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Biomedical subjects

Li Li

Publications and source records attributed to Li Li.

At least 127 records · Page 7Linked to original sources
PubMed2006

Identification of blood biomarkers of rheumatoid arthritis by transcript profiling of peripheral blood mononuclear cells from the rat collagen-induced arthritis model.

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease that results in joint destruction and subsequent loss of function. To better understand its pathogenesis and to facilitate the search for novel RA therapeutics, we profiled the rat model of collagen-induced arthritis (CIA) to discover and characterize blood biomarkers for RA. Peripheral blood mononuclear cells (PBMCs) were purified using a Ficoll gradient at various time points after type II collagen immunization for RNA preparation. Total RNA was processed for a microarray analysis using Affymetrix GeneChip technology. Statistical comparison analyses identified differentially expressed genes that distinguished CIA from control rats. Clustering analyses indicated that gene expression patterns correlated with laboratory indices of disease progression. A set of 28 probe sets showed significant differences in expression between blood from arthritic rats and that from controls at the earliest time after induction, and the difference persisted for the entire time course. Gene Ontology comparison of the present study with previous published murine microarray studies showed conserved Biological Processes during disease induction between the local joint and PBMC responses. Genes known to be involved in autoimmune response and arthritis, such as those encoding Galectin-3, Versican, and Socs3, were identified and validated by quantitative TaqMan RT-PCR analysis using independent blood samples. Finally, immunoblot analysis confirmed that Galectin-3 was secreted over time in plasma as well as in supernatant of cultured tissue synoviocytes of the arthritic rats, which is consistent with disease progression. Our data indicate that gene expression in PBMCs from the CIA model can be utilized to identify candidate blood biomarkers for RA.

Animals↗
PubMed2006

A novel substitution at the translation initiator codon (ATG-->ATC) of the lipoprotein lipase gene is mainly responsible for lipoprotein lipase deficiency in a patient with severe hypertriglyceridemia and recurrent pancreatitis.

A patient with severe hypertriglyceridemia and recurrent pancreatitis was found to have significantly decreased lipoprotein lipase (LPL) activity and normal apolipoprotein C-II concentration in post-heparin plasma. DNA analysis of the LPL gene revealed two mutations, one of which was a novel homozygous G-->C substitution, resulting in the conversion of a translation initiation codon methionine to isoleucine (LPL-1). The second was the previously reported heterozygous substitution of glutamic acid at residue 242 with lysine (LPL-242). In vitro expression of both mutations separately or in combination demonstrated that LPL-1 had approximately 3% protein mass and 2% activity, whereas LPL-242 had undetectable activity but normal mass. The combined mutation LPL-1-242 exhibited similar changes as for LPL-1, with markedly reduced mass, and for LPL-242, with undetectable activity. These results suggest that the homozygous initiator codon mutation rather than the heterozygous LPL-242 alteration was mainly responsible for the patient phenotypes.

Adolescent↗
PubMed2006

Soluble human p55 and p75 tumor necrosis factor receptors reverse spontaneous arthritis in transgenic mice expressing transmembrane tumor necrosis factor alpha.

