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Biomedical subjects

Fang Li

Publications and source records attributed to Fang Li.

106 records · Page 6Linked to original sources
PubMed2003

[Phase II clinical study of intratumoral H101, an E1B deleted adenovirus, in combination with chemotherapy in patients with cancer].

BACKGROUND & OBJECTIVE: In recent years,great development have been made in cancer therapeutics with replication-competent viruses (oncolytic viruses), E1B deleted adenovirus is one of promising viruses. The current study was designed to evaluate the efficacy and toxicity of intratumoral H101, a E1B-deleted adenovirus, in combination with chemotherapy on patients with cancer. METHODS: A total of 50 patients with malignant tumors in multiple centers clinical trial were treated with H101, 0.5ml 5x10(11) viral particle per day for 5 consecutive days every three weeks. Routine chemotherapy was performed at the same time. And the efficacy and toxicity were recorded. RESULTS: Among 46 valuable cases, the overall response rate was 30.4%. The response rate was 28.0% (14/50) among ITT population, including 3 complete response (CR) and 11 partial response (PR). The overall response rate of control lesion was 13.0%, including 1 case of CR and 5 cases of PR. Thus, the response rate in injected lesion is clearly higher than that in control lesion (P< 0.001). Main side effects were injection site pain (26.9%) and fever (30.2%). Grade 1 hepatic dysfunction was found in 4 patients, grade 2 in 1 patients, grade 4 in 1 patients. Grade 4 hematological toxicities were found in 4 patients. CONCLUSION: The study showed that the combination of genetically modified adenovirus (H101) and chemotherapy possessed some effect for treating the patients with refractory malignant tumors, and the toxicities were lower, well tolerated.

Adenoviridae↗
PubMed2003

[Noninvasive continuous measurement of blood glucose concentration via animal skin].

In this study we deliberated over the principles and methods and then took the noninvasive continuous measurement of blood glucose concentration through the skin of rabbits. The glucose oxidase sensor was made by covalent immobilization. The best making method of sensor and stable working condition were sifted. Ten female and 10 male adult white rabbits were allocated into the groups of the ante-ultrasound and post-ultrasound, the injection of glucose, and the high and low frequency ultrasounds. After the skin surface was treated by high or low frenquency ultrasound for 5 minutes on the rabbits, obvious changes (P < 0.01) of post-ultrasound and post-injection of glucose were observed by means of glucose oxidase sensor and microcurrent apparatus. After application of ultrasound to the skin of rabbits, the penetration of glucose through the rabbit skin increased obviously. The change of microcurrent signal that was exchanged by the glucose sensor correlated positively with the concentration of glucose of rabbit body. The blood glucose can be tested by the glucose sensor on the skin surface of living animal.

Animals↗
PubMed2002

Crystal structures of the Bacillus stearothermophilus CCA-adding enzyme and its complexes with ATP or CTP.

CCA-adding enzymes polymerize CCA onto the 3' terminus of immature tRNAs without using a nucleic acid template. The 3.0 A resolution crystal structures of the CCA-adding enzyme from Bacillus stearothermophilus and its complexes with ATP or CTP reveal a seahorse-shaped subunit consisting of four domains: head, neck, body, and tail. The head is structurally homologous to the palm domain of DNA polymerase beta but has additional structural features and functions. The neck, body, and tail represent new protein folding motifs. The neck provides a specific template for the incoming ATP or CTP, whereas the body and tail may bind tRNA. Each subunit has one active site capable of switching its base specificity between ATP and CTP, an important component of the CCA-adding mechanism.

Adenosine Triphosphate↗
PubMed2002

C-terminal domain phosphatase-like family members (AtCPLs) differentially regulate Arabidopsis thaliana abiotic stress signaling, growth, and development.

Cold, hyperosmolarity, and abscisic acid (ABA) signaling induce RD29A expression, which is an indicator of the plant stress adaptation response. Two nonallelic Arabidopsis thaliana (ecotype C24) T-DNA insertional mutations, cpl1 and cpl3, were identified based on hyperinduction of RD29A expression that was monitored by using the luciferase (LUC) reporter gene (RD29ALUC) imaging system. Genetic linkage analysis and complementation data established that the recessive cpl1 and cpl3 mutations are caused by T-DNA insertions in AtCPL1 (Arabidopsis C-terminal domain phosphatase-like) and AtCPL3, respectively. Gel assays using recombinant AtCPL1 and AtCPL3 detected innate phosphatase activity like other members of the phylogenetically conserved family that dephosphorylate the C-terminal domain of RNA polymerase II (RNAP II). cpl1 mutation causes RD29ALUC hyperexpression and transcript accumulation in response to cold, ABA, and NaCl treatments, whereas the cpl3 mutation mediates hyperresponsiveness only to ABA. Northern analysis confirmed that LUC transcript accumulation also occurs in response to these stimuli. cpl1 plants accumulate biomass more rapidly and exhibit delayed flowering relative to wild type whereas cpl3 plants grow more slowly and flower earlier than wild-type plants. Hence AtCPL1 and AtCPL3 are negative regulators of stress responsive gene transcription and modulators of growth and development. These results suggest that C-terminal domain phosphatase regulation of RNAP II phosphorylation status is a focal control point of complex processes like plant stress responses and development. AtCPL family members apparently have both unique and overlapping transcriptional regulatory functions that differentiate the signal output that determines the plant response.

