• IMMUNE NETWORK
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• v.23 no.2
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• pp.17.1-17.16
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• 2023

Latent membrane protein 2A (LMP2A), a latent Ag commonly expressed in Epstein-Barr virus (EBV)-infected host cells, is a target for adoptive T cell therapy in EBV-associated malignancies. To define whether individual human leukocyte antigen (HLA) allotypes are used preferentially in EBV-specific T lymphocyte responses, LMP2A-specific CD8⁺ and CD4⁺ T cell responses in 50 healthy donors were analyzed by ELISPOT assay using artificial Ag-presenting cells expressing a single allotype. CD8⁺ T cell responses were significantly higher than CD4⁺ T cell responses. CD8⁺ T cell responses were ranked from highest to lowest in the order HLA-A, HLA-B, and HLA-C loci, and CD4⁺ T cell responses were ranked in the order HLA-DR, HLA-DP, and HLA-DQ loci. Among the 32 HLA class I and 56 HLA class II allotypes, 6 HLA-A, 7 HLA-B, 5 HLA-C, 10 HLA-DR, 2 HLA-DQ, and 2 HLA-DP allotypes showed T cell responses higher than 50 spot-forming cells (SFCs)/5×105 CD8⁺ or CD4⁺ T cells. Twenty-nine donors (58%) showed a high T cell response to at least one allotype of HLA class I or class II, and 4 donors (8%) had a high response to both HLA class I and class II allotypes. Interestingly, we observed an inverse correlation between the proportion of LMP2A-specific T cell responses and the frequency of HLA class I and II allotypes. These data demonstrate the allele dominance of LMP2A-specific T cell responses among HLA allotypes and their intra-individual dominance in response to only a few allotypes in an individual, which may provide useful information for genetic, pathogenic, and immunotherapeutic approaches to EBV-associated diseases.

• Journal of Korean Medicine Rehabilitation
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• v.34 no.2
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• pp.15-28
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• 2024

Objectives We used the D-galactose (D-gal) induced C2C12 myoblast senescence model to investigate whether ethanol extract of Perilla. fructescens leaves (EEPF) could delay cellular senescence and regulate related mechanisms. Methods C2C12 myogenic cells were cultured in an incubator under 37 ℃ and 5% CO₂ conditions. EEPF, dried perilla leaves were pulverized and extracted at 1:10 (v/v) at 50 ℃ for 4 hours. Cell counting kit-8 and western blot analysis was performed. Annexin V-FITC apoptosis detection kit and DAPI staining was applied. Catalase (CAT), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and malondialdehyde analysis kits were used. To measure the level of reactive oxygen species generation, staining and flow cytometry was used. To analyze the mitochondrial activity, membrane potential changes were measured using JC-1. 𝛽-gal activity was analyzed using SA-𝛽-gal staining solution, and DNA damage was analyzed by using 𝛾-H2AX. Quantikine ELISA kit was used to analyze inflammatory cytokine production. Results According to the results of this study, EEPF significantly alleviated the decrease in cell viability in C2C12 cells treated with D-gal and suppressed the decrease in the expression of proliferating cell nuclear antigen. EEPF also markedly blocked D-gal-induced C2C12 cell apoptosis and restored reduced activity of CAT, GSH-Px, T-AOC, SOD. In addition, EEPF suppressed the decrease in 𝛽-galactosidase activity, the induction of DNA damage and the increase in expression of senescence-associated secretory phenotype proteins such as p16, p53 and p21 in D-gal-treated C2C12 cells. Furthermore, EEPF significantly attenuated D-gal-induced production and expression of inflammatory cytokines such as interleukin (IL)-6 and IL-18. Conclusions The results of this study indicate that EEPF can be used as a potential candidate for the prevention and treatment of muscle aging.

