Biomedical subjects

Jing Liu

Publications and source records attributed to Jing Liu.

At least 253 records · Page 14Linked to original sources

PubMed2004

Two kinds of ENU-induced scant hair mice and mapping of the mutant genes.

OBJECTIVE: To establish mouse models for human diseases through N-ethyl-N-nitrosourea (ENU) mutagenesis, and to provide groundwork to clone genes and study their functions after mapping the mutant genes. METHODS: 18 male D2 mice (G0) at age of 8-10 weeks old were injected intraperitoneally with ENU (100 mg/kg) once a week for three consecutive weeks. The treated male mice were mated with females of the same strain, and their offspring (G1) were used to screen for dominant and recessive mutation. After breeding the mutant F2 (D2B6 F1 intercrossing) mice, 39 microsatellites that are equally distributed on the mouse genome and are different between B6 and D2 strains were used to scan the genome. According to the log odds score (LODS) we determined whether these microsatellites were linked to the mutant genes and calculated the location of mutant genes based on their recombination ratio. RESULTS: We screened 532 G1 mice, of which 14 exhibited mutation phenotypes. None was dominantly hereditable. Two cases of recessive inheritable scant hair mice were obtained through testing 30 G1 mice with normal phenotype and potential recessive mutant genes. All showed scant coat hair, grew slowly, and hyperkeratoses of epidermis and bollicular horn plug in histological sections. Their visceral organs were not markedly different from normal, and they were named scant hair 1 Baojin (symbol is snthr(-1Bao)) and scant hair 2 Baojin (symbol is snthr(-2Bao)). Through microsatellite screening we found that the LODS between snthr(-1Bao) and D9Mit243 was 7.73, and the linkage was determined. After analyzing the recombination ratio between snthr(-1Bao) and microsatellite D9Mit18 which was near snthr(-1Bao) based on a total number of 126 F2 mice with the scant hair phenotype, we determined that snthr(-1Bao) was located at chromosome 9 and was 71cM from centromere. Using the same technique, snthr(-2Bao) was mapped to the same position as snthr(-1Bao). CONCLUSION: In our research, two cases of scant hair mice provide good models for the study of dermatology, and the location of mutant genes provides a solid foundation for cloning new mice scant hair genes.

Alkylating Agents↗

PubMed2004

Possible mode of action of antiherpetic activities of a proteoglycan isolated from the mycelia of Ganoderma lucidum in vitro.

A bioactive fraction (GLPG) was extracted and purified from the mycelia of Ganoderma lucidum by EtOH precipitation and DEAE-cellulose column chromatography. GLPG was a proteoglycan and had a carbohydrate:protein ratio of 10.4:1. Its antiviral activities against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) were investigated by the cytopathic effect (CPE) inhibition assay in cell culture. This kind of polysaccharide inhibited the development of the cytopathic effect in dose-dependent manner in HSV-infected cells, moreover did not show any cytotoxic effects on cells even when a concentration was as high as 2000 microg/ml. In order to study the possible mode of action of the antiviral activity of GLPG, cells were treated with GLPG before, during and after infection, and the viral titers in the supernatant of cell culture 48 h post-infection were tested by TCID(50) assay. The antiviral effects in pre-treated and treated during virus infection with GLPG were more remarkable than the treatment of post-infection. Although the precise mechanism has yet to be defined, our work suggested that GLPG inhibits viral replication by interfering with the early events of viral adsorption and entry into target cells. Thus, this proteoglycan seems to be a potential candidate for anti-HSV agents.

Animals↗

PubMed2004

Binding of Cu2+ to S-adenosyl-L-homocysteine hydrolase.

