• Genomics & Informatics
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• v.20 no.2
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• pp.24.1-24.8
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• 2022

Hypomyelinating leukodystrophy type 2 (HLD2), is an inherited genetic disease of the central nervous system caused by recessive mutations in the gap junction protein gamma 2 (GJC2/GJA12). HLD2 is characterized by nystagmus, developmental delay, motor impairments, ataxia, severe speech problem, and hypomyelination in the brain. The GJC2 sequence encodes connexin 47 protein (Cx47). Connexins are a group of membrane proteins that oligomerize to construct gap junctions protein. In the present study, a novel missense mutation gene c.760G>A (p.Val254Met) was identified in a patient with HLD2 by performing whole exome sequencing. Following the discovery of the new mutation in the proband, we used Sanger sequencing to analyze his affected sibling and parents. Sanger sequencing verified homozygosity of the mutation in the proband and his affected sibling. The autosomal recessive inheritance pattern was confirmed since Sanger sequencing revealed both healthy parents were heterozygous for the mutation. PolyPhen2, SIFT, PROVEAN, and CADD were used to evaluate the function prediction scores of detected mutations. Cx47 is essential for oligodendrocyte function, including adequate myelination and myelin maintenance in humans. Novel mutation p.Val254Met is located in the second extracellular domain of Cx47, both extracellular loops are highly conserved and probably induce intramolecular disulfide interactions. This novel mutation in the Cx47 gene causes oligodendrocyte dysfunction and HLD2 disorder.

• Applied Microscopy
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• v.6 no.1
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• pp.21-32
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• 1976

The origins and the functions of the multi vesicular bodies and the various structures of the membranes related to the cytolysomes were studied in the mycelium cells of Rhizopus nigricans, Aspergillus niger and A. ochraceus, in the hymenium and basidium cells of Agricus bisporus sand Rhizopogon rubesecens, in the cells of assimilation tissue of Marchtantia polymorpha and Pogonalum inflexum and in the mesophyll cells of Pteridium aqiulinum, Pinus densiflora, Ginkgo biloba and Panax ginseng fixed with glutaraldehyde-paraformaldehyde-$ OsO_4$. In Rhizopus nigricans, Aspergillus niger, A. ochraceus, Agricus bisporus sand Rhizopogon rubescens, the concentric multilamellar, multivesicular, myelin-vesicle-tubular and concentric parallel-lamellar complexes were originated from the plasmalemma, while in Marehantia polymorpha, Pogonatum inflexum, Pteridium aquilinum, Pinus densiflora, Ginkgo biloba and Panax ginseng, they were originated from plasmalemma and the cytoplasm. The structures originated from the plasmalemma may be grouped into multi vesicular body and myelin-like structure, both forming the secondary vacuoles or protruding into the central vacuoles and finally degrading, In some cases, endoplasmic reticulum within the cytoplasm encloses some part of the cytoplasm to form a circle where the membranous lamellae increase in number, while the enclosed cytoplasm decrease to be eventually replaced by the multilamellar structure which is released into the vacuoles and subsquently degraded. The structures originated from the cytoplasm are believed to be the cytosegresomes or cytolysomes closely related to the differentiation of the vacuoles. The possible fate of these structures are also discussed.

• The Journal of Korean Society of Virology
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• v.27 no.1
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• pp.39-47
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• 1997

A large number of viruses belonging to Genus Hantavirus in Family Bunyaviridae are etiologic agents for hemorrhagic fever with renal syndrome (HFRS), or hantavirus pulmonary syndrome (HPS). Hantaan (HTN), Seoul (SED), Belgrade (BEL), Puumala (PUU) serotype viruses are well known causative agents for HFRS in Eurasian continent. Among those viruses Hantaan and Seoul serotypes are well known to cause HFRS in Korea, but there are some sporadic incidence by other than Hantaan or Seoul viruses. Recently we have developed the combined Hantaan-Puumala virus vaccine to prevent world-wide occuring HFRS. This combined vaccine is formalin inactivated, suckling mouse and suckling hamster brain extracts for Hantaan and Puumala viruses, respectively. Protein contents of this purified candidate vaccine is $27\;{\mu}g/ml$, which contains 1,024 ELISA antigen units to each virus, but content of myelin basic protein which is causing experimental allergic encephalomyelitis is less than 0.1 ng/ml. Thirty hamsters were given twice at one month interval intra-muscularly and bled on 30 days after each vaccination from retro-orbital sinus vein. Antibody titers were tested against 5 major serotype viruses, Hantaan, Seoul, Belgrade, Puumala and Sin Nombre viruses by IFA and PRNT. The mean IF antibody titers on 30 days after primary shot were 78.4, 68.8, 68.8, 37.9, and 15.6; mean neutralizing antibody titers were 65.4, 12, 6.1, 65.6 and 0.5 against Hantaan, Seoul, Belgrade, Puumala and Sin Nombre viruses, respectively. The mean IF antibody titers on 30 days after booster shot were 686.9, 567.5, 550.4, 516.3, and 430.9; and neutralizing antibody titers were 710.8, 41.9, 24.3, 409.9, and 1.6 against Hantaan, Seoul, Belgrade, Puumala and Sin Nombre viruses, respectively.

