Neuromyelitis optica (Devic disease) is a rare demyelinating disorder of unknown etiology in which unilateral or bilateral optic neuritis and transverse myelitis occur within 8 weeks. The disease has no clinical involvement beyond the spinal cord or optic nerves. This illness occurs more commonly in adults than in children. The prognosis is better in children than in adults. The authors experienced a case of neuromyelitis optica (Devic disease) in a 5-year-old female who developed acute visual loss of the left eye, paraplegia, sensory change above the 4th thoracic dermatome, nuchal rigidity and fever. We diagnosed this case through neurologic features, magnetic resonance imaging, ophthalmoscopy and cerebrospinal fluid findings. The patient improved with conservative treatment without sequelae.
Adult ; Cerebrospinal Fluid ; Child ; Child, Preschool ; Demyelinating Diseases ; Female ; Fever ; Humans ; Magnetic Resonance Imaging ; Muscle Rigidity ; Myelitis, Transverse ; Neuromyelitis Optica ; Ophthalmoscopy ; Optic Nerve ; Optic Neuritis ; Paraplegia ; Prognosis ; Spinal Cord

Embryonic stem cells (ESCs) can be propagated in vitro on feeder layers of mouse STO fibroblast cells. The STO cells secrete several cytokines that are essential for ESCs to maintain their undifferentiated state. In this study, we found significant growth inhibition of mouse ESCs (mESCs) cultured on STO cells infected with adenovirus containing a dominant-negative mutant form of IkappaB (rAd-dnIkappaB). This blockage of the NF-kappaB signal pathway in STO cells led to a significant decrease in [3H]thymidine incorporation and colony formation of mESCs. Expression profile of cytokines secreted from the STO cells revealed an increase in the bone morphogenetic protein4 (BMP4) transcript level in the STO cells infected with adenoviral vector encoding dominant negative IkappaB (rAd-dnIkappaB). These results suggested that the NF-kappaB signaling pathway represses expression of BMP4 in STO feeder cells. Conditioned medium from the rAd-dnIkappaB-infected STO cells also significantly reduced the colony size of mESCs. Addition of BMP4 prevented colony formation of mESCs cultured in the conditioned medium. Our finding suggested that an excess of BMP4 in the conditioned medium also inhibits proliferation of mESCs.
Animals ; *Bone Morphogenetic Protein 4/genetics/metabolism ; Cell Differentiation/genetics ; Cell Proliferation ; Culture Media, Conditioned ; *Embryonic Stem Cells/cytology/metabolism ; *Feeder Cells/cytology/metabolism ; *Fibroblasts/cytology/metabolism ; Gene Expression Regulation/genetics ; *I-kappa B Proteins/genetics/metabolism ; Mice ; Mutation ; NF-kappa B/genetics/metabolism ; Signal Transduction

Many fungi including Penicillium, Aspergillus, Gliocladium, and Thermoascus produce an epipolythiodioxopiperazine class of fungal metabolite, gliotoxin, which contirbutes the pathogenesis of fungal infection as an immunomodulator and cytotoxic agent. This study is designed to define the mechanism by which gliotoxin exerts the cytotoxic effect of gliotoxin on human promyelocytic leukemic cells, HL-60. Gliotoxin induces the apoptosis of HL-60 cells which is characterized by the ladder pattern fragmentation of DNA. Gliotoxin induces the activation of DEVD-specific cysteine protease in a time- and dose-dependent rnanner. It also increases the phosphotransferase activities of c-Jun N-terminal kinase1 (JNK1) and p38 in gliotoxin-treated HL-60 cells. Furthermore, gliotoxin decreases the activation of transcriptional activator, actiating protein (AP-1) and NF-kB. These results suggest that gliotoxin induces the apoptotic death of HL-60 cells via activation of DEVD- specific caspase as well as mitogen activated protein kinases (MAP kinases) including JNK1 and p38, and inhibition of transcriptional activators, AP-1 and NF-kB.
Apoptosis* ; Aspergillus ; Caspase 3 ; Cysteine Proteases ; DNA ; Fungi ; Gliocladium ; Gliotoxin* ; HL-60 Cells* ; Humans ; Mitogen-Activated Protein Kinases ; NF-kappa B ; Penicillium ; Thermoascus ; Transcription Factor AP-1 ; Transcription Factors