S-Adenosylhomocysteine (AdoHcy) hydrolase regulates biomethylation and homocysteine metabolism. It has been proposed to be a copper binding protein playing an important role in copper transport and distribution. In the present work, the kinetics of binding and releasing of copper ions was studied using fluorescence method. The dissociation constant for copper ions with AdoHcy hydrolase was determined by fluorescence quenching titration and activity titration methods using ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), and glycine as competitive chelators. The experimental results showed that copper ions bind to AdoHcy hydrolase with a K(d) of approximately 10(-11) M. The association rate constant was determined to be 7 x 10(6) M(-1)s(-1). The releasing of copper ions from the enzyme was found to be biphasic with a k(1) of 2.8 x 10(-3) s(-1) and k(2) of 1.7x10(-5) s(-1). It is suggested that copper ions do not bind to the substrate binding sites because the addition of adenine substrate did not compete with the binding of copper to AdoHcy hydrolase. Interestingly, it was observed that EDTA could bind to AdoHcy hydrolase with a dissociation constant of K(1) = 8.0 x 10(-5) M and result in an increased affinity (K(d) = approximately 10(-17) M) of binding of copper ions to the enzyme.

Adenosylhomocysteinase↗

PubMed2004

A gene family of cathepsin L-like proteases of filarial nematodes are associated with larval molting and cuticle and eggshell remodeling.

Cysteine proteinases are involved in a variety of important biological processes and have been implicated in molting and tissue remodeling in free living and parasitic nematodes. We show that in the lymphatic filarial nematode Brugia pahangi molting of third-stage larvae (L3) to fourth-stage larvae is dependent on the activity of a cathepsin L-like cysteine protease (CPL), which can be detected in the excretory/secretory (ES) products of molting L3. Directed cloning of a cysteine protease gene in B. pahangi and analysis of the expressed sequence tag (EST) and genomic sequences of the closely related human lymphatic filarial nematode Brugia malayi have identified a family of CPLs. One group of these enzymes, Bm-cpl-1, -4, -5 and Bp-cpl-4, is highly expressed in the B. malayi and B. pahangi infective L3 larvae. Immunolocalization indicates that the corresponding enzymes are synthesized and stored in granules of the glandular esophagus of L3 and released during the molting process. Functional analysis of these genes in Brugia and closely related CPL genes identified in the filarial nematode Onchocerca volvulus and the free living model nematode Caenorhabditis elegans indicate that these genes are also involved in cuticle and eggshell remodeling.

Animals↗

PubMed2004

RNA interference targeting cathepsin L and Z-like cysteine proteases of Onchocerca volvulus confirmed their essential function during L3 molting.

We describe the successful use of RNA interference (RNAi) to investigate gene function in the human filarial parasite Onchocerca volvulus third-stage larvae (L3). We targeted two specific gene products, the O. volvulus cathepsin L (Ov-CPL) and cathepsin Z-like (Ov-CPZ) cysteine proteases, which were proposed to function during O. volvulus L3 molting. We show that fluorescent-labeled Cy3-dsRNA corresponding to cpl or cpz regions encoding the mature enzymes can enter the larvae. The molting rate of larvae treated overnight with 0.5 mg ml(-1) cpl was reduced by 92% and 86% in comparison to normal control worms. It appeared that although the larvae started the molting process the last stage of molting, ecdysis was inhibited. The effect was gene specific, as larvae that did not molt in the presence of cpl or cpz dsRNA expressed the other cysteine protease, CPZ and CPL, respectively. This was confirmed by immunoelectron microscopy using antibodies directed against each enzyme. Our present study validate conclusively that both enzymes are essential for the molting of O. volvulus L3 to fourth-stage larvae. We also confirmed that the activity of the enzymes is specific to the changes that occur during the molting process on days 1-3, when the separation between the cuticles is in progress. The development of RNAi in O. volvulus L3 could further help study many of the abundant L3 and molting L3 genes identified through the filarial genome project, many of which, although have no attributed function, were identified as vaccine candidates or potential drug targets.

Animals↗

PubMed2004

Mathematical modeling of temperature mapping over skin surface and its implementation in thermal disease diagnostics.

In non-invasive thermal diagnostics, accurate correlations between the thermal image on skin surface and interior human pathophysiology are often desired, which require general solutions for the bioheat equation. In this study, the Monte Carlo method was implemented to solve the transient three-dimensional bio-heat transfer problem with non-linear boundary conditions (simultaneously with convection, radiation and evaporation) and space-dependent thermal physiological parameters. Detailed computations indicated that the thermal states of biological bodies, reflecting physiological conditions, could be correlated to the temperature or heat flux mapping recorded at the skin surface. The effect of the skin emissivity and humidity, the convective heat transfer coefficient, the relative humidity and temperature of the surrounding air, the metabolic rate and blood perfusion rate in the tumor, and the tumor size and number on the sensitivity of thermography are comprehensively investigated. Moreover, several thermal criteria for disease diagnostic were proposed based on statistical principles. Implementations of this study for the clinical thermal diagnostics are discussed.

