Variants in the Gene EBF2 Are Associated with Kawasaki Disease in a Korean Population

PURPOSE: Kawasaki disease (KD) is a mucocutaneous lymph node syndrome. It is mainly seen in young children under the age of five. KD is a multifactorial disorder that includes genetic variants. The present study investigated the association between KD and single nucleotide polymorphisms (SNPs) in the candidate gene early B cell factor 2 (EBF2), which is associated with inflammation markers. MATERIALS AND METHODS: An SNP analysis was performed by whole exon sequencing of the EBF2 gene. Our study comprised a total of 495 subjects (295 KD patients and 200 unrelated normal controls) from a Korean population. Tag SNPs were discovered using the Haploview program. Genotyping of the EBF2 gene was performed with the TaqMan® assay with real-time PCR methods. RESULTS: Polymorphism of rs10866845 showed a significant difference in allele frequency between KD patients and controls (p=0.040). The EBF2 gene polymorphisms were significantly associated with KD on logistic regression analysis. CONCLUSION: EBF2 gene variants can contribute to KD in the Korean population.

An Evolutionary Concept Analysis of Helicopter Parenting

PURPOSE: Helicopter parenting is an emerging concept as a way of rearing adolescents and adult children. However, helicopter parenting from a nursing perspective has not been elucidated. Therefore, we undertook a concept analysis to understand the attributes, antecedents and consequences of helicopter parenting in the context of nursing. METHODS: Using Rodgers' evolutionary concept analysis, we analyzed literature on helicopter parenting to discover critical attributes, antecedents, and consequences of this phenomenon. Data were collected from seven electronic search engines. Twelve studies matching inclusion criteria were reviewed RESULTS: Three core attributes of helicopter parenting were hovering, highly deep involvement, and proxy decision making. The antecedents and consequences were retrieved from three important domains including social, parent, and child aspects. Surrogate terms were black hawk, hummingbird, and hovercraft parenting, and related terms were stealth fighter and Kamikaze parenting. CONCLUSION: Based on the results of this study, helicopter parenting has both positive and negative effects on both children and parents. To enhance the positive effects, measurement tools for helicopter parenting and nursing interventions on parenting need to be developed.

Prostaglandin E2 Induces IL-6 and IL-8 Production by the EP Receptors/Akt/NF-kappaB Pathways in Nasal Polyp-Derived Fibroblasts

PURPOSE: Interleukin 6 (IL-6) and IL-8 participate in the pathogenesis of chronic rhinosinusitis with nasal polyps, and their levels are increased by prostaglandin E2 (PGE2) in different cell types. The purposes of this study were to determine whether PGE2 has any effect on the increase in the levels of IL-6 and IL-8 in nasal polyp-derived fibroblasts (NPDFs) and subsequently investigate the possible mechanism of this effect. METHODS: Different concentrations of PGE2 were used to stimulate NPDFs at different time intervals. NPDFs were treated with agonists and antagonists of E prostanoid (EP) receptors. To determine the signaling pathway for the expression of PGE2-induced IL-6 and IL-8, PGE2 was treated with Akt and NF-kappaB inhibitors in NPDFs. Reverse transcription-polymerase chain reaction for IL-6 and IL-8 mRNAs was performed. IL-6 and IL-8 levels were measured byenzyme-linked immunosorbent assay (ELISA). The activation of Akt and NF-kappaB was evaluated by western blot analysis. RESULTS: PGE2 significantly increased the mRNA and protein expression levels of IL-6 and IL-8 in NPDFs. The EP2 and EP4 agonists and antagonists induced and inhibited IL-6 expression. However, the EP4 agonist and antagonist were only observed to induce and inhibit IL-8 expression level. The Akt and NF-kappaB inhibitors significantly blocked PGE2-induced expression of IL-6 and IL-8. CONCLUSIONS: PGE2 increases IL-6 expression via EP2 and EP4 receptors, and IL-8 expression via the EP4 receptor in NPDFs. It also activates the Akt and NF-kappaB signal pathways for the production of IL-6 and IL-8 in NPDFs. These results suggest that signaling pathway for IL-6 and IL-8 expression induced by PGE2 might be a useful therapeutic target for the treatment of nasal polyposis.

