Primary Hyperoxaluria in Korean Pediatric Patients

Background Primary hyperoxaluria (PH), a rare inborn error of glyoxylate meta bolism causing overproduction of oxalate, is classified into three genetic subgroups: type 1–3 (PH1–PH3) caused by AGXT, GRHPR, and HOGA1 gene mutations, respectively. We performed a retrospective case series study of Korean pediatric patients with PH. Methods In total, 11 unrelated pediatric patients were recruited and their phenotypes and genotypes were analyzed by a retrospective review of their medical records. Results Mutational analyses revealed biallelic AGXT mutations (PH1) in nine patients and a single heterozygous GRHPR and HOGA1 mutation in one patient each. The c.33dupC was the most common AGXT mutation with an allelic frequency of 44%. The median age of onset was 3 months (range, 2 months–3 years), and eight patients with PH1 presented with end stage renal disease (ESRD). Patients with two truncating mutations showed an earlier age of onset and more frequent retinal involvement than patients with one truncating mutation. Among eight PH1 patients presenting with ESRD, five patients were treated with intensive dialysis followed by liver transplantation (n=5) with/without subsequent kidney transplantation (n=3). Conclusion Most patients presented with severe infantile forms of PH. Patients with two truncating mutations displayed more severe phenotypes than those of patients with one truncating mutation. Sequential liver and kidney transplantation was adopted for PH1 patients presenting with ESRD. A larger nation-wide multicenter study is needed to confirm the genotype-phenotype correlations and outcomes of organ transplantation

Plasma etching and surface characteristics depending on the crystallinity of the BaTiO3 thin film

Due to its high dielectric constant (κ), the BaTiO3 (BTO) thin film has significant potential as a next-generation dielectric material for metal oxide semiconductor field-effect transistors (MOSFETs). Hence, the evaluation of the BTO thin film etching process is required for such nanoscale device applications. Herein, the etching characteristics and surface properties are examined according to the crystallinity of the BTO thin film. The results demonstrate that the etching rate is low in the high-crystallinity thin film, and the surface residues are much lower than in the low-crystallinity thin film. In particular, the accelerated Cl radicals in the plasma are shown to penetrate more easily into the low-crystallinity thin film than the high-crystallinity thin film. After the etching process, the surface roughness is significantly lower in the high-crystallinity thin film than in the low-crystallinity thin film. This result is expected to provide useful information for the process design of high-performance electronic devices

KNOW-Ped CKD (KoreaN cohort study for outcomes in patients with pediatric CKD): Design and methods

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background The global prevalence of chronic kidney disease (CKD) is increasing. In children, CKD exhibits unique etiologies and can have serious impacts on childrens growth and development. Therefore, an aggressive approach to preventing the progression of CKD and its complications is imperative. To improve the understanding and management of Asian pediatric patients with CKD, we designed and launched KNOW-Ped CKD (KoreaN cohort study for Outcome in patients With Pediatric Chronic Kidney Disease), a nationwide, prospective, and observational cohort study of pediatric CKD with funding from the Korean government. Methods/design From seven major centers, 450 patients <20 years of age with CKD stages I to V are recruited for the comprehensive assessment of clinical findings, structured follow-up, and bio-specimen collection. The primary endpoints include CKD progression, defined as a decline of estimated glomerular filtration rate by 50 %, and a requirement for renal replacement therapy or death. The secondary outcomes include the development of left ventricular hypertrophy or hypertension, impairment of growth, neuropsychological status, behavioral status, kidney growth, and quality of life. Discussion With this study, we expect to obtain more information on pediatric CKD, which can be translated to better management for the patients. Trial registration NCT02165878(ClinicalTrials.gov), submitted on June 11, 2014

Immuno-chromatographic Analysis for HPV-16 and 18 E7 Proteins as a Biomarker of Cervical Cancer Caused by Human Papillomavirus

