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Biomedical subjects

H Guo

Publications and source records attributed to H Guo.

At least 19 recordsLinked to original sources
PubMed2006

Protection of chickens against avian hepatitis E virus (avian HEV) infection by immunization with recombinant avian HEV capsid protein.

Avian hepatitis E virus (avian HEV) is an emerging virus associated with hepatitis-splenomegaly syndrome in chickens in North America. Avian HEV is genetically and antigenically related to human HEV, the causative agent of hepatitis E in humans. In the lack of a practical animal model, avian HEV infection in chickens has been used as a model to study human HEV replication and pathogenesis. A 32 kDa recombinant ORF2 capsid protein of avian HEV expressed in Escherichia coli was found having similar antigenic structure as that of human HEV containing major neutralizing epitopes. To determine if the capsid protein of avian HEV can be used as a vaccine, 20 chickens were immunized with purified avian HEV recombinant protein with aluminum as adjuvant and another 20 chickens were mock immunized with KLH precipitated in aluminum as controls. Both groups of chickens were subsequently challenged with avian HEV. All the tested mock-immunized control chickens developed typical avian HEV infection characterized by viremia, fecal virus shedding and seroconversion to avian HEV antibodies. Gross hepatic lesions were also found in portion of these chickens. In contrast, none of the tested chickens immunized with avian HEV capsid protein had detectable viremia, fecal virus shedding or observable gross hepatitis lesions. The results from this study suggested that immunization of chickens with avian HEV recombinant ORF2 capsid protein with aluminum as adjuvant can induce protective immunity against avian HEV infection. Chickens are a useful small animal model to study anti-HEV immunity and pathogenesis.

Animals↗
PubMed2006

Extracellular matrix metalloproteinase inducer regulates metalloproteinases in human uterine endometrium.

CONTEXT: Endometrial remodeling occurs during each menstrual cycle in women and also during the establishment of endometriosis. Both processes involve the production of metalloproteinases (MMPs) by uterine endometrial cells. OBJECTIVE: The objective of this study was to determine whether tissue remodeling and endometrial invasion involve activation of MMPs by extracellular matrix metalloproteinase inducer (EMMPRIN). MAIN OUTCOME MEASURES: EMMPRIN expression was examined by immunohistochemistry and real-time PCR in ectopic and eutopic endometria. For functional assays, human uterine fibroblasts were treated in the absence or presence of IL-1beta (10 ng/ml) or purified native EMMPRIN (0.5 or 1 microg/ml) for 24 h. Cellular RNA and conditioned medium were assayed by real-time PCR or immunoblotting. RESULTS: EMMPRIN protein localized to epithelial and fibroblast cells of eutopic and ectopic endometria. The pattern of localization was regulated by ovarian hormones. EMMPRIN mRNA levels varied throughout the menstrual cycle in parallel with the cyclic changes in estradiol. EMMPRIN treatment (0.5 microg/ml) of human uterine fibroblast cells stimulated MMP-1 (5.23-fold) and MMP-2 (8.55-fold), but not MMP-3, mRNA levels over levels in control cells (P < 0.05). EMMPRIN treatment (1 microg/ml) stimulated endogenous EMMPRIN (1.6-fold) mRNA levels (P > 0.05). IL-1beta stimulated MMP-1 (5.6-fold), MMP-2 (2.8-fold), and MMP-3 (75-fold) gene expression, but not EMMPRIN, over levels in control cells (P < 0.05). Both EMMPRIN and IL-1beta treatments stimulated MMP-1, -2, and -3, but not EMMPRIN protein secretion, with 0.5 microg/ml producing the greatest response. CONCLUSIONS: The ability of EMMPRIN to stimulate MMP secretion by endometrial fibroblasts indicates its potential role in uterine remodeling and the pathogenesis of endometriosis.

Basigin↗
PubMed2006

Regulation of antisense RNA expression during cardiac MHC gene switching in response to pressure overload.

