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Biomedical subjects

L Y Kang

Publications and source records attributed to L Y Kang.

At least 19 recordsLinked to original sources
PubMed2005

Cost effectiveness and delivery study for future HIV vaccines.

Research teams from five countries, Brazil, China, Kenya, Peru and Thailand, have initiated a policy-maker survey on vaccine delivery, cost studies for future HIV vaccination programmes, and associated simulation modeling exercises analysing the relative cost-effectiveness of potential HIV vaccination strategies. The survey assesses challenges and opportunities for future country-level HIV vaccination strategies, providing data on the vaccine characteristics (e.g. vaccine efficacies for susceptibility, infectiousness and disease progression) and vaccination programme strategies to be considered in the cost-effectiveness modeling analyses. The study will provide decision-makers with modeling data on vaccination policy considerations that will assist in developing country-level capacities for future HIV vaccine policy adoption and effective delivery systems, and will help delineate the long-term financial requirements for sustainable HIV vaccination programmes. The WHO-UNAIDS HIV Vaccine Initiative and the collaborating researchers welcome comments or questions from policy makers, health professionals and other stakeholders in the public and private sectors about this effort to help advance policy and capacity related to future potential HIV vaccines.

AIDS Vaccines↗
PubMed1999

Prevalence of TT virus and GBV-C infections among patients with liver diseases and the general population in Shanghai, China.

To determine the prevalence of TT virus (TTV) and GB virus C/hepatitis G virus (GBV-C) infections among patients with liver disease and the general population in Shanghai, China, we studied 90 patients with liver diseases (acute hepatitis, 28; chronic hepatitis, 27; liver cirrhosis, 20; hepatocellular carcinoma, 15) and 90 age, sex matched healthy blood donors as controls. There were no significant differences in the clinical and demographic characteristics between the two groups, except for liver function test values. There was a statistical difference between the patient group and the control group with regard to the prevalence of TTV DNA (23.5% in patient group, 11.1% in control group, P < 0.05), although no differences in clinical features could be found between TTV DNA-positive and negative subjects. Also, no differences in TTV DNA prevalence among various categories of liver diseases were noted (P = NS). The prevalence of HBsAg was significantly different between the patient group (36.7%) and the control group (3.3%) (P0.01), whereas the prevalence of anti-HCV and GBV-C RNA were not significantly different between the two groups. The nucleotide sequences were determined in the TTV DNA-positive samples and evaluated using phylogenetic analysis which suggested that they could be divided into two main genotypes designated as genotype 1 and 2. There were five samples clustered into 3 hitherto unknown subtypes of genotype 2. We concluded that (1) although TTV infection is widespread among both groups and there is a statistical difference of TTV infection between them, no hepatic damaging evidence and correlation with certain liver disease could be found in this study, suggest that TTV may not be major cause of liver disease, (2) GBV-C infection is frequent, but the virus is not the cause of liver diseases, and (3) new subtypes of TTV may exist in Shanghai, China.

Adult↗
PubMed1999

Chinese herbal formula XQ-9302: pilot study of its clinical and in vitro activity against human immunodeficiency virus.

OBJECTIVES: To evaluate the effectiveness of XQ-9302--a purified, precise mixture of 20 Chinese herbs--against infection with human immunodeficiency virus in vitro and in the clinic. DESIGN: In vitro cell culture assay, heavy metal content analysis, and pilot non-randomised clinical trial. SETTING: Drug rehabilitation centre and municipal surveillance centre, Shanghai, China. PATIENTS: Forty-eight patients who had various clinical histories, such as drug abuse, cancer, and infection with human immunodeficiency virus, participated in the clinical study. INTERVENTION: During the clinical trial, multiple 15-day courses of XQ-9302 10.8 g/d were given to participants. MAIN OUTCOME MEASURES: CD4 count, P24 antigen level, level of antibody against human immunodeficiency virus, number of copies per millilitre of human immunodeficiency virus in the plasma (viral load), and any side effects. RESULTS: XQ-9302 protected cultured MT4 cells from infection with human immunodeficiency virus in vitro. Clinical tests showed that the herbal formula relieved the symptoms of acquired immunodeficiency syndrome and enhanced CD4 counts in patients infected by the human immunodeficiency virus. There were no observable side effects, even after taking the drug for several months. In three patients who had acquired immunodeficiency syndrome, treatment with XQ-9302 reduced the magnitude of the viral load by more than 1 log. CONCLUSION: XQ-9302 not only improves the immune function of patients infected with the human immunodeficiency virus, but also interrupts viral replication and slows the progression of the disease without detectable side effects. In addition, the heavy metal content of XQ-9302 is well within safety levels set by the Government of China.