• Korean Journal of Veterinary Pathology
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• v.1 no.1
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• pp.26-32
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• 1997

Protein kinase C an enzyme of signal transduction has been known to regulate cell proliferation activation as well as apoptosis in some cancer cell lines. To explore the role of PKC in the course of cell mediated autoimmune disease such as experimental autoimmune encephalomyelitis (EAE) EAE was induced in Lewis rats(6-8 weeks old) with immunization of myelin basic protein supplemented with complete Freund's adjuvants and affected spinal cords were sampled at days 13 postimmunization(PI) as peak stage of EAE and at days 21 PI as recovery stage. The spinal cords with EAE were subjected to Northern blot analysis and insitu hybridization of PKC delta which is one of prominant isotypes of PKC in the haematopoietic cells. Northern blot analysis showed that levels of PKS delta mRNA in the spinal cords of rats withEAE was significantly increased at days 13 PI in which inflammatory cells including T cells and macrophages in the EAE lesions appeared. however the stage. By in situ hybridization signals of PKC delta in EAE lesions was intensely expressed on the delta is also expressed on some brain cells in normal rat central nervous system This finding suggests that PKC plays an important role on either activation of inflammatory cells including encephalitogenic T cells and macrophages or apoptotic elimination of some inflammatory cells depending on the stge of EAE.

• Toxicological Research
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• v.13 no.4
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• pp.317-322
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• 1997

Acute delayed neurotoxicity of KH-502 [O.O-Diethyl O-(1-phenyyl-3-trifluoromethyl-5-pyrazoyl) thiophosphoric acid ester], an insecticide synthesized newly in Korea, was studied in White Leghorn hens. The doses were determined on the basis of preliminary $LD_{50}$ study. High, middle and low doses were determined to be 1123 mg/kg, 762 mg/kg and 518 mg/kg, respectively. The animals were pretreated with atropine (30 mg/kg) prior to administration of KH-502. The chemical was administrated at the first and 21st day of the study. As positive controls, animals were admlnistrated with triorthocresylphosphate (TOCP 1000 mg/kg and 500 mg/kg). Animals administrated with TOCP or KH-502 were sacrificed by perfusion-fixation at 21st and 42nd day of the study, respectively. The central and peripheral nerve tissues were routinely treated for microscopic observation. As results, eight, three, one, and one chickens died within 2 day after adminiatration with signs of cholinergic acute toxicity in high, middle low and TOCP dose-group (500 mg/kg), respectively. No abnormal clinical signs were observed in the survived chickens administrated with KH-502 in the duration of the study. The chickens in positive control groups showed ataxia and incoordination at the 14th day after administration of TOCP. From necropsy, macroscopic changes were not observed in all groups including positive control groups. Histopathologically, oxonal swelling with myelin loss, focal gliosis, distention around axonal space were observed in the spinal cords of the chickens administrated with TOCP 1000 mg/kg. The lesions were distinct in the dorsal and lateral funiculi of cervical spinal cord, in the lateral and ventral funiculi of thoracic spinal cord and in ventral funiculi of lumbosacral spinal cord. Axonal swelling and mlcrogliosis were infrequently observed in the chickens of other groups including negative control one. However, they were nonspecifically distributed in the spinal cords. In this study, we concluded that the new chemical, KH-502 did not have acute delayed neurotoxicity in White Leghorn hens.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.1
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• pp.66-70
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• 2014

X-linked adrenoleukodystrophy (ALD) is a uncommon metabolic disorder which derived by peroxismal ${\beta}$-oxidation and elevation of serum very long chain fatty acid (VLCFA). VLCFA is mainly accumulated in the myelin of the central nervous system and adrenal cortex, by which the expressed symptoms of this disease are mainly neurologic and endocrinologic (such as adrenal insufficiency). The mutations in the ABCD1 gene causes X-linked ALD, nevertheless its phenotypes and genotypes are poorly coordinated. We report the case of a 12-year-old boy with X-linked ALD who developed vomiting, fatigue and poor oral intake. Severe dehydration and hyponatremia were found in initial physical examination and laboratory test, but his motor/sensory nerve function and mental status were completely normal. We diagnosed ALD with diffuse high-intensity signal in both parietotemporal cerebellar white matter in brain MRI and elevated serum VLCFA. Later, we confirmed a novel c.1635-1G>A (IVS6-1G>A) mutations of the ABCD1 gene. With the discrepancy between its phenotypes and genotypes, various phenotypes could be seen in X-ALD patient. Careful examination and further studies for these patients will be needed.

