Kyung-Hoon Lee

The presence and localization of onychodermis (specialized nail mesenchyme) containing onychofibroblasts in the nail unit: a morphological and immunohistochemical study

Lee D‐Y, Park J‐H, Shin H‐T, Yang J‐M, Jang K‐T, Kwon G Y, Lee K‐H & Shim J S u2028(2012) Histopathology 61, 123–130

Erythropoietin Attenuates Brain Injury, Subventricular Zone Expansion, and Sensorimotor Deficits in Hypoxic-Ischemic Neonatal Rats

The aim of this study was to investigate the effect of erythropoietin (EPO) on histological brain injury, subventricular zone (SVZ) expansion, and sensorimotor function deficits induced by hypoxia-ischemia (HI) in newborn rat pups. Seven-day-old male rat pups were divided into six groups: normoxia control, normoxia EPO, hypoxia control, hypoxia EPO, HI control, and HI EPO group. Sham surgery or HI was performed in all animals. HI was induced by ligation of the right common carotid artery followed by 90 min of hypoxia with 8% oxygen. Recombinant human EPO 3 U/g or saline was administered intraperitoneally, immediately, at 24- and 48-hr after insult. At two weeks after insult, animals were challenged with cylinder-rearing test for evaluating forelimb asymmetry to determine sensorimotor function. All animals were then sacrificed for volumetric analysis of the cerebral hemispheres and the SVZ. The saline-treated HI rats showed marked asymmetry by preferential use of the non-impaired, ipsilateral paw in the cylinder-rearing test. Volumetric analysis of brains revealed significantly decreased preserved ipsilateral hemispheric volume and increased ipsilateral SVZ volume compared with the sham-operated animals. Treatment of EPO significantly improved forelimb asymmetry and preserved ipsilateral hemispheric volume along with decreased expansion of ipsilateral SVZ following HI compared to the saline-treated HI rats. These results support the use of EPO as a candidate drug for treatment of neonatal hypoxic-ischemic brain damage.

Determination of Plasma Warfarin Concentrations in Korean Patients and Its Potential for Clinical Application

BACKGROUNDnWarfarin is a widely used oral anticoagulant with broad within- and between-individual dose requirements. Warfarin concentrations can be monitored by assessing its pharmacologic effects on International Normalized Ratio (INR). However, this approach has not been applied in the routine clinical management of patients receiving warfarin therapy. We performed a plasma warfarin assay using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) to determine if such an assay can be utilized in routine clinical practice.nnnMETHODSnWe included a total of 105 patients with atrial fibrillation, and who were receiving warfarin for more than 1 yr. The plasma concentrations of total warfarin and 7-hydroxywarfarin were determined by HPLC-MS/MS (Waters, UK). We assessed the association between warfarin dose, concentration, and INR as well as the effects of these factors on warfarin concentrations.nnnRESULTSnThe mean maintenance dose of warfarin in 105 patients was 4.1 +/-1.3 mg/day (range, 1.7-8.0 mg/day) and their mean plasma warfarin concentration was 1.3+/-0.5 mg/L. We defined a concentration range of 0.6-2.6 mg/L (corresponding to the 2.5th to 97.5th percentile range of the Plasma warfarin levels in the 74 patients showing INR within target range) as the therapeutic range for warfarin. The correlation of warfarin dose with warfarin concentration (r(2)=0.259, P<0.001) was higher than that with INR (r(2)=0.029, P=0.072).nnnCONCLUSIONSnThere was a significant correlation between warfarin dose and plasma warfarin concentrations in Korean patients with atrial fibrillation. Hence, plasma warfarin monitoring can help determine dose adjustments and improve our understanding of individual patient response to warfarin treatment.

Reduction of the HIV seroconversion window period and false positive rate by using ADVIA Centaur HIV antigen/antibody combo assay.

