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Hui Zhuang

Publications and source records attributed to Hui Zhuang.

At least 19 recordsLinked to original sources
PubMed2005

Effects of severe acute respiratory syndrome (SARS) coronavirus infection on peripheral blood lymphocytes and their subsets.

INTRODUCTION: Severe acute respiratory syndrome (SARS) caused large outbreaks of atypical pneumonia in 2003, with the largest localized outbreak occurring in Beijing, China. Lymphopenia was prominent amongst the laboratory abnormalities reported in acute SARS. METHODS: The effect of SARS on peripheral blood lymphocytes and their subsets was examined in 271 SARS coronavirus-infected individuals. RESULTS: There was a significant decrease in the CD45+, CD3+, CD4+, CD8+, CD19+ and CD16+/56+ cell counts over the five weeks of the SARS illness although CD4+/CD8+ ratios did not change significantly. The lymphopenia was prolonged, reaching a nadir during days 7-9 in the second week of illness before returning towards normal after five weeks, with the lowest mean CD4+ cell count of 317 cellsx10(6)/L at day 7, and CD8+ cell count of 239 cellsx10(6)/L at day 8. Patients with more severe clinical illness, or patients who died, had significantly more profound CD4+ and CD8+ lymphopenia. DISCUSSION: Lymphopenia is a prominent part of SARS-CoV infection and lymphocyte counts may be useful in predicting the severity and clinical outcomes. Possible reasons for the SARS-associated lymphopenia may be direct infection of lymphocytes by SARS-CoV, lymphocyte sequestration in the lung or cytokine-mediated lymphocyte trafficking. There may also be immune-mediated lymphocyte destruction, bone marrow or thymus suppression, or apoptosis.

Adolescent↗
PubMed2005

Multiple organ infection and the pathogenesis of SARS.

After >8,000 infections and >700 deaths worldwide, the pathogenesis of the new infectious disease, severe acute respiratory syndrome (SARS), remains poorly understood. We investigated 18 autopsies of patients who had suspected SARS; 8 cases were confirmed as SARS. We evaluated white blood cells from 22 confirmed SARS patients at various stages of the disease. T lymphocyte counts in 65 confirmed and 35 misdiagnosed SARS cases also were analyzed retrospectively. SARS viral particles and genomic sequence were detected in a large number of circulating lymphocytes, monocytes, and lymphoid tissues, as well as in the epithelial cells of the respiratory tract, the mucosa of the intestine, the epithelium of the renal distal tubules, the neurons of the brain, and macrophages in different organs. SARS virus seemed to be capable of infecting multiple cell types in several organs; immune cells and pulmonary epithelium were identified as the main sites of injury. A comprehensive theory of pathogenesis is proposed for SARS with immune and lung damage as key features.

Adult↗
PubMed2005

Detection of the nucleocapsid protein of severe acute respiratory syndrome coronavirus in serum: comparison with results of other viral markers.

A capture enzyme-enhanced chemiluminescence immunoassay (ECLIA) based on three specific monoclonal antibodies to detect the nucleocapsid (N) protein of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in the serial serum samples from SARS patients was developed. The anti-SARS-CoV IgG and the viral RNA were also detected in the sera by ELISA and RT-PCR, respectively. During the first 10 days after onset, anti-SARS-CoV IgG, SARS-CoV RNA and the N protein were detected in 21.4, 42.9, and 90% of the patients' sera, respectively. The detection rate of the N protein during days 11-15 of the disease was still significantly higher than those of anti-SARS-CoV IgG and SARS-CoV RNA. The data demonstrated that detection of the N protein with the capture ECLIA appears to be more useful than detection of other viral makers for rapid diagnosis of SARS in patients.

Adult↗
PubMed2005

Combinatorial approach to identification of tyrphostin inhibitors of cytokine signaling.

