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Ethyl carbamate (EC) has been identified as a possible human carcinogen belonging to Group 2A. EC is naturally formed during the fermentation and storage of alcoholic drinks and fermented foods. When ingested in large amounts, EC can cause various health problems, such as gastroenteric hemorrhage, vomiting, and cancer. In this study, optimization of EC formation from cyanate was examined using response surface methodology (RSM), a central composite design that includes variables such as alcohol concentration (10, 15, 20, 25, and 30%), pH (2.5, 3.0, 3.5, 4.0, and 4.5), storage temperature (5, 10, 15, 20, and 25°C), and storage duration (2, 4, 6, 8, and 10 days). EC content was determined using gas chromatography with flame ionization detection and the results were optimized using RSM. EC formation from cyanate degradation was found to increase with storage duration and temperature, acidity, and alcohol concentration. Cy-anate degradation was associated with the formation of EC. Approximately 83.1±0.1% of cyanate was degraded to 538±9 μM of EC. However, not all of the cyanate reacted with ethanol during fermentation to form EC. This study aimed to develop the ideal conditions for EC analysis to reduce EC production in alcoholic drinks and fermented foods.

Background: The purpose of this study is to see if exfoliative pulmonary airway pathology in cancer-free coal workers’ pneumoconiosis (CWP) can be used as a biomarker for predicting pulmonary morbidity. Methods: We investigated persistent metaplastic changes in bronchoscopic washing cytology and differential cell counts in bronchoalveolar lavages (BAL) in 97 miners with CWP and 80 miners without CWP as the control. Clinicopathological parameters were examined including pulmonary function tests and the presence of progressive massive fibrosis. Results: When compared to the control group, severe alveolitis, severe goblet cell hyperplasia (GCH), severe hyperplastic epithelial change, and severe squamous metaplasia were the distinguishing biomarkers in CWP. Multivariate analysis revealed that severe alveolitis and severe GCH, along with miner duration and current smoker, were independent predictors of pulmonary mortality. The survival analysis revealed a significantly different survival rate between the three groups: no evidence of severe alveolitis and severe GCH, presence of severe alveolitis or severe GCH but not both, and both severe alveolitis and severe GCH. Conclusions: The severities of alveolitis and goblet cell hyperplasia in the bronchoscopic study are independent prognostic factors for CWP. A pathologic grading system based on these two parameters could be used in the stratification and clinical management of CWP patients.

A major outbreak of the Middle East Respiratory Syndrome Corona Virus (MERS-CoV) was first reported in Riyadh, Saudi Arabia from 2012 to 2014 (1). The computed tomography (CT) images of patients in Saudi Arabia predominantly showed ground-glass opacity, mostly in the lower peripheral lobes of the lungs (2). On May 20, 2015, the first case of MERS-CoV infection was reported in South Korea. A subsequent major outbreak in health care settings caused the disease to spread nationwide. Concerns over this outbreak were heightened, owing to a novel MERSCoV with the potential to rapidly disseminate from person to person and devastate the lungs. Herein, we described the radiologic appearance of a fatal case of a novel MERS-CoV infection. The Yeouido St. Mary’s Hospital Institutional Review Board (IRB) determined that our case report was exempt from IRB review on June 30, 2015.

To detect threat signals in electronic warfare support systems, a detector that uses a plurality of windows with various sizes should be designed such that the length of all the signal sources can be considered. Since a large number of these windows cause excessive computational complexity, the number of windows of the detector is reduced by using a small number of representative windows. In this case, since a window is dedicated to the unknown signal of a certain interval, deterioration of the detection performance is inevitable owing to the inconsistency between the lengths of the received signal and the window size. Hence, the deterioration of the detection performance should be minimised by analysing the relation between the lengths of a window and a signal. However, the conventional analysis methods of detection performance are not suitable because they are based on the premise that the lengths of the signal and window are consistent with each other. The authors propose a novel analysis method using processing gain to overcome this limitation, which can be applied irrespective of the inconsistency between the lengths of a window and a signal. Based on this analysis, they present a method to obtain an optimal window length that minimises degradation of the detection performance and subsequently verify the result using simulation.

