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The dietary reference intake (DRI) of vitamin D for Korean children was reduced from 400 IU/day in 2005 to 200 IU/day in 2010. We evaluated the risk factors for low 25-hydroxyvitamin D [25(OH)D] status and its relationships with bone health in peripubertal nonobese children living in Seoul or Gyeonggi-do. One hundred children (9.3 ± 1.9 years, 71 prepubertal, 45 boys) participated in the winter (n = 38, December through March) and summer (June through September). Bone mineral content (Z_BMC), fat mass (Z_FM), lean mass (Z_LM), and bone mineral density for the total body (Z_TB) and lumbar spine (Z_L1–4) were measured using dual-energy X-ray absorptiometry. Twenty-nine percent of children (47.4 % in winter, 17.7 % in summer) were vitamin D deficient (25(OH)D level of

Purpose: This study aimed to evaluate the clinical features of juvenile polyp and the usefulness of polypectomy with entire colonoscopy in children. Methods: We retrospectively reviewed the medical records of 83 children who were diagnosed with having juvenile polyps. Results: The mean age of the patients was 6.5±3.7 (range 1.3-14.5 years) years. The male to female ratio was 2.1 : 1. Eighty one patients (97.6%) had hematochezia, of which the observed characteristics included red stool (74.1%), blood on wipe (13.6%). The time interval between the 1st episode of hematochezia and colonoscopy was 8.9±20.4 (ranged 0.1-48.0) months. The most proximal regions of colonoscopic approach were terminal ileum (96.4%). Sixty three patients (75.9%) had a solitary polyp and 20 patients (24.1%) had multiple polyps. The sites of the polyps were rectum (61.4%), sigmoid colon (23.5%). Eighteen polyps (15.1%) were found more proximal locations than rectosigmoid. The polyp size ranged from 0.3 to 5 cm. After the polypectomy, hematochezia recurred in 9 patients. Endoscopic hemostasis was performed in 2 patients due to severe bleeding. All procedures were carried out without using general anesthesia. Conclusion: Juvenile polyp occurred in a wide range locations and had variable sizes and numbers, suggesting that colonoscopy on the entire colon is necessary. Colonoscopic polypectomy is a simple and useful therapeutic method in children with juvenile polyp. (Pediatr Gastroenterol Hepatol Nutr 2012; 15: 250∼255)

A 1-y-old male miniature pig housed in our laboratory facility was evaluated for weight loss and rough coat condition. CBC results revealed neutrophilia. Radiography of the thoracic area showed increased opacity throughout the thoracic cavity except for the right caudal lobe. 18F-labeled fluorodeoxyglucose positron emission tomography–computed tomography (FDG-PET–CT) revealed elevated standard uptake values in the area corresponding to the radiologic findings. Follow-up thoracic radiography taken 2 wk after FDG-PET–CT showed several interval changes, including markedly decreased opacity throughout the entire thoracic cavity. Necropsy revealed adhesions between the upper portion of the caudal lobe of the left lung and thoracic wall. ELISA for several closely related infectious species confirmed the presence of antibody to Actinobacillus pleuropneumoniae serovar V.

This study used positron emission tomography–computed tomography (PET–CT) to evaluate the effects of 4 anesthetic protocols on 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) accumulation in the brains and hearts of miniature pigs (Sus scrofa domestica). The 18F-FDG standard uptake value was quantified by dividing the brain into 6 regions: cerebellum, brainstem, and frontal, parietal, temporal, and occipital lobes. Five (2 female and 3 male) clinically normal miniature pigs were premedicated with medetomidine (200 μg/kg IM) after which the following 4 anesthetic protocols were administered by using a crossover design: 1) propofol (4 mg/kg IV)–isoflurane inhalation; 2) propofol (4 mg/kg IV); 3) ketamine (5 mg/kg IV); 4) tiletamine–zolazepam (4.4 mg/kg IM). Compared with levels after other protocols, brain accumulation of 18F-FDG increased during propofol anesthesia but decreased with tiletamine–zolazepam. Relative to that due to other protocols, heart accumulation of 18F-FDG increased with propofol–isoflurane anesthesia but decreased with tiletamine–zolazepam. Comparing glucose accumulation in the brain and heart of miniature pigs by using PET–CT, we found that glucose accumulation varied according to the anesthetic protocol and between the 2 organs. These results can be used to evaluate how different anesthetic agents affect glucose metabolism in brain and heart of miniature pigs. Furthermore, these data should be considered when selecting an anesthetic agent for miniature pigs that will undergo PET–CT imaging with 18F-FDG.

We measured bone mineral densities in 28 intracranial germ cell tumor long-term survivors. There was the high prevalence of osteoporosis and osteopenia, 25.0% and 42.9%, respectively, and three additional risk factors, male sex, a low lean mass, and adult growth hormone replacement, were identified.Intracranial germ cell tumor long-term survivors (iGCTLS) have many risk factors for osteoporosis, including irradiation from cancer therapy and multiple hormone deficiencies. However, no study of bone mineral density (BMD) has been conducted in iGCTLS because these tumors are rare. The aims of this study were to evaluate the prevalence of osteoporosis and to identify risk factors associated with reduced bone mass in iGCTLS.We evaluated BMD and body composition of 28 iGCTLS (10.9 ± 5.2 years after cancer treatment; 13 males) using dual-energy X-ray absorptiometry. To determine risk factors, we analyzed the medical history, including the nature of the tumor, treatment modality, endocrine status, hormone replacement therapy, lifestyle, and biochemical parameters.Twenty-five percent of iGCTLS were diagnosed with osteoporosis and 42.9% with osteopenia. Most males (92.3%) had low BMD. Lean mass (LM) was positively correlated with BMD in all regions of interest, and the starting age of adult growth hormone (GH) replacement was negatively correlated with the BMD Z-score at the femur neck. In logistic regression analysis, male sex and low LM were related to low BMD.The iGCTLS had a high prevalence of low BMD. We found that male sex, low LM, and delayed start of adult GH replacement were risk factors for osteoporosis. Therefore, the BMD of all iGCTLS should be evaluated, and if it is low, proper management should be started early.