Aberrant or deregulated activity of certain cellular kinases has been shown to cause certain malignancies and other disorders. The tyrphostin molecule AG490 inhibits the action of the janus kinases JAK2 and JAK3. JAK2 is an indispensable molecule for transducing the signals conveyed by a large number of cytokines including IL-3 while JAK3 is essential for signaling by a smaller number of cytokines including IL-7. A synthetic combinatorial chemical library containing 599 compounds was created and screened for the ability to inhibit proliferation of IL3- and IL7-dependent cell lines to focus on molecules that interrupt those signaling pathways. This screen identified a meta-trifluoromethyl derivative of AG490, 5H4, that is approximately twice as potent as AG490 in cell-based assays. 5H4 blocked the factor-dependent proliferation of both of these cell lines, actively promoted cell death, and diminished the JAK kinase activity. Administration of 5H4 to lymphoma-prone IL-7 transgenic mice reduced their spontaneous lymphadenopathy. The improved characteristics of this novel compound bring this class of molecules closer to therapeutic utility.

Animals↗
PubMed2005

Analysis of hepatitis E virus neutralization sites using monoclonal antibodies directed against a virus capsid protein.

The dimeric form of the recombinant peptide (E2), comprising amino acid 394-606 of the capsid protein of hepatitis E virus (HEV), is strongly recognized by HEV reactive human serum, and when used as a vaccine, it protects rhesus monkeys against experimental HEV infection. In this work, the relationship of E2 to HEV has been probed using three murine monoclonal antibodies, 8C11, 13D8 and 8H3, all of which react predominantly against the E2 dimer, and can effect immune capture of the virus as well. 8C11 and 8H3 were further found to neutralize HEV infectivity in animals. Cross-blocking patterns between these antibodies discerned two spatially separate antigenic domains, one identified by 8C11 and 13D8, and the other, by 8H3. Kinetic studies using BIAcore biosensor suggest that the epitope to which 8H3 is directed is partially masked, and thus has limited access by the native antibody. However, this is not the case with the smaller Fab. Access to the 8H3 epitope was enhanced by the binding of 8C11, and inhibited by the binding of 13D8 to a distal site on the peptide. Similar to the effects of binding 8H3 to E2, 8C11 was found to enhance immune capture by 8H3, while 13D8 was inhibitory. Moreover, 8C11 and 8H3 act synergistically to neutralize HEV infectivity. The parallel cross-reaction patterns that these antibodies exhibit against the peptide and the virus, respectively, implicate two interacting conformationally dependent neutralization sites on the HEV particle. These sites might cooperate in the adsorption and penetration of the HEV virus.

Animals↗
PubMed2005

Nonstructural 5A gene variability of hepatitis C virus (HCV) during a 10-year follow up.

BACKGROUND: Seven patients with chronic hepatitis C virus (HCV) infection were followed up for 10 years in order to analyze the molecular evolution of the HCV nonstructural 5A (NS5A) gene. METHODS: Serum samples were obtained from seven patients with anti-HCV who were HCV-RNA positive. The HCV NS5A region, including the interferon sensitivity-determining region (ISDR), protein kinase R binding domain (PKR-BD), and V3 was amplified and cloned, and then sequenced. The nucleotide sequences of the region at the beginning and at the end of the 10 years were aligned with the CLUSTAL W program, version 1.8, and the corresponding amino-acid sequences were deduced. RESULTS: The three serine residues at positions 2197, 2201, and 2204, suggested to be important for hyperphosphorylation of NS5A, were highly conserved in different patients and were within the quasispecies of each patient. The wild-type ISDR or minimally mutated strain was dominant in all the patients and the number of quasispecies decreased over time. CONCLUSIONS: Our findings showed that the functional domains of NS5A were generally conserved over an interval of 10 years. Quasispecies distribution was variable and distinctly clustered over time during the natural course of HCV infection. These results may contribute to better understanding of HCV natural infection.

Adult↗
PubMed2005

Development and evaluation of an enzyme-linked immunosorbent assay for detection of antibodies against the spike protein of SARS-coronavirus.

