Expression of toll-like receptor 2 and 4 is increased in the respiratory epithelial cells of chronic idiopathic interstitial pneumonia patients

Go, H.,Koh, J.,Kim, H.S.,Jeon, Y.K.,Chung, D.H. Baillière Tindall, in association with the 2014 Respiratory medicine Vol.108 No.5

Background: Idiopathic interstitial pneumonia (IIP) is characterized by chronic interstitial inflammation and fibrosis. Although mounting evidence has suggested that toll-like receptor (TLR) 2 and TLR4 are involved in the pathogenesis of non-infectious lung injury in vitro and in mouse models, their roles in human IIP remain unknown. Methods: To address this issue, we investigated the expression patterns of TLR2 and TLR4 by immunohistochemistry in resected lung tissues from patients with usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP). Results: Type II pneumocytes, bronchial epithelial cells (BECs), and alveolar macrophages accounted for the majority of TLR2- and TLR4-expressing cells in both UIP and NSIP. The numbers of TLR2 and TLR4-positive respiratory epithelial (RE) cells, including type II pneumocytes and BECs, were significantly greater in UIP and NSIP than in the control. In particular, the numbers of TLR2-positive RE cells were much greater in UIP than in NSIP. The intensities of TLR2 and TLR4 expression in type II pneumocytes were also significantly stronger in UIP and NSIP than in the control. A comparison of the TLR expression patterns between the fibroblastic and fibrotic areas in UIP indicated that the numbers TLR2 and TLR4-positive RE cells were similar in fibroblastic areas, whereas the TLR2-positive RE cells outnumbered the TLR4-positive RE cells in the fibrotic areas. Conclusions: This study demonstrates that RE cells over-express TLR2 and TLR4 in the lungs of IIP patients. These findings suggest that high expression of TLRs may contribute to the pathogenesis of human IIP.

Comparison of MRI features and surgical outcome among the subtypes of focal cortical dysplasia

Kim, D.W.,Kim, S.,Park, S.H.,Chung, C.K.,Lee, S.K. Baillière Tindall ; W.B. Saunders 2012 SEIZURE Vol.21 No.10

Purpose: Focal cortical dysplasia (FCD) is the most common pathological diagnosis in patients who have undergone surgical treatment for intractable neocortical epilepsy. However, presurgical identification of MRI abnormalities in FCD patients remains difficult, and there are no highly sensitive imaging parameters available that can reliably differentiate among FCD subtypes. The purpose of our study was to investigate the surgical outcome in FCD patients with identifiable MRI abnormalities and to evaluate the prognostic role of the various MRI features and the characteristics of FCD pathology. Methods: We retrospectively recruited epilepsy patients who had undergone surgical treatment for refractory epilepsy with focal MRI abnormalities and the pathological diagnosis of FCD. We evaluated the surgical outcome according to the pathological subtypes, and studied the prognostic roles of various MRI features. We used recently proposed three-tiered FCD classification system which included FCD type III when FCD occurs in association with other potentially epileptogenic pathologies. Results: A total of 69 patients were included, and 68.1% of patients became seizure free. Patients with FCD type III had a lower chance for achieving seizure freedom (7/15) than in patients with isolated FCD (FCD types I and II) (40/54, p=0.044). Cortical thickness and blurring of gray-white matter junction were more common in isolated FCD than in FCD type III, but most MRI features failed to differentiate between FCD types I and II, and only the transmantle sign was specific for FCD type II. We failed to find a prognostic value of specific MRI abnormalities of prognostic value in terms of post-epilepsy surgery outcome in FCD patients. Conclusions: Our study showed that patients with FCD III have poor surgical outcome. Typical MRI features of isolated FCD such as cortical thickness and blurring of gray-white matter junction were less common in FCD type III and only transmantle sign was helpful in differentiating between FCD types I and II.

RUNX3 confers sensitivity to pheophorbide a-photodynamic therapy in human oral squamous cell carcinoma cell lines.

