• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.340-349
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• 2023

Mad2B (Mad2L2), the human homolog of the yeast Rev7 protein, is a regulatory subunit of DNA polymerase ζ that shares sequence similarity with the mitotic checkpoint protein Mad2A. Previous studies on Mad2B have concluded that it is a mitotic checkpoint protein that functions by inhibiting the anaphase-promoting complex/cyclosome (APC/C). Here, we demonstrate that Mad2B is activated in response to cisplatin-induced DNA damage. Mad2B co-localizes at nuclear foci with DNA damage markers, such as proliferating cell nuclear antigen and gamma histone H2AX (γ-H2AX), following cisplatin-induced DNA damage. However, unlike Mad2A, the binding of Mad2B to Cdc20 does not inhibit the activity of APC/C in vitro. In contrast to Mad2A, Mad2B does not localize to kinetochores or binds to Cdc20 in spindle assembly checkpoint-activated cells. Loss of the Mad2B protein leads to damaged nuclei following cisplatin-induced DNA damage. Mad2B/Rev7 depletion causes the accumulation of damaged nuclei, thereby accelerating apoptosis in human cancer cells in response to cisplatin-induced DNA damage. Therefore, our results suggest that Mad2B may be a critical modulator of DNA damage response.

• The Journal of the Korean Society for Microbiology
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• v.16 no.1
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• pp.71-82
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• 1981

An electron microscopic study was carried out on the morphogenesis of herpes simplex type 2 virus in BHK-21 cells BHK-21 cells was found susceptible to infection and replication of herpes simplex type 2 virus cytopathic effects of the herpes type appeared at approximately 1 day postinoculation. Foci consisting of rounded refractile cells and syncytia were observed. Projection of the nuclear membrane in the infected cells was also seen, Several infected cells showed a track-shaped structure which apparently consisted of multiple layered membranes of the nucleus.

• Korean Journal of Veterinary Research
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• v.21 no.1
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• pp.41-43
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• 1981

The occurrence of inclusion body hepatitis was confirmed for the first time in Korea from chickens submitted for diagnosis to this Institute from a farm located in the vicinity of Anyang. The chickens showed no specific clinical signs except for moderate anemic conditions. At autopsy, livers were swollen and mottled with numerous stellate subcapsular hemorrhages and necrotic foci. Severe nephritis and catarrhal enteritis were also seen. The most notable microscopic changes were seen in the liver. These included eosinophilic intra-nuclear inclusion bodies in the hepatocyes, massive hemorrhages and necrosis and fatty changes in the liver parenchema.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.3
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• pp.177-185
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• 2006

Purpose: Purpose of this study is to synthesize $^{99m}Tc$-labeled transferrin for injection imaging and to compare it with $^{67}Ga$-titrate for the detection of infectious foci. Materials and methods: Succinimidyl 6-hydrazino-nicotinate hydrochloride-chitosan-transferrin (Transferrin) was synthesized and radiolabeled with $^{99m}Tc$. Labeling efficiencies of $^{99m}Tc$-Transferrin were determined at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 8 hr. Biodistribution and imaging studies with $^{99m}Tc$-Transferrin and $^{67}Ga$-citrate were performed in a rat abscess model induced with approximately $2{\times}10^8$ colony forming unit of Staphylococcus aureus ATCC 25923. Results: Successful synthesis of Transferrin was confirmed by mass spectrometry. Labeling efficiency of $^{99m}Tc$-Transferrin was $96.2{\pm}0.7%,\;96.4{\pm}0.5%,\;96.6{\pm}1.0%,\;96.9{\pm}0.5%,\;97.0{\pm}0.7%\;and\;95.5{\pm}0.7%$ at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 8 hr, respectively. The injected dose per tissue gram of $^{99m}Tc$-Transferrin was $0.18{\pm}0.01\;and\;0.18{\pm}0.01$ in the lesion and $0.05{\pm}0.01\;and\;0.04{\pm}0.01$ in the normal muscle, and lesion-to-normal muscle uptake ratio was $3.7{\pm}0.6\;and\;4.7{\pm}0.4$ at 30 min and 3 hr, respectively. On image, lesion-to-background ratio of $^{99m}Tc$-Transferrin was $2.18{\pm}0.03,\;2.56{\pm}0.11,\;3.08{\pm}0.18,\;3.77{\pm}0.17,\;4.70{\pm}0.45\;and\;5.59{\pm}0.40$ at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 10 hr and those of $^{67}Ga$-citrate was $3.06{\pm}0.84,\;4.12{\pm}0.54\;and\;4.55{\pm}0.74 $ at 2 hr, 24 hr and 48 hr, respectively. Conclusion: Transferrin is successfully labeled with $^{99m}Tc$, and its labeling efficiency was higher than 95% and stable for 8 hours. $^{99m}Tc$-Transferrin scintigraphy showed higher image quality in shorter time compared to $^{67}Ga$-citrate image. $^{99m}Tc$-transferrin is supposed to be useful in the detection of the infectious foci.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.166-171
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• 2007

GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, $GABA_{A}-receptor$ that allows chloride to pass through a ligand gated ion channel and $GABA_{B}-receptor$ that uses G-proteins for signaling. The $GABA_{A}$-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate $GABA_{A}$-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with $^{11}C-FMZ$, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, $^{18}F-fluoroflumazenil$ (FFMZ) has been developed to overcome $^{11}C's$ short half-life. $^{18}F-FFMZ$ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using $^{11}C-FMZ$ PET instead of $^{18}F-FDG$ PET, restrict the foci better and may also help find lesions better than high resolution MR. $GABA_{A}$ receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, $GAB_{A}$ imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

• Fisheries and Aquatic Sciences
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• v.9 no.3
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• pp.107-114
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• 2006

A dermal sarcoma was found in a freshwater, soft-shelled turtle Pelodiscus sinensis. The neoplasm consisted of proliferating fibrous tissue and extended from the dermis. The overlying epidermis was hyperplastic and partially folded. The deeper dermis and hypodermis contained three large, discrete necrotic foci of -10 mm diameter. Numerous eosinophilic granule cells and macro phages surrounded the necrotic areas. A mixed population of cells with nuclear pleomorphism was observed between the papillary layers of vessels. This area also had regions of different histological structures: (l) regularly arranged, spindle-shaped cells with compact nuclei in a fine-fibrillar matrix; (2) haphazardly arranged cells ($\leq$ 23 11m diameter) with ovoid, highly hypertrophic, faintly stained nuclei; and (3) cells (3.6-5.8 11m diameter) with irregularly shaped nuclei and marginal condensed chromatin in a myxomatous matrix. Some mitotic figures, binucleate cells, and multinucleate giant cells of up to 50 11m in length were also found. Flow cytometry of propidium iodide-stained cells yielded different histograms for the normal skin and the skin (primarily epidermis) and fibrous dermis of the tumor, indicating DNA heterogeneity in the dermal portion of the tumor. The ploidy indices for the dermal cells were 1.91 and 0.78, as compared to normal cells.

• Nutritional Sciences
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• v.8 no.4
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• pp.219-225
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• 2005

This study examined the effect of viable bifidobacteria and non-digestible carbohydrates on the cecal pH, colonic neoplastic lesion (aberrant crypt) and proliferating cell nuclear antigen (PCNA) labeling index in carcinogen-treated mts. Animals received s.c. injection of dimethylhydrazine (DMH) (15 mg/kg body weight) twice 3 days apart. Three days after the second carcinogen administration, the treatments were begun. 1he treatments were basal diet (AIN-76) with skim milk (Basal/skim), or the following diets with daily gavage of $10^8$ bifidobacteria: basal (Basal/bifido), $2\%$ fructo-oligosaccharide (FOS/bifido), $2\%$ soybean oligosaccharide (SBO/bifido), $2\%$ wheat bran oligosaccharide (WBO/bifido) and $8.4\%$ wheat bran (WB/bifido). After 4 weeks of treatment, cecal pH was measured using a pH probe. The number of aberrant crypt (AC), aberrant crypt foci (ACF) and crypt multiplicity were enumerated and colonic PCNA labeling index was determined using immunohistochemistry. Cecal pH was significantly reduced in SBO/bifido and FOS/bifido groups compared to control group. However, there were no significant differences in either number of AC or rates of cell proliferation as shown by PCNA labeling index among the groups, although mts fed FOS/bifido reduced the numbers of ACF compared to Basal/skim group. The SBO/bifido group did not reduce the number of ACF or PCNA labeling index. Also, other oligosaccharides did not reduce the risk of colon cancer compared to control group. The concomitant reduction of cecal pH and number of ACF suggest that the combination of bifidobacteria and FOS may reduce the risk of colon cancer.

