Search PubMed⌕ Search

Biomedical subjects

L Cao

Publications and source records attributed to L Cao.

At least 37 records · Page 2Linked to original sources
PubMed2001

Supramolecular organometallic polymer chemistry: multiple morphologies and superstructures from the solution self-assembly of polyferrocene-block-polysiloxane-block-polyferrocene triblock copolymers.

The solution self-assembly of an organometallic-inorganic triblock copolymer, poly(ferrocenyldimethylsilane)-block-poly(dimethylsiloxane)-block-poly-(ferrocenyldimethylsilane) (PFDMS-b-PDMS-b-PFDMS, 3b; block ratio 1:13:1; Mn = 2.88 x 10(4) gmol(-1), polydispersity (PDI) 1.43 (gel permeation chromatography, GPC)) was studied in n-hexane, a PDMS block selective solvent. Transmission electron microscopy (TEM), atomic force microscopy (AFM), and TEM with negative staining analysis of these micellar solutions after solvent evaporation revealed the presence of multiple micellar morphologies including spheres, cylinders, and novel flower-like supramolecular aggregates. TEM analysis of samples fractionated by ultracentrifugation and preparative size-exclusion chromatography suggest that the formation of multiple morphologies is a consequence of compositional variations. When micellar solutions were prepared at 50 degrees C (above the glass transition of the PFDMS core-forming block) flower-like micellar aggregates similar to those present in micellar solutions prepared at room temperature also formed. However, after solvent evaporation, TEM analysis of micellar solutions prepared in decane at about 150 degrees C, above the melt temperature of the PFDMS core (ca. 120-145 degrees C), revealed the presence of spherical micelles (when decane solutions at 150 degrees C were rapidly cooled to room temperature) and rod-like cylindrical micelles (when decane solutions at 150 degrees C were slowly cooled to room temperature). In contrast, poly(ferrocenylmethylethylsilane)block-poly(dimethylsiloxane)-block-poly(ferrocenylmethylethylsilane) (PFMES-b-PDMS-b-PFMES, 4; block ratio 1:16:1; Mn=2.90x10(4)g mol(-1), PDI= 1.42 (GPC)) and poly(ferrocenylmethylphenylsilane)-block-poly(dimethylsiloxane)-block-poly(ferrocenylmethylphenylsilane) (PFMPS-b-PDMS-b-PFMPS, 5; block ratio 1:15:1; Mn=3.00 x 10(4) gmol(-1), PDI = 1.38 (GPC)), which possess completely amorphous organometallic core-forming blocks, formed only spherical micelles in hexane at room temperature. These observations indicate that crystallinity of the insoluble polyferrocenylsilane block is a critical factor in the formation of the nonspherical micelle morphologies.

Journal Article↗
PubMed2001

Glial cell line-derived neurotrophic factor enhances axonal regeneration following sciatic nerve transection in adult rats.

Adult rat sciatic nerve was transected and sutured with an entubulation technique. The nerve interstump gap was filled with either collagen gel (COL) or collagen gel mixed with glial cell line-derived neurotrophic factor (COL/GDNF). Four weeks after nerve transection, horseradish peroxidase (HRP)-labelled spinal cord motoneurons and the myelinated distal stump axons were quantified. Compared with the COL group, the percentages of labeled spinal somas and axon number were significantly increased after topically applied glial cell line-derived neurotrophic factor (GDNF). The functional recovery of the transected nerve was improved in COL/GDNF group. GAP-43 expression was also significantly higher in COL/GDNF group 1 and 2 weeks after sciatic nerve axotomy vs. COL group. These data provide strong evidence that GDNF could promote axonal regeneration in adult rats, suggesting the potential use of GDNF in therapeutic approaches to peripheral nerve injury and neuropathies.

Animals↗
PubMed2001

Roles of aggrecan domains in biosynthesis, modification by glycosaminoglycans and product secretion.