BACKGROUND: Severe acute respiratory syndrome (SARS) is caused by infection with SARS-associated coronavirus (CoV). Amino acid residues 450-650 of the spike (S) glycoprotein of SARS-CoV (S450-650) contains dominant epitopes for anti-viral antibodies (Abs) in patient sera. OBJECTIVES: To develop and evaluate an ELISA system for detection of anti-S Abs in patient sera. STUDY DESIGN: Express recombinant S450-650 in E. Coli and evaluate the sensitivity and specificity of an ELISA system based on the S450-650 polypeptide. RESULTS: The S450-650-based ELISA detected IgG Abs in 41 out of 51 serum samples from 22 hospitalized patients with probable SARS, a result closely correlated with that obtained with a virus-based ELISA (r = 0.75, k = 0.8). Differential anti-S IgG responses were observed amongst SARS patients. Some of them produced anti-S Abs early during their infection, while others failed to make IgG Abs against the S450-650 polypeptide. None of the serum samples from 100 healthy blood donors was positive in the S450-650-based assay. CONCLUSION: The S450-650-based ELISA can detect anti-S IgG Abs with high sensitivity and specificity.

Adolescent↗
PubMed2005

Decreased numbers and impaired function of circulating dendritic cell subsets in patients with chronic hepatitis B infection (R2).

BACKGROUND AND AIM: To investigate the frequencies, numbers and function of circulating dendritic cell (DC) subsets in patients with hepatitis B virus (HBV) infection, we assayed the circulating precursor DC subsets (including pDC1 and pDC2) and their ability in patients at various stages of HBV infection in vitro. METHODS: Circulating pDC1 and pDC2 frequencies in peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometric analysis. Costimulatory molecule expression and allostimulatory mixed lymphocyte reaction (AMLR) of DC1, cultured from PBMC in vitro, were detected in patients with chronic hepatitis B (CHB). On behalf of pDC2, interferon (IFN)-alpha production of PBMC was determined by the ELISA method in HBV-infected patients. RESULTS: The number of circulating pDC1 decreased only in patients with liver cirrhosis (LC) compared with that in normal controls. However, pDC2 numbers decreased in both CHB and LC patients. DC1 from CHB patients showed lower expression of costimulatory molecules CD80, CD86 and impaired allostimulatory mixed lymphocyte reaction (AMLR) compared with those in normal controls. The ability of PBMC to secrete IFN-alpha also decreased significantly in patients with chronic HBV infection. CONCLUSIONS: Our results suggest that patients with chronic HBV infection have a significantly lower expression of costimulatory molecules and impaired AMLR of pDC1, as well as decreased number and impaired function of circulating pDC2, which may be partially related to HBV disease progression in these patients.

Adult↗
PubMed2005

Significance of the signal-to-cutoff ratios of anti-hepatitis C virus enzyme immunoassays in screening of Chinese blood donors.

BACKGROUND: The correlation between signal-to-cutoff (S/CO) ratios of a second-generation hepatitis C virus (HCV) enzyme immunoassay (EIA; Abbott) and a third-generation HCV enzyme-linked immunosorbent assay (ELISA; Ortho) and confirmed HCV infection has been reported. The utility of the values for the Chinese anti-HCV EIA kits, however, has not been studied in evaluating test results in Chinese blood donors. STUDY DESIGN AND METHODS: A total of 156 donor samples repeat reactive for anti-HCV at routine screening from five representative regions of China were retested for anti-HCV by the Ortho third-generation HCV ELISA and six Chinese EIA kits and for HCV RNA by a human immunodeficiency virus-1 and HCV assay (Procleix, Chiron Corp.). The HCV RNA-nonreactive samples were further tested for anti-HCV by a third-generation recombinant immunoblot assay RIBA (Chiron Corp.). The positive result by either nucleic acid amplification test or RIBA was interpreted as confirmed HCV infection. RESULTS: The confirmed HCV prevalence rate in donors in five representative regions obtained in this study was 0.20 percent (77/37,900) in 2004. All seven anti-HCV EIA kits had a significant correlation between S/CO ratios and confirmed HCV infection. The threshold S/CO ratios, which predicted more than 95 percent of confirmed HCV infections for the Ortho, SABC, BGI-GBI, InTec, GWK, KHB, and WANTAI kits, were 3.8, 6.0, 7.0, 8.6, 10.0, 10.0, and 14.0, respectively. CONCLUSIONS: Anti-HCV EIA kits commonly used in Chinese donors screening demonstrate good correlation between S/CO ratios and the confirmed infection. For the Ortho third-generation HCV ELISA, the S/CO ratio of 3.8 determined by the US Centers for Disease Control and Prevention is applicable to Chinese blood donors. The Chinese domestic EIA kits evaluated show a diverse range of threshold S/CO ratios.

