Biomedical subjects

W Song

Publications and source records attributed to W Song.

At least 37 records · Page 2Linked to original sources

PubMed2004

Size-dependent properties of nanocrystalline silicalite synthesized with systematically varied crystal sizes.

Silicalite-1 powders with crystal sizes ranging from 20 to 1000 nm were synthesized by systematically varying synthesis gel composition, pressure, temperature, and time duration. These samples were characterized by powder X-ray diffraction, scanning electron microscopy, nitrogen adsorption isotherms, solid-state nuclear magnetic resonance, and toluene adsorption. The effect of crystal size on the physical properties of crystals is observed, including a large increase of both total and external surface area when crystal size decreases. The relationship between particle size and external surface area was modeled by assuming a cubic crystal geometry. The nanosized silicalite samples with crystal sizes less than 100 nm have a higher adsorption capacity for toluene, showing promising potential for its application in volatile organic compound removal.

Journal Article↗

PubMed2004

Molecular typing of human leukocyte antigen and related polymorphisms following whole genome amplification.

Reliable, high-resolution genotyping of human leukocyte antigen (HLA) polymorphisms is often compromised by DNA samples of suboptimal quality or limited quantity. We tested the feasibility of molecular typing for variants at HLA and neighboring loci using whole genome amplification (WGA) strategy facilitated by the Phi29 DNA polymerase. With little (5-100 ng) starting genomic DNA of varying quality and source materials, WGA was deemed successful in 167 of 169 DNA from 47 cell lines, 100 European Americans, and 22 native Africans. The Phi29-processed DNA provided adequate templates for polymerase chain reaction (PCR)-based analyses of several HLA (A, B, C, DRB1, and DQB1) and related loci (HFE, MICA, and 10 microsatellites) in the 6p24.3-6p21.3 region, with PCR amplicons ranging from 92 to 2200 bp. Five different genotyping techniques resolved and confirmed 364 genotypes when both original and Phi29-processed DNA worked in PCRs. General population genetic analyses provided additional evidence that WGA may represent a reliable and simple approach to securing ample genomic DNA for typing HLA, MICA, and related variants.

Africa↗

PubMed2003

In vitro activity of beta-lactams in combination with other antimicrobial agents against resistant strains of Pseudomonas aeruginosa.

Using the chequerboard titration method, the activity in combination of beta-lactams, fluoroquinolones and aminoglycosides was investigated against 24 Pseudomonas aeruginosa isolates resistant to these antibiotics. Synergy was detected with one or more antimicrobial combinations against 15 of 24 (63%) isolates and partial synergy was detected with one or more combinations against all 24 isolates. No antagonism was seen with any combination. Ceftazidime and cefepime with aztreonam, amikacin and isepamicin showed synergy or partial synergy against 12-20 (50-80%) isolates. Imipenem and meropenem with amikacin and isepamicin showed synergy or partial synergy against eight to 12 (33-50%) isolates. The results of this study indicate that against P. aeruginosa, synergy may occur between beta-lactams, fluoroquinolones and aminoglycosides although the strains are resistant to the individual antibiotics.

Anti-Bacterial Agents↗

PubMed2003

Icteric flare of chronic hepatitis B in a 95-year old patient.

A 95-year old gentleman developed fatal icteric flare of chronic hepatitis B despite lamivudine treatment. This article highlights the atypical presentations of chronic hepatitis B in elderly patient and the need to consider this possibility for acute fulminant hepatitis in endemic areas.

Aged↗

PubMed2002

Ablation of microvessels in vivo upon dimerization of iCaspase-9.

Anti-angiogenic therapies based on targeted disruption of the tumor microvascular network have been proposed for cancer treatment. Inhibitors of the endothelial cell pro-survival pathway mediated by VEGF were shown to activate caspases and cause microvascular regression, but the efficacy of this strategy can be hindered by the engagement of redundant survival pathways. Alternatively, if direct activation of an apical pro-apoptotic caspase is sufficient to disrupt microvessels in vivo, such a strategy could potentially override upstream endothelial cell survival inputs and disrupt tumor neovascular networks. Here, we fused caspase-9 to a mutated FKBP12 domain to express an inducible caspase-9 molecule (iCaspase-9) that can be activated by a cell-permeable dimerizer drug, and transduced this construct into primary endothelial cells. We found that drug-induced dimerization of iCaspase-9 is sufficient to activate endogenous caspase-3 and trigger apoptosis even when endothelial cells are treated with the pro-survival factors VEGF or bFGF. A single intraperitoneal injection of the dimerizer drug induced apoptosis of endothelial cells expressing iCaspase-9 and elimination of human microvessels engineered in immunodeficient mice. These results demonstrate that the activation of iCaspase-9 disrupts microvessels in vivo, and suggest a novel anti-angiogenic strategy based on the expression and controlled activation of an inducible death gene in neovascular endothelial cells.