Effect of Prostaglandin E2 on Vascular Endothelial Growth Factor Production in Nasal Polyp Fibroblasts

PURPOSE: Angiogenesis is involved in the pathogenesis of chronic rhinosinusitis with nasal polyps. We aimed to investigate the effects of prostaglandin E2 (PGE2) on vascular endothelial growth factor (VEGF) production, the role of E-prostanoid (EP) 4 receptors, and the signal transduction pathway mediating VEGF production in nasal polyp-derived fibroblasts (NPDFs). METHODS: Eight primary NPDF cultures were established from nasal polyps, which were incubated with or without PGE2. Reverse transcription-polymerase chain reaction amplification of EP receptors (EP1, EP2, EP3, and EP4) and immunofluorescence staining for VEGF production were performed. VEGF production via the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) and phosphatidylinositol 3-kinase (PI3K) pathways was evaluated by enzyme-linked immunosorbent assay. RESULTS: All EP receptors were expressed in NPDFs. PGE2 significantly increased VEGF production concentration- and time dependently, and VEGF production was regulated by an EP4 receptor. Activation of intracellular cAMP regulated VEGF production. VEGF production was decreased by PKA and PI3K inhibitors via intracellular cAMP. CONCLUSIONS: PGE2 stimulates VEGF production via the EP4 receptor in NPDFs. These results indicate that PGE2-induced VEGF production is mediated, at least partially, through cAMP-dependent signaling pathways. Therapies targeting the EP4 receptor may be effective in inhibiting the development of nasal polyps.

Potential role(s) of cysteine cathepsins in cancer progression and metastasis / 동물의과학연구지

Cancer is the result of damage to the genetic system, i.e., dysfunction of the DNA repair system, resulting in dysregulated expression of various molecules, leading to cancer formation, migration, and invasion. In cancer progression, several proteases play a critical role in metastasis; however, their biological mechanism in cancer metastasis is not clearly understood. Among these proteases, cathepsins are a family of lysosomal proteases found in most animal cells. Cathepsins have an important role in protein turnover of mammalian, and are classified into 15 types based on their structure as serine (cathepsin A and G), aspartic (cathepsin D and E), and cysteine cathepsins (cathepsin B, C, F, H, K, L, O, S, V, X, and W). Cysteine cathepsins appear to accelerate the progression of human and rodent cancers, which can be a biomarker of the potency of malignancy or metastasis in mammalian. Overexpression of cyteine cathepsins causes the activation of angiogenesis promoting factor, whereas their downregulation reduces the angiogenesis of cancer progression. Under physiological conditions, cysteine cathepsins are essential in inflammation, infection, and cancer development. Activity of cysteine proteases, i.e., cathepsin B, is required for cancer progression or metastasis. Elevation of cysteine cathepsin is associated with cancer metastasis, angiogenesis, and immunity. Therefore, in this review, we suggest that cysteine cathepsin may be an anticancer target of strong clinical interest, although the exact mechanism of cathepsins in cancer metastasis is under investigation.

Modulation of lipid metabolism by mixtures of protamine and chitooligosaccharide through pancreatic lipase inhibitory activity in a rat model / 한국실험동물학회지