Hypertension has been shown to cause cardiac hypertrophy and a shift in myosin heavy chain (MHC) gene expression from the faster alpha- to slower beta-MHC isoform. The expression of the beta- and alpha-MHC pre-mRNAs, mRNAs, as well as the newly discovered antisense beta-RNA were analyzed in three regions of the normal control (NC) and 12-day pressure-overloaded (AbCon) hearts: the left ventricle apex, left ventricle base, and the septum. The RNA analyses in the AbCon heart targeted both the 5' and the 3' ends of each RNA molecule. beta-MHC mRNA expression significantly increased relative to control in all three regions, regardless of the target site (5' or 3' end). In contrast, beta-MHC pre-mRNA expression in the AbCon heart depended on the site of the measurement (5' vs. 3' end). For example, whereas the pre-mRNA did not change when targeted at the 3' end (last intron), it increased significantly in the AbCon heart when measurement targeted the 5' end (2nd intron) of the 25-kb molecule. Analyses of the antisense beta-RNA revealed that its expression in the AbCon heart was significantly decreased relative to control regardless of its measurement site. A negative correlation was observed between the beta-mRNA expression and the antisense beta-RNA (P < 0.05), suggesting an inhibitory role of antisense RNA on the sense beta-MHC gene expression. In contrast, a positive correlation was observed between the antisense beta-RNA and the alpha-MHC pre-mRNA (P < 0.05). This latter observation along with the alpha-MHC gene position relative to that of the beta-antisense suggest that the alpha-MHC sense and beta-antisense transcription are coregulated likely via common intergenic regulatory sequences. Our results suggest that the increased beta-MHC expression in the AbCon heart not only is the result of increased beta-MHC transcription but also involves an antisense beta-RNA regulation scheme. Although the exact mechanism concerning antisense regulation is not clear, it could involve modulation of both transcriptional activity of the beta-MHC gene and posttranscriptional processing.

Animals↗
PubMed2006

Experimental study on genistein prevention and treatment of transplant arteriosclerosis in aortic transplants of rat.

OBJECTIVE: Our objective was to study the effects of genistein, a soy isoflavone, on transplant arteriosclerosis, in addition to its immunosuppressive and antioxidant properties. MATERIALS AND METHODS: We performed male Brown-Norway to male Lewis aortic transplantation. The recipients were randomly assigned to 3 groups: no treatment controls, dimethyl sulfoxide (DMSO; 5 mL/kg) solvent controls, and experimental group that received genistein (20 mg/kg/d) by daily intraperitoneal injection. On postoperative day 60, the graft was harvested and blood obtained. The transplanted aorta was analyzed by histology and immunohistochemistry. The serum was analyzed by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the 2 controls, leukocyte recruitment to the graft was significantly inhibited by genistein, with a profound reduction in the number of CD69 macrophages infiltrating the adventitia of the transplanted aortas. Moreover, genistein significantly inhibited the expression of VEGF and IFN-gamma production (P < .01). CONCLUSION: These results suggested that the protein tyrosine kinase inhibitor genistein inhibited graft arteriosclerosis.

Animals↗
PubMed2006

Prolonged cardiac allograft survival in presensitized rats after a high activity Yunnan-cobra venom factor therapy.

UNLABELLED: Complement-dependent antibody-mediated acute humoral rejection is the major obstacle of clinical transplantation across ABO incompatibility and human leukocyte antigen presensitization. We previously demonstrated that Yunnan-cobra venom factor (Y-CVF) could almost completely abrogate complement activity and successfully prevent hyperacute rejection in some xenotransplant models without any obvious toxicity. In this study we investigated whether depletion of complement by Y-CVF prevented acute humoral allograft rejection in presensitized rats thereby prolonging graft survival. METHODS: Presensitization was achieved in Lewis rats by sequential grafting of three full-thickness skin pieces from Brown Norway rats. Serum cytotoxic alloantibody titers were determined by a modified in vitro complement-dependent microcytotoxicity assay. After presensitization, each Lewis rat received a heterotopic Brown Norway cardiac allograft. Fifteen recipients were divided into two groups: (1) no treatment control (n = 7); (2) Y-CVF therapy group (86 u/kg, IV, day -1) (n = 8). After cessation of the heart beat, allograft rejection was confirmed by pathologic as well as IgG and C3 immunohistochemical examinations. RESULTS: The mean graft survival time was significantly prolonged to 99.50 +/- 38.72 hours among rats that received Y-CVF vs 12.71 +/- 13.94 hours in nontreated controls (P < .001). Upon pathological and immunohistochemical examination, acute humoral rejection was mainly exhibited in the control group, whereas acute cellular rejection was mainly displayed in the Y-CVF therapy group. CONCLUSIONS: Our study demonstrated that complement depletion by Y-CVF significantly inhibited acute humoral allograft rejection in presensitized rats. As a therapeutic immunointervention tool for complement, Y-CVF has shown potential efficacy across ABO incompatible and positive cross-match barriers.

