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Biomedical subjects

S Zhang

Publications and source records attributed to S Zhang.

At least 91 records · Page 5Linked to original sources
PubMed2002

Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: implications for cartilage tissue repair.

Emerging medical technologies for effective and lasting repair of articular cartilage include delivery of cells or cell-seeded scaffolds to a defect site to initiate de novo tissue regeneration. Biocompatible scaffolds assist in providing a template for cell distribution and extracellular matrix (ECM) accumulation in a three-dimensional geometry. A major challenge in choosing an appropriate scaffold for cartilage repair is the identification of a material that can simultaneously stimulate high rates of cell division and high rates of cell synthesis of phenotypically specific ECM macromolecules until repair evolves into steady-state tissue maintenance. We have devised a self-assembling peptide hydrogel scaffold for cartilage repair and developed a method to encapsulate chondrocytes within the peptide hydrogel. During 4 weeks of culture in vitro, chondrocytes seeded within the peptide hydrogel retained their morphology and developed a cartilage-like ECM rich in proteoglycans and type II collagen, indicative of a stable chondrocyte phenotype. Time-dependent accumulation of this ECM was paralleled by increases in material stiffness, indicative of deposition of mechanically functional neo-tissue. Taken together, these results demonstrate the potential of a self-assembling peptide hydrogel as a scaffold for the synthesis and accumulation of a true cartilage-like ECM within a three-dimensional cell culture for cartilage tissue repair.

Amino Acid Sequence↗
PubMed2002

Mechanisms of spin-polarized current-driven magnetization switching.

The mechanisms of the magnetization switching of magnetic multilayers driven by a current are studied by including exchange interaction between local moments and spin accumulation of conduction electrons. It is found that this exchange interaction leads to two additional terms in the Landau-Lifshitz-Gilbert equation: an effective field and a spin torque. Both terms are proportional to the transverse spin accumulation and have comparable magnitudes.

Journal Article↗
PubMed2002

Dy-complexes as high field T2 contrast agents: influence of water exchange rates.

Dy complexes can act as suitable negative (T2) contrast agents for Magnetic Resonance Imaging (MRI). As clinical MRI moves toward higher fields, tuning of the exchange rate of coordinated water molecules will become necessary to optimize the r2 relaxivity. For Dy complexes, this will require lengthening of the water residence time, a strategy opposite that required to optimize the r1 relaxivity of Gd complexes. However, very slow water exchange can be deleterious. This is illustrated here by a Dy complex that is characterized by a very slow water exchange. This complex, Dy-DOTA-4AmCE, is compared with several Dy-DTPA derivatives known for their efficacy as T2 contrast agents at high magnetic fields.

Body Water↗
PubMed2002

In vitro cytotoxicity of the organophosphorus insecticide methylparathion to FG-9307, the gill cell line of flounder (Paralichthys olivaceus).

FG-9307, a cell line derived from the gill of flounder Paralichthys olivaceus, was used to determine the acute cytotoxic effects of the organophosphorus insecticide methylparathion. The cytotoxic effects of methylparathion were initially measured by three endpoint systems: neutral red (NR) uptake assay, tetrazolium (MTT) assay, and cell protein assay. Results indicated that concentrations of methylparathion ranging from 5 microg/ml to 60 microg/ml were toxic, and there was no significant difference in cytotoxic effects between the three test systems. Thus, the FG-9307 cell line is one of several choices for evaluating the acute toxicities of organophosphorus insecticides such as methylparathion. The ultrastructure of the cells was also studied. It was found that the ultrastructure of the cells was markedly altered by methylparathion, as evidenced by dilation of mitochondria, breakdown of rough endoplasmic reticulum, nuclear necrosis, and production of numerous lysosomes and lipid vacuoles. This appears to be the first report that a marine fish cell line can be used for acute in vitro cytotoxicity evaluation of methylparathion.

Animals↗
PubMed2002

Matrix metalloproteinase-2 from bronchial epithelial cells induces the proliferation of subepithelial fibroblasts.