To review clinical and CT findings of airway foreign bodies (FBs) among children, with an emphasis on delayed diagnosis and differentiation from mucus plugs (MPs). The CT findings and medical records of 27 patients (M:F = 17:10; mean age, 18.2 months) confirmed for FB (n = 20) and MP (n = 7) were reviewed. These findings were correlated with the bronchoscopic results and clinical outcomes. CT revealed air-trapping (70 %), atelectasis (35 %), pneumonia (25 %), and pneumomediastinum (5 %). Three patients with FB in the carina did not show air-trapping. The densities of the FBs ranged from 17 to 123 Hounsfield units (HU) (n = 17). Eight out of 20 patients (33 %) had a delayed diagnosis of FB. The CT of eight patients revealed air-trapping (n = 2), air-trapping with pneumonia or atelectasis (n = 3), and atelectasis only (n = 1). The airway MPs had a low density (0–5 HU) and were associated with atelectasis (29 %), atelectasis with pneumonia (43 %), and pneumonia (14 %). Air-trapping of the ipsilateral lung may not be a reliable finding among patients with an FB located in the carina and with a small-calibered FB. The absence of air-trapping, the difference in the HU, and the shape of the endobronchial lesion are helpful findings in the differential diagnosis of an MP.

A 52-year-old woman with rheumatoid arthritis who had been treated with prednisone and hydroxychloroquine for >12 years presented with chest discomfort and a seizure. She was diagnosed with restrictive cardiomyopathy combined with sick sinus syndrome. A myocardial muscle biopsy was performed to identify the underlying cardiomyopathy, which showed marked muscle fiber hypertrophy, fiber dropout, slightly increased interstitial fibrous connective tissue, and extensive cytoplasmic vacuolization of the myocytes under light microscopy. Electron microscopy of the myocytes demonstrated dense, myeloid, and curvilinear bodies. The diagnosis of hydroxychloroquine-induced cardiomyopathy was made based on the clinical, hemodynamic, and pathologic findings. This is the first case report describing chloroquine-induced cardiomyopathy involving the heart conduction system.

To retrospectively evaluate magnetic resonance imaging (MRI) features of breast cancer after high-intensity focused ultrasound (HIFU) ablation.Six patients with invasive ductal carcinomas underwent HIFU ablation. In all patients, dynamic MRI was performed prior to and two weeks after HIFU. Serial follow-up studies were performed. Changes in signal intensity and size of the index tumour in addition to peripheral enhancement patterns were evaluated. Histopathological results were compared with MRI findings.All patients had a single index tumour with a mean size 25.6 mm (range 12 to 37 mm) at the ablation time. In three of six patients, thin rim enhancement around the ablation zone was seen on the subtraction image after first ablation, which showed no change on follow-up MRI. Complete ablation was confirmed by the histopathology (biopsy in two and surgery in one). In the remaining three patients, nodular or irregular thick enhancement was shown on the subtraction image and viable tumour was confirmed by surgery and biopsy in two patients.The MR characteristics of successfully ablated breast cancers included central dark signal intensities with thin rim enhancement on subtraction images. Nodular or irregular thick enhancements should raise concern of partial ablation. We propose MRI plays a critical role in assessing the effectiveness of HIFU treatment.

Sarcoidosis is a systemic disorder of unknown cause that is characterized by the presence of noncaseating granulomas. The radiological findings associated with sarcoidosis have been well described. The findings include symmetric, bilateral hilar and paratracheal lymphadenopathy, with or without concomitant parenchymal abnormalities (multiple small nodules in a peribronchovascular distribution along with irregular thickening of the interstitium). However, in 25% to 30% of cases, the radiological findings are atypical and unfamiliar to most radiologists, which cause difficulty for making a correct diagnosis. Many atypical forms of intrathoracic sarcoidosis have been described sporadically. We have collected cases with unusual radiological findings associated with pulmonary sarcoidosis (unilateral or asymmetric lymphadenopathy, necrosis or cavitation, large opacity, ground glass opacity, an airway abnormality and pleural involvement) and describe the typical forms of the disorder as well. The understanding of a wide range of the radiological manifestations of sarcoidosis will be very helpful for making a proper diagnosis.