• BMB Reports
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• v.44 no.1
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• pp.46-51
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• 2011

Osteosarcoma is a primary bone cancer which occurs mainly in children. Neuroguidin/CANu1 is a nucleolar protein involved in the maintenance of ribosomal structure. In this study, we investigated the effect of Neuroguidin/CANu1 depletion on the response of osteosarcoma cells to doxorubicin. In normal circumstances, Neuroguidin/CANu1 is localized at nucleoli, which translocates to nuclear foci in the presence of doxorubicin. shRNA knockdown of Neuroguidin/CANu1 did not affect cell viability in the absence of doxorubicin, but led to enhanced cytotoxicity in doxorubicin-treated cells. Doxorubicin increased the population of apoptotic cells by 3-fold in Neuroguidin/CANu1-depleted cells compared to that in control cells. Depletion of Neuroguidin/CANu1 mRNA induced the expression of p21 and the cleavage of PARP, leading to increased caspase-3/7 activity. Together, these results suggest that Neuroguidin/CANu1 is required for maintaining cellular homeostasis and may contribute to the improved efficiency of chemotherapy.

• Journal of Microbiology
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• v.41 no.4
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• pp.295-299
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• 2003

Adenovirus (Ad) precursor to the terminal protein (pTP) plays an essential roles in the viral DNA replication. Ad pTP serves as a primer for the synthesis of a new DNA strand during the initiation step of replication. In addition, Ad pTP forms organized spherical replication foci on the nuclear matrix (NM) and anchors the viral genome to the NM. Here we identified the interferon inducible gene product 1-8D (Inid) as a pTP binding protein by using a two-hybrid screen of a HeLa cDNA library. Of the clones obtained in this assay, nine were identical to the Inid, a 13-kDa polypeptide that shares homology with genes 1-8U and Leu-13/9-27, most of which have little known functions. The entire open reading frame (ORF) of Inid was cloned into the tetracycline inducible expression vector in order to determine the biological functions related with adenoviral infection. When Inid was introduced to the cells along with adenoviruses, fifty to sixty percent of Ad-infected cells expressing Inid had rounded morphology, which was suggestive of apoptosis. Results from the terminal deoxynucleotidyl transferase (TdT) and DNA fragmentation assays confirmed that Inid induces apoptosis in Ad-infected or in uninfected cells. The Inid binding to pTP may target the cell for apoptotic destruction as a host defense mechanism against the viral infection.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.3
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• pp.247-251
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• 2007

A 38-year-old man who was diagnosed with malignant paraganglioma underwent computed tomography (CT) and I-131 metaiodobenzylguanidine (MIBG) san. CT showed extensive lymph node enlargement in right iliac area and retroperitoneum with severe hydronephrosis and mass on posterior bladder wall. However, I-131 MIBG scan didn't showed abnormal uptake. He also underwent F-18 fluorodeoxyglucose (FDG) positron emisson tomography/CT for localizing accurate tumor site. F-18 FDG PET/CT showed multiple metastases of left supraclavicular, hilar, mediastinal para-aortic, inguinal, right iliac lymph nodes, lung, vertebrae, and pelvis. There are a few reports showing that the F-18 FDG PET/CT is helpful for staging and localizing tumor site of patients who are diagnosed with negative on the MIBG scans. Thus, we report a case with paraganglioma which showed negative I-131 MIBG scan, but revealed multiple intense hypermetabolic foci in F-18 FDG PET/CT.