Overweight and obesity are usually related with high fat and calorie intake, and seriously causative of lifestyle-related diseases such as cardiovascular disorders, arteriosclerosis, and colon cancer. In this study, we propose a novel dietary therapy against overweight and obesity using mixtures of protamine and chitooligosaccharide (COS), which are known to interrupt the lipid metabolism in the body. Protamine is a dietary protein originated from salmon reproductive organ, and COS is an oligosaccharide made from chitin or chitosan by chemical or enzymatic hydrolysis. In the enzyme activity analysis in vitro, protamine and COS strongly suppressed the activity of pancreatic lipase, which is the primary enzyme for the digestion and absorption of lipids in the intestine. In in vivo animal test, the mixtures of protamine and COS significantly reduced the serum levels of triglyceride (TG), total cholesterol (T-CHO), and low density lipoprotein-cholesterol (LDLC) and inhibited the accumulation of lipids in liver tissue of Sprague Dawley (SD) rats fed high fat diets. On the other hand, they increased fecal TG and T-CHO contents. From these alterations in lipid metabolism, we verified that protamine and COS mixtures could effectively interrupt the digestion and absorption of dietary lipids in the body by inhibiting pancreatic lipase activity. In addition, protamine and COS mixtures increased the serum level of high density lipoprotein-cholesterol (HDLC), responsible for removing cholesterol from cells and protecting atherosclerosis, and therefore decreased the potential risks of cardiovascular diseases by lowering values of the atherogenic index (AI) and cardiac risk factor (CRF). Taken together, we suggest protamine and COS mixtures as a prominent dietary therapy for the prevention of overweight, obesity, and further cardiovascular diseases related with hyperlipidemia.

Functions and physiological roles of two types of estrogen receptors, ERalpha and ERbeta, identified by estrogen receptor knockout mouse / 한국실험동물학회지

Estrogens, a class of steroid hormones, regulate the growth, development, and physiology of the human reproductive system. Estrogens also involve in the neuroendocrine, skeletal, adipogenesis, and cardiovascular systems. Estrogen signaling pathways are selectively stimulated or inhibited depending on a balance between the activities of estrogen receptor (ER) alpha or ERbeta in target organs. ERs belong to the steroid hormone superfamily of nuclear receptors, which act as transcription factors after binding to estrogen. The gene expression regulation by ERs is to modulate biological activities, such as reproductive organ development, bone modeling, cardiovascular system functioning, metabolism, and behavior in both females and males. Understanding of the general physiological roles of ERs has been gained when estrogen levels were ablated by ovariectomy and then replenished by treatment with exogenous estrogen. This technique is not sufficient to fully determine the exact function of estrogen signaling in general processes in living tissues. However, a transgenic mouse model has been useful to study gene-specific functions. ERalpha and ERbeta have different biological functions, and knockout and transgenic animal models have distinct phenotypes. Analysis of ERalpha and ERbeta function using knockout mouse models has identified the roles of estrogen signaling in general physiologic processes. Although transgenic mouse models do not always produce consistent results, they are the useful for studying the functions of these genes under specific pathological conditions.

The Isotype of Antiperinuclear Factor in Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVE: Antiperinuclear factor (APF)is regarded as a marker antibody with high sensitivity and specificity for rheumatoid arthritis (RA).However, the precise role of APF in the pathogenesis of RA has not yet been elucidated. Studying the isotype of APF may be a step in revealing the nature of this anti-body,but such studies have been rare,and none have been done in Korea.The present study is set out to identify the isotype of APF from sera of Korean patients with RA,and to determine whether certain isotypes are related to specific clinical aspects. METHODS: A total of 114 APF positive RA sera were tested against IgG,IgA and IgM separately by indirect immunofluorescence method,and the medical records were retrospectively reviewed. RESULTS: All 114 serum samples were positive for IgG-APF,100 positive for only IgG-APF (G group,87.7%),9 positive for IgG and IgA-APF (GA group, 7.9%),4 positive for IgG and IgM-APF (GM group,3.5%),and one sample was positive for IgG,IgA and IgM-APF (0.9%).The levels of rheumatoid factor (RF)and C-reactive protein (CRP)were different between the 3 groups (ANOVA test),and the RF and CRP of the GM group was higher than the other 2 groups (Bonferroni test). CONCLUSION: The APF identified in Korean patients with RA was always IgG-APF.IgM-APF may be used as a serological marker to assess disease activity in conjunction with CRP.The differences in the laboratory parameters between each isotype groups indicate the possibility of utilizing the isotype of APF to determine the disease activity or prognosis of RA.