Animals↗
PubMed2006

Antisense ERK1/2 oligodeoxynucleotide gene therapy attenuates graft arteriosclerosis of aortic transplant in a rat model.

UNLABELLED: Chronic rejection is a major cause of transplant loss that is effected by the extracellular signal-regulated kinases (ERK) pathway. This study investigated the effects of antisense ERK1/2 oligodeoxynucleotide(ODN) gene therapy on chronic rejection. METHODS: Lewis (RT1(1)) rats served as recipients of Brown-Norway (BN, RT1n) grafts. The BN rat abdominal aortas were harvested and orthotopically grafted into Lewis rats. The recipients were divided into three groups: (1) control group (n = 9), (2) random ODN transfer group (n = 10), and (3) antisense ODN transfer group (n = 10). At day 60 after transplantation, the recipients were sacrificed; the grafted aortas were evaluated histologically and immunohistochemically. ERK1/2 protein expression in the grafts was determined using Western Blot assays. Serum levels of slCAM-1 were detected by ELISA. RESULTS: In the control group and random ODN transfer group, we observed a remarkable degree of intimal hyperplasia and inflammatory cell infiltration, including macrophages and T cells. Compared with the control group, antisense ERK1/2 ODN gene therapy resulted in a significant reduction in neointimal proliferation (P < .01), inhibition of ERK1/2 protein expression (P < .01), decreased graft infiltration with CD4+ T lymphocytes (P < .01), CD8+ T lymphocytes(P < .05), and ED-1 macrophages (P < .01) with decreased serum levels of sICAM-1 (P < .05). We obtained a negative correlation between ERK1/2 expression and immune cell infiltration or ICAM-1 level. CONCLUSIONS: Antisense ERK1/2 gene therapy can attenuate graft arteriosclerosis so as to protect aortic allografts. The protection seemed to correlate with inhibition of inflammatory infiltration, implying that the ERK1/2 signal transduction pathway plays an important role in the process of chronic vascular rejection.

Animals↗
PubMed2006

Adenovirus-mediated antisense-ERK2 gene therapy attenuates chronic allograft nephropathy.

BACKGROUND: The aim of this study was to investigate the effects of adenovirus-mediated antisense ERK2 (Adanti-ERK2) gene therapy on chronic allograft nephropathy. METHODS: We employed a rat kidney transplantation mode (F344-->Lewis) and studied four groups: (1) controls (n = 6); (2) vector controls (n = 6); (3) an Adanti-ERK2 group (n = 10); and (4) an isograft group (n = 4). The animals were monitored for proteinuria, graft histology, infiltrating cells, and immune-related gene (interleukin-2 [IL-2] and intracellular adhesion molecule-1 [ICAM-1]) expression for 20 weeks after transplantation. RESULTS: The control group had increasing proteinuria during the 20-week follow-up. All rats showed advanced chronic renal failure associated with strong immune cell infiltration and immune gene expression. Chronic graft injury was accelerated in the vector-control group, but no significant difference was observed compared with the control group. In contrast, the Adanti-ERK2 group showed less inflammation and improved graft histology/function compared with controls. Moreover, ERK2 protein expression in the Adanti-ERK2 group was lower than in the control group (P < .05) and vector-control group (P < .05). Furthermore, serial estimates of genes (IL-2, ICAM-1) related to chronic rejection showed significant downregulation in the Adanti-ERK2 group (P < .01). CONCLUSIONS: Adenovirus-mediated antisense ERK2 gene therapy attenuated chronic allograft nephropathy. The protective effects of antisense ERK2 gene therapy may have derived from a blocked ERK signal transduction pathway, which reduced ERK expression as well as those of immune-related genes.

