• Animal cells and systems
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• v.9 no.4
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• pp.191-198
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• 2005

The effects of 6-aminonicotinamide (6-AN) on viability of IMR32 neuroblastoma cells in the presence of ATP or $NAD^+$ have been investigated. 6-AN caused marked reduction in cell viability and similar observations were also made with cells treated with 6-AN+ATP. However, cells treated with $6-AN+NAD^+$ showed cell viability similar to untreated cells. Morphologically, 6-AN and 6-AN+ATP treated cells showed loss of neurites, polyhedric shapes, shrinkage of cell bodies and formation of lysed cells, while $6-AN+NAD^+$ cells did not show any such changes. The flow cytometry analysis demonstrated that 6-AN increased cell population in $G_0/G_1$ phase and decreased cell population in Sand $G_2/M$ phase following a 72 h exposure. Western blot analysis showed that 6-AN stimulated a substantial increase in the level of the cdk inhibitor $p27^{kip1}$, but lowered the levels of cdk2, cyclin E and p-Rb. However, cdc25A and p53R2 were not significantly affected. Immunofluorscence staining of $p27^{kip1}$, cdk2, cyclin E and p-Rb revealed close correlation between the signal observed in the Western blot analysis. 6AN+ATP treated cells showed similar results obtained with 6-AN treated cells in expression of cdk2, cyclin E, p-Rb proteins and $p27^{kip1}$, $6-AN+NAD^+$ cells showed greater expression of cdk2, cyclin E and p-Rb than those in 6-AN and 6-AN+ATP treated cells. The results suggest that 6-AN induced the $G_0/G_1$ phase arrest in IMR32 neuroblastoma cell lines through the increase of $p27^{kip1}$ and the decrease of cdk2, cyclin E and p-Rb.

• Animal cells and systems
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• v.11 no.1
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• pp.17-22
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• 2007

The effects of antimetabolite 6-AN (6-amino-nicotinamide) on viability and morphology of L6 myoblast cells have been investigated. 6-AN ($100{\mu}M$) induced a time-dependent decrease in cell viability with respect to the untreated control cells. Following 6-AN administration the viability rate started to decline sharply, reaching about 23% of the untreated control cells at 48 h. Inverted phase-contrast microscopy revealed that 6-AN caused characteristic morphological changes such as irregularly elongated and stellate shape of cells, round-shaped nucleus, cytoplasmic vacuolization, irregular cell arrangements and formation of large spaces among cell clusters. The concentrations of ATP and $NAD^{+}$ in the 6-AN treated cells were significantly lower (p < 0.01) than those of the untreated control cells. In contrast, the concentration of AMP was significantly increased by the 6-AN treatment. Activities of catalase, superoxide dismutase and glutathione peroxidase in 6-AN treated cells were significantly higher (p < 0.01) than those of the untreated control cells. The activities of glyceraldehyde-3-phosphate dehydrogenase in 6-AN treated cells were significantly lower (p < 0.01) than those of the untreated control cells. The results suggest that 6-AN caused marked reduction of cell viability and alterations of some important metabolites and enzymes.

• Biomedical Science Letters
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• v.12 no.3
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• pp.233-240
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• 2006

We investigated enzyme activity and histochemical changes in hind limb of mouse treated with 6-aminonicotinamide (6-AN). The activity of aspartate aminotransferase, alanine aminotransferase and creatine phosphokinase in 6-AN treated group were significantly higher than those of the control and pair-fed groups. Also, the activity of lactic dehydrogenase in 6-AN treated group was the highest among the three groups, whereas that of the pair-fed group were higher than that of the control group. In the 6-AN treated group, oxidative histochemical stains, nicotinamide adenine dinucleotide reductase (NADH), succinyl dehydrogenase (SDH) showed increased scattered fibers in 6-AN treated subsarcolemma. Cytochrome c oxidase (COX) stain showed decreased up to 85% in 6-AN treated fibers. These results demonstrate that 6-AN antagonizes cell metabolism and induces the morphological deformity like the other mitochondrial muscle diseases. Therefore, we suppose that these data would be useful indexes for disclosing the mechanism of mitochondrial muscle disease.