BACKGROUND: In bronchial asthma, subepithelial fibrosis in the conducting airways is associated with increased numbers of subepithelial fibroblasts. OBJECTIVE: This study examined the hypothesis that MMP-2 from airway epithelial cells induces the proliferation of subepithelial fibroblasts. METHODS: Using primary bronchial epithelial cells MMP-2, MT1-MMP and TIMP-2 mRNA expression were assessed by Northern blotting and RT-PCR. Primary bronchial epithelial cells transfected with constructs encoding pro-MMP-2 and MT1-MMP (MMP-14). RESULTS: Transfected cells showed enhanced expression of the appropriate mRNA species by RT-PCR and enhanced MMP-2 or MT1-MMP activity by zymography. Active MMP-2 levels in epithelial supernatants were increased most by cotransfection with pro-MMP-2 and MT1-MMP encoding constructs. By measuring tritiated thymidine incorporation, supernatants from transfected cells were found to enhance DNA synthesis of primary airway fibroblast cultures compared with controls. There was a strong correlation (r = 0.9, P < 0.01) between MMP-2 levels in epithelial cell conditioned media and fibroblast proliferation as indicated by DNA synthesis. The MMP inhibitor 1,10-phenanthroline attenuated the increased proliferation, while the addition of exogenous purified MMP-2 alone also increased fibroblast proliferation. CONCLUSIONS: Our results support a role for MMP-2 in mediating cross-talk between epithelial cells and myofibroblasts.

Bronchi↗
PubMed2002

Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro.

Entecavir (ETV) is a potent and selective inhibitor of hepatitis B virus (HBV) replication in vitro and in vivo that is currently in clinical trials for the treatment of chronic HBV infections. A major limitation of the current HBV antiviral therapy, lamivudine (3TC), is the emergence of drug-resistant HBV in a majority of treated patients due to specific mutations in the nucleotide binding site of HBV DNA polymerase (HBV Pol). To determine the effects of 3TC resistance mutations on inhibition by ETV triphosphate (ETV-TP), a series of in vitro studies were performed. The inhibition of wild-type and 3TC-resistant HBV Pol by ETV-TP was measured using recombinant HBV nucleocapsids, and compared to that of 3TC-TP. These enzyme inhibition studies demonstrated that ETV-TP is a highly potent inhibitor of wild-type HBV Pol and is 100- to 300-fold more potent than 3TC-TP against 3TC-resistant HBV Pol. Cell culture assays were used to gauge the potential for antiviral cross-resistance of 3TC-resistant mutants to ETV. Results demonstrated that ETV inhibited the replication of 3TC-resistant HBV, but 20- to 30-fold higher concentrations were required. To gain further perspective regarding the potential therapeutic use of ETV, its phosphorylation was examined in hepatoma cells treated with extracellular concentrations representative of drug levels in plasma in ETV-treated patients. At these concentrations, intracellular ETV-TP accumulated to levels expected to inhibit the enzyme activity of both wild-type and 3TC-resistant HBV Pol. These findings are predictive of potent antiviral activity of ETV against both wild-type and 3TC-resistant HBV.

Antiviral Agents↗
PubMed2002

Morphologic and molecular characterization of Salmonella typhimurium infection in neonatal calves.

The host response to Salmonella plays a major role in the outcome of infection. The present study was undertaken to further characterize Salmonella typhimurium infection in neonatal calves at both the morphologic and the molecular level using the ligated ileal loop model. Eight 4-5-week-old male Holstein calves underwent laparotomy, and loops were prepared in the ileum. The loops were either inoculated with an S. typhimurium strain pathogenic for cattle or injected with sterile LB broth as control. Samples for histology, transmission and scanning electron microscopy, and RNA extraction were collected at various time points between 5 minutes and 12 hours postinfection. Invasion of both M cells and enterocytes began at 15 minutes postinfection. No specific cell type was the main target for invasion. Intracellular bacteria were observed in the lamina propria after 1 hour postinfection. A severe acute neutrophilic response was associated with invasion of the Peyer's patches. Upregulated expression of CXC chemokines (interleukin [IL]-8, growth-related oncogenes, [GRO] alpha and gamma, and granulocyte chemotactic protein [GCP]2) was detected by reverse transcription polymerase chain reaction beginning at 1 hour postinfection. Expression of proinflammatory (IL-1beta, IL-18, and tumor necrosis factor [TNF]alpha) and anti-inflammatory (IL-10, IL-IRa, and IL-4) cytokines was also assessed. A marked increase in expression of IL-1beta was observed, whereas the profile of expression of IL-18 and TNFalpha did not change after infection. Upregulation of IL-1Ra and IL-4 but not of IL-10 was observed. These findings indicate that infection of bovine ligated ileal loops with S. typhimurium results in an acute neutrophilic inflammatory response that is associated with the upregulation of CXC chemokines (IL-8, GROalpha and gamma, and GCP2), IL-1beta, IL-IRa, and IL-4.

