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Biomedical subjects

S S Cho

Publications and source records attributed to S S Cho.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of repeated seizure experiences on tyrosine hydroxylase immunoreactivities in the brain of genetically epilepsy-prone rats.

The genetically epilepsy-prone rat (GEPR) is a model of generalized tonic/clonic epilepsy, and has functional noradrenergic deficiencies that act as partial determinants for the seizure predisposition and expression. The present study investigated the effect of repeated seizure experiences by acoustic stimulation (110 dB, 10 times) on the immunoreactivities of tyrosine hydroxylase (TH), a rate-determining enzyme in the synthesis of norepinephrine, in brain regions of GEPRs. TH immunoreactivity in locus coeruleus, the major noradrenergic nucleus in brain, was lower in GEPRs than control Sprague-Dawley rats. It was also decreased in several regions including inferior colliculus of GEPRs. Repeated experiences of audiogenic seizures further decreased TH immunoreactivities in locus coeruleus and inferior colliculus of GEPRs. The results from the present study suggest that the lower immunoreactivities of TH in locus coeruleus and inferior colliculus contribute, at least in part, to the noradrenergic deficits in GEPRs, and repeated seizure experiences further intensified these noradrenergic deficits, which may be related to the altered seizure expression by repetitive audiogenic seizure in GEPRs.

Animals↗
PubMed1999

Immunohistochemical detection of oxidative DNA damage induced by ischemia-reperfusion insults in gerbil hippocampus in vivo.

There is much evidence to suggest that ischemic injury occurs during the reperfusion phase of ischemia-reperfusion insults, and that the injury may be due to reactive-oxygen-species (ROS)-mediated oxidative events, including lipid peroxidation and DNA damage. However, oxidative DNA damage has until now not been examined in situ. In the present study, we report for the first time observation of cell type- and region-specific oxidative DNA damages in 5 min transient ischemic model by immunohistochemical methods, using monoclonal antibody against 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative DNA product. The cell types containing 8-OHdG immunoreactivity were neurons, glia and endothelial cells in the hippocampus. The 8-OHdG immunoreactivity was present in the nucleus but not the cytoplasm of these cells. The level of 8-OHdG in CA1 increased significantly (P<0.05) at the end of 30 min after ischemia, but there was no increase within CA2 and CA3 areas. The 8-OHdG levels in the hippocampus increased significantly (about fourfold) after 3 h of reperfusion and remained significantly (P<0.01) elevated for at least 12 h. At 4 days after ischemia, 8-OHdG levels in the CA2 and CA3 areas decreased to levels of the sham without neuronal loss, while disappearance of 8-OHdG immunoreactivity in the CA1 coincided with neuronal death in this area. These findings strongly suggest that ischemia-induced DNA damage evolves temporally and spatially, and that oxidative DNA damage may be involved in delayed neuronal death in the CA1 region.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

In situ localization of neuronal nitric oxide synthase (nNOS) mRNA in the rat retina.

We performed a comparative study on the distribution of neuronal nitric oxide synthase (nNOS) immunoreactivity and mRNA in a normal rat retina using immunocytochemistry and in situ hybridization technique. As in previous studies, we found NOS immunoreactive (NOS-IR) cells and fibers in inner and outer plexiform layers (IPL and OPL), inner nuclear layer (INL) and inner photoreceptor segment (IPS). However, very little nNOS-IR could be detected in groups of amacrine cells and ganglion cells localized in ganglion cell layer (GCL). However, in situ hybridization showed that intense NOS mRNA signals were mainly found in the GCL and INL while weak or no mRNA signals were detected in IPL, OPL, outer nuclear layer (ONL) and IPS. This difference suggests that nNOS proteins may be transported through axons into the terminals in the IPL and OPL after they were synthesized with nNOS mRNA templates in the INL. In the case of nNOS mRNA in GCL, synthesizing nNOS proteins may move outside the eyeball and carry out tasks in central nervous system. The difference of nNOS mRNA and nNOS IR means that the complete concurrence of nNOS IR and in situ hybridization results may not always occur in the rat retina.