Evaluation of Genedia HBsAg Rapid and Genedia Anti-HBs Rapid for the Screening of HBsAg and Anti-HBs / 대한임상병리학회지

BACKGROUND: We evaluated a rapid screening kit for the detection of hepatitis surface antigen (HBsAg) and antibody (anti-HBs) using an immunochromatographic method. MATERIALS AND METHODS: We selected 499 serum specimens for the evaluation. Each specimen was tested by enzyme immunoassay (EIA; Cobas Core, Roche, Switzerland), reverse passive hemagglutination (RPHA; Serodia HBs, Asan, Korea) for HBsAg, passive hemagglutination (PHA; Serodia Anti-HBs, Asan, Korea) for anti-HBs, and with the Genedia HBsAg and Anti-HBs Rapid (Green Cross Corp., Korea) kits. Results of each assay were compared with those of the EIA. RESULTS: The sensitivities and specificities of the Genedia HBsAg Rapid kit were 98.0% and 100%, and those for the Genedia Anti-HBs Rapid kit were 95.3% and 98.0%, respectively. These were higher than those for RPHA (96.0% and 100%), and PHA (83.2% and 96.0%). Concordance rates between EIA and Genedia HBsAg Rapid, Genedia Anti-HBs Rapid, RPHA, and PHA were 98.8%, 96.4%, 97.6%, and 88.4%, respectively. Extending the incubation time from the recommended 30 minutes to 2 hours increased the sensitivities of the Genedia kits. CONCLUSION: The Genedia HBsAg and Anti-HBs Rapid kits are simple, sensitive, and inexpensive assays suitable for screening or use in emergency situations.

Usefulness of Anti-beta2-Glycoprotein I Antibody Test for the Diagnosis of Antiphospholipid Syndrome / 대한임상병리학회지

BACKGROUND: The conventional anticardiolipin antibody (aCL)-ELISA test that has been widely used to diagnose antiphospholipid syndrome (APS) has drawbacks in that false-positive reactions can occur. There have been considerable controversy as to the exact nature of the epitopes to which antiphosholipid antibodies (a PL) are directed. Almost all investigators now agree that the actual antigen to which aPL derived from patient with APS is directed, is beta2-glycoprotein I (beta2GPI). Therefore, we thought that anti-beta2GPI antibodies (abeta2GPI) might be a more specific marker for APS, and attempted to evaluate the usefulness of abeta2GPI test. METHODS: ELISA tests for a CL-IgG and abeta2GPI-IgG were performed simultaneously using the sera from 70 patients with clinically suspected APS and 10 healthy volunteers. The results of abeta2GPI were compared with those of aCL and evaluated clinically by reviewing the medical records. RESULTS: The correlation coefficient between the two was 0.54 (p<0.005). Twelve of 70 patients were abeta2GPI-positive and they were also positive for aCL (mean 45GPL). Forty of 58 abeta2GPI- negative patients were aCL-positive, and many of them were diagnosed to have APS clinically. There was no case showing aCL-negative but abeta2GPI-positive result. CONCLUSIONS: According to our results, abeta2GPI test seems specific but too insensitive to differentiate APS by itself, so it has no additional diagnostic value superior to aCL test. We believe that a study which includes more cases and various test methods will be needed for the precise assessment of abeta2GPI test.

Diagnostic Availability of the Soluble Transferrin Receptor in RA Patients / 대한임상병리학회지

BACKGROUND: The transferrin receptor (TfR) is expressed on almost all cellular surfaces and is shedded into the blood to form the soluble transferrin receptor (sTfR). The sTfR has been known to be a good marker to reflect cellular iron status and to differentiate between iron deficiency anemia (IDA) and anemia of chronic disease (ACD) without the need for a bone marrow aspiration in rheumatoid arthritis (RA) patients. So we aimed to evaluate the diagnostic availability of sTfR in patients with RA and degenerative joint disease (DJD). METHODS: Eighty-seven outpatients visiting the Department of Rheumatology at HYUH were studied and divided into anemic and non-anemic groups according to their Hb levels (female< 12 g/dL, male< 14 g/dL). The sTfR was measured by ELISA method (Quantikine IVDTM, R&D system). To differentiate whether the anemia was due to iron deficiency or other causes, we used the RBC parameters and a discriminant index which was calculated from serum iron, ferritin and TIBC instead of a bone marrow aspiration, an invasive procedure of which interpretation can be subjective. RESULTS: The median was higher (31.09 nM) than the normal reference values (9-28 nM) only in the anemic group of RA. The medians were within normal limit in all the other groups. sTfR levels were high in 15 of the 28 RA anemic patients which were composed of 10 patients with IDA, 4 with non-anemic RA and 1 with non-anemic RA & DJD. CONCLUSIONS: In the present study, sTfR was increased not only in IDA but also in ACD of RA patients and also in non-anemic patients, which showed that sTfR cannot be used to differentiate these two types of anemia by itself and the further tests are needed. We conclude that the expression of TfR in RA patients was dependent not only on iron deficiency but also on the disease itself.

