The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves’ Disease

Background@#To determine whether baseline thyroid-stimulating immunoglobulin (TSI) bioassay or its early response upon treatment with an anti-thyroid drug (ATD) can predict prognosis of Graves’ disease (GD) in real-world practice. @*Methods@#This retrospective study enrolled GD patients who had previous ATD treatment with TSI bioassay checked at baseline and at follow-up from April 2010 to November 2019 in one referral hospital. The study population were divided into two groups: patients who experienced relapse or continued ATD (relapse/persistence), and patients who experienced no relapse after ATD discontinuation (remission). The slope and area under the curve at 1st year (AUC1yr) of thyroid-stimulating hormone receptor antibodies including TSI bioassay and thyrotropin-binding inhibitory immunoglobulin (TBII) were calculated as differences between baseline and second values divided by time duration (year). @*Results@#Among enrolled 156 study subjects, 74 (47.4%) had relapse/persistence. Baseline TSI bioassay values did not show significant differences between the two groups. However, the relapse/persistence group showed less decremental TSI bioassay in response to ATD than the remission group (–84.7 [TSI slope, –198.2 to 8.2] vs. –120.1 [TSI slope, –204.4 to –45.9], P=0.026), whereas the TBII slope was not significantly different between the two groups. The relapse/persistence group showed higher AUC1yr of TSI bioassay and TBII in the 1st year during ATD treatment than the remission group (AUC1yr for TSI bioassay, P=0.0125; AUC1yr for TBII, P=0.001). @*Conclusion@#Early changes in TSI bioassay can better predict prognosis of GD than TBII. Measurement of TSI bioassay at beginning and follow-up could help predict GD prognosis.

Awareness Survey on Community Water Fluoridation by Region / 치위생과학회지

Background@#The purpose of this study is to investigate the pro-con of re-implementation by administrative areas and the difference in perception of community water fluoridation in implemented and non-implemented areas after the community water fluoridation in Korea was suspended. Through this, we intend to provide basic data that can help find ways to increase the support and interest of local residents. @*Methods@#The 601 questionnaires collected through the survey and statistical analysis was conducted using SPSS Statistics 28.0. @*Results@#As a result of analyzing the perception of the community water fluoridation according to the understanding of fluorine, the proportion of people who were not recognized by both fluorine and community water fluoridation was the highest (p＜0.05). As a result of the analysis of the pro-con of re-implementation of community water fluoridation, the approval was high. Among those who responded in favor, the place of re-implementation showed that ‘implementation nationwide’ was high. As for the reason for favor, it was found that it was possible to prevent dental caries disease. The reason for the objection was the lack of knowledge about fluoride. @*Conclusion@#The results of the survey for the pro-con of the re-implementation of community water fluoridation showed a higher degree of ‘agree’ and showed that people in the area where community water fluoridation was not implemented showed higher interest in oral health prevention and management. Through this, not only oral education, but also correct information on the implementation method of community water fluoridation, the benefits of community water fluoridation, and the facts that were misunderstood in the past, as well as oral education, can be provided to raise interest in community water fluoridation. It is thought that the expected effect of the re-implementation of community water fluoridation can be obtained if such activities are carried out.

Evaluation and Management of Bone Health in Patients with Thyroid Diseases: a Position Statement from the Korean Thyroid Association

Thyroid hormones have an important physiological role in maintaining adult bone structure and strength. Therefore, thyroid dysfunction is inevitably associated with various degrees of skeletal consequences. Endogenous overt hyperthyroidism is an established cause of high bone turnover with accelerated bone loss, resulting in osteoporosis and an increased risk of fractures. Hyperthyroidism induced by thyroid stimulating hormone suppression therapy in patients with differentiated thyroid cancer also has emerged as a contributing factor to osteoporosis and fragility fractures. While, there is lack of evidence that hypothyroidism negatively affects bone health. Although there is growing clinical evidence of the importance of bone health in hyperthyroidism, clinical guidelines on how to evaluate and manage bone health in these diseases have not yet been published worldwide. The Task Force from the Korean Thyroid Association Committee of Clinical Practice Guideline has developed this position statement for the evaluation and management of bone health in patients with thyroid diseases, particularly focused on endogenous hyperthyroidism and thyroid stimulating hormone suppression therapyassociated hyperthyroidism in patients with differentiated thyroid cancer.