Journal Article↗
PubMed1996

Multiple transcription factors are required for activation of human interleukin 9 gene in T cells.

The genetic elements and regulatory mechanisms responsible for human interleukin 9 (IL-9) gene expression in a human T cell leukemia virus type I-transformed human T cell line, C5MJ2, were investigated. We demonstrated that IL-9 gene expression is controlled, at least in part, by transcriptional activation. Transient expression of the luciferase reporter gene linked to serially deleted sequences of the 5'-flanking region of the IL-9 gene has revealed several positive and negative regulatory elements involved in the basal and inducible expression of the IL-9 gene in C5MJ2 cells. An AP-1 site at -146 to -140 was shown to be involved in the expression of the IL-9 gene. A proximal region between -46 and -80 was identified as the minimum sequence for the basal and inducible expression of the IL-9 gene in C5MJ2 cells. Within this region, an NF-kappaB site at -59 to -50 and its adjacent 20-base pair upstream sequence were demonstrated to play a critical role for the IL-9 promoter activity. DNA-protein binding studies indicated that NF-kappaB, c-Jun, and potentially novel proteins (around 35 kDa) can bind to this important sequence. Mutations at different sites within this proximal promoter region abolished the promoter activity as well as the DNA binding. Taken together, these results suggest that the cooperation of different transcription factors is essential for IL-9 gene expression in T cells.

Base Sequence↗
PubMed1996

Differential expression in human cells from the p6 promoter of human parvovirus B19 following plasmid transfection and recombinant adeno-associated virus 2 (AAV) infection: human megakaryocytic leukaemia cells are non-permissive for AAV infection.

Expression from the human parvovirus B19p6 promoter fused to the firefly luciferase ('Luc') reporter gene was evaluated in a non-erythroid human nasopharyngeal carcinoma cell line, KB, and a human megakaryocytic leukaemia cell line, MB-02, known to become permissive for B19 replication following erythroid-differentiation. The B19p6-Luc construct was introduced into KB and MB-02 cells, both in undifferentiated and differentiated states, either via DNA-mediated transfection, or via infection with recombinant adeno-associated virus 2 (AAV), a non-pathogenic human parvovirus known to possess a broad host-range. Although Luc activity was readily detected in KB cells following transfection of the B19p6-Luc plasmid DNA, no expression from the B19p6 promoter was observed following infection with recombinant virus. In addition, transfection of the reporter plasmid resulted in high-level expression of Luc in differentiated but not in undifferentiated MB-02 cells. However, no Luc activity was detected, even in differentiated MB-02 cells, following infection with recombinant virus. Further studies with an additional recombinant as well as wild-type (wt) AAV revealed that MB-02 cells were non-permissive for AAV infection. A second human megakaryocytic leukaemia cell line, M07e, was likewise resistant to infection by recombinant as well as wt AAV. Taken together, these studies identify the first human cell type that cannot be infected by AAV. They indicate that expression from the B19p6 promoter, in the context of an AAV genome, is restricted to primary human haematopoietic cells, perhaps because parvoviral DNA replication and transcription are intrinsically coupled.

Cell Differentiation↗
PubMed1995

Activation of junB and c-myc primary response genes by interleukin 9 in a human factor-dependent cell line.

Interleukin 9 (IL-9) stimulates the proliferation of various hematopoietic cell types. To elucidate the molecular mechanisms underlying the cell proliferation action, immediate-early gene expression elicited by IL-9 in a human factor-dependent cell line, MO7e, was studied. IL-9 stimulation resulted in a rapid and transient elevation of primary response genes including junB and c-myc. The differential effects of protein kinase inhibitors, herbimycin A, genistein, and H-7 on the steady-state mRNA level and the transcription rate of junB and c-myc genes triggered by IL-9 were also investigated. Herbimycin A, but not genistein, specifically inhibited the expression of junB steady-state mRNA and the in vitro transcription of the junB gene. IL-9-enhanced c-myc gene expression was completely inhibited by both herbimycin A and genistein at the level of transcriptional initiation. H-7 failed to inhibit c-myc, but partially abolished junB mRNA induction. The role of protein kinase C in IL-9-mediated junB induction was also examined. The different responses of junB and c-myc messages to protein kinase inhibitors suggested that more than one pathway may be involved in IL-9-mediated signal transduction which leads to the expression of junB and c-myc genes.

Benzoquinones↗
PubMed1995

Molecular and functional interactions of transcription factor USF with the long terminal repeat of human immunodeficiency virus type 1.