Animals↗

PubMed2001

Combined intratumoral injection of bone marrow-derived dendritic cells and systemic chemotherapy to treat pre-existing murine tumors.

Dendritic cells (DCs) are attractive candidates for innovative cancer immunotherapy by virtue of their potential to function as professional antigen-presenting cells for initiating cellular immune responses. In this study, we evaluated a possible synergy of conventional chemotherapy together with intratumoral injection of syngeneic bone marrow-derived DCs for the treatment of preexisting tumors. Using murine CT26 colon adenocarcinoma cells (parental or modified to express beta-galactosidase as a model tumor antigen) to produce s.c. tumors in syngeneic BALB/c mice, the data demonstrate that direct injections of DCs at the tumor site result in partial eradication of established tumors. Strikingly, the addition of systemic chemotherapy (cyclophosphamide) combined with local intratumoral injection of DCs led to complete tumor regression in the treated animals. The tumor-free mice were able to resist a repeat challenge with the same tumor, suggesting that the animals had acquired long term antitumor immunity. Supporting evidence for the paradigm of systemic chemotherapy and intratumoral administration of DCs was obtained using melanoma B16 syngeneic tumor treated with Adriamycin plus DCs. These novel findings raise the possibility of using this potent strategy of combined intratumoral injections of DCs and systemic chemotherapy for cancer treatment.

Animals↗

PubMed2001

In vitro targeted killing of prostate tumor cells by a synthetic amoebapore helix 3 peptide modified with two gamma-linked glutamate residues at the COOH terminus.

Prostate-specific membrane antigen (PSMA) is a trans-membrane protein specifically expressed in LNCaP cells, malignant human prostate tissues, and the surrounding neovasculature. PSMA is a unique exopeptidase with reactivity toward poly-gamma-glutamated folates. It can sequentially remove the poly-gamma-glutamyl termini. To target prostate tumor cells, a novel procytolytic peptide was designed with a backbone consisting of an amoebapore H3 domain modified by two gamma-linked glutamate residues at the epsilon-amino group of the COOH-terminal lysine residue. The strategy behind the design of this prolytic peptide was to inactivate the lytic amoebapore H3 peptide by replacing its functionally important COOH-terminal positive charge with negatively charged groups, which in turn might be selectively removed by the PSMA exopeptidase. This peptide exhibited little cytolytic activity toward PSMA-negative cells, such as PC-3 cells. On the other hand, this peptide exhibited strong cytolytic activity toward PSMA-positive LNCaP cells in a concentration-dependent manner. The carboxypeptidase inhibitor 4,4'-phosphonicobis (butane-1,3-dicarboxylic acid) can inhibit this activity. Moreover, this peptide also exhibited cytolytic activity toward PSMA cDNA-transfected PC-3 cells.

Amino Acid Sequence↗

PubMed2001

Extensive eosinophil degranulation and peroxidase-mediated oxidation of airway proteins do not occur in a mouse ovalbumin-challenge model of pulmonary inflammation.

Paradigms of eosinophil effector function in the lungs of asthma patients invariably depend on activities mediated by cationic proteins released from secondary granules during a process collectively referred to as degranulation. In this study, we generated knockout mice deficient for eosinophil peroxidase (EPO) to assess the role(s) of this abundant secondary granule protein in an OVA-challenge model. The loss of EPO had no effect on the development of OVA-induced pathologies in the mouse. The absence of phenotypic consequences in these knockout animals extended beyond pulmonary histopathologies and airway changes, as EPO-deficient animals also displayed OVA-induced airway hyperresponsiveness after provocation with methacholine. In addition, EPO-mediated oxidative damage of proteins (e.g., bromination of tyrosine residues) recovered in bronchoalveolar lavage from OVA-treated wild-type mice was <10% of the levels observed in bronchoalveolar lavage recovered from asthma patients. These data demonstrate that EPO activities are inconsequential to the development of allergic pulmonary pathologies in the mouse and suggest that degranulation of eosinophils recruited to the lung in this model does not occur at levels comparable to those observed in humans with asthma.

Allergens↗

PubMed2001

Supramolecular origins of product selectivity for methanol-to-olefin catalysis on HSAPO-34.