Animals↗
PubMed1999

In situ localization of p53, bcl-2 and bax mRNAs in rat ocular tissue.

We mapped p53, bcl-2 and bax mRNAs, which are known to have correlation with apoptotic cell death, in the rat ocular tissue. p53 mRNA signals were present in several layers of retina, optic nerve, corneal epithelium, ciliary process and posterior surface of the iris. While almost the same pattern as p53 was recognized in the case of bcl-2 mRNA, bax signals were not found in ocular tissue except for ganglion cell layer (GCL). These results suggest that in the normal ocular tissue, p53 and bcl-2 genes play opposing parts in the physiological control of cell survival and death. A p53 mediated tumor-suppressing action might occur through the induction of transcriptional targets other than bax because only in GCL were p53 and bax mRNA expression co-localized.

Animals↗
PubMed1999

Are substance P neurons of the paraventricular nucleus related to the osmotic regulation in the Mongolian gerbil?

In recent years, the gerbil has been used as an experimental animal for study osmotic regulation, because of its inherent high degree of water re-uptake in kidney. Many evidences to explain this characteristic accumulated on the kidney level, it do not, however, manifest what concerns on hypothalmo-hypophyseal level. In this study, we have focused on the difference between the colchicine treated gerbil and rat in distributions of substance P (SP), which is known to have antidiuretic property. Unlike rat, in which a few SP+ neuron is present, SP+ neurons were abundantly observed in the paraventricular nucleus (PVN) of the gerbil. Furthermore SP+ cells in PVN were manifested in dehydrated gerbils, in spite of non-colchicine treatment. Therefore, we suggest that the abundant SP+ neurons in PVN may be a clue to address the neuroendocrinal mechanism concerning the high degree of osmotic regulation in this animal.

Animals↗
PubMed1999

Rat osteopontin antibody is cross-reactive to a novel myelin-associated protein in chick.

Osteopontin (OPN) was initially identified as glycosylated phosphoprotein in bones of vertebrates. Recently, OPN is reported to express in the primitive neuroepithelia of early chick embryonic hindbrain. We have demonstrated that rat OPN is immunohistochemically localized in the white matter of chick CNS. We have further confirmed the specificity of OPN cross-immunoreaction in myelin using demyelinated optic nerve induced by lysophosphatidylcholine (LPC), where the intensity of immunoreaction was closely related to the degree of demyelination. Immunoblot analyses showed that rat OPN antibody recognized a protein with molecular weights of approximately 47 kDa from chick CNS. Our data suggest that the antigen recognized by rat OPN is a previously undescribed myelin-associated protein in the chick CNS.

Animals↗
PubMed1999

Transferrin binding protein is expressed by oligodendrocytes in the avian retina.

It has been documented that some axons of ganglion cells in the nerve fiber layer of avian retina are wrapped in a myelin sheath. However, the identity of myelin-forming cells has not been established. In this study we demonstrated immunohistochemical evidence for the existence of a large population of oligodendrocytes in avian retina, using an antiserum against transferrin binding protein (TfBP), the avian homologue of the mammalian GRP 94 family of stress-regulated proteins. TfBP+ cells were mostly confined to the ganglion cell and optic nerve fiber layers of the retina, in which they were closely associated with the soma and axons of ganglion cells. The double-labeling experiments clearly show that TfBP is specific to oligodendrocytes. The morphology, distribution, and antigenic properties indicated by our findings suggest that TfBP+ cells are retinal oligodendrocytes that may be responsible for the myelination of ganglion cell axons in avian retina. A putative tropic role of TfBP+ oligodendrocytes to the ganglion cells is also discussed in conjunction with the physical properties of TfBP and avascular retinae of birds.

Animals↗
PubMed1999

Purification and characterization of glutamate dehydrogenase as another isoprotein binding to the membrane of rough endoplasmic reticulum.

