcium-evoked insulin secretion. In rat beta cells transfected with green fluorescent protein-tagged PKC-alpha (PKC-alpha-EGFP), a depolarizing concentration of potassium induced transient elevation of cytoplasmic free calcium ([Ca(2)(+)](c)), which was accompanied by transient translocation of PKC-alpha-EGFP from the cytosol to the plasma membrane. Potassium also induced transient translocation of PKC-theta-EGFP, the C1 domain of PKC-gamma and PKC-epsilon-GFP. A high concentration of glucose induced repetitive elevation of [Ca(2)(+)](c) and repetitive translocation of PKC-alpha-EGFP. Diazoxide completely blocked both elevation of [Ca(2)(+)](c) and translocation of PKC-alpha-EGFP. We then studied the role of conventional PKC in calcium-evoked insulin secretion using rat islets. When islets were incubated for 10 min with high potassium, Go-6976, an inhibitor of conventional PKC, and PKC-alpha pseudosubstrate fused to antennapedia peptide (Antp-PKC(19-31)) increased potassium induced secretion. Similarly, insulin release induced by high glucose for 10 min was enhanced by Gö-6976 and Antp-PKC(19-31). However, when islets were stimulated for 60 min with high glucose, both Gö-6976 and Antp-PKC(19-31) reduced glucose-induced insulin secretion. Similar results were obtained by transfection of dominant-negative PKC-alpha using adenovirus vector. Taken together, PKC-alpha is activated when cells are depolarized by a high concentration of potassium or glucose. Conventional PKC is inhibitory on depolarization-induced insulin secretion per se, but it also augments glucose-induced secretion.

Animals↗

PubMed2004

Androgen receptor polymorphisms and risk of biochemical failure among prostatectomy patients.

BACKGROUND: Little is known about the role of inherited genotypes in prostate cancer (PC) progression. This prospective study evaluated the predictive value of androgen receptor (AR) polymorphisms (CAG and GGC repeats) among prostatectomy patients. METHODS: We studied 354 patients registered at M. D. Anderson Cancer Center from 1991 to 2001. Kaplan-Meier and Cox proportional hazard analyses were used. RESULTS: During an average follow-up of 56 months, 66 (19%) post-prostatectomy patients experienced biochemical failure (BF). Patients with higher CAG repeats (CAG > or = 24) had significantly longer BF-free survival (BFFS) than those with fewer repeats (CAG < or = 23) (P = 0.04). Higher CAG repeats were significantly associated with lower BF risk among Whites and African Americans. Among Whites, longer CAG repeats (relative risk (RR) = 0.45, P = 0.03) and Gleason score > or = 8 (RR = 19.33, P = 0.005) remained significant BFFS predictors in multivariate analysis. GGC repeats were not associated with BF. CONCLUSIONS: Our data showed that an inherited polymorphism (CAG repeats) in the AR is related to differences in genetic susceptibility to BF, supporting the hypothesis that increased AR activity may play a role in PC progression.

Adenocarcinoma↗

PubMed2004

KIAA0008 gene is associated with invasive phenotype of human hepatocellular carcinoma--a functional analysis.

PURPOSE: To investigate the function of the KIAA0008 gene, one of the leading genes in the signature associated with hepatocellular carcinoma (HCC) metastasis selected by cDNA microarray, and especially its possible roles in invasion and metastasis of hepatocellular carcinoma. METHODS: Expression levels of KIAA0008 in 27 primary tumors and 23 matched non-tumor liver tissues from HCC patients, and four HCC cell lines with different metastatic potentials were detected by semi-quantitative RT-PCR and real-time RT-PCR. Recombinant expression plasmid vectors of the KIAA0008 gene were constructed and transfected into HCC cells. The subcellular localization of the KIAA0008 gene product and in vitro effects of KIAA0008 overexpression on proliferation and invasion of HCC cell line were also investigated. RESULTS: Expression levels of KIAA0008 in HCC tissues were statistically higher than those of paired non-tumorous liver tissues (P < 0.001, paired Wilcoxon test), and in HCCs with high invasiveness these were statistically higher than those with low invasiveness (P = 0.002, Mann-Whitney test). In the four HCC cell lines with an identical genetic background and stepwise higher invasiveness potentials, its expression was consistent with their invasiveness potential. The KIAA0008 gene product was concentrated on the nucleus and cell membrane of HCC cells, without any distribution in the cytoplasm. Overexpression of KIAA0008 in the MHCC97L cell line resulted in increased cell proliferation, colony formation, and invasion. CONCLUSIONS: KIAA0008 expression is associated with invasiveness of HCC; overexpression of KIAA0008 leads to a more invasive phenotype of HCC cell lines.

