• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.3
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• pp.262-267
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• 2007

Implantation of allografts has increased widely with not only the availability of many allogenic bone but also allogenic soft tissues. The aim of tissue banking is to provide surgeons with safe tissues compatible with their intended clinical application. The incidence of tissue transplant-transmitted infection is unknown and can only be inferred from prospective studies. The possibility of donor-to-recipient disease transmission through soft tissue transplantation can be considered by reviewing the risk associated with other transplanted hard tissues. Viral, bacterial, and fungal infections have been transmitted via transplantation of soft tissue allografts such as skin, cornea, dura, pericardium. fascia lata, and heart valves. Corneas have transmitted rabies, Creutzfeldt-Jakob disease (CJD), hepatitis B (HBV), cytomegalovirus (CMV), herpes simplex virus (HSV), bacteria, and fungi. Heart valves have been implicated in transmitting tuberculosis, hepatitis B. HIV-1 and CMV. CJD has been transmitted by dura and pericardium transplants. Skin has transmitted CMV, bacteria, and fungi. Cadaveric skin, pericardium, dura, and fascia lata have been used in dental patients with intra-oral soft tissue injuries and GBR. This study is review of the considering transmission of infectious disease in allogenic soft tissues and guidelines of reducing the risk. Prior to use, many tissues are exposed to antibiotics, disinfectants, and sterilants, which further reduce or remove the risk of transmitted disease. Because some soft tissue grafts cannot be subjected to sterilization steps, the risk of infectious disease transmission remains and thorough donor screening and testing is especially important.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.4
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• pp.218-227
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• 2006

Purpose: The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), $9-(4-[^{18}F]Fluoro-3-hydroxymethylbutyl)$guanine ($[^{18}F]FHBG$) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. Materials and Methods: Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with $K[^{18}F]/K2.2.2.$ in acetonitrile using N2-monomethoxytrityl-9-14-(tosyl)-3-monomethoxytritylmethylbutyl]guanine as a precursor, followed by deprotection with 1 N HCl. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of $[^{18}F]FHBG$ were performed, and was analyzed correlation between $[^{18}F]FHBG$ uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor bearing Balb/c-nude mouse model. Results: $[^{18}F]FHBG$ was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiothemical yield was about 20-25%) (corrected for decay), radiochemical purity was >95% and specific activity was around >55.5 $GBq/{\mu}\;mol$. Specific accumulation of $[^{18}F]FHBG$ was observed in HSV1-tk gene transduced MCA-tk cells but not in MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked $[^{18}F]FHBG$ was retained inside of cells. The uptake of $[^{18}F]FHBG$ was showed a highly significant linear correlation ($R^2=0.995$) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors. Conclusion: $[^{18}F]FHBG$ appears to be a useful as non-invasive PET imaging substrate in HSV1-tk expressing hepatoma model.

• The Korean Journal of Nuclear Medicine Technology
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• v.15 no.2
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• pp.72-75
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• 2011

Purpose: The HSV1-tk reporter gene system is the most widely used system because of its advantage is that it is possible to monitor directly without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. This study was performed to automate 9-(4-[$^{18}F$] Fluoro-3-hydroxymethylbutyl) guanine ([$^{18}F$] FHBG) that are widely used as substrate for the HSV1-tk reporter gene in living organisms with positron emission tomography (PET) and find the optimized conditions of synthesis. Materials and Methods: Fully automated synthesis of [$^{18}F$] FHBG was performed using Explora-RN (CTI, USA) module. We have changed of reaction time (3, 5, 10 min) and temperature (110, 120, $130^{\circ}C$) for the optimized conditions of synthesis. Also we experimented to find the optimal concentration of precursor (5, 7, 10 mg). Results: [$^{18}F$] FHBG was purified by HPLC system and collected at around 10-12 min. Synthesis using Explora-RN module showed a $32.0{\pm}1.2%$ yield of radiochemical (decay corrected), the purity was greater than 98%. And the entire synthesis time was less than 48 min. Temperature of the highest synthesis yield was $130^{\circ}C$, reaction time was 5 minutes and concentration of precursor was 10 mg (recommended volume in manual) (n=36). In contrast to radiochemical yield of precursor 10 mg ($32{\pm}1.2%$), yield of 5 and 7 mg precursor was unstable. Conclusion: Automation of [$^{18}F$] FHBG synthesis at Explora-RN module has been completed. In addition, we were able to obtain optimized reaction time, temperature and concentration of precursor. Therefore this study would be provided more rapid synthesis and higher radiochemical yield.