Aggrecan is a member of the chondroitin sulphate (CS) proteoglycan family, which also includes versican/PG-M, neurocan and brevican. Members of this family exhibit structural similarity: a G1 domain at the N-terminus and a G3 domain at the C-terminus, with a central sequence for modification by CS chains. A unique feature of aggrecan is the insertion of three additional domains, an inter-globular domain (IGD), a G2 domain and a keratan sulphate (KS) domain (sequence modified by KS chains), between the G1 domain and the CS domain (sequence modified by CS chains). The G1 and G3 domains have been implicated in product secretion, but G2, although structurally similar to the tandem repeats of G1, performs an unknown function. To define the functions of each aggrecan domain in product processing, we cloned and expressed these domains in various combinations in COS-7 cells. The results indicated that the G3 domain enhanced product secretion, alone or in combination with the KS or CS domain, and promoted glycosaminoglycan (GAG) chain attachment. Constructs containing the G1 domain were not secreted. Addition of a CS domain sequence to G1 reduced this inhibition, but GAG chain attachment was still decreased. The potential GAG chain attachment site in the IGD was occupied by GAGs, and IGD product was secreted efficiently. The KS domain was modified by GAG chains and secreted. Finally, the G2 domain was expressed but not secreted, and inhibited secretion of the IGD when expressed as an IGD-G2 combination.

Aggrecans↗
PubMed2001

Versican modulates embryonic chondrocyte morphology via the epidermal growth factor-like motifs in G3.

This investigation was designed to characterize the effect of the extracellular matrix molecule versican on chondrocyte morphology, using the well-studied chondrocyte cell culture system. When cultured chondrocytes reverted or "dedifferentiated" to a fibroblast-like morphology, we found that versican expression was significantly enhanced. Transfection of chondrocytes, isolated from embryonic chicken sterna, with a chicken miniversican construct accelerated the reversion process, while expression of an antisense construct inhibited it. A mutant miniversican lacking two epidermal growth factor-like motifs (versicanDeltaEGF) promoted differentiation, as shown by morphological changes and changes in the expression of other extracellular matrix molecules. A truncated versican mutant, the G3DeltaEGF, a G3 domain lacking its two epidermal growth factor-like motifs, also enhanced differentiation. This effect is related to G3DeltaEGF-induced change in cytoskeleton, since transfected cells exhibited misassembly of actin filaments. This article thus provides the first evidence that versican modulates chondrocyte morphology via changes in cytoskeletal structure, and may imply that extracellular matrix molecules play an important role in cell differentiation.

Actins↗
PubMed2001

Identification of the motif in versican G3 domain that plays a dominant-negative effect on astrocytoma cell proliferation through inhibiting versican secretion and binding.

This study was designed to investigate the mechanisms by which mutant versican constructs play a dominant-negative effect on astrocytoma cell proliferation. Although a mini-versican or a versican G3 construct promoted growth of U87 astrocytoma cells, a mini-versican lacking epidermal growth factor (EGF) motifs (versicanDeltaEGF) and a G3 mutant (G3DeltaEGF) exerted a dominant-negative effect on cell proliferation. G3DeltaEGF-transfected cells formed smaller colonies, arrested cell cycle at G(1) phase, inhibited expression of cell cycle proteins cdk4 and cyclin D1, and contained multiple nucleoli. In cell surface binding assays, G3 products expressed in COS-7 cells and bacteria bound to U87 cell surface. G3DeltaEGF products exhibited decreased binding activity, but higher levels of G3DeltaEGF products were able to inhibit the binding of G3 to the cell surface. G3DeltaEGF expression inhibited secretion of endogenous versican in astrocytoma cells and also inhibited the secretion of mini-versican in COS-7 cells co-transfected with the mini-versican and G3DeltaEGF constructs. The effect seems to depend on the expression efficiency of G3DeltaEGF, and it occurred via the carbohydrate recognition domain.