• Korean Journal of Radiology
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• v.25 no.2
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• pp.179-188
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• 2024

Objective: ¹⁷⁷Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [¹⁷⁷Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [¹⁷⁷Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [¹⁷⁷Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organand tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. Results: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. Conclusion: [¹⁷⁷Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

• Korean Journal of Radiology
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• v.24 no.11
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• pp.1102-1113
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• 2023

Objective: To elucidate the use of radiological studies, including nuclear medicine, and biopsy for the diagnosis and staging of prostate cancer (PCA) in clinical practice and understand the current status of PCA in Asian countries via an international survey. Materials and Methods: The Asian Prostate Imaging Working Group designed a survey questionnaire with four domains focused on prostate magnetic resonance imaging (MRI), other prostate imaging, prostate biopsy, and PCA backgrounds. The questionnaire was sent to 111 members of professional affiliations in Korea, Japan, Singapore, and Taiwan who were representatives of their working hospitals, and their responses were analyzed. Results: This survey had a response rate of 97.3% (108/111). The rates of using 3T scanners, antispasmodic agents, laxative drugs, and prostate imaging-reporting and data system reporting for prostate MRI were 21.6%-78.9%, 22.2%-84.2%, 2.3%-26.3%, and 59.5%-100%, respectively. Respondents reported using the highest b-values of 800-2000 sec/mm² and fields of view of 9-30 cm. The prostate MRI examinations per month ranged from 1 to 600, and they were most commonly indicated for biopsy-naïve patients suspected of PCA in Japan and Singapore and staging of proven PCA in Korea and Taiwan. The most commonly used radiotracers for prostate positron emission tomography are prostate-specific membrane antigen in Singapore and fluorodeoxyglucose in three other countries. The most common timing for prostate MRI was before biopsy (29.9%). Prostate-targeted biopsies were performed in 63.8% of hospitals, usually by MRI-ultrasound fusion approach. The most common presentation was localized PCA in all four countries, and it was usually treated with radical prostatectomy. Conclusion: This survey showed the diverse technical details and the availability of imaging and biopsy in the evaluation of PCA. This suggests the need for an educational program for Asian radiologists to promote standardized evidence-based imaging approaches for the diagnosis and staging of PCA.

• IMMUNE NETWORK
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• v.21 no.5
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• pp.34.1-34.16
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• 2021

Sjögren's syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and eyes. The glandular dysfunction in SS involves not only T cell-mediated destruction of the glands but also autoantibodies against the type 3 muscarinic acetylcholine receptor or aquaporin 5 (AQP5) that interfere with the secretion process. Studies on the breakage of tolerance and induction of autoantibodies to these autoantigens could benefit SS patients. To break tolerance, we utilized a PmE-L peptide derived from the AQP5-homologous aquaporin of Prevotella melaninogenica (PmAqp) that contained both a B cell "E" epitope and a T cell epitope. Repeated subcutaneous immunization of C57BL/6 mice with the PmE-L peptide efficiently induced the production of Abs against the "E" epitope of mouse/human AQP5 (AQP5E), and we aimed to characterize the antigen specificity, the sequences of AQP5E-specific B cell receptors, and salivary gland phenotypes of these mice. Sera containing anti-AQP5E IgG not only stained mouse Aqp5 expressed in the submandibular glands but also detected PmApq and PmE-L by immunoblotting, suggesting molecular mimicry. Characterization of the AQP5E-specific autoantibodies selected from the screening of phage display Ab libraries and mapping of the B cell receptor repertoires revealed that the AQP5E-specific B cells acquired the ability to bind to the Ag through cumulative somatic hypermutation. Importantly, animals with anti-AQP5E Abs had decreased salivary flow rates without immune cell infiltration into the salivary glands. This model will be useful for investigating the role of anti-AQP5 autoantibodies in glandular dysfunction in SS and testing new therapeutics targeting autoantibody production.