OBJECTIVE: The roles of the transmembrane and secreted forms of tumor necrosis factor alpha (TNFalpha) in rheumatoid arthritis (RA) remain unclear. Agents used to inhibit TNFalpha have shown varying efficacy in RA patients, suggesting that anti-TNFalpha agents possess dissimilar mechanisms of action, including the ability to neutralize transmembrane (tmTNFalpha) and secreted TNFalpha. In this study, TNFalpha-knockout (TNFalpha-KO) mice that were genetically altered to express elevated levels of tmTNFalpha were constructed to further understand the roles of the 17-kd secreted, trimeric, and 26-kd transmembrane forms of TNFalpha. METHODS: A speed-congenic mating scheme was used to generate 3 unique strains of mice: 1) transgenic tmTgA86 mice overexpressing 26-kd tmTNFalpha and also secreting 17-kd trimeric TNFalpha (tmTNFalpha-transgenic), 2) TNFalpha-/- mice (TNFalpha-KO), and 3) transgenic mice overexpressing tmTNFalpha backcrossed to TNFalpha-KO mice (tmTNFalpha-transgenic/TNFalpha-KO). Mice were treated with phosphate buffered saline (as vehicle control), dexamethasone (as positive control), or modified recombinant human soluble TNF receptor (sTNFR) p55 or p75, and were assessed clinically and histopathologically for signs of inflammation and development of arthritis. RESULTS: The tmTNFalpha-transgenic/TNFalpha-KO mice were born with crinkled tails and spinal deformities similar to those in ankylosing spondylitis. By 2-4 weeks, these mice developed symmetric inflammatory arthritis, characterized by tissue swelling, pannus formation, and bone deformities. The tmTNFalpha-transgenic mice also developed spontaneous-onset arthritis, but at a slower rate (100% incidence by 10-12 weeks). Clinical and histologic progression of arthritis in the tmTNFalpha-transgenic/TNFalpha-KO mice was reduced by treatment with dexamethasone or with the p55 or p75 sTNFR (69% and 63% reduction in total histologic score, respectively). CONCLUSION: These data show that arthritis is sufficiently initiated and maintained in tmTNFalpha-transgenic/TNFalpha-KO mice, and that it can be neutralized by recombinant human p55 or p75 sTNFR, resulting in amelioration of the biologic and subsequent histologic destructive effects of tmTNFalpha.

Animals↗
PubMed2006

Liquid chromatography-tandem mass spectrometry for the identification of L-tetrahydropalmatine metabolites in Penicillium janthinellum and rats.

L-tetrahydropalmatine (L-THP) is an active alkaloid from Stephania ainiaca Diels. In order to compare the similarities and differences of microbial and mammalian metabolisms of L-THP, the microbial transformation by Penicillium janthinellum and metabolism in rats were investigated. Biotransformation of L-THP by Penicillium janthinellum AS 3.510 resulted in the formation of three metabolites. Their structures were identified as L-corydalmine, L-corypalmine and 9-O-desmethyl-L-THP, respectively, by comprehensive nuclear magnetic resonance and mass spectrometry (MS) analysis. Six metabolites (M1-M6) were detected from the in vivo study in rats and three of which (L-corydalmine, L-corypalmine and 9-O-desmethyl-L-THP) were identified as the same compounds as those obtained from microbial metabolism by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and comparison with reference standards obtained from microbial metabolism. The structures of the additional three metabolites were tentatively deduced as 2-O-desmethyl-L-THP and two di-O-demethylated L-THP by LC-MS/MS analysis. Time courses of microbial and rat metabolisms of L-THP were also investigated.

Animals↗
PubMed2006

Enhanced cell survival of Hep3B cells by the hepatitis B x antigen effector, URG11, is associated with upregulation of beta-catenin.

Intrahepatic expression of hepatitis B x antigen (HBxAg) is associated with the development of hepatocellular carcinoma (HCC), perhaps through trans-activation of selected cellular genes. When this was examined by PowerBlot analysis, upregulated levels of beta-catenin and several known beta-catenin effectors were observed in HBxAg-positive compared with HBxAg-negative HepG2 cells. When HBxAg was introduced into Hep3B cells, upregulated expression of wild-type beta-catenin was observed. This was also observed in Hep3B cells overexpressing the HBxAg upregulated gene, URG11. Upregulated expression of URG11 and beta-catenin correlated with HBxAg trans-activation function. Transient transfection assays with fragments of the beta-catenin promoter showed that it was activated by both HBxAg and URG11 and inhibited by URG11-specific small inhibitory RNA. The latter also inhibited the growth of Hep3BX cells in a serum-free medium, which correlated with depressed levels of beta-catenin. Activation of beta-catenin effector genes was observed in cells stably expressing HBxAg or overexpressing URG11 compared with control cells transfected with the pTOPFLASH reporter plasmid. Extensive costaining between HBxAg, URG11, and beta-catenin was observed in infected liver and HCC nodules, suggesting a close relationship in vivo. In conclusion, wild-type beta-catenin is activated by HBxAg, in part, through the upregulated expression of the HBxAg effector URG11. URG11 stimulates the beta-catenin promoter and hepatocellular growth and survival. These observations also suggest that URG11 may be a regulatory element in the beta-catenin signaling pathway and may be a target for chemoprevention of HCC.