Amino Acid Motifs↗
PubMed2001

Study on apoptosis and expression of P53, bcl-2, Bax in cardiac myocytys of congestive heart failure induced by ventricular pacing.

The apoptosis and the expression of p53, bcl-2 and Bax in myocytes of chronic rapid ventricular pacing-induced congestive heart failure (CHF) in rabbits were investigated. The CHF rabbit model (P, n = 7) was established by chronic rapid ventricular pacing for 3 weeks. By using TUNEL technique the apoptosis in the myocytes in the rabbit model was studied and the expression of p53, bcl-2 and Bax in myocytes was detected by using immunohistochemical method. Sham-operated (C, n = 9) group served as control group. The results showed that there were about 4033 +/- 884.56 apoptotic cells/10(6) myocytes in P group, but no apoptotic cells were found in C group. Myocytes positive for p53 immunoreactivity (18.86 +/- 8.48 vs 5.06 +/- 0.87, P < 0.01) and positive for Bax immunoreactivity (7.15 +/- 1.91 vs 0.43 +/- 0.09, P < 0.01) were increased in P group as compared with those in C group, while the myocytes positive for bcl-2 immunoreactivity (7.08 +/- 1.05 vs 14.97 +/- 4.47, P < 0.01) and the ratio of bcl-2/Bax were decreased in P group as compared with those in C group. Apoptosis was involved in the development of CHF induced by continuously rapid ventricular pacing in rabbit. The expression of p53 and Bax was increased, while the expression of bcl-2 was inhibited. These might play an important role in the acceleration of the apoptosis.

Animals↗
PubMed2001

Glial cell line-derived neurotrophic factor promotes survival and induces differentiation through the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathway respectively in PC12 cells.

PC12-GFRalpha1 cells, a clonal cell line engineered to express glial cell line-derived neurotrophic factor receptor alpha1 were constructed. Given glial cell line-derived neurotrophic factor could induce the differentiation and promote the survival of PC12-GFRalpha1 cells at low concentrations, the cells provide an unlimited source of monoclonal cells for studies on the signal transduction pathway of glial cell line-derived neurotrophic factor. To characterize the involvement of the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways in the biological effect of glial cell line-derived neurotrophic factor, we used the mitogen-activated protein kinase kinase inhibitor PD98059 and the phosphatidylinositol 3-kinase inhibitor LY294002. PD98059 blocked glial cell line-derived neurotrophic factor-induced PC12-GFRalpha1 cells neurite formation in a dose-dependent manner, without significantly altering cell viability. LY294002 reversed the survival-promoting effect of glial cell line-derived neurotrophic factor on the PC12-GFRalpha1 cells in serum-deprived medium. The present study demonstrates that phosphatidylinositol 3-kinase pathway seems to mediate the survival-promoting effect of glial cell line-derived neurotrophic factor on PC12-GFRalpha1 cells, while the activation of mitogen-activated protein kinase pathway could be an important step in mediating PC12-GFRalpha1 cells differentiation induced by glial cell line-derived neurotrophic factor. Therefore, it is inferred that similar intracellular signaling components are used by distinct growth factors toward a common biological effect.

Animals↗
PubMed2001

Genetic interactions between tumor suppressors Brca1 and p53 in apoptosis, cell cycle and tumorigenesis.

