• Clinical and Experimental Vaccine Research
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• 제12권1호
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• pp.60-69
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• 2023

Purpose: Although the fast development of safe and effective messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 has been a success, waning humoral immunity has led to the recommendation of booster immunization. However, knowledge of the humoral immune response to different booster strategies and the association with adverse reactions is limited. Materials and Methods: We investigated adverse reactions and anti-spike protein immunoglobulin G (IgG) concentrations among health care workers who received primary immunization with mRNA-1273 and booster immunization with mRNA-1273 or BNT162b2. Results: Adverse reactions were reported by 85.1% after the first dose, 94.7% after the second dose, 87.5% after a third dose of BNT162b2, and 86.0% after a third dose of mRNA-1273. They lasted for a median of 1.8, 2.0, 2.5, and 1.8 days, respectively; 6.4%, 43.6%, and 21.0% of the participants were unable to work after the first, second, and third vaccination, respectively, which should be considered when scheduling vaccinations among essential workers. Booster immunization induced a 13.75-fold (interquartile range, 9.30-24.47) increase of anti-spike protein IgG concentrations with significantly higher concentrations after homologous compared to heterologous vaccination. We found an association between fever, chills, and arthralgia after the second vaccination and anti-spike protein IgG concentrations indicating a linkage between adverse reactions, inflammation, and humoral immune response. Conclusion: Further investigations should focus on the possible advantages of homologous and heterologous booster vaccinations and their capability of stimulating memory B-cells. Additionally, understanding inflammatory processes induced by mRNA vaccines might help to improve reactogenicity while maintaining immunogenicity and efficacy.

• Nuclear Engineering and Technology
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• 제56권6호
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• pp.2195-2207
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• 2024

To enhance skeletal dosimetry in conjunction with the adult mesh-type reference Korean phantoms (MRKPs), Korean/Asian photon fluence-to-skeletal dose response functions (DRFs) were established utilizing an updated version of micro-CT-based detailed bone models from Tsinghua University. These bone models were incorporated into the MRKPs using the parallel geometry feature of Geant4. We calculated bone-site-specific electron absorbed fractions and used them to generate DRFs, following a similar methodology employed for ICRP-116 DRFs that have been used with the ICRP reference phantoms for skeletal dosimetry. To assess dosimetric implications of the Korean/Asian DRFs, we calculated RBM and BE doses for the MRKPs exposed to photon beams in the antero-posterior direction using the Korean/Asian and ICRP-116 DRFs. For energies ≥200 keV, the Korean/Asian DRFs-based skeletal doses exhibited excellent agreement with the ICRP-116 DRFs-based skeletal doses, attributed to the existence of charged particle equilibrium across the bone site. Conversely, significant differences of up to ~2.3 times were observed at lower energies, due to differences in the skeletal tissue distributions of bone models used to derive the Korean/Asian and ICRP-116 DRFs. The DRFs established in this study are expected to yield more accurate skeletal doses for Korean and Asian populations compared to the ICRP-116 DRFs.

• The Korean journal of internal medicine
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• 제39권2호
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• pp.338-346
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• 2024

Background/Aims: Systemic lupus erythematosus (SLE) responder index (SRI)-4 response has been achieved with belimumab treatment in patients with moderate disease activity in cornerstone clinical trials and following studies. However, most studies involved patients treated with a mean prednisolone-equivalent dose of approximately 10 mg/d and focused on the steroid-sparing effect of belimumab. We aimed to identify the effect of belimumab in patients with mild-to-moderate SLE who were treated with low-dose or no corticosteroids. Methods: We retrospectively reviewed the electronic medical records of patients treated with belimumab for at least 6 months between May 2021 and June 2022. The primary endpoint was SRI-4 response at 6 months. Results: Thirty-one patients were included (13 low dose- and 18 steroid non-users). The mean age was 39.2 ± 11.4 years, and 90.3% of patients were female. The baseline Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score was 6.0 (4.0-9.0). The primary endpoint was achieved in 32.3% (10/31) of patients. Significant improvements in anemia, C4 levels, and SELENA-SLEDAI score were observed during treatment. Univariate analysis showed that the baseline SELENA-SLEDAI and arthritis were significantly associated with SRI-4 response at 6 months, and only the SELENA-SLEDAI remained significant (p = 0.014) in multivariate analysis. Conclusions: This cohort study is the first to report the efficacy of belimumab after minimizing the effect of corticosteroids. Belimumab showed efficacy in improving the SELENA-SLEDAI score, anemia, and low C4 in patients who did not receive corticosteroids or received only low doses.