Adolescent↗
PubMed2006

Evaluation of solution oxygenation requirements for azonitrile-based oxidative forced degradation studies of pharmaceutical compounds.

AIBN and ACVA oxidative forced degradation models are examined for two drug molecules whose predominant oxidation chemistries arise from different reaction mechanisms (i.e., free radical vs. nucleophilic). Stress was conducted under a variety of initiator concentrations, and under ambient and pressurized oxygen atmospheres. In each case examined, the azonitrile initiator solutions served as a good predictive model of the major oxidative degradation products observed in pharmaceutical formulations. At low to moderate inititator concentrations, the degradation product distributions and degree of reactivity were similar for samples stored in ambient and pressurized oxygen environments. These results are rationalized with reference to the oxygen consumption kinetics of AIBN and ACVA solutions as a function of initiator concentration. The data suggests that ambient air provides sufficient oxygen to enable chain propagation of peroxy radicals in azonitrile solutions of concentrations appropriate to the forced degradation of pharmaceutical compounds.

Acetonitriles↗
PubMed2006

Nucleophilic group transfer reactivity for fibric acid derived drug molecules.

A novel group transfer reaction is reported in which a drug molecule undergoes a thermally induced 2-methyl-2-yl-propionic acid group transfer from one drug molecule to the carboxylic acid functional group of another. The resulting product, the 2-carboxy isopropyl ester of the parent compound, can itself participate in further reactions to yield a series of homologous products. The structural requirements and solvent dependence of this reactivity were investigated, and the resulting implications for the reaction mechanism were discussed. The experimental data is consistent with solvent-assisted nucleophilic substitution reaction mechanism, where the solvent is a small molecule or a second drug molecule. Hydrogen bonding appears to play an important role in both intramolecular activation of the leaving group, as well as intermolecular interaction with the attacking nucleophile. The reactivity is found to be intrinsic to the 2-arenoxy-2-methylpropionic acid structure, which is common to the extended class of fibrate PPAR drug molecules, suggesting that the potential for this reactivity exists for many of these drug molecules as well.

Chemical Phenomena↗
PubMed2006

Analysis on antimicrobial resistance of clinical bacteria isolated from county hospitals and a teaching hospital.

The distinction of antimicrobial resistance of clinical bacteria isolated from county hospitals and a teaching hospital was investigated. Disc diffusion test was used to study the antimicrobial resistance of isolates collected from county hospitals and a teaching hospital. The data was analyzed by WHONET5 and SPSS statistic software. A total of 655 strains and 1682 strains were collected from county hospitals and a teaching hospital, respectively, in the year of 2003. The top ten pathogens were Coagulase negative staphylococci (CNS), E. coli, Klebsiella spp., S. areus, P. aeruginosa, Enterococcus spp., Enterobacter spp., otherwise Salmonella spp., Proteus spp., Shigella spp. in county hospitals and Streptococcus spp., Acinetobacter spp., X. maltophilia in the teaching hospital. The prevalence of multi-drug resistant bacteria was 5% (4/86) of methicillin-resistant S. areus (MRSA), 12% (16/133) and 15.8% (9/57) of extended-spectrum beta-lactamases producing strains of E. coli and Klebsiella spp., respectively, in county hospitals. All of the three rates were lower than that in the teaching hospital and the difference was statistically significant (P < 0. 01). However, the incidence of methicillin-resistant CNS (MRCNS) reached to 70% (109/156) in the two classes of hospitals. Generally, the antimicrobial resistant rates in the county hospitals were lower than those in the teaching hospital, except the resistant rates of ciprofloxacin, erythromycin, clindamycin, SMZco which were similar in the two classes of hospitals. There were differences between county hospitals and the teaching hospital in the distribution of clinical isolates and prevalence of antimicrobial resistance. It was the basis of rational use of antimicrobial agents to monitor antimicrobial resistance by each hospital.

