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Biomedical subjects

Z Q Yao

Publications and source records attributed to Z Q Yao.

At least 19 recordsLinked to original sources
PubMed2006

Characterization of HLA-B*5516, -B*1313, -B*9512, and -DRB1*1457 alleles identified in a southwest Chinese population.

The human leukocyte antigen (HLA)-B*5516 allele differs from the B*5502 by a single 97 T --> C substitution (His to Tyr at position 33) in exon 2. The B*1313 allele results from 419 T --> A and 420 A --> C substitutions, encoding a Leu to Tyr substitution at 140 in exon 2 of the B*1301 allele. The B*9512 allele differs from B*1502 by a single 360 G --> C substitution (Gln to His at 120) in exon 3. The DRB1*1457 allele appears to be a hybrid molecule generated by recombination between the DRB1*13 and DRB1*14 alleles. The serological equivalents of these new alleles are HLA-B22, -B13, -B15, and DR13, respectively. Family studies detected two rare haplotypes: A*11, B*9512, DRB1*14 and A*24, B*52, Cw*07, DRB1*1457, DRB3*020201, DQB1*050301. The gene frequencies of these alleles in the Chinese population are less than 0.0001.

Alleles↗
PubMed2002

Kinase-deficient CMVpp65 triggers a CMVpp65 specific T-cell immune response in HLA-A*0201.Kb transgenic mice after DNA immunization.

CMVpp65, a candidate component of human cytomegalovirus (CMV) vaccines, has phosphokinase (PK) activity that could affect vaccine safety. A mutated form of CMVpp65 substituting asparagine for lysine at the adenosine triphosphate (ATP)-binding site (CMVpp65mII) is kinase-deficient. Using DNA immunizations in a transgenic human leucocyte antigen (HLA)A*0201.Kb mouse model, the mutated CMVpp65 induced cytotoxic T lymphocytes (CTL) immunity similarly to native CMVpp65. Murine CTL lines generated from these immunizations killed human cells either after sensitization with CMVpp65-specific peptides or after infection with either CMV-Towne strain or rvac-pp65. It is proposed that CMVpp65mII be evaluated in candidate vaccines for CMV.

Amino Acid Sequence↗
PubMed2001

Hepatitis C virus core protein inhibits human T lymphocyte responses by a complement-dependent regulatory pathway.

Complement proteins are involved in early innate immune responses against pathogens and play a role in clearing circulating viral Ags from the blood of infected hosts. We have previously demonstrated that hepatitis C virus (HCV) core, the first protein to be expressed and circulating in the blood of infected individuals, inhibited human T cell proliferative response through interaction with the complement receptor, globular domain of C1q receptor (gC1qR). To investigate the mechanisms of HCV core/gC1qR-induced inhibition of T cell proliferation, we examined the effect of core protein on the early events in T cell activation. We found that HCV core inhibited phosphorylation of extracellular signal-regulated kinase (ERK) and mitogen-activated ERK kinase (MEK). HCV core-induced impairment of ERK/MEK mitogen-activated protein kinase resulted in the inhibition of IL-2 and IL-2Ralpha gene transcription, which led to the inhibition of IL-2 production and high-affinity IL-2R expression. Importantly, the ability of anti-gC1qR Ab treatment to reverse HCV core-induced inhibition of ERK/MEK phosphorylation reveals that the interaction between HCV core and gC1qR is linked to the interference of ERK/MEK mitogen-activated protein kinase activation. These results imply that HCV core-induced blockage of intracellular events in T cell activation by a complement-dependent regulatory pathway may play a critical role in the establishment of HCV persistence during the acute phase of viral infection.

Carrier Proteins↗
PubMed2001

Site-directed mutation in a conserved kinase domain of human cytomegalovirus-pp65 with preservation of cytotoxic T lymphocyte targeting.

The major target of human cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTL) is the tegument protein CMVpp65. However, this protein has protein kinase (PK) activity, and the unknown effects on cell replication of an exogenous PK in healthy cells could limit the use of CMVpp65 as a vaccine, especially in children. In this report we show that a point mutation converting lysine to asparagine at the invariant lysine (K436), an essential site for phosphotransfer, abolishes the threonine kinase activity. The mutant CMVpp65 maintains its immunologic target characteristics, including antibody and CTL reactivity. This kinase-deficient CMVpp65 is a candidate for evaluation in future CMV vaccine development.

Amino Acid Sequence↗
PubMed2001

Hepatitis C virus: immunosuppression by complement regulatory pathway.