Arabidopsis↗
PubMed2002

[Effect of interleukin I receptor antigonist gene therapy on arthritis induced by type II collagen in mice].

OBJECTIVE: To investigate the effect of interleukin-1 receptor antagonist gene therapy on type II collagen induced arthritis in DBA/1 mice. METHODS: Plasmid pcDI-IL-1ra that expresses IL-1ra in eukaryotes was constructed by inserting human IL-1ra cDNA into the eukaryotic expression vector pcDI. Eukaryotes were transfected with the plasmid pcDI-IL-1ra in vivo and in vitro. The expression of 8 IL-1ra was examined by ELISA and immunohistochemistry. Type II collagen was used to induced arthritis in 32 DBA/1 mice. This plasmid was injected into the muscles of DBA/1 mice with arthritis induced by type II collagen by gene gun (20 micro g/mouse) and into the muscle of 8 mice by intramuscular injection (200 micro g/mouse). After the administration, the condition of arthritis was observed. The serum IL-ira was examined 6 and 12 days after administration. The expression of IL-ira in muscles was tested by computerized imaging analysis. RESULTS: PCR and DNA sequencing proved the accuracy of the inserted fragment. ELISA and immunohistochemistry detected high expression of IL-ira in vivo and in vitro. The absorbance ( A ) 490 value of IL-ira in the mouse muscle was 0.52 +/- 0.03 in gene gun group, and 0.48 +/- 0.02 in intramuscular injection group, all higher than that in the control group (0.41 +/- 0.02,P < 0.01 and P < 0.05). The serum IL-ira values in the gene gun group and in tramuscular injection group 6 days and 12 days after therapy were all significantly higher than that in the control group (all P < 0.01; and P < 0.01 and P < 0.05). Since the 6 th day after therapy, the redness and swelling of joints in both therapies groups were alleviated. Pathological examination made 12 days after therapy showed relief at different degrees of the infiltration of inflammatory cells, hyperplasia of synovia, bone infiltration, and cartilage destruction, especially in the gene gun group. CONCLUSION: Gene therapy of IL-ira via non-virus eukaryotic expression vactor, especially by gene gun, is effective in treating arthritis induced by type II collagen.

Animals↗
PubMed2002

CXCL8((3-73))K11R/G31P antagonizes ligand binding to the neutrophil CXCR1 and CXCR2 receptors and cellular responses to CXCL8/IL-8.

We recently reported that CXCL8((3-73))K11R is a high affinity agonist of neutrophil activation and chemotactic responses. In this report we employed CXCL8((3-73))K11R as a template to generate CXCL8/IL-8 analogues with antagonist activities, using site-directed mutagenesis to introduce conservative amino acid substitutions into the first turn within the molecule's beta-pleated sheet region (G31P, P32G) and, in association with these, into the putative receptor-recognition site (T12S, H13F, F17S). We then examined their impact on the analogues' biological activities and found that a G31P substitution rendered CXCL8((3-73))K11R a high affinity antagonist of CXCL8/IL-8. The ranking (in the order of decreasing CXCL8/IL-8 antagonist activities) of the CXCL8((3-73))K11R analogues we generated was, G31P>T12S/G31P>H13F/G31P>T12S/H13F/G31P>>P32G approximately T12S/P32G approximately H13F/P32G>T12S/H13F/P32G; CXCL8((3-73))K11R/F17S did not inhibit CXCL8/IL-8-dependent responses. CXCL8((3-73))K11R/G31P had no discernible agonist (beta-glucuronidase release, chemotactic) activity, but at 12.5 ng/ml it bound to purified neutrophils more avidly than did 1.25 microg/ml CXCL8/IL-8. Furthermore, CXCL8((3-73))K11R/G31P competitively antagonized the binding of CXCR1- and CXCR2-specific antibodies to these receptors. Taken together, these data thus provide further impetus to the study of the potential efficacy of CXCL8((3-73))K11R/G31P as a broad-spectrum antagonist of the ELR-CXC chemokines in experimental and clinical settings.

