Biomedical subjects

Sang-Hun Lee

Publications and source records attributed to Sang-Hun Lee.

At least 37 records · Page 2Linked to original sources

PubMed2004

Binocular battles on multiple fronts.

The visual percept fluctuates over time when dissimilar patterns are shown to the two eyes (binocular rivalry). Where in the brain are the corresponding fluctuations of neuronal activity? Conflicting results from studies using various techniques have rendered this question unresolved at present. A recent paper by Wilson, however, promises to reconcile previous disagreements, as it demonstrates that rivalry can be located at different stages of the neuronal hierarchy, depending on the nature of stimulation.

Cerebral Cortex↗

PubMed2004

A fresh look at interocular grouping during binocular rivalry.

During binocular rivalry, observers sometimes perceive one complete visual object even though component features of that perceptually dominant object are distributed between the two eyes and are in rivalry against other, dissimilar features. This interocular grouping cannot be explained by models of rivalry in which one eye or the other is completely dominant at any given moment. But perhaps global interocular grouping is achieved by simultaneous local eye dominance, wherein portions of one eye's view and complementary portions of the other eye's view become dominant simultaneously. To test this possibility, we performed two experiments using relatively large, complex figures as rival targets. In one experiment we used an "eye-swap" technique to confirm that within given, local spatial regions of rivalry it was the region of an eye--not a given stimulus feature--that was usually dominant. In a second experiment, we measured dominance durations for multiple, local zones of rivalry and then created 1-min animations of a global "montage" in which dominance within local regions was governed by the distributions of dominance measured empirically. These animations included significant periods of time during which global interocular grouping was evident; observers viewed these animations intermixed with actual rivalry displays, and the resulting tracking data confirmed the similarity in global dominance of the two display types. Thus interocular grouping during rivalry does not rule out local, eye-based rivalry, although synergistic and top-down influences almost certainly provide additional force in the promotion of interocular grouping.

Adult↗

PubMed2004

Lithium selectively increases neuronal differentiation of hippocampal neural progenitor cells both in vitro and in vivo.

Lithium has been demonstrated to increase neurogenesis in the dentate gyrus of rodent hippocampus. The present study was undertaken to investigate the effects of lithium on the proliferation and differentiation of rat neural progenitor cells in hippocampus both in vitro and in vivo. Lithium chloride (1-3 mM) produced a significant increase in the number of bromodeoxyuridine (BrdU)-positive cells in high-density cultures, but did not increase clonal size in low-density cultures. Lithium chloride at 1 mM (within the therapeutic range) also increased the number of cells double-labeled with BrdU antibody and TuJ1 (a class III beta-tubulin antibody) in high-density cultures and the number of TuJ1-positive cells in a clone of low-density cultures, whereas it decreased the number of glial fibrillary acidic protein-positive cells in both cultures. These results suggest that lithium selectively increased differentiation of neuronal progenitors. These actions of lithium appeared to enhance a neuronal subtype, calbindin(D28k)-positive cells, and involved a phosphorylated extracellular signal-regulated kinase and phosphorylated cyclic AMP response element-binding protein-dependent pathway both in vitro and in vivo. These findings suggest that lithium in therapeutic amounts may elicit its beneficial effects via facilitation of neural progenitor differentiation toward a calbindin(D28k)-positive neuronal cell type.

Animals↗

PubMed2004

Survival and migration of transplanted neural stem cell-derived dopamine cells in the brain of parkinsonian rat.

Dopamine cells derived from neural stem cells were transplanted into the dopamine-denervated striatum in the rat. Survival of the dopamine cells, gliosis, and immunological reaction were examined by immunostaining. Tyrosine hydroxylase immunoreactive (TH+) cells were seen in the needle tract, walls of the lateral ventricle, thalamus, hippocampus, and external and internal capsules for up to 3 weeks examination. Most TH+ cells had mature-looking polygonal shapes with processes. Some cells migrated into the striatum. Behavioral improvement was not seen

Adrenergic Agents↗

PubMed2003

Investigation of cocaine plumes using surface acoustic wave immunoassay sensors.