Adenoviridae↗
PubMed2006

Caspase-1 activation of caspase-6 in human apoptotic neurons.

Active caspase-6 (Csp-6) induces cell death in primary cultures of human neurons and is abundant in the neuropathological lesions of Alzheimer's disease. However, the mode of Csp-6 activation is not known. Here, we show that the Csp-1 inhibitor, Z-YVAD-fmk specifically prevents activation of Csp-6 and cell death in human neurons. A transient increase in Csp-1-like activity and an increase in the p23Csp-1 subunit occur early after serum deprivation. Recombinant active Csp-1 (R-Csp-1) cleaves recombinant and neuronal pro-Csp-6 in vitro resulting in Csp-6 activity. However, R-Csp-1 does not induce cell death when microinjected in human neurons despite the inhibition of serum-deprivation induced cell death with a Csp-1 dominant negative construct. These results show that Csp-1 is an upstream positive regulator of Csp-6-mediated cell death in primary human neurons. Furthermore, these results suggest that the activation of Csp-1 must be accompanied by an apoptotic insult to induce Csp-6-mediated cell death.

Amino Acid Chloromethyl Ketones↗
PubMed2006

Identification of B-cell epitopes in the capsid protein of avian hepatitis E virus (avian HEV) that are common to human and swine HEVs or unique to avian HEV.

Avian hepatitis E virus (avian HEV) was recently discovered in chickens from the USA that had hepatitis-splenomegaly (HS) syndrome. The complete genomic sequence of avian HEV shares about 50 % nucleotide sequence identity with those of human and swine HEVs. The open reading frame 2 (ORF2) protein of avian HEV has been shown to cross-react with human and swine HEV ORF2 proteins, but the B-cell epitopes in the avian HEV ORF2 protein have not been identified. Nine synthetic peptides from the predicted four antigenic domains of the avian HEV ORF2 protein were synthesized and corresponding rabbit anti-peptide antisera were generated. Using recombinant ORF2 proteins, convalescent pig and chicken antisera, peptides and anti-peptide rabbit sera, at least one epitope at the C terminus of domain II (possibly between aa 477-492) that is unique to avian HEV, one epitope in domain I (aa 389-410) that is common to avian, human and swine HEVs, and one or more epitopes in domain IV (aa 583-600) that are shared between avian and human HEVs were identified. Despite the sequence difference in ORF2 proteins between avian and mammalian HEVs and similar ORF2 sequence between human and swine HEV ORF2 proteins, rabbit antiserum against peptide 6 (aa 389-399) recognized only human HEV ORF2 protein, suggesting complexity of the ORF2 antigenicity. The identification of these B-cell epitopes in avian HEV ORF2 protein may be useful for vaccine design and may lead to future development of immunoassays for differential diagnosis of avian, swine and human HEV infections.

Animals↗
PubMed2005

Identification and characterization of mErk5-T, a novel Erk5/Bmk1 splice variant.

Extracellular regulated kinase 5 (ERK5) is an unusually large member of the MAP kinase family of signaling molecules that plays an important role in cellular proliferation, differentiation and survival. Recently, three transcriptional variants of murine Erk5 were described (mErk5-a, -b and -c) that result from alternate splicing across introns 1 and/or 2, the net effect of which is translation of a peptide that lacks the kinase domain. It has been demonstrated that expression of mErk5-b and -c impinge on the function of the full length mErk5 protein product via a dominant negative effect. Here, we report the identification of another murine Erk5 splice variant and the orthologous human transcript that arise due to alternate splicing of intron 4. Failure to splice out intron 4 introduces a premature in-frame stop codon that directs translation of a peptide lacking the nuclear localization signal (NLS) and proline-rich region (PR). Experimental characterization demonstrated that like mERK5, mERK5-T becomes phosphorylated by co-expression with a constitutively active mMEK5 (mMEK5DD), and is able to coimmunoprecipitate with both itself and mERK5. Unlike mERK5, however, activated ERK5-T is unable to translocate from the cytoplasm to the nucleus in HeLaS3 cells, causing the retention of active mERK5 in the cytoplasm. Taken together with previous reports of domain content modification of ERK5 via alternate splicing, these observations add to the suggestion that regulation of ERK5 signaling may be mediated, at least in part, at the level of RNA processing.