Moon, Sook,Bae, Jung Yoon,Son, Hwa-Kyung,Lee, Doo Young,Park, Gyeongju,You, Hyun,Ko, Hyojin,Kim, Yong-Chul,Kim, Jin Baillière Tindall ; Springer London 2015 LASERS IN MEDICAL SCIENCE Vol.30 No.2

<P>Photodynamic therapy (PDT) with photosensitizer is one of the promising modalities for cancer treatment. For clinical use of PDT, screening process should be preceded to enhance sensitivity to PDT. Thus, we investigated a molecular biomarker to determine the sensitivity to pheophorbide a (Pa)-PDT in immortalized human oral keratinocytes (IHOK) and oral squamous cell carcinoma (OSCC) cell lines. Two IHOK and several OSCC cell lines were used. After Pa-PDT, cell viability was reduced by more than 50%, and reactive oxygen species were generated in IHOK and OSCC cell lines. Additionally, apoptosis occurred in PDT-treated cells. IHOK(S) and IHOK(P), the two IHOK cell lines derived from the same source, showed a difference in cytotoxicity after Pa-PDT. To explain this difference in cytotoxicity, we looked at the expression of Wnt signaling-related genes in these two cell lines, for the morphology of IHOK(S) which was spindle like and elongated and distinct from IHOK(P) and the parent cell. Among the relevant genes, runt-related transcription factor 3 (RUNX3), an apoptosis-related gene, was selected as a potential marker that confers sensitivity to PDT. We found that the cytotoxicity by Pa-PDT was proportional to RUNX3 expression in OSCC cell lines. Additionally, knockdown of RUNX3 expression reduced cytotoxicity by Pa-PDT, suggesting that RUNX3 might be a biomarker to determine sensitivity to Pa-PDT. This was the first study to find a new target molecule that enhances Pa-PDT effects in IHOK and OSCC cell lines. Hence, the development of a PDT-dependent biomarker could provide a novel approach to improve the effects of PDT on oral precancerous and cancerous lesions.</P>

Therapeutic effects of systemic photodynamic therapy in a leukemia animal model using A20 cells.

Wen, Lan Ying,Bae, Su-Mi,Chun, Heung-Jae,Park, Kye-Shin,Ahn, Woong Shick Baillière Tindall ; Springer London 2012 LASERS IN MEDICAL SCIENCE Vol.27 No.2

<P>Photodynamic therapy (PDT) is attracting attention because of its noticeable inhibitory effects on the growth of dermatological and other solid tumors. Here, we studied the use of PDT in systemic diseases such as leukemia, lymphoma, and metastatic cancer, for which tumor formation areas cannot be clearly compartmentalized. We developed a systemic PDT method and examined its effect in a leukemia mouse model. Growth inhibition of A20 cells (H-2(d), murine B-lymphoma/leukemia, and Balb/c origin) induced by PDT/Photodithazine was evaluated by EZ-Cytox assay. After PDT, changes in cell morphology were assessed by light microscopy. Induction of apoptosis, as well as changes in the cell cycle, were assessed by fluorescence-activated cell sorting (FACS) analysis. A20 cells were injected into Balb/c mice through the tail veins, and PDT was performed. A total of 10 mg kg(-1) body weight of Photodithazine concentration was injected intravenously. After 5 min, micro photofibers (diameter, 200 μm) were inserted into the tail veins and irradiated at 1,200 J with a laser. PDT inhibited growth of A20 cells and resulted in marked morphological changes. PDT also induced apoptosis and G1 arrest. In a leukemia mouse model, systemic PDT increased the survival rate (p < 0.01). This is the first report of the effects of systemic PDT in a leukemia animal model. PDT has been applied only locally in most cases, for example to solid tumors. This study provides experimental evidence that systemic PDT could effectively be applied to systemic and spread tumors, for which tumor formation areas cannot clearly be determined.</P>

Effect of 635 nm irradiation on high glucose-boosted inflammatory responses in LPS-induced MC3T3-E1 cells.

Kwon, HyukIl,Lim, WonBong,Kim, JiSun,Jeon, SangMi,Kim, SangWoo,Karna, Sandeep,Cha, HyunRok,Kim, OkJoon,Choi, HongRan Baillière Tindall ; Springer London 2013 Lasers in medical science Vol.28 No.3