Background Early diagnosis of HIV infection reduces morbidity and mortality. Fourth-generation HIV detection assays are more sensitive because they can detect p24 antigen as well as anti-HIV antibodies. In this study, we evaluated the performance of a new fourth-generation ADVIA Centaur HIV antigen/antibody combo (CHIV) assay (Siemens Healthcare Diagnostics Inc., USA) for early detection of HIV infection and reduction of false positive rate. Methods Four seroconversion panels were included. The third-generation ADVIA Centaur HIV 1/O/2 enhanced (EHIV) assay (Siemens Healthcare Diagnostics Inc., USA) and fourth-generation CHIV assay were used to test each panel for HIV infection. The presence of antigen was confirmed using HIV p24 antigen assay. To evaluate false-positivity and specificity, 54 HIV false-positive and HIV-negative serum samples from 100 hospitalized patients and 600 healthy subjects were included. Results Compared to the EHIV assay, the CHIV assay had a shorter window for three of the seroconversion panels: a difference of 10 days and two bleeds in one panel, and 4 days and one bleed in the other two panels. Only 34 of the 54 (63%) samples known to yield false-positive results by EHIV assay had repeatedly yielded reactive results in the CHIV assay. One of the 600 healthy subjects had a false-positive result with the CHIV assay; thus, the specificity was 99.85% (699/700). CHIV accurately determined the reactive results for the HIV-confirmed serum samples from known HIV patients and Korea Food & Drug Administration (KFDA) panels. Conclusions The new fourth-generation ADVIA Centaur HIV assay is a sensitive and specific assay that shortens the serological window period and allows early diagnosis of HIV infection.

Angiotensin II type 1 receptor 1166A/C polymorphism in association with blood pressure response to exogenous angiotensin II

BackgroundThe angiotensin II type 1 receptor (AT1R) 1166A/C polymorphism is reported to be implicated in cardiovascular diseases. The association between the 1166A/C polymorphism and diastolic blood pressure (DBP) changes in response to exogenous angiotensin II and valsartan was evaluated by pharmacokinetic and pharmacodynamic modeling.MethodsThirteen normotensive, healthy adults (six with the 1166A/A polymorphism and seven with 1166A/C) were enrolled in this clinical study. Angiotensin II was infused continuously over a 2-min period at four different rates (from 5xa0ng/kg/min and increased by 5xa0ng/kg/min) at 0 (before valsartan dosing), 2, 4, 8, 12, and 24xa0h after a single oral dose of valsartan (40xa0mg). BP was measured serially before and at the end of each rate of angiotensin II infusion. Plasma concentration-time profiles of valsartan were established over a 24-h period. We analyzed data using NONMEM and studied the relationship between the AT1R1166A/C genotypes and BP responses.ResultsPlasma valsartan concentrations and DBP data best fitted into a two-compartment linear model and Emax model (Emax with baseline for angiotensin II and inhibitory Emax for valsartan), respectively. The ED50 for angiotensin II in the subjects with 1166A/C [95% confidence interval (CI): 4.30∼14.02xa0ng/kg/min] was significantly lower than in those with 1166A/A (95% CI: 14.23∼28.77xa0ng/kg/min), while the Emax for angiotensin II and EC50 for valsartan was similar in both genotype groups.ConclusionsThese results suggest that exogenous human angiotensin II increases the BP more potently in subjects with 1166A/C than in those with 1166A/A.

Effect of additives on the viability of bifidobacteria loaded in alginate poly-l-lysine microparticles during the freeze-drying process.

Bifidobacteria-loaded alginate poly-l-lysine microparticles (bap microparticles) were prepared using an air atomization method and then freeze-dried. The viability of the bap microparticles was investigated as a function of the amount of the bifidobacteria cultures, and the addition of a yeast extract, cryoprotectants, antioxidants and neutralizer. The size of the bap microparticles with and without the bifidobacteria was 84.8±28.5 μm (mean±standard deviation) and 113.1±38.5 μm, respectively. The surface morphology was slightly ellipsoid and wrinkled regardless of the incorporating bifidobacteria. The viability gradually decreased with increasing freeze-drying time. Free-flowing powdered bap microparticles were obtained at least 12 h after freeze-drying the wetted slurry of bap microparticles. However, the particles tended to aggregate when either lactose or ascorbic acid was added. The addition of a yeast extract, cryoprotectants (glycerol and lactose), antioxidants (NaHSO3 and ascorbic acid) and neutralizer (Mg3(PO4)2) resulted in a significantly higher viability of the bifidobacteria in the bap microparticles after freeze-drying (0.34–1.84 log) compared with the culture alone.