Alternative Splicing↗
PubMed2005

Glial cell line-derived neurotrophic factor (GDNF) is required for differentiation of pontine noradrenergic neurons and patterning of central respiratory output.

Genetic mutations affecting signaling by glial cell line-derived neurotrophic factor (GDNF) perturb development of breathing in mice and are associated with congenital central hypoventilation syndrome in humans. However, the role of GDNF in development of brainstem neurons that control breathing is largely unknown. The present study demonstrates that genetic loss of GDNF decreases the number of tyrosine hydroxylase (TH) neurons in the pontine A5 noradrenergic cell group, a major source of inhibitory input to the medullary respiratory pattern generator. This phenotype is associated with a significant increase in the frequency of central respiratory output recorded from the fetal medulla-spinal cord in vitro. In dissociate cultures of the A5 region from rat embryos, GDNF increases TH cell number and neurite growth without affecting total neuronal survival or proliferation of TH neurons. These effects of GDNF are inhibited by function blocking antibodies against endogenous brain-derived neurotrophic factor (BDNF), indicating that GDNF requires BDNF as a cofactor to stimulate differentiation of A5 neurons. Our findings demonstrate that GDNF is required for development of pontine noradrenergic neurons in vivo and indicate that defects in the A5 cell group may contribute to the effects of genetic disruption of GDNF signaling on respiratory control.

Age Factors↗
PubMed2005

Modulation of intra-pulmonary TGF-beta expression by mycophenolate mofetil in lupus prone MRL/lpr mice.

We investigated the expression profile of inflammatory cytokines in the lung of lupus-prone MRL/lpr mice and evaluated the therapeutic potential of mycophenolate mofetil (MMF) in reducing pulmonary cytokines in active lupus. Eight-week old female MRL/lpr mice (n = 20) were treated with MMF in vehicle by oral gavage. Disease control MRL/lpr mice (n = 30) or normal control MRL mice (n = 20) received vehicle alone. The mice were sacrificed after eight or 12 weeks of treatment. Gene expression and protein synthesis of IL-1beta, MCP-1 and TGF-beta1 in lung tissues were determined. We found an increase in the gene expression of IL-1beta, MCP-1 and TGF-beta1 in lung tissues of untreated MRL/lpr mice compared with MRL mice at either 16 weeks or 20 weeks of age. MMF treatment significantly prolonged the survival of MRL/lpr mice, down-regulated the gene expression of IL-1beta, MCP-1 and TGF-beta1 in lung tissues at the end of eight or 12 weeks of treatment. Protein synthesis of TGF-beta1 was decreased following eight weeks of MMF treatment. We conclude that MMF treatment can reduce the TGF-beta1 gene expression and protein synthesis in lung tissues of lupus-prone mice. Our findings provide experimental data suggesting a beneficial potential of MMF therapy in pulmonary involvement of lupus.

Animals↗
PubMed2004

Extraction of plumes in turbulent thermal convection.

We present a scheme to extract the velocity of buoyant structures in turbulent thermal convection from simultaneous local velocity and temperature measurements. Applying this scheme to measurements taken at positions within the convection cell where the buoyant structures are dominated by plumes, we obtain the temperature dependence of the plume velocity and understand our results using the equations of motion. We further obtain the scaling behavior of the average local heat flux in the vertical direction at the cell center with the Rayleigh number and find that the scaling exponent is different from that measured for the Nusselt number. This difference leads to the conclusion that heat cannot be mainly transported through the central region of the convection cell.

Journal Article↗
PubMed2004

Indoor air quality investigation at air-conditioned and non-air-conditioned markets in Hong Kong.