− Previously, we identified albumin as an inhibitory factor in serum for cell adhesion of T cells such ashuman Jurkat T and primary cultured human T cells. In the present study, we found that other hematopoieticcell lines including U-937 human monocytes, THP-1 human monocytes, K-562 promyelocytic leukemia cells,and HL-60 human leukemia cells, also adhere to tissue culture flasks when serum is withdrawn, and albuminexerts an inhibitory effect on cell adhesion by those cells, implying that this inhibition is a common phenomenonin hematopoietic cells. Furthermore, we found that cell adhesion is inhibited by antioxidants such as (-)-epigal-locatechin-3-gallate (EGCG), morin, and a-tocopherol. Our results suggest that albumin may inhibit basal celladhesion of hematopoietic cells and that the oxidative balance in the plasma may be important for cell adhe-sion of hematopoietic cells in vivo . Keywords : Monocytes, Leukocytes, Albumin, Adhesion, Hematopoietic cells, Oxidative signaling

Aim: To study the effects of dibenzocyclooctadiene lignans isolated from Schisandra chinensis , such as wuweizisu C, gomisin N, gomisin A, and schisandrin, on the membrane potential in C6 glioma cells. Methods: The membrane potential was estimated by measuring the fluorescence change in DiBAC-loaded glioma cells. Results: Wuweizisu C decreased the membrane potential in a concentration-dependent manner. Gomisin N and gomisin A, however, showed differential modulation and no change was induced by schisandrin or dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylene dioxybipheny 1-2,2′-dicarboxylate, a synthetic drug derived from dibenzocyclooctadiene lignans. We found no involvement of Gi/o proteins, phospholipase C, and extracellular Na + on the wuweizisu C-induced decrease of the membrane potential. Wuweizisu C by itself did not change the intracellular Ca 2+ [Ca 2+ ]i concentration, but decreased the ATP-indu-ced Ca 2+ increase in C6 glioma cells. The 4 lignans at all concentrations used in this study did not induce any effect on cell viability. Furthermore, we found a similar decrease of the membrane potential by wuweizisu C in PC12 neuronal cells. Conclusion: Our results suggest that the decrease in the membrane potential and the modulation of [Ca 2+ ]i concentration by wuweizisu C could be important action mechanisms of wuweizisu C.

Previously, we studied N,N-dimethyl- d -erythro-sphingosine (DMS)-induced cell death and signaling in U937 human monocytes; we found that DMS-induced sphingosine kinase- and PKC-independent apoptosis. In the present study, we studied apoptotic responses by three N-methyl derivatives of sphingosine: N-monomethyl- d -erythro-sphingosine (MMS), N,N,N-trimethyl- d -erythro-sphingosine (TMS), and d -erythro-sphingosine (SPH). The potency order in the apoptotic response was DMS ≥ MMS > TMS > SPH. We compared cellular responses to the derivatives in terms of activities of MAPK signaling molecules, mitochondrial membrane potential (ΔΨm), and reactive oxygen species (ROS) generation. Our results suggest that the degree of N-methylation affects the apoptosis-inducing capacity and other related responses including MAPK modulation, ΔΨm, and ROS generation. Dimethylation and monomethylation on the C2 amine of sphingosine enhance the apoptotic response; however, trimethylation induces differential modulation of signaling molecules and less cytotoxicity. Our investigation will be useful for understanding the actions of sphingolipids in apoptosis and for developing chemotherapeutics based on DMS structure.