Glutamate dehydrogenase (GDH) was purified from rough endoplasmic reticulum (RER) in rat liver using anion-exchange and affinity chromatography. As GDH has been known as an enzyme that exists mainly in the matrix of mitochondria, the properties of purified GDH were compared with those of mitochondrial GDH. The GDH activity in 0. 1% Triton X-100-treated RER subcellular fraction was nearly the same as intact RER, whereas that of the mitochondrial fraction increased by 50% after the detergent treatment. In kinetic values, in addition, mitochondrial GDH had a higher K(m) value for NADP(+) than NAD(+), whereas the K(m) value for NAD(+) was higher than that for NADP(+) in the case of GDH of RER, which showed a difference in specificity to cofactors. Moreover, when two GDH isoproteins were incubated at 42 degrees C or treated with trypsin, GDH from RER was more stable against heat inactivation and less susceptible to proteolysis than mitochondrial GDH in both cases. In addition, GDH of RER had at least five amino acids different from mitochondrial GDH when sequences of N-terminal and several internal peptide fragments were analyzed. These results showed that GDH of RER is another isoprotein of GDH, of whose properties are different from those of mitochondrial GDH.

Amino Acid Sequence↗
PubMed1999

Spatial and temporal expression of UDP-galactose: ceramide galactosyl transferase mRNA during rat brain development.

We studied the expression of UDP-galactose: ceramide galactosyl transferase (CGT) mRNA in postnatal rat brains using an in situ hybridization technique. From P0 to P16, there was a defined temporal and spatial pattern to the earliest acquisition of CGT mRNA expression. In the forebrain, CGT mRNA-expressing (CGT+) cells were first detected in regions outside the subventricular zone around the lateral ventricle at P2. Cells in the external capsule, internal capsule and corpus callosum were later found to be CGT-positive. At P8 to P16, CGT+ cells were found in the thalamus, striatum, occipital and frontal cortex. In the case of midbrain and hindbrain, the first CGT+ signals were detected in the medullary raphe of the medulla oblongata at P0. CGT+ cells were subsequently located in the cerebellum, midbrain and pons from P4 to P16. That is, in regions closer to the areas in which CGT+ cells were first found, CGT mRNA expression was observed much earlier. These findings support the notion that there are at least two discrete waves of CGT mRNA signal expression in the forebrain and hindbrain.

Animals↗
PubMed1998

Localization of transferrin binding protein in relation to iron, ferritin, and transferrin receptors in the chicken cerebellum.

We have demonstrated that transferrin binding protein (TfBP), ferritin, and iron, are specifically localized in Bergmann glia, while the transferrin receptor is confined to Purkinje cells in the chicken cerebellum. The results of this study suggest that Bergmann glia have previously undescribed functions related to iron regulation such as sequestration of iron and the maintenance of iron homeostasis in the cerebellum.

Animals↗
PubMed1998

Engagement of CD99 induces apoptosis through a calcineurin-independent pathway in Ewing's sarcoma cells.

Programmed cell death (PCD) is a prominent feature of the development of the immune and nervous systems. In both systems, widespread PCD occurs in primitive progenitor cells during development. In this study, we demonstrated that Ewing's sarcoma (ES) cells, undifferentiated neural precursors, underwent apoptosis upon engagement of CD99 with anti-CD99 monoclonal antibody. Apoptosis via CD99 occurred only in the undifferentiated state of ES cells, but not in differentiated ES cells. CD99-induced apoptosis in ES cells appeared to require de novo synthesis of RNA and protein as well as caspase activation. Cyclosporin A, known to be a potent inhibitor of both calcineurin activation and mitochondrial permeability transition pore opening, inhibited CD99-mediated apoptosis, whereas FK-506, a specific calcineurin inhibitor, did not, indicating the induction of CD99-mediated apoptosis through a calcineurin-independent pathway. Furthermore, the dying cells displayed the reduction of mitochondrial transmembrane potential (delta psi m). These results suggest that CD99 engagement induce CsA-inhibitable mitochondrial permeability transition pore opening, followed by a reduction of delta psi m and caspase activation, thereby leading to apoptosis. Based on these results, we suggest the possible involvement of CD99 in the apoptotic processes that occur during nervous system development and also its application in immunotherapeutic trials for ES cases.