Algorithms↗

PubMed2004

beta(3) Adrenergic receptor polymorphism and obesity-related phenotypes in hypertensive patients.

OBJECTIVES: Obesity is a complex trait that is affected by both environmental and genetic risk factors. The beta(3) adrenergic receptor (ADRB3) is expressed in adipose tissue and plays a role in energy metabolism. A missense mutation on codon 64 of this gene (W64R) is associated with receptor malfunction. Previous studies examining the relation between this polymorphism and obesity produced inconsistent findings. The current study assessed the association between the W64R genotype and obesity-related phenotypes, including body weight, BMI, and serum triglycerides, cholesterol, and glucose. RESEARCH METHODS AND PROCEDURES: We determined the ADRB3 W64R genotypes and fasting serum lipid and glucose concentrations for 695 hypertensive adults (336 men,359 women) from a rural county in Anhui Province, China. Multivariate linear regression models were fit to detect associations between the genetic polymorphism and obesity-related phenotypes. RESULTS: The ADRB3 W64R polymorphism was significantly associated with body weight and BMI in men but not in women. After controlling for potential confounding variables, men who were homozygous for the R64 allele were 11.8 kg heavier (p < 0.001) and had a BMI that was 3.7 kg/m(2) greater (p = 0.001) than men who were homozygous for the W64 allele. Serum concentrations of lipids and glucose were found not associated with the genetic polymorphism. DISCUSSION: The ADRB3 R64 allele was associated with increased body weight and BMI in men but not in women. The genetic association was not modified by triglyceride, cholesterol, blood glucose, or blood pressure levels of the subjects.

Adult↗

PubMed2004

Beta2 adrenergic receptor gene Arg16Gly polymorphism is associated with therapeutic efficacy of benazepril on essential hypertension in Chinese.

BACKGROUND: There is considerable variability in individual response to antihypertensive agents. The reason for this is not known, but may be related to individual genetic variability. This study examined whether the therapeutic efficacy of benazepril on essential hypertension is modified by beta2 adrenergic receptor gene (ADRB2) Arg16Gly (R16G) polymorphism. METHODS AND RESULTS: We conducted a family-based study of 321 and 610 hypertensive subjects from Yuexi and Huoqiu Counties of Anhui, China, respectively. Both systolic and diastolic blood pressures (SBP and DBP) before and after a 15-day benazepril treatment were measured. ADRB2 R16G genotypes were determined for all subjects. ADRB2 G16 allele frequency was found to be 41.0% and. 47.4% in Huoqiu and Yuexi, respectively. In Yuexi family-based association test (FBAT) revealed that the G16 allele was associated with a greater DBP decrease in response to a 15-day benazepril treatment (Z = 2.12, P = 0.03), and the data were consistent with a dominant inheritance model. A similar trend was observed in Huoqiu Chinese, but the magnitudes of effects were smaller and did not reach statistical significance. The FBAT results were further confirmed by using a generalized estimating equation model. CONCLUSION: Our family-based study provided the first evidence that ADRB2 R16G polymorphism may play an important role in DBP response to benazepril treatment, although the magnitude of the effect appears to be modified by other risk factors such as plasma lipid and glucose profiles.

Adult↗

PubMed2004

The time course of hydroxyl radical formation following spinal cord injury: the possible role of the iron-catalyzed Haber-Weiss reaction.