Purpose This study evaluated whether 2% hydrogen (H 2 ) gas therapy protects against testicular ischemia/reperfusion injury which results in increased formation of reactive oxygen species and/or reactive nitrogen species, leading to testicular apoptosis and impaired spermatogenesis. Methods Pubertal six-week-old Spraque-Dawley rats were assigned to 5 groups (10 animals/group) as follows: group A was a sham operated group; groups B, C, D, and E underwent 5 hours of left testicular ischemia followed by 0, 30, 60, and 120 minutes of 2% H 2 gas therapy, respectively. Histological analysis was performed to verify structure and morphology of the testes and to investigate Johnsen scores, mean seminiferous tubule diameter, and the number of germ cell layers to classify spermatogenesis. Germ cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and Bax/Bcl-2 ratio real-time polymerase chain reaction. We also investigated malondialdehyde levels as an indicator of lipid peroxidation. Results Compared to the sham group (A), germ cell apoptosis and lipid peroxidation in the ischemia group (B) were significantly increased with abnormal morphology and impaired spermatogenesis. In contrast, amelioration of testicular damages was evident in the H 2 therapy groups (C, D, and E). Conclusions Our results showed that inhalation of 2% H 2 gas may be a promising therapy with anti-apoptotic and anti-oxidant properties in cases of testicular ischemia/reperfusion injury.

A single measurement of serum 17α-hydroxyprogesterone (17OHP) level can be unreliable because of its marked diurnal variation. We investigated the relationship of serum level of 17OHP with that of androstenedione (AD), which shows a smaller diurnal variation. And we tested whether the responses of these two hormones to low-dose ACTH stimulation are correlated in patients with 21-hydroxylase deficiency. Baseline serum 17OHP and AD levels were measured in 87 patients and a low-dose ACTH stimulation test was performed in 41 patients. The basal 17OHP level correlated positively with the basal AD level independently of sex, type of 21-hydroxylase deficiency, and the time of day of blood sampling (n = 87, R(2) = 0.75, P < 0.001). The area under the curve of 17OHP and AD correlated positively with their respective basal levels. The fold-change increase in 17OHP after ACTH injection correlated negatively with the basal 17OHP level, but that of AD did not correlate with the basal AD level. The random serum 17OHP level, used in the clinic, is a reliable guide and a low-dose ACTH stimulation test provides no extra benefit for assessing the treatment adequacy in patients with 21-hydroxylase deficiency.

Development of a testicular adrenal rest tumor (TART) is common in males with congenital adrenal hyperplasia, and it can be an important cause of infertility. In the present study, we observed the prevalence of TARTs, and analyzed its associated factors in patients with 21-hydroxylase deficiency. Testicular ultrasonography was performed in 48 postpubertal male patients aged 10.6 to 27.1 years. To determine whether patients were undertreated, we analyzed the serum 17-hydroxyprogesterone (17-OHP) levels to the time of ultrasonographic measurement and calculated the percentage of measurements when serum 17-OHP level was10 ng/mL relative to the total number of measurements during the follow-up period. We divided the 6-year period before ultrasonographic measurement (time 0) into three 2-year intervals and calculated the average concentration of serum 17-OHP in each interval to give a -2(nd) to 0 year-average concentration (-2-0YAC), -4-2YAC and -6-4YAC. A TART was detected by ultrasonography in 31 of 48 patients (64.6%) and the median maximal cross-sectional area of the TARTs was 0.71 (0.03, 4.95) cm(2). The corrected final adult height was lower, and -4-2YAC and body mass index were higher in patients with TART than in those without. After controlling for the type of 21-hydroxylase deficiency, hydrocortisone-equivalent dose, age, and -6-4YAC, the size of TART was associated with a high undertreatment percentage with a marginal statistical significance. These results suggest that strict disease control is mandatory and regular examination with testicular ultrasonography is recommended in male patients, regardless of the type of 21-hydroxylase deficiency.

Trichomonas vaginalis is a flagellated protozoan parasite that causes human trichomoniasis. Although T. vaginalis itself can secrete lipid mediator leukotriene (LT) B(4) leading to neutrophil activation, information regarding the signaling mechanism involved in neutrophil activation induced by T. vaginalis-secreted LTB(4) is limited. We investigated whether LTB(4) contained in the T. vaginalis-derived secretory products (TvSP) is closely involved in interleukin (IL)-8 production in human neutrophils via LTB(4) receptors BLT1 or BLT2.T. vaginalis produced more than 714 pg/ml of LTB(4) per 1 × 10(7) trichomonads. The ability of trichomonads to secrete LTB(4) was inhibited by treatment of trichomonads with the 5-lipo-oxygenease inhibitor AA861, but not the cyclo-oxygenease I inhibitor FR122047. When neutrophils were incubated with TvSP obtained from 1 × 10(7) trichomonads, IL-8 protein secretion was significantly increased compared to results for cells incubated with medium alone. The stimulatory effect of TvSP on IL-8 production was strongly inhibited by pretreatment of TvSP with lipase, although pretreatment with heat or proteinase K showed little inhibitory effect. Moreover, TvSP-induced IL-8 production was efficiently inhibited when trichomonads were pretreated with AA861 or when neutrophils were pretreated with antagonists for BLT1 or BLT2.Our results suggest that LTB(4) receptors BLT1 and BLT2 are involved in IL-8 production in neutrophils induced by T. vaginalis.