• 대한예방의학회:학술대회논문집
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• 대한예방의학회 1994년도 교수 연수회(환경)
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• pp.431-438
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• 1994

As currently conducted, standard rodent bioassays do not provide sufficient information to assess carcinogenic risk to humans at doses thousands of times below the maximum tolerated dose. Recent analyses indicate that measures of carcinogenic potency from these tests are restricted to a narrow range about the maximum tolerated dose and that information on shape of the dose-response is limited in experiments with only two doses and a control. Extrapolation from high to low doses should be based on an understanding of the mechanisms of carcinogenesis. We have postulated that administration of the maximum tolerated dose can increase mitogenesis which, in turn. increases rates of mutagenesis and, thus, carcinogenesis. The animal data are consistent with this mechanism, because about half of all chemicals tested are indeed rodent carcinogens, and about 40% of the positives are not detectably mutagenic. Thus, at low doses where cell killing does not occur, the hazards to humans of rodent carcinogens may be much lower than commonly assumed. In contrast, for high-dose exposures in the workplace, assessment of hazard requires comparatively little extrapolation. Nevertheless. permitted workplace exposures are sometimes close to the tumorigenic dose-rate in animal tests. Regulatory policy to prevent human cancer has primarily addressed synthetic chemicals, yet similar proportions of natural chemicals and synthetic chemicals test positive in rodent studies as expected from an understanding of toxicological defenses, and the vast proportion of human exposures are to natural chemicals. Thus, human exposures to rodent carcinogens are common. The natural chemicals are the control to evaluate regulatory strategies, and the possible hazards from synthetic chemicals should be compared to the possible hazards from natural chemicals. Qualitative extrapolation of the carcinogenic response between species has been investigated by comparing two closely related species: rats and mice. Overall predictive values provide moderate confidence in interspecies extrapolation; however, knowing that a chemical is positive at any site in one species gives only about a 50% chance that it will be positive at the same site in the other species.

• Biomolecules & Therapeutics
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• 제8권1호
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• pp.78-83
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• 2000

The objective of this study was to prevalidate the Organization for Economic Cooperation and Development's (OECD) rodent uterotrophic assay as a test method for screening of potential endocrine disrupting chemicals (EDCs). This study was conducted exactly as described in the OECD protocol documents. A positive control substance, 17$\alpha$-ethinyl estradiol (EE), was administered daily for three days to ovariectomized (OVX) Sprague-Dawley rats at various doses for determine the dose-response curve. Additionally, a pure antiestrogenic chemical, ZM189, 154 was administered to OVX rats at the same time EE to determine the effectiveness of the material against blocking the estrogenic effects of EE. At higher concentration of EE (10 $\mu\textrm{g}$/kg), a statistically significant difference in body weight gain and food consumption was observed compared to vehicle controls. In uterine responses, EE produced a dose-related increase in uterus weights compared to vehicle control. These increases were statistically significant at the >1.0 $\mu\textrm{g}$/kg doses. However, a similar dose-response relationship was not observed in vagina weight. A comparison of the two groups receiving ZM189,154 (0.1 and 1.0 mg/kg) with 0.3 $\mu\textrm{g}$/kg of EE and the group receiving only 0.3 $\mu\textrm{g}$/kg of EE showed dose-related decreases in uterus weights. However, statistical significance was shown in 1.0 mg/kg of ZM189,154. In conclusion, administration of EE produced a dose-related increase in uterine (wet and blotted) weights. Additionally, the 1.0mg/kg dose of ZM189,154 was effective in blocking the estrogenic activity of EE. These data suggest 3-day uterotrophic assay using OVX rats may serve as a good tool for EDCs screening.

• 대한방사선기술학회지:방사선기술과학
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• 제25권1호
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• pp.73-76
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• 2002

In order to evaluate the exposure to the radiologic technologists from patients who had been administrated with radiopharmaceuticals, we measured the spatial dose rates at 5 cm, 50 cm, and 100 cm from skin surface of patients using an proportional digital surveymeter, both 5 min after injection and right before the studies. In results, the exposure to the technologists in each procedure was small, compared nth the dose limits of the medical workers. However, the dose-response relationships in cancer and hereditary effects, referred to as the stochastic effects, have been assumed linear and no threshold models ; therefore, the exposure should be minimized. For this purpose, the measurements of spatial dose rate distributions were thought to be useful.