Amino Acid Sequence↗
PubMed2002

Synergistic enhancement of antitumor immunity with adoptively transferred tumor-specific CD4+ and CD8+ T cells and intratumoral lymphotactin transgene expression.

The lack of efficient T-cell infiltration of tumors is a major obstacle to successful adoptive T-cell therapy. We have shown that transplanted SP2/0 myeloma tumors that have been engineered to express lymphotactin (Lptn) invariably regress under the influence of infiltrating XCR1+T cells and neutrophils. Herein, we characterize these T cells and investigate their therapeutic efficacy, either alone or with Lptn gene therapy. After stimulation with SP2/0 cells, these T cells were CD25+FasL+L-selectin-, expressed XCR-1, and were chemoattracted by Lptn in vitro. They comprised 66% CD4+ Th1 and 33% CD8+ Tc1 cells, both of which expressed significant amounts of IFN-gamma, perforin, and tumor necrosis factor-alpha, but not interleukin-4. The CD4+ Th1 and CD8+ Tc1 cells, which were inhibited and stimulated, respectively, for proliferation with Lptn signaling, displayed 38 and 84% specific killing, respectively, for Ia(d)/H-2K(d)-expressing SP2/0 tumor cells (E:T ratio, 100). In vivo, combined intratumoral Lptn gene transfer and adoptive immunotherapy with these CD4+ and CD8+ T cells eradicated well-established SP2/0 tumors in six of eight mice, and dramatically slowed tumor growth in the other two mice. Cell tracking using labeled T cells confirmed that these cells infiltrated better into the Lptn-expressing tumors than non-Lptn-expressing ones. Control or Lptn adenoviral treatments by themselves did not alter the lethal outcome for tumor-bearing mice, nor did T-cell therapy by itself, although the latter two treatments did slow its time frame. Combined Lptn gene transfer and adoptive CD4+ or CD8+ cell transfers were not nearly as efficacious as the combined Lptn gene and unfractionated T-cell transfers. Taken together, our data provide solid evidence of a potent synergy between adoptive CD4+ and CD8+ T-cell therapy and Lptn gene transfer into tumor tissues, which culminated in the eradication of well-established tumor masses.

Adenoviridae↗
PubMed2002

Tumor antigen drives a persistent oligoclonal expansion of CD8+ T cells in aged mice.

Oligoclonal T cell expansions (TCE) are common in old humans and mice, but it is not known whether the T cell response to a specific antigen is more restricted in old vs. young animals. Herein, we describe an enhanced and prolonged response of tumor antigen-specific CD8 cells in old mice identified by K(d)/peptide tetramers and Vbeta10 staining. At the onset of the response CD8 T cell numbers and Vbeta10+CD8+ cells at the site of tumor injection were lower in old mice, hinting that control of initial tumor growth may not be optimal. As further evidence of a dysregulated response in old mice, antibody titers to the tumor were deficient and the CD8 tumor antigen-specific response was greater and more prolonged in the blood and spleen. Old mice selected a more oligoclonal TCR repertoire based on TCRbeta chain CDR3 length analysis and sequences. Persistent expansions of Vbeta10+CD8+ cells in old mice had memory/activation phenotypes. This induced tumor antigen-specific response may represent a model for the spontaneous TCE observed with aging and demonstrates that the CD8 response to a defined peptide/MHC antigen is indeed more oligoclonal in old mice.

Aging↗
PubMed2002

Preparation of oxidized glucose-crosslinked N-alkylated chitosan membrane and in vitro studies of pH-sensitive drug delivery behaviour.

Glucose was oxidized to generate a glucose dialdehyde and chitosan (CS) was hydrophobicallly modified with butyl bromide, octyl bromide and dexyl bromide. The analysis of IR and X-ray diffraction results of CS derivatives confirms that the hydrogen bonds and crystallinity were weakened by the incorporation of pendant alkyl. The permeability coefficient P and diffusion coefficient D for model drug vitamin B2 through oxidized glucose-crosslinked alkylated CS membrane were determined under different pH media. The results show that for the same alkylated CS in different pH media, P and D decrease with an increase in pH; for different alkxylated CSs in acidic media, P and D diminish with the increase in the length of alkyl side, which is supposedly originated from the enhancement of hydrophobicity. In alkali medium, P and D show a rising trend with the increase in the length of alkyl chain, which might be related to the loose stacking of network as it occurs to shrink in alkali medium. The preliminary cytotoxicity assay indicates that oxidized glucose-crosslinked alkylate CS membrane is non-toxic in vitro.