Anti-Bacterial Agents↗
PubMed2006

Upregulation of brain-derived neurotrophic factor in the sensory pathway by selective motor nerve injury in adult rats.

Selective motor nerve injury by lumbar 5 ventral root transection (L5 VRT) induces neuropathic pain, but the underlying mechanisms remain unknown. Previously, increased expression and secretion of brain-derived neurotrophic factor (BDNF) had been implicated in injury-induced neuropathic pain in the sensory system. In this study, as a step to examine potential roles of BDNF in L5 VRT-induced neuropathic pain, we investigated BDNF gene and protein expression in adult rats with L5 VRT. L5 VRT induced a dramatic upregulation of BDNF mRNA in intact sensory neurons in the ipsilateral L5 dorsal root ganglia (DRG), in non-neuronal cells in the ipsilateral sciatic nerve, and in motoneurons in the ipsilateral spinal cord. L5 VRT also induced de novo synthesis of BDNF mRNA in spinal dorsal horn neurons and in glial cells in the white matter of the ipsilateral spinal cord. Consistent with the mRNA expression pattern, BDNF protein was also mainly upregulated in all populations of sensory neurons in the ipsilateral L5 DRG and in spinal neurons and glia. Quantitative analysis by ELISA showed that the BDNF content in the DRG and sciatic nerve peaked on day 1 and remained elevated 14 days after L5 VRT. These results suggest that increased BDNF expression in intact primary sensory neurons and spinal cord may be an important factor in the induction of neuropathic pain without axotomy of sensory neurons.

Animals↗
PubMed2006

DRD2/DARPP-32 expression correlates with lymph node metastasis and tumor progression in patients with esophageal squamous cell carcinoma.

BACKGROUND: Dopamine receptors (DRs) are members of seven transmembrane domain trimeric guanosine 5'-triphosphate (GTP)-binding protein-coupled receptor family. Through dopamine receptor activation, dopamine plays a significant role in regulating gene expression, such as induced tumor cell migration. MATERIALS AND METHODS: We investigated DRD1 and DRD2 expressions in patients with esophageal squamous cell carcinoma (ESCC) for immunohistochemistry and analyzed differences between DRD1, DRD2, and DARPP-32 expressions of clinicopathological features in 122 patients with ESCC. RESULTS: DRD1 immunostaining correlated with the pathologic grade (P = 0.0127), and DRD2 immunostaining correlated with the pathologic stage (P = 0.0432) and pN classification (P = 0.0112). A significant correlation was found between DRD1 and DRD2 expression (P = 0.0292). However, no correlation was observed between DRD1/DRD2 expression and DARPP-32 expression (P = 0.4555 and 0.4774, respectively). No correlation was observed between the DRD1/DRD2 expression and patient prognosis. To find the cooperative role between DRD1, DRD2, and DARPP-32 expressions, patients were classified into the different groups. In the DRD2/DARPP-32 combination, the (+/-) group was significantly correlated with pathologic stage (P = 0.0006), lymph node metastasis (P = 0.0001), pT (P = 0.0287), and tumor size (P = 0.0202). Moreover, patients with this combination showed a lower survival rate compared with the other three groups (P = 0.0287). CONCLUSIONS: We conclude that DRD2/DARPP-32 expression is associated with tumor progression and that DRD2/DARPP-32 expressions may help predict prognosis in patients with ESCC.

Adult↗
PubMed2006

HIV/STD stigmatization fears as health-seeking barriers in China.