N,N-dimethyl-D-erythro-sphingosine (DMS), an N-methyl derivative of sphingosine, is an inhibitor of protein kinase C (PKC) and sphingosine kinase (SK). In previous reports, DMS-induced intracellular Ca2+ increase concentration ([Ca2+]i) was studied in T lymphocytes, monocytes, astrocytes and neuronal cells. In the present study, we studied DMS-induced increase of [Ca2+]i in HCT116 human colon cancer cells. We found that the DMS-induced increase of [Ca2+]i in colon cancer cells is composed of Ca2+ release from intracellular Ca2+ stores and subsequent Ca2+ influx. The Ca2+ release is not related to modulation of inositol 1,4,5-trisphosphate (IP3) receptor or ryanodine receptor. On the other hand, the Ca2+ influx is mediated largely through Ca2+ channels sensitive to verapamil, nifedipine, Ga3+, and La3+. Furthermore, we found that the response is inhibited by bepridil and Ni2+, specific inhibitors of Na+-Ca2+-exchanger, suggesting involvement of Na+-Ca2+ exchanger in the DMS-induced [Ca2+]i increase in colon cancer cells. This inhibition was also observed in U937 monocytes, but not in 1321N1 astrocytes.

We investigated the effects of serum on lysophospholipid-induced cytotoxicity in Jurkat T cells. We found that sphingosylphosphorylcholine (SPC, also known as lysosphingomyelin) induced cytotoxicity and that albumin in serum could protect cells by binding directly to SPC. Furthermore, we also found that SPC induced ROS generation, increased [Ca(2+)](i), and decreased MMP. However, those effects were only observed at concentrations higher than 10 microM and were only induced in albumin-free media. Therefore, SPC may be trapped by albumin in plasma and unable to exert its effects under normal conditions, although at high concentrations, SPC could induce several responses such as ROS generation, increased [Ca(2+)](i), and decreased MMP in Jurkat T cells.

In the present study, we have tested the effect of dioleoyl phosphatidic acid (PA) on intracellular concentration () in two human colon cancer cell lines (HCT116 and HT29). PA and lysophosphatidic acid (LPA), a bioactive lysolipid, increased in both HCT116 and HT29 cell lines. Increases of by PA and LPA were more robust in HCT116 cells than in HT29 cells. A specific inhibitor of phospholipase C (U73122), however, was not inhibitory to the cell responses. Pertussis toxin, a specific inhibitor of type G proteins, however, had an inhibitory effect on the responses except for an LPA-induced one in HT29 cells. Ruthenium red, an inhibitor of the ryanodine receptor, was not inhibitory on the responses, however, 2-APB, a specific inhibitor of inositol 1,4,5-trisphosphate receptor, completely inhibited both lipid-induced increases in both cell types. Furthermore, by using Ki16425 and VPC32183, two structurally dissimilar specific antagonists for receptors, an involvement of endogenous LPA receptors in the responses was observed. Ki16425 completely inhibited the responses but the susceptibility to VPC32183 was different to PA and LPA in the two cell types. Expression levels of five LPA receptors in the HCT116 and HT29 cells were also assessed. Our data support the notion that PA could increase in human colon cancer cells, probably via endogenous LPA receptors, G proteins and receptors, thereby suggesting a role of PA as an intercellular lipid mediator.

Previously, we reported on the distinct effects of bioactive lysophospholipids, including lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC), and sphingosylphosphorylcholine (SPC), on membrane potentials in rat C6 glioma cells. In the present report we have tested lysophosphatidylserine (LPS), another bioactive lysophospholipid, on membrane potentials in the same cell line. Membrane potentials were estimated by measuring the fluorescence changes of DiBAC-loaded glioma cells. LPS largely increased membrane potentials in a concentration-dependent manner. The LPS-induced membrane potential increases were not affected by treatment with pertussis toxin, implying no involvement of Gi/o proteins. In contrast to other lysophospholipids, the LPS-induced membrane potential increase was not diminished by a Na(+)-free media but was enhanced by suramin. Furthermore, this change was blunted by EIPA, an inhibitor of Na(+)/H(+) exchanger, but not by SITS, a specific inhibitor of bicarbonate transporter. Our observations suggest that LPS acts on membrane potentials in a unique manner in the C6 glioma cells, although the precise action mechanism requires additional investigation.