Breast cancer is a chief cause of cancer-related mortality that affects women worldwide. About 8% of cases are hereditary, and approximately half of these are associated with germline mutations of the breast tumor suppressor gene BRCA1 (refs. 1,2). We have previously reported a mouse model in which Brca1 exon 11 is eliminated in mammary epithelial cells through Cre-mediated excision. This mutation is often accompanied by alterations in transformation-related protein 53 (Trp53, encoding p53), which substantially accelerates mammary tumor formation. Here, we sought to elucidate the underlying mechanism(s) using mice deficient in the Brca1 exon 11 isoform (Brca1Delta11/Delta11). Brca1Delta11/Delta11 embryos died late in gestation because of widespread apoptosis. Unexpectedly, elimination of one Trp53 allele completely rescues this embryonic lethality and restores normal mammary gland development. However, most female Brca1Delta11/Delta11 Trp53+/- mice develop mammary tumors with loss of the remaining Trp53 allele within 6-12 months. Lymphoma and ovarian tumors also occur at lower frequencies. Heterozygous mutation of Trp53 decreases p53 and results in attenuated apoptosis and G1-S checkpoint control, allowing Brca1Delta11/Delta11 cells to proliferate. The p53 protein regulates Brca1 transcription both in vitro and in vivo, and Brca1 participates in p53 accumulation after gamma-irradiation through regulation of its phosphorylation and Mdm2 expression. These findings provide a mechanism for BRCA1-associated breast carcinogenesis.

Animals↗
PubMed2001

Enantioselective sensor based on microgravimetric quartz crystal microbalance with molecularly imprinted polymer film.

We report a novel quartz crystal microbalance sensor that provides enantioselectivity to dansylphenylalanine enantiomers by using a molecularly imprinted polymer film as a recognition element. The polymeric recognition thin film, imprinted with chiral dansyl-L-phenylalanine, was immobilised on a gold electrode modified with a photoactive precursor monolayer via a self-assembly process using photopolymerization. The fabricated sensor was able to discriminate between L- and D-dansylphenylalanine enantiomers in solution owing to the enantioselectivity of the imprinted sites. The enantiomeric composition of L- and D-enantiomeric mixtures could be quantitatively determined by the fabricated sensor. The detection limit is 5 micrograms mL-1 with a response range of 5-500 micrograms mL-1 at pH 10.0. The influence of the template concentration on the sensitivity and selectivity of the synthesised polymer membranes was investigated and optimised. The surface characteristics of the polymer coating were studied by varying the pH value of the buffer solution, and a convenient regeneration process was proposed to increase the reproducibility and reusability of the sensor by flushing with pH 2.0 buffer. The selectivity and recognition mechanism of the imprinted polymer film were studied with compounds that are structurally related to the template. The method presented in this work provides a novel means of preparing highly selective and sensitive chemical sensors via self-assembly and molecularly imprinting techniques.

Journal Article↗
PubMed2001

High sensitivity microgravimetric biosensor for qualitative and quantitative diagnostic detection of polychlorinated dibenzo-p-dioxins.

A piezoelectric immunosensor system was developed for the rapid detection of polychlorinated dibenzo-p-dioxins (PCDDs). The system uses a competitive inhibition enzyme immunoassay (EIA) based on a mouse monoclonal antibody that is specific for 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and a conjugate of a dioxin-like competitor coupled to the enzyme horseradish peroxidase (HRP). The anti-dioxin antibody was deposited on a 10 MHz AT-cut quartz crystal resonator modified with a self-assembly monolayer of dithiobis-N-succinimidyl propionate. PCDDs at different concentrations in the range 0.001-10 ng mL-1 were mixed with a constant amount of HRP-conjugated competitor. The frequency responses due to the adsorption of the mixed samples on the biosensor surface were measured. The results show that 2,3,7,8-TCDD can be quantitatively detected with the developed immunosensor in the concentration range 0.01-1.3 ng mL-1. Cross-reactivities of the biosensor to various PCDD congeners were also investigated. The sensitivity and selectivity of the quartz crystal microbalance (QCM) biosensor is comparable to EIA and ELISA methods in the detection of polychlorinated dibenzo-p-dioxins. The developed QCM immunosensing system offers significant improvements in speed, sample throughout and cost for the qualitative and quantitative detection of PCDDs compared with GC-MS.

Journal Article↗
PubMed2001

Chorioamnionitis and inflammation of the fetal lung.