OBJECTIVE: Triptolide (TP) has been reported to suppress the expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), of which main function is to inactivate the extracellular signal-regulated kinase-1/2 (ERK-1/2), the p38 MAPK and the c-Jun N-terminal kinase-1/2 (JNK-1/2), and to exert antiproliferative and pro-apoptotic activities. However, the mechanisms underlying antiproliferative and pro-apoptotic activities of TP are not fully understood. The purpose of this study was to examine whether the down-regulation of MKP-1 expression by TP would account for antiproliferative activity of TP in immortalized HT22 hippocampal cells. METHODS: MKP-1 expression and MAPK phosphorylation were analyzed by Western blot. Cell proliferation was assessed by 3H-thymidine incorporation. Small interfering RNA (siRNA) against MKP-1, vanadate (a phosphatase inhibitor), U0126 (a specific inhibitor for ERK-1/2), SB203580 (a specific inhibitor for p38 MAPK), and SP600125 (a specific inhibitor for JNK-1/2) were employed to evaluate a possible mechanism of antiproliferative action of TP. RESULTS: At its non-cytotoxic dose, TP suppressed MKP-1 expression, reduced cell growth, and induced persistent ERK-1/2 activation. Similar growth inhibition and ERK-1/2 activation were observed when MKP-1 expression was blocked by MKP-1 siRNA and its activity was inhibited by vanadate. The antiproliferative effects of TP, MKP-1 siRNA, and vanadate were significantly abolished by U0126, but not by SB203580 or SP600125. CONCLUSION: Our findings suggest that TP inhibits the growth of immortalized HT22 hippocampal cells via persistent ERK-1/2 activation by suppressing MKP-1 expression. Additionally, this study provides evidence supporting that MKP-1 may play an important role in regulation of neuronal cell growth.
Anthracenes ; Blotting, Western ; Butadienes ; Cell Proliferation ; Diterpenes ; Down-Regulation ; Epoxy Compounds ; Imidazoles ; Neurons ; Nitriles ; p38 Mitogen-Activated Protein Kinases ; Phenanthrenes ; Phosphorylation ; Protein Kinases ; Pyridines ; RNA, Small Interfering ; Vanadates

Amebiasis is an infectious disease caused by Entameba histolytica. Amebiasis remains an extremely important consideration in the differential diagnosis of diarrhea, especially when there is associated bleeding. It is imperative that appropriate studies to establish or exclude the diagnosis of amebiasis be carried out in all patients who present with a clinical and sigmoidoscopic picture of colitis, and that patients treated with metronidazole for amebiasis have adequate clinical and parasitological follow-up. We have experienced one case of intestinal amebiasis with protein losing enteropathy in 30month-old boy whose chief complaint was mild fever, vomiting and blood tinged diarrhea. His laboratory findings were compatible with protein losing enteropathy. The diagnosis of amebiasis is confirmed by observation of trophozoite of E. histolytica in the stools. A brief review with related literatures is also presented.
Amebiasis ; Colitis ; Communicable Diseases ; Diagnosis ; Diagnosis, Differential ; Diarrhea ; Dysentery, Amebic* ; Fever ; Follow-Up Studies ; Hemorrhage ; Humans ; Male ; Metronidazole ; Protein-Losing Enteropathies* ; Tolnaftate ; Trophozoites ; Vomiting