12E7 Antigen↗
PubMed1997

New scoring system using tumor markers in diagnosing patients with moderate pericardial effusions.

We performed diagnostic and therapeutic pericardiostomy with drainage and biopsy in 51 patients with moderate to large pericardial effusions of different etiologies from August 1991 to July 1995. Patients were divided into 4 groups (group 1, tuberculous pericarditis; group 2, suspected tuberculous pericarditis; group 3, acute pericarditis; group 4, malignancy). The pericardial fluid adenosine deaminase level in tuberculosis (87 +/- 10 U/l) was significantly higher than that in malignancy or acute pericarditis (21 +/- 4 U/l, 23 +/- 7 U/l, respectively) (P = 0.0001). The mean pericardial fluid carcinoembryonic antigen level (1.8 +/- 0.3 ng/ml) in benign disease was significantly lower than that (170.7 +/- 46.4 ng/ml) in malignant disease (P = 0.0001). Follow-up study has been done. With a new scoring system (each score 1 for adenosine deaminase > or = 40 U/l, or carcinoembryonic antigen < or = 5 ng/ml) in 25 patients since November 1993, we could diagnose 5 among 7 patients (71%) with tuberculosis, 11 among 13 patients (85%) with malignancy (adenosine deaminase < or = 40 U/l, or carcinoembryonic antigen > or = 5 ng/ml) and 5 among 5 patients (100%) with acute pericarditis (adenosine deaminase < or = 40 U/l, or carcinoembryonic antigen < or = 5 ng/ml), respectively. Our long-term follow-up study suggests that with the new scoring system we can decrease complications or avoid unnecessary procedures or treatments of patients.

Adenosine Deaminase↗
PubMed1997

Distribution of transferrin binding protein immunoreactivity in the chicken central and peripheral nervous systems.

Transferrin binding protein (TfBP) is a glycoprotein originally purified from chicken oviduct that exhibits transferrin binding activity. Recent work has shown that TfBP is a post-translationally modified form of the heat shock protein (HSP108), the avian homologue of a glucose regulated protein, GRP94. The function of this protein, however, has not yet been clearly defined. Antiserum to TfBP was found to selectively stain oligodendrocytes of the avian brain. In this study, we further describe these oligodendrocytes and other cell types positive to anti-TfBP in the chick nervous system. In accordance with previous studies, the most prominent cell type that labels with antiserum to TfBP is the oligodendrocyte. At the electron microscopic level, the immunoreactive product is confined to the perinuclear cytoplasm and fine processes of the oligodendrocytes, whereas myelin and axoplasm are devoid of staining. The immunoreactive product is found both in the cytoplasmic matrix and bound to the endoplasmic reticulum and plasma membrane, suggesting that TfBP may have properties of both a soluble and an integral membrane protein. There is great variability in the number of TfBP-oligodendrocytes in different areas of the central nervous system (CNS); large numbers of cells are associated with the white matter regions and are found in the myelinated tracts, whereas few cells are present in the gray matter regions. In the retina, TfBP is localized specifically in the cells, that are morphologically oligodendrocytic and is present in the optic nerve fiber layer and the ganglion cell layer. Obvious staining is also seen in the Bergmann glial cells of the cerebellum and in the Schwann cells of the sciatic nerve. Furthermore, the choroid plexus cells similarly exhibit a strong reaction. The association of TfBP in these specific cell types responsible for myelination and sequestering iron and transferrin implies that TfBP may be involved in myelination and iron metabolism of the chick nervous system, perhaps through a role in transferrin concentration in these cells. A putative role of TfBP, as HSP108, is considered.

Animals↗
PubMed1996

Activation of STAT4 by IL-12 and IFN-alpha: evidence for the involvement of ligand-induced tyrosine and serine phosphorylation.