<P>Hyperglycemia occurs in patients with poorly controlled diabetes mellitus and contributes to bone resorption and increased susceptibility to bacterial infections. Hyperglycemia can incite low-grade inflammation that can contribute to the resorption of bone, especially the periodontal bone. The increased susceptibility to periodontal infections can contribute to bone resorption through the activation of osteoclasts. In this study, the osteoblastic, clonal cell line, MC3T3-E1, was used in an in vitro model of hyperglycemia and lipopolysaccharide-induced reactive oxygen species generation to determine the potential anti-inflammatory effect of 635 nm light-emitting diode (LED) irradiation or whether 635 nm LED irradiation can be a potential anti-inflammatory treatment. LED irradiation of MC3T3-E1 cells stimulated with lipopolysaccharide in a high glucose-containing medium decreased the level of cyclooxygenase gene and protein expression and reduced the level of prostaglandin E2 expression by decreasing the amount of reactive oxygen species generation. LED irradiation also inhibited the osteoclastogenesis in MC3T3-E1 cells by regulating the receptor activator of nuclear factor kappa-B ligand and osteoprotegerin. These findings reveal the mechanisms which are important in the pathogenesis of diabetic periodontitis and highlight the beneficial effects of 635 nm LED irradiation in reducing the adverse effects of diabetic periodontitis.</P>

Association of interleukin-25 levels with development of aspirin induced respiratory diseases

Lee, J.U.,Chang, H.S.,Lee, H.J.,Bae, D.J.,Son, J.H.,Park, J.S.,Choi, J.S.,Hwang, H.G.,Park, C.S. Baillière Tindall, in association with the 2017 Respiratory medicine Vol.123 No.-

<P>Conclusions: IL-25 is associated with bronchospasm after aspirin challenge, possibly via mechanisms other than altered LTC4 and PGD2 production. (C) 2016 Elsevier Ltd. All rights reserved.</P>

The effects of minimally invasive laser needle system on suppression of trabecular bone loss induced by skeletal unloading.

Ko, Chang-Yong,Kang, Heesung,Ryu, Yeonhang,Jung, Byungjo,Kim, Hyunsoo,Jeong, Daewon,Shin, Hong-In,Lim, Dohyung,Kim, Han Sung Baillière Tindall ; Springer London 2013 Lasers in medical science Vol.28 No.6

<P>This study was aimed to evaluate the effects of low-level laser therapy (LLLT) in the treatment of trabecular bone loss induced by skeletal unloading. Twelve mice have taken denervation operation. At 2 weeks after denervation, LLLT (wavelength, 660 nm; energy, 3 J) was applied to the right tibiae of 6 mice (LASER) for 5 days/week over 2 weeks by using a minimally invasive laser needle system (MILNS) which consists of a 100 μm optical fiber in a fine needle (diameter, 130 μm) [corrected]. Structural parameters and histograms of bone mineralization density distribution (BMDD) were obtained before LLLT and at 2 weeks after LLLT. In addition, osteocyte, osteoblast, and osteoclast populations were counted. Two weeks after LLLT, bone volume fraction, trabeculae number, and trabeculae thickness were significantly increased and trabecular separations, trabecular bone pattern factor, and structure model index were significantly decreased in LASER than SHAM (p?<?0.05). BMDD in LASER was maintained while that in SHAM was shifted to lower mineralization. Osteocyte and osteoblast populations were significantly increased but osteoclast population was significantly decreased in LASER when compared with those in SHAM (p?<?0.05). The results indicate that LLLT with the MILNS may enhance bone quality and bone homeostasis associated with enhancement of bone formation and suppression of bone resorption.</P>

Epithelial apoptosis as a clinical marker in idiopathic interstitial pneumonia

Chung, W.Y.,Sun, J.S.,Park, J.H.,Lee, H.L.,Lee, K.S.,Kim, Y.S.,Sheen, S.S.,Park, K.J.,Hwang, S.C.,Lee, K.B.,Park, K.J. Baillière Tindall, in association with the 2010 Respiratory medicine Vol.104 No.11

Backgrounds: Epithelial cell apoptosis plays an important role in the pathogenesis of idiopathic interstitial pneumonia (IIP). Methods: Serum levels of caspase-cleaved cytokeratin-18 (M30) were measured in 55 patients with IIP and 34 healthy controls using enzyme-linked immunosorbent assays. The IIP cases included usual interstitial pneumonia (UIP; n = 30), nonspecific interstitial pneumonia (NSIP; n = 15), and cryptogenic organizing pneumonia (COP; n = 10). The radiological scoring was performed based on high-resolution computed tomography (HRCT) findings. Results: Patients with IIP had higher serum M30 levels than did the control group (178.6 +/- 91.5 vs. 113.7 +/- 46.8 U/L, p < 0.05). Among IIP patients, COP patients had higher serum M30 levels than did UIP or NSIP patients (264.9 +/- 132.7, 139.2 +/- 49.7, and 201.2 +/- 81.1 U/L, respectively; COP vs. UIP, p < 0.01). Serum M30 levels were negatively correlated with forced vital capacity (FVC; r<SUB>s</SUB> = -0.31), percent-predicted FVC (FVC%; r<SUB>s</SUB> = -0.38), and percent-predicted forced expiratory volume in 1 s (FEV<SUB>1</SUB>%; r<SUB>s</SUB> = -0.36). Serum M30 levels were correlated with radiological ground-glass opacity scores (r<SUB>s</SUB> = 0.61). Conclusion: The epithelial apoptosis marker serum level was correlated with IIP clinical status and is a potential marker to assess IIP.

