Seung Mook Jo

Aarhus University, Aarhus, Central Jutland, Denmark

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Publications (25)58.91 Total impact

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    ABSTRACT: Zinc enriched (ZEN) neurons and terminals are abundant in the rodent spinal cord. Zinc ions have been suggested to modulate the excitability of primary afferent fibers believed to be important in nociceptive transmission. To test the hypothesis that vesicular zinc concentration is related to neuropathic pain we applied Chung's rodent pain model on BALB/c mice, and traced zinc transporter 3 (ZnT3) proteins and zinc ions with immunohistochemistry and autometallography (AMG), respectively. Under anesthesia the left fifth lumbar spinal nerve was ligated in male mice in order to produced neuropathic pain. The animals were then sacrificed 5 days later. The ZnT3 immunoreactivity was found to have decreased significantly in dorsal horn of fourth, fifth, and sixth lumbar segments. In parallel with the depressed ZnT3 immunoreactivity the amount of vesicular zinc decreased perceptibly in superficial gray matters of especially layer I-IV of the same segments. The transection-induced reduction of vesicular zinc in ZEN terminals of the dorsal horn was synchronic to reduced pain threshold, as measured by von Frey method. In a separate study, we observed intensive zinc selenite precipitation in somata of the smaller spinal ganglion cell, but 5 days after spinal nerve transection zinc precipitation was also found in the lager ganglion cells. The present results indicate that zinc may be involved in pain mechanism in the spinal ganglion level. These results support the hypothesis that vesicular zinc might have a modulatory role for neuropathic pain. Thus, increased pain sensitivity might be related to reduce vesicular zinc level in the dorsal spinal gray matter.
    BioMetals 05/2008; 21(2):151-8. DOI:10.1007/s10534-007-9103-x · 2.69 Impact Factor
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    ABSTRACT: The effects of adrenalectomy (ADX) on the vesicular zinc content of zinc-enriched (ZEN) terminals in mouse hippocampus were investigated at light microscopic levels using zinc transporter-3 immunohistochemistry (ZnT3IHC) and zinc selenium autometallography (ZnSeAMG). ZnT3 resides in the synaptic vesicle membranes of ZEN neurons and is believed to move zinc ions into the vesicles. ZnT3IHC staining closely corresponds to the ZnSeAMG staining, but in the present study we present evidence of a delayed decrease of ZEN zinc, as compared to downregulation of the ZnT3 protein following ADX. Twenty-four hours after adrenalectomy the level of ZnT3IHC was visibly reduced while the ZnSeAMG staining intensity seemed unchanged. After 10 and 30 days, however, downregulation of ZnT3 was paralleled by a distinct reduction in ZnSeAMG staining. The total protein concentration of ZnT3 was reduced by about 53%, and the total zinc concentration in the hippocampus of the same mice was reduced by 43-64%, 30 days after the adrenalectomy. The present results support previous results suggesting that ZnT3 is responsible for transport of zinc ions into a pool of synaptic vesicles in ZEN terminals.
    Neuroscience Letters 05/2005; 377(3):164-9. DOI:10.1016/j.neulet.2004.11.096 · 2.06 Impact Factor
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    ABSTRACT: We examined the presence of Zn-transporters (ZnT1, ZnT3, ZnT4, and ZnT6) proteins and zinc ions in rat choroid epithelium with immunohistochemistry and zinc selenide autometallography (ZnSe(AMG)). The four ZnT proteins were all expressed in the choroid epithelial cells. ZnT3 immunostaining was found in vesicle membranes in the apical part of the cells, associated to the microvillus membrane. Correspondingly, the ZnSe(AMG) technique revealed zinc ions in small vesicles, in microvilli, and multivesicular bodies in the epithelial cells. Traceable zinc ions were also found in lysosome-like organelles of fenestrated endothelial cells, but here no corresponding ZnT3 immunostaining was seen. The observations suggests that the choroid plexus is instrumental to regulation of the level of zinc ions in the cerebrospinal fluid.