Hepatitis C virus (HCV) infection in humans is almost invariably associated with viral persistence and chronic hepatitis. HCV-induced chronic hepatitis is a major risk factor for the development of hepatocellular carcinoma. The high incidence of HCV persistence suggests that this virus has evolved one or more mechanisms to evade and possibly suppress host immune responses. To understand the mechanism(s) involved in the establishment of HCV persistence, we have identified an HCV core protein as an immunomodulatory molecule to suppress host immune response. We have further determined a molecular mechanism of HCV core-mediated immune suppression by searching for a potential host protein(s) capable of associating with the HCV core protein. Interestingly, the Clq complement receptor, gC1qR, can bind to the HCV core. Clq is a ligand of gClqR and is involved in the early defense against viral infection as well as regulation of adaptive immune response. Similar to Clq, the HCV core can inhibit human T-lymphocyte proliferative response through its interaction with the gC1qR. It implicates that HCV core/gClqR-induced immune suppression may play a critical role in the establishment of persistent infection.

Animals↗
PubMed2001

Infrequent occurrence of natural mutations in the pp65(495-503) epitope sequence presented by the HLA A*0201 allele among human cytomegalovirus isolates.

To determine if mutations of an immunodominant HLA-restricted cytomegalovirus (CMV) peptide sequence occur in nature, the sequence corresponding to the HLA A*0201-specific peptide CMVpp65(495-503) was determined in 50 human CMV isolates. Rare mutations were detected; 6 of 50 were silent mutations at the amino terminus of the peptide, while 3 of 50 were mutations of the native methionine residue to isoleucine (M499I). The observed M499I mutation in three isolates decreased cytolytic targeting.

Alleles↗
PubMed2000

Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation.

Hepatitis C virus (HCV) is an important human pathogen that is remarkably efficient at establishing persistent infection. The HCV core protein is the first protein expressed during the early phase of HCV infection. Our previous work demonstrated that the HCV core protein suppresses host immune responses, including anti-viral cytotoxic T-lymphocyte responses in a murine model. To investigate the mechanism of HCV core-mediated immunosuppression, we searched for host proteins capable of associating with the core protein using a yeast two-hybrid system. Using the core protein as bait, we screened a human T cell-enriched expression library and identified a gene encoding the gC1q receptor (gC1qR). C1q is a ligand of gC1qR and is involved in the early host defense against infection. Like C1q, HCV core can inhibit T-cell proliferative responses in vitro. This core-induced anti-T-cell proliferation is reversed by addition of anti-gC1qR Ab in a T-cell proliferation assay. Furthermore, biochemical analysis of the interaction between core and gC1qR indicates that HCV core binds the region spanning amino acids 188 to 259 of gC1qR, a site distinct from the binding region of C1q. The inhibition of T-cell responsiveness by HCV core may have important implications for HCV persistence in humans.

Animals↗
PubMed1996

Inhibition of hepatitis B virus in vitro by antisense oligonucleotides.

A series of antisense phosphorothioate oligodeoxynucleotides against hepatitis B virus (HBV) were synthesized and evaluated for their antiviral effect in Hep-G2 cells transfected with HBV genome. The inhibitory effect of the tested antisense oligonucleotides was sequence-specific, dose-and time-dependent, and synergistic for certain combinations. In virus-inhibitory concentrations the oligonucleotides were harmless to 2.2.15 cells. The most effective antisense oligonucleotides were found directed against the HBV mRNA transcribed from the cap site of SP II promoter, the portion of polyadenylation signal and the initiation region of gene S, with an inhibition of the HBsAg and HBeAg production by 85-95% and 50- 60%, respectively. To our surprise, antisense oligonucleotides directed against three key sites of HBV X gene blocked the expression of HBsAg, HBeAg and HBxAg. This fact might be related to the trans-activation of HBV X protein. Using radioisotope labelling, we demonstrated that Lipofectin promoted the cellular uptake and antiviral effect of antisense oligomers in 2.2.15 cells. These results suggest a therapeutic potential of antisense oligonucleotides in the treatment of patients chronically infected with HBV.

Antiviral Agents↗
PubMed1995

Inhibition of hepatitis B viral gene expression by antisense phosphorothioate oligodeoxynucleotides.

