[show abstract][hide abstract] ABSTRACT: Gelsolin and matrix metalloproteinase 12 (MMP12) expression has been reported in Langerhans cell histiocytosis (LCH), but the clinical significance of this expression is unknown. We investigated the associations of these proteins with clinical manifestations in patients diagnosed with LCH.
We performed a retrospective analysis of clinical data from patients diagnosed with LCH and followed up between 1998 and 2008. Available formalin-fixed, paraffin-embedded specimens were used for gelsolin and MMP12 immunohistochemical staining. We analyzed the expression levels of these proteins and their associations with LCH clinical features.
Specimens from 36 patients (20 males, 16 females) with a diagnosis of LCH based on CD1a positivity with clinical manifestations were available for immunohistochemical staining. Median patient age was 62 months (range, 5 to 207). The expression of gelsolin varied; it was high in 17 patients (47.2%), low in 11 patients (30.6%), and absent in 8 patients (22.2%). The high gelsolin expression group had a higher tendency for multi-organ and risk organ involvement, although the trend was not statistically significant. MMP12 was detected only in 7 patients (19.4%) who showed multi-system involvement (P=0.018) and lower event-free survival (P=0.002) in comparison to patients with negative MMP12 staining.
Gelsolin and MMP12 expression may be associated with the clinical course of LCH, and MMP12 expression may be particularly associated with severe LCH. Further studies of larger populations are needed to define the precise role and significance of gelsolin and MMP12 in the pathogenesis of LCH.
The Korean journal of hematology 12/2012; 47(4):267-72.
[show abstract][hide abstract] ABSTRACT: Ventilator-associated pneumonia (VAP) requires prompt and appropriate treatment. Since methicillin-resistant Staphylococcus aureus (MRSA) is a frequent pathogen in VAP, rapid identification of it, is pivotal. Our aim was to evaluate the utility of quantitative polymerase chain reaction (qPCR) as a useful method for etiologic diagnoses of MRSA pneumonia.
We performed qPCR for mecA, S. aureus-specific femA-SA, and S. epidermidis-specific femA-SE genes from bronchoalveolar lavage or bronchial washing samples obtained from clinically-suspected VAP. Molecular identification of MRSA was based on the presence of the mecA and femA-SA gene, with the absence of the femA-SE gene. To compensate for the experimental and clinical conditions, we spiked an internal control in the course of DNA extraction. We estimated number of colony-forming units per mL (CFU/mL) of MRSA samples through a standard curve of a serially-diluted reference MRSA strain. We compared the threshold cycle (Ct) value with the microbiologic results of MRSA.
We obtained the mecA gene standard curve, which showed the detection limit of the mecA gene to be 100 fg, which corresponds to a copy number of 30. We chose cut-off Ct values of 27.94 (equivalent to 1×10(4) CFU/mL) and 21.78 (equivalent to 1×10(5) CFU/mL). The sensitivity and specificity of our assay were 88.9% and 88.9% respectively, when compared with quantitative cultures.
Our results were valuable for diagnosing and identifying pathogens involved in VAP. We believe our modified qPCR is an appropriate tool for the rapid diagnosis of clinical pathogens regarding patients in the intensive care unit.
Tuberculosis and Respiratory Diseases 03/2012; 72(3):293-301.
[show abstract][hide abstract] ABSTRACT: Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT) are caused by a mutation in the WAS gene on Xp11.22. We report two patients with IVS6+5G>A of WAS in a Korean family. The proband presented with classic WAS, whereas his maternal cousin had symptoms limited to XLT. Their mothers were proved to be carriers. The IVS6+5G>A mutation was reported to result in incomplete splicing of the donor site and typically associated with mild form of disease, XLT. Our observation of the intrafamilial variability of clinical manifestations of WAS further expands the genotype-phenotype correlations and suggests the presence of modifying genetic factors.
Pediatric Blood & Cancer 02/2012; 58(2):297-9. · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Atopic dermatitis is a chronic, allergic inflammatory skin disease that is accompanied by markedly increased levels of inflammatory cells, including eosinophils, mast cells, and T cells. Arctium lappa L. is a traditional medicine in Asia. This study examined whether a butanol extract of A. lappa (ALBE) had previously unreported anti-allergic or anti-inflammatory effects.
This study examined the effect of ALBE on the release of β-hexosaminidase in antigen-stimulated-RBL-2H3 cells. We also evaluated the ConA-induced expression of IL-4, IL-5, mitogen-activated protein kinases (MAPKs), and nuclear factor (NF)-κB using RT-PCR, Western blotting, and ELISA in mouse splenocytes after ALBE treatment.