• The Korean Journal of Nuclear Medicine Technology
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• v.27 no.2
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• pp.111-127
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• 2023

Purpose: Gallium-68 (⁶⁸Ga) is increasingly used in nuclear medicine imaging for various conditions such as lymphoma and neuroendocrine tumors by labeling tracers like Prostate Specific Membrane Antigen (PSMA) and DOTA-TOC. However, compared to Fluorine-18 (¹⁸F) used in conventional nuclear medicine imaging, ⁶⁸Ga has lower spatial resolution and relatively higher Signal to Background Ratio (SBR). Therefore, this study aimed to investigate the optimized parameters and reconstruction methods for PET/CT imaging using the ⁶⁸Ga radiotracer through model-based image evaluation. Materials and Methods: Based on clinical images of ⁶⁸Ga-PSMA PET/CT, a NEMA/IEC 2008 PET phantom model was prepared with a Hot vs Background (H/B) ratio of 10:1. Images were acquired for 9 minutes in list mode using DMIDR (GE, Milwaukee WI, USA). Subsequently, reconstructions were performed for 1 to 8 minutes using OS-EM (Ordered Subset Expectation Maximization) + TOF (Time of Flight) + Sharp IR (VPFX-S), and BSREM (Block Sequential Regularized Expectation Maximization) + TOF + Sharp IR (QCFX-S-400), followed by comparative evaluation. Based on the previous experimental results, images were reconstructed for BSREM + TOF + Sharp IR / 2 minutes (QCFX-S-2min) with varying β-strength values from 100 to 700. The image quality was evaluated using AMIDE (freeware, Ver.1.0.1) and Advanced Workstation (GE, USA). Results: Images reconstructed with QCFX-S-400 showed relatively higher values for SNR (Signal to Noise Ratio), CNR (Contrast to Noise Ratio), count, RC (Recovery Coefficient), and SUV (Standardized Uptake Value) compared to VPFX-S. SNR, CNR, and SUV exhibited the highest values at 2 minutes/bed acquisition time. RC showed the highest values for a 10 mm sphere at 2 minutes/bed acquisition time. For small spheres of 10 mm and 13 mm, an inverse relationship between β-strength increase and count was observed. SNR and CNR peaked at β-strength 400 and then decreased, while SUV and RC exhibited a normal distribution based on sphere size for β-strength values of 400 and above. Conclusion: Based on the experiments, PET/CT imaging using the ⁶⁸Ga radiotracer yielded the most favorable quantitative and qualitative results with a 2 minutes/bed acquisition time and BSREM reconstruction, particularly when applying β-strength 400. The application of BSREM can enhance accurate quantification and image quality in ⁶⁸Ga PET/CT imaging, and an optimization process tailored to each institution's imaging objectives appears necessary.

• Journal of the Korean Applied Science and Technology
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• v.41 no.2
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• pp.159-171
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• 2024

This study confirmed the antioxidant activity and antimicrobial efficacy and formulation stability for the effectiveness experiment of Rumex crispus. L root extract. For antioxidant activity, DPPH radical scavenging, FRAP activity, ABTS+ radical scavenging, and SOD-like activity were performed. Antimicrobial activity was evaluated for Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans strains. In addition, skin containing Rumex crispus. L root extract is checked over time for pH, temperature, and daylight for 21 days. As a result of antioxidant evaluation, it was confirmed that the activity increased in a concentration-dependent manner at a concentration of 0.0625-1 mg/mL. The clear zones of each bacterium at 100mg/mL concentrations were 10.45±0.34, 9.77±0.59, 9.92±0.22, and 10.08±0.12, which were superior to the control group Methyl paraben, and the antibacterial power of S. aureus and E. coli was confirmed at 100mg/mL concentration for MIC. There was little change in absorbance when the pH of the skin was 4.0, 6.0, and 7.0 and At 4℃, 25℃, and 40℃, it was discolored as the temperature increased. It was also observed that discoloration occurred when exposed to daylight. This is presumed to be able to prevent discoloration when it is shielded and stored at low temperatures. When the results of this study are summarized, Rumex crispus. L root extract is considered to have high value in use as a cosmetic raw material that can expect antioxidant and antibacterial activities.