Is the LE Cell Test Necessary? / 대한임상병리학회지

BACKGROUND: Before the introduction of the antinuclear antibody test (ANA), the lupus erythematosus (LE) cell test was a useful diagnostic test for systemic lupus erythematosus(SLE) But, the ANA test has replaced the LE cell test in virtually all laboratories as the current routine test for SLE. However, because the LE cell test is still performed in some laboratories, the authors compared the LE cell test with the ANA test to reevaluate the LE cell test. METHODS: A total of 522 cases were evaluated from Aug. 1990 to Aug. 1994. In these cases, the LE cell test and the ANA test were performed simultaneously, and the results were compared. The authors defined the 'True LE Phenomenon' as only when the LE cell test results agreed with the anti-histone antibody pattern of the ANA test. RESULTS: Of the total 522 cases, 56 cases(10.7%) were SLE. The LE cell test was positive in 22 cases(39.3%) and the ANA test in 56 cases(100%). The LE cell test produced 6(27%) false positive cases and 3 (8.8%) false negative cases. Therefore, the sensitivity of the LE cell test that was verified by the ANA test was only 28.6%. On the other hand, the sensitivity of the ANA test was 100%. In 2 cases, the LE cell results were different in repetitive tests although the ANA results were the same. In 2 other cases, it was impossible to interprete the results of the LE cell test because of severe leukopenia. CONCLUSIONS: The authors concluded that the LE cell test showed markedly low sensitivity and a high false positive and false negative rates for SLE, and that the LE cell test was difficult to perform and interpret accurately due to numerous interfering factors. Therefore, for accurate diagnosis of SLE, the LE cell test must be replaced by more definitive and quantitative immunologic tests in all laboratories such as the ANA test.

Is the LE Cell Test Necessary? / 대한임상병리학회지

BACKGROUND: Before the introduction of the antinuclear antibody test (ANA), the lupus erythematosus (LE) cell test was a useful diagnostic test for systemic lupus erythematosus(SLE) But, the ANA test has replaced the LE cell test in virtually all laboratories as the current routine test for SLE. However, because the LE cell test is still performed in some laboratories, the authors compared the LE cell test with the ANA test to reevaluate the LE cell test. METHODS: A total of 522 cases were evaluated from Aug. 1990 to Aug. 1994. In these cases, the LE cell test and the ANA test were performed simultaneously, and the results were compared. The authors defined the 'True LE Phenomenon' as only when the LE cell test results agreed with the anti-histone antibody pattern of the ANA test. RESULTS: Of the total 522 cases, 56 cases(10.7%) were SLE. The LE cell test was positive in 22 cases(39.3%) and the ANA test in 56 cases(100%). The LE cell test produced 6(27%) false positive cases and 3 (8.8%) false negative cases. Therefore, the sensitivity of the LE cell test that was verified by the ANA test was only 28.6%. On the other hand, the sensitivity of the ANA test was 100%. In 2 cases, the LE cell results were different in repetitive tests although the ANA results were the same. In 2 other cases, it was impossible to interprete the results of the LE cell test because of severe leukopenia. CONCLUSIONS: The authors concluded that the LE cell test showed markedly low sensitivity and a high false positive and false negative rates for SLE, and that the LE cell test was difficult to perform and interpret accurately due to numerous interfering factors. Therefore, for accurate diagnosis of SLE, the LE cell test must be replaced by more definitive and quantitative immunologic tests in all laboratories such as the ANA test.

A study on the analysis of urine which is delayed in room temperature

No abstract available.