Entamoeba histolytica, which causes amebic colitis and occasional liver abscesses in humans, can induce host cell death through apoptosis and necrosis. Recently, we have demonstrated that E. histolytica can induce cell death in neutrophils via diphenyleneiodonium-sensitive NADPH oxidase (NOX)-derived reactive oxygen species (ROS). Although there are enzyme systems similar to the phagocyte NADPH oxidase system in many non-phagocytic cell types, the signaling role of NOX-derived ROS in cell death of human colon epithelial cells induced by E. histolytica remains obscure. Incubation of colon epithelial Caco2 tumor cell lines with amebic trophozoites resulted in intracellular ROS generation and cell death in a caspase-independent manner. Pretreatment with DPI, an inhibitor of NOX, strongly decreased E. histolytica-induced cell death in Caco2 cells. As identified by RT-PCR, NOX1 transcripts were highly expressed in Caco2 cells. siRNA-mediated suppression of NOX1 protein significantly inhibited E. histolytica-induced cell death and ROS response in Caco2 cells. These results suggest that NOX1 participates in the ROS-dependent cell death of colon epithelial cells induced by amebic adhesion during the early phase of intestinal amebiasis.

Lee YA, Yoo JH, Kim JH, Lee SH, Kim JH, Lim HH, Kang MJ, Chung HR, Lee SY, Shin CH, Yang SW. Independent relationships of obesity and insulin resistance with serum proinsulin level in prepubertal children with normal glucose tolerance. Objectives: We compared the fasting serum proinsulin levels in lean, overweight, and obese prepubertal children with normal glucose tolerance (NGT). We also evaluated the relationship between fasting proinsulin level and indices of insulin resistance (IR). Subjects and methods: One hundred nine prepubertal children (mean age, 8.6 yr) with NGT were included. The indices of IR included the homeostasis model assessment of IR (HOMA-IR) and adiponectin level. We recorded the presence of one or more of the following metabolic derangements: triglycerides ≥150 mg/dL, HDL-cholesterol

Background There is ethnic variation in the variable number of tandem repeats of the insulin gene (INS VNTR), one of the susceptibility loci for developing type 1 diabetes (T1D). We evaluated the influence of the genotypes and subdivisions of INS VNTR on the development of T1D in Korean subjects. Methods The study included 352 Korean patients, under the age of 18 years who were diagnosed as having T1D, and 356 control subjects. The insulin − 23HphI A/T single nucleotide polymorphism was used as a marker of class I and III alleles. Surrounding polymorphisms at nucleotide positions + 1127, + 1140, + 2331 and + 2336 were determined as subdivisions of INS VNTR. Results Classes I/I, I/III and III/III were observed at frequencies of 95.8, 4.2 and 0% among all subjects, respectively. Class I/III genotype was significantly less frequent in patients with T1D than in controls (2.56 versus 5.90%; odds ratio 0.419; P = 0.039). In a subdivision analysis, the ID/ID genotype was decreased among patients (P = 0.017, adjusted P = 0.085) and the IC allele tended to increase. The frequency of the class I/III genotype was significantly lower among patients who were diagnosed when younger than 7 years of age than in controls (odds ratio 0.115; P = 0.011). Conclusions INS VNTR has predominance of class I over class III alleles and is associated with susceptibility to T1D in Koreans. In addition, INS VNTR shows distinctive susceptibility according to the age at the onset of T1D. Copyright © 2010 John Wiley & Sons, Ltd.

Purpose The aim of this study was to investigate the clinical features and extraintestinal manifestations (EIMs) of Crohn disease (CD) in Korean pediatric patients. Methods The medical records of 73 children diagnosed with CD were retrospectively reviewed. Data regarding baseline demographic and clinical characteristics, including CD phenotype at diagnosis based on the Montreal classification, and clinical features and course of EIMs were investigated. Results Fifty-two (71.2%) of the patients were males. The mean age of the patients was 12.5 years. The mean follow-up period was 3.4 years. The disease location was ileal in 3 (4.1%) of the patients, colonic in 13 (17.8%), ileocolonic in 56 (76.7%). The clinical behavior was inflammatory in 62 (84.9%) of the patients, stricturing in 8 (11.0%), and penetrating in 3 (4.1%). Perianal abscesses or fistulas were found in 37 (50.7%) of the patients. EIMs observed during the study period were anal skin tag in 25 patients (34.2%), hypertransaminasemia in 20 (27.4%), peripheral arthritis in 2 (2.7%), erythema nodosum in 2 (2.7%), vulvitis in 1 (1.4%), uveitis in 1 (1.4%), and pulmonary thromboembolism in 1 (1.4%). Conclusion Perianal diseases and manifestations were present in more than half of Korean pediatric CD patients at diagnosis. Inspection of the anus should be mandatory in Korean children with suspicious CD, as perianal fistulas, abscesses, and anal skin tags may be the first clue to the diagnosis of CD.

Research in Taiwan has shown that aboriginal students often have low self-esteem and a negative view of their life due to their heritage. This research studied 14 Taiwan aboriginal students to understand how the experience of aboriginal dance club influenced their ethnic identity. The result showed that the experiences of socializing with other aboriginal group members and learning about traditional tribal culture creating a more positive ethnic identity. Moreover, through international performances, they gained self-confidence and diverse perspectives. The study suggests that schools should give support to students to learn about their ethnic culture to explore their ethnic identity.

