• International Journal of Vascular Biomedical Engineering
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• v.2 no.1
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• pp.17-24
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• 2004

Tumor angiogenesis was simulated using a two-dimensional computational model. The equation that governed angiogenesis comprised a tumor angiogenesis factor (TAF) conservation equation in time and space, which was solved numerically using the Galerkin finite element method. The time derivative in the equation was approximated by a forward Euler scheme. A stochastic process model was used to simulate vessel formation and vessel elongation towards a paracrine site, i.e., tumor-secreted basic fibroblast growth factor (bFGF). In this study, we assumed a two-dimensional model that represented a thin (1.0 mm) slice of the tumor. The growth of the tumor over time was modeled according to the dynamic value of bFGF secreted within the tumor. The data used for the model were based on a previously reported model of a brain tumor in which four distinct stages (namely multicellular spherical, first detectable lesion, diagnosis, and death of the virtual patient) were modeled. In our study, computation was not continued beyond the 'diagnosis' time point to avoid the computational complexity of analyzing numerous vascular branches. The numerical solutions revealed that no bFGF remained within the region in which vessels developed, owing to the uptake of bFGF by endothelial cells. Consequently, a sharp, declining gradient of bFGF existed near the surface of the tumor. The vascular architecture developed numerous branches close to the tumor surface (the brush-border effect). Asymmetrical tumor growth was associated with a greater degree of branching at the tumor surface.

• Toxicological Research
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• v.31 no.1
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• pp.17-23
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• 2015

Excessive manganese (Mn) in the brain promotes a variety of abnormal behaviors, including memory deficits, decreased motor skills and psychotic behavior resembling Parkinson's disease. Hereditary hemochromatosis (HH) is a prevalent genetic iron overload disorder worldwide. Dysfunction in HFE gene is the major cause of HH. Our previous study has demonstrated that olfactory Mn uptake is altered by HFE deficiency, suggesting that loss of HFE function could alter manganese-associated neurotoxicity. To test this hypothesis, Hfe-knockout ($Hfe^{-/-}$) and wild-type ($Hfe^{+/+}$) mice were intranasally-instilled with manganese chloride ($MnCl_2$ 5 mg/kg) or water daily for 3 weeks and examined for memory function. Olfactory Mn diminished both short-term recognition and spatial memory in $Hfe^{+/+}$ mice, as examined by novel object recognition task and Barnes maze test, respectively. Interestingly, $Hfe^{-/-}$ mice did not show impaired recognition memory caused by Mn exposure, suggesting a potential protective effect of Hfe deficiency against Mn-induced memory deficits. Since many of the neurotoxic effects of manganese are thought to result from increased oxidative stress, we quantified activities of anti-oxidant enzymes in the prefrontal cortex (PFC). Mn instillation decreased superoxide dismutase 1 (SOD1) activity in $Hfe^{+/+}$ mice, but not in $Hfe^{-/-}$ mice. In addition, Hfe deficiency up-regulated SOD1 and glutathione peroxidase activities. These results suggest a beneficial role of Hfe deficiency in attenuating Mn-induced oxidative stress in the PFC. Furthermore, Mn exposure reduced nicotinic acetylcholine receptor levels in the PFC, indicating that blunted acetylcholine signaling could contribute to impaired memory associated with intranasal manganese. Together, our model suggests that disrupted cholinergic system in the brain is involved in airborne Mn-induced memory deficits and loss of HFE function could in part prevent memory loss via a potential up-regulation of anti-oxidant enzymes in the PFC.

• The Korean Journal of Nuclear Medicine
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• v.24 no.2
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• pp.215-221
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• 1990

HM-PAO was synthesized by two step reaction. d, 1-HM-PAO was separated from the racemic product by fractional recrystalization in ethylacetate, and the chemical structure and purity was confirmed by proton NMR spectroscopy. The synthesized 0, 1-HM-PAO was labeled with $^{99m}Tc$ and studied the biodistribution in mice. From the results we could find that liver uptake of synthesized $^{99m}Tc$ d, 1-HM-PAO was higher than that of Amersham kit, but no conspicuous difference was found in brain and other tissues (blood, lung, stomach, intestine, muscle, spleen and kidney).