Identification of novel PKD1 and PKD2 mutations in Korean patients with autosomal dominant polycystic kidney disease

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder. It is caused by mutations in the PKD1 and PKD2 genes, and manifests as progressive cyst growth and renal enlargement, resulting in renal failure. Although there have been a few studies on the frequency and spectrum of mutations in PKD1 and PKD2 in Korean patients with ADPKD, only exons 36–46, excluding the duplicated region, were analyzed, which makes it difficult to determine accurate mutation frequencies and mutation spectra.MethodsWe performed sequence analysis of 20 consecutive unrelated ADPKD patients using long-range polymerase chain reaction (PCR) to avoid pseudogene amplification, followed by exon-specific PCR and sequencing of the all exons of these two genes. Multiplex ligation-dependent probe amplification was performed in patients in whom pathogenic mutations in PKD1 or PKD2 were not identified by LR-PCR and direct sequencing to detect large genomic rearrangements.ResultsAll patients met the diagnostic criteria of ADPKD, and pathogenic mutations were found in 18 patients (90.0%), comprising 15 mutations in PKD1 and three in PKD2. Among 10 novel mutations, eight mutations were found in the PKD1 gene while two mutations were found in the PKD2 gene. Eight of 14 PKD1 mutations (57.1%) were located in the duplicated region.ConclusionsThis study expands the spectra of mutations in the PKD1 and PKD2 genes and shows that the mutation frequencies of these genes in Korean ADPKD patients are similar to those reported in other ethnicities. Sequence analysis, including analysis of the duplicated region, is essential for molecular diagnosis of ADPKD.

The Concept of Onychodermis (Specialized Nail Mesenchyme) Is Applicable in Normal Adult Nail Unit

234 Ann Dermatol Received January 14, 2016, Revised March 30, 2016, Accepted for publication April 6, 2016 Corresponding author: Dong-Youn Lee, Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. Tel: 82-2-3410-3543, Fax: 82-2-3410-3869, E-mail: dylee@skku.edu This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright

CD13 is a marker for onychofibroblasts within nail matrix onychodermis: Comparison of its expression patterns in the nail unit and in the hair follicle

We previously demonstrated the presence of onychodermis, a specialized mesenchymal cell population beneath the nail matrix and proximal nail bed demonstrating CD10 expression. We hypothesize that the onychodermis could be the nail analog of the follicular dermal papilla, which is known to express CD13. We compare CD13 expression patterns between specialized mesenchymes of nail and hair, and compare these findings with CD10 expression patterns.

First Report on Familial Hemophagocytic Lymphohistiocytosis with an Abnormal Immunophenotype and T Cell Monoclonality in Korea