A large proportion of the increased mortality in Turner syndrome (TS) is related to cardiovascular complications. Increased arterial stiffness may be an important predictor related to cardiovascular complications in TS patients. A novel method of evaluating arterial stiffness, which is relatively independent of changes in blood pressure (BP), is the cardio-ankle vascular index (CAVI). The aim of this study was to compare arterial stiffness using CAVI between TS patients and healthy controls and to evaluate for possible factors affecting arterial stiffness within the patient group. Known TS patients (n=24) with confirmed karyotypes were recruited from the outpatient clinic of Seoul National University Children’s Hospital between August, 2010 and June, 2013. Patients with type 2 diabetes and/or hypertension requiring medication were excluded. There were 5 patients with one or more combined congenital heart anomalies (aortic coarctation (n=2), bicuspid aortic valve (n=2), aortic stenosis (n=3). Anthropometric data, fasting blood lab and measurements of CAVI and pulse wave velocity were collected. A healthy control group (n=23) matched for age and body mass index (BMI) were recruited for comparison. The mean age and BMI of the TS patients were 27.0 years and 22.8 kg/m2 respectively while that of the control were 28.2 years and 22.04 kg/m2. CAVI was significantly higher in the TS patients compared to controls (6.05 vs. 6.65, P < 0.001), while there was no significant difference in pulse wave velocity. Univariate analysis for factors affecting CAVI within the TS patient group showed that CAVI was associated with waist circumference (P = 0.04) and systolic BP (P = 0.045). There were no significant factors related to CAVI using multivariate regression analysis including age, systolic BP, waist circumference, HOMA-IR and presence of cardiac anomalies. TS patients showed an increased arterial stiffness compared to age- and BMI-matched controls using CAVI measurement. Further prospective studies in larger TS patient group are mandatory in order to find significant factors related to increased arterial stiffness.

Background: Eosinophils play a key role in allergic inflammation and parasitic infections. The synthetic peptide, Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), has been previously shown to activate eosinophils and thus to enhance respiratory burst through the formyl peptide receptors. Objective: This study was undertaken to determine the intracellular signaling pathway involved in WKYMVm-stimulated superoxide production by human eosinophils. Methods: Purified eosinophils from peripheral blood were stimulated with various concentrations (10–3 to 10 µM) of WKYMVm and the involvement of PI3-kinase and MAP kinases in WKYMVm-triggered superoxide production was investigated using pharmacological inhibitors. Results: WKYMVm-induced superoxide production by eosinophils was strongly inhibited by pretreatment with the PI3-kinase inhibitor LY294002. In addition, pretreatment with the ERK1/2 kinase inhibitor PD98059 resulted in marked inhibition of superoxide production induced by WKYMVm. Indeed, WKYMVm strongly induced phosphorylation of ERK1/2. The ERK1/2 activation by the peptide was transient and peaked after 2 min of stimulation. Furthermore, ERK1/2 activation by WKYMVm was completely inhibited by pretreatment with the PI3-kinase inhibitor LY294002, but not by the PKC inhibitor Ro-31-8220. Conclusion: These results suggest that WKYMVm stimulates human eosinophils to induce superoxide production via a PI3-kinase-mediated ERK1/2 pathway.

To obtain the low birth weight (LBW) rate, the very low birth weight (VLBW) rate, and gestational age (GA)-specific birth weight distribution based on a large population in Korea, we collected and analyzed the birth data of 108,486 live births with GA greater than 23 weeks for 1 yr from 1 January to 31 December 2001, from 75 hospitals and clinics located in Korea. These data included birth weight, GA, gender of the infants, delivery type, maternal age, and the presence of multiple pregnancy. The mean birth weight and GA of a crude population are 3,188 +/-518 g and 38.7+/-2.1 weeks, respectively. The LBW and the VLBW rates are 7.2% and 1.4%, respectively. The preterm birth rate (less than 37 completed weeks of gestation) is 8.4% and the very preterm birth rate (less than 32 completed weeks of gestation) is 0.7%. The mean birth weights for female infants, multiple births, and births delivered by cesarean section were lower than those for male, singletons, and births delivered vaginally. The risk of delivering LBW or VLBW infant was higher for the teenagers and the older women (aged 35 yr and more). We have also obtained the percentile distribution of GA-specific birth weight in infants over 23 weeks of gestation.

Acute graft-versus-host disease, a major obstacle to the overall success of allogeneic hematopoietic stem cell transplantation, is primarily induced by a subset of donor T cells. Most strategies to prevent acute graft-versus-host disease target all T cells regardless of their specificity, and this leads to prolonged posttransplantation immunodeficiency. Selective depletion of alloreactive T cells could spare protective immunity and facilitate engraftment and graft-versus-leukemia effects. Recently described depletion strategies target activation markers such as CD25 that are expressed by alloreactive T cells. However, incomplete depletion may occur when a single surface epitope or pathway of apoptosis is targeted that may not be fully and concurrently expressed among all alloreactive cells. We now report on a novel strategy effective in both cord blood and peripheral blood stem cell alloreactive T cells that simultaneously induces 2 independent pathways of apoptosis after stimulation by recipient dendritic cells or Epstein-Barr virus-transformed B cells. First, we demonstrate that the folate antagonist trimetrexate selectively depletes proliferating alloreactive precursors in vitro in a dose- and time-dependent manner. Similarly, a second agent, denileukin diftitox, kills activated alloreactive T cells expressing CD25. Most importantly, these 2 agents can exert their effects in concert with superior efficacy while sparing resting bystander T cells, which remain available to mount antimicrobial or third-party responses.

Background: Eosinophils play an important role in the pathogenesis of allergic diseases. Sensitization and exposure to cockroach allergen have been demonstrated to be one of the major risk factors for the development of bronchial asthma. However, little is known regarding the functional capacity of cockroach extract antigen to activate human eosinophils. Objective: We investigated whether German cockroach extract can activate human eosinophils to release cytotoxic inflammatory mediators. Methods: Purified eosinophils from the peripheral blood were incubated with various concentrations (0–200 µg/ml) of German cockroach extract antigen. Effector functions of eosinophils were checked by degranulation and superoxide anion production. In addition, we examined surface expression of CD11b and CD69, and intracellular activation of p38 mitogen-activated protein kinase (p38 MAP kinase) in cockroach-stimulated eosinophils. Results: German cockroach extract induced degranulation and superoxide production from human eosinophils. In addition, incubation of eosinophils for 3 h with the cockroach extract resulted in an increased level of the surface expression of CD11b and CD69. Furthermore, cockroach-induced superoxide production from eosinophils was significantly inhibited by the pretreatment of cells with a p38 MAP kinase inhibitor SB202190. Indeed, a large amount of phosphorylated forms of p38 MAP kinase was detected in cockroach-stimulated eosinophils. Conclusions: Our results suggest that German cockroach extract induces activation of human eosinophils to release cytotoxic inflammatory mediators such as superoxide and granular proteins.