    Neuroreport 09/2004; 15(11):1801-4. DOI:10.1097/01.wnr.0000132918.05366.81 · 1.64 Impact Factor
  • Article: P36-1
    Structure 01/2004; 36:2. · 6.79 Impact Factor
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    ABSTRACT: We report, for the first time, the light microscopical and ultrastructural appearance of ZnT3-immunoreactivities in the ependymal cells of the central canal of the mouse spinal cord. Light microscopy revealed the presence of ZnT3-immunoreactive (Ir) ependymal cells in 1 microm thick epon sections stained by the ABC method. The ZnT3-Ir cells were observed at all levels of the spinal cord, but were a little more numerous in lumbosacral segments than in cervicothoracic segments. The ZnT3-Ir cells had large, ovoid nuclei with abundant cytoplasm, and protruded into the lumen of the central canal. Our ultrastructural findings suggest that the ZnT3-Ir ependymal cells possess secretory activity directed towards the central canal. We propose that they may play a role in the trans-ependymal mechanism responsible for zinc homeostasis between cerebrospinal fluid and the central area of the gray matter.
    Neuroscience Letters 06/2003; 342(1-2):81-4. DOI:10.1016/S0304-3940(03)00253-2 · 2.06 Impact Factor
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    ABSTRACT: Zinc ions seem to be important to several neurological functions and have been connected to the pathophysiology of epilepsy, neuronal cell death after seizure or stroke, and Alzheimer's disease. Both epilepsy and Alzheimer's disease are clinical conditions believed to involve the olfactory bulb. The mammalian olfactory bulb is densely innervated by zinc-enriched (ZEN) neurons, and the distribution of the ZEN terminals in the mouse olfactory bulb has previously been described. The aim of this study was to describe the origins of ZEN terminals projecting into the main olfactory bulb of the rat. Selective labeling of ZEN terminals was accomplished by intracerebral infusion of sodium selenide, whereby zinc selenium clusters are created in the ZEN terminals. Some of these clusters move by retrograde axonal transport to the somata where they can be silver-enhanced by autometallography (AMG). After infusion of sodium selenide into the main olfactory bulb, retrogradely labeled ZEN somata were found (1) ipsilaterally in all anterior olfactory nuclei, taenia tecta, piriform cortex and lateral entorhinal cortex, and (2) contralaterally in anterior olfactory nuclei except the external division. The ipsilateral anterior olfactory nucleus had the densest population of ZEN somata, and it was found that these somata originated mainly from pyramidal neurons in layers II and III of each area. The olfactory-related centrifugal afferents to the main olfactory bulb are discussed.
    Brain Research 12/2002; 956(2):230-5. DOI:10.1016/S0006-8993(02)03544-8 · 2.83 Impact Factor
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    ABSTRACT: In the present study, we showed for the first time the presence of inhibitory zinc-enriched neuron terminals in the mouse cerebellar cortex by means of double-immunohistochemistry for zinc transporter 3 (ZnT3) and glutamate decarboxylase (GAD). The co-localization of ZnT3 and GAD in the cerebellar cortex was analyzed by confocal microscopy. Strong, punctuate ZnT3-immunoreactivity (Ir) was predominantly distributed in the granule cell layer, while GAD-Ir was seen throughout the cerebellar cortical layers. All of the ZnT3-immunoreactive structures were also immunopositive to GAD, but not vice versa. Based on size and position, these double-labeled elements were axonal terminals of the Golgi and basket cells, in the granule cell and molecular layers, respectively. Observations by electron microscopy revealed that ZnT3-immunoreactive terminals showed typical characteristics of the inhibitory synapses like the following: (1) presynaptic terminals containing flat vesicles; and (2) symmetrical synaptic contacts with dendritic elements. The present results indicate that a zinc-containing GABAergic system exists in the mouse cerebellar cortex.