PURPOSE: Subacute sclerosing panencephalitis(SSPE) is a severe and usually fatal neurodegenerative disorder of childhood and adolescence. The etiology is related to previous measles infection especially during the first 2 years of life. Since recent measles epidemics in Korea may increase the late risk of SSPE, the authors investigated the clinical characteristics of SSPE focusing on brain MRI. METHODS: Six cases(4 males, 2 females) of SSPE patients were retrospectively reviewed for clinical, EEG, laboratory and brain MRI findings. RESULTS: Four of 6 had a history of measles infection in the first year of life. Clinical manifestations were as follows:myoclonus(6), falling(4), ataxia(4), dysarthria(3), seizures (2), involuntary movements(2), tremor(2), head drop(1), sleep disturbance(1). In all cases, CSF IgG, CSF IgG/albumin ratio, and CSF/serum IgG index increased, oligoclonal bands were positive, and CSF antimeasles antibodies were positive. Frontal high amplitude sigma activities and anteriorly-accentuated multifocal epileptiform discharges were noted on EEG. Brain MRI revealed T2-weighted high signal intensity of the deep white matter. CONCLUSION: The diagnosis of SSPE depends on characteristic clinical features and elevation of measles antibodies in CSF, supported by others including EEG, CSF and brain MRI findings. We hope the clinical characteristics we mentioned may be useful for the early diagnosis and active management of SSPE in Korea.
Adolescent ; Antibodies ; Brain ; Diagnosis ; Early Diagnosis ; Electroencephalography ; Head ; Hope ; Humans ; Immunoglobulin G ; Korea ; Magnetic Resonance Imaging ; Male ; Measles ; Neurodegenerative Diseases ; Oligoclonal Bands ; Retrospective Studies ; Seizures ; Subacute Sclerosing Panencephalitis*

BACKGROUND: Telomeres are repetitive DNA fragments at the termini of chromosomes functioning as stabilizing elements of the DNA. A ribonucleoprotein polymerase, called telomerase, is responsible for the synthesis of such telomeric repeats in embryo and germ cells. During ontogenesis of most normal human somatic cells, there exists a physiological telomerase repressing mechanism. In contrast, malignant cells are characterized by an unlimited progressive potential. Certain physiological agents, such as all-trans retinoic acid (ATRA), 13-cis retinoic acid (13-cisRA), 1alpha-25 dihydroxy vitamin D3 (VD3) and cytosine arabinoside (Ara-C), promote further differentiation of leukemic cells into mature granulocytes and monocytes and subsequently undergo apoptosis. METHODS: To determine if a potential linkage is present between telomerase regulation and the differentiation of malignant hematopoietic cells, the changes in telomerase activity during the maturation of HL-60 cells induced by ATRA, 13-cisRA, VD3 and Ara-C were investigated. RESULTS: Differentiating agents induce HL-60 cells to differentiate into CD11b+ granulocytes and monocyte/macrophages, respectively. Approximately 98% of HL-60 cells acquired the expression of CD11b+ antigen after ATRA, 13-cisRA or Ara-C treatment for 5 days. After 1 day treatment with differentiating agents, no significant difference in telomerase activity was shown between untreated and treated HL-60 cells. A dramatic inhibition of telomerase activity occurred at 3 days treatment of ATRA compared to untreated HL-60 cells. Longer treatment for 5 days with differentiating agents resulted in further decrease of telomerase activity. However, telomerase activity in HL-60 cells was decreased slightly by the VD3 or Ara-C treatment, even though for 5 days. No evidence of differentiation and slight decrease of telomerase activity were observed in ATRA-treated K-562 cells for 5 days. These decrease of telomerase activity were dependent on the incubation time and dose. CONCLUSION: These data clearly show the role of telomerase activity during the differentiation of HL-60 cells. This in vitro model can be useful for studies of the mechanisms controlling telomerase activity and in the search for physiological telomerase modulators.
Apoptosis ; Cholecalciferol ; Cytarabine ; DNA ; Embryonic Structures ; Germ Cells ; Granulocytes ; HL-60 Cells* ; Humans ; Monocytes ; Ribonucleoproteins ; Telomerase* ; Telomere ; Tretinoin