Ethylene selectivity in methanol-to-olefin (MTO) catalysis is related to the number of methyl groups on benzene rings trapped in the nanocages of the preferred catalyst HSAPO-34. By correlating the time evolutions of the catalysts' 13C NMR spectra and the volatile product distribution following abrupt cessation of methanol flow, we discovered that (in the absence of other adsorbates) propene is favored by methylbenzenes with four to six methyl groups but ethylene is predominant from those with two or three methyl groups. We substantially increased ethylene selectivity by operating at lower methanol partial pressures or higher temperatures, either of which reduces the steady-state average methyl substitution. As a step toward a kinetic analysis of the MTO reaction on HSAPO-34, we treated each nanocage with a methylbenzene molecule as a supramolecule capable of unimolecular dissociation into ethylene or propene and a less highly substituted methylbenzene. Addition of a water molecule to a nanocage containing a methylbenzene produces a distinct supramolecule with unique properties. Indeed, co-feeding water with methanol significantly increased the average number of methyl groups per ring at steady state relative to identical conditions without additional water, and also increased ethylene selectivity, apparently through transition state shape selectivity.

Journal Article↗

PubMed2001

Enhanced infection of an X4 strain of HIV-1 due to capping and colocalization of CD4 and CXCR4 induced by capsianoside G, a diterpene glycoside.

We investigated whether capsianosides, diterpene glycosides, extracted from Capsicum plants could affect human immunodeficiency virus type 1 (HIV-1) infection. Significant effect on virus infection in MAGI/CCR5 cells was neither observed for the X4 virus by capsianosides II, XI, and A, nor for an R5 virus by capsianoside G. Apparent enhancement of X4 HIV-1 infection by capsianoside G was observed and exclusively related to the usage of the CXCR4 coreceptor. The capsianoside G-treated cells had no change in the expression level of CD4, CXCR4, and CCR5, however, colocalization and capping of CD4 and CXCR4, but not of CD4 and CCR5 was observed. Our results suggested that capsianoside G enhanced X4 virus infection at the level of viral penetration through the capping and colocalization of receptors needed for infection.

Adsorption↗

PubMed2001

Translocation of the B cell antigen receptor into lipid rafts reveals a novel step in signaling.

The cross-linking of the B cell Ag receptor (BCR) leads to the initiation of a signal transduction cascade in which the earliest events involve the phosphorylation of the immunoreceptor tyrosine-based activation motifs of Ig alpha and Ig beta by the Src family kinase Lyn and association of the BCR with the actin cytoskeleton. However, the mechanism by which BCR cross-linking initiates the cascade remains obscure. In this study, using various A20-transfected cell lines, biochemical and genetic evidence is provided that BCR cross-linking leads to the translocation of the BCR into cholesterol- and sphingolipid-rich lipid rafts in a process that is independent of the initiation of BCR signaling and does not require the actin cytoskeleton. Translocation of the BCR into lipid rafts did not require the Ig alpha/Ig beta signaling complex, was not dependent on engagement of the FcR, and was not blocked by the Src family kinase inhibitor PP2 or the actin-depolymerizing agents cytochalasin D or latrunculin. Thus, cross-linking or oligomerization of the BCR induces the BCR translocation into lipid rafts, defining an event in B cell activation that precedes receptor phosphorylation and association with the actin cytoskeleton.

Actins↗

PubMed2001

Adenovirus-mediated transfer of inducible caspases: a novel "death switch" gene therapeutic approach to prostate cancer.

In patients with localized prostate cancer, radical prostatectomy and radiation therapy, although effective in controlling localized disease, are often associated with significant side effects attributable to injury of adjacent tissues. Moreover, patients with metastatic disease eventually fail systemic hormonal or chemotherapy because of the development of progressive, refractory disease. In this study, we evaluated the safety and efficacy of a novel suicide gene therapy that could potentially spare normal tissue while bypassing molecular mechanisms of apoptosis resistance by using chemically inducible effector caspases to trigger apoptosis in prostate cancer cells. Initially, we compared the ability of a panel of inducible Fas signaling intermediates to kill human and murine prostate cancer cell lines. On the basis of the superior killing by downstream caspase-1 and caspase-3, replication-deficient adenoviral vectors expressing conditional caspase-1 (Ad-G/iCasp1) or caspase-3 (Ad-G/iCasp3), regulated by nontoxic, lipid-permeable, chemical inducers of dimerization (CID), were constructed. Upon vector transduction followed by CID administration, aggregation and activation of these recombinant caspases occur, leading to rapid apoptosis. In vitro, both human (LNCaP and PC-3) and murine (TRAMP-C2 and TRAMP-C2G) prostate cancer cell lines were efficiently transduced and killed in a CID-dependent fashion. In vivo, direct injection of Ad-G/iCasp1 into s.c. TRAMP-C2 tumors caused focal but extensive apoptosis without evidence for a bystander effect at the maximal viral dose (i.e., 2.5 x 10(10) viral particles/25 microl) in host animals that also received CID compared with control animals. Treatment with Ad-G/iCasp1 plus CID resulted in a transient, yet significant, reduction both in tumor growth and volume compared with tumors treated with vector but not CID (P < 0.035) or vector-diluent plus CID (P < 0.022), both of which grew more rapidly. These results demonstrate that CID-regulated, caspase-based suicide gene therapy is safe and can inhibit the growth of experimental prostate cancer in vitro and in vivo through potent induction of apoptosis, providing a rationale for further development.