    Neuroscience Letters 04/2002; 321(1-2):37-40. DOI:10.1016/S0304-3940(01)02560-5 · 2.06 Impact Factor
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    ABSTRACT: It is well established that GABA degradation may play a key role in epileptogenesis. However, whether or not the expression of GABA-transaminase (GABA-T), which catalyzes GABA degradation and participates in the neuronal metabolism via GABA shunt, changes chronologically after on-set of seizure remains to be clarified. To identify the change of GABA-T expression in seizure, GABA-T expression in the gerbil hippocampus, associated with different sequelae of spontaneous seizures, was investigated. The distribution pattern of GABA-T immunoreactive neurons in the hippocampus between the seizure-resistant and pre-seizure group of seizure sensitive gerbils was similar. Interestingly, at 30 min postictal, the enhancement of GABA-T immunoreactivity in the perikarya was apparently observed. This contrasted with the decline in GABA-T immunoreactivity in the granular and pyramidal layer. At 12-24 h postictal, GABA-T immunoreactivity in the hilar neurons had declined significantly. However, the GABA-T immunoreactivity in the granular layer increased. These findings suggest that in the gerbil, the alteration in GABA-T expressions may play an important role in the self-recovery mechanism from seizure attack via both GABA degradation and regulation of neuronal metabolism.
    Neurochemistry International 07/2001; 38(7):609-14. DOI:10.1016/S0197-0186(01)00002-X · 2.65 Impact Factor
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    ABSTRACT: The zinc selenide autometallographic (ZnSeAMG) technique for tracing the retrograde axonal transport of zinc ions in zinc-enriched (ZEN) neurons was used to map the distribution of ZEN neuronal somata in rat spinal cord. After a local injection of sodium selenide into the dorsal or ventral horn, ZnSeAMG-labeled ZEN neurons appeared in Rexed’s laminae V, VII and X while laminae I and II were void. A few scattered ZEN somata were observed in the remaining laminae. The labeled neurons differed in shape and size, and the relatively high level of labeled somata around the injection site suggests that many ZEN neurons have relatively short axons or boutons en passage close to the neuronal origin. Ultrastructurally, the retrogradely transported zinc selenide clusters were found in the lysosomes of ZEN somata and proximal dendrites. Electron microscopic studies also revealed two different kinds of ZEN terminals: (1) terminals with flat synaptic vesicles making symmetric synaptic contacts; and (2) terminals with round vesicles making asymmetric synaptic contacts. The present study suggests the existence of propriospinal systems of ZEN neurons comprising both segmental and intersegmental ZEN connections and having either inhibitory or excitatory ZEN terminals. The ZEN neurons seem to form a vast network of terminals located primarily in the gray matter, but also contacting dendrites radiating into the white matter. Important functions of this rather massive system of ZEN terminals can not be deduced from our present knowledge, but the systems appear to be involved in both motor and sensory functions.
    Brain Research 06/2001; 900(1-900):80-87. DOI:10.1016/S0006-8993(01)02261-2 · 2.83 Impact Factor
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    ABSTRACT: The distribution of serotonin immunoreactivity in the main olfactory bulb (MOB) of the Mongolian gerbil (Meriones unguiculatus) was examined by immunohistochemistry. Seven distinct layers of the Mongolian gerbil MOB-stained with cresyl violet were identified. Serotonin-immunoreactive (IR) cell bodies were not found in the MOB. The serotonin-IR nerve fibres had a specific laminar distribution and morphology in the gerbil MOB. Serotonin-IR nerve fibres were observed in the glomerular, external plexiform and granule cell layers of the MOB. These serotonin-IR nerve fibres showed varicosities that were larger than the thickness of the axon. The highest density of serotonin-IR nerve fibres was in glomeruli of the glomerular layer. The average fibre density in the glomerular layer was more than three to four times the density in the infraglomerular layers. Glomerular serotonin-IR fibres were much more intensively stained than infraglomerular serotonin-IR fibres. This result suggests that serotonin-IR nerve fibres of Mongolian gerbil MOB are extrinsic and may act to modulate the olfactory transmission.