The purpose of this study is to analyze morphological characteristics of maxillary primary molar’s root and root canal. 268 children aged 3 - 7 years (175 boys, 93 girls) who had CBCT (152 children) and 3D CT (116 children) taken in Seoul National University Dental Hospital from January 2006 to April 2020 were included. The number of roots and root canals were analyzed in 1002 teeth without any root resorption or periapical pathologies. Curvature, angulation, length of root and root canal, as well as cross-sectional shapes of the root canal were analyzed in 218 teeth. By using Mimics and 3-Matics software, volume, surface area, and volume ratio of root canal was analyzed in 48 teeth.
More than half of maxillary primary molars have 3 roots and 3 root canals. The degree of symmetry of root canal type was about 0.63 (Cohen’s kappa coefficient). The most frequent shape of roots and canals was linear in 1st primary molars and curved in 2nd primary molars. Angulation, length of root and root canals was the largest on palatal roots. Most teeth showed ovoid or round shapes at apex. The largest root canal volume, surface area, volume ratio was found in the palatal roots.

Granulocytic sarcoma (GS) is an extramedullary tumor composed of immature myeloid cells, typically occurring during the course of acute myelogenous leukemia. Non-leukemic GS, that is, GS with no evidence of overt leukemia and no previous history of leukemia, is very rare, and even more unusual is nonleukemic GS of the bile duct. We report a case of nonleukemic GS of the bile duct. The patient was initially misdiagnosed as a bile duct carcinoma arising in the hilum of the liver (so-called Klatskin tumor), and received a right lobectomy of the liver. Histological examination of the tumor yielded the diagnosis of GS, and the bone marrow biopsy did not show any evidence of leukemia. Considering the risk of subsequent development of overt leukemia, the patient was treated with two cycles of combination chemotherapy as used in the cases of acute myelogenous leukemia. To date, he has remained free of disease 15 months after treatment.
Tomography, X-Ray Computed/methods ; Sarcoma, Granulocytic/*diagnosis/metabolism/radiography ; Radiography, Abdominal ; Peroxidase/analysis ; Male ; Immunohistochemistry ; Humans ; Diagnosis, Differential ; Bile Ducts/chemistry/pathology ; Bile Duct Neoplasms/*chemically induced/metabolism/radiography ; Antigens, CD45/analysis ; Adult

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) induces apoptosis selectively in cancer cells while sparing normal cells. However, many cancer cells are resistant to TRAIL-induced cell death. Here, we report that paxilline, an indole alkaloid from Penicillium paxilli, can sensitize various glioma cells to TRAIL-mediated apoptosis. While treatment with TRAIL alone caused partial processing of caspase-3 to its p20 intermediate in TRAIL-resistant glioma cell lines, co-treatment with TRAIL and subtoxic doses of paxilline caused complete processing of caspase-3 into its active subunits. Paxilline treatment markedly upregulated DR5, a receptor of TRAIL, through a CHOP/GADD153-mediated process. In addition, paxilline treatment markedly downregulated the protein levels of the short form of the cellular FLICE-inhibitory protein (c-FLIPS) and the caspase inhibitor, survivin, through proteasome-mediated degradation. Taken together, these results show that paxilline effectively sensitizes glioma cells to TRAIL-mediated apoptosis by modulating multiple components of the death receptor-mediated apoptotic pathway. Interestingly, paxilline/TRAIL co-treatment did not induce apoptosis in normal astrocytes, nor did it affect the protein levels of CHOP, DR5 or survivin in these cells. Thus, combined treatment regimens involving paxilline and TRAIL may offer an attractive strategy for safely treating resistant gliomas.
Antineoplastic Agents/*pharmacology ; Apoptosis/*drug effects ; Astrocytes/metabolism ; CASP8 and FADD-Like Apoptosis Regulating Protein/genetics/*metabolism ; Caspase 3/metabolism ; Cell Line, Tumor ; Drug Discovery ; Flow Cytometry ; Glioma/*metabolism/pathology ; Humans ; Indoles/*pharmacology ; Inhibitor of Apoptosis Proteins/metabolism ; RNA, Small Interfering ; Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; TNF-Related Apoptosis-Inducing Ligand/metabolism/*pharmacology ; Transcription Factor CHOP/analysis