• Journal of the Health Care and Life Science
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• v.10 no.1
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• pp.89-98
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• 2022

This study conducted a survey using a Google questionnaire targeting 380 male and female college students to find out the perceptions of college students about health masks at the time of transition from the COVID-19 pandemic to the recovery stage. As a result, at the time when the obligation to wear an outdoor mask was relaxed, they still wore an outdoor mask (3.63±1.34). As for the reasons for wearing a mask, 27.8% said 'wearing a mask became a habit' and 'fear of infection' was 19.4%. Hand washing to prevent COVID-19 was observed well (4.07±1.00), and when infection was suspected, they showed an attitude of checking for infection with a home kit or rapid antigen test (3.88±1.17). In addition, it was recognized that COVID-19 is not threatening (3.19±1.28) and that it will recover easily after infection (3.19±1.28). In a situation where the number of COVID-19 infections continues to decrease, the government is pushing for a gradual recovery of new daily life. Therefore, it is necessary to provide correct information that affects individual awareness and to promote it through various media, and I would like to emphasize the importance of education on the autonomous practice of individual quarantine rules.

• Korean Circulation Journal
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• v.54 no.6
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• pp.325-335
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• 2024

Background and Objectives: The number of sensitized heart failure patients on waiting lists for heart transplantation (HTx) is increasing. Using the Korean Organ Transplantation Registry (KOTRY), a nationwide multicenter database, we investigated the prevalence and clinical impact of calculated panel-reactive antibody (cPRA) in patients undergoing HTx. Methods: We retrospectively reviewed 813 patients who underwent HTx between 2014 and 2021. Patients were grouped according to peak PRA level as group A: patients with cPRA ≤10% (n= 492); group B: patients with cPRA >10%, <50% (n=160); group C patients with cPRA ≥50% (n=161). Post-HTx outcomes were freedom from antibody-mediated rejection (AMR), acute cellular rejection, coronary allograft vasculopathy, and all-cause mortality. Results: The median follow-up duration was 44 (19-72) months. Female sex, re-transplantation, and pre-HTx renal replacement therapy were independently associated with an increased risk of sensitization (cPRA ≥50%). Group C patients were more likely to have longer hospital stays and to use anti-thymocyte globulin as an induction agent compared to groups A and B. Significantly more patients in group C had positive flow cytometric crossmatch and had a higher incidence of preformed donor-specific antibody (DSA) compared to groups A and B. During follow-up, group C had a significantly higher rate of AMR, but the overall survival rate was comparable to that of groups A and B. In a subgroup analysis of group C, post-transplant survival was comparable despite higher preformed DSA in a desensitized group compared to the non-desensitized group. Conclusions: Patients with cPRA ≥50% had significantly higher incidence of preformed DSA and lower freedom from AMR, but post-HTx survival rates were similar to those with cPRA <50%. Our findings suggest that sensitized patients can attain comparable post-transplant survival to non-sensitized patients when treated with optimal desensitization treatment and therapeutic intervention.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.4
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• pp.363-374
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• 2022

Backgrounds/Aims: To analyze the results of the neoadjuvant treatment of patients in our center with early pancreatic cancer. Methods: Eighty-four patients with early pancreatic cancer (I-II) were included, of which 59 were considered "bioborderline" (carbohydrate antigen [CA] 19-9 > 37 U/L), and 25 were considered "non-bioborderline" (CA19-9 < 37 U/L). The R0 resection rate, presence of negative nodes, survival, and recurrence rates were analyzed in two groups, the NEO group (neoadjuvant + surgery) and the nonNEO group (upfront surgery). Results: A 28.6% pathologic complete response was observed in the NEO group of the whole sample. The residual R0 was 85.7%, and nodes were negative in 78.6% of the patients in the NEO group of bioborderline patients. All non-bioborderline patients treated with neoadjuvant were R0, and no affected nodes were observed in any of them. The median overall survival (OS) in patients with elevated CA19-9 levels in the NEO group was 31.4 months vs. 13.1 months in the non-NEO (log-rank test p = 0.006), with a 62% relative reduction in the mortality rate (hazard ratio = 0.38, 95% confidence interval: 0.20-0.79; p= 0.008). The median OS in patients with normal CA19-9 levels in the NEO group was 65.9 months vs. 16.2 months in the non-NEO group, without statistically significant differences between the two but with a trend toward significance (log-rank test p = 0.08). Conclusions: A neoadjuvant strategy seemed to improve local control and the survival of patients with early pancreatic cancer, both those with elevated CA19-9 and normal marker levels.