Blood Donors↗
PubMed2005

[Immunological characteristics of primary biliary cirrhosis patients].

OBJECTIVE: To study the clinical significance of the immunological characteristics in patients with primary biliary cirrhosis (PBC). METHODS: 3000 patients with abnormal liver functions were examined for anti-nuclear antibodies (ANA), anti-mitochondrial antibodies (AMA), anti-smooth muscle antibodies (SMA) and anti-liver kidney microsomal antibody (LKM) using immunofluorescent assays (IFA). LKM-1, liver cytosolic-1 (LC-1), soluble liver antigen (SLA)/liver- pancreas antigen (LP) and subtype of AMA (M2, M4, M9) as well as ANA profile were detected by an immune blotting assay and an enzyme-linked immune absorbent assay (ELISA), respectively. Cytokines were tested by flow cytometry. RESULTS: Of the 3000 patients with liver diseases, 52 (1.7%) were diagnosed with PBC. All the PBC cases were positive for AMA and M2. 94% of them showed high titer of AMA (> or = 1:320), and in 79% of them M2 was >200 RU/L, and 78% of them were ANA positive. Three main fluorescent patterns of ANA seen were nuclear membrane, nuclear dots and centromere patterns. Sjogren's Syndrome A/B (SS-A/B), homogenous, nucleolar or nuclear granular patterns were seen in only a few patients. IgM, ALP and GGT in PBC patients were significantly higher than those in hepatitis B related liver cirrhosis patients. The levels of IL-6, IL-10, TNF-alpha and IFN-gamma in PBC patients were higher than in the normal controls. Among the 52 PBC patients, 5 had autoimmune liver disease overlap syndromes. Two of them were SLA/LP positive, indicated as AIH type III and PBC overlapping, and 1 was LKM-1 positive showing AIH type II overlapping PBC, and 2 had ANA positive and were identified as AIH and PBC by liver biopsy. CONCLUSION: The percentage of PBC in Chinese liver disease patients is about 1% to 2%. Most of the PBC patients have high levels of AMA and AMA-M2, IgM, ALP, GGT and several cytokines, indicating that abnormality of humeral and cellular immunity may be associated with the pathogenesis of PBC.

Adult↗
PubMed2005

[Correlation between signal/cutoff ratios of anti-HCV enzyme immunoassay (EIA) and their true positivity in blood donors].

OBJECTIVES: To evaluate the correlation between signal/cutoff (S/CO) ratios of anti-HCV EIA and their true positivity for determining the predictive value of S/CO ratios. METHODS: One hundred and fifty-nine samples of blood from donors positive for anti-HCV at the initial screening were collected from Beijing, Guangzhou, Hangzhou, Kunming and Urumchi. All the samples were retested by Ortho and 6 Chinese domestic anti-HCV EIA kits in duplicate, and detected for HCV RNA (NAT) using Chiron Procleix HIV/HCV system (transcription mediated amplification, TMA). The HCV RNA negative samples were further tested for anti-HCV by Chiron RIBA 3.0. Either NAT or RIBA positive samples were interpreted as the true positive. RESULTS: All 7 anti-HCV EIA kits had a significant correlation between S/CO ratios and true positivity. The S/CO ratio of Ortho > or = 3.8 predicted the true positivity in 96.1% of the samples tested. The S/CO ratios of BGI-GBI, GWK, SABC, KHB, InTec, and Wantai were > or = 7.0, > or = 10.0, > or = 6.0, > or = 10.0, > or = 8.6, > or = 14.0 and predicted 96.1%, 96.1%, 97.3%, 96.0%, 96.1%, 96.0% of the true positivity, respectively. CONCLUSIONS: The S/CO ratios of anti-HCV EIA kits are associated with the true positivity. S/CO ratios of Ortho, BGI-GBI, GWK, SABC, KHB, InTec and Wantai predicting > or = 95% true positivity are > or = 3.8, > or = 7.0, > or = 10.0, > or = 6.0, > or = 1 0.0, > or = 8.6 and > or = 14.0, respectively.