• The Korean Journal of Nuclear Medicine
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• v.29 no.1
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• pp.9-14
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• 1995

뇌졸증환자의 뇌 SPECT 소견상 나타나는 소뇌교차해리현상(crossed cerebellar diaschisis)은 잘 알려진 현상이다. 한편 간질 환자의 발작시 뇌 SPECT에서 반대편 소뇌에 혈류증가를 보이는 역교차해리현상(reverse type of crossed cerebellar diashisis)은 드물게 보고되었었다. 따라서 본 저자들은 발작시 뇌 SPECT에서 역교차해리현상의 빈도 및 간질병소를 찾는데 있어서의 유용성에 대해 알아보고자 하였다. 복합부분발작환자 중 임상적, 뇌파검사상 및 SPECT 소견등에서 간질병소가 일치하는 12명의 환자를 대상으로 하였다. 환자 모두에서 시행한 발작시 스캔은 발작중 혹은 환자가 aura를 호소할때 $^{99m}Tc$-HMPAO 15-20mCi를 정맥주입 후 시행하였으며 발작간 스캔은 11명의 환자에서 발작시 스캔 후 적어도 3일 간격을 두고 시행하였다. 간질병소는 우측측두엽이 6예, 좌측측두엽이 4예, 우측후두엽이 1예, 좌측전두엽이 1예 등이었다. 발작시 스캔상 간질병소 및 반대편 소뇌에 혈류가 증가하는 역해리현상은 모두 8명(75%)의 환자에서 나타났으며 특히 2명의 환자에서는 간질병소보다 반대편 소뇌의 동위원소 섭취가 더욱 뚜렸했다. 역해리현상을 보였던 환자의 발작간 스캔소견에서는 발작시 증가되었었던 소뇌의 동위원소 섭취가 7예에서 정상화되었고 나머지 1예에서는 감소되었다. 따라서 소뇌의 역교차해리현상은 발작시 뇌 SPECT의 자주 볼 수 있는 현상으로 간질병소의 편측화에 도움을 줄 수 있을 것으로 생각된다.

• Clinical Pain
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• v.20 no.1
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• pp.53-57
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• 2021

We report a case of neurolymphomatosis of lumbosacral plexus. A 63-year-old man, who had no past history except for diabetes mellitus, complained of severe pain and weakness on left lower extremity. Idiopathic lumbosacral plexopathy was diagnosed by electromyography. There were no abnormal findings except for FDG-PET/CT and MRI. They showed high uptake and thickening lesion in sciatic nerve and sacral plexus. However, about 7 months later, mass like lesion in left thigh was detected by FDG-PET/CT and MRI. Also, multiple hypermetabolic lesions were found in brain. Through brain biopsy, diffuse large B-cell lymphoma was confirmed. When a patient with idiopathic lumbosacral plexopathy complains of severe pain, it is necessary to consider FDG-PET/CT and MRI to differentiate neurolymphomatosis, even in patients who have no past history of lymphoma before. Especially, if FDG-PET/CT and MRI show sciatic and/or lumbosacral plexus lesion, neurolymphomatosis of lumbosacral plexus should be considered.

• Journal of Yeungnam Medical Science
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• v.16 no.2
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• pp.237-243
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• 1999

We conducted this study to find the optimal correction factor(${\alpha}$) of Lassen's linearization algorithm which has been applied for correction of flow-limited uptake at a high flow range in $^{99m}Tc$ d,l-hexamethylpropy leneamine oxime(HMPAO) and $^{99m}Tc$ ethyl cysteinate dimer(ECD). Ten patients with chronic cerebral infarction were involved in this study. We obtained the corrected $^{99m}Tc$ HMPAO and $^{99m}Tc$-ECD brain SPECT(single photon emission computed tomography) using the algorithm with ${\alpha}$ values that varied from 0.1 to 10 and compared the results with regional cerebral blood flow determined by positron emission tomography (PET-rCBF). The multi-modal volume registration by maximization of mutual information was used for matching between PET-rCBF and SPECT images. The highest correlation coefficient between $^{99m}Tc$-HMPAO and $^{99m}Tc$-ECD brain uptake and PET-rCBF was revealed at ${\alpha}$ 1.4 and 2.1, respectively. We concluded that the ${\alpha}$ values of Lassen's linearization algorithm for $^{99m}Tc$-HMPAO and $^{99m}Tc$-ECD brain SPECT images were 1.4 and 2.1, respectively to indicate cerebral blood flow with comparison of PET-rCBF.