Internationally, stigma prohibits effective HIV/STD identification, prevention, and care. Interviews with 106 persons in an urban center in Eastern China, some known to have engaged in stigmatized risk acts (sex workers, STD clinic patients) and some vulnerable for stigmatization fears to influence health-seeking behaviors (market employees, rural-to-urban migrants). Interviews focused on community norms, values, beliefs, and emotional and behavioral reactions to HIV/STD stigmatization related events. Attributions for infection were found to mark individual's failure to adhere to sexuality norms; define a condition warranting the avoidance of infected persons and dismissal by medical professionals; and promote anticipation of negative emotions (i.e., shame, fear, and embarrassment) and devalued social roles and status. Strategies reported to avoid stigmatization include avoiding HIV/STD knowledge; avoiding health care professionals, particularly in public settings; and conforming to community norms of shunning those suspected of risky behaviors. Results have direct implications for community marketing campaigns in China.

Adolescent↗
PubMed2006

Understanding family support for people living with HIV/AIDS in Yunnan, China.

This study examines how family support affects people living with HIV/AIDS (PLHA) in China. In-depth, semi-structured interviews (n=30) were conducted with people living with HIV/AIDS who were infected through different routes (e.g., intravenous drug use, sex) and of different age groups. Findings showed that all of the participants were in great need of help and the primary source of support came from their families. Family support included financial assistance, support in the disclosure process, daily routine activities, medical assistance, or psychological support. This study illustrates that the support provided by family makes multiple levels of positive impact on people living with HIV/AIDS, suggesting the importance of including families in HIV/AIDS interventions.

Adult↗
PubMed2006

The CXCR4 antagonist AMD3100 releases a subset of G-CSF-primed peripheral blood progenitor cells with specific gene expression characteristics.

OBJECTIVE: AMD3100 is a new CXCR4 antagonist that induces a rapid release of hematopoietic progenitors from the bone marrow to the peripheral blood. We conducted a clinical study where patients with multiple myeloma and non-Hodgkin's lymphoma were treated with AMD3100 (A) to increase the number of peripheral blood progenitor cells (PBPCs) when given a mobilization regimen of granulocyte colony-stimulating factor (G-CSF, G). Because experimental data suggest that A+G-mobilized PBPCs are functionally different from G-mobilized PBPCs, we were interested in an intraindividual comparison of the gene expression profile of CD34+ cells in the two different settings. METHODS: To this end peripheral blood CD34+ cells of three patients (three G, three A+G samples) were isolated by immunomagnetic followed by flow cytometric sorting to a purity of >99%. Total RNA was purified. Differentially expressed genes were analyzed by using the Affymetrix GeneChip Human Genome U133 Plus2.0 and the software package Micro Array Solutions 1.3 (SAS Institute Inc.). RESULTS: We found a pattern of unanimously higher (81 genes, log2 ratio > 0.5; p < 0.0001) or lower (29 genes, log2 ratio < -0.4; p < 0.0001) expressed genes in the A+G-mobilized vs G-mobilized CD34+ PBPCs. Significant changes of four selected genes noted in the microarray analysis were validated by quantitative real-time polymerase chain reaction. Genes were grouped according to gene function. Only increased expression was found in the categories antiapoptosis (e.g., MPO, HSPA1B), cell cycle (e.g., MS4A3, RRM2), replication/DNA repair (e.g., MPO, HSPA1B), cell motility (e.g., TNFSF4, HMMR), and oxygen transport. Decreased expression occurred in the proapoptosis gene group (e.g., MDA5, BCL10). CXCR4 receptor gene expression itself was significantly 1.5-fold higher in the A+G vs G group. CONCLUSION: We conclude that A+G-mobilized CD34+ PBPCs express significantly higher amounts of genes that potentially promote superior engraftment after myeloablative therapy than G-mobilized CD34+ PBPCs.

Benzylamines↗
PubMed2006

Chronic myeloid leukemia cells express tumor-associated antigens eliciting specific CD8+ T-cell responses and are lacking costimulatory molecules.

