Down-regulation of IFN-gamma-producing CD56+ T cells after combined low-dose cyclosporine/prednisone treatment in patients with Behcet's uveitis

PURPOSE: To investigate the effects of combined low-dose cyclosporine and prednisone (Cs/Pd) treatment on circulating CD56+ T cells in patients with Behcet's uveitis. METHODS: Ten patients with Behcet's uveitis and 10 healthy control subjects were prospectively recruited. The patients were treated with Cs/Pd for 2 months. Phenotypic and functional changes in circulating CD56+ T cells were assayed before and after treatment. CD56+ T-cell subsets were determined by flow cytometric analysis with monoclonal antibodies for CD3, CD4, CD8, CD56, pan gammadelta TCR, and Valpha24. The absolute numbers of cells in the lymphocyte subsets were calculated. Cytokine (IFN-gamma, IL-4, and IL-10) expressions were measured by ELISA and by intracellular cytokine staining. RESULTS: The proportions of CD56+ T cells, specifically CD8highCD56+ and CD56+gammadelta T-cell subsets, were significantly higher in active Behcet's uveitis but normalized after treatment, whereas the total T-lymphocyte count and the absolute numbers of CD56- T cells were unaffected by treatment. The levels of IFN-gamma and IL-4 were elevated in aqueous humor and serum in Behcet's uveitis (P < 0.001), whereas IL-10 was not detected. After treatment, serum IL-4 levels markedly increased (P < 0.001), and IFN-gamma production by circulating CD56+ T cells was then suppressed. IL-4 and -10 production by CD56+ T cells was increased by treatment, but in contrast, minimal changes were found in CD56- T cells. CONCLUSIONS: The results imply that Cs/Pd treatment for Behcet's uveitis selectively affects the population of and the cytokine expression in CD56+ T cells, but without significant changes in CD56- T cells, and that IFN-gamma-producing CD56+ T cells are the central pathogenic immune cells in Behcet's uveitis

Epidemics of enterovirus infection in Chungnam Korea, 2008 and 2009

Previously, we explored the epidemic pattern and molecular characterization of enteroviruses isolated in Chungnam, Korea from 2005 to 2006. The present study extended these observations to 2008 and 2009. In this study, enteroviruses showed similar seasonal prevalent pattern from summer to fall and age distribution to previous investigation. The most prevalent month was July: 42.9% in 2008 and 31.9% in 2009. The highest rate of enterovirus-positive samples occurred in children < 1-year-old-age. Enterovirus-positive samples were subjected to sequence determination of the VP1 region, which resolved the isolated enteroviruses into 10 types in 2008 (coxsackievirus A4, A16, B1, B3, echovirus 6, 7, 9, 11, 16, and 30) and 8 types in 2009 (coxsackievirus A2, A4, A5, A16, B1, B5, echovirus 11, and enterovirus 71). The most prevalent enterovirus serotype in 2008 and 2009 was echovirus 30 and coxsackievirus B1, respectively, whereas echovirus 18 and echovirus 5 were the most prevalent types in 2005 and 2006, respectively. Comparison of coxsackievirus B1 and B5 of prevalent enterovirus type in Korea in 2009 with reference strains of each same serotype were conducted to genetic analysis by a phylogenetic tree. The sequences of coxsackievirus B1 strains segregated into four distinct clusters (A, B, C, and D) with some temporal and regional sub-clustering. Most of Korean coxsackievirus B1 strains in 2008 and 2009 were in cluster D, while only "Kor08-CVB1-001CN" was cluster C. The coxsackievirus B5 strains segregated in five distinct genetic groups (clusters A-E) were supported by high bootstrap values. The Korean strains isolated in 2001 belonged to cluster D, whereas Korean strains isolated in 2005 and 2009 belonged to cluster E. Comparison of the VP1 amino acid sequences of the Korean coxsackievirus B5 isolates with reference strains revealed amino acid sequence substitutions at nine amino acid sequences (532, 562, 570, 571, 576-578, 582, 583, and 585)

Association of Cytotoxic T Lymphocyte Antigen-4 Gene Polymorphisms and HLA Class II Alleles with the Development of Type 1 Diabetes in Korean Children and Adolescents