The immunoregulatory cytokine IL-12 plays a central role in cell-mediated immune responses through its effects on NK cells and T lymphocytes. While IL-12 is known to share some functions with other cytokines, such as IFN-alpha, it also maintains distinct roles, such as its ability to induce Th1 differentiation. The molecular basis for these unique and overlapping functions is not well understood. IL-12 has previously been shown to induce tyrosine phosphorylation and DNA-binding of STAT3 and STAT4, members of the signal transducers and activators of transcription (STAT) family. Because STAT4 has only been shown to be activated in response to IL-12, this specificity has been suggested to be a basis for the unique actions of IL-12. In this study, we demonstrated that STAT4 activation by IL-12 is not unique; IL-12 and IFN-alpha, but not IFN-gamma, induced tyrosine phosphorylation and DNA binding of STAT4. Since tyrosine and serine phosphorylation of STAT1 have previously been shown to be important in IFN-alpha-mediated signaling, we also investigated IL-12- and IFN-alpha-induced serine phosphorylation of STAT4. We demonstrated that both cytokines induced serine phosphorylation. This modification was not required for DNA binding, but may be important in STAT-mediated transcription. Thus, STAT4 activation was not IL-12 specific, and IL-12 and IFN-alpha activated STAT4 through both tyrosine and serine phosphorylation. These findings have significant implications for understanding the role of STAT4 in mediating biologic functions; specifically, the data argue that the unique effects of IL-12 cannot be solely explained by STAT4 activation.

Animals↗
PubMed1996

3-Aryl-1,2-diacetamidopropane derivatives as novel and potent NK-1 receptor antagonists.

Early structure-activity studies on racemic tryptophan ester and amide NK-1 antagonists 5-7 led to the discovery that the potency of the series could be markedly increased by moving the carbonyl function in these molecules to an off-chain position as in the 3-aryl-1,2-diacetamidopropane 9. Further medicinal chemistry incorporating this change resulted in the discovery of a novel series of highly potent aryl amino acid derived NK-1 antagonists of the R stereoisomeric series (IC50's = 100 pM to > 5 microM). Compounds in this series were shown to be competitive antagonists using an in vitro NK-1 smooth muscle assay, and this data correlated well with observed human NK-1 binding affinities. Two of these agents, (R)-25 and (R)-32, blocked intrathecal NK-1 agonist-driven [Ac-[Arg6,Sar9,Met(O2)11]- substance P 6-11 (Ac-Sar9)] nociceptive behavior in mice. Both compounds potently blocked the neurogenic dural inflammation following trigeminal ganglion stimulation in the guinea pig after intravenous administration. Further, upon oral administration in this model, (R)-32 was observed to be very potent (ID50 = 91 ng/kg) and have a long duration of action (> 8 h at 1 micrograms/kg). Compound (R)-32, designated LY303870, is currently under clinical development as an NK-1 antagonist with a long duration of action.

Amides↗
PubMed1996

An immunohistochemical localization of transferrin binding protein in the chicken respiratory tract.

Transferrin binding protein (TfBP), a glycoprotein, is originally purified from the chicken oviduct. Recently, TfBP has been revealed as a novel transferrin binding protein, structurally related to the chicken heat shock protein 108. The physiological function of this protein, however, has not yet been established. Antiserum to TfBP was found to stain selectively transferrin- and iron-rich oligodendrocytes of the normal chicken brain, suggesting a role for this protein in connection with transferrin and iron storage in these cells. In this study, we further demonstrate a TfBP-immunoreactivity in the chicken respiratory tract mucosa, where transferrin is known to be present and have antioxidant and antibacterial properties. A strong TfBP immunoreactivity was revealed in certain regions of the respiratory tract. In the trachea and bronchi, TfBP-immunoreactive product was localized specifically to the mucous gland cells, whereas ciliated epithelial cells were negative. In the lung, TfBP immunoreactivity was mostly confined to the parabronchi and atria. The immunoreactive products were found in the cytoplasm of the epithelial cells lining the parabronchial and atrial walls. These findings suggest that the presence of TfBP in the airway mucosa may be a necessary condition for transferrin concentration in the extracellular milieu of the respiratory tract.

Animals↗