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Biomedical subjects

R Qian

Publications and source records attributed to R Qian.

At least 19 recordsLinked to original sources
PubMed2005

Prevalence of Type 2 diabetes in urban and rural Chinese populations in Qingdao, China.

AIMS: To determine the prevalence of diabetes in the Chinese adult population in rural and urban areas of Qingdao city. METHODS: A population-based cross-sectional study of diabetes was performed in 12 436 (5346 men) Chinese adults (20-74 years old) from 2001 to 2002. Fasting capillary whole blood glucose test (FCG) was performed in all participants and a 2-h 75-g oral glucose tolerance test in those with FCG > or = 6.1 mmol/l following initial screening. The 1999 World Health Organization diagnostic criteria for diabetes were used. RESULTS: The age-standardized prevalence of diabetes was 6.1% (4.1% for undiagnosed and 2.1% for previously known diabetes) in adults aged 20-74 years. Diabetes prevalence increased with age up to the oldest age group (70-74); in subjects over 50 years of age, the prevalence reached 10%. Men tended to have a higher prevalence of known diabetes than women, whereas the prevalence of undiagnosed diabetes was lower in men than in women (4.6% vs. 3.3%, d.f. = 1, P = 0.001). Diabetes was more prevalent in the urban than in the rural population (6.9% vs. 5.6%, d.f. = 1, P < 0.001). However, the proportion of undiagnosed diabetes was higher in the rural than in the urban areas (70.5% vs. 58.0%, d.f. = 1, P < 0.001). CONCLUSIONS: The prevalence of Type 2 diabetes in Qingdao city is moderately high, but much higher than reported in 1996. The large proportion of undiagnosed cases of diabetes indicates the lack of public awareness of diabetes and shortage of medical facilities. In view of the huge population in China, the results of this study emphasize the need to improve the early detection and prevention of diabetes in China to prevent the emerging diabetes epidemic.

Adult↗
PubMed2001

Location and mechanism of alpha 2,6-sialyltransferase dimer formation. Role of cysteine residues in enzyme dimerization, localization, activity, and processing.

A significant proportion of the alpha2,6-sialyltransferase of protein Asn-linked glycosylation (ST6Gal I) forms disulfide-bonded dimers that exhibit decreased activity, but retain the ability to bind asialoglycoprotein substrates. Here, we have investigated the subcellular location and mechanism of ST6Gal I dimer formation, as well as the role of Cys residues in the enzyme's trafficking, localization, and catalytic activity. Pulse-chase analysis demonstrated that the ST6Gal I disulfide-bonded dimer forms in the endoplasmic reticulum. Mutagenesis experiments showed that Cys-24 in the transmembrane region is required for dimerization, while catalytic domain Cys residues are required for trafficking and catalytic activity. Replacement of Cys-181 and Cys-332 generated proteins that are largely retained in the endoplasmic reticulum and minimally active or inactive, respectively. Replacement of Cys-350 or Cys-361 inactivated the enzyme without compromising its localization or processing, suggesting that these amino acids are part of the enzyme's active site. Replacement of Cys-139 or Cys-403 generated proteins that are catalytically active and appear to be more stably localized in the Golgi, since they exhibited decreased cleavage and secretion. The Cys-139 mutant also exhibited increased dimer formation suggesting that ST6Gal I dimers may be critical in the oligomerization process involved in stable ST6Gal I Golgi localization.

Amino Acid Substitution↗
PubMed2001

Acute cytokine response to systemic adenoviral vectors in mice is mediated by dendritic cells and macrophages.

We investigated the cellular basis for secretion of inflammatory cytokines in mice following intravenous administration of adenoviral vectors (Ad). Serum inflammatory cytokines including interleukin-6 (IL-6), IL-12, and tumor necrosis factor-alpha (TNF-alpha) were detected as early as 6 h following intravenous injection of Ad-expressing Escherichia coli beta-galactosidase (Ad-lacZ). Ad-lacZ readily accumulated in the splenic marginal zone 1 h after intravenous infusion, where both dendritic cells (DCs) and macrophages were transduced and activated within 6 h. Flow cytometric analyses showed that the expression of Ia and CD86 antigens was markedly enhanced on splenic DCs indicating their activation in vivo by Ad-lacZ. Upon ex vivo culture, these early-activated splenic DCs spontaneously produced high levels of IL-6 and IL-12. By contrast, activated splenic macrophages spontaneously secreted only IL-6. Elimination of tissue macrophages and splenic DCs in vivo considerably reduced the early release of IL-12, IL-6, and TNF-alpha and significantly blocked the specific cellular immune response to Ad and the transgene product in vivo. Our findings indicate that preferential activation of DCs and macrophages may account for Ad-triggered acute inflammatory response in vivo in mice. Moreover, DCs and macrophages may play different roles in this process in terms of their abilities to produce distinct patterns of inflammatory cytokines.