The human transcription factor USF, purified from HeLa cells, and its recombinant 43-kDa component bind to the long terminal repeat (LTR) of human immunodeficiency virus type 1. The proteins footprint over nucleotides from position -173 to -157 upstream of the transcription start site, generating strong DNAse I hypersensitivity sites at the 3' sides on both strands. As detected by methylation protection studies, the factor forms symmetric contacts with the guanines of the palindromic CACGTG core of the recognized sequence. Its binding ability is abolished by the mutation of this core sequence and is strongly reduced by the cytosine methylation of the central CpG dinucleotide. Upon binding, both recombinant and purified USFs bend the LTR DNA template. The role of USF in the control of transcription initiation from the LTR was tested by in vitro transcription assays. Upon addition of the protein, transcription from constructs containing an intact binding site is increased, while the responsiveness in constructs with a mutated sequence is abolished. Furthermore, the addition of a decoy plasmid which contains multiple repeats of the target sequence results in downregulation of transcription from the LTR. These results suggest that USF is a positive regulator of LTR-mediated transcriptional activation.

Base Sequence↗
PubMed1994

Adeno-associated virus 2-mediated high efficiency gene transfer into immature and mature subsets of hematopoietic progenitor cells in human umbilical cord blood.

Recombinant adeno-associated virus 2 (AAV) virions were constructed containing a gene for resistance to neomycin (neoR), under the control of either the herpesvirus thymidine kinase (TK) gene promoter (vTK-Neo), or the human parvovirus B19 p6 promoter (vB19-Neo), as well as those containing an upstream erythroid cell-specific enhancer (HS-2) from the locus control region of the human beta-globin gene cluster (vHS2-TK-Neo; vHS2-B19-Neo). These recombinant virions were used to infect either low density or highly enriched populations of CD34+ cells isolated from human umbilical cord blood. In clonogenic assays initiated with cells infected with the different recombinant AAV-Neo virions, equivalent high frequency transduction of the neoR gene into slow-cycling multipotential, erythroid, and granulocyte/macrophage (GM) progenitor cells, including those with high proliferative potential, was obtained without prestimulation with growth factors, indicating that these immature and mature hematopoietic progenitor cells were susceptible to infection by the recombinant AAV virions. Successful transduction did not require and was not enhanced by prestimulation of these cell populations with cytokines. The functional activity of the transduced neo gene was evident by the development of resistance to the drug G418, a neomycin analogue. Individual high and low proliferative colony-forming unit (CFU)-GM, burst-forming unit-erythroid, and CFU-granulocyte erythroid macrophage megakaryocyte colonies from mock-infected, or the recombinant virus-infected cultures were subjected to polymerase chain reaction analysis using a neo-specific synthetic oligonucleotide primer pair. A 276-bp DNA fragment that hybridized with a neo-specific DNA probe on Southern blots was only detected in those colonies cloned from the recombinant virus-infected cells, indicating stable integration of the transduced neo gene. These studies suggest that parvovirus-based vectors may prove to be a useful alternative to the more commonly used retroviral vectors for high efficiency gene transfer into slow or noncycling primitive hematopoietic progenitor cells, without the need for growth factor stimulation, which could potentially lead to differentiation of these cells before transplantation.

Antigens, CD↗
PubMed1992

An efficacy trial of a mammalian cell-derived recombinant DNA hepatitis B vaccine in infants born to mothers positive for HBsAg, in Shanghai, China.

We conducted a randomized, double-blind clinical trial of an experimental mammalian cell-derived DNA hepatitis B vaccine (Betagen, Connaught Laboratories Ltd, Toronto, Canada) to determine its efficacy in infants born to mothers who were carriers of hepatitis B surface antigen (HBsAg). Four groups of 55 infants received injections as follows: (1) a licensed plasma-derived vaccine (Lanzhou, Lanzhou Institute for Biological Products, Lanzhou, People's Republic of China), 20 micrograms; (2) Betagen, 20 micrograms; (3) Betagen, 20 micrograms+hepatitis B immune globulin (HBIG); and (4) Betagen, 10 micrograms+HBIG. Vaccine injections were given at birth and at 1 and 6 months and HBIG was given at birth. The vaccines were compared to a historical placebo control group. The efficacy of Betagen alone was 82.6% compared to 51.0% for the Lanzhou. Efficacy of Betagen increased with the concomitant use of HBIG. No infants who were HBsAg negative at birth and/or were born to hepatitis B e antigen (HBeAg) negative mothers became carriers. The rate of HBsAg in infants receiving Betagen alone, and born to mothers who were HBeAg positive, decreased from 60% at birth to 20% by the ninth month, compared to 62.5% and 50% (respectively) for Lanzhou. The percentage of infants with protective levels of antiHBs was significantly higher for Betagen alone than for Lanzhou, but the geometric mean titre of antiHBs for responders was not significantly different. We have shown that Betagen alone is highly efficacious in preventing the development of hepatitis B in infants born to mothers who are carriers of HBsAg and is also highly effective in reducing the carriage of HBsAg in infants who are HBsAg positive at birth and/or born to HBeAg positive mothers.