Clinical Outcome of Fine Needle Aspiration Cytology and Washout Thyroglobulin in Suspicious Lymph Nodes in Differentiated Thyroid Carcinoma: Discordant Results in Real-World Practice

Background and Objectives@#Fine needle aspiration cytology (FNAC) combined with washout thyroglobulin (Tg) measurement is the gold standard for the evaluation of metastatic lymph nodes (LNs) in thyroid cancer. However, few studies have assessed the clinical outcomes of discordant results between FNAC and washout Tg based on surgery status and follow-up imaging in real-world practice. @*Materials and Methods@#A total of 707 LNs in 512 patients who underwent FNAC and washout Tg measurements from 2015 to 2017 were analyzed. The final LN outcomes were confirmed through postoperative histology, or through metastatic FNAC findings combined with high washout Tg level, follow-up imaging studies, or repeat FNA, if LNs were not dissected. @*Results@#The cut-off values of washout Tg for indicating LN metastasis in preoperative and postoperative LNs were 9.6 ng/mL and 2.1 ng/mL. The diagnostic accuracy was improved by applying washout Tg according to surgery status and the results of discordant rate was reduced, Discordant between results of FNAC with washout Tg and final outcome were 9.2% (27/295) of preoperative LNs and 8.7% (36/412) of postoperative LNs. Due to inconclusive results, unnecessary neck dissection can occur in 13.9% (36/259 dissected cases). @*Conclusion@#To improve diagnostic accuracy, cut-off values of washout Tg should be applied depending on surgery status. New biomarkers in washout fluid is necessary to resolve discordant findings.

Protocol for a Korean Multicenter Prospective Cohort Study of Active Surveillance or Surgery (KoMPASS) in Papillary Thyroid Microcarcinoma

Background@#A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study. @*Methods@#Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases. @*Conclusion@#KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.

Clinical Outcome of Fine Needle Aspiration Cytology and Washout Thyroglobulin in Suspicious Lymph Nodes in Differentiated Thyroid Carcinoma: Discordant Results in Real-World Practice

Background and Objectives@#Fine needle aspiration cytology (FNAC) combined with washout thyroglobulin (Tg) measurement is the gold standard for the evaluation of metastatic lymph nodes (LNs) in thyroid cancer. However, few studies have assessed the clinical outcomes of discordant results between FNAC and washout Tg based on surgery status and follow-up imaging in real-world practice. @*Materials and Methods@#A total of 707 LNs in 512 patients who underwent FNAC and washout Tg measurements from 2015 to 2017 were analyzed. The final LN outcomes were confirmed through postoperative histology, or through metastatic FNAC findings combined with high washout Tg level, follow-up imaging studies, or repeat FNA, if LNs were not dissected. @*Results@#The cut-off values of washout Tg for indicating LN metastasis in preoperative and postoperative LNs were 9.6 ng/mL and 2.1 ng/mL. The diagnostic accuracy was improved by applying washout Tg according to surgery status and the results of discordant rate was reduced, Discordant between results of FNAC with washout Tg and final outcome were 9.2% (27/295) of preoperative LNs and 8.7% (36/412) of postoperative LNs. Due to inconclusive results, unnecessary neck dissection can occur in 13.9% (36/259 dissected cases). @*Conclusion@#To improve diagnostic accuracy, cut-off values of washout Tg should be applied depending on surgery status. New biomarkers in washout fluid is necessary to resolve discordant findings.

Association of serum free thyroxine and glucose homeostasis: Korea National Health and Nutrition Examination Survey

Background/Aims@#Thyroid hormones are involved in wide range of glucose metabolism functions. Overt thyroid dysfunctions are related to altered glucose homeostasis. However, it is not conclusive as to whether subtle changes in thyroid hormones within normal ranges can induce alterations in glucose homeostasis. The aim of this study was to evaluate the association between thyroid hormone and glucose homeostasis parameters in subjects without overt thyroid dysfunction based on nationwide population data. @*Methods@#In the Sixth Korea National Health and Nutrition Examination Survey 2015 (n = 7,380), data were collected from subjects with insulin and thyroid function measurements who were older than 19-years-old. After the exclusion of 5,837 subjects, a total of 1,543 patients were included in the analysis. Subjects were categorized into the quartiles of the free thyroxine (FT4). Fasting glucose, insulin, homeostatic model assessment of insulin resistance and hemoglobin A1c (HbA1c) levels were considered to be glucose homeostasis parameters. @*Results@#Subjects with the highest FT4 quartile showed significantly lower fasting insulin and HbA1c levels. A significant inverse correlation FT4 and HbA1c levels was observed (β = –0.261, p = 0.025). In the logistic regression analysis, the highest quartile of FT4 was demonstrated to lower the risk of HbA1c to a greater degree than the median by approximately 40%, after adjusting for confounders, compared to the lowest quartile (p = 0.028). @*Conclusions@#We demonstrated subjects with a lower FT4 quartile exhibited high risk of HbA1c levels above the median value in a representative Korean population. Subjects with the lowest FT4 quartile should be cautiously managed in terms of altered glucose homeostasis.