• The Journal of the Korea Contents Association
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• v.15 no.9
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• pp.418-424
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• 2015

In this study, we proceed if there are any changes in binding ability of receptor-ligand in some degree of SA and in radioactive uptake from the corpus striatum based on small animal experiment in vivo based on the S.A values. By dividing 18F-Fallypride into 3 S.A values(high S.A : 43.29~74 GBq/umol, ordinary S.A : 20.72~29.23 GBq/umol, low S.A : 6.29~8.51 GBq/umol), we injected directly into the veins and performed 90 minutes of dynamic scan using Micro PET. After scanning, we compared and analyzed with Binding Potential (Binding Potential) from the bilateral striatum. high SA and low SA, ordinary SA and low SA showed significant differences. Also, in the image comparison using 18F-Fallypride show high radioactive uptake in the striatum at high SA and ordinary SA, but the radioactive uptake at low SA is lower than other two SA. Since 18F-Fallypride has affinity to dopamine D2/3 pharmacokinetic, the difference of Binding Potentials at decreased level of SA values was not that significant. However, further PET research of the corpus striatum using 18F-Fallypride is necessary because the differences in images and Binding Potentials at 6.5 times smaller SA values compared to high SA value showed were significant.

• BMB Reports
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• v.48 no.3
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• pp.147-152
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• 2015

Small interfering RNA (siRNA) functions through pairing with specific mRNA sequences and results in the mRNA's degradation. It is a potential therapeutic approach for many diseases caused by altered gene expression. The delivery of siRNA is still a major problem due to its rapid degradation in the circulation. Various strategies have been proposed to help with the cellular uptake of siRNA and short or small hairpin RNA (shRNA). Here, we reviewed recently published data regarding local applications of siRNA. Compared with systemic delivery methods, local delivery of siRNA/shRNA has many advantages, such as targeting the specific tissues or organs, mimicking a gene knockout effect, or developing certain diseases models. The eye, brain, and tumor tissues are 'hot' target tissues/organs for local siRNA delivery. The siRNA can be delivered locally, in naked form, with chemical modifications, or in formulations with viral or non-viral vectors, such as liposomes and nanoparticles. This review provides a comprehensive overview of RNAi local administration and potential future applications in clinical treatment.

• Journal of Korean Neurosurgical Society
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• v.30 no.5
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• pp.638-641
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• 2001

Carboplatin intra-arterial chemotherapy(IAC) has an advantage of increased uptake during the first passage of the drugs through tumor capillaries. Although not common, this type of therapy is known to cause neurological complications, myelosuppression, and ototoxicity. However, the incidence of ocular toxicity is reported to be rare. Eleven of our patients with glioma(Grade II Astrocytoma : 3, Grade III Astrocytoma : 1, Grade IV Astrocytoma : 5, Gliofibroma : 1, Oligodendroglioma : 1) underwent IAC regimen with carboplatin($300mg/m^2$) which were administrated after blood-brain barrier disruption. Of there, 3 patients had ocular complications after supra-ophthalmic IAC injection of carboplatin but fully recovered following steroid therapy. Although our results from IAC seem to be favorable for these patients, we suggest that its complications, such as ocular toxicity, need to be carefully considered prior to treatment.

• Archives of Pharmacal Research
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• v.20 no.4
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• pp.379-383
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• 1997

Cyclosporin A, an potent immunosuppressant, has been known to be one of the modulators of drug resistance as well as a cytostatic drug. Despite many attempts to basic or clinical application of cyclosporin A, there are few reports on the inhibition of brain tumor cells. In the present experiment, the possibility of cyclosporin A as synergic adjuvant was investigated by MTT assay, $[^{3}H]$ thymidine uptake and through flowcytometric anaysis. Sole treatment of cyclosporin A on the CRT and CH235-MG glioma cell line revealed dose dependent cytotoxicity within a range of tested dose. Combined treatment of cyclosporin A with ACNU, BCNU and hydroxyurea on various glioma cancer cell line led to a significant synergistic cytotoxicity as well as inhibition of DNA synthesis with dose-dependency. In addition, cyclosporin A alone or combined treatment caused discernible changes of cell cycle in the tested cells. These data provide that cyclosporin A could potentiate the effect of nitrosourea compounds in vitro on human glioma cells.