Adenoviridae↗
PubMed2001

Activation of innate immunity in nonhuman primates following intraportal administration of adenoviral vectors.

The innate immune response to intraportally infused adenoviral vector was evaluated in rhesus monkeys. A first-generation adenovirus-expressing lacZ (Ad-lacZ) was administered at a dose just below that which causes severe morbidity. The response to vector was evaluated for the initial 24 h following infusion. Clinical findings during this time were primarily limited to petechiae, consistent with the development of thrombocytopenia and biochemical evidence of disseminated intravascular coagulation. Serum transaminases were elevated and a lymphopenia developed. Tracking of fluorescent-labeled vector demonstrated distribution to macrophages and dendritic cells of the spleen and Kupffer cells of the liver. A systemic release of the cytokine IL-6 occurred soon after vector infusion. Analysis of splenic cells revealed acute activation of macrophages and dendritic cells followed by massive apoptosis. Bone marrow cultures demonstrated normal erythroid and primitive progenitors with a significant decrease in myeloid progenitors. Similar findings, except the abnormality in bone marrow cultures, were observed in monkeys who received an identical dose of Ad-lacZ in which vector genes were inactivated with psoralen and UV irradiation. These data suggest that inadvertent targeting of antigen-presenting cells following intraportal infusion of vector leads to a systemic cytokine syndrome which may be triggered by the viral capsid proteins.

Adenoviridae↗
PubMed2001

The association between PPP1R3 gene polymorphisms and type 2 diabetes mellitus.

OBJECTIVE: To detect the relationship between the polymorphism of the glycogen-targeting regulatory subunit of the skeletal muscle glycogen-associated protein phosphatase 1 (PPP1R3) gene and type 2 diabetes by case-control study. METHODS: We genotyped the PPP1R3 gene Asp905Tyr polymorphism and a common 3'-untranslated region AT (AU)-rich element (ARE) polymorphism in 101 type 2 diabetic patients and 101 controls by oligonucleotide ligation assay (OLA) and polyacrylamide gel elecrophoresis, respectively. RESULTS: Subjects with Tyr/Tyr genotypes whose body mass index (BMI) < 25 were used as the reference group. Those whose BMI > or = 25 with Asp905 had a 3.66-fold increase (95% CI: 1.48-9.06, P = 0.005) in type 2 diabetes risk. No association was found between 3'UTR ARE polymorphism and type 2 diabetes mellitus (OR = 1.15; 95% CI: 0.62-2.14, P = 0.65). CONCLUSION: A joint effect between the Asp905 and BMI increases the risk of type 2 diabetes, and Asp905Tyr and ARE polymorphism of PPP1R3 gene are not the major diabetogenic gene variants in Chinese population.

AT Rich Sequence↗
PubMed2001

Informatics application provides instant research to practice benefits.

A web-based research information system was designed to enable our research team to efficiently measure health related quality of life among frail older adults in a variety of health care settings (home care, nursing homes, assisted living, PACE). The structure, process, and outcome data is collected using laptop computers and downloaded to a SQL database. Unique features of this project are the ability to transfer research to practice by instantly sharing individual and aggregate results with the clinicians caring for these elders and directly impacting the quality of their care. Clinicians can also dial in to the database to access standard queries or receive customized reports about the patients in their facilities. This paper will describe the development and implementation of the information system. The conference presentation will include a demonstration and examples of research to practice benefits.

Abstracting and Indexing↗
PubMed2000

[Study on therapeutic mechanism of anti-rheumatism action of herba siegesbeckiae].

OBJECTIVE: To explore the mechanism of anti-rheumatism action of the active fraction of Herba Siegesbeckiae (AFHS). METHODS: Adjuvant arthritis model of rat was made to observe the effect of AFHS on lymphocyte proliferation, interluekin-1 (IL-1) and IL-2 activity, pathologic section of ankle joint, and analgesic effect of AFHS in model rat. RESULTS: AFHS could reduce the inflammatory pathologic response of ankle joint, it functions well as analgesics, the analgesic rate being 65%, AFHS could also improve T-lymphocyte proliferation, improve IL-2 activity and inhibit IL-1 activity, as compared with the control group, the difference was significant (P < 0.01). CONCLUSION: Through regulating the immune function of organism, AFHS could improve the local pathologic response so as to antagonise against rheumatism, therefore, it is a good anti-rheumatism herbal medicine.

Animals↗
PubMed1999

Sialyltransferase isoforms are phosphorylated in the cis-medial Golgi on serine and threonine residues in their luminal sequences.