Vapor sensors, aka electronic noses, are becoming an increasingly popular analytical tool for detection and identification of small molecules in the gas phase. In this paper, we present the results of a series of experiments demonstrating real-time vapor phase detection of cocaine molecules. A distinctive response or signature was observed under laboratory conditions in which the cocaine vapors were presented using an INEL vapor generator and under "field" conditions facilitated by the Georgia Bureau of Investigation (GBI) Crime Lab. For these experiments, the sensor component was a two-port resonator on ST-X quartz with a center frequency of approximately 250 MHz. On this cut of quartz, a temperature-compensated surface acoustic wave is generated via an interdigital transducer. Antibenzoylecgonine (anti-BZE) antibodies are attached to the electrodes on the device surface via a protein-A cross linker. We observed a large transient frequency shift accompanied by baseline shift with the anti-BZE coated sensor. After repeated experiments and the use of numerous controls, we believe that we have achieved real time molecular recognition of cocaine molecules.

Acoustics↗

PubMed2003

Significance of chin-brow vertical angle in correction of kyphotic deformity of ankylosing spondylitis patients.

STUDY DESIGN: A prospective study. OBJECTIVES: To assess the significance of chin-brow vertical angle in planning and evaluating the correction of kyphotic deformity with ankylosis of the cervical spine in ankylosing spondylitis patients. SUMMARY OF BACKGROUND DATA: Accurate assessment and measurement of spinal kyphotic deformity is required when planning treatment and assessing its results. METHODS: Thirty-four ankylosing spondylitis patients with cervical ankylosis who had undergone pedicle subtraction extension osteotomy for correction of kyphotic deformity were studied. Radiographic assessment for sagittal balance was performed by measuring thoracic kyphosis, lumbar lordosis, the distance between the vertical line on the anterosuperior point of T1 and that of S1, and sacral inclination. Chin-brow vertical angle was measured on the clinical photos of the patients. Clinical outcomes were assessed by a questionnaire. RESULTS: The preoperative and postoperative chin-brow vertical angles were 35.5 degrees and 1.8 degrees, respectively. Final follow-up radiographs showed an increase in lumbar lordosis from 5.5 degrees to 43.2 degrees (an increase of 37.7 degrees ), and thoracic kyphosis remained stable from 50.4 degrees to 50.2 degrees. Sagittal imbalance significantly improved from 101.5 mm to 12.7 mm. The decreased chin-brow vertical angle correlated negatively with the correction angle. The patients with a chin-brow vertical angle of less than -10 degrees had significantly low scores on horizontal gaze. CONCLUSIONS: Chin-brow vertical angle was an objective index for evaluating horizontal gaze. Based on the results of this study, measurement of chin-brow vertical angle is recommended for planning correction of kyphosis and accurate evaluation of treatment outcome.

Adult↗

PubMed2003

Erythropoietin and bone morphogenetic protein 7 mediate ascorbate-induced dopaminergic differentiation from embryonic mesencephalic precursors.

Mesencephalic precursors derived from early (embryonic day 12; E12) rat embryos were grown in vitro using mitogen basic fibroblast growth factor (bFGF) and these cells efficiently differentiated into dopaminergic (DA) neurons. However, this in vitro DA differentiation was poor in mesencephalic precursors isolated from later embryos (E13-15). Ascorbate (AA) treatment enhanced yields of DA neurons from E12 precursors, and increased the number of DA neurons generated from E13 precursors to levels attained when using E12 precursors. AA markedly up-regulated expression of bone morphogenetic protein 7 (BMP7) and erythropoietin (Epo) in precursors, but did not affect expression of a number of genes known to regulate midbrain DA development. The addition of these recombinant proteins or blockers revealed that both BMP7 and Epo mediate AA-induced DA neuron differentiation.

Animals↗

PubMed2003

Ascorbate-induced differentiation of embryonic cortical precursors into neurons and astrocytes.

A specific role for ascorbate (AA) in brain development has been postulated based on a rise of AA levels in fetal brain (Kratzing et al., 1985). To evaluate the role of AA during CNS development, we analyzed the survival, proliferation, and differentiation of AA-treated CNS precursor cells isolated from rat embryonic cortex. Immunocytochemical analyses revealed that AA promoted the in vitro differentiation of CNS precursor cells into neurons and astrocytes in a cell density-dependent manner. Additionally, AA increased the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) of postmitotic neurons in primary neuronal cultures. Differential expression analysis of genes specific to neuronal or glial differentiation revealed an AA-dependent increase in the expression of genes that could potentially compound the effects of AA on cell differentiation. These data suggest that AA may act in the developing brain to stimulate the generation of CNS neurons and glia, thereby assisting in the formation of neural circuits by promoting the acquisition of neuronal synaptic functions.