This study explores whether the hydroxyl radical (*OH)-one of the most destructive reactive oxygen species-plays a role in secondary spinal cord injury (SCI). First, we measured the time course of *OH formation in rat spinal tissue after impact SCI by administering salicylate as a trapping agent into the intrathecal space of the cord and measuring the hydroxylation products of salicylate, 2,3- and 2,5-dihydroxybenzoic acid (2,3- and 2,5-DHBA) by HPLC. The 2,3-DHBA concentration was significantly higher in injured spinal tissue than in sham controls at 5 min, 1 and 3 h, but not at 5 h post-injury. Second, we generated *OH by administering H(2)O(2) and FeCl(2)/EDTA (Fenton's reagents) at the concentrations produced by SCI into the gray matter of the cord for 4 h and found that it induced significant cell loss at 24 h post-*OH exposure. Mn (III) tetrakis (4-benzoic acid) porphyrin(MnTBAP)-a broad spectrum reactive species scavenger-significantly reduced *OH-induced cell death. Finally, we generated superoxide and administered FeCl(3)/EDTA in the intrathecal space of the cord at the concentration produced by SCI and measured extracellular *OH formation in the gray matter of the cord by microdialysis sampling. We found that the levels of *OH significantly increased compared to the pre-administration level, indicating that *OH can be produced in vivo by the iron-catalyzed Haber-Weiss reaction. All together, we demonstrated that *OH is an endogenous secondary damaging agent following SCI and the metal-catalyzed Haber-Weiss reaction may contribute to early *OH formation after SCI.

Animals↗

PubMed2004

Expression of hepatitis C virus E2 ectodomain in E. coli and its application in the detection of anti-E2 antibodies in human sera.

The second envelope glycoprotein (E2) of hepatitis C virus has been shown to bind human target cells and has become a major target for the development of anti-HCV vaccines. Anti-E2 antibodies have been suggested to be of clinical significance in diagnosis, treatment and prognosis of hepatitis C. However, large-scale expression and purification of E2 proteins in mammalian cells is difficult. As an alternative, E2 fragment (aa 385 C730) with a four-amino-acid mutation (aa 568 C571 PCNI to RVTS) was expressed as hexa-histidine-tagged full length protein [E2N730(m)] in E. coli and purified to over 85% purity. Purified E2N730(m) was specifically recognized by homologous hepatitis C patient serum in Western blot, suggesting that it displayed E2-specific antigenicity. Rabbit antiserum raised against E2N730(m) recognized E2 glycoproteins expressed in mammalian cells in Western blot. Purified E2N730(m) was used to detect anti-E2 antibodies in human sera and showed better specificity and sensitivity than previously reported C-terminally truncated E2 fragment (aa 385 C565). Association between anti-E2 antibodies in patient sera and HCV RNA status was also demonstrated using this E. coli-derived protein. E2N730(m) might serve as an inexpensive alternative to mammalian cell-expressed E2 proteins in clinical and research applications.

Amino Acid Sequence↗

PubMed2004

A new recombinant single chain trispecific antibody recruits T lymphocytes to kill CEA (carcinoma embryonic antigen) positive tumor cells in vitro efficiently.

Anti-tumor associated antigen (TAA).CD3.CD28 trispecific antibody(TsAb) is able to provide two signals for fully and continuously activation of T lymphocytes and recruit them around tumor cells, presenting an attractive concept in tumor immunotherapy. Here, a new single chain trispecific antibody (scTsAb), named CEA-scTsAb, was constructed by fusion of anti-CEA (Carcinoma Embryonic Antigen) single chain antibody (scFv), anti-CD3 scFv and anti-CD28 VH, spaced by polypeptide interlinkers taken from the fragment of constant region (FC) of human IgG and human serum albumin (HSA). It was expressed in Escherichia coli at low temperature (30 degrees C) with up to 50% of the antibody being present in soluble form. After one step of DEAE anion chromatography, the soluble product was sufficiently pure for further in vitro activity assays. First, it was proved that CEA-scTsAb could recognize three antigens (CEA, CD28 and Jurkat cell membrane antigen) specifically and could distinguish antigen positive cells from antigen negative cells in vitro. Then fresh PBMC (peripheral blood mononuclear cells), without being pre-treated by co-stimulatory reagents, such as IL-2 or CD28 mAb, were used as effector cells to test their ability to mediate tumor specific cytolysis of CEA-positive tumor cells, SW1116. It was found by photomicrography that T lymphocytes were attracted to SW1116 cells in the presence of CEA-scTsAb, which resulted in effective cytolysis of tumor cells. As shown by MTT assay, the efficacy of tumor specific cytolysis mediated by CEA-scTsAb related to both the quantity and activation of PBMC. At an effector cells/target cells ratio (E/T) of 5, it was proved by dual-color FACS with propidium iodide (PI) and FITC-annexin V that both necrosis and apoptosis of tumor cells were causes of tumor specific cytolysis. In summary, a new single chain trispecific (CEA x CD3 x CD28) antibody was constructed and characterized carefully in this paper and was found to possess functions: (i) to activate T lymphocytes independently of additional co-stimulatory signal, (ii) to attract activated T lymphocytes around CEA-positive tumor cells, (iii) to attack CEA-positive tumor cells with recruited T lymphocytes. Because it recognizes a widely distributed tumor antigen (CEA), with moderate molecular weight (about 75 kDa) and a simple production procedure, and is able to mediate a high level of tumor specific cytolysis without any additional co-stimulating reagents, CEA-scTsAb is very promising for the task of immunotherapy in future.