ST6Gal-I (alpha2,6-sialyltransferase) is expressed as two isoforms, STTyr and STCys, which exhibit differences in catalytic activity, trafficking through the secretory pathway, and proteolytic processing and secretion. We have found that the ST6Gal-I isoforms are phosphorylated on luminal Ser and Thr residues. Immunoprecipitation of 35S- and 32P-labeled proteins expressed in COS-1 cells suggests that the STTyr isoform is phosphorylated to a greater extent than the STCys isoform. Analysis of domain deletion mutants revealed that STTyr is phosphorylated on stem and catalytic domain amino acids, whereas STCys is phosphorylated on catalytic domain amino acids. An endoplasmic reticulum retained/retrieved chimeric Iip33-ST protein demonstrates drastically lower phosphorylation than does the wild type STTyr isoform. This suggests that the bulk of the ST6Gal-I phosphorylation is occurring in the Golgi. Treatment of cells with the ionophore monensin does not significantly block phosphorylation of the STTyr isoform, suggesting that phosphorylation is occurring in the cis-medial Golgi prior to the monensin block. This study demonstrates the presence of kinase activities in the cis-medial Golgi and the substantial phosphorylation of the luminal sequences of a glycosyltransferase.

Animals↗
PubMed1999

Fas-Fas ligand interactions play a major role in effector functions of cytotoxic T lymphocytes after adenovirus vector-mediated gene transfer.

Adenovirus vectors transduce liver hepatocytes with extreme efficiency; however, transgene expression is eliminated within 2 weeks. Extinction of transgene expression has been attributed to infiltrating cytotoxic T lymphocytes (CTLs) in the liver in a process that resembles a number of human diseases, including viral and autoimmune hepatitis. In this study we investigated the role of Fas-Fas ligand interactions in killing of vector-transduced hepatocytes in vitro and in vivo. Intrahepatic lymphocytes (IHLs) isolated from livers of mice administered adenovirus vector demonstrated cytolytic activity against vector-infected primary hepatocytes. The in vitro CTL activity of the IHLs involving both CD4+ and CD8+ T cells was MHC class I restricted and could be blocked by soluble Fas-IgG. Adoptive transfer of IHLs from immune-competent mice immunized with Ad-lacZ into Ragl-deficient mice previously infused with Ad-lacZ resulted in rapid elimination of beta-galactosidase-transduced hepatocytes. Transfer of these cells into Fas-deficient mice (B6-lpr) failed to eliminate lacZ expression; likewise IHLs from immunized FasL-deficient mice (B6-gld) failed to eliminate lacZ expression in Rag1-deficient mice. Finally, in vivo administration of soluble Fas-IgG abrogated the ability of Ad-lacZ-primed IHLs to eliminate transgene expression. These studies establish an essential role for Fas-Fas ligand interactions in the mechanism of elimination of adenoviral vector-mediated transgene expression in the liver.

Adenoviridae↗
PubMed1999

Factors affecting the degradation rate of poly(lactide-co-glycolide) microspheres in vivo and in vitro.

The purpose of this work was to study the degradation of poly(lactide-co-glycolide) (PLG) microspheres in vivo and in vitro. Degradation rate constants were determined by measuring the polymer molecular weight as a function of time by gel-permeation chromatography. The effects of PLG chemistry and the effects of encapsulating the sparingly soluble salt zinc carbonate and the protein recombinant human growth hormone (rhGH) on the degradation rate were assessed. It was found that in vivo degradation was faster than in vitro degradation. In addition, different types of PLGs were found to degrade at different rates depending on the chemistry of the polymer end group and, to a lesser extent, the molecular weight. Finally, zinc carbonate was found to retard the degradation of some PLGs. These degradation studies have proved valuable in the design of sustained release microsphere products.

Animals↗
PubMed1999

Immune responses to adenovirus and adeno-associated virus in humans.

Vectors based on human adenovirus (Ad) and adeno-associated virus (AAV) are being evaluated for human gene therapy. The response of the host to the vector, in terms of antigen-specific immunity, will play a substantial role in clinical outcome. We have surveyed cohorts of normal subjects and cystic fibrosis patients for pre-existing immunity to these viruses, caused by naturally acquired infections. A number of humoral and cellular assays to adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 2 (AAV2) were performed from serum and peripheral blood mononuclear cells. Virtually all subjects had Ig to Ad5 although only 55% of these antibodies neutralized virus (NAB). Approximately two of three patients demonstrated CD4+ T cells that proliferated to Ad antigens of which most were of the TH1 subset, based on cytokine secretion. A substantially different pattern of immune responses was observed to AAV2. Although virtually all patients had Ig to AAV2, most of these antibodies were not neutralizing (32% NAB) and only 5% of patients had peripheral blood lymphocytes that proliferated in response to AAV2 antigens. These studies demonstrate marked heterogeneity in pre-existing immunity to Ad5 and AAV2 in human populations. The impact of these findings on outcome following gene therapy will require further study.