We studied the association of cytotoxic T lymphocyte antigen-4 gene (CTLA4) polymorphisms with the development of type 1 diabetes (T1D) in Korean children and adolescents. A total of 176 Korean subjects (92 females and 84 males) with childhood-onset T1D were studied. The A/G polymorphism at position 49 in CTLA4 exon 1 and the C/T polymorphism at position -318 in the CTLA4 promoter were analyzed by PCR-RFLP methods. The genotype and allele frequencies of the CTLA4 polymorphisms in the T1D patients were not different from those in the controls. These polymorphisms were not associated with the clinical characteristics or the development of autoimmune thyroid disease in the T1D patients. The frequency of the A allele was significantly higher in the patients that did not have two out of the three susceptible HLA-DRB1 alleles, which were DRB1*0301, *0405 and *09012, compared to the controls (P<0.05). These results suggest that CTLA4 polymorphisms do not directly confer any susceptibility to T1D. However, a CTLA4-mediated susceptibility effect on the development of T1D might be significant in children and adolescents that do not have susceptible HLA class II alleles.Steck AK, 2005, DIABETES, V54, P2482Yu J, 2004, CLIN IMMUNOL, V113, P318, DOI 10.1016/j.clim.2004.08.009Ueda H, 2003, NATURE, V423, P506, DOI 10.1038/nature01621Mochizuki M, 2003, DIABETES CARE, V26, P843Field LL, 2002, DIABETOLOGIA, V45, P21Abe T, 2001, DIABETIC MED, V18, P726Ligers A, 2001, GENES IMMUN, V2, P145Takara M, 2000, DIABETES CARE, V23, P975Park YJ, 2000, THYROID, V10, P453Lee YJ, 2000, CLIN ENDOCRINOL, V52, P153Abe T, 1999, DIABETES RES CLIN PR, V46, P169Park MH, 1999, HUM IMMUNOL, V60, P901Yanai K, 1999, CLIN EXP ALLERGY, V29, P29Gonzalez-Escribano MF, 1999, TISSUE ANTIGENS, V53, P296Badenhoop K, 1999, EXP CLIN ENDOCR DIAB, V107, pS89Heward JM, 1998, CLIN ENDOCRINOL, V49, P331Donner H, 1998, DIABETES, V47, P1158Djilali-Saiah I, 1998, DIABETES, V47, P125Yanagawa T, 1997, THYROID, V7, P843Marron MP, 1997, HUM MOL GENET, V6, P1275Owerbach D, 1997, DIABETES, V46, P1069Donner H, 1997, J CLIN ENDOCR METAB, V82, P143Lane P, 1997, ANN NY ACAD SCI, V815, P392Deichmann K, 1996, BIOCHEM BIOPH RES CO, V225, P817Nistico L, 1996, HUM MOL GENET, V5, P1075Walunas TL, 1996, J EXP MED, V183, P2541WALUNAS TL, 1994, IMMUNITY, V1, P405BANNAI M, 1994, EUR J IMMUNOGENET, V21, P1LUCASSEN AM, 1993, NAT GENET, V4, P305EISENBARTH GS, 1986, NEW ENGL J MED, V314, P1360

Representative levels of blood lead, mercury, and urinary cadmium in youth: Korean Environmental Health Survey in Children and Adolescents (KorEHS-C), 2012–2014

AbstractBackgroundThis study examined levels of blood lead and mercury, and urinary cadmium, and associated sociodemographic factors in 3–18 year-old Korean children and adolescents.Materials and methodsWe used the nationally representative Korean Environmental Health Survey in Children and Adolescents data for 2012–2014 and identified 2388 children and adolescents aged 3–18 years. The median and 95th percentile exposure biomarker levels with 95% confidence intervals (CIs) were calculated. Multivariate regression analyses were performed on log transformed exposure biomarker levels adjusted for age, sex, area, household income, and father’s education level. The median exposure biomarker levels were compared with data from Germany, the US, and Canada, as well as the levels of Korean children measured at different times.ResultsThe median levels of blood lead and mercury, as well as urinary cadmium were 1.23μg/dL, 1.80μg/L, and 0.40μg/L (95% CIs, 1.21–1.25, 1.77–1.83, and 0.39–0.41, respectively). The blood lead levels were significantly higher in boys and younger children (p<0.0001) and children with less educated fathers (p=0.004) after adjusting for covariates. Urinary cadmium level increased with age (p<0.0001). The median levels of blood mercury and urinary cadmium were much higher in Korean children and adolescents than those in their peers in Germany, the US, and Canada. Blood lead levels tended to decrease with increasing age and divergence between the sexes, particularly in the early teen years. Median levels of blood lead and urinary cadmium decreased since 2010.ConclusionSociodemographic factors, including age, sex, and father’s education level were associated with environmental exposure to heavy metals in Korean children and adolescents. These biomonitoring data are valuable for ongoing surveillance of environmental exposure in this vulnerable population