Adult↗

PubMed2004

The role of myosin heavy chain phosphorylation in Dictyostelium motility, chemotaxis and F-actin localization.

To assess the role of myosin II heavy chain (MHC) phosphorylation in basic motility and natural chemotaxis, the Dictyostelium mhcA null mutant mhcA(-), mhcA(-) cells rescued with a myosin II gene that mimics the constitutively unphosphorylated state (3XALA) and mhcA(-) cells rescued with a myosin II gene that mimics the constitutively phosphorylated state (3XASP), were analyzed in buffer and in response to the individual spatial, temporal and concentration components of a cAMP wave using computer-assisted methods. Each mutant strain exhibited unique defects in cell motility and chemotaxis. Although mhcA(-) cells could crawl with some polarity and showed chemotaxis with highly reduced efficiency in a spatial gradient of cAMP, they were very slow, far less polar and more three-dimensional than control cells. They were also incapable of responding to temporal gradients of cAMP, of chemotaxis in a natural wave of cAMP or streaming late in aggregation. 3XASP cells were faster and chemotactically more efficient than mhcA(-) cells, but still incapable of responding to temporal gradients of cAMP, chemotaxis in natural waves of cAMP or streaming late in aggregation. 3XALA cells were fast, were able to respond to temporal gradients of cAMP, and responded to natural waves of cAMP. However, they exhibited a 50% reduction in chemotactic efficiency, could not stream late in aggregation and could not enter the streams of control cells in mixed cultures. F-actin staining further revealed that while the presence of unphosphorylated MHC was essential for the increase in F-actin in the cytoplasm in response to the increasing temporal gradient of cAMP in the front of a natural wave, the actual dephosphorylation event was essential for the associated increase in cortical F-actin. The results of these studies indicate that MHC phosphorylation-dephosphorylation, like myosin II regulatory light chain phosphorylation-dephosphorylation, represents a potential downstream target of the regulatory cascades emanating from the different phases of the wave.

Actins↗

PubMed2004

Cpc1, a Chlamydomonas central pair protein with an adenylate kinase domain.

Mutations at CPC1 disrupt assembly of a central pair microtubule-associated complex and alter flagellar beat frequency in Chlamydomonas. Sequences of wild-type genomic clones that complement cpc1, and of corresponding cDNAs, reveal the gene product to be a 205 kDa protein with two predicted functional domains, a single EF hand motif near the C-terminus and an unusual centrally located adenylate kinase domain. Homologs are expressed in mammals (testis and tracheal cilia) as well as ciliated lower eukaryotes. Western blots confirm that Cpc1 is one of six subunits in a 16S central pair-associated complex. Motility defects associated with cpc1 alleles in vivo are partially rescued in vitro by reactivation of axonemes or cell models in saturating concentrations of ATP; thus the Cpc1 complex is essential for maintaining normal ATP concentrations in the flagellum.

Adenosine Triphosphate↗

PubMed2004

Evaluation of left ventricular ejection fraction by tissue locus imaging.

The newly developed echocardiographic technique called "tissue locus imaging" (TLI) can visualize temporal series of images in a single picture by maintaining the display of previous images with a shading function; therefore, it can display the whole systolic shift of the mitral leaflets toward the apex in a single picture and can potentially offer useful information on left ventricular (LV) function. In 36 consecutive patients with varying degrees of LV dysfunction (15 with coronary artery disease, 9 with cardiomyopathy, 3 with hypertension, 2 with aortic stenosis, 1 with aortic regurgitation, and 6 controls), the systolic shift of the mitral leaflets (X) by TLI showed a significant correlation with the LV ejection fraction (Y) by 2-dimensional echocardiography (Y = 7.2 x+13, r(2) = 0.83, p <0.01). TLI enables the evaluation and visualization of LV systolic function by displaying the whole systolic shift of the mitral leaflets toward the apex.