Carrier State↗
PubMed1991

An epidemic of hepatitis A attributable to the ingestion of raw clams in Shanghai, China.

An epidemic of hepatitis A in 1988 in Shanghai had an overall attack rate of 4083/100,000 population (292,301 cases). The epidemic curve showed three peaks in January and February. A case-control study of 1208 matched pairs supported that clams were the vehicle for the virus (summary odds ratio, 9.47; P less than .001). Analysis of subsets who had eaten clams indicated that only 3.5% with hepatitis A had cooked their clams compared with 18.1% without hepatitis A, and those with the disease consumed more clams. A historical cohort study indicated that approximately 31.7% of the population had eaten clams one or more times between 9 December 1987 and 3 January 1988. The estimated attack rates in those who had and had not eaten clams were 11.93% and 0.52%, respectively (relative risk, 22.94; attributable risk, 11.41%). The three peaks in the consumption curve correlated with those in the epidemic curve. Hepatitis A virus was demonstrated in clams taken from the Shanghai markets and from the catching area.

Acute Disease↗
PubMed1990

A DNA helicase from human cells.

We have initiated the characterization of the DNA helicases from HeLa cells, and we have observed at least 4 molecular species as judged by their different fractionation properties. One of these only, DNA helicase I, has been purified to homogeneity and characterized. Helicase activity was measured by assaying the unwinding of a radioactively labelled oligodeoxynucleotide (17 mer) annealed to M13 DNA. The apparent molecular weight of helicase I on SDS polyacrylamide gel electrophoresis is 65 kDa. Helicase I reaction requires a divalent cation for activity (Mg2+ greater than Mn2+ greater than Ca2+) and is dependent on hydrolysis of ATP or dATP. CTP, GTP, UTP, dCTP, dGTP, dTTP, ADP, AMP and non-hydrolyzable ATP analogues such as ATP gamma S are unable to sustain helicase activity. The helicase activity has an optimal pH range between pH8.0 to pH9.0, is stimulated by KCl or NaCl up to 200mM, is inhibited by potassium phosphate (100mM) and by EDTA (5mM), and is abolished by trypsin. The unwinding is also inhibited competitively by the coaddition of single stranded DNA. The purified fraction was free of DNA topoisomerase, DNA ligase and nuclease activities. The direction of unwinding reaction is 3' to 5' with respect to the strand of DNA on which the enzyme is bound. The enzyme also catalyses the ATP-dependent unwinding of a DNA:RNA hybrid consisting of a radioactively labelled single stranded oligodeoxynucleotide (18 mer) annealed on a longer RNA strand. The enzyme does not require a single stranded DNA tail on the displaced strand at the border of duplex regions; i.e. a replication fork-like structure is not required to perform DNA unwinding. The purification of the other helicases is in progress.

Adenosine Triphosphate↗
PubMed1985

Isolation and characterization of a novel nucleic acid binding protein from calf lenses.

The transitional process of lens cellular differentiation is accompanied by several unique morphological and biochemical changes. Pyknosis or apoptosis of the nucleus involves extensive degradation of genetic materials. In an attempt to search for a gene product responsible for such a regulatory process, we have adopted DNA-cellulose affinity chromatography to enrich the specific binding protein. A binding protein was isolated by high salt (0.8M KCl) wash of the lens polysomal fraction and purified to apparent homogeneity by DNA-cellulose affinity column and chromatofocusing. The nucleic acid binding protein has an apparent molecular weight of 36,000, designated as regulatory factor 36 (RF-36), as determined by SDS/PAGE. Amino acid composition analysis indicated that RF-36 contains high proportions of glycine, alanine, characteristic of the core heteronucleus RNP proteins. Comparative immunological studies with other DNA binding protein antigen (e.g. helix destabilizing protein) suggest the existence of some common overlapping determinant. However, when monoclonal anti-RF-36 was used as immunoprobe, no cross immunoactivity was detected between these homologous binding proteins, suggesting some antigenic diversity among these two nucleic acid binding proteins from different organisms.

Amino Acids↗