Specific immunotherapies for patients with chronic myeloid leukemia (CML) might eliminate residual CML cells after therapy with imatinib or chemotherapy and might enhance a specific graft-versus-leukemia effect after allogeneic stem cell transplantation. Here, we investigated the mRNA expression and T-cell recognition of tumor-associated antigens or leukemia-associated antigens (LAAs) in 34 patients with CML. Several LAAs are expressed in CML and therefore are candidate structures for specific immunotherapies: bcr-abl (100%), G250 (24%), hTERT (53%), MPP11 (91%), NEWREN60 (94%), PRAME (62%), Proteinase3 (71%), RHAMM/CD168 (83%), and WT1 (53%), but not BAGE, MAGE-A1, SSX2, or NY-ESO-1. The frequency of mRNA expression of RHAMM/CD168, Proteinase3, and PRAME was higher in acceleration phase and blast crisis. In flow cytometry, CD34+ progenitor cells typed positive for HLA molecules but were deficient for CD40, CD80, CD83, and CD86. However, RHAMM/CD168 R3-peptide (ILSLELMKL)-specific T-cell responses in CML patients were demonstrated by ELISPOT analysis and specific lysis of RHAMM/CD168 R3-pulsed T2 cells and CD34+ CML cells in chromium-51 release assays. RHAMM-R3-specific T cells could be phenotyped as CD8+R3*tetramer+CD45RA+CCR7-CD27- early effector T cells by tetramer staining. Therefore, vaccination strategies inducing such RHAMM-R3-directed effector T cells might be a promising approach to enhance specific immune responses against CML cells.

Adult↗
PubMed2006

beta-Carotene accumulation induced by the cauliflower Or gene is not due to an increased capacity of biosynthesis.

The cauliflower (Brassica oleracea L. var. botrytis) Or gene is a rare carotenoid gene mutation that confers a high level of beta-carotene accumulation in various tissues of the plant, turning them orange. To investigate the biochemical basis of Or-induced carotenogenesis, we examined the carotenoid biosynthesis by evaluating phytoene accumulation in the presence of norflurazon, an effective inhibitor of phytoene desaturase. Calli were generated from young seedlings of wild type and Or mutant plants. While the calli derived from wild type seedlings showed a pale green color, the calli derived from Or seedlings exhibited intense orange color, showing the Or mutant phenotype. Concomitantly, the Or calli accumulated significantly more carotenoids than the wild type controls. Upon treatment with norflurazon, both the wild type and Or calli synthesized significant amounts of phytoene. The phytoene accumulated at comparable levels and no major differences in carotenogenic gene expression were observed between the wild type and Or calli. These results suggest that Or-induced beta-carotene accumulation does not result from an increased capacity of carotenoid biosynthesis.

Brassica↗
PubMed2006

Blocking the immune response in ischemic acute kidney injury: the role of adenosine 2A agonists.

Acute kidney injury (AKI) is associated with a high degree of morbidity and mortality and its incidence is increasing. These factors, together with a lack of successful clinical trials, necessitate a comprehensive evaluation of the pathogenesis of AKI and trial design. The progress that has been made in elucidating the pathogenesis of AKI has defined inflammation as an early event and therefore a potential target for therapeutic intervention. This Review summarizes recent advances in our understanding of the role of inflammation in AKI as well as our approach to limiting inflammation using compounds that stimulate adenosine 2A receptors (A(2A)Rs). A(2A)Rs are members of a family of guanine nucleotide-binding proteins that have become a focus of interest primarily because of their ability to broadly inactivate the inflammatory cascade. An A(2A) agonist-ATL146 ester (ATL146e)-is currently being tested in a phase III clinical trial as a pharmacological stress agent in cardiac perfusion imaging studies. This study, together with extensively published preclinical data, will facilitate testing of ATL146e in human trials of AKI.

Adenosine A2 Receptor Agonists↗
PubMed2006

Controlling chaotic robots with kinematical redundancy.

Robots with kinematical redundancy under the pseudoinverse control exhibit undesirable chaotic joint motion, which leads to erratic behaviors. In this study, we used the delayed feedback method to control chaotic motions of a planar 3R rigid and a planar 3R flexible redundant robot under the pseudoinverse control when the end-effector traces a closed-path repeatedly in the work space. It was demonstrated that chaotic motions of robots with kinematical redundancy can be turned into regular motion when the delayed feedback method was applied with some appropriate parameters. This study provides a new insight helpful to solve the repeatability problem of redundant manipulators.

Biomechanical Phenomena↗