Endocrine disorders and the neurologic manifestations

The nervous system and the endocrine system are closely interrelated and both involved intimately in maintaining homeostasis. Endocrine dysfunctions may lead to various neurologic manifestations such as headache, myopathy, and acute encephalopathy including coma. It is important to recognize the neurologic signs and symptoms caused by the endocrine disorders while managing endocrine disorders. This article provides an overview of the neurologic manifestations found in various endocrine disorders that affect pediatric patients. It is valuable to think about 'endocrine disorder' as a cause of the neurologic manifestations. Early diagnosis and treatment of hormonal imbalance can rapidly relieve the neurologic symptoms. Better understanding of the interaction between the endocrine system and the nervous system, combined with the knowledge about the pathophysiology of the neurologic manifestations presented in the endocrine disorders might allow earlier diagnosis and better treatment of the endocrine disorders

Clinical features of childhood diabetes mellitus focusing on latent autoimmune diabetes

PurposeThis study was designed to evaluate the clinical characteristics of childhood diabetes mellitus (DM) according to its classification as well as the clinical course of latent autoimmune diabetes (LAD) that initially showed noninsulin dependence despite autoantibody positivity.MethodsA total of 91 subjects diagnosed between 2001 and 2015 were enrolled in the study. They were classified into 3 groups: type 1 DM, LAD, and type 2 DM. Clinical features and laboratory findings were compared among groups.ResultsAmong 91 subjects, type 1 DM, LAD, and type 2 DM were 51 (56.0%), 7 (7.7%), and 33 (36.3%), respectively. In LAD, age at diagnosis and BMI Z-scores were higher, as compared with those in type 1 DM. Initial serum c-peptide levels were higher in LAD than those in type 1 DM, but lower than those in type 2 DM. In LAD, the mean follow-up duration was 4.56 years, and 43% of the patients ultimately required intensive insulin treatment with dosage of > 0.5 U/kg/day. HbA1C and serum c-peptide levels at the time of intensive insulin treatment were 9.43±0.93% and 1.37±1.36 ng/mL, respectively. Recent serum c-peptide/glucose ratio was lower in the group requiring intensive insulin treatment than the group without intensive insulin treatment, with P-value of 0.057 (0.003±0.005 vs. 0.071±0.086).ConclusionInitial autoantibody evaluation is useful for classification and management. Close monitoring of the patients with LAD is important due to the expected need for intensive insulin treatment within several years

Risk factors of vitamin D deficiency in children with epilepsy taking anticonvulsants at initial and during follow-up

PurposeVitamin D status was evaluated in children with epilepsy taking anticonvulsants to determine the prevalence and risk factors of vitamin D deficiency.MethodsThis study was designed as both a cross-sectional and a retrospective cohort study. A sum of 198 children who were diagnosed with epilepsy at the Department of Pediatrics in Dankook University Hospital was included. Their serum vitamin D levels were reviewed based on clinical information, and analyzed using IBM SPSS ver. 20.0.ResultsOne hundred twenty-four children (62.6%) had vitamin D deficiency. Two risk factors were associated: winter to spring season (odds ratio [OR], 3.71; 95% confidence interval [CI], 1.835-7.492) and age more than 12 years (OR, 3.22; 95% CI, 1.377-7.542). Out of the 57 patients who were not vitamin D deficient at the time of initial assay, 47 patients (82.5%) became vitamin D deficient during followup. The change of serum 25-hydroxy vitamin D3 (25(OH)D) levels during follow up showed a weak negative correlation with the duration of medication (r=-0.283, P=0.033). Medication duration was longer and brain magnetic resonance imaging (MRI) abnormality, abnormal underlying conditions, and nonambulatory status were more frequently present in twenty-five patients (44%) who showed a decline of more than 15 ng/mL during follow-up (P<0.05).ConclusionVitamin D deficiency is common in children with epilepsy taking anticonvulsants, especially in adolescents more than 12 years of age. This study emphasizes the regular monitoring of vitamin D level, especially in the presence of longer duration of medication, brain MRI abnormality, abnormal underlying conditions, and nonambulatory status