Protocol for a Korean Multicenter Prospective Cohort Study of Active Surveillance or Surgery (KoMPASS) in Papillary Thyroid Microcarcinoma

Background@#A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study. @*Methods@#Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases. @*Conclusion@#KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.

Comparison of Natural Course between Thyroid Cancer Nodules and Thyroid Benign Nodules

BACKGROUND: The natural course of thyroid cancer nodules and benign nodules is different. This study was to compare the changes in size between thyroid cancer nodules and thyroid benign nodules. The risk factors associated with the changes of thyroid cancer nodules were assessed. METHODS: This study contains retrospective observational and prospective analysis. A total of 113 patients with 120 nodules were recruited in the cancer group, and 116 patients with 119 nodules were enrolled in the benign group. Thyroid ultrasonography was performed at least two times at more than 1-year interval. RESULTS: The mean follow-up durations were 29.5±18.8 months (cancer group) and 31.9±15.8 months (benign group) (P=0.32). The maximum diameter change in length was 0.36±0.97 mm/year in the cancer group and –0.04±0.77 mm/year in the benign group (P<0.01). The volume was significantly increased in the cancer group compared with the benign group (0.06±0.18 mL/year vs. 0.004±0.05 mL/year, respectively, P<0.01; 26.9%±57.9%/year vs. 1.7%±26.0%/year, P<0.01). Initial maximum diameter (β=0.02, P<0.01) and initial volume (β=0.13, P<0.01) were significantly associated with volume change (mL)/year. Initial maximum standardized uptake value did not predict the nodule growth. CONCLUSION: It is suggested that thyroid cancer nodules progress rapidly compared with benign nodules. Initial size and volume of nodule were independent risk factors for cancer nodule growth.

FGF-17 from Hypoxic Human Wharton's Jelly-Derived Mesenchymal Stem Cells Is Responsible for Maintenance of Cell Proliferation at Late Passages

BACKGROUND AND OBJECTIVES: Although it is well known that hypoxic culture conditions enhance proliferation of human mesenchymal stem cells, the exact mechanism is not fully understood. In this study, we investigated the effect of fibroblast growth factor (FGF)-17 from hypoxic human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs) on cell proliferation at late passages. METHODS AND RESULTS: hWJ-MSCs were cultured in α-MEM medium supplemented with 10% fetal bovine serum (FBS) in normoxic (21% O₂) and hypoxic (1% O₂) conditions. Protein antibody array was performed to analyze secretory proteins in conditioned medium from normoxic and hypoxic hWJ-MSCs at passage 10. Cell proliferation of hypoxic hWJ-MSCs was increased compared with normoxic hWJ-MSCs from passage 7 to 10, and expression of secretory FGF-17 was highly increased in conditioned medium from hypoxic hWJ-MSCs at passage 10. Knockdown of FGF-17 in hypoxic and normoxic hWJ-MSCs decreased cell proliferation, whereas treatment of hypoxic and normoxic hWJ-MSCs with recombinant protein FGF-17 increased their proliferation. Signal transduction of FGF-17 in hypoxic and normoxic hWJ-MSCs involved the ERK1/2 pathway. Cell phenotypes were not changed under either condition. Differentiation-related genes adiponectin, Runx2, and chondroadherin were downregulated in normoxic hWJ-MSCs treated with rFGF-17, and upregulated by siFGF-17. Expression of alkaline phosphatase (ALP), Runx2, and chondroadherin was upregulated in hypoxic hWJ-MSCs, and this effect was rescued by transfection with siFGF-17. Only chondroadherin was upregulated in hypoxic hWJ-MSCs with rFGF-17. CONCLUSIONS: In hypoxic culture conditions, FGF-17 from hypoxic hWJ-MSCs contributes to the maintenance of high proliferation at late passages through the ERK1/2 pathway.