Hemophagocytic lymphohistiocytosis (HLH) can be divided into primary (genetic or familial) and secondary (acquired or reactive) forms. Abnormal immunophenotyping and downregulation of CD5 or CD7 in T cells have been well characterized in Epstein-Barr virus (EBV)-associated HLH [1, 2]. A few studies have also reported abnormal immunophenotyping of T cells in patients with familial HLH (FHL) [1, 3]. Here, we report a case of FHL with immunophenotypically abnormal T cells and monoclonal T cells confirmed by a T-cell receptor (TCR) gene rearrangement test. n nA 2-month-old infant was referred to our hospital for further evaluation and treatment of persistent fever and thrombocytopenia. Hepatosplenomegaly and petechiae were observed on physical examination. The total leukocyte count was 1.64×109/L, consisting of 65% lymphocytes, with 1% atypical lymphoid cells. The Hb level was 9.1 g/dL, and the platelet count was 20×109/L. Blood chemistry results were as follows: 570 IU/L AST, 454 IU/L ALT, 657 IU/L lactate dehydrogenase (LDH), 11.4 mg/dL total bilirubin, and 147 mg/dL fibrinogen. The prothrombin time (PT) and activated partial thromboplastin time (aPTT) was 15.3 sec (reference range; 12.6-14.9 sec) and 40.3 sec (reference range; 29.1-41.9 sec), respectively. A serological test to detect any underlying viral infection showed (+, positive; -, negative): anti-CMV IgG (+), anti-CMV IgM (-), anti-EB-VCA IgG (+), anti-EB-VCA IgM (-), EBV-EA (-), and anti-EB-NA IgG (+). The results of a chromosome study were normal (46,XY). Atypical lymphocytes were observed on peripheral blood smear (Fig. 1A). Hemophagocytic histiocytes were observed on bone marrow biopsy (Fig. 1B, C, and D). EBV was not detected by in situ hybridization. We performed mutation analysis of the FHL-related genes UNC13D and PRF1 using DNA isolated from peripheral blood. Sequencing analysis revealed compound heterozygous mutations in UNC13D [c.118-308 C>T (;)754-1G>C] (Fig. 2A and B). These mutations are frequently observed in Korean FHL patients [4]. Immunophenotyping using bone marrow aspirate revealed an abnormal population of CD8+ T cells with downregulated levels of CD5 or CD7 (14.61% of total events; Fig. 2C, D, and E). A TCR gene rearrangement study using paraffin-embedded tissue revealed T cell monoclonality [5] (Fig. 2F). The patient was treated with HLH-2004 chemotherapy and allogenic bone marrow transplantation. Bone marrow studies were performed before and after allogenic bone marrow transplantation. Hemophagocytic histiocytes were not observed in the follow-up bone marrow study. The patient remained in remission (follow-up time: 12 months after diagnosis). A familial study for UNC13D gene mutation was not performed. n n n nFig. 1 n nPeripheral blood smear, bone marrow biopsy and aspirate. (A) Pancytopenia and atypical lymphoid cells were observed in peripheral blood smear (Wright-Giemsa stain; magnification, ×1,000). (B) Hemophagocytic histiocytes were frequently observed ... n n n n n nFig. 2 n nSequencing analysis, flow cytometry results, and single-strand conformational polymorphism (SSCP) analysis of the T cell receptor by using paraffin-embedded tissue samples. (A) Compound heterozygous mutations in the UNC13D gene were observed: C to T substitution ... n n n nAbnormal immunophenotype of CD8+ T cells with downregulation of CD5 is a common finding in HLH associated with viruses, especially EBV-associated HLH [1, 6, 7]. McCall et al. [1] reported that 6 of 9 cases (76%) of EBV-associated HLH had expansion of CD8+ T cell populations with variable downregulation of CD5, CD7, and/or CD3, whereas 1 of 8 cases (13%) of non-EBV-associated HLH showed downregulation of CD7 expression [1]. There are few reports on abnormal immunophenotype of T cells in FHL [1, 3, 8]. Karandikar et al. [3] reported a case of FHL associated with a perforin gene mutation that showed CD8+ T cells with loss of CD5 expression. Wada et al. [8] also reported a case of FHL associated with a perforin gene mutation that showed CD8+ T cells with loss of CD5 expression. Downregulation of CD5, CD7, CD3 and aberrant expression of HLA-DR is a common finding in both FHL and EBV-associated HLH or other acquired HLH [1, 3]. In this case, downregulation of CD5 and CD7 was found, as reported previously [1, 3]. The cause of downregulation of CD5 expression in acquired HLH or FHL remains unclear. Some authors have suggested a link between CD5 downregulation in T cells and monoclonal proliferation [6]. n nOur case also showed monoclonality in the TCR gene rearrangement study. Monoclonality in the TCR gene rearrangement study is also a common finding in EBV-associated HLH [9]. Monoclonal T cell proliferation in FHL has also been reported [10]. Moreover, the study also reported clonal changes in T cell populations after treatment (monoclonal to polyclonal) [10]. These results might help shed light on the pathogenesis underlying clonal proliferation of T cells and downregulation of CD5 in HLH. n nTo the best of our knowledge, this is the first report on FHL with an abnormal immunophenotype and T cell monoclonality in Korea. Further studies are needed to characterize the immunophenotypic features and clonality of T cells in FHL and their diagnostic or clinical significance.