• The KIPS Transactions:PartC
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• v.18C no.5
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• pp.343-360
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• 2011

The objective of this paper is to analyze and characterize to simulate routing observations on end-to-end routing circuits and a ping experiment of a virtual network after modeling, such as IPv6 migration, an OSPFv3 routing experiment based on an IPv6 environment, and a ping experiment for IPv4/IPv6 dual-stack networks and IPv6 network for OSPFv3 routing using IPv6 planning and operations in an OPNET Modeler. IPv6 deployment based largely on the integrated wired and wireless network was one of the research tasks at hand. The previous studies' researchers recommended that future research work be done on the explicit features of both OSPFv3 and EIGRP protocols in the IPv4/IPv6 environment, and more research should be done to explore how to improve the end-to-end IPv6 performance. Also, most related work was performed with an IPv4 environment but lacked studies related to the OSPFv3 virtual network based on an end-to-end IPv6 environment. Hence, this research continues work in previous studies in analyzing IPv6 migration, an OSPFv3 routing experiment based on IPv6, and a ping experiment for IPv4/IPv6 dual-stack networks and IPv6 network for OSPFv3 routing. In the not too distant future, before enabling the default IPv6, it would help to understand network design and deployment based on an IPv6 environment through IPv6 planning and operations for the end-user perspective such as success or failure of connection on IPv6 migration, exploration of an OSPFv3 routing circuit based on an end-to-end IPv6 environment, and a ping experiment for IPv4/IPv6 dual-stack networks and IPv6 network for OSPFv3 routing. We were able to observe an optimal route for modeling of an end-to-end virtual network through simulation results as well as find what appeared to be a fast ping response time VC server to ensure Internet quality of service better than an HTTP server.

• Applied Microscopy
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• v.27 no.3
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• pp.281-293
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• 1997

The effects of antimetabolite, 6-aminonicotinamide (6-AN), on ultrastrudural changes in the spinal cord of golden hamster were investigated. Intraperitoneal administration of 6-AN (10 mg/kg body weight) every two days gave rise to a marked reduction of about $30\sim40%$ in body weight after $26\sim28$ days ($13\sim14th$ injection). In the lesions of the spinal cord, neuroglial cells such as astrocytes and oligodendrocytes were severely damaged, but neurons and blood vessels were not affected by 6-AN. The myelin sheath was also affected by 6-AN. Vacuoles observed in the lesions were produced by the swelling and degenerating changes of neuropils and neuroglial cells. Numerous swollen mitochondria and cisterns of rough endoplasmic reticulum were observed in the watery cytoplasm of damaged neuroglial cells, but intermediate filaments were well preserved. Especially in the damaged astrocytes, the outer nuclear membrane were partially swollen and formed a halfmoonlike structure. It is suggested that as well as the multivesicular bodies protruding from the swollen dendrites, the conjugation of adjacent vacuoles also participated in the formation of large vacuoles.

• The Korean Journal of Zoology
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• v.33 no.4
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• pp.493-498
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• 1990

The effects of an antimetabolite, 6-aminonicotinamide (6-AN) on the levels of enzymes and metabolites in rabbit serum were investigated. The intraperitoneal administration of 6-AN (multiple doses of l5mg/kg body weight) gave tise to a remarkable increase in glucose and cholesterol levels but did not exert any appreciable influence on the concentration of albumin and total protein. Alkaline phosphatase activity was significantly reduced by administration of 6-AN, whereas creatine phophokinase, serum glutamic oxaloacetate transaminase and serum glutamic pyruvate transaminase activities were matkedly enhanced. Nevettheless, the levels of Ca, P, Na, K, Cl and Co were not affeded to any extent by 6-AN.