1p36 deletion syndrome confirmed by fluorescence hybridization and array-comparative genomic hybridization analysis

Pediatric epilepsy can be caused by various conditions, including specific syndromes. 1p36 deletion syndrome is reported in 1 in 5,000–10,000 newborns, and its characteristic clinical features include developmental delay, mental retardation, hypotonia, congenital heart defects, seizure, and facial dysmorphism. However, detection of the terminal deletion in chromosome 1p by conventional G-banded karyotyping is difficult. Here we present a case of epilepsy with profound developmental delay and characteristic phenotypes. A 7-year- and 6-month-old boy experienced afebrile generalized seizure at the age of 5 years and 3 months. He had recurrent febrile seizures since 12 months of age and showed severe global developmental delay, remarkable hypotonia, short stature, and dysmorphic features such as microcephaly; small, low-set ears; dark, straight eyebrows; deep-set eyes; flat nasal bridge; midface hypoplasia; and a small, pointed chin. Previous diagnostic work-up, including conventional chromosomal analysis, revealed no definite causes. However, array-comparative genomic hybridization analysis revealed 1p36 deletion syndrome with a 9.15-Mb copy loss of the 1p36.33-1p36.22 region, and fluorescence in situ hybridization analysis (FISH) confirmed this diagnosis. This case highlights the need to consider detailed chromosomal study for patients with delayed development and epilepsy. Furthermore, 1p36 deletion syndrome should be considered for patients presenting seizure and moderate-to-severe developmental delay, particularly if the patient exhibits dysmorphic features, short stature, and hypotonia

Synergistic Effects of Korean Red Ginseng Extract and the Conventional Systemic Therapeutics of Atopic Dermatitis in a Murine Model

The synergistic effects of Korean Red ginseng (KRG, Panax ginseng C.A. Mey.) on conventional systemic therapeutics of atopic dermatitis (AD) have not been studied yet. To analyze the synergistic effects of KRG extract and the conventional systemic therapeutics of AD in TNCB-induced AD mouse model, we determined the change in modified scoring of index, the transepidermal water loss, the skin pathology, serum IgE, and the expression of various cytokines after combination treatment to the five-week-old NC/Nga female mice. The severity of AD was significantly decreased in the KRG + hydroxyzine (AH) group than AH group, and in the KRG + evening primrose oil (EPO) group than EPO group. A significant decrease in dermal inflammation was observed in the KRG + AH group than that in the AH group, and in the KRG + EPO group than that in the EPO group (p = 0.008), respectively. A decrease in CD1a expression was observed in the KRG + AH group when compared to the AH group (p = 0.008), and KRG + EPO group when compared to the EPO group. Compared to the CS group, the KRG + CS group showed a significant decrease in IL-17 expression. A combination of KRG and conventional systemic therapeutics can safely and effectively manage the AD

Clinical usefulness of the measurement of serum fructosamine in childhood diabetes mellitus

PurposeGlycosylated hemoglobin (HbA1c) is often used as an indicator of glucose control. It usually reflects the average glucose levels over two to three months, and is correlated with the development of long-term diabetic complications. However, it can vary in cases of hemoglobinopathy or an altered red blood cell lifespan. The serum fructosamine levels reflect the mean glucose levels over two to three weeks. This study was designed to determine the clinical usefulness of the combined measurement of serum fructosamine and HbA1c in the management of childhood diabetes mellitus and the correlation between them.MethodsClinical data on 74 Korean children and adolescents with diabetes mellitus who were under management at the Department of Pediatrics of Dankook University Hospital were evaluated. Their fructosamine and HbA1c levels were reviewed based on clinical information, and analyzed using IBM SPSS Statistics ver. 21.ResultsTheir HbA1c levels showed a strong correlation with their fructosamine levels (r=0.868, P<0.001). The fructosamine level was useful for the prompt evaluation of the recent therapeutic efficacy after the change in therapeutic modality. It was also profitable in determining the initial therapeutics and for the estimation of the onset of the disease, such as fulminant diabetes.ConclusionThe measurement of both fructosamine and HbA1c was useful in managing childhood diabetes mellitus, especially when there was discrepancy between the clinical information and the HbA1c level