To characterize indoor air quality at the markets in Hong Kong, three non-air-conditioned and two air-conditioned markets were selected for this study. The indoor air pollutants measured included PM(10) (particulate matters with aerodynamic diameter less than 10 microm), total bacteria count (TBC), carbon monoxide (CO), nitric oxide (NO), nitrogen dioxide (NO(2)) and sulfur dioxide (SO(2)). The indoor and outdoor concentrations of these target air pollutants at these markets were measured and compared. The effects of air conditioning, temperature/relative humidity variation and different stalls on the indoor air quality were also investigated. The results indicated that all of the average indoor concentrations of PM(10), TBC, CO and NO(2) at the markets were below the Hong Kong Indoor Air Quality Objectives (HKIAQO) standards with a few exceptions for PM(10) and TBC. The elevated PM(10) concentrations at Hung Hom, Ngau Tau Kok and Wan Chai markets were probably due to the air filtration of outdoor airborne particulates emitted from vehicular exhaust, whereas high concentrations of airborne bacteria at Sai Ying Pun and Tin Shing markets were linked to the use of air conditioning. Correlation analysis demonstrated that indoor bacteria concentrations were correlated with temperature and relative humidity. The operation of air conditioning did not significantly reduce the levels of air pollutants at the markets. However, the higher indoor/outdoor ratios demonstrated that the operation of air conditioning had influence on the levels of bacteria at the markets. It was found that average PM(10) concentration at poultry stalls was higher than the HKIAQO standard of 180 microg/m(3), and was over two times that measured at vegetable, fish and meat stalls. Furthermore, the concentration of airborne bacteria at the poultry stalls was as high as 1031 CFU/m(3), which was above the HKIAQO standard of 1000 CFU/m(3). The bacteria levels at other three stalls were all below the HKIAQO standard. Statistical analysis indicated that there were no significant differences among the four stalls for CO, NO(x) and SO(2).

Air Conditioning↗
PubMed2004

Seasonal and diurnal variations of volatile organic compounds (VOCs) in the atmosphere of Hong Kong.

Ambient VOCs samples were collected at three locations (PolyU campus (PU), Kwun Tong (KT), Hok Tsui (HT)) in Hong Kong during the periods of November 2000-February 2001 and June 2001-August 2001. Also the concentrations of VOCs in Cross Harbor tunnel in Hong Kong were obtained in order to determine the vehicular sources of VOCs. Toluene was the most abundant VOC detected in Hong Kong. At the PU station, which is close to a main road, the concentrations of most VOCs were higher in summer than in winter. However, at the background location HT, the concentrations of all VOCs except tetrachloroethene were higher in winter than in summer. Regional physical dispersion/transportation and mixing depth may be the reasons for higher VOC concentrations in winter at HT. The BTEX (benzene:toluene:ethylbenzene:xylene) ratios of PU and KT during winter period were (1.9:10.1:1.0:1.8) and (1.9:10.4:1.0:1.5), and (0.9:8.3:1.0:2.2) and (0.8:29.6:1.0:1.8) for summer season, respectively. The xylene/ethylbenzene (X/E) ratio was used to assess the relative age of the air parcels in this study. The concentrations of VOCs in the atmosphere in Hong Kong were mainly affected by direct emissions from vehicles, evaporation of fuels, photochemical reactions and few industrial emissions. The BTEX ratio in the tunnel was 2:10.4:1:3.2. The BTEX ratios at PU and KT during the winter period were similar to that in tunnel (except for xylenes). The X/E ratio in the tunnel was higher than that in the ambient air. This indicated that the freshly emitted xylenes in the tunnel decayed at different rates from OH-oxidation in the atmosphere. Good BTEX correlations (r>0.8) were found at PU and KT in winter (**P<0.01). Vehicular exhaust was the dominant source at PU and KT stations, and less evaporation of fuel or additive occurred at low temperature in winter. Diurnal variations of mean BTEX concentrations at the roadside monitoring station (PU) showed two peaks associated with traffic density and vehicle type.

Journal Article↗