Adenoviridae↗
PubMed1998

Two soluble glycosyltransferases glycosylate less efficiently in vivo than their membrane bound counterparts.

Many Golgi glycosyltransferases are type II membrane proteins which are cleaved to produce soluble forms that are released from cells. Cho and Cummings recently reported that a soluble form of alpha1, 3-galactosyltransferase was comparable to its membrane bound counterpart in its ability to galactosylate newly synthesized glycoproteins (Cho,S.K. and Cummings,R.D. (1997) J. Biol. Chem., 272, 13622-13628). To test the generality of their findings, we compared the activities of the full length and soluble forms of two such glycosyltransferases, ss1,4 N-Acetylgalactosaminyltransferase (GM2/GD2/ GA2 synthase; GalNAcT) and beta galactoside alpha2,6 sialyltransferase (alpha2,6-ST; ST6Gal I), for production of their glycoconjugate products in vivo . Unlike the full length form of GalNAcT which produced ganglioside GM2 in transfected cells, soluble GalNAcT did not produce detectable GM2 in vivo even though it possessed in vitro GalNAcT activity comparable to that of full length GalNAcT. When compared with cells expressing full length alpha2,6-ST, cells expressing a soluble form of alpha2,6-ST contained 3-fold higher alpha2,6-ST mRNA levels and secreted 7-fold greater alpha2,6-ST activity as measured in vitro , but in striking contrast contained 2- to 4-fold less of the alpha2,6-linked sialic acid moiety in cellular glycoproteins in vivo . In summary these results suggest that unlike alpha1,3-galactosyltransferase the soluble forms of these two glycosyltransferases are less efficient at glycosylation of membrane proteins and lipids in vivo than their membrane bound counterparts.

Animals↗
PubMed1998

Changes of activity of liver glycogen synthase in experimental diabetes mellitus rats.

OBJECTIVE: To study the activity of liver glycogen synthase in analogous model of NIDDM rats. METHODS: Male Wistar rats were injected with low dose of streptozotocin (STZ) (30 mg/kg body weight) via tail vena and those animals with glucose tolerance impaired and level of insulin equal to or higher than that of the controls at 18th week were taken as the analogous rat model of NIDDM. The activity of liver glycogen synthase (GS) was assayed at the end of experiment. RESULTS: Type I-enzyme: 0.18 +/- 0.06 mumol/min.g versus 0.24 +/- 0.09 mumol/min.g, P < 0.05, and total-enzyme: 1.52 +/- 0.43 mumol/min. g versus 1.84 +/- 0.42 mumol/min.g, P < 0.05. CONCLUSION: The GS activity of diabetic rats was significantly lower than that of control.

Animals↗
PubMed1997

Two naturally occurring alpha2,6-sialyltransferase forms with a single amino acid change in the catalytic domain differ in their catalytic activity and proteolytic processing.

The alpha2,6-sialyltransferase (ST) is a Golgi glycosyltransferase that adds sialic acid residues to glycoprotein N-linked oligosaccharides. Here we show that two forms of alpha2,6-sialyltransferase are expressed by the liver and are encoded by two different RNAs that differ by a single nucleotide. The ST tyr possesses a Tyr at amino acid 123, whereas the ST cys possesses a Cys at this position. The ST tyr is more catalytically active than the ST cys; however, both are functional when introduced into tissue culture cells. The proteolytic processing and turnover of the ST tyr and ST cys proteins differ dramatically. The ST cys is retained intact in COS-1 cells, whereas the ST tyr is rapidly cleaved and secreted. Analysis of the N-linked oligosaccharides of these proteins demonstrates that both proteins enter the late Golgi. However, differences in ST tyr and ST cys proteolytic processing may be related to differences in their localization, because ST tyr but not ST cys is expressed at low levels on the cell surface. The possibility that the ST tyr is cleaved in a post-Golgi compartment is supported by the observation that a 20 degrees C temperature block, which stops protein transport in the trans Golgi network, blocks both cleavage and secretion of the ST tyr.

Animals↗
PubMed1995

Analysis of thermal injury process based on enzyme deactivation mechanisms.

Based upon the analysis of enzyme-catalyzed reactions occurring in living tissue, a model of thermal injury process is presented in which the fraction of denatured enzyme protein was taken as the indicator of thermal damage degrees. The results from this model describe the dependence of thermal damage on exposure time and temperature elevation.

Burns↗