The inhibitory effect of antisense phosphorothioate oligodeoxyribonucleotides (S-oligos) on the production of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) was studied using Hep G2 cells transfected with hepatitis B virus (HBV). Synthetic antisense oligos (15-mers) directed against the cap site of mRNA transcribed from the SP II promoter and regions of the translational initiation site of the S gene showed a sequence-specific, dose-dependent inhibitory effect on HBV gene expression between concentrations of 1.0 microM-5.0 microM. Oligos directed against the middle of the S gene had little effect on HBsAg and HBeAg expression, as did non-complementary random-sequence control. The cells remained viable throughout the experiments and no morphological abnormalities were observed with antisense S-oligos at concentrations below 20.0 microM. These results suggest a therapeutic potential for antisense oligonucleotides in the treatment of patients who are chronically infected with HBV.

Cell Division↗
PubMed1995

Specific inhibition of hepatitis b virus gene expression by an antisense oligonucleotide in vitro.

It was previously shown that a number of antisense oligonucleotides against hepatitis B virus (HBV) mRNAs were highly effective in inhibition of HBV gene expression (Yao et al., 1995). Here, using radioisotope techniques, we report a specific inhibition of HBV surface antigen (HBsAg) production in vitro by 2.2.15 cells (Hep-G2 cells transfected with HBV genome) by the antisense oligonucleotide 15-S-asON, a 15-mer phosphorothioate analogue complementary to the cap site of the SPII promoter of HBV mRNA, at a concentration of 2-5 mumol/l. After 24 and 48 hrs of incubation of cells with 15-S-asON, the intracellular concentration of the latter rose to 69.4 and 75.8 nmol/l, respectively, and the HBsAg level assayed by ELISA was reduced by 50.0% and 70.6%, respectively. These results were checked by use of the radioimmunoprecipitation method: 2.2.15 cells exposed to 15-S-asON and labelled with [35S]-methionine for 48 hrs showed a decrease of the HBsAg level by 81.26% but almost none of the total proteins. No cytotoxicity of the 15-S-asON was observed with regard to the cell morphology and growth. These results indicate that the tested antisense oligonucleotide specifically inhibits the HBV gene expression.

Cell Line↗
PubMed1994

[Gene variation in the pre-C region of hepatitis B virus].

We examined the serum HBV DNA of the chronic hepatitis B patients with positive c-system by using polymerase chain reaction (PCR). Twenty samples of HBeAg(+)/anti-HBe(-) positive PCR products and 20 samples of HBeAg(-)/anti-HBe(+) positive PCR products were selected. These products were dot-hybridized by synthetic HBV pre-C region geno oligonucleotide probes M0 (non mutated), M1 (one) point-mutated), M2 (two point-mutated). The results thus obtained showed that for 85% (17/20) of the chronic hepatitis patients with HBeAg(-)/anti-HBe(+), point mutation occurred at the 1,896th nucleotide, resulting in the stop codon, and half (10/20) of the patients suffered two points mutation. The direct determination of the sequence of some mutation PCR products selected proved the existence of point mutation. The result indicated that the natural conversion of hepatitis patients' HBeAg(+) to anti-HBe(+) may have resulted from the genovariation in the pre-c region of HBVDNA rather than from the decreased of virus replication.

Base Sequence↗
PubMed1994

[Inhibition of hepatitis B viral gene expression by antisense phosphrothioate oligonucleotides].

Hep G2 cells transfected with HBV genomes were used to study the inhibitory effect of antisense phosphrothiate oligodeoxynucleotides on HBsAg and HBeAg production. The synthetic antisense 15-s-oligomers against the cap site of mRNA transcribed from the SPII promoter and regions of the translational initiation site of the S gene showed a dose-dependent and sequence-specific inhibitory effect on HBV gene expression between concentrations of 1.0-5.0 mumol/L. But the oligomers directed on the middle site of the S gene exerted little effect on HBsAg and HBeAg expression as well as the non-complementary random sequence control. The cells remained viable throughout the experiments and no morphological abnormalities and cytotoxicity were observed with antisense S-oligomers at concentrations below 20.0 mumol/L. These results suggest a therapeutic potential for antisense oligonucleotides in the treatment of patients who are chronically infected with HBV.

Base Sequence↗
PubMed1993

Purification and characterization of human hepatic stimulator substance.

Human hepatic stimulator substance (hHSS) was purified from fetal liver with 6,000-fold decrease in protein content and 840-fold increase in specific growth stimulative activity. Purification procedures included the heating of a homogenate in 35% (W/V) Tris-HCL at 95 degrees C for 20 min, high and ultra speed centrifugation, passage over Sephadex G100 gel filtration, DEAE-cellulose ion exchange, TSK G3000 SWG high performance liquid chromatography (HPLC) and YWG C-18 reverse phase HPLC techniques. The most purified material (HP-HSS) revealed cell-specific and dose dependent increase in 3H-TdR incorporation into cellular DNA. As little as 38 ng of the HP-HSS per ml of culture medium produced a 2.5-fold increase in DNA synthesis. Further studies indicate that HP-HSS in combination with insulin and epidermal growth factor stimulate DNA synthesis 16-fold compared with serum and hormone free controls and nearly 3-fold over hepatoma growth with HP-HSS alone. Sodium dedecyl sulfate polyacrylamide gel electrophoresis with silver stain and ultrascan XL laser densitrometer quantitative scanning revealed only one band at 12,800.