Adult↗

PubMed2004

Salt cress. A halophyte and cryophyte Arabidopsis relative model system and its applicability to molecular genetic analyses of growth and development of extremophiles.

Salt cress (Thellungiella halophila) is a small winter annual crucifer with a short life cycle. It has a small genome (about 2 x Arabidopsis) with high sequence identity (average 92%) with Arabidopsis, and can be genetically transformed by the simple floral dip procedure. It is capable of copious seed production. Salt cress is an extremophile native to harsh environments and can reproduce after exposure to extreme salinity (500 mm NaCl) or cold to -15 degrees C. It is a typical halophyte that accumulates NaCl at controlled rates and also dramatic levels of Pro (>150 mm) during exposure to high salinity. Stomata of salt cress are distributed on the leaf surface at higher density, but are less open than the stomata of Arabidopsis and respond to salt stress by closing more tightly. Leaves of salt cress are more succulent-like, have a second layer of palisade mesophyll cells, and are frequently shed during extreme salt stress. Roots of salt cress develop both an extra endodermis and cortex cell layer compared to Arabidopsis. Salt cress, although salt and cold tolerant, is not exceptionally tolerant of soil desiccation. We have isolated several ethyl methanesulfonate mutants of salt cress that have reduced salinity tolerance, which provide evidence that salt tolerance in this halophyte can be significantly affected by individual genetic loci. Analysis of salt cress expressed sequence tags provides evidence for the presence of paralogs, missing in the Arabidopsis genome, and for genes with abiotic stress-relevant functions. Hybridizations of salt cress RNA targets to an Arabidopsis whole-genome oligonucleotide array indicate that commonly stress-associated transcripts are expressed at a noticeably higher level in unstressed salt cress plants and are induced rapidly under stress. Efficient transformation of salt cress allows for simple gene exchange between Arabidopsis and salt cress. In addition, the generation of T-DNA-tagged mutant collections of salt cress, already in progress, will open the door to a new era of forward and reverse genetic studies of extremophile plant biology.

Abscisic Acid↗

PubMed2004

Heterosynaptic dopamine neurotransmission selects sets of corticostriatal terminals.

Dopamine input to the striatum is required for voluntary motor movement, behavioral reinforcement, and responses to drugs of abuse. It is speculated that these functions are dependent on either excitatory or inhibitory modulation of corticostriatal synapses onto medium spiny neurons (MSNs). While dopamine modulates MSN excitability, a direct presynaptic effect on the corticostriatal input has not been clearly demonstrated. We combined optical monitoring of synaptic vesicle exocytosis from motor area corticostriatal afferents and electrochemical recordings of striatal dopamine release to directly measure effects of dopamine at the level of individual presynaptic terminals. Dopamine released by either electrical stimulation or amphetamine acted via D2 receptors to inhibit the activity of subsets of corticostriatal terminals. Optical and electrophysiological data suggest that heterosynaptic inhibition was enhanced by higher frequency stimulation and was selective for the least active terminals. Thus, dopamine, by filtering less active inputs, appears to reinforce specific sets of corticostriatal synaptic connections.

Afferent Pathways↗

PubMed2004

Frequency-dependent modulation of dopamine release by nicotine.

Although nicotine activation of dopamine release is implicated in addiction, it also desensitizes nicotinic acetylcholine receptors (nAChRs), leading to a prolonged depression of evoked dopamine release. Here we show that nicotine's effects depend on the firing pattern of dopamine neurons, so that while desensitization of nAChRs indeed curbs dopamine released by stimuli emulating tonic firing, it allows a rapid rise in dopamine from stimuli emulating phasic firing patterns associated with incentive/salience paradigms. Nicotine may thus enhance the contrast of dopamine signals associated with behavioral cues.

Action Potentials↗

PubMed2004

Methyl-CpG-binding domain 2: a protective role in bladder carcinoma.