Blood Donors↗
PubMed2005

[Relationship between B virus hepatitis genotypes and therapeutic efficacy in early treatment for chronic hepatitis B by using lamivudine].

OBJECTIVE: To investigate the relationship between hepatitis B virus (HBV) genotype and therapeutic efficacy during the early phase of lamivudine treatment. METHODS: Totally 595 patients with chronic hepatitis B were treated with lamivudine 100 mg/day for 12 months. HBV genotypes, contents of HBV DNA, HBeAg/anti-HBe and YMDD mutation after lamivudine treatment for 12 months were determined. The data were analyzed with SPSS software. RESULTS: In 595 patients, 8 (1.4%) were genotype A; 53 (8.9%) genotype B; 360 (60.5%) genotype C; 112 (18.8%) were coinfection of genotype B and C; 14 (2.4%) of A and C; 15 (2.5%) A and B; 6 (1.0%) of A, B, and C, and remaining 27 (4.5%) were unspecified. Patients were treated with lamivudine 100 mg/day for 12 months. Genotype B with HBV DNA levels turned to be negative (HBV DNA < 0.1 ng/L) was 87.2%, genotype C was 89.51%, coinfection of genotype B and C was 93.04% (P > 0.05). HBeAg seroconversion of genotype B was 11.65%, of genotype C was 20.64%, and of coinfection of genotype B and C was 18.57% (P > 0.05). All 69 strains of YMDD mutation were detected after lamivudine treatment for 12 months, in which genotype B was in 16.98%, genotype C in 15.38%, and coinfection of genotype B and C was in 13.86% (P > 0.05). CONCLUSION: There was no difference in HBV genotypes and the rate of development of YMDD mutations, HBeAg seroconversion, descending of HBV DNA level in Chinese patients with chronic hepatitis B.

China↗
PubMed2005

[Hepatitis B virus genotypes and alanine aminotransferase levels in HBeAg negative patients with chronic hepatitis B and liver cirrhosis].

OBJECTIVE: To investigate genotypes of the hepatitis B virus (HBV) and alanine aminotransferase (ALT) levels of HBeAg negative patients with chronic hepatitis B and liver cirrhosis. METHODS: HBV serological markers and ALT levels were detected in 62 patients with chronic hepatitis B and 41 cases with liver cirrhosis, using enzyme linked absorbent immunoassays and an enzyme method, respectively. A polymerase chain reaction of S region was used for HBV genotyping. RESULTS: Of the 62 patients with chronic hepatitis B, 21 (33.9%) were HBeAg negative, and 41 (66.1%) HBeAg positive. Among 41 cases with liver cirrhosis, 28 (68.3%) were HBeAg negative, and 13 (31.7%) HBeAg positive. Of these 62 patients with chronic hepatitis B, 53 (85.5%) were infected with HBV genotype C, and 9 (14.5%) with genotype B. Thirty-nine (95.1%) of the 41 patients with liver cirrhosis were infected with genotype C, and 2 (4.9%) with genotype B. The proportion of HBeAg negative chronic hepatitis B patients with ALT level > 40 U/L was lower than that of the HBeAg positive group (47.6% and 85.4%, respectively) (P < 0.01). The percentage of ALT levels > 40 U/L of the negative patients with liver cirrhosis was also lower as compared to that of the HBeAg positive patients, but there was no statistical difference between the two groups, because of the small sample size (P > 0.05). CONCLUSION: The proportion of HBeAg negative patients is high in the group of chronic hepatitis B and liver cirrhosis. These patients have relatively low ALT levels, and mainly have HBV genotype C infection.

Alanine Transaminase↗
PubMed2005

[Distribution and clinical significance of hepatitis B virus (HBV) genotypes and subtypes in HBV-infected patients].