N,N-Dimethyl-D-ribo-phytosphingosine (DMPH) is an N-methyl derivative of sphingosine. In the present paper, we studied effects of DMPH on intracellular Ca concentration, pH, glutamate uptake, and cell viability in human 1321N1 astrocytes. DMPH increased intracellular Ca concentration and cytosolic pH significantly in a dose-dependent manner. DMPH also inhibited glutamate uptake by 1321N1 astrocytes. Finally, treatment of cells with DMPH for 24 h reduced viability of cells largely and concentration-dependently. In summary, DMPH increased intracellular Ca concentration and pH, inhibited glutamate uptake and evoked cytotoxicity in 1321N1 astrocytes. Our observations with DMPH in the 1321N1 astrocytes would enhance understanding of DMPH actions in the brain.

Ginseng has an anti-cancer effect in several cancer models. As a mechanism study of ginsenoside-induced growth inhibition in cancer cells, we measured change of membrane potential in prostate cancer and glioma cells by ginsenosides, active constituents of ginseng. Membrane potential was estimated by measuring fluorescence change of DiBAC-loaded cells. Among 11 ginsenosides tested, ginsenosides Rb₂, Rg₃, and Rh₂ increased significantly and robustly the membrane potential in a concentration-dependent manner in prostate cancer and glioma cells. Ginsenosides Rc, Ro, and Rb₁ slightly increased membrane potential. The ginsenoside-induced membrane potential increase was not affected by treatment with pertussis toxin or U73122. The ginsenoside-induced membrane potential increase was not diminished in Na?-free or HCO₃?-free media. Furthermore, the ginsenoside-induced increase of membrane potential was not changed by EIPA (5-(N-ethyl-N-isopropyl)-amiloride), SITS (4-acetoamido-4’-isothiocyanostilbene-2,2’-disulfonic acid), and omeprazole. In summary, ginsenosides Rb₂, Rg₃, and Rh₂ increased membrane potential in prostate cancer and glioma cells in a GPCR-independent and Na? independent manner.

Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare, recently classified entity that consists of pleural and subjacent parenchymal fibrosis predominantly in the upper lungs. In an official American Thoracic Society/European Respiratory Society statement in 2013, this disease is introduced as a group of rare idiopathic interstitial pneumonias. We describe a case of a 76-year-old woman with cough and recurrent pneumothorax. She was admitted to our hospital with severe cough at first. High resolution computed tomography (HRCT) disclosed multifocal subpleural consolidations with reticular opacities in both lungs, primarily in the upper lobes, suggesting interstitial pneumonia. Rheumatoid lung was diagnosed initially through an elevated rheumatoid factor, HRCT and surgical biopsy at the right lower lobe. However, one month later, pneumothorax recurred. Surgical biopsy was performed at the right upper lobe at this time. The specimens revealed typical subpleural fibroelastosis. We report this as a first case of idiopathic PPFE in Korea after reviewing the symptoms, imaging and pathologic findings.

The aim of this study was to review the chest computed tomography (CT) findings in children with swine-origin influenza (H1N1) virus (S-OIV) infection.The radiologists retrospectively reviewed chest CT findings in 12 children with S-OIV infection and recorded the following findings: ground-glass opacities (GGO), consolidation, nodules, reticular opacities, peribronchial cuffing, and air trapping; distribution; affected lobes. The presence of pleural effusions, pneumomediastinum, pulmonary interstitial emphysema (PIE), and lymphadenopathy was also recorded.Chest CT revealed GGO (67%), consolidation (67%), nodules (25%), peribronchial cuffing (42%), and air trapping (33%). The distribution of the lesions was random (75%), peribronchial (17%), or subpleural (8%). The lobes affected were the lower (92%), upper (58%), and middle (17%) lobes. There were associated pleural effusions (42%), PIE (42%), pneumomediastinum (33%), and lymphadenopathy (75%). Among five patients with air-leak complications, three had a history of allergies and three required the intensive care unit.Chest CT findings in children with S-OIV infection were peribronchial thickening and a mixture of airspace consolidation and GGO with random distribution and lower lobe predominance. Pleural effusion, lymphadenopathy, PIE, and pneumomediastinum may be associated findings.