Alkylation↗
PubMed2002

CXCL8((3-73))K11R/G31P antagonizes the neutrophil chemoattractants present in pasteurellosis and mastitis lesions and abrogates neutrophil influx into intradermal endotoxin challenge sites in vivo.

The ELR(+) CXC chemokines are critical for protective neutrophil responses to most bacterial infections, but nevertheless can contribute importantly to the pathogenic effects of many inflammatory responses. We recently engineered a series of high affinity CXCL8/IL-8 antagonists, one of which, CXCL8((3-73))K11R/G31P, binds very strongly to neutrophils via the CXCR1 and CXCR2. Herein we show in competitive 125I-ligand binding assays that bovine CXCL8((3-73))K11R/G31P has an affinity for neutrophils that is 2-3 orders of magnitude higher than that of CXCL8/IL-8. Furthermore, when used at approximately 0.5 nM, CXCL8((3-73))K11R/G31P inhibited by 50% the chemotactic responses of neutrophils to 129 nM CXCL8/IL-8, but it also blocked chemotactic responses to the alternate ELR-CXC chemokines CXCL1/GRO alpha and CXCL5/ENA-78. Furthermore, CXCL8((3-73))K11R/G31P could inhibit by 93-97% the spectrum of neutrophil chemotactic activities present within wash fluids from clinical bacterial pneumonia or experimental endotoxin-induced mastitis lesions. Finally, intramuscular or subcutaneous application of CXCL8((3-73))K11R/G31P (75 micro g/kg) reduced by up to 97% neutrophil infiltration into intradermal endotoxin challenge sites in cattle, and prevented their circulating neutrophils from responding to CXCL8/IL-8 or ENA-78 in vitro. This data thus encourages further investigation of the potential impact of this novel antagonist on ELR-CXC chemokine-driven inflammatory disorders.

Animals↗
PubMed2002

Modulation of osteoblast function using poly(D,L-lactic acid) surfaces modified with alkylation derivative of chitosan.

Poly(D,L-lactic acid) (PDLLA) was modified with alkylated chitosan (N-butyl chitosan and N-cetyl chitosan), and the effects of modified films on the functions of rat osteoblasts were investigated. The characteristics of surfaces (both modified and control) were examined by water contact angle measurement and electron spectroscopy for chemical analysis (ESCA). Cell morphologies on these surfaces were taken using scanning electron microscopy (SEM). Cell attachment and proliferation were used to assess cell behavior on modified surface and control. MTT assay was used to determined cell viability, and alkaline phosphatase (ALP) activity was taken to evaluate differentiated cell function. Compared with the untreated films, no significant difference in cell attachment of osteoblasts was found on the modified films at a period of 8 h (p > 0.05). However, cell proliferation of N-butyl chitosan rather than N-cetyl chitosan modified PDLLA films was significantly higher than that found on control one (p < 0.05) at the end of the 4th and 7th days. The cell viability of osteoblasts on N-butyl chitosan modified PDLLA films were found higher than that on control (p < 0.05). These results suggested that N-butyl chitosan contributed greater than N-cetyl chitosan when used to modify PDLLA films for improving its biocompatibility.

Alkaline Phosphatase↗
PubMed2001

The Adsorption of Gemini and Conventional Surfactants onto Some Soil Solids and the Removal of 2-Naphthol by the Soil Surfaces.

The adsorption of two cationic gemini surfactants, [C(n)H(2n+1) N(+)(CH(3))(2)-CH(2)CH(2)](2).2Br(-), where n=12 and 14, on limestone, sand, and clay (Na-montmorillonite) from their aqueous solution in double-distilled water and the effect of this adsorption on the removal of 2-naphthol have been studied. Compared to those of conventional cationic surfactants with similar single hydrophilic and hydrophobic groups (C(n)H(2n+1)N(+)(CH(3))(3).Br(-), where n=12 and 14), the molar adsorptions of the gemini and the conventional surfactants on Na-montmorillonite are almost identical and very close to their cation exchange capacities. On sand and limestone, the molar adsorption of the cationic gemini surfactants is much larger than that of their corresponding conventional surfactants. Adsorption studies of the pollutants onto the three kinds of solids treated by either the gemini or the conventional surfactants show that the former are both more efficient and more effective at removing 2-naphthol from the aqueous phase. On all three soil solids, the addition of KBr increases the efficiency of the adsorption of both types of cationics and for most cases increases also the maximum amount adsorbed, but decreases slightly the efficiency of removal of 2-naphthol. On limestone, the anionic gemini adsorbs with one hydrophilic group oriented toward the Ca(2+) sites on the surface and its second hydrophilic group oriented toward the aqueous phase. The conventional anionic surfactant forms a double layer. The gemini anionic is more efficient and more effective than the conventional anionic in the removal of 2-naphathol from the aqueous phase. Both anionic conventional and gemini surfactants have no adsorption on sand. The adsorption mechanisms for all the surfactants on the three soil solid surfaces are discussed. Copyright 2001 Academic Press.