• Applied Microscopy
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• v.27 no.2
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• pp.177-187
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• 1997

Hydrocephalus is induced experimentally in prenatal and suckling animals following an injection of 6-aminonicotinamide (6-AN). The most remarkable characteristic of these animals is aqueduct stenosis caused by swellings of the ependymal cells and subependymal cells in the periaqueductal gray matter and the central canal of the spinal cord. The present study was undertaken to investigate the morphological changes of the ependymal cells in the central canal of the spinal cord of 3.5 months old hamster after treatment with 6-AN. Intraperitoneal administrations of 6-AN (10 mg/kg body weight) every two days gave rise to partial central canal stenosis of the spinal cord after 27-29 days (13-l4th injection), but cilia and microvilli were located in the strictural area of the con#rat canal. The vacuolations in the ependymal cells were not observed and degenerating changes of intracellular organelles of the ependymal cells did not occur, so that the ependymal cells lining the central canal of the hamster spinal cord were not affected by 6-AN. But the present study demonstrate that 6-AN causes to create numerous vacuoles in the subependymal area of the central canal. Although the vacuoles were well developed in the neuroglial cells and the neuropils of the subependymal area, the neurons were not affected by 6-AN. These results strongly suggests that partial central canal stenosis occurred by 6-AN was due to vacuolations and swellings of the neuroglial cells and nueropils in the subependymal area.

• Bulletin of the Korean Chemical Society
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• v.35 no.10
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• pp.3030-3034
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• 2014

Bis-chloroethylnitrosourea (BCNU) is currently used as an anti-cancer drug for glioblastoma therapy. In this study, BCNU was loaded into the hydrophobic cores of R3V6 amphiphilic peptide micelles for efficient delivery into brain tumors. The scanning electron microscope (SEM) study showed that the BCNU-loaded R3V6 peptide micelles (R3V6-BCNU) formed spherical micelles. MTT assay showed that R3V6-BCNU more efficiently induced cell death in C6 glioblastoma cells than did BCNU. In the Annexin V assay, R3V6-BCNU more efficiently induced apoptosis than did BCNU alone. Furthermore, the results showed that R3V6 was not toxic to cells. The positive charges of the R3V6 peptide micelles may facilitate the interaction between R3V6-BCNU and the cellular membrane, resulting in an increase in cellular uptake of BCNU. In vivo evaluation with an intracranial glioblastoma rat model showed that R3V6-BCNU more effectively reduced tumor size than BCNU alone. The results suggest that R3V6 peptide micelles may be an efficient carrier of BCNU for glioblastoma therapy.

• The Journal of Korean Institute of Communications and Information Sciences
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• v.30 no.7A
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• pp.597-602
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• 2005

This paper proposes an efficient multicast scheme for the hierarchical mobile IPv6(HMIPv6). If a mobility anchor point(MAP) in a new domain does not support multicasting, an entering group member cannot join the multicast group through the new MAP The group member thus keeps receiving multicast packets from its home agent(HA) using Mobile IPv6 (MIPv6). This increases the propagation delay of binding update (BU) messages. However, our scheme enables an entering group member to keep receiving packets from the old multicast MAP. It can also reduce tunneling costs, total delivery costs and handover latency. We simulated the performance of our scheme by comparing it with the seamless multicast handover in a hierarchical mobile Pv6 (M-HMIPv6) using the delivery cost and handover latency factors.

• BMB Reports
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• v.33 no.4
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• pp.332-336
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• 2000

Phenazine 1-carboxylic acid (PCA) is an antifungal antibiotic isolated from a culture filtrate of Bacillus sp. B-6 producing an acyl CoA synthetase inhibitor. This antibiotic is reported as an inhibitor of an acyl CoA synthetase from Pseudomonas sp.. Bacillus sp. B-6 was resistant to PCA up to 350 ${\mu}g/ml$. We investigated the mechanism of the resistance of Bacillus sp. B-6 to PCA. The rate of growth in a medium containing up to 100 ${\mu}g/ml$ was as rapid as the PCA-free medium. At a PCA concentration of 300 ${\mu}g/ml$, the growth rate was more than half that of the control. In this work, we purified acyl CoA synthetase from Bacillus sp. B-6 and found that this acyl CoA synthetase was much less sensitive to PCA than the acyl CoA synthetase from other source. These findings suggested that the insensitivity of Bacillus sp. B-6 acyl CoA synthetase plays an important role in the PCA resistance of this bacterium.