Risk factors for hypothyroidism in euthyroid thyroid nodule patients with lymphocytic thyroiditis on fine needle aspiration cytology

BACKGROUND/AIMS@#Lymphocytic thyroiditis as cytology diagnosis from fine needle aspiration (FNA) is frequently detected in patients with thyroid nodules. However, the clinical outcome for upcoming hypothyroid events has been rarely clarified in euthyroid patients.@*METHODS@#We retrospectively reviewed the data of patient who had lymphocytic thyroitidis on FNA cytology of thyroid nodule from January 2005 to December 2010 at a tertiary referral hospital. In total, 109 patients with follow-up thyroid function tests (TFT) were enrolled. Final outcomes included overt and subclinical hypothyroidism with thyroid stimulating hormone (TSH) levels ≥ 10 mIU/L. Potential parameters predicting clinical hypothyroidism were analyzed by multivariate analysis.@*RESULTS@#Over the mean follow-up duration of 51.6 months, 14 out of 109 patients (12.8%) developed clinical hypothyroidism that required thyroid hormone replacement. The median onset time to hypothyroidism was 16 months (range, 3 to 88) and ≥ 60% of patients experienced clinical hypothyroidism within 1 year. By multivariate analysis, background thyroiditis (relative risk [RR], 9.78; p = 0.004), thyroid peroxidase antibody positivity (RR, 9.90; p = 0.003), nodule size (RR, 1.24; p < 0.001), and initial TSH (RR, 1.47; p = 0.009) were the independent risk factors for predicting hypothyroidism in euthyroid patients.@*CONCLUSIONS@#Hypothyroidism frequently occurs during the follow-up in euthyroid patients with thyroid nodules which show lymphocytic thyroiditis on FNA cytology. Close surveillance and regular TFT are needed in high-risk patients for upcoming clinical hypothyroidism.

A Case of an AUPBD Treated by Drainage of Major Papilla / 대한췌담도학회지

Anomalous union of the pancreaticobiliary duct (AUPBD) is a rare congenital anomaly, defined as the pancreaticobiliary ductal union located outside of the duodenal wall, usually forming a markedly long common channel. This anomaly is associated with congenital choledochal cyst, carcinoma of the biliary tract and pancreatitis, and is more commonly seen in Asian than in Western countries. AUPBD is frequently accompanied by biliary dilatation, but some patients with AUPBD have no biliary dilatation. The causal relationship between AUPBD and biliary dilatation associated with this anomaly has not been fully established. Here, we report a case of type IIIc2 AUPBD without biliary duct dilatation that was treated by drainage of major papilla.

Tuberous Sclerosis Complex with Crohn's Disease / 대한소아신경학회지

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutation of one of two genes, TSC1 (encoding hamartin, 9q34) and TSC2 (encoding tuberin, 16p13). It invades the central nervous system and various parts of the body, causing various symptoms. Crohn's disease (CD) is a chronic immune-mediated disease that has not been clearly elucidated. It is thought to be caused by an excessive immune response of the body to bacteria that normally exist in the digestive tract with genetic factors. No cases have been reported in which both of the above-mentioned diseases occurred simultaneously. We report a case of CD in a patient with TSC. A 12-year-old boy was brought to our hospital because of abdominal pain. Skin lesions were observed in the TSC. Fundus examination revealed a hamartoma in the right retina. Brain magnetic resonance imaging revealed a subendothelial giant cell astrocytoma (SEGA). On the basis of these findings, he was diagnosed as having TSC. Blood test results showed increased levels of inflammatory markers. On abdominal ultrasonography, his colon walls were observed to be thickened with increased vascularity of the proximal ascending colon, ileocecal valve, and terminal ileum. Colonoscopy revealed discontinuous ulcerations and inflammations of the ileum, IC valve, and cecum, similar to those found in CD. Everolimus was administered orally for the SEGA but was discontinued frequently owing to the exacerbation of CD. The possibility of CD should be kept in mind in patients with TSC considering to undergo treatment for SEGA.