Journal Article↗
PubMedDate not supplied

Identification of Candida albicans genes that induce Saccharomyces cerevisiae cell adhesion and morphogenesis.

Morphogenesis and adhesion to host tissues and medical devices contribute to the virulence of Candida albicans, the most common fungal pathogen isolated from humans. However, identification of molecular mechanisms of C. albicans adhesion and morphogenesis has been impaired by the lack of effective molecular and genetic tools available for this organism. Saccharomyces cerevisiae provides an attractive model system for studying C. albicans adhesion and morphogenesis because of its well-characterized genetics and gene expression systems. To gain insight into the genetic mechanisms of C. albicans adhesion and morphogenesis, we used a parallel plate flow chamber to screen and quantitatively characterize attachment to polystyrene of an adhesion-deficient nonfilamentous flo8Delta S. cerevisiae strain expressing a C. albicans genomic library. We identified six C. albicans genes that are capable of promoting cell adhesion and pseudohyphal development in S. cerevisiae. We also analyzed the ability of these adhesion-promoting genes to regulate the expression of FLO11, which encodes an endogenous S. cerevisiae adhesin. One C. albicans gene, EAP1, appears to directly mediate adhesion and morphogenesis while the remaining five (EAP2, SWI1, MSB1, AAF1, and TEC1) upregulate expression of endogenous S. cerevisiae adhesins. These results suggest that S. cerevisiae is a useful system for molecular characterization of factors that regulate C. albicans adhesion and morphogenesis and that parallel plate flow chamber-based adhesion assays can be used in conjunction with genetic screens to identify molecular mechanisms regulating fungal cell adhesion.

Biotechnology↗
PubMedDate not supplied

Inhibition of polycystin-L channel by the Chinese herb Sparganum stoloniferum Buch.-Ham.

The Chinese herb Sparganum stoloniferum Buch.-Ham. (SBH) is frequently used to improve blood circulation and to rehabilitate vascular obstruction in traditional Chinese medicine. It was recently reported that SBH reduces the proliferation of renal epithelial cells stimulated by epidermal growth factor (EGF), and inhibits the phosphorylation of the EGF receptor. SBH has also been used as a trial drug to treat polycystic kidney disease (PKD) patients in China. The potential molecular actions of SBH on PKD remain unknown. Autosomal dominant PKD (ADPKD) is associated with mutations in polycystin-1 or polycystin-2 (PC2). PC2 and its homologue, polycystin-L (PCL), are nonselective cation channels permeable to potassium, sodium, and calcium. Here, we examine the effects of SBH on the human PCL channel expressed in Xenopus oocytes, using 2-microelectrode voltage-clamp electrophysiology and radiotracer uptake measurements. In PCL-expressing oocytes, with or without preincubation with SBH, the PCL channel was inhibited by SBH in a dose-dependent and reversible manner; a concentration of 2% SBH completely abolished the channel activation. The IC50 value for SBH was 0.48% +/- 0.03%, with a 10-min preincubation period. SBH was also found to inhibit the PCL-mediated 45Ca tracer uptake in oocytes. Our study suggests that SBH contains 1 or more yet-to-be determined components that are inhibitors of PCL channel. The therapeutic potential of SBH for ADPKD and its chemical composition remain to be investigated.

Animals↗
PubMedDate not supplied

Shape optimization of plate with static and dynamic constraints via virtual laminated element.

The virtual laminated element method (VLEM) can resolve structural shape optimization problems with a new method. According to the characteristics of VLEM, only some characterised layer thickness values need be defined as design variables instead of boundary node coordinates or some other parameters determining the system boundary. One of the important features of this method is that it is not necessary to regenerate the FE(finite element) grid during the optimization process so as to avoid optimization failures resulting from some distortion grid elements. The thickness distribution in thin plate optimization problems in other studies before is of stepped shape. However, in this paper, a continuous thickness distribution can be obtained after optimization using VLEM, and is more reasonable. Furthermore, an approximate reanalysis method named "behavior model technique" can be used to reduce the amount of structural reanalysis. Some typical examples are offered to prove the effectiveness and practicality of the proposed method.

Computer Simulation↗