Animals↗
PubMed2002

The influence of chain length and base sequence on the pharmacokinetic behavior of 99mTc-morpholinos in mice.

BACKGROUND: Despite in vivo use now over several years, in particular for nuclear medicine imaging, the influences on pharmacokinetics of chain length and base sequence of radiolabeled oligomers has not been investigated. METHODS: As test oligomer, morpholinos (MORFs), a DNA analogue, were radiolabeled with 99mTc via MAG3 and the pharmacokinetics in normal mice determined for 3 chain lengths (15, 18 and 25 mer) and 2 base sequences (MORF and its complement cMORF). In addition, LS174T-tumor bearing nude mice received the anti-CEA antibody MN14 (Immunomedics) conjugated either with MORF15 or MORF18 and subsequently received 99mTc-labeled cMORF15 or cMORF18 respectively in a pretargeting strategy. RESULTS: In normal mice, after 1 hr, regardless of chain length or sequence, all labeled MORFs and cMORFs accumulated only slightly in all tissues (e.g. at 3 hr <0.15 ID%/g) except in kidneys. Besides being excessive, the kidneys were the only tissue with levels dependent upon chain length (e.g. at 1 hr, 5, 7 and 22 ID%/g for MORF15, 18 and 25, respectively) and sequence (e.g. at 3 hrs 9 ID%/g for MORF25 and 21 ID%/g for cMORF25). Identical biodistribution trends were observed in tumored mice with all tissues including tumor showing levels independent of chain length or base sequence except for kidneys. Furthermore, while all other tissues cleared in the interval from 1-3 hrs, kidney levels remained constant in both normal and tumored animals. Largely because of these differences in kidneys, images obtained by pretargeting with 99mTc-cMORF15 were superior compared to 99mTc-cMORF18 (images of control animals not receiving the antibody showed no tumor at all). CONCLUSIONS: Judged by radiolabel accumulations in tissue, the pharmacokinetics of 99mTc labeled morpholinos were independent of chain length and base sequence. The only obvious exception was kidneys in which accumulations were significantly higher for the longer chain lengths and significantly different for cMORF vs MORF. These results show that chain length and base sequences may be varied to alter the pharmacokinetics of radiolabeled oligomers in nuclear medicine imaging studies.

Animals↗
PubMed2002

Over-expression of beta-1,4-galactosyltransferase V increases the growth of astrocytoma cell line.

Our previous study showed that the gene expression of beta-1,4-galactosyltransferase V (beta-1,4-GalT V), preferentially galactosylating GlcNAc1-->6Man of oligosaccharides, increased in the process of astrocytoma progress, with the highest level in grade IV astrocytoma. To investigate the function of this beta-1,4-GalT in cell proliferation, the sense and antisense cDNA of beta-1,4-GalT V was constructed as pcDNA3-HA-GalT V and pcDNA3-anti-GalT V respectively and transfected into SHG cell, a kind of human astrocytoma cell line. The transfection was confirmed with Northern and Western blot assay. It was found that the growth of SHG/HA-GalT V in serum-containing medium was faster than that of mock-transfectant with the vector pcDNA3, whereas the growth of SHG/GalTV-AS was slower than that of mock-transfectant. GalTV-HA/SHG showed a stronger capability for colony formation than that of GalTV-AS/SHG as evaluated by anchorage-independent growth in soft agar assay. This result was consistent with that of the growth curve. By RCA-1 lectin assay, the galactosylation on the surface of GalTV-HA/SHG and SHG/GalTV-AS was stained stronger (P<0.001) and weaker (P<0.05) respectively compared with the mock transfectant. This indicates that beta-1,4-GalT V was involved in the malignant phenotype of astrocytoma cells, possibly causing the high galactosylation on the cell surface.

Astrocytoma↗
PubMed2001

Further studies on the contribution of electrostatic and hydrophobic interactions to protein adsorption on dye-ligand adsorbents.