Eosinophils are important cells in host immunity to infections by parasitic worms. Tissue-invasive helminthic parasites have been known to induce apoptosis of immune cells for their successful establishment in vivo. We have previously found that high doses of excretory-secreted products (ESP) secreted by lung fluke Paragonimus westermani newly excysted metacercariae (PwNEM), which cause pulmonary or extrapulmonary paragonimiasis in human beings, accelerate eosinophil cell death. However, little is known about the mechanism of eosinophil apoptosis induced by the Paragonimus-derived products.We examined involvement of caspase 3 activation in eosinophil cell death induced by ESP produced by PwNEM.Eosinophils were isolated from the peripheral blood of healthy donors by CD16-negative immunomagnetic selection. We examined the inhibitory effect of pan-caspase inhibitor on ESP-triggered phosphatidylserine (PS) externalization on the outer surface of eosinophils and intracellular activation of caspase 3 in cell lysates treated with the ESP.When ESP secreted by PwNEM were incubated for up to 3 h with eosinophils, they increased surface exposure of PS on eosinophils in a time- and dose-dependent manner. This proapoptotic effect of the ESP on eosinophils was significantly inhibited by pretreatment of cells with pan-caspase inhibitor z-VAD-fmk, and was completely abolished by heat inactivation of ESP at 56 degrees C. The activated forms of caspase 3 were also clearly detected in eosinophils incubated with ESP. Moreover, ESP potently inhibited prolonged survival of eosinophils induced by cytokines such as IL-5, IL-3, and GM-CSF.These results suggest that ESP secreted by PwNEM contain biological active factors causing caspase-3-mediated apoptosis of human eosinophils, thereby enabling the larvae to evade and to subvert the tackle by eosinophils during the early phase of the infection.

On the basis of our previous findings that bright-light exposure during the daytime has profound influence on physiological parameters such as melatonin secretion and tympanic temperature in humans, we proposed the hypothesis that bright vs. dim light-exposure during the daytime has a different influence on the activity of the digestive system via the endocrine and/or autonomic nervous system. To examine this hypothesis, we conducted a series of counterbalanced experiments in which subjects stayed the daytime (7:00 to 15:00h) under either a dim (80 lux) or bright (5,000 lux) light condition. We measured gastrointestinal activity using a breath hydrogen (indicative of carbohydrate malabsorption) and an electrogastrography (EGG, indicative of gastric myoelectric activity) test. The results showed the postprandial breath hydrogen excretion during the following nighttime period after daytime exposure to the dim-light condition was significantly higher than under the bright-light condition (p < 0.05). In addition, the spectrum total power of the EGG recorded after taking the evening meal was significantly lower for the dim than bright-light condition (p < 0.05). These results support our hypothesis and indicate that dim-light exposure during the daytime suppresses the digestion of the evening meal, resulting in malabsorption of dietary carbohydrates in it.

We assessed whether the urokinase could increase the yield of progenitor cells during processing in elapsed, anticoagulated cord blood (CB) after collection, and we also determined the optimal dose of urokinase. The total nucleated cell (TNC) counts after red cell depletion in 48-hr-elapsed CB were significantly higher in samples treated with 10,000 and 50,000 IU of urokinase/mL than in untreated samples or treated with 5,000 IU of urokinase/mL. The CD34+ cell counts were significantly higher in samples treated with 10,000 IU of urokinase/mL than in untreated samples and in samples treated with 5,000 or 50,000 IU of urokinase/mL. In 6-, 12-, and 24-hr-elapsed CB, however, there were no significant differences of TNC, CD34+ cells, or CFU-GM counts between untreated samples and samples treated with 10,000 IU of urokinase/mL. These findings suggest that the addition of 10,000 IU of urokinase/mL before red cell depletion in 48-hr-elapsed, anticoagulated CB could increase the yield of progenitor cells. However, there are no advantages in using urokinase for processing CB prior to 24 hr after collection. Am. J. Hematol. 71:336–339, 2002. © 2002 Wiley-Liss, Inc.

The present experiment investigated the effects of skin pressure produced by a body compensatory brassiere on defecation activity. Seven healthy females (11-41 yrs) volunteered as participants, being free of medication and constipation. The experiment lasted 3 weeks. The participants did not wear the body compensatory brassiere for the first week, wore it during waking hours for the second week, and again did not wear it for the third week. Whenever they desired to defecate, they did so and then weighted the amount of feces immediately by themselves. Eating times, daily amounts of foods and drinks, their menu, work intensity and its duration, retiring and rising time were controlled to be as similar as possible from day to day. The main finding was that the amount of feces was significantly smaller during the second week (wearing the body compensatory brassiere) than the first and third weeks (not wearing the body compensatory brassiere). These observations are discussed in terms of the suppression of the parasympathetic nervous system and intestine motility, and the delayed transit time in the large intestine.

The sonographic findings of Mobius syndrome with brain stem calcification are presented. Prenatal and neonatal sonography disclosed characteristic hyperechoic dots or linear bands in the brain stem representing calcification, which suggests prenatal ischemic insult to the brain stem.