    Anantomia Histologia Embryologia 05/2001; 30(2):117-20. DOI:10.1046/j.1439-0264.2001.00314.x · 0.74 Impact Factor
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    ABSTRACT: Chelatable zinc ions from synaptic vesicles have been suggested to be involved in neuronal death caused by stroke, epilepsy and head trauma. Elevated glucocorticoid concentration exacerbates such neuron loss, while low levels protect. We have tested the notion that the neuroprotective effect of prior glucocorticoid reduction is mediated by a reduction of zinc ions contained in zinc-enriched (ZEN) synaptic vesicles. The level of vesicular zinc ions was evaluated by toluene sulfonamide quinoline (TSQ) fluorometry and zinc autometallography (ZnSAMG) 10 and 30 days, respectively, after adrenalectomy. The hippocampus showed significant vesicular zinc ion depletion following adrenalectomy. After the kainate injection, adrenalectomized rats showed proconvulsive seizure behavior, i.e. shortened latency to seizure onset time and increased seizure score. Additionally they showed decreased hippocampal CA3 neuronal death as compared to control animals. The present data suggest that zinc ions released from damaged ZEN terminals are involved in seizure-induced neuronal death.
    Brain Research 04/2001; 895(1-2-895):25-32. DOI:10.1016/S0006-8993(01)01996-5 · 2.83 Impact Factor
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    ABSTRACT: The ultrastructural localization of zinc transporter-3, glutamate decarboxylase and zinc ions in zinc-enriched terminals in the mouse spinal cord was studied by zinc transporter-3 and glutamate decarboxylase immunohistochemistry and zinc selenium autometallography, respectively. The distribution of zinc selenium autometallographic silver grains, and zinc transporter-3 and glutamate decarboxylase immunohistochemical puncta in both ventral and dorsal horns as seen in the light microscope corresponded to their presence in the synaptic vesicles of zinc-enriched terminals at ultrastructural levels. The densest populations of zinc-enriched terminals were seen in dorsal horn laminae I, III and IV, whereas the deeper laminae V and VI contained fewer terminals. At ultrastructural levels, zinc-enriched terminals primarily formed symmetrical synapses on perikarya and dendrites. Only relatively few asymmetrical synapses were observed on zinc-enriched terminals. In general, the biggest zinc-enriched terminals contacted neuronal somata and large dendritic elements, while medium-sized and small terminals made contacts on small dendrites. The ventral horn was primarily populated by big and medium-sized zinc-enriched terminals, whereas the dorsal horn was dominated by medium-sized and small zinc-enriched terminals. The presence of boutons with flat synaptic vesicles with zinc ions and symmetric synaptic contacts suggests the presence of inhibitory zinc-enriched terminals in the mammalian spinal cord, and this was confirmed by the finding that zinc ions and glutamate decarboxylase are co-localized in these terminals. The pattern of zinc-enriched boutons in both dorsal and ventral horns is compatible with evidence suggesting that zinc may be involved in both sensory transmission and motor control.
    Neuroscience 02/2001; 105(4):941-7. DOI:10.1016/S0306-4522(01)00243-3 · 3.33 Impact Factor
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    ABSTRACT: Glutamate is the major excitatory amino acid transmitter in vertebrate retinae. Glutamate transporters therefore play an important role in the precise control of glutamate concentration in the synaptic cleft by regulating extracellular glutamate concentration. In the present study, we performed an analysis of the expressions of three glutamate transporters in gerbil retina using immunohistochemistry. In the gerbil retina, excitatory amino acid carrier 1 and glutamate transporter 1 immunoreactivity was predominant in the ganglion cells but not amacrine or bipolar cells. Glutamate/aspartate transporter (GLAST) immunoreactivity was observed in the radial gliocytes of which the dense network of fine processes was localized in the inner and outer plexiform layers. GLAST immunoreactivity was also detected in astrocytes in the nerve fibre layer. These results demonstrate that three glutamate transporters show specific distributions in the gerbil retina and suggest that the glutamate re-uptake system in the gerbil retina may be different from that of the rat.