We observed significant inhibition of β-hexosaminidase release in RBL-2H3 cells and suppressed mRNA expression and protein secretion of IL-4 and IL-5 induced by ConA-treated primary murine splenocytes after ALBE treatment. Additionally, ALBE (100 μg/mL) suppressed not only the transcriptional activation of NF-κB, but also the phosphorylation of MAPKs in ConA-treated primary splenocytes.
These results suggest that ALBE inhibits the expression of IL-4 and IL-5 by downregulating MAPKs and NF-κB activation in ConA-treated splenocytes and supports the hypothesis that ALBE may have beneficial effects in the treatment of allergic diseases, including atopic dermatitis.
Clinical and Molecular Allergy 02/2011; 9(1):4. · 1.39 Impact Factor
[show abstract][hide abstract] ABSTRACT: It has been hypothesized that genetic alteration at the cellular level may have a significant effect on cellular mechanisms controlling the proliferation and apoptosis of Langerhans cells (LCs).
We examined whether p16 protein expression can be used to predict the outcome of Langerhans cell histiocytosis (LCH). Archival paraffin blocks from children diagnosed with LCH and followed at the Asan Medical Center and Chungnam National University Hospital between March 1998 and February 2008 were studied.
Slides were stained with p16 antibody and evaluated semi-quantitatively using the following scale: negative, no staining; ±, weakly positive; 1+, staining similar to lymphocytes surrounding the LCs; 2+, stronger staining than lymphocytes; 3+, much stronger staining than lymphocytes. Negative and ± groups were assigned to a lower expression group (LEG) and the 1+, 2+, and 3+ groups were assigned to a higher expression group (HEG). The median age of the 51 patients (24 girls, 27 boys) was 49 (range, 0.6-178) months, and LCH was diagnosed based on CD1a positivity. p16 protein was expressed to varying degrees in all but one specimen. There was a greater tendency toward multisystem disease, risk organ involvement, and relapse in the HEG than in the LEG.
The p16 protein may have a significant effect on cellular mechanisms controlling the proliferation and apoptosis of LCs, and thus may influence the clinical outcome and prognosis of LCH.
The Korean journal of hematology 12/2010; 45(4):247-52.
[show abstract][hide abstract] ABSTRACT: Up to 90% of neonates with congenital or perinatal cytomegalovirus (CMV) infection are asymptomatic, and little is known about CMV-associated thrombocytopenia after the neonatal period. We investigated the clinical findings of a series of infants diagnosed with CMV infection and thrombocytopenia.
From July 2005 to July 2008, infants aged younger than 6 months with thrombocytopenia were screened for CMV infection, using CMV IgM. Those who were positive for CMV IgM were then tested for CMV IgG via polymerase chain reaction (PCR) for CMV and CMV pp65 Ag and urine culture. Brain magnetic resonance imaging (MRI) and otologic and ophthalmologic evaluations were also performed.
Twenty-one patients aged between 1 and 6 months (11 boys and 10 girls) were admitted and tested for CMV infection. Six patients (28.6%) were positive for CMV IgM; these were also positive for CMV IgG, CMV PCR, and urine culture, and 4 were also positive for CMV pp65 Ag. The median platelet count at admission was 6,500/µL (range, 2,000-105,000/µL). One patient (16.7%) was diagnosed with Evans syndrome and had calcifications on brain MRI. One patient had unilateral sensorineural hearing loss.
Thrombocytopenia can be the main clinical manifestation of otherwise asymptomatic CMV infection after the neonatal period, and close follow-up of neurodevelopmental sequelae is needed.
The Korean journal of hematology 03/2010; 45(1):29-35.
[show abstract][hide abstract] ABSTRACT: Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by pure red cell aplasia, various congenital anomalies, and cancer predisposition. We report a novel mutation in the RPS17 gene in a Korean patient with DBA. The mutation occurred in the translation initiation codon, changing Atg to Gtg (c.1A>G), thus disrupting the natural start of the RPS17 protein biosynthesis. This is the third case of DBA from a RPS17 mutation in the literature and is the second case of a RPS17 mutation in the translation initiation codon, following c.2T>G.
Pediatric Blood & Cancer 12/2009; 54(4):629-31. · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Spontaneous regression of cancers is extremely rare and is associated with specific malignancies. Spontaneous regression of bronchogenic lung cancer has rarely been reported, and regression of small cell lung cancer is even less common. Such regression is generally ascribed to immunological factors but is not well understood. This case report describes a patient with spontaneous regression of small cell lung cancer that has persisted for 11 years and considers possible mechanisms.