Carcinoma, Hepatocellular↗
PubMed1992

Hepatic stimulator substance from human fetal liver for treatment of experimental hepatic failure.

The authors previously reported the successful reversal of lethal D-Gal induced hepatic necrosis in rats by human hepatic stimulator substance (hHSS), a liver specific growth factor partially purified from human fetal liver cells, which promoted hepatocyte proliferation. In this study, they further investigated the mechanism of hHSS in improving survival of experimental acute hepatic failure. Our results demonstrated that the level of alanine transaminase and endotoxin in the plasma and lipid peroxides in the liver of chemically poisoned rats were reduced by hHSS to different extent at different periods of observation compared with the saline control group. The apparent recovery of liver function and the increase of 3H-TdR incorporation into hepatic DNA correlated with the morphologic changes observed under light and electron microscopes, showing that the damages inflicted on the cellular and subcellular structure in the liver of hHSS-treated rats were greatly alleviated and rapidly repaired. Therefore, hHSS, which can prevent liver deterioration and promote hepatocyte regeneration, may be a new hepatic stimulator factor readily available for clinical use.

Animals↗
PubMed1990

Human hepatic regenerative stimulator substance: partial purification and biological characterization of hepatic stimulator substance from human fetal liver cells.

Current support or replacement therapies for fulminant acute hepatic failure are frequently very disappointing. In this study, human hepatic stimulator substance--a liver-specific growth factor--was partially purified from human fetal liver cells and characterized by its biological effects. Almost 70-fold protein content was purified with an approximately 80-fold increase in specific growth stimulator activity. Human hepatic stimulator substance proved to be heat-stable, protease-sensitive, organ-specific and species-nonspecific. Human hepatic stimulator substance produced a two- to threefold increase of 3H-thymidine incorporation into hepatic DNA when injected intraperitoneally into growing weanling mice (nonhepatectomized) or regenerating rats (34% hepatectomy). The effects of hHSS in reversing the lethality of D-galactosamine (1.6 gm/kg body weight)-induced hepatic necrosis in rats were further evaluated. A survival rate of 4% (n = 24), 41% (n = 12, p less than 0.05), 33% (n = 12, p less than 0.05), 31% (n = 13, p less than 0.05) and 18% (n = 11, p greater than 0.05) was observed when the rats were injected with 4 ml of saline intraperitoneally, 4 ml of human intact fetal hepatocytes (2.4 x 10(8] intraperitoneally, 4 ml of human hepatic stimulator substance intraperitoneally, 2 ml of twofold concentrated human hepatic stimulator substance intravenously and 1 ml of fourfold human hepatic stimulator substance intramuscularly, respectively, 20 hr after poisoning.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The duration of viremia patients with epidemic hemorrhagic fever.

The duration of viremia in patients with epidemic hemorrhagic fever (EHF) was studied using immunofluorescence technique and cell culture assays. The duration of virus in plasma of EHF patients was about 1 week, which was concomitant with the febrile phase of the disease. Comparatively, the separation rate of viruses in peripheral blood mononuclear cells (PBMC) was greater (1.8 times) than in plasma, while the detected peak of EHF (in 4-7 days after onset of the disease) was found to be 2 or 3 days less than that of plasma, thus the detectable viremia was prolonged until the 8th to 11th day of the disease. High titre EHF antibody of IgG, TgM was unable to neutralize the virus in human blood. The results revealed that a blood-cell-associated prolonged viremia is one of the characteristics of EHF infection.

Antibodies, Viral↗
PubMed1985

Changes in health conditions in the Huainan coal mine in the past three decades.

Health conditions in the Huainan Coal Mine have improved greatly since 1950. In particular, the work and living environments, the underground dust concentration, the water supply and waste disposal systems, and the nutritional value of miners' food have become much better. Thus the rates of occupational, infectious, and parasitic diseases and nutritional deficiency diseases have decreased considerably among miners. The decreases in the prevalence of anthracosilicosis and hookworm have been especially striking.

Anthracosilicosis↗