Antibodies, Monoclonal↗

PubMed2004

Cardiovascular disease risk factor levels and their relations to CVD rates in China--results of Sino-MONICA project.

BACKGROUND: The Sino-MONICA project is a 7-year study monitoring trends and determinants of cardiovascular disease (CVD) in geographically defined populations in different parts of China. This report focuses on risk factor levels and their relations to CVD rates. DESIGN: Successive surveys on smoking habits, blood pressure (BP), serum total cholesterol (TC), weight and height were conducted in independent random samples of the same populations early (1987-1988) and late (1992-1993) in the study period, by the methodology and criteria of the WHO MONICA project. Associations between risk levels and CVD rates were also assessed by correlation analysis. RESULTS: In general, the mean level of BP in the populations studied was high by international standards. Serum TC and body mass index (BMI) were low compared with the world average. There were significant geographic variations in CVD risk levels, being higher in the north and lower in the south, which correlated with the north-south difference of CVD event rates. CONCLUSIONS: The Sino-MONICA study has established the feasibility of long-term monitoring of CVD events and risk factors with international standardized methods in Chinese communities. The results will have significance in curbing the CVD epidemic not only in China, but also internationally.

Adult↗

PubMed2004

Hyalinizing Spitz nevus: spindle and epithelioid cell nevus with paucicellular collagenous stroma.

Hyalinizing spindle and epithelioid cell nevus (Spitz nevus) is an uncommon melanocytic lesion. The histologic features of this benign tumor can mimic those of certain benign (dermatofibroma and desmoplastic cellular blue nevus) and malignant (metastatic carcinoma and malignant melanoma) neoplasms. We report a woman with a hyalinizing Spitz nevus and review the clinical characteristics, histologic features, and differential diagnosis of this lesion. The lesion presented as an asymptomatic red firm nodule on her abdomen. Microscopic examination showed a symmetric lesion in the dermis. The neoplastic cells were large and epithelioid-shaped or plump and spindle-shaped. They were present as isolated individual cells, single cells in a linear pattern, small nests, and fascicles in a paucicellular hyalinized stroma. Neoplastic cells with prominent eosinophilic nucleoli were evenly exhibited from the superficial to deep lesion. Diffuse expression of S-100 protein and absence of staining with antibodies to cytokeratin and HMB-45 were observed. The features were diagnostic of a hyalinizing Spitz nevus. Hyalinizing Spitz nevus is a benign lesion whose histologic features may mimic dermatofibroma, desmoplastic cellular blue nevus, metastatic carcinoma, and malignant melanoma. Immunohistochemical studies are helpful to differentiate these lesions.

Abdomen↗

PubMed2004

A multiagent genetic algorithm for global numerical optimization.