Clinical characteristics of health care-associated pneumonia in a Korean teaching hospital

Park, H.K.,Song, J.U.,Um, S.W.,Koh, W.J.,Suh, G.Y.,Chung, M.P.,Kim, H.,Kwon, O.J.,Jeon, K. Baillière Tindall, in association with the 2010 Respiratory medicine Vol.104 No.11

Background: Health care-associated pneumonia (HCAP) has been proposed as a new category of respiratory infection. ATS/IDSA guidelines state that all patients with HCAP should receive empirical therapy directed at multidrug-resistant pathogens. However, recent data from other countries have reported a different picture of HCAP. Methods: We conducted a retrospective observational study of patients with HCAP and CAP who were hospitalized through the emergency department in January-December 2008 at Samsung Medical Center, Seoul, Korea, and compared clinical characteristics, severity, distribution of pathogen, and outcomes. Results: In total, 345 patients hospitalized with pneumonia were eligible, 182 (52.8%) with HCAP and 163 (47.2%) with CAP. Patients with HCAP had greater comorbidity and higher Pneumonia Severity Index (PSI) score (P < 0.001). Although Streptococcus pneumoniae was the most frequently isolated pathogen in HCAP and CAP patients, the occurrence of potentially drug-resistant pathogens (29.3% vs. 13.0%; P = 0.044) and inappropriate initial antimicrobial treatment (24.6% vs. 8.7%; P = 0.032) were significantly higher in HCAP patients. Patients with HCAP had a longer duration of hospital stay (13 [8-18] vs. 8 [6-12] days; P < 0.001), and higher in-hospital mortality (19.2% vs. 7.4%; P = 0.001). In a multiple logistic regression analysis, however, in-hospital mortality was independently associated with higher PSI class (OR 2.82, 95% CI 1.19-6.70) and ICU admission (OR 15.37, 95% CI 3.58-66.05). Conclusions: Severity of illness, rather than type of pneumonia, was the main predicting factor for in-hospital mortality among patients with pneumonia hospitalized through the emergency department.

Apoptotic effect of pheophorbide a-mediated photodynamic therapy on DMBA/TPA-induced mouse papillomas.

Zhang, Xianglan,Choi, Eun Joo,Zheng, Zhenlong,Zhu, Lianhua,Cho, Sung Bin,Kim, Ki-Yoel,Kim, Jin,Cha, In-Ho Baillière Tindall ; Springer London 2015 LASERS IN MEDICAL SCIENCE Vol.30 No.1

<P>Pheophorbide a (Pa) is a chlorine-based photosensitizer, and Pa-mediated photodynamic therapy (PDT) reportedly exhibits antitumor activity against various malignancies. The aim of our study was to investigate the therapeutic effect of Pa-mediated PDT on 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorobol-13-acetate (TPA)-induced mouse papillomas. Thirty mice received a topical application of DMBA/TPA on their backs to induce mouse papillomas. One week after two sessions of Pa-mediated PDT, immunohistochemical stains and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed to evaluate the apoptotic effects thereof on the papillomas. Among 63 mouse papillomas treated with Pa-mediated PDT, 17.5% of the lesions were completely removed 1 week after the first treatment, while 31.7% disappeared 1 week after the second treatment. Statistical analyses revealed significant differences in therapeutic outcomes for the Pa-mediated PDT group in comparison to a solvent-PDT group and a Pa group. Additionally, a marked downregulation of proliferating cell nuclear antigen expression, as well as upregulation of cleaved caspase 3 and cleaved poly(ADP-ribose) polymerase expression, was noted in the Pa-PDT group, compared to the solvent-PDT group and Pa group. TUNEL assay revealed higher apoptotic cell counts in the Pa-PDT group, although the difference was not statistically significant. Our data demonstrated that Pa-mediated PDT is effective in treating DMBA/TPA-induced mouse papillomas.</P>