Animals↗

PubMed2003

Embryonic cortical stem cells secrete diffusible factors to enhance their survival.

Neural stem cells play major roles in brain development. The precise regulation of neural stem cell survival and proliferation is important for determining numbers of terminally differentiated neurons and glia. In this study, we demonstrate that embryonic neural stem cells positively regulate their own survival by secreting diffusible factors. Single cells isolated from embryonic day 14 (E14) rat cortices were plated at clonal densities to avoid direct cell-cell contact. Clones positive for nestin, a neural stem cell marker, were formed from single cells in the presence of basic fibroblast factor (bFGF). The numbers of viable cells and clones were markedly increased by supplementing conditioned medium (stem cell conditioned medium, SCM) prepared from dense cultures of embryonic cortical stem cells. TUNEL and LDH assays confirmed SCM-mediated survival of embryonic cortical stem cells.

Animals↗

PubMed2003

Effect of the CYP2D6 genotype on the pharmacokinetics of tropisetron in healthy Korean subjects.

OBJECTIVE: To evaluate the effect of the CYP2D6 genotype on the pharmacokinetics of tropisetron in healthy Korean subjects. METHODS: A single 5-mg capsule of tropisetron was administered orally to 13 healthy subjects. Plasma concentrations were determined by validated HPLC procedures and data were analyzed by using noncompartmental linear PK methods. Four alleles, CYP2D6*1, CYP2D6*2 x2, CYP2D6*5, and CYP2D6*10, were identified by PCR. RESULTS: Thirteen subjects, consisting of two homozygous carriers of the wild type allele ( *1/*1), four heterozygous carriers of poor metabolizer (PM)-associated allele (* 1/*10), six homozygous carriers of PM-associated alleles (four with *10/*10 and two with *5/*10), and one carrier of a duplicated allele *1/*2 x2. All tested pharmacokinetic parameters (AUC(inf), AUC(inf)(NL70), Cmax, Cmax(NL70), T(1/2), and Tec) were significantly different among four different genotypic groups. The mean AUCs of carriers with the heterozygous PM-associated allele and the homozygous PM-associated allele were 1.9- and 6.8-higher than those of carriers with the wild type allele, respectively. In contrast, the mean AUC of carriers with a duplicated allele was 0.5-fold lower than that of those carriers with the wild type allele. CONCLUSION: The presence of CYP2D6*5, CYP2D6*10, and CYP2D6*2 x2 has an important impact on the pharmacokinetics of tropisetron, which may influence clinical response to tropisetron therapy.

Adult↗

PubMed2003

Vasoactive intestinal peptide selectively depolarizes thalamic relay neurons and attenuates intrathalamic rhythmic activity.

The reciprocal synaptic relationship between the relay thalamus and surrounding thalamic reticular nucleus can lead to the generation of various rhythmic activities that are associated with different levels of behavioral states as well as certain pathophysiological conditions. Intrathalamic rhythmic activities may be attenuated by numerous neuromodulators that arise from a variety of brain stem nuclei. This study focuses on the potential role of a particular neuropeptide, vasoactive intestinal peptide (VIP). VIP and its receptors are localized within the thalamic circuit and thus may serve as an endogenous modulator of the rhythmic activity. Using extracellular multiple-unit recording techniques, we found that VIP strongly attenuated the slow, 2- to 4-Hz intrathalamic rhythm. This rhythm is similar to that observed during slow wave sleep and certain pathophysiological conditions such as generalized absence epilepsy. Using intracellular recording techniques, we found that VIP selectively depolarized relay neurons in the ventrobasal nucleus but had negligible actions on neurons in thalamic reticular nucleus. The VIP-mediated depolarization is produced via an enhancement of the nonselective cation conductance, Ih. The antioscillatory actions of VIP likely occur by shifting the membrane potential to decrease the probability of burst discharge by relay neurons, a requirement to maintain the rhythmic activity. Not only does VIP alter the intrathalamic rhythmic activity, this peptide that is endogenous to the thalamic circuit may also play a significant role in the regulation of information transfer through the thalamocortical circuit.