Entamoeba histolytica is an enteric tissue-invasion protozoan parasite that causes amoebic colitis and liver abscess in humans. E. histolytica can induce host cell apoptosis to evade host immune responses. Protein O-GlcNAcyation has been thought to contribute to the various cellular signal processes including apoptosis and proliferation. O-GlcNAc addition and removal are regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. However, it is unknown whether the alteration of O-GlcNAcylated protein level in host cells can affect E. histolytican-induced cell death. In this study, co-incubation of HepG2 cells with virulent amoeba HM-1 strain remarkably increased DNA fragmentation and LDH release compared to cells incubated with medium alone. In addition, Entamoeba HM-1 induced activation of caspases-3 and calpain in HepG2 cells. Amoebic adherence to the HepG2 cells showed the decrease of O-GlcNAcylated protein levels in HepG2 cells within 2 min, while non-virulent Rahman strain did not. Indeed, pretreatment of host cells with O-GlcNAcase inhibitors (PUGNAc or Thi-Met G) or OGA siRNA prevented the E. histolytica-induced protein deGlcNAcylation and cell death in HepG2 cells. These results suggest that decrease of protein O-GlcNAcylation is an important process required for hepatocyte cell death induced by adherence of E. histolytica.

Obesity and its related factors are known to suppress the secretion of growth hormone (GH). We aimed to evaluate the influence of body mass index (BMI) on the peak GH response to provocative testing in short children without GH deficiency. We conducted a retrospective review of medical records of 88 children (2-15 yr old) whose height was less than 3 percentile for one's age and sex, with normal results (peak GH level > 10 ng/mL) of GH provocative testing with clonidine and dopamine. Peak stimulated GH level, height, weight, pubertal status and serum IGF-1 level were measured. Univariate analysis showed that the BMI standard deviation score (SDS) correlated negatively with the natural log (ln) of the peak stimulated GH level (ln peak GH). BMI SDS did not correlate significantly with sex, age, pubertal status, or ln IGF-1 level. BMI SDS correlated negatively with ln peak GH level induced by clonidine but not by dopamine. In stepwise multivariate regression analysis, BMI SDS was the only significant predictor of ln peak GH level in the combination of tests and the clonidine test, but not in the dopamine test. In children without GH deficiency, BMI SDS correlates negatively with the peak GH level. BMI SDS should be included in the analysis of the results of GH provocation tests, especially tests with clonidine.

1 the pubertal response group of patients who had 5 IU/L peak LH levels in the GnRH stimulation test, and the prepubertal response group of patients who had LH levels

There have been few reports of concomitant moyamoya disease (MMD) with type 1 diabetes mellitus. We report a case of MMD associated with type 1 diabetes mellitus in a 9-year-old boy who presented with altered mentality and left side motor weakness. Laboratory test results indicated diabetic ketoacidosis (DKA), but his stuporous mental state and hemiparesis persisted despite DKA management. Brain magnetic resonance imaging revealed multiple cerebral infarcts and stenosis of cerebral arteries with basal collateral vessels, suggesting MMD. After management of DKA and successive surgery for MMD, his hemiparesis improved without further ischemic attacks. Although rare, the possibility of comcomitant MMD should be considered in a type 1 diabetes mellitus patient with neurologic symptoms and cerebral infarction.

Purpose: Our purpose was to evaluate the clinical presentations at diagnosis and treatment outcomes of functional pituitary adenoma (PA) and nonfunctional PAs (NFPA) in childhood and adolescence. Methods: We performed a retrospective review of the medical records of patients diagnosed with PA before 18 years of age. Results: The mean age at diagnosis of 24 patients (9 males, 15 females) was 12.3 years, and the mean follow-up period was 4.5 years. PAs were categorized as follows: prolactinoma (n=7, 29.2%), adrenocorticotropic hormone secreting adenomas (n=4, 16.7%), growth hormone secreting adenomas (n=3, 12.5%), and NFPAs (n=10, 41.7%). The proportion of macroadenoma (n=13, 54.2%) was similar to that of microadenoma (n=11, 45.8%). Sixteen patients (66.7%) who were diagnosed with functional PA (including all prolactinomas), and two NFPAs underwent surgery due to mass effects. The patients who received surgery had a higher risk for hypopituitarism than those who did not (75.0% vs. 12.5%; P=0.008). Recurrence occurred in five patients, all of whom had residual tumors after surgery for macroadenoma. The degree of obesity at latest follow-up was associated with that at diagnosis (P

Purpose: The aims of this study are to estimate the frequency of thyrotoxicosis associated with autoimmune thyroiditis (TAIT) and to investigate the characteristics of TAIT in children and adolescents. Methods: 220 subjects who had shown thyroid autoimmunity before the age of 18 were included. All the subjects were divided as autoimmune thyroiditis (AIT), Graves’ disease and unspecified group. In addition, AIT was subdivided as TAIT and euthyroid or hypothyroid AIT. Clinical data were review and the variation of thyroid hormone status was investigated among the subjects with TAIT. Results: Of 220 subjects who showed thyroid autoimmunity, 147 subjects were diagnosed as AIT and 47 were as Graves' disease. Among 147 subjects with AIT, 14 subjects (9.5%) had presented TAIT. Among 65 subjects who had initially presented with thyrotoxicosis, 8 subjects (12.3%) were compatible with TAIT. Whereas presenting symptoms of TAIT were similar to those of Graves’ disease, Technetium-99m scan had showed thyroid with decreased uptake. The durations of thyrotoxicosis were several weeks. 6 of 14 TAIT subjects showed recurrent thyrotoxicosis, and 4 of 8 patients who had initially presented with thyrotoxicosis showed subclinical or overt hypothyroidism during follow-up. Conclusions: Possibility of TAIT should not be overlooked when a patient presents thyrotoxicosis, because this condition is not so rare in children and adolescents. Long term follow-up after resolution of thyrotoxicosis is necessary because of a diverse clinical course.