Among the more than 120 different types of human papillomavirus (HPV), types 16 and 18 have been known to be high risk agents that cause cervical cancer. We examined, in an immuno-chromatographic analysis, the potential of using the early gene product. E7 protein, as a diagnostic marker of cervical cancer caused by HPV. We developed monoclonal antibodies specific to HPV-16 and 18 E7 proteins that were produced from bacterial cells using, gene recombinant technology. For each E7 protein, the optimal antibody pair was selected using the immuno-chromatographic sandwich-type binding system based on the lateral flow through membrane pores. Under these conditions, this rapid testing assay had a detection capability as low as 2 ng/mL of E7 protein. Furthermore, since viral analysis required the host cell to be lysed using chemicals such as detergents, it was possible that the E7 protein was structurally damaged during this process, which would result in a decrease in detection sensitivity. Therefore, we examined the detrimental effects caused by different detergents on the E7 protein using HeLa cells as the host. In these experiments, we found that the damage caused by the detergent, nonylphenylpolyethylene glycol (NP-40), was minimal relative to Triton X-100 commonly used or the cell lysis. Temperature also affected the stability oldie E7 protein, and we found that the E7 protein was stabilized at 4 T. for about 2 h, which was 4 times longer than at room temperature. Finally, a HPV-infected cervical cancer cell line, which was used as a real sample model, was treated using the optimized conditions and the presence of E7 proteins were analyzed by immuno-chromatography. The results of this experiment demonstrated that this rapid test could specifically detect HPV-infected samples.Cho IH, 2009, ANAL CHIM ACTA, V632, P247, DOI 10.1016/j.aca.2008.11.019Liang YJ, 2008, INT J BIOCHEM CELL B, V40, P2431, DOI 10.1016/j.biocel.2008.04.003Ressler S, 2007, CLIN CANCER RES, V13, P7067, DOI 10.1158/1078-0432.CCR-07-1222Jeon JH, 2007, EXP MOL MED, V39, P621Mirecka EA, 2006, PROTEIN EXPRES PURIF, V48, P281, DOI 10.1016/j.pep.2006.04.017Nishimura A, 2006, MICROBES INFECT, V8, P984, DOI 10.1016/j.micinf.2005.10.015Cho JH, 2006, ANAL CHEM, V78, P793, DOI 10.1021/ac051453vHuh KW, 2005, P NATL ACAD SCI USA, V102, P11492, DOI 10.1073/pnas.0505337102Ono T, 2003, J IMMUNOL METHODS, V272, P211DeFilippis RA, 2003, J VIROL, V77, P1551, DOI 10.1128/JVI.77.2.1551-1563.2003Jeon JH, 2002, EXP MOL MED, V34, P496VINCE A, 2002, J CLIN VIROL, V25, P109Chen XJS, 2001, J MOL BIOL, V307, P173Paek SH, 2000, METHODS, V22, P53, DOI 10.1006/meth.2000.1036Walboomers JMM, 1999, J PATHOL, V189, P12Wertlake P, 1999, J REPROD MED, V44, P11JEON S, 1995, P NATL ACAD SCI USA, V92, P1654WILBUR DC, 1994, AM J CLIN PATHOL, V101, P209SCHEFFNER M, 1993, CELL, V75, P495SELVEY LA, 1992, J VIROL METHODS, V37, P119MAY K, 1991, AM J OBSTET GYNECOL, V165, P2000DYSON N, 1989, SCIENCE, V243, P934NELSON PH, 1989, EMBO J, V8, P3905GISSMANN L, 1986, VIRAL ETIOLOGY CERVI, P217CHANG JY, 1985, EUR J BIOCHEM, V151, P217

Mineral bone disorder in children with chronic kidney disease: Data from the KNOW-Ped CKD (Korean cohort study for outcome in patients with pediatric chronic kidney disease) study

BackgroundChildren with chronic kidney disease (CKD) are at high risk of mineral bone disorder (MBD), which leads to fractures, growth retardation, and cardiovascular disease. We aimed to comprehensively understand the relationship between renal function and factors related to MBD and evaluate the prevalence and distribution characteristics of MBD, specifically among Korean patients from the KNOW-PedCKD cohort.MethodsFrom the baseline data of the KNOW-PedCKD cohort, we examined the prevalence and distribution of MBD in 431 Korean pediatric CKD patients, including the level of corrected total calcium, serum phosphate, serum alkaline phosphatase, serum intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF-23), serum vitamin D, fractional excretion of phosphate (FEP), and bone densitometry Z-scores.ResultsThe median serum calcium level remained relatively normal regardless of the CKD stage. The levels of 1,25-dihydroxy vitamin D, urine calcium-to-creatinine ratio, and bone densitometry Z-score significantly decreased with advancing CKD stage, while those of serum phosphate, FGF-23, and FEP significantly increased with CKD stage. The prevalence of hyperphosphatemia (17.4%, 23.7%, and 41.2% from CKD stages 3b, 4, and 5, respectively) and hyperparathyroidism (37.3%, 57.4%, 55.3%, and 52.9% from CKD stages 3a, 3b, 4, and 5, respectively) significantly increased with the CKD stage. Prescriptions of medications, such as calcium supplements (39.1%, 42.1%, 82.4%), phosphate binders (39.1%, 43.4%, 82.4%), and active vitamin D (21.7%, 44.7%, and 64.7%) significantly increased with CKD stage 3b, 4, and 5, respectively.ConclusionsThe results demonstrated the prevalence and relationship of abnormal mineral metabolism and bone growth according to CKD stage in Korean pediatric CKD patients for the first time