Adenocarcinoma↗

PubMed2001

Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins.

Glutamate is the main excitatory neurotransmitter in the mammalian central nervous system and is removed from the synaptic cleft by sodium-dependent glutamate transporters. To date, five distinct glutamate transporters have been cloned from animal and human tissue: GLAST (EAAT1), GLT-1 (EAAT2), EAAC1 (EAAT3), EAAT4, and EAAT5 (refs 1-5). GLAST and GLT-1 are localized primarily in astrocytes, whereas EAAC1 (refs 8, 9), EAAT4 (refs 9-11) and EAAT5 (ref 5) are neuronal. Studies of EAAT4 and EAAC1 indicate an extrasynaptic localization on perisynaptic membranes that are near release sites. This localization facilitates rapid glutamate binding, and may have a role in shaping the amplitude of postsynaptic responses in densely packed cerebellar terminals. We have used a yeast two-hybrid screen to identify interacting proteins that may be involved in regulating EAAT4--the glutamate transporter expressed predominately in the cerebellum--or in targeting and/or anchoring or clustering the transporter to the target site. Here we report the identification and characterization of two proteins, GTRAP41 and GTRAP48 (for glutamate transporter EAAT4 associated protein) that specifically interact with the intracellular carboxy-terminal domain of EAAT4 and modulate its glutamate transport activity.

Amino Acid Sequence↗

PubMed2001

A novel clathrin homolog that co-distributes with cytoskeletal components functions in the trans-Golgi network.

A clathrin homolog encoded on human chromosome 22 (CHC22) displays distinct biochemistry, distribution and function compared with conventional clathrin heavy chain (CHC17), encoded on chromosome 17. CHC22 protein is upregulated during myoblast differentiation into myotubes and is expressed at high levels in muscle and at low levels in non-muscle cells, relative to CHC17. The trimeric CHC22 protein does not interact with clathrin heavy chain subunits nor bind significantly to clathrin light chains. CHC22 associates with the AP1 and AP3 adaptor complexes but not with AP2. In non-muscle cells, CHC22 localizes to perinuclear vesicular structures, the majority of which are not clathrin coated. Treatments that disrupt the actin-myosin cytoskeleton or affect sorting in the trans-Golgi network (TGN) cause CHC22 redistribution. Overexpression of a subdomain of CHC22 induces altered distribution of TGN markers. Together these results implicate CHC22 in TGN membrane traffic involving the cytoskeleton.

Cells, Cultured↗

PubMed2001

Acid-base chemistry of a carbenium ion in a zeolite under equilibrium conditions: verification of a theoretical explanation of carbenium ion stability.

The 1,3-dimethylcyclopentenyl carbenium ion (C7H11(+)) was reproducibly prepared on zeolite HZSM-5 using a pulse-quench reactor, and then each of a number of bases was coadsorbed into the catalyst channels to either compete with the cation for protonation or to possibly react with it as a nucleophile. For seven bases with proton affinities (PA) between 142 and 212.1 kcal/mol, there was no reaction with C7H11(+). Coadsorption of smaller amounts of dimethylacetamide (PA = 217 kcal/mol) also produced no reaction, but with a higher loading, a proton was transferred from the carbenium ion to the base to leave 1,3-dimethylcyclopenta-1,3-diene in the zeolite as a neutral olefin. Deprotonation was the primary reaction with coadsorption of either pyridine (PA = 222 kcal/mol) or trimethylphosphine (PA = 229.2 kcal/mol). The estimated experimental deprotonation enthalpy for C7H11(+), approximately 217 kcal/mol in the zeolite, is in excellent agreement with MP4/6-311G gas-phase value of 215.6 kcal/mol. Coadsorption of either NH3 (PA = 204.0 kcal/mol) or PH3 (PA = 188 kcal/mol) does not deprotonate the carbenium ion, but these species do react as nucleophiles to form onium ion derivatives of C7H11(+). Analogous onium complexes with pyridine or trimethylphosphine formed in lower yields due to steric constraints in the zeolite channels. The essential experimental observations were all predicted and explained by density functional calculations (B3LYP/6-311G) and extensions of our recently developed theory of carbenium ion stability in zeolites. In addition, we report theoretical geometries for several complexes which contain unusual C-H- - -X hydrogen bonds.