Action Potentials↗

PubMed2003

Chronic lithium enhances hippocampal long-term potentiation, but not neurogenesis, in the aged rat dentate gyrus.

We investigated the hippocampal long-term potentiation (LTP), neurogenesis, and the activation of signaling molecules in the 20-month-old aged rats following chronic lithium treatment. Chronic lithium treatment produced a significant 79% increase in the numbers of BrdU(+) cells after treatment completion in the dentate gyrus (DG). Both LTP obtained from slices perfused with artificial cerebrospinal fluid (ACSF-LTP), and LTP recorded in the presence of bicuculline (bicuculline-LTP) were significantly greater in the lithium group than in the saline controls. Our results show that as with young rats, chronic lithium can substantially increase LTP and the number of BrdU(+) cells in the aged rats. However, neurogenesis, assessed by colocalization of NeuN and BrdU, was not detected in the aged rat DG subjected to chronic lithium treatment. Therefore, it is concluded that the increase in LTP and the number of BrdU(+) cells might not be associated with increases in neurogenesis in the granule cell layer of the DG. Lithium might has a beneficial effects through other signaling pathways in the aged brain.

Aging↗

PubMed2003

Neurons and astrocytes secrete factors that cause stem cells to differentiate into neurons and astrocytes, respectively.

We examined the role of soluble factors secreted by neurons and astrocytes in the differentiation of CNS stem cells. We showed that the soluble factors from neurons strongly induced multipotent cortical stem cells to acquire neuronal identity, while the factors from astrocytes promoted astrocytic differentiation. Neurons secreted the brain-derived neurotrophic factor and neurotrophin-3 to induce neuron differentiation, while astrocytes secreted ciliary neurotrophic factor for astrocyte differentiation. Both neurons and astrocytes secrete bone morphogenetic proteins (BMPs). Using BMP antagonists it was shown that BMPs were responsible for the neuron-induced neuronal differentiation, as well as the astrocyte-induced astrocytic differentiation. These findings demonstrate the importance of soluble signals in lineage-specific differentiation and provide evidence for the roles of neurons and astrocytes in stem cell differentiation.

Animals↗

PubMed2003

Lithium enhances long-term potentiation independently of hippocampal neurogenesis in the rat dentate gyrus.

We measured the temporal and spatial profiles of neural precursor cells, hippocampal long-term potentiation (LTP), and signaling molecules in neurogenesis-induced adult rats. Chronic lithium treatment produced a significant 54% and 40% increase in the numbers of bromodeoxyuridine [BrdU(+)] cells after 12 h and 28 days, respectively, after treatment completion in the dentate gyrus (DG). Both LTP obtained from slices perfused with artificial cerebrospinal fluid (ACSF-LTP) and LTP recorded in the presence of bicuculline (bicuculline-LTP) were significantly greater in the lithium group than in the saline controls. Although the number of BrdU(+) cells, approximately 90% of which were double-labeled with a neural marker neuronal nuclear protein, were markedly increased in the granule cell layer (GCL) 28 days after the completion of the 28-day lithium treatment, the magnitude of LTP observed at this time was similar to that observed 12 h after completing the 28-day lithium treatment. However, protein levels of calcium and calmodulin-dependent protein kinase II, p-Elk and TrkB were highly elevated until 28 days after the 28-day lithium treatment. Acute lithium treatment for 2 days also enhanced LTP, which was accompanied by the elevated expression of p-CREB, but not by neurogenesis. Our results suggest that the enhancement of LTP is independent of the increased number of neurons per se and it is more closely associated with key molecules, which are probably involved in neurogenesis.

Animals↗

PubMed2003

Dopaminergic neuronal differentiation from rat embryonic neural precursors by Nurr1 overexpression.