Trichomonas vaginalis is a flagellated lumen-dwelling extracellular protozoan parasite that causes human trichomoniasis via sexual intercourse. Human neutrophils play a crucial role in acute tissue inflammatory responses in T. vaginalis infection. In this study, we investigated the signaling mechanism of neutrophil responses when stimulated with T. vaginalis-derived secretory products (TvSP), which were collected from 1×10(7) live trichomonads. Incubation of human neutrophils isolated from peripheral blood with TvSP induced up-regulation of IL-8 protein secretion. In addition, stimulation with TvSP induced phosphorylation of NF-κB and CREB in neutrophils. Moreover, TvSP-induced IL-8 production was also significantly inhibited by pretreatment of neutrophils with iκB inhibitor or CREB inhibitor. These results suggest that transcription factors NF-κB and CREB are involved in IL-8 production in human neutrophils induced by stimulation with T. vaginalis infection.

The Relationship between Initial Body Mass Index and Body Mass Index after One Year of Gonadotropin-Releasing Hormone Agonist Therapy in Idiopathic True Precocious Puberty Girls Ju Young Yoon, M.D., Min Jae Kang, M.D., Se Young Kim, M.D., Ji Young Seo, M.D., Sei Won Yang, M.D., Young Ah Lee, M.D., Ji Eun Lee, M.D., Hye Rim Chung, M.D and Choong Ho Shin, M.D. Department of Pediatrics , Seoul National University College of Medicine, Seoul, Department of Pediatrics, Bundang Jesaeng General Hospital, Seongnam, Department of Pediatrics, Eulji University School of Medicine, Seoul, Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea

Purpose: The aim of this study was to evaluate the efficacy of pamidronate therapy in children and adolescents with secondary osteoporosis. Methods: Nine patients (7 males, 2 females, 13.2 ± 2.5 years, 10.1-17.4 years) with secondary osteoporosis who had a history of severe bone pain and/or fracture were enrolled. Intravenous pamidronate 1.5 mg/kg (0.5 mg/kg for 3 consecutive days) was given every 6 to 8 weeks for 0.86 ± 0.15 years (6 or 8 cycles). Bone mineral density (BMD) in lumbar spine and femoral neck and their Z-scores were measured before treatment, after the fourth and last cycle (sixth or eighth cycle). Results: Underlying diseases were as follows; neurofibromatosis type 1 (n = 2), epilepsy with/without cerebral palsy (N=2), autoimmune disease treated with steroid (n = 2), hematologic malignancy (n = 3). Bone pain was relieved in most of the patients after the first cycle of treatment, and no more fracture occurred thereafter. There was a significant increase in BMD Z-score of the lumbar spine and femoral neck after the last cycle of therapy, compared to baseline values (from -3.91 ± 1.79 to 1.86 ± 1.18, in L1-4 and -3.71 ± 1.83 to -2.53 ± 1.77 for femoral neck; P = 0.008 and 0.011, respectively). However, there was no significant change in BMD Z-scores between the fourth cycle and the last cycle. Fever developed in 7 out of 9 patients (77.8%), which was relieved by antipyretics. Total serum levels of calcium and phosphorus were significantly decreased (calcium, P = 0.008; phosphorus, P = 0.015) after pamidronate therapy, and three of them experienced symptomatic hypocalcemia during the first cycle. The growth velocity was normal during follow-up periods (mean, 4.47 ± 1.69 years; range, 1.05 to 6.77 years). Conclusion: In conclusion, pamidronate can be administered to the patients with secondary osteoporosis, relieving the symptoms and signs effectively and safely. However, its side effects should be monitored during treatment.

Tribromoethanol (2,2,2-tribromoethanol, TBE) is a popular injectable anesthetic agent used in mice in Korea. Our goal was to assess the risks associated with side effects (lesions) in the abdominal cavity, especially at high doses. To understand the underlying pathophysiological changes, we examined levels of cytokines through ELISA of abdominal lavage fluid and spleen collected from mice treated with low and high-dose TBE. ICR mice were anesthetized using one of the following protocols: a combination of TBE 200 mg/kg (1.25%) and xylazine 10 mg/kg; TBE 400 mg/kg (1.25%); and TBE 400 mg/kg (2.5%). Administration of high-dose TBE (400 mg/kg) increased the interleukin-1β and interleukin-6 levels in the peritoneal cavity over the short term (

The present study was carried out to provide a guideline for injecting tribromoethanol (TBE) as the main anesthetic agent, while adjusting the doses of xylazine (X) and medetomidine (M) according to different strains of mice (male ICR, C57BL/6, and BALB/c). Seven intraperitoneal injection anesthesia protocols using TBE and mixtures of TBE and α –adrenergic agonists (TBE/X and TBE/M) were compared in terms of their efficacy and safety (anesthetic duration, death rate, and the development of pathological lesions of abdominal organs). All animals that were injected with a low dose of TBE (200 mg/kg) displayed clear signs of light anesthesia with a strong pedal withdrawal reflex. Despite the good anesthetic effect, a high dose of TBE (400 mg/kg) was not a suitable anesthetic for major surgery in all mouse strains because of the risk of pathologic changes in the abdominal organs, such as retention of the digestive tract, peritonitis, and fibrinoid adhesion. TBE200/X10 and TBE200/M0.5 (TBE, 200 mg/kg; X, 10 mg/kg; M, 0.5 mg/kg) appeared to be safe and provided satisfactory anesthesia in ICR mice. Finally, there were clear differences in anesthetic efficacy among ICR, C57BL/6, and BALB/c strains. TBE/M and TBE/X did not anesthetize BALB/c mice, and it anesthetized C57BL/6 mice for a short time. When administered with TBE/X and TBE/M maintained the sedation of ICR mice. We were able to establish different regimes for each strain (TBE200/X20 for C57BL/6, TBE300/X10 and TBE200/M1 for BALB/c). Our results showed that TBE/X and TBE/M could be recommended as an anesthetic mixture, with the dose appropriately adjusted according to mouse strain.