• Korean Journal of Veterinary Research
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• v.52 no.3
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• pp.199-203
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• 2012

Neurofascin, one of the members of L1CAM, has been known to have some important roles during the development of nerve fibers. In order to investigate the role of neurofascin associated with the development of nerve fibers in the rat sciatic nerve, the initial development of NF155 in the paranode was studied with immuno-fluorescence and immuno-electron microscopy. The result of the present study showed NF155 was not detected in the fetal sciatic nerve and began to reveal at the postnatal day 0 (P0) and dramatically increased by time lapse until postnatal day 7 (P7). NF155 was prominently localized in the axolemma of paranode and not detected in the central region of node of Ranvier. According to the present study, NF155 is likely to have some relationships with the formation of paranode and myelin sheath.

• Journal of Pharmacopuncture
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• v.12 no.1
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• pp.67-76
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• 2009

Objective : Following central nervous system(CNS) injury, inhibitory influences at the site of axonal damage occur. Glial cells become reactive and form a glial scar, gliosis. Also myelin debris such as MAG inhibits axonal regeneration. Astrocyte-rich gliosis relates with up-regulation of GFAP and CD81, and eventually becomes physical and mechanical barrier to axonal regeneration. MAG is one of several endogenous axon regeneration inhibitors that limit recovery from CNS injury and disease. It was reported that molecules that block such inhibitors enhanced axon regeneration and functional recovery. Recently it was reported that treatment with anti-CD81 antibodies enhanced functional recovery in the rat with spinal cord injury. So in this current study, the author investigated the effect of the water extract of Uncariae Ramulus et Uncus on the regulation of CD81, GFAP and MAG that increase when gliosis occurs. Methods : MTT assay was performed to examine cell viability, and cell-based ELISA, western blot and PCR were used to detect the expression of CD81, GFAP and MAG. Then also immunohistochemistry was performed to confirm in vivo. Results : Water extract of Uncariae Ramulus et Uncus showed relatively high cell viability at the concentration of 0.05%, 0.1% and 0.5%. The expression of CD81, GFAP and MAG in astrocytes was decreased after the administration of Uncariae Ramulus et Uncus water extract. These results was confirmed in the brain sections following cortical stab injury by immunohistochemistry. Conclusion : The authors observed that Uncariae Ramulus et Uncus significantly down-regulates the expression of CD81, GFAP and MAG. These results suggest that Uncariae Ramulus et Uncus can be a candidate to regenerate CNS injury.

• Science of Emotion and Sensibility
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• v.7 no.2
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• pp.179-186
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• 2004

Acute spinal cord injury can produce neurologic injury with many physical, psychological and social ramifications. It has been shown that two separate components combine to produce neurologic damage in acute spinal cord injury : the primary and secondary injuries. The primary mediators of spinal cord injury include the actual mechanical tissue disruption which is a passive process that occurs immediately following the trauma. A secondary injury cascade follows which appears mediated by cellular and molecular processes working through complex mechanisms. Both the primary and secondary injury cascades produce cell death both in neuronal and supporting cell tissues. Recovery from central nervous system(CNS) disorders is hindered by the limited ability of the vertebrate CNS to regenerate injured cells, replace damaged myelin sheath, and re-establish functional neuronal connections. Of many CNS disorders including multiple sclerosis, stroke, and other trauma, spinal cord injury is one of the important diseases because of the direct association with the functional loss of the body. Previous studies suggest that substantial recovery of function might be achieved through regeneration of lost neuronal cells and remyelination of intact axon in spinal cord injury which is occurred frequently. As a therapeutic approach in spinal cord injury, recently, cell transplantation provides a potential solution for the treatment of spinal cord injury. This review describes the characteristics of spinal cord injury and presents some evidence supporting functional recovery after cell transplantation following spinal cord injury.

• Anatomy and Cell Biology
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• v.51 no.4
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• pp.292-298
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• 2018

Experimental autoimmune encephalomyelitis (EAE) is a T-cell-mediated autoimmune central nervous system disease characterized by inflammation with oxidative stress. The aim of this study was to evaluate an anti-inflammatory effect of Ishige okamurae on EAE-induced paralysis in rats. An ethanolic extract of I. okamurae significantly delayed the first onset and reduced the duration and severity of hind-limb paralysis. The neuropathological and immunohistochemical findings in the spinal cord were in agreement with these clinical results. T-cell proliferation assay revealed that the ethyl-acetate fraction of I. okamurae suppressed the proliferation of myelin basic protein reactive T cells from EAE affected rats. Flow cytometric analysis showed $TCR{\alpha}{\beta}^+$ T cells was significantly reduced in the spleen of EAE rats with I. okamurae treatment with concurrent decrease of inflammatory mediators including tumor necrosis $factor-{\alpha}$ and cyclooxygenase-2. Collectively, it is postulated that I. okamurae ameliorates EAE paralysis with suppression of T-cell proliferation as well as decrease of pro-inflammatory mediators as far as rat EAE is concerned.