OBJECTIVE: Fetal intrauterine exposure to proinflammatory cytokines present in amniotic fluid has been associated with an increased risk of chronic lung disease. However, the impact of histologically confirmed chorioamnionitis on the fetal lung has not yet been elucidated. We therefore investigated cellular immune response, cell proliferation, and messenger ribonucleic acid cytokine expression in fetal pulmonary tissue in the presence or absence of chorioamnionitis. STUDY DESIGN: Serial tissue sections were obtained from 27 fetuses at the time of autopsy. Three mothers had received antibiotics for treatment of clinical chorioamnionitis before abortion. Immunohistochemical staining of lung tissue comprised lineage-specific markers (CD68(+), CD3(+), neutrophil elastase). Positively stained cells were evaluated with a graticule, and cells per 5 mm(2) were counted. We undertook in situ hybridization to assess the expression of interleukin 8 messenger ribonucleic acid in the fetal lung. RESULTS: Seven of 27 fetuses had been exposed to chorioamnionitis. Fetal lungs showed a marked increase in the presence of histologically confirmed chorioamnionitis in densities of CD68(+) macrophages (68 vs 9.5 cells/5 mm(2), median group vs control group; P =.02) and lymphocytes (7 vs 2.5 cells/5 mm(2), median chorioamnionitis vs control group; P =.05) and a similar but lesser increase in neutrophil density (16 vs 4 cells/5 mm(2); difference not significant). Interleukin 8 messenger ribonucleic acid was expressed in 4 of 6 tissue specimens investigated in the chorioamnionitis group. Exposure to chorioamnionitis resulted in interleukin 8 messenger ribonucleic acid expression 7-fold higher than in the nonchorioamnionitis group; however, this difference did not achieve statistical significance. CONCLUSION: Chorioamnionitis was associated with an intrauterine inflammatory response of the fetal lung characterized by a severe infiltration of macrophages, neutrophils, and lymphocytes and also by an increased expression of interleukin 8 messenger ribonucleic acid.

Antigens, CD↗
PubMed2001

Formation and evolution of haloacetic acids in drinking water of Beijing City.

The formation and evolution of haloacetic acids (HAAs) in drinking water were examined in five water treatment plants in Beijing City, China. It was found that HAAs in water increased due to prechlorination and postchlorination. The conventional treatment processes removed the HAAs in less than 20%. By comparison, activated carbon bed removed 49-86% of HAAs and was considered to be an effective treatment unit for HAAs removal. The HAAs concentration in distribution system was associated with water sources, especially the total organic carbon in raw water, while its fluctuation appeared small.

Acetates↗
PubMed2001

Assessing clusters and motifs from gene expression data.

Large-scale gene expression studies and genomic sequencing projects are providing vast amounts of information that can be used to identify or predict cellular regulatory processes. Genes can be clustered on the basis of the similarity of their expression profiles or function and these clusters are likely to contain genes that are regulated by the same transcription factors. Searches for cis-regulatory elements can then be undertaken in the noncoding regions of the clustered genes. However, it is necessary to assess the efficiency of both the gene clustering and the postulated regulatory motifs, as there are many difficulties associated with clustering and determining the functional relevance of matches to sequence motifs. We have developed a method to assess the potential functional significance of clusters and motifs based on the probability of finding a certain number of matches to a motif in all of the gene clusters. To avoid problems with threshold scores for a match, the top matches to a motif are taken in several sample sizes. Genes from a sample are then counted by the cluster in which they appear. The probability of observing these counts by chance is calculated using the hypergeometric distribution. Because of the multiple sample sizes, strong and weak matching motifs can be detected and refined and significant matches to motifs across cluster boundaries are observed as all clusters are considered. By applying this method to many motifs and to a cluster set of yeast genes, we detected a similarity between Swi Five Factor and forkhead proteins and suggest that the currently unidentified Swi Five Factor is one of the yeast forkhead proteins.

Amino Acid Motifs↗
PubMed2001

Antitumor effect of the idiotypic cascade induced by an antibody encapsulated in poly(d,l-lactide-co-glycolide) microspheres.