To study the effects of dibenzocyclooctadiene lignans isolated from Schisandra chinensis, such as wuweizisu C, gomisin N, gomisin A, and schisandrin, on the membrane potential in C6 glioma cells.The membrane potential was estimated by measuring the fluorescence change in DiBAC-loaded glioma cells.Wuweizisu C decreased the membrane potential in a concentration-dependent manner. Gomisin N and gomisin A, however, showed differential modulation and no change was induced by schisandrin or dimethyl- 4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate, a synthetic drug derived from dibenzocyclooctadiene lignans. We found no involvement of G(i/o ) proteins, phospholipase C, and extracellular Na(+) on the wuweizisu C-induced decrease of the membrane potential. Wuweizisu C by itself did not change the intracellular Ca(2+)[Ca(2+)](i) concentration, but decreased the ATP-induced Ca(2+) increase in C6 glioma cells. The 4 lignans at all concentrations used in this study did not induce any effect on cell viability. Furthermore, we found a similar decrease of the membrane potential by wuweizisu C in PC12 neuronal cells.Our results suggest that the decrease in the membrane potential and the modulation of [Ca(2+)](i) concentration by wuweizisu C could be important action mechanisms of wuweizisu C.

Calcium is a ubiquitous second messenger that controls a broad range of cellular functions, and store-operated calcium entry (SOCE) is the primary mechanism of regulated Ca2+ entry in non-excitable immunocytes. In this study, we found that N,N-dimethyl-D-erythro-sphingosine (DMS) inhibited SOCE. In U937 cells, treatment with DMS for 2 h inhibited thapsigargin-induced SOCE by about 70%. DMS inhibited SOCE in a concentration-dependent manner when it was added to the cells after SOCE reached a plateau. DMS-induced SOCE inhibition was also confirmed by the Mn2+-quenching method, which monitors only Ca2+ influx. Because sphingosine kinase inhibitors or protein kinase C (PKC) inhibitors could not mimic the SOCE inhibition, sphingosine kinase and PKC could be excluded as targets of DMS-induced inhibition of SOCE. Furthermore, disruption of lipid rafts with methyl-β-cyclodextrin and bacterial sphingomyelinase did not influence DMS-induced inhibition of SOCE. DMS-induced inhibition of SOCE in U937 human monocytes is a unique observation and could serve as a basis to study modulation of intracellular Ca2+ concentration by sphingolipids, although the precise mechanism should be elucidated in the future. Keywords:: dimethylsphingosine, dimethylphytosphingosine, sphingosine, store-operated Ca2+ entry, calcium

Previously, we suggested that dioleoyl phosphatidic acid (PA) and lysophosphatidic acid (LPA) increased [Ca(2+)](i) through endogenous LPA receptors coupled to pertussis toxin-sensitive G proteins in rat C6 glioma cells. In the present report, we investigated morphological changes and cytotoxicity induced by PA and LPA in C6 glioma cells. Isoproterenol treatment led to changes in the cell morphology of rat C6 glioma cells, which were reverted by the addition of PA and LPA. PA-and LPA-induced morphological reversions were inhibited by treatment with Ki16425, an LPA(1)/LPA(3) receptor antagonist. VPC32183, another LPA(1)/LPA(3) receptor antagonist with a different structure, only inhibited PA-induced morphological reversion but not LPA-induced reversion. However, the reversions were not inhibited by treatment with pertussis toxin, a specific inhibitor of G(i/o) proteins. In addition, cytotoxicity was only induced by LPA but not by PA in C6 glioma cells. Our results suggest that PA may act as a partial agonist at endogenous LPA receptors, which are sensitive to Ki16425 and coupled to PTX-insensitive G proteins, to evoke morphological changes in C6 glioma cells.