BACKGROUND: MBD2, a methyl-CpG-binding domain 2 protein, has attracted much attention because of its role in epigenetic regulation of gene expression. In addition to transcriptional repression, MBD2 has also been shown to catalyze demethylation by directly removing methyl groups from 5-methylcytosine residues in DNA. Although the demethylase activity of MBD2 remains controversial, reduction of MBD2 messenger RNA expression has been observed in various tumor tissue types. In the current case-control study, the authors investigated the association between MBD2 expression and bladder carcinoma risk. METHODS: RNA was isolated from the peripheral blood lymphocytes of 98 bladder carcinoma case patients and 135 frequency-matched control patients. MBD2 expression was measured by real-time quantitative reverse transcription-polymerase chain reaction assays. RESULTS: Overall, there was a significantly reduced risk associated with high levels of MBD2 expression (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.21-0.90). This relation was maintained when the data were categorized according to quartile distribution for MBD2 expression (P for trend < 0.05). It is noteworthy that the protective effects were more apparent in women (OR, 0.25; 95% CI, 0.06-1.02) compared with men (OR, 0.58; 95%; CI, 0.24-1.42), in older individuals (OR, 0.12; 95% CI, 0.03-0.45) compared with younger individuals (OR, 1.16; 95% CI, 0.40-3.33), and in heavier smokers (OR, 0.40; 95% CI, 0.18-0.93) compared with lighter smokers (OR, 0.71; 95% CI, 0.18-2.86). CONCLUSIONS: Although the underlying molecular mechanisms remain unclear, the data obtained in the current study represent the first evidence demonstrating a protective role against bladder carcinoma risk for MBD2. MBD2 expression may prevent age-related, gender-related, and smoking-induced hypermethylation, which are predisposing factors for tumor development.

Base Sequence↗

PubMed2004

Periplasmic proteins of Escherichia coli are highly resistant to aggregation: reappraisal for roles of molecular chaperones in periplasm.

Periplasmic proteins of Gram-negative bacteria like Escherichia coli are subjected to immediate affect of environmental fluctuation that may unfold proteins, due to the permeability of the outer membrane to small molecules. They are thus supposedly protected by certain molecular chaperones. Nevertheless, no homologues of typical molecular chaperones have so far been found in periplasm, and the recently reported chaperone activities of periplasmic protein disulfide isomerase (PDI) and peptidyl prolyl isomerase (PPI) seem to be too weak to satisfy such assumed needs. In an attempt to reveal whether periplasmic proteins exhibit certain unusual properties, we discovered that such proteins as a whole are highly resistant to aggregation under a wide variety of denaturing conditions. Furthermore, in an effort to unveil the nature behind this phenomenon we purified and examined four prominent periplasmic proteins. Our results demonstrate that these proteins unfold at rather mild denaturing conditions and expose hydrophobic surfaces during such unfolding process, but hardly form complexes with a typical molecular chaperone. Based on these observations, we propose that the periplasmic proteins have been evolved to resist the formation of aggregates when subjected to various denaturing conditions and molecular chaperones may thus not be needed in periplasm.

Animals↗

PubMed2004

[Effects of selective cyclooxygenase-2 inhibitor NS-398 on 5-fluorouracil chemotherapy and progression of colon cells: an experimental study].

OBJECTIVE: To investigate the effects of selective cyclooxygenase-2 (COX-2) inhibitor NS-398 on 5-fluorouracil (5-Fu) chemotherapy and on the progression of colon cells. METHODS: Colon cancer cells of HT-29 and SW480 lines were cultured. Selective COX-2 inhibitor NS-398, 5-Fu, or NS-398 combining with 5-Fu were added into the cultures to be co-cultured for 24, 48, and 72 hours respectively. RT-PCR and ELISA analysis were performed to detect the level of COX-2 mRNA expression and prostaglandin 2 (PGE2) concentration in the cells of both HT-29 and SW480 lines. The proliferation and apoptosis of the two cell lines were observed with MTT assay and flow cytometry. RESULTS: Expression of COX-2 mRNA were negative in SW480 line and positive in HT-29 line. Compared with SW480 line, the HT-29 line showed an obvious decline of PGE2 concentration following NS-398 treatment. Both NS-398 and 5-Fu inhibited the cells' proliferation and induced apoptosis in a dose-dependent manner, and a more significant inhibition was found when the cells were co-treated with NS-398 and 5-Fu. Although, there was no significant difference between these in inducing apoptosis. CONCLUSION: Selective COX-2 inhibitor NS-398 can inhibit the proliferation of colon cancer cells and induce apoptosis thereof. The mechanism of NS-398 against colon cancer may be independent upon the expression levels of COX-2 mRNA and PGE2 of colon cancer. NS-398 may be a subsidiary drug in 5-Fu chemotherapy in treating colon cancer.