Relationship between metabolic syndrome and thyroid nodules in healthy Koreans

BACKGROUND/AIMS: This study evaluated the relationship between thyroid nodules and metabolic syndrome (MS) and its components in apparently healthy Koreans. METHODS: We reviewed the records of 3,298 subjects with no noticeable symptoms who underwent thyroid ultrasound imaging as part of a routine check-up between July 2009 and June 2010; of these, 1,308 were excluded based upon predefined criteria. Among the remaining 1,990 patients, we examined the association between MS and its components and the incidence of thyroid nodules. RESULTS: Of the 1,990 subjects included in this study, 38.4% (n = 764) had thyroid nodules and 12.7% (n = 253) had MS. Female sex, older age, higher body mass index, larger waist circumference, higher glycated hemoglobin level, lower thyroid stimulating hormone level, and presence of MS were all closely related with the presence of thyroid nodules (all p < 0.05). Furthermore, the relevant number of MS components showed a positive linear correlation with the occurrence of thyroid nodules (p < 0.001). Evidence of MS alone was not independently associated with thyroid nodules after adjusting for sex and age in a multivariate binary logistic regression analysis; however, glycated hemoglobin for females and waist circumference for males, as well as both age and thyroid stimulating hormone for all patients, were identified as independent predictors for the existence of thyroid nodules (all p < 0.05). CONCLUSIONS: This study suggests a positive relationship between the components of MS and thyroid nodules in an ostensibly healthy Korean population. Our data support the idea that the recent increase in thyroid nodules is partly due to increases in both MS and obesity.

Factors Associated with Ketamine Use in Pancreatic Cancer Patient in a Single Hospice Center / 한국호스피스완화의료학회지

PURPOSE: Up to 90% of pancreatic cancer patients suffer from neuropathic pain. In a palliative care setting, pain control in pancreatic cancer patient is one of the major goals. Ketamine is a N-methyl-D-aspartate (NMDA) receptor antagonist, effective in neuropathic pain. Additionally, there have been studies about the opioid sparing effect of ketamine. This study was held in the palliative care unit among pancreatic cancer patients to determine the factors related to ketamine use and the opioid sparing effect. METHODS: The medical records of pancreatic cancer patients admitted to St. Mary's hospital palliative care unit between January, 2013 and December, 2014 were reviewed. Patients were divided into 2 categories according to ketamine use. Also, opioid use before and after ketamine use was compared in the ketamine group. RESULTS: Compared to the non-ketamine use group, patients in the ketamine group required a higher dose of opioid. The total opioid dose, daily opioid dose, number of daily rescue medications, and daily average rescue dose were statistically significantly higher in the ketamine group. The opioid requirement was increased after ketamine administration. CONCLUSION: In this retrospective study, ketamine was frequently considered in patients with severe pain, requiring higher amount of opioid. Studies about palliative use of ketamine in a larger number of patients with diverse types of cancer pain are required in the future.

Effects of a Hospital Based Follow-Up Program for Mothers with Very Low Birth Weight Infants

PURPOSE: This paper reports the results of a hospital centered follow-up program on parenting stress, parenting efficacy and coping for mothers with very low birth weight (VLBW) infants. METHODS: The follow-up program consisted of home visiting by an expert group and self-help program for 1 year. A non-equivalent control group pre-post quasi-experimental design was used. Participants were 70 mothers with low birth weight infants and were assigned to one of two groups, an experimental groups (n=28), which received the family support program; and a control group (n=27), which received the usual discharge education. Data were analyzed using chi2-test, t-test, and ANCOVA with IBM SPSS statistics 20.0. RESULTS: Mothers' parenting stress (F=5.66, p=.004) was significantly decreased in the experimental group. There were also significant increases in parenting efficacy (F=13.05, p<.001) and coping (F=8.91, p=.002) in the experimental group. CONCLUSION: The study findings suggest that a follow-up program for mothers with VLBW infants is an effective intervention to decrease mothers' parenting stress and to enhance parenting efficacy and coping.

Obesity and Hyperglycemia in Korean Men with Klinefelter Syndrome: The Korean Endocrine Society Registry

BACKGROUND: The aim of this study was to investigate the prevalence of obesity in Korean men with Klinefelter syndrome (KS) and the associated risk factors for obesity and hyperglycemia. METHODS: Data were collected retrospectively from medical records from 11 university hospitals in Korea between 1994 and 2014. Subjects aged ≥18 years with newly diagnosed KS were enrolled. The following parameters were recorded at baseline before treatment: chief complaint, height, weight, fasting glucose level, lipid panel, blood pressure, testosterone, luteinizing hormone, follicle-stimulating hormone, karyotyping patterns, and history of hypertension, diabetes, and dyslipidemia. RESULTS: Data were analyzed from 376 of 544 initially enrolled patients. The rate of the 47 XXY chromosomal pattern was 94.1%. The prevalence of obesity (body mass index ≥25 kg/m²) in Korean men with KS was 42.6%. The testosterone level was an independent risk factor for obesity and hyperglycemia. CONCLUSION: Obesity is common in Korean men with KS. Hypogonadism in patients with KS was associated with obesity and hyperglycemia.