In the present study, we studied N , N -dimethyl- d - erythro -sphingosine (DMS)-induced cell death and its signaling mechanism in U937 human monocytes. We found that DMS induced cell death in a concentration-dependent manner, while sphingosine 1-phoshate did not. DMS also induced DNA fragmentation, nuclear disruption, and cytochrome c release from mitochondria in a concentration- and time-dependent manner, implying apoptotic cell death. DMS was found to increase mitochondrial membrane potential (MMP) immediately after addition of DMS and to decrease MMP at 2 h after addition. However, sphingosine kinase inhibitors and PKC inhibitors did not induce cell death in U937 cells, a result that appears to exclude sphingosine kinase and PKC as target molecules of DMS in the cell death induction process. Furthermore, DMS modulated the activity of several signaling molecules. DMS induced activation of JNK and p38 MAP kinase, while it decreased the activity of ERK and Akt kinase. However, decrease of MMP, inhibition of JNK, p38 MAP kinase, ERK, or Akt with specific inhibitors could not mimic the DMS-induced cell death, implying multiple concerted processes are involved in DMS-induced cell death. In summary, DMS induced apoptotic cell death via modulation of MMP, JNK, p38 MAP kinase, ERK, and Akt kinase, but not through inhibition of sphingosine kinase or PKC in U937 cells.

Treatment with isoprenaline led to a change in the cell morphology of rat C6 glioma cells. This morphological change was reverted by the addition of sphingosine 1-phosphate (S1P). Using this morphological change as a response marker we determined that DS-SG-44 ((2S,3R)-2-amino-3-hydroxy-4-(4-octylphenyl)butyl phosphoric acid) was an agonist of S1P receptors. The DS-SG-44-induced morphological reversion was not observed with such structurally related molecules as DS-SG-45 ((2S,3R)-2-amino-3-hydroxy-4-(3-octylphenyl)butyl phosphoric acid) and DS-SG-12 ((2S,3R)-2-amino-4-(4-octylphenyl)butane-1,3-diol). The S1P- and DS-SG-44-induced shape changes were nseither reproduced with the S1P1/S1P3 receptor agonist VPC24191 nor inhibited by the S1P1/S1P3 receptor antagonist, VPC23019. Transfection with small interfering RNA (siRNA) for the S1P2 receptor greatly inhibited the DS-SG-44-induced shape change, and in part an S1P-induced response. In the presence of VPC23019, siRNA transfection for the S1P2 receptor almost completely blocked the S1P- and DS-SG-44-induced shape changes. Our results suggested that DS-SG-44, a newly-synthesized S1P analogue, acted as an S1P receptor agonist and that the S1P-induced shape change in rat C6 glioma cells was mediated mainly through the S1P2 receptor, and cooperatively through the S1P1/S1P3 receptors.

Lysophosphatidylserine (LPS) can be generated following phosphatidylserine-specific phospholipase A2 activation. The effects of LPS on cellular activities and the identities of its target molecules, however, have not been fully elucidated. In this study, we observed that LPS stimulated intracellular calcium increased in mouse bone marrow-derived mast cells (BMMC), and rat C6 glioma and human HCT116 colon cancer cells and compared the LPS-induced Ca2+ increases with the response by lysophosphatidic acid (LPA), a structurally related bioactive lysolipid. In order to test involvement of signaling molecules in the LPS-induced Ca2+ signaling, we used pertussis toxin (PTX), U73122, and 2-APB, which are specific inhibitors for G proteins, phospholipase C (PLC), and IP3 receptors, respectively. The increases due to LPS and LPA were inhibited by PTX, U-73122 and 2-APB, suggesting that both lipids stimulate calcium signaling via G proteins (Gi/o types), PLC activation, and subsequent IP3 production, although the sensitivity to pharmacological inhibitors varied from complete inhibition to partial inhibition depending on cell type and lysolipid. Furthermore, we observed that Ki16425 completely inhibited an LPS-induced Ca2+ response in three cell types, but that the effect of VPC32183 varied from complete inhibition in BMMC and C6 glioma cells to partial inhibition in HCT116 cells. Therefore, we conclude that LPS increases [Ca2+]i through Ki16425/VPC32183-sensitive G protein-coupled receptors (GPCR), G protein, PLC, and IP3 in mouse BMMC, rat C6, and human HCT116 cells.