A major difficulty encountered during development of antibody vaccines is their weak immunogenicity. In this study, a monoclonal antibody CS20.5 to human breast cancer antigen CA15.3 was coencapsulated in poly(d,l-lactide-co-glycolide) microspheres with monophosphoryl lipid A. The antitumor effect of this formulation was investigated in a murine model. The induced Ab2 biologically mimics antigen as it competed with CA15.3 for the same idiotope on Ab1. Ab3 induction was also observed. After five sequential administrations of encapsulated antibody, mice showed statistically significant tumor regression. These results indicate that this formulation may serve as a potential treatment for breast cancer.

Animals↗
PubMed2001

Characterization of AFMP1: a novel target for serodiagnosis of aspergillosis.

We cloned the AFMP1 gene, which encodes the first antigenic cell wall galactomannoprotein in Aspergillus fumigatus. AFMP1 codes for a protein, Afmp1p, of 284 amino acid residues, with a few sequence features that are present in Mp1p, the antigenic cell wall mannoprotein in Penicillium marneffei that we described previously, as well as several other cell wall proteins of Saccharomyces cerevisiae and Candida albicans. It contains a serine- and threonine-rich region for O glycosylation, a signal peptide, and a putative glycosylphosphatidyl inositol attachment signal sequence. Specific anti-Afmp1p antibody was generated with recombinant Afmp1p protein purified from Escherichia coli to allow further characterization of Afmp1p. Afmp1p has a high affinity for Galanthus nivalis agglutinin, a characteristic indicative of a mannoprotein. Furthermore, it was recognized by a rat monoclonal antibody against the galactofuran side chain of galactomannan, indicating that it is a galactomannoprotein. Ultrastructural analysis by immunogold staining indicated that Afmp1p is present in the cell walls of the hyphae and conidia of A. fumigatus. Finally, it was observed that patients with aspergilloma and invasive aspergillosis due to A. fumigatus develop a specific antibody response against Afmp1p. This suggested that the recombinant protein and its antibody may be useful for serodiagnosis in patients with aspergilloma or invasive aspergillosis, and the protein may represent a good cell surface target for host humoral immunity.

Amino Acid Sequence↗
PubMed2001

Differences in clinical and laboratory diagnostic characteristics of penicilliosis marneffei in human immunodeficiency virus (HIV)- and non-HIV-infected patients.

We compared the clinical and laboratory features of human immunodeficiency virus (HIV)- and non-HIV-infected patients with penicilliosis marneffei. HIV-infected patients had a higher incidence of fungemia. A total of 85.7% of the HIV-negative patients had underlying diseases including hematologic malignancies or had received therapy with corticosteroids or cytotoxic agents. By a Penicillium marneffei-specific mannoprotein Mp1p enzyme-linked immunosorbent assay, serum antigen titers were found to be higher in HIV-positive patients, whereas serum antibody levels were found to be higher in HIV-negative patients.

AIDS-Related Opportunistic Infections↗
PubMed2001

TRADD domain of Epstein-Barr virus transforming protein LMP1 is essential for inducing immortalization and suppressing senescence of primary rodent fibroblasts.

Mutation analysis of latent membrane protein 1 (LMP1) in Epstein-Barr virus (EBV)-induced B-cell immortalization revealed two transformation effector sites, TES1 and TES2. TES2 mediates the interaction with tumor necrosis factor receptor-associated death domain protein (TRADD) and plays a key role in transactivating NF-kappa B and AP-1. Recombinant EBV containing LMP1 with TES2 deleted induces a limited proliferation of B cells. The present study shows that a mutant with an LMP1 site-specific mutation at TES2, LMP1(TRADD), initially stimulates cell growth and significantly extends the life span of MEF. However, it is not sufficient for the immortalization of MEF, and MEF-LMP1(TRADD) cells eventually enter growth arrest. Further analysis reveals that although LMP1(TRADD) promotes cell growth, it does not prevent the eventual onset of senescence and the expression of tumor suppressor p16(Ink4a).

Animals↗