The adsorption equilibria of bovine serum albumin (BSA), gamma-globulin, and lysozyme to three kinds of Cibacron blue 3GA (CB)-modified agarose gels, 6% agarose gel-coated steel heads (6AS), Sepharose CL-6B, and a home-made 4% agarose gel (4AB), were studied. We show that ionic strength has irregular effects on BSA adsorption to the CB-modified affinity gels by affecting the interactions between the negatively charged protein and CB as well as CB and the support matrix. At low salt concentrations, the increase in ionic strength decreases the electrostatic repulsion between negatively charged BSA and the negatively charged gel surfaces, thus resulting in the increase of BSA adsorption. This tendency depends on the pore size of the solid matrix, CB coupling density, and the net negative charges of proteins (or aqueous - phase pH value). Sepharose gel has larger average pore size, so the electrostatic repulsion-effected protein exclusion from the small gel pores is observed only for the affinity adsorbent with high CB coupling density (15.4 micromol/mL) at very low ionic strength (NaCl concentration below 0.05 M in 10 mM Tris-HCl buffer, pH 7.5). However, because CB-6AS and CB-4AB have a smaller pore size, the electrostatic exclusion effect can be found at NaCl concentrations of up to 0.2 M. The electrostatic exclusion effect is even found for CB-6AS with a CB density as low as 2.38 micromol/mL. Moreover, the electrostatic exclusion effect decreases with decreasing aqueous-phase pH due to the decrease of the net negative charges of the protein. For gamma-globulin and lysozyme with higher isoelectric points than BSA, the electrostatic exclusion effect is not observed. At higher ionic strength, protein adsorption to the CB-modified adsorbents decreases with increasing ionic strength. It is concluded that the hydrophobic interaction between CB molecules and the support matrix increases with increasing ionic strength, leading to the decrease of ligand density accessible to proteins, and then the decrease of protein adsorption. Thus, due to the hybrid effect of electrostatic and hydrophobic interactions, in most cases studied there exists a salt concentration to maximize BSA adsorption.

Adsorption↗
PubMed2001

Synthesis and NMR studies of new DOTP-like lanthanide(III) complexes containing a hydrophobic substituent on one phosphonate side arm.

Three derivatives of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonic acid) (DOTP) containing a hydrophobic substituent on one side chain were prepared and their lanthanide complexes examined by NMR. The new ligands include 1-(1-octyl-methyl-phosphonic acid)-4,7,10-tris(methylene phosphonic acid)-1,4,7,10-tetraazacyclododecane (C(8)-DOTP), 1-(1-undecyl-methyl-phosphonic acid)-4,7,10-tris(methylene phosphonic acid)-1,4,7,10-tetraazacyclododecane (C(11)-DOTP), and 1-(1-4-nitro-phenyl-methyl-phosphonic acid)-4,7,10-tris(methylene phosphonic acid)-1,4,7,10-tetraazacyclododecane (NO(2)-Ph-DOTP). (1)H NMR spectra of the ytterbium(III) complexes were assigned by using a combination of COSY spectroscopy and a fitting procedure that matches experimental NMR hyperfine shifts with those estimated from a MMX-derived structure. The analysis showed that a single isomer is present in solution and that the bulky hydrophobic substituent occupies the less sterically demanding H(6) equatorial position in the YbL(5)(-) complexes. Although the YbL(5)(-) complexes have lower symmetry due to the added substituent, the average (1)H hyperfine shifts are 5-10% larger in these complexes compared to YbDOTP(5)(-). This was magnified further in the hyperfine (23)Na NMR shifts of ion-paired sodium ions where the extracellular Na(+) signal in perfused rat hearts displayed a 28% larger hyperfine shift in the presence of Tm(C(11)-DOTP)(5)(-) than with an equivalent amount of TmDOTP(5)(-).

Animals↗
PubMed2001

The genome of the natural genetic engineer Agrobacterium tumefaciens C58.

The 5.67-megabase genome of the plant pathogen Agrobacterium tumefaciens C58 consists of a circular chromosome, a linear chromosome, and two plasmids. Extensive orthology and nucleotide colinearity between the genomes of A. tumefaciens and the plant symbiont Sinorhizobium meliloti suggest a recent evolutionary divergence. Their similarities include metabolic, transport, and regulatory systems that promote survival in the highly competitive rhizosphere; differences are apparent in their genome structure and virulence gene complement. Availability of the A. tumefaciens sequence will facilitate investigations into the molecular basis of pathogenesis and the evolutionary divergence of pathogenic and symbiotic lifestyles.