Entamoeba histolytica is a tissue-invasive protozoan parasite causing dysentery in human beings. During the infection in the colonic tissues, amoebic trophozoites have a capability to kill host cells via apoptosis or necrosis, which triggers IL-8-mediated acute inflammatory responses. However, signaling pathways involved in host cell death by E. histolytica is not fully defined. In this study, we examined whether calpain is closely involved in cleavage of transcription factors and XIAP, which are responsible for cell survival, during cell death of colon epithelial cells induced by live trophozoites of E. histolytica. Incubation with amoebic trophozoites induced PS externalization in CaCo2 cells in a time and dose-dependent manner. In addition, E. histolytica activated m-calpain and caspase-3 in CaCo2 cells. Moreover, incubation with amoeba resulted in marked degradation of STAT proteins (STAT1, 2, 3, 5, and 6), NF-¿B (p65 or p50), and XIAP in CaCo2 cells. However, I¿B, an inhibitor of NF-¿B, was not cleaved in CoCo2 cells following adherence of E. histolytica. Entamoeba-induced cleavage of STAT proteins, NF-kB, and XIAP was inhibited by pretreatment of cells with a cell permeable calpain inhibitor, calpeptin. Furthermore, calpeptin, but not z-VAD-fmk, reduced Entamoeba-induced DNA fragmentation in CoCo2 cells. These results suggest that calpain-mediated degradation of anti-apoptotic proteins, such as transcription factors and XIAP, is required for acceleration of cell death in colon epithelial cells induced by Entamoeba histolytica.

Purpose:Medical therapy is the initial treatment for children with Graves disease to avoid complications of other treatments. However, optimal treatment for childhood Graves disease is controversial because most patients require relatively long periods of medical therapy and relapse is common after medication discontinuation. Therefore, this study aimed to search clinical or biochemical characteristics that could be used as remission predictors in Graves disease. Methods:We retrospectively studied children diagnosed with Graves disease, treated with anti-thyroid agents, and observed for at least 3 years. Patients were categorized into remission and non-remission groups, and the groups were compared to determine the variables that were predictive of achieving remission. Results:Sixty-four patients were enrolled, of which 37 (57.8%) achieved remission and 27 (42.2%) could not achieve remission until the last visit. Normalization of thyroid-stimulating hormone-binding inhibitory immunoglobulin (TBII) after treatment was faster in the remission group than in the non-remission group (remission group, 15.5112.07 vs. non-remission group, 41.6935.70 months). Thyrotropin-releasing hormone (TRH) stimulation tests were performed in 28 patients. Only 2 (8.3%) of 26 patients who showed normal or hyper-response in TRH stimulation test relapsed. Binary logistic regression analysis identified rapid achievement of TBII normalization after treatment as a significant predictor of remission. Six percent of patients achieved remission within 3 years and 55.8% achieved it within 6 years. Conclusion:Rapid achievement of TBII normalization can be a predictor of remission in childhood Graves disease. The TRH stimulation test can be a predictor of maintenance of remission.

Purpose : Macrovascular complications are the main cause of mortality in type 1 diabetes mellitus (T1DM). The purpose of this study was to clarify the presence of early vascular changes and to assess the risk factors of macrovascular complications in young adults with T1DM diagnosed in childhood and adolescence. Methods : Seventy-two patients (23.92.4 years) with T1DM diagnosed before 18 years of age and twenty normal controls were included. The incidence of hypertension, dyslipidemia, and other risk factors of macrovascular complication were reviewed. Flow-mediated vasodilation (FMD) and mean intima-media thickness (IMT) measured by ultrasound were compared between patients and control subjects, and their correlations with macrovascular risk factors were analyzed. Results : Of the 72 patients, 32 (44.4%) had hypertension. The proportions of maleness (P=0.03) and mean body mass index (P=0.04) were higher in the hypertensive patients than in normotensive patients. Thirty-one (N=69, 44.9%) patients had dyslipidemia and LDL-cholesterol was positively correlated with mean HbA1c (r=0.32, P=0.008) and total daily insulin dose (r=0.27, P=0.02). The mean IMT was significantly higher in patients than in control subjects (0.430.06 mm vs 0.390.06 mm, P=0.03). There was no difference in the value of FMD between patients and controls, but the duration of the disease after pubertal onset was negatively correlated with FMD (r=-0.34, P=0.01). Conclusion : Hypertension, dyslipidemia and atherosclerotic vascular change were observed in young adults with T1DM diagnosed during childhood and adolescence; this strongly suggests that meticulous screening of macrovascular complications and control of their risk factors should be conducted.

* , Seoul National University Bundang Hospital, Seong-Nam, Korea Purpose: The aim was to investigate the clinical characteristics and responses to growth hormone (GH) therapy in children with attenuated growth who showed normal GH responses to GH stimulation tests (GHST). Methods: The study included 39 patients with height velocity (HV) of less than 4 cm/yr and normal GHST results. Clinical characteristics of patients were analyzed retrospectively. Results: Eleven were born as small for gestational age (SGA) and 28 as appropriate for age (AGA). In the SGA group, the standard deviation score (SDS) of age and height measured at their first visit was significantly low. Sixteen patients were treated with GH and six of 23 without GH therapy were followed for 1 year after GHST. The mean (range) of HV was 7.7 (4.9 to 11.1) cm/yr in patients with GH therapy and 3.7 (2.7 to 4.5) cm/yr in those without GH therapy, which was statistically significant (P

Eosinophilic leukocytes function in host protection against parasitic worms. In turn, helminthic parasites harbor specific molecules to evade or paralyze eosinophil-associated host immune responses; these molecules facilitate the migration and survival of parasitic helminths in vivo. This competition between eosinophil and worm leads to stable equilibria between them. An understanding of such dynamic host-eosinophil interactions will help us to uncover mechanisms of cross talk between host and parasite in helminth infection. In this review, we examine recent findings regarding the innate immune responses of eosinophils to helminthic parasites, and discuss the implications of these findings in terms of eosinophil-mediated tissue inflammation in helminth infection.