Journal Article↗

PubMed2001

Novel pH-sensitive citrate cross-linked chitosan film for drug controlled release.

Turbidimetric titration revealed that there were electrostatic attractive interactions between citrate and chitosan in the pH region of 4.3-7.6, depending on their degree of ionization. Citrate cross-linked chitosan film was prepared simply by dipping chitosan film into sodium citrate solution. The swelling ratio of citrate/chitosan film was sensitive to pH, ionic strength etc. Under acidic conditions, citrate/chitosan film swelled and even dissociated in the pH less than 3.5, and the model drugs (brilliant blue and riboflavin) incorporated in the film were released quickly (usually within 2 h released completely in simulated gastric fluid at 37 degrees C) while under neutral conditions the swelling ratio of citrate/chitosan film was less significant and the release rate of brilliant blue and riboflavin was low (less than 40% released in simulated intestinal fluid in 24 h). Sodium chloride weakened the electrostatic interaction between citrate and chitosan, and therefore facilitated the film swelling and accelerated drug release. The parameters of film preparation such as citrate concentration, solution pH etc. influencing the film swelling and drug release profiles were examined. The lower concentration and the higher pH of citrate solution resulted in a larger swelling ratio and quicker riboflavin release. To improve the drug controlled release properties of citrate/chitosan film, heparin, pectin and alginate were further coated on the film surface. Among them only the coating of alginate prolonged riboflavin release noticeably (for 80% of drug released the time was extended from 1.5 to 3.5 h with 0.5% w/v alginate used). The results indicated that the citrate/chitosan film was useful in drug delivery such as for the site-specific drug controlled release in stomach.

Chitin↗

PubMed2001

Emerging erythromycin resistance among group B streptococci in Korea.

In order to determine possible trends in the susceptibility and distribution of group B streptococci (GBS) serotypes in a Korean population and to elucidate any relationship between the serotypes and the antimicrobial susceptibility patterns found, 185 clinical isolates of GBS were investigated between 1990 and 1998. The rate of erythromycin resistance increased from 0% during the period 1990-1995 to 26% in 1996 and 40% in 1998. The overall rates of resistance to erythromycin and clindamycin were 20% and 22.2%, respectively. GBS serotype V was not detected until 1995, but it was isolated in 1996 and ranked third in frequency (18.8%) in 1997. Among the 37 erythromycin-resistant strains detected, 54.1% and 29.7% were of serotype III and V, respectively. The emerging erythromycin resistance detected among these GBS isolates was mainly due to a sudden increase in the incidence of GBS serotypes with multidrug-resistant phenotypes.

Anti-Bacterial Agents↗

PubMed2001

Microbiologic aspects of predominant bacteria isolated from the burn patients in Korea.

The risk of infection in burns is well-known. In recent decades, the antimicrobial resistance of bacteria isolated from burn patients has increased. For this reason, we have carried out a study of the predominant bacterial profiles and antimicrobial resistance patterns of isolates from a burn center in Korea. A retrospective study was undertaken at Hallym University, Hangang Sacred Heart Hospital to examine the bacterial isolates from the burn patients and to compare the antibiograms of the predominant bacteria isolated from these patients with those of the other wards over a period of 3 years. Pseudomonas aeruginosa was the most common (n=2997, 45.7%) isolate from the burn patients followed by Staphylococcus aureus (n=21261, 19.2%) and Acinetobacter baumannii (n=878, 13.4%). These bacteria, isolated from the burn patients, were almost all higher in antimicrobial resistance rate than those in the non-burn patients (P<0.05). Because these bacteria showed very high resistant rates, they must be avoided in order to control a hospital-acquired infection. Our results seem helpful in providing useful guidelines for choosing effective empiric antimicrobial therapy against bacteria isolated from the burn patients in Korea.

Adolescent↗