• Molecules and Cells
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• v.38 no.9
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• pp.773-780
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• 2015

3D8 single chain variable fragment (scFv) is a recombinant monoclonal antibody with nuclease activity that was originally isolated from autoimmune-prone MRL mice. In a previous study, we analyzed the nuclease activity of 3D8 scFv and determined that a HeLa cell line expressing 3D8 scFv conferred resistance to herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PRV). In this study, we demonstrate that 3D8 scFv could be delivered to target tissues and cells where it exerted a therapeutic effect against PRV. PRV was inoculated via intramuscular injection, and 3D8 scFv was injected intraperitoneally. The observed therapeutic effect of 3D8 scFv against PRV was also supported by results from quantitative reverse transcription polymerase chain reaction, southern hybridization, and immunohistochemical assays. Intraperitoneal injection of 5 and $10{\mu}g$ 3D8 scFv resulted in no detectable toxicity. The survival rate in C57BL/6 mice was 9% after intramuscular injection of 10 $LD_{50}$ PRV. In contrast, the 3D8 scFv-injected C57BL/6 mice showed survival rates of 57% ($5{\mu}g$) and 47% ($10{\mu}g$). The results indicate that 3D8 scFv could be utilized as an effective antiviral agent in several animal models.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.8 no.1
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• pp.41-48
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• 2005

Purpose: Non-A, B, C viral hepatitis is the name given to the disease with clinical viral hepatitis, but in which serologic evidence of A, B, C hepatitis has not been found. Little is known about the etiology and clinical features of non-A, B, C viral hepatitis in children. Methods: A clinical analysis of 45 cases with non-A, B, C viral hepatitis who were admitted to the Department of Pediatrics, Pusan National University Hospital, from January 2001 to June 2004 was carried out retrospectively. Patients who were positive for HBsAg, anti-HAV and anti-HCV and had toxic, metabolic, autoimmune, or neonatal hepatitis were excluded in this study. Results: Among 45 cases of non-A, B, C viral hepatitis, the etiology was unknown in 26 (57.8%), CMV (cytomegalovirus) in 14 (31.1%), EBV (Epstein Barr virus) in 2 (4.4%), HSV (herpes simplex virus) in 2 (4.4%) and RV (rubella virus) in 1 (2.2%). Twenty seven out of 45 (60.0%) patients were under 1 year of age. Sixteen (33.3%) patients had no specific clinical symptoms and were diagnosed incidentally. On physical examination, twenty seven out of 45 patients (60.0%) had no abnormal findings. Forty three out of 45 patients (95.6%) showed classic clinical course of acute viral hepatitis, whereas fulminant hepatitis developed in two patients. Mean serum ALT (alanine aminotransferase) level was $448.7{\pm}771.9IU/L$. Serum ALT level was normalized in 31 out of 45 patients (81.6%) within 6 months and all patients within 18 months. Aplastic anemia was complicated in a case. Conclusion: Although most patients with non-A, B, C viral hepatitis showed a good prognosis, a careful follow-up would be necessary because some of them had a clinical course of chronic hepatitis, fulminant hepatitis and severe complication such as aplastic anemia.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.8 no.2
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• pp.213-221
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• 2005

Purpose: Hemophagocytic syndrome (HPS) is characterized by persistent high fever, hepatosplenomegaly, cytopenias, hypertriglyceridemia, and/or hypofibrinogenemia. Hepatic manifestations including overt hepatic failure and fulminant hepatitis are common in HPS. Liver transplantation (LT) should be considered in a case of fulminant hepatitis by other than HPS, but LT is contraindicated and complete cure is possible by chemotherapy in HPS. Therefore, we conducted this study to define the characteristics of HPS presenting as severe acute hepatitis. Methods: Among the total of 23 patients diagnosed as HPS by bone marrow examination between 1994 and 2005 in Asan Medical Center, 11 cases presented as severe acute hepatitis were enrolled in this study. We analyzed the clinical features, laboratory findings and outcome retrospectively. Results: Seven (64%) of the 11 children with HPS and hepatitis were referred to pediatric gastroenterologist at first. The mean age of onset was 50 months. There was no case with family history of primary HPS. Epstein-Barr virus was positive in 4, and herpes Simplex virus was positive simultaneously in 1 case. As the presenting symptoms and signs, fever was present in 10, hepatosplenomagaly was noted in all and jaundice in 10. Anemia was observed in 10, thrombocytopenia in 10, leukopenia in 8, hypertriglyceridemia in 9, hypofibrinogenemia in 8 and hyperferritinemia in 7 cases, respectively. Nine children received chemotherapy including etopside. The overall mortality rate was 72% (8/11). Conclusion: HPS, which needs chemotherapy, should be considered as a cause of severe acute hepatitis especially when accompanied with prolonged high fever and cytopenias.