    Anantomia Histologia Embryologia 01/2001; 29(6):381-3. DOI:10.1046/j.1439-0264.2000.00291.x · 0.74 Impact Factor
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    ABSTRACT: In present study, we investigated the immunohistochemical distribution of somatostatin (SRIF) in the hippocampal complex of the Mongolian gerbil and its association with different sequelae of spontaneous seizures, in an effort to identify the roles of SRIF in the self-recovery mechanisms in these animals. In the dentate gyrus and subiculum, SRIF immunoreactive (SRIF(+)) cells were similar in both the seizure resistant and the pre-seizure group of seizure sensitive gerbils. Interestingly, SRIF immunoreactivity was markedly decreased until 12 h postictal. Twenty-four hours after the on-set of seizure, the distribution of SRIF immunoreactivity in these regions had slightly increased. In contrast, in the entorhinal cortex the population of SRIF(+) cells and their density were significantly elevated compared to pre-seizure group 30 min postictal. Twelve hours after the on-set of seizure, however, the population of SRIF(+) cells and their density declined, approximately 70-80% compared to the situation at 30 min postictal. These findings suggest that the enhancement of SRIF expression in gerbil entorhinal cortex may affect tissue excitability and have a role in modulating recurrent excitation following seizures.
    Brain Research 12/2000; 882(1-2):55-61. DOI:10.1016/S0006-8993(00)02824-9 · 2.83 Impact Factor
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    ABSTRACT: gamma-Aminobutyric acid-transaminase (GABA-T) plays an important role in the metabolism of GABA, particularly in the neurons or glial cells. The present study was undertaken to determine the alteration of GABA-T expression in the gerbil hippocampus after ischemia-reperfusion. In the sham, GABA-T(+) neurons were scattered in the hippocampus proper and dentate gyrus. The intensity of the GABA-T immunoreactivity had nearly disappeared in the interneurons at 12 h after ischemia. In contrast, 24 h post-ischemia the dramatic augmentation of GABA-T immunoreactivity in the pyramidal cells was observed in the CA1 area but not in the CA2 or CA3 areas. Forty-eight hours after ischemia-reperfusion, its immunoreactivity was preserved in the CA1 neurons. These results suggest that the over-expression of GABA-T in the CA1 area may be related to delayed neuronal death after ischemia-reperfusion insult.
    Neuroscience Letters 12/2000; 294(1):33-6. DOI:10.1016/S0304-3940(00)01541-X · 2.06 Impact Factor
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    ABSTRACT: The change of neuropeptide Y (NPY)-immunoreactive (IR) neurons in the rat main olfactory bulb as a result of aging was investigated at several aging stages over a two-year period; postnatal 1-24 months (P 1-P 24). From P 1 to P 12, the number of NPY-IR neurons and fibers increased with highest number in P 12, and the type of NPY-IR neurons had changed from bipolar neurons with short processes to bipolar/multipolar neurons with long processes. At P 24 the population of NPY-IR neurons and fibers had significantly decreased. Furthermore, the morphology of NPY-IR neurons showed a tendency to decrease in size and processes. It is suggested that the decrease of the number and size of NPY-IR neurons and fibers may underlie the age-related changes in the olfactory processes.
    Neuroscience Letters 09/2000; 289(2):119-22. DOI:10.1016/S0304-3940(00)01282-9 · 2.06 Impact Factor
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    ABSTRACT: Recent studies reported changes in neuropeptide Y (NPY) expression induced by seizures in the experimental epileptic models. However, there have been few reports of the alteration of NPY expression in hippocampal complexes of genetic epilepsy models. In the present study, we performed spatial and temporal analyses of NPY expression in the hippocampal complexes of the seizure-resistant (SR) and seizure-sensitive (SS) gerbils, one of the genetic models. In SR gerbils, most NPY(+) cells were located at the dentate hilus (DH) and the subiculum (SC). In the pre-seizure group of SS gerbils, neurons in the DH and SC were nearly devoid of NPY immunoreactivity. Interestingly, the acute NPY expressions were observed in these areas of the post-seizure group at 30 min, and its immunoreactivity was declined at 12 h after the onset of seizure. These findings suggest that in seizure, the deficiency of NPY in DH and SC may be one of the factors, and that the acute expression of NPY after seizure in these areas may be the compensatory response for reduction of seizure activity in this animal.