• 약학회지
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• 제35권5호
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• pp.401-415
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• 1991

Effects of quercetin on the specific and non-specific immune responses were studied in vivo. Quercetin at a dose of 2.5, 5, 10, 20 and 40 mg/kg were orally administered to ICR male mice once daily for 28 consecutive days. Cyclophosphamide was injected intraperitoneally to ICR mice with a single dose of 5 mg/kg 2 days before secondary immunization. Mice were sensitized and challenged with sheep red blood cells (S-RBC). Immune responses were evaluated by humoral and cellular immune reponses and non-specific immune response. The results of this study were summarized as followings; 1. Quercetin significantly decreased the body weight, and introduced the atrophy of liver, spleen and thymus gland dose-dependently, but increased the numbers of white blood cell. 2. Querectin significantly depressed the hemagglutination titer, Arthus reaction and hemolytic plaque forming cell. 3. Quercetin significantly depressed the delayed type hypersensitivity and rosette forming cell. 4. Quercetin at a dose of 2.5, 5 and 40 mg/kg significantly depressed phagocytic activity. 5. Quercetin at a dose of 10 and 20 mg/kg significantly increased natural killer cell activity.

• 한국식품위생안전성학회지
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• 제29권4호
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• pp.299-304
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• 2014

본 연구는 정량적 미생물 위해평가(Quantitative microbial risk assessment: QMRA)에 절대적으로 필요하지만 국내의 경우 관련 정보 및 자료가 부족한 주요 식중독 원인 미생물에 대한 용량-반응모델(dose-response models) 관련 자료를 수집 정리하여 가장 적합한 용량-반응 모델을 분석 및 선정하였다. 1980년부터 2012년까지 식중독 발생과 관련이 있는 26종의 세균, 9종의 바이러스, 8종의 원생동물관련 용량-반응 모델 및 위해평가 자료들을 중심으로 국내 NDSL (National Digital Science Library), 국외 PubMed, ScienceDirect database에서 총 193개의 논문을 추출하여 정리하였다. 조사된 자료로부터 세균별, 바이러스별, 원생동물별 용량-반응 모델의 미생물 위해평가 활용여부를 확인하고, 위해평가에 활용된 모델들을 메타분석(meta-analysis)에서 사용되고 있는 Relative frequency (fi, 상대빈도 값)를 계산하여 가장 적정한 용량-반응 모델을 제시하였다. 주요 식중독 원인 미생물들인 Campylobacter jejuni, pathogenic E. coli O157:H7 (EHEC / EPEC / ETEC), Listeria monocytogenes, Salmonella spp., Shigella spp., Staphylococcus aureus, Vibrio parahaemolyticus, Vibrio cholera, Rota virus, Cryptosporidium pavum의 적정 용량-반응 모델은 beta-poisson (${\alpha}=0.15$, ${\beta}=7.59$, fi = 0.72), beta-poisson (${\alpha}=0.49$, ${\beta}=1.81{\times}10^5$, fi = 0.67) / beta-poisson (${\alpha}=0.22$, ${\beta}=8.70{\times}10^3$, fi = 0.40) / beta-poisson (${\alpha}=0.18$, ${\beta}=8.60{\times}10^7$, fi = 0.60), exponential ($r=1.18{\times}10^{-10}$, fi = 0.14), beta-poisson (${\alpha}=0.11$, ${\beta}=6,097$, fi = 0.09), beta-poisson (${\alpha}=0.21$, ${\beta}=1,120$, fi = 0.15), exponential ($r=7.64{\times}10^{-8}$, fi = 1.00), beta-poisson (${\alpha}=0.17$, ${\beta}=1.18{\times}10^5$, fi = 1.00), beta-poisson (${\alpha}=0.25$, ${\beta}=16.2$, fi = 0.57), exponential ($r=1.73{\times}10^{-2}$, fi = 1.00), and exponential ($r=1.73{\times}10^{-2}$, fi = 0.17)로 각각 선정하였다. 본 연구에서 제시된 용량-반응 모델들은 향후 국내 QMRA 관련 연구 및 진행에 많은 도움이 될 것으로 기대된다.

• 월간산업보건
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• 통권368호
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• pp.14-15
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• 2018

• Radiation Oncology Journal
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• 제7권1호
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• pp.45-50
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• 1989

From Feb.1985 to Feb.1988,76 patients with squamous cell carcinoma of the lung treated at the Department of Therapeutic Radiology in Kyungpook National University Hospital were available for the analysis of this study. All patients received radiation of 4000cGy-6600cGy with curative aim. The overall rate of complete response was 25.0% and partial response was 452.6% The complete and partial regression of tumor was 14.3% in patients treated with dose below 5000cGy and 84.1% in the group treated with dose above 5000cGy (p<0.01). The complete response was seen only in the group of patients received radiation at least 6000cGy. The patterns of failure were as follows. The rate of initial intrathoracic recurrence was 52.6% in patients with complete response. The overall rate of failure was 68.8%. Distant metastasis was found in 47.4% of patients. Bone, contralateral lung, and brain were common metastatic sites in decreasing order All of the distant metastases and 80% of local recurrences were found within the first year after treatment.