N,N-dimethyl-D-erythro-sphingosine (DMS) is an N-methyl derivative of sphingosine and an inhibitor of protein kinase C (PKC) and sphingosine kinase (SK). In the present study, we examined the effects of DMS on intracellular Ca2+ concentration, pH, and glutamate uptake in human 1321N1 astrocytes. DMS increased intracellular Ca2+ concentration and cytosolic pH in a concentration-dependent manner. Pretreatment of the cells with the Gi/o protein inhibitor PTX and the PLC inhibitor U73122 had no obvious effect. However, removal of extracellular Ca2+ with the Ca2+ chelator EGTA or depletion of intracellular Ca2+ stores with thapsigargin impeded the DMS-induced increase of intracellular Ca2+ concentration. Pretreatment of cells with NH4Cl or monensin reduced the DMS-induced Ca2+ increase. However, inhibition of the DMS-induced Ca2+ increase with BAPTA did not influence the DMS-induced pH increase. DMS also inhibited glutamate uptake by the 1321N1 astrocytes in a concentration-dependent manner. It also increased intracellular Ca2+ and pH in PC12 neuronal cells. Our observations on the effects of DMS on 1321N1 astrocytes and PC12 neuronal cells point to a physiological role of DMS in the brain.

Phosphatidic acid (PA) increased intracellular Ca(2+) concentration ([Ca(2+)](i)) in C6 rat glioma and L2071 mouse fibroblast cells. Dioleoyl PA (PA, 18:1) was the most efficacious, followed by dipalmitoyl PA (16:0 PA) and dimyristoyl PA (14:0 PA). Lysophosphatidic acid (LPA) also increased the [Ca(2+)](i) in the both cells. PA desensitized LPA-induced Ca(2+) response completely in C6 cells, but partly in L2071 cells. Treatment of pertussis toxin (PTX), a specific inhibitor of G(i/o)-type G proteins, completely ameliorated LPA- and PA-induced Ca(2+) response in C6 cells. However, in L2071 cells, PTX inhibited PA-induced Ca(2+) increase by 80% and LPA-induced one by 20%. Ki16425, a specific inhibitor of LPA(1)/LPA(3) receptors, completely inhibited both LPA- and PA-induced Ca(2+) responses in C6 cells. On the other hand, in L2071 cells, Ki16425 completely inhibited PA-induced Ca(2+) response, but partly LPA-induced one. VPC32183, another specific inhibitor of LPA(1)/LPA(3) receptors, completely inhibited LPA- and PA-induced Ca(2+) responses in both C6 and L2071 cells. Therefore, PA and LPA appear to increase [Ca(2+)](i) through Ki16425/VPC32183-sensitive LPA receptor coupled to PTX-sensitive G proteins in C6 cells. In L2071 cells, however, LPA increases [Ca(2+)](i) through Ki16425-insensitive LPA receptor coupled to PTX-insensitive G proteins and Ki16425-sensitive LPA receptor coupled to PTX-sensitive G protein, whereas PA utilized only the latter pathway. Our results suggest that PA acts as a partial agonist on endogenous LPA receptors, which are sensitive to Ki16425 and coupled to PTX-sensitive G protein, but not on LPA receptors, which are not sensitive to Ki16425 and coupled to PTX-insensitive G protein.

Mature teratomas are the most common mediastinal germ cell tumors. Most mature teratomas are located in the anterior mediastinum, and only 3–8% of mature teratomas occur in the posterior mediastinum (1). Mature teratomas may rarely rupture into adjacent structures (2). Based on a review of the literature, ruptured mature teratomas in the posterior mediastinum have not been reported previously. Ruptured teratomas with invasion of adjacent structures, such as the pleural space, pericardium, or lung parenchyma, have rarely been reported, but all reported mediastinal mature teratomas have been located in the anterior mediastinum (2). In this case report, we noted an unusual tumor location and imaging findings of ruptured mature teratomas in the mediastinum. We present a case of ruptured mature cystic teratoma located in the posterior mediastinