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Biomedical subjects

Kwang S Kim

Publications and source records attributed to Kwang S Kim.

At least 19 recordsLinked to original sources
PubMed2007

Human neural stem cells over-expressing VEGF provide neuroprotection, angiogenesis and functional recovery in mouse stroke model.

BACKGROUND: Intracerebral hemorrhage (ICH) is a lethal stroke type. As mortality approaches 50%, and current medical therapy against ICH shows only limited effectiveness, an alternative approach is required, such as stem cell-based cell therapy. Previously we have shown that intravenously transplanted human neural stem cells (NSCs) selectively migrate to the brain and induce behavioral recovery in rat ICH model, and that combined administration of NSCs and vascular endothelial growth factor (VEGF) results in improved structural and functional outcome from cerebral ischemia. METHODS AND FINDINGS: We postulated that human NSCs overexpressing VEGF transplanted into cerebral cortex overlying ICH lesion could provide improved survival of grafted NSCs, increased angiogenesis and behavioral recovery in mouse ICH model. ICH was induced in adult mice by unilateral injection of bacterial collagenase into striatum. HB1.F3.VEGF human NSC line produced an amount of VEGF four times higher than parental F3 cell line in vitro, and induced behavioral improvement and 2-3 fold increase in cell survival at two weeks and eight weeks post-transplantation. CONCLUSIONS: Brain transplantation of F3 human NSCs over-expressing VEGF near ICH lesion sites provided differentiation and survival of grafted human NSCs and renewed angiogenesis of host brain and functional recovery of ICH animals. These results suggest a possible application of the human neural stem cell line, which is genetically modified to over-express VEGF, as a therapeutic agent for ICH-stroke.

Animals↗
PubMed2007

Brain transplantation of immortalized human neural stem cells promotes functional recovery in mouse intracerebral hemorrhage stroke model.

We have generated stable, immortalized cell lines of human NSCs from primary human fetal telencephalon cultures via a retroviral vector encoding v-myc. HB1.F3, one of the human NSC lines, expresses a normal human karyotype of 46, XX, and nestin, a cell type-specific marker for NSCs. F3 has the ability to proliferate continuously and differentiate into cells of neuronal and glial lineage. The HB1.F3 human NSC line was used for cell therapy in a mouse model of intracerebral hemorrhage (ICH) stroke. Experimental ICH was induced in adult mice by intrastriatal administration of bacterial collagenase; 1 week after surgery, the rats were randomly divided into two groups so as to receive intracerebrally either human NSCs labeled with beta-galactosidase (n = 31) or phosphate-buffered saline (PBS) (n = 30). Transplanted NSCs were detected by 5-bromo-4-chloro-3-indolyl-beta-d-galactoside histochemistry or double labeling with beta-galactosidase (beta-gal) and mitogen-activated protein (MAP)2, neurofilaments (both for neurons), or glial fibrillary acidic protein (GFAP) (for astrocytes). Behavior of the animals was evaluated for period up to 8 weeks using modified Rotarod tests and a limb placing test. Transplanted human NSCs were identified in the perihematomal areas and differentiated into neurons (beta-gal/MAP2(+) and beta-gal/NF(+)) or astrocytes (beta-gal/GFAP(+)). The NSC-transplanted group showed markedly improved functional performance on the Rotarod test and limb placing after 2-8 weeks compared with the control PBS group (p < .001). These results indicate that the stable immortalized human NSCs are a valuable source of cells for cell replacement and gene transfer for the treatment of ICH and other human neurological disorders. Disclosure of potential conflicts of interest is found at the end of this article.

Animals↗
PubMed2007

A color version of the Hinsberg test: 1 degrees -3 degrees amine indicator.

The Hinsberg test to recognize the type of amine (1 degrees -3 degrees amines), which has been established for more than 100 years and well documented in textbooks, is not possible without conducting complicated organic reactions. We report for the first time unique chemosensors that are capable of showing selective color changes toward 1 degrees -3 degrees amines as a color version of the Hinsberg test. This simple and straightforward qualitative analysis, using the synthesized novel compounds herein, can be considered a new innovative tool for discriminating 1 degrees -3 degrees amines as an alternative to the historical Hinsberg test.

Amines↗
PubMed2006

Structure and spectral features of H+(H2O)7: Eigen versus Zundel forms.

The two dimensional (2D) to three dimensional (3D) transition for the protonated water cluster has been controversial, in particular, for H(+)(H(2)O)(7). For H(+)(H(2)O)(7) the 3D structure is predicted to be lower in energy than the 2D structure at most levels of theory without zero-point energy (ZPE) correction. On the other hand, with ZPE correction it is predicted to be either 2D or 3D depending on the calculational levels. Although the ZPE correction favors the 3D structure at the level of coupled cluster theory with singles, doubles, and perturbative triples excitations [CCSD(T)] using the aug-cc-pVDZ basis set, the result based on the anharmonic zero-point vibrational energy correction favors the 2D structure. Therefore, the authors investigated the energies based on the complete basis set limit scheme (which we devised in an unbiased way) at the resolution of the identity approximation Moller-Plesset second order perturbation theory and CCSD(T) levels, and found that the 2D structure has the lowest energy for H(+)(H(2)O)(7) [though nearly isoenergetic to the 3D structure for D(+)(D(2)O)(7)]. This structure has the Zundel-type configuration, but it shows the quantum probabilistic distribution including some of the Eigen-type configuration. The vibrational spectra of MP2/aug-cc-pVDZ calculations and Car-Parrinello molecular dynamics simulations, taking into account the thermal and dynamic effects, show that the 2D Zundel-type form is in good agreement with experiments.

Chemistry, Physical↗
PubMed2006

Hydration phenomena of sodium and potassium hydroxides by water molecules.

The hydrated structures, dissociation energies, thermodynamic quantities, infrared spectra, and electronic properties of alkali-metal hydroxides (MOH, M = Na and K) hydrated by up to six water molecules [MOH(H(2)O)(n=1-6)], are investigated by using the density functional theory and Møller-Plesset second-order perturbation theory. Further accurate analysis based on the coupled cluster theory with singles, doubles, and perturbative triples excitations is more consistent with the MP2 results. NaOH shows a peculiar trend in dissociation: it begins to form a partially dissociated structure for n = 3, and it dissociates for n = 4 and 6, whereas it is undissociated for n = 5. However, for n = 5, the dissociated structure is nearly isoenergetic to the undissociated structure. For KOH, it begins to show partial dissociation for n = 5, and complete dissociation for n = 6.

Hydroxides↗
PubMed2006

Homology modeling and molecular dynamics study of West Nile virus NS3 protease: a molecular basis for the catalytic activity increased by the NS2B cofactor.

The West Nile virus (WNV) NS3 serine protease, which plays an important role in assembly of infective virion, is an attractive target for anti-WNV drug development. Cofactors NS2B and NS4A increase the catalytic activity of NS3 in dengue virus and Hepatitis C virus, respectively. Recent studies on the WNV-NS3 characterize the catalytically active form of NS3 by tethering the 40-residue cofactor NS2B. It is suggested that NS2B is essential for the NS3 activity in WNV, while there is no information of the WNV-NS3-related crystal structure. To understand the role of NS2B/substrate in the NS3 catalytic activity, we built a series of models: WNV-NS3 and WNV-NS3-NS2B and WNV-NS3-NS2B-substrate using homology modeling and molecular modeling techniques. Molecular dynamics (MD) simulations were performed for 2.75 ns on each model, to investigate the structural stabilization and catalytic triad motion of the WNV NS3 protease with and without NS2B/substrate. The simulations show that the NS3 rearrangement occurs upon the NS2B binding, resulting in the stable D75-OD1...H51-NH hydrogen bonding. After the substrate binds to the NS3-NS2B active site, the NS3 protease becomes more stable, and the catalytic triad is formed. These results provide a structural basis for the activation and stabilization of the enzyme by its cofactor and substrate.

Amino Acid Sequence↗
PubMed2006

Spatial structure of Au8: Importance of basis set completeness and geometry relaxation.

The relative stabilities of the lowest energy structures are calculated for the gold octamer, Au8, employing highly correlated ab initio methods. The question of dimensionality of these clusters is addressed, and a guideline for future structural studies of such systems is provided. In particular, the importance of geometry relaxation beyond the MP2 level of theory as well as the need for basis sets toward the complete limit (CBS) are discussed. The planar D(4h) symmetric structure of Au8 is the lowest energy structure. At the CCSD(T)/CBS limit, it is separated by 16 kJ mol(-1) from the next higher Td symmetric isomer.

Journal Article↗
PubMed2006

Pseudorotation-driven dynamical structure of the tropyl radical.

Despite intensive studies of the neutral tropyl radical, none of its structure, energetics, and vibrational modes are still clear. This system has puzzled scientists for over a decade since one vibrational mode frequency sharply varies from imaginary number 3000i cm-1 to the real number 6000 cm-1, depending on the calculation methods employed. We find that the origin of this peculiar mode is due to the pseudorotation (omegairot) involved in the interconversion of two nearly isoenergetic Jahn-Teller configurations (elongated structure 2B1 and compressed structure 2A2 with C2v symmetry). Here, we first report that this interconversion is not via D7h or C2v symmetry configuration but via Cs symmetry (i.e., by changing the C2v axis). This interconversion barrier is found negligibly small. Thus, the two conformers are considered to be not two different structures but a dynamically identical structure with partial quantum statistical distributions on the potential energy surface. Owing to the nearly barrierless pseudorotation, the overall structure in a short time scale (less than femtosecond) would be Cs-like between 2A2 and 2B1 configurations with small fluctuation of bond distances. However, the dynamical transitions between the 2B1 and 2A2 configurations via 14 different pseudorotation pathways would make the tropyl radical have the effective D7h structure in either a nonshort time scale (greater than femtosecond) or at nonlow temperatures, which explains the high temperature electron spin resonance experiments.

Journal Article↗
PubMed2006

Organic-inorganic hybrid compounds of Li with bisimidazole derivatives: Li ion binding study and topochemical properties.

The imidazole-based ligands, bis(imidazol-1-yl)methane (Bizm, 1a) and (pyrenyl)bis(imidazol-1-yl) methane (Pbizm,2a) were prepared. With LiClO4, these two compounds formed two novel organic-inorganic hybrid materials: a 3D network polymer Li(Bizm).ClO4 (1b) and a 1D chain polymer Li(Pbizm)2.ClO4 (2b). The intriguing topological and physiochemical characteristics of 1b and 2b are reported on the basis of the X-ray single-crystal structure analysis and Li ion binding studies.

Journal Article↗
PubMed2006

Interaction of a neurotropic strain of Borrelia turicatae with the cerebral microcirculation system.

Relapsing fever (RF) is a spirochetal infection characterized by relapses of a febrile illness and spirochetemia due to the sequential appearance and disappearance of isogenic serotypes in the blood. The only difference between isogenic serotypes is the variable major outer membrane lipoprotein. In the absence of specific antibody, established serotypes cause persistent infection. Studies in our laboratory indicate that another consequence of serotype switching in RF is a change in neuroinvasiveness. As the next step to elucidate this phenomenon, we studied the interaction of the neurotropic Oz1 strain of the RF agent Borrelia turicatae with the cerebral microcirculation. During persistent infection of antibody-deficient mice, we found that serotype 1 entered the brain in larger numbers and caused more severe cerebral microgliosis than isogenic serotype 2. Microscopic examination revealed binding of B. turicatae to brain microvascular endothelial cells in vivo. In vitro we found that B. turicatae associated with brain microvascular endothelial cells (BMEC) significantly more than with fibroblasts or arachnoidal cells. The binding was completely eliminated by pretreatment of BMEC with proteinase K. Using transwell chambers with BMEC barriers, we found that serotype 1 crossed into the lower compartment significantly better than serotype 2. Heat killing significantly reduced BMEC crossing but not binding. We concluded that the interaction of B. turicatae with the cerebral microcirculation involves both binding and crossing brain microvascular endothelial cells, with significant differences among isogenic serotypes.

Animals↗
PubMed2006

Hydration and dissociation of hydrogen fluoric acid (HF).

The hydration and dissociation phenomena of HF(H(2)O)(n)() (n < or = 10) clusters have been studied by using both the density functional theory with the 6-311++G[sp] basis set and the Møller-Plesset second-order perturbation theory with the aug-cc-pVDZ+(2s2p/2s) basis set. The structures for n > or = 8 are first reported here. The dissociated form of the hydrogen-fluoric acid in HF(H(2)O)(n) clusters is found to be less stable at 0 K than the undissociated form until n = 10. HF may not be dissociated at 0 K solely by water molecules because the HF H bond is stronger than the OH H bond, against the expectation that the dissociated HF(H(2)O)(n) would be more stable than the undissociated one in the presence of a number of water molecules. The dissociation would be possible for only a fraction of a number of hydrated HF clusters by the Boltzmann distribution at finite temperatures. This is in sharp contrast to other hydrogen halide acids (HCl, HBr, HI) showing the dissociation phenomena at 0 K for n > or = 4. The IR spectra of dissociated and undissociated structures of HF(H(2)O)(n) are compared. The structures and binding energies of HF(H(2)O)(n) are found to be similar to those of (H(2)O)(n+1). It is interesting that HF(H(2)O)(n=5,6,10) are slightly less stable compared with other sizes of clusters, just like the fact that (H(2)O)(n=6,7,11) are slightly less stable. The present study would be useful for the experimental/spectroscopic investigation of not only the dissociation phenomena of HF but also the similarity of the HF-water clusters to the water clusters.

Journal Article↗
PubMed2006

Interactions of neutral and cationic transition metals with the redox system of hydroquinone and quinone: theoretical characterization of the binding topologies, and implications for the formation of nanomaterials.

To understand the self-assembly process of the transition metal (TM) nanoclusters and nanowires self-synthesized by hydroquinone (HQ) and calix[4]hydroquinone (CHQ) by electrochemical redox processes, we have investigated the binding sites of HQ for the transition-metal cations TM(n+)=Ag(+), Au(+), Pd(2+), Pt(2+), and Hg(2+) and those of quinone (Q) for the reduced neutral metals TM(0), using ab initio calculations. For comparison, TM(0)-HQ and TM(n+)-Q interactions, as well as the cases for Na(+) and Cu(+) (which do not take part in self-synthesis by CHQ) are also included. In general, TM-ligand coordination is controlled by symmetry constraints imposed on the respective orbital interactions. Calculations predict that, due to synergetic interactions, silver and gold are very efficient metals for one-dimensional (1D) nanowire formation in the self-assembly process, platinum and mercury favor both nanowire/nanorod and thin film formation, while palladium favors two-dimensional (2D) thin film formation.

Cations↗
PubMed2006

Characterization of weak NH-pi intermolecular interactions of ammonia with various substituted pi-systems.

Among the several weak intermolecular interactions pervading chemistry and biology, the NH-pi interaction is one of the most widely known. Nevertheless its weak nature makes it one of the most poorly understood and characterized interactions. The present study details the results obtained on gas-phase complexes of ammonia with various substituted pi systems using both laser vibrational spectroscopy and ab initio calculations. The spectroscopic measurements carried out by applying one-color resonant two-photon ionization (R2PI) and IR-vibrational predissociation spectroscopy in the region of the NH stretches yield the first experimental NH stretching shifts of ammonia upon its interaction with various kinds of pi-systems. The experiments were complemented by ab initio calculations and energy decompositions, carried out at the second-order Møller-Plesset (MP2) level of theory. The observed complexes show characteristic vibrational spectra which are very similar to the calculated ones, thereby allowing an in-depth analysis of the interaction forces and energies. The interaction energy of the conformers responsible for the observed vibrational spectra has the maximum contribution from dispersion energies. This implies that polarizabilities of the pi-electron systems play a very important role in governing the nature and geometry of the NH-pi interaction. The larger polarizability of ammonia as compared to water and the tendency to maximize the dispersion energy implies that the characteristics of the NH-pi interactions are markedly different from that of the corresponding OH-pi interactions.

Journal Article↗
PubMed2006

Homology modeling and molecular dynamics study of chorismate synthase from Shigella flexneri.

Shigellosis is a major public health problem in many developing countries. Antibiotic therapy can reduce the severity of the dysentery and prevent potentially lethal complication. However, owing to the increased resistance to most of the widely used and inexpensive antibiotics, there is an urgent need for new antibacterial agents, particularly those that act on novel targets. Chorismate synthase (CS) is a key enzyme in the shikimic acid pathway, which is essential for the synthesis of aromatic amino acids in bacteria. As an anti-bacterial drug target, CS has been well validated. A homology model of Shigella-CS with the flavin mononucleotide (FMN) binding was constructed using the crystal structure of CS from other species. The substrate 5-enolpyruvylshikimate 3-phosphate (EPSP) was subsequently docked into the active site based on previous theoretical studies. Molecular dynamics (MD) was used to refine the starting ternary model. The model was well conserved during the 1.8 ns MD simulation with the equilibrium root mean square deviation (RMSD) value of 3.5 angstrom. The substrate binding energy was calculated and the electrostatic energy was found to be the most important term for binding. Decomposition of binding energies revealed that R129, R125, R327, R134 and R48 are important residues involved in substrate binding, which is useful for further site-directed mutagenesis experiments. In the absence of crystal structure, our study provides an early insight into the structure of CS from Shigella flexneri and its binding to the substrate and cofactor, thus facilitating the inhibitor design.

Amino Acid Sequence↗
PubMed2006

Mycobacterium tuberculosis invasion and traversal across an in vitro human blood-brain barrier as a pathogenic mechanism for central nervous system tuberculosis.

BACKGROUND: Central nervous system (CNS) tuberculosis is a serious, often fatal disease that disproportionately affects young children. It is thought to develop when Mycobacterium tuberculosis breaches the blood-brain barrier (BBB), which is composed of tightly apposed brain microvascular endothelial cells. However, the mechanism(s) involved in this process are poorly understood. METHODS: To better understand these processes, we developed an in vitro model of M. tuberculosis BBB infection using primary human brain microvascular endothelial cells. RESULTS: M. tuberculosis was found to both invade and traverse the model BBB significantly more than did M. smegmatis (a nonpathogenic mycobacterium). Invasion by M. tuberculosis across the BBB required host-cell actin cytoskeletal rearrangements. By microarray expression profiling, we found 33 M. tuberculosis genes to be highly up-regulated during the early stages of invasion of the BBB by M. tuberculosis; 18 of them belong to a previously described in vivo-expressed genomic island (Rv0960-Rv1001). Defined M. tuberculosis isogenic transposon mutants for the up-regulated genes Rv0980c, Rv0987, Rv0989c, and Rv1801 were found to be deficient in their ability to invade the BBB model. CONCLUSIONS: We developed an in vitro model of M. tuberculosis BBB infection and identified M. tuberculosis genes that may be involved in CNS invasion.

Actins↗
PubMed2006

Magic structures and quantum conductance of silver nanowires.

We investigate the pathway of thinning process for transient [110] nanowires (NWs) of Ag. The result is in good agreement with experimental observations. An unambiguous identification of the structure of a NW requires at least two views along different directions. In the cases where two views of different NW structures are practically the same for very thin NWs which pose experimental difficulty due to small signal-to-noise ratio, our theoretical analysis helps distinguish these structures. On the basis of conductance (G) calculations vis-á-vis the structure of transient NWs, the puzzling experimental observation of fractionally quantized G values is explained by considering the existence of mixed structures for thin wires.

Journal Article↗
PubMed2006

Electric field effects on water clusters (n = 3-5): systematic ab initio study of structures, energetics, and transition states.

The structures, energetics, and transition states of water clusters (trimer to pentamer, n = 3-5) are investigated as a function of electric field by using ab initio calculations. With an increasing strength of the field, the most stable cyclic structures of trimer, tetramer, and pentamer open up to align their dipole moments along the direction of the field. For the lower strength (below 0.3 V/angstroms) of the electric field, the dipole moment of each water monomer is along the same direction with the field, while it retains the cyclic structure. For the higher strength of the field, to have a higher dipole moment for the cluster along the field direction, each cyclic structure opens up to form a linear chain or "water wire." We have investigated the transition state structures between the cyclic and linear forms for the field strengths of 0.3-0.4 V/angstroms where both cyclic and linear forms are energetically comparable.

Journal Article↗