In this paper, multiagent systems and genetic algorithms are integrated to form a new algorithm, multiagent genetic algorithm (MAGA), for solving the global numerical optimization problem. An agent in MAGA represents a candidate solution to the optimization problem in hand. All agents live in a latticelike environment, with each agent fixed on a lattice-point. In order to increase energies, they compete or cooperate with their neighbors, and they can also use knowledge. Making use of these agent-agent interactions, MAGA realizes the purpose of minimizing the objective function value. Theoretical analyzes show that MAGA converges to the global optimum. In the first part of the experiments, ten benchmark functions are used to test the performance of MAGA, and the scalability of MAGA along the problem dimension is studied with great care. The results show that MAGA achieves a good performance when the dimensions are increased from 20-10,000. Moreover, even when the dimensions are increased to as high as 10,000, MAGA still can find high quality solutions at a low computational cost. Therefore, MAGA has good scalability and is a competent algorithm for solving high dimensional optimization problems. To the best of our knowledge, no researchers have ever optimized the functions with 10,000 dimensions by means of evolution. In the second part of the experiments, MAGA is applied to a practical case, the approximation of linear systems, with a satisfactory result.

Journal Article↗

PubMed2004

Control reconfiguration of discrete event systems controllers with partial observation.

In this paper, we develop a framework for reconfiguration of a discrete event system (DES) controller, which has a dynamic event observation set. We will show the designed reconfiguration yields a more tolerable controller than the one designed in [5]. Starting with a maximally permissive controller that has a full observation of its DES, we design a mega-controller that monitors the observation set of the DES controller and its state continuously. Upon a change in the observation set, the mega-controller reconfigures the controller by a aggregation or disaggregation of the controller states. The mega-controller is also responsible for feedback function adjustments if the available observation set causes a conflict in control. We illustrate the reconfiguration procedures by an example.

Algorithms↗

PubMed2004

Study on immunological status of Chinese HIV-infected individuals.

HIV-1 infection is characterized by a gradual decline of immune function, and the immune dysfunction is widely regarded as one of the most important determinants of disease progression. The present study was performed to analyze in more detail the immunological status of HIV-infected people in China. T cell counts, activation of T cells, HIV-1 specific CTL and plasma levels of cytokines were determined with flow cytometry, IFN-gamma Elispot or ELISA techniques. The HIV viral load was negatively correlated with CD4(+), CD8(+) T cell counts (r=-0.654, P<0.001; r=-0.228, P<0.05); the breadth and magnitude of HIV-1 specific CTL responses against HIV-1 Gag peptides was related to disease progression; the activation of CD8(+) T cells was significantly higher than that in HIV-negative controls; the level of plasma IL-12 was much lower and the plasma IFN-gamma, IL-10 and IL-6 were much higher in HIV-infected persons than in HIV-negative controls (P<0.05). Study on immunological status in HIV-infected Chinese is very important in predicting the disease progression and providing information for HAART therapy in China.

Amino Acid Sequence↗

PubMed2004

Displacements of prohead protease genes in the late operons of double-stranded-DNA bacteriophages.

Most of the known prohead maturation proteases in double-stranded-DNA bacteriophages are shown, by computational methods, to fall into two evolutionarily independent clans of serine proteases, herpesvirus assemblin-like and ClpP-like. Phylogenetic analysis suggests that these two types of phage prohead protease genes displaced each other multiple times while preserving their exact location within the late operons of the phage genomes.

Amino Acid Sequence↗

PubMed2004

c-Jun N-terminal protein kinase 1 (JNK1), but not JNK2, is essential for tumor necrosis factor alpha-induced c-Jun kinase activation and apoptosis.

Two ubiquitously expressed isoforms of c-Jun N-terminal protein kinase (JNK), JNK1 and JNK2, have shared functions and different functions. However, the molecular mechanism is unknown. Here we report that JNK1, but not JNK2, is essential for tumor necrosis factor alpha (TNF-alpha)-induced c-Jun kinase activation, c-Jun expression, and apoptosis. Using mouse fibroblasts deficient in either Jnk1 or Jnk2, we found that JNK1 was activated by TNF-alpha, whereas JNK2 activation was negligible. In addition, JNK2 interfered with JNK1 activation via its "futile" phosphorylation by upstream kinases. Consequently, expression and activation of c-Jun, which depends on JNK activity, were impaired in Jnk1 null cells but enhanced in Jnk2 null cells. TNF-alpha-induced apoptosis was also suppressed in Jnk1 null fibroblasts but increased in Jnk2 null cells. Thus, our results provide a molecular mechanism underlying the different biological functions of JNK isoforms.

Animals↗