Easy Diagnosis of Asthma: Computer-Assisted, Symptom-Based Diagnosis

Diagnosis of asthma is often challenging in primary-care physicians due to lack of tools measuring airway obstruction and variability. Symptom-based diagnosis of asthma utilizing objective diagnostic parameters and appropriate software would be useful in clinical practice. A total of 302 adult patients with respiratory symptoms responded to a questionnaire regarding asthma symptoms and provoking factors. Questions were asked and recorded by physicians into a computer program. A definite diagnosis of asthma was made based on a positive response to methacholine bronchial provocation or bronchodilator response (BDR) testing. Multivariate logistic regression analysis was used to evaluate the significance of questionnaire responses in terms of discriminating asthmatics. Asthmatic patients showed higher total symptom scores than non-asthmatics (mean 5.93 vs. 4.93; p<0.01). Multivariate logistic regression analysis identified that response to questions concerning the following significantly discriminated asthmatics; wheezing with dyspnea, which is aggravated at night, and by exercise, cold air, and upper respiratory infection. Moreover, the presence of these symptoms was found to agree significantly with definite diagnosis of asthma (by kappa statistics). Receiver-operating characteristic curve analysis revealed that the diagnostic accuracy of symptom-based diagnosis was high with an area under the curve of 0.647±0.033. Using a computer-assisted symptom-based diagnosis program, it is possible to increase the accuracy of diagnosing asthma in general practice, when the facilities required to evaluate airway hyperresponsiveness or BDR are unavailable

Therapeutic Effect of Chung-Pae, an Experimental Herbal Formula, on Acute Lung Inflammation Is Associated with Suppression of NF- κ

Acute lung injury (ALI) is an inflammatory disease with high mortality, but therapeutics against it is unavailable. Recently, we elaborated a formula, named Chung-pae (CP), that comprises four ethnic herbs commonly prescribed against various respiratory diseases in Asian traditional medicine. CP is being administered in aerosol to relieve various respiratory symptoms of patients in our clinic. Here, we sought to examine whether CP has a therapeutic effect on ALI and to uncover the mechanism behind it. Reporter assays show that CP suppressed the transcriptional activity of proinflammatory NF-κB and activated that of anti-inflammatory Nrf2. Similarly, CP suppressed the expression of NF-κB dependent, proinflammatory cytokines and induced that of Nrf2 dependent genes in RAW 264.7. An aerosol intratracheal administration of CP effectively reduced neutrophilic infiltration and the expression of pro-inflammatory cytokines, hallmarks of ALI, in the lungs of mice that received a prior intraperitoneal injection of lipopolysaccharide. The intratracheal CP administration concomitantly enhanced the expression of Nrf2 dependent genes in the lung. Therefore, our results evidenced a therapeutic effect of CP on ALI, in which differential regulation of the two key inflammatory factors, NF-κB and Nrf2, was involved. We propose that CP can be a new therapeutic formula against ALI

Customized Asthma Control Test with Reflection on Sociocultural Differences

We evaluated the utility and feasibility of customizing Asthma Control Test (ACT) items to generate a Korean Asthma Control Test (KACT) specific for Korean patients. We surveyed 392 asthma patients with 19 items, selected to reflect the Korean sociocultural context. Guideline ratings were integrated with the evaluations of specialists (i.e., using both guide base rating together with specialist's rating), and items with the greatest discriminating validity were identified. Stepwise regression methods were used to select items. KACT scale scores showed significant differences between the asthma control ratings generated by integrating ratings (r=0.77, P<0.001), by specialist's evaluations (r=0.54, P<0.001), or by FEV1 percent predicted (r=0.39, P<0.001). Specialist's and guideline ratings detected 56% and 48.6% of patients with well-controlled asthma, respectively. However, the integrated ratings indicated that only 34.3% of the patients in the test sample were well controlled. The overall agreement between KACT and the integrated rating ranged from 45% to 78%, depending on the cut-off points used. It is possible to formulate a valid, useful country-specific diagnostic tool for the assessment of asthma patients based on the original ACT that reflect differences in sociocultural context