Antibody to FcεRIα Suppresses Immunoglobulin E Binding to High-Affinity Receptor I in Allergic Inflammation

PURPOSE: High-affinity receptor I (FcεRI) on mast cells and basophils plays a key role in the immunoglobulin E (IgE)-mediated type I hypersensitivity mediated by allergen cross-linking of the specific IgE-FcεRI complex. Thus, prevention of IgE binding to FcεRI on these cells is an effective therapy for allergic disease. We have developed a strategy to disrupt IgE binding to FcεRI using an antibody targeting FcεRIα. MATERIALS AND METHODS: Fab fragment antibodies, which lack the Fc domain, with high affinity and specificity for FcεRIα and effective inhibitory activity against IgE-FcεRI binding were screened. IgE-induced histamine, β-hexosaminidase and Ca2+ release in basophils were determined by ELISA. A B6.Cg-Fcer1a(tm1Knt) Tg(FCER1A)1Bhk/J mouse model of passive cutaneous anaphylaxis (PCA) was used to examine the inhibitory effect of NPB311 on allergic skin inflammation. RESULTS: NPB311 exhibited high affinity to human FcεRIα (KD=4 nM) and inhibited histamine, β-hexosaminidase and Ca2+ release in a concentration-dependent manner in hFcεRI-expressing cells. In hFcεRIα-expressing mice, dye leakage was higher in the PCA group than in controls, but decreased after NPB311 treatment. NPB311 could form a complex with FcεRIα and inhibit the release of inflammation mediators. CONCLUSION: Our approach for producing anti-FcεRIα Fab fragment antibody NPB311 may enable clinical application to a therapeutic pathway in IgE/FcεRI-mediated diseases.

Antibody to FcεRIα Suppresses Immunoglobulin E Binding to High-Affinity Receptor I in Allergic Inflammation

PURPOSE: High-affinity receptor I (FcεRI) on mast cells and basophils plays a key role in the immunoglobulin E (IgE)-mediated type I hypersensitivity mediated by allergen cross-linking of the specific IgE-FcεRI complex. Thus, prevention of IgE binding to FcεRI on these cells is an effective therapy for allergic disease. We have developed a strategy to disrupt IgE binding to FcεRI using an antibody targeting FcεRIα. MATERIALS AND METHODS: Fab fragment antibodies, which lack the Fc domain, with high affinity and specificity for FcεRIα and effective inhibitory activity against IgE-FcεRI binding were screened. IgE-induced histamine, β-hexosaminidase and Ca2+ release in basophils were determined by ELISA. A B6.Cg-Fcer1a(tm1Knt) Tg(FCER1A)1Bhk/J mouse model of passive cutaneous anaphylaxis (PCA) was used to examine the inhibitory effect of NPB311 on allergic skin inflammation. RESULTS: NPB311 exhibited high affinity to human FcεRIα (KD=4 nM) and inhibited histamine, β-hexosaminidase and Ca2+ release in a concentration-dependent manner in hFcεRI-expressing cells. In hFcεRIα-expressing mice, dye leakage was higher in the PCA group than in controls, but decreased after NPB311 treatment. NPB311 could form a complex with FcεRIα and inhibit the release of inflammation mediators. CONCLUSION: Our approach for producing anti-FcεRIα Fab fragment antibody NPB311 may enable clinical application to a therapeutic pathway in IgE/FcεRI-mediated diseases.

A Case of Rotavirus Infection Presenting with Direct Hyperbilirubinemia / 대한주산의학회잡지

Rotavirus is the most common cause of infectious gastroenteritis in infants and young children and estimated to cause more than 111 million cases of diarrhea annually. Most patients show no specific symptom or experience mild fever, vomiting, non-bloody diarrhea and symptoms often resolve within several days. However, some of patients suffer from severe complication such as necrotizing enterocolitis, intussusception, seizure, encephalitis, and cholestasis. We report a neonatal case of rotavirus infection presenting with reversible direct hyperbilirubinemia with a brief review of associated literatures.