    Brain Research 08/2000; 870(1-2):179-84. DOI:10.1016/S0006-8993(00)02431-8 · 2.83 Impact Factor
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    ABSTRACT: The general distribution of zinc-enriched (ZEN) terminals in mouse spinal cord was investigated at light microscopic level by means of zinc transporter-3 immunohistochemistry (ZnT3(IHC)) and zinc selenium autometallography (ZnSe(AMG)). Staining for ZnT3(IHC) corresponded closely to the ZnSe(AMG) staining. Both appeared as dense grains of variable sizes and densities in the gray matter with a characteristic segmental laminar pattern. The white matter was unstained but contained rows of stained terminals radiating from the gray matter. In the dorsal horn, laminae I, III and IV were heavily stained, whereas lamina II appeared as the least stained area in the gray matter. Moderate staining was seen in laminae V and VI. In the ventral horn, large ZnT3(IHC) and ZnSe(AMG) grains, known from previous papers to represent ZEN terminals, were observed related in particular to motor neuronal somata and big dendrites. These ZEN terminals in the ventral horn were in general larger than those in the dorsal horn. This is the first description of the pattern of ZEN terminals in mouse spinal cord.
    Brain Research 08/2000; 870(1-2):163-9. DOI:10.1016/S0006-8993(00)02418-5 · 2.83 Impact Factor
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    ABSTRACT: The rat spinal cord reveals a complex pattern of zinc-enriched (ZEN) boutons. As a result of in vivo exposure to selenide ions, nanosized clusters of zinc selenide are created in places where zinc ions are present, including the zinc-containing synaptic vesicles of ZEN boutons. The clusters can be silver enhanced by autometallographic (AMG) development. A description of the ZEN bouton patterns is presented and discussed. The distribution of ZEN boutons could indicate that these terminal systems have a differentiated influence on sensory and motor systems.
    Brain Research 07/2000; 868(1):119-22. DOI:10.1016/S0006-8993(00)02238-1 · 2.83 Impact Factor
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    ABSTRACT: The present study was designed to localize zinc-enriched (ZEN) terminals in mouse olfactory bulb by means of ZnT3 immunocytochemistry (ICC) and zinc autometallography (AMG). The immunocytochemical staining of ZnT3 was closely correlated with the AMG pattern. ZEN terminals were defined as terminals showing both ZnT3 immunoreactivities and AMG granules. At the light microscopic level, dense staining patterns for ZnT3 immunoreactivity were seen in the granule cell layer and the olfactory glomerular layer. At the ultrastructural level, ZEN terminals were restricted to presynaptic terminals with single or multiple postsynaptic thickenings. The postsynaptic profiles contacting ZEN terminals appeared to be dendrites or somata of granule cells in the granule cell layer and periglomerular cells and mitral/tufted (M/T) cells in the olfactory glomerular layer. This suggests that two main sources of ZEN terminals are present in mouse olfactory bulb: (1) centrifugal fibres making asymmetrical synapses with granule cells and periglomerular cells, and (2) olfactory receptor terminals contacting dendritic profiles of M/T cells or periglomerular cells. The close correlation between ZEN terminals and the glutamatergic system is discussed.
    Brain Research 06/2000; 865(2):227-36. DOI:10.1016/S0006-8993(00)02227-7 · 2.83 Impact Factor

Publication Stats

407 Citations
58.91 Total Impact Points


  • 2000–2005
    • Aarhus University
      • Institute of Anatomy
      Aarhus, Central Jutland, Denmark
  • 2004
    • University of California, Davis
      Davis, California, United States
  • 1997–2003
    • Hallym University
      • College of Medicine
      Sŏul, Seoul, South Korea