OBJECTIVE: To study hepatitis B virus (HBV) genotype and subtype distribution and its clinical significance in HBV-infected patients. METHODS: We used type/subtype-specific primers and PCR to detect HBV genotype and subtype of 445 HBV-infected patients from Beijing, Changchun, Hanchuan Shenzhen, Qingyuan and Nanjing, including 7 acute hepatitis (AH), 36 asymptomatic HBV carriers (ASC), 352 chronic hepatitis (CH), 28 liver cirrhosis (LC), and 22 hepatocellular carcinoma (HCC) cases. Genotyping results were confirmed by PCR product sequencing. RESULTS: Among 445 HBV-infected patients, the proportions of genotype B, C, and B/C were 32.6% (145/445), 53.7% (239/445), and 13.7% (61/445), respectively. In genotype C, 13 (5.4%) were subtype C1, 135 (56.5%) were subtype C2, and the remaining 91 (38.1%) were neither C1 nor C2. In genotype B, 100 (69.0%) were subtype Ba, 25 (17.2%) subtype Bj, and the other 20 (13.8%) were neither Ba nor Bj. In genotype B/C, 15 (24.6%) were Ba/C2, 8 (13.1%) Bj/C2, 6 (9.8%) Ba/C1, 3 (4.9%) Bj/C1, 11 (18.0%) Ba/neither C1 nor C2, 7 (11.5%) Bj/neither C1 nor C2, and 6 (9.8%) neither Ba nor Bj/neither C1 nor C2, 2 (3.3%) neither Ba nor Bj/C1, 3 (4.9%) neither Ba nor Bj/C2. The HBV genotype and subtype distribution we found exhibited significant differences in the various clinical types of HBV infection tested, and showed that genotype C was predominant among patients with liver cirrhosis (78.6%) and hepatocellular carcinoma (86.4%) while genotype B was predominant in asymptomatic carriers (72.2%). In addition, genotype and subtype distribution showed no significant differences between male and female patients, but genotype and subtype distribution showed significant differences in patients positive or negative with HBeAg. CONCLUSION: Subtypes Ba and C2 are predominant in patients with hepatitis B from these 6 cities, and genotype C may be associated with the development of liver cirrhosis and hepatocellular carcinoma.

Genotype↗
PubMed2004

Hepatitis B virus genotypes, phylogeny and occult infection in a region with a high incidence of hepatocellular carcinoma in China.

AIM: To determine the genotypes and phylogeny of hepatitis B viruses (HBVs) in asymptomatic HBV carriers, and the prevalence of occult HBV infection in Long An County, Guangxi Zhuang Autonomous Region, an area with a high incidence of hepatocellular carcinoma. METHODS: A nested polymerase chain reaction (nPCR) was used for detection of HBV DNA in serum samples from 36 blood donors with asympmatic HBV infection, and in serum samples from 52 HBsAg negative family members of the children who did not receive hepatitis B vaccination in Long An County. PCR products were sequenced, and the genotype of each HBV sequence was determined by comparison with sequences of known genotypes in the GenBank and EMBL nucleotide databases using the BLAST programme. Phylogenetic trees were constructed by the quartet maximum likelihood analysis using the TreePuzzle software. RESULTS: Twenty (55.56%) of 36 HBV asymptomatic carriers were positive for HBV DNA. They were all genotype C by comparison with sequences of known genotypes in the GenBank and EMBL nucleotide databases. The full-length HBV DNA sequence isolated from the sample No. 624 contained 3 215 bases. No interesting mutations were found in this isolate. The homology analysis showed that this strain was closer to the Vietnamese HBV genotype C strain, with a homology of 97%, compared its relation to the same genotype of HBV isolated in Shanghai. Six (11.5%) of the 52 HBsAg negative family members were positive for HBV DNA. A point mutation was found in the sample No. 37, resulting in the substitution of amino acid glycine to arginine in the "a" determinant. Other samples with positive HBV DNA did not have any unusual amino acid substitutions in or around the "a" determinant, and were attributed to the wild-type HBV. CONCLUSION: The HBVs isolated from asymptomatic carriers of Long An County were all identified as genotype C, and the prevalence of occult HBV infection in the population of the county is as high as 11.5%. It is suggested that genotype C and persistent occult HBV infection may play an important role in the development of HCC in the county.

Adolescent↗