Antimetabolites, Antineoplastic↗

PubMed2004

Regulation of the development of mesencephalic dopaminergic systems by the selective expression of glial cell line-derived neurotrophic factor in their targets.

Glial cell line-derived neurotrophic factor (GDNF) has been shown to protect and restore dopamine (DA) neurons in injury models and is being evaluated for the treatment of Parkinson's disease. Nevertheless, little is known of its physiological role. We have shown that GDNF suppresses apoptosis in DA neurons of the substantia nigra (SN) postnatally both in vitro and during their first phase of natural cell death in vivo. Furthermore, intrastriatal injection of neutralizing antibodies augments cell death, suggesting that endogenous GDNF plays a role as a target-derived factor. Such a role would predict that overexpression of GDNF in striatum would increase the surviving number of SN DA neurons. To test this hypothesis, we used the tetracycline-dependent transcription activator (tTA)/tTA-responsive promoter system to create mice that overexpress GDNF selectively in the striatum, cortex, and hippocampus. These mice demonstrate an increased number of SN DA neurons after the first phase of natural cell death. However, this increase does not persist into adulthood. As adults, these mice also do not have increased dopaminergic innervation of the striatum. They do, however, demonstrate increased numbers of ventral tegmental area (VTA) neurons and increased innervation of the cortex. This morphologic phenotype is associated with an increased locomotor response to amphetamine. We conclude that striatal GDNF is necessary and sufficient to regulate the number of SN DA neurons surviving the first phase of natural cell death, but it is not sufficient to increase their final adult number. GDNF in VTA targets, however, is sufficient to regulate the adult number of DA neurons.

Age Factors↗

PubMed2004

Dopamine neurons mediate a fast excitatory signal via their glutamatergic synapses.

Dopamine neurons are thought to convey a fast, incentive salience signal, faster than can be mediated by dopamine. A resolution of this paradox may be that midbrain dopamine neurons exert fast excitatory actions. Using transgenic mice with fluorescent dopamine neurons, in which the axonal projections of the neurons are visible, we made horizontal brain slices encompassing the mesoaccumbens dopamine projection. Focal extracellular stimulation of dopamine neurons in the ventral tegmental area evoked dopamine release and early monosynaptic and late polysynaptic excitatory responses in postsynaptic nucleus accumbens neurons. Local superfusion of the ventral tegmental area with glutamate, which should activate dopamine neurons selectively, produced an increase in excitatory synaptic events. Local superfusion of the ventral tegmental area with the D2 agonist quinpirole, which should increase the threshold for dopamine neuron activation, inhibited the early response. So dopamine neurons make glutamatergic synaptic connections to accumbens neurons. We propose that dopamine neuron glutamatergic transmission may be the initial component of the incentive salience signal.

Animals↗

PubMed2004

Comparison of immune responses and protective efficacy of suicidal DNA vaccine and conventional DNA vaccine encoding glycoprotein C of pseudorabies virus in mice.

In the present study, the immunogenicity and protective efficacy of a suicidal DNA vaccine (pSFVC1.5) incorporating Semliki Forest virus (SFV) replicon and expressing glycoprotein C (gC) of pseudorabies virus (PrV) was investigated and compared with a conventional plasmid DNA vaccine (pcDC) encoding the same antigen. In vitro, pSFVC1.5 could express gC protein and induce apoptosis of the transfected cells. After immunization in BALB/c mice, the gC-specific ELISA antibodies and neutralizing antibodies induced by pSFVC1.5 were relatively lower than those obtained in mice immunized with pcDC. However, mice immunized with pSFVC1.5 could confer more efficient protection than pcDC (100 and 62.5%, respectively) when challenged with the field PrV at 4 weeks after secondary immunization. Further analyses of cell-mediated immune responses showed that pSFVC1.5 induced stronger lymphocyte proliferative responses and higher levels of IFN-gamma, suggesting pSFVC1.5 could induce an enhanced Th1-type immune response. Collectively these results indicated that suicidal DNA vaccine is an alternative strategy to conventional DNA vaccine and can be considered a promising approach for the development of an efficacious vaccine against PrV.

Animals↗