Agrobacterium tumefaciens↗
PubMed2001

Developmental and functional evidence of a role for Zfhep in neural cell development.

The rat Zfhep gene encodes a member of the Zfh family of transcription factors having a homeodomain-like sequence and multiple zinc fingers. We examined expression of Zfhep in the rat forebrain during embryonic and postnatal development. Zfhep mRNA was strongly expressed in the progenitor cells of the ventricular zone around the lateral ventricles on E14 and E16, but showed little expression in cells that had migrated to form the developing cortex. Dual labeling with PCNA demonstrated expression of Zfhep mRNA in proliferating cells. Expression of Zfhep in the ventricular zone decreases during late development as the population of progenitor cells decreases. This pattern is distinctly different from other members of the Zfh family. We also examined the expression of Zfhep protein during retinoic acid-induced neurogenesis of P19 embryonal carcinoma cells. Zfhep is highly expressed in P19 neuroblasts, and expression decreases by the time of morphological neurogenesis. Hence, both P19 cells and embryonic brain demonstrate a loss of Zfhep expression during the transition from proliferating precursor to differentiated neural cells. We investigated a possible link between Zfhep and proliferation by treating human glial cell lines with Zfhep antisense phosphorothioate oligodeoxynucleotides. Two Zfhep antisense oligonucleotides repressed proliferation of either U-138 or U-343 glioblastoma cells more than control oligonucleotides. Based on the expression patterns of Zfhep in vivo and in the P19 cell model of neurogenesis, we suggest that Zfhep may play a role in proliferation or differentiation of neural cells.

Animals↗
PubMed2001

Novel erythromycin derivatives with aryl groups tethered to the C-6 position are potent protein synthesis inhibitors and active against multidrug-resistant respiratory pathogens.

A novel series of erythromycin derivatives has been discovered with potent activity against key respiratory pathogens, including those resistant to erythromycin. These compounds are characterized by having an aryl group tethered to the C-6 position of the erythronolide skeleton. Extensive structural modification of the C-6 moiety led to the discovery of several promising compounds with potent activity against both mef- and erm-mediated resistant Streptoccoccus pneumoniae. Preliminary mechanistic studies indicated that the new macrolides are potent protein synthesis inhibitors, which interact with methylated ribosomes isolated from resistant organisms. In experimental animal models, these compounds exhibited excellent in vivo efficacy and balanced pharmacokinetic profiles.

Animals↗
PubMed2001

Changes in nitric oxide production and cerebral blood flow before development of hyperbaric oxygen-induced seizures in rats.

The predictive value of increase in cerebral blood flow (CBF) was examined to detect hyperbaric oxygen (HBO(2))-induced electrical discharge in artificially ventilated rats at three PaCO(2) levels under 5 atmospheric pressures. The possible involvement of NO production in the mechanism of the increase in CBF was also assessed by measurement of major NO metabolites (NO(2)(-) plus NO(3)(-)) using a microdialysis technique at the left parietal cortex during HBO(2) exposure. The onset times of electrical discharge, measured in the right frontal region, were significantly prolonged and shortened in the low PaCO(2) group (79+/-21 min) and high PaCO(2) group (27+/-7 min), respectively, compared to that in the normal PaCO(2) group (37+/-5 min). Increase in CBF (200% of the pre-exposure level) was observed in every animal and was sustained until the appearance of electrical discharge. The onset time of increase in CBF was closely related to that of electrical discharge (R(2)=0.987), and the durations of increase in CBF were almost identical (11-14 min in mean) regardless of the PaCO(2) level. The level of NO(2)(-) plus NO(3)(-) was unaffected by the initiation of HBO(2) exposure and simultaneously increased up to 246+/-59% of control level with the onset of increase in CBF. There was a close relationship between changes in CBF and levels of NO(2)(-) plus NO(3)(-) (R(2)=0.544). These results indicate that monitoring of CBF is useful for the prediction of electrical discharge in artificially ventilated rats regardless of their PaCO(2) levels and that the increase in NO production is related to the mechanism of increase in CBF.

Animals↗