In vitro expanded CNS precursors could provide a renewable source of dopamine (DA) neurons for cell therapy in Parkinson's disease. Functional DA neurons have been derived previously from early midbrain precursors. Here we demonstrate the ability of Nurr1, a nuclear orphan receptor essential for midbrain DA neuron development in vivo, to induce dopaminergic differentiation in naïve CNS precursors in vitro. Independent of gestational age or brain region of origin, Nurr1-induced precursors expressed dopaminergic markers and exhibited depolarization-evoked DA release in vitro. However, these cells were less mature and secreted lower levels of DA than those derived from mesencephalic precursors. Transplantation of Nurr1-induced DA neuron precursors resulted in limited survival and in vivo differentiation. No behavioral improvement in apomorphine-induced rotation scores was observed. These results demonstrate that Nurr1 induces dopaminergic features in naïve CNS precursors in vitro. However, additional factors will be required to achieve in vivo function and to unravel the full potential of neural precursors for cell therapy in Parkinson's disease.

Animals↗

PubMed2002

Neural cell adhesion molecule (NCAM) promotes the differentiation of hippocampal precursor cells to a neuronal lineage, especially to a glutamatergic neural cell type.

Rat hippocampal precursor cells isolated from hippocampi of embryonic day 16.5 (E16.5) rat embryos were found to proliferate in the presence of basic fibroblast growth factor. Addition of soluble neural cell adhesion molecule (NCAM) to these precursor cells reduced cell proliferation in a dose dependent manner and enhanced the induction of precursor cells' differentiation to the neuronal lineage. Given these findings that NCAM induces the differentiation of hippocampal precursor cells, we investigated possible effects of NCAM on the expression of basic helix-loop-helix (bHLH) transcription factors during the differentiation. Soluble NCAM upregulated the transcription of bHLH transcription factors, neurogenin1 and NeuroD, but decreased HES5. Western blot analysis showed that NCAM increased the expression levels of CaMKII, p-MAPK, GluR1 and NR1 but decreased p-STAT3. These results support a role for NCAM in the inhibition of proliferation and the induction of neural differentiation of hippocampal neural precursor cells, and act as developmental regulators of the bHLH families, ultimately leading to the generation of glutamatergic neural cell types in the differentiation of hippocampal precursor cells.

Animals↗

PubMed2002

Reciprocal actions of NCAM and tPA via a Ras-dependent MAPK activation in rat hippocampal neurons.

In an attempt to identify the functions of neural cell adhesion molecule (NCAM) and tissue plasminogen activator (tPA) in hippocampal synaptic plasticity, we investigated the relationship between the two molecules by focusing on mitogen-activated protein kinase (MAPK), an essential enzyme in this process. NCAM clustering in cultured hippocampal neurons transiently induced MAPK within 10min. Moreover, soluble NCAM also induced a Ras-dependent MAPK activation. Conversely, MAPK activation led to an increase in the expressions of all three isoforms of NCAM. Treatment of neurons with tPA and plasminogen induced a Ras-dependent MAPK activation and tPA-plasmin degradation of NCAM was mediated in a MAPK-dependent manner. Soluble NCAM transiently inhibited tPA mRNA expression levels in a MAPK-dependent manner, while stimulation of MAPK alone induced tPA reduction in cells. These results collectively indicate that NCAM and tPA reciprocally act as important regulators in the modulation of synaptic plasticity via a Ras-MAPK-involved signaling pathway. In turn, MAPK activation may cause tPA degradation or a decrease in expression to promote synaptic plasticity.

Animals↗

PubMed2002

Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease.

Parkinson's disease is a widespread condition caused by the loss of midbrain neurons that synthesize the neurotransmitter dopamine. Cells derived from the fetal midbrain can modify the course of the disease, but they are an inadequate source of dopamine-synthesizing neurons because their ability to generate these neurons is unstable. In contrast, embryonic stem (ES) cells proliferate extensively and can generate dopamine neurons. If ES cells are to become the basis for cell therapies, we must develop methods of enriching for the cell of interest and demonstrate that these cells show functions that will assist in treating the disease. Here we show that a highly enriched population of midbrain neural stem cells can be derived from mouse ES cells. The dopamine neurons generated by these stem cells show electrophysiological and behavioural properties expected of neurons from the midbrain. Our results encourage the use of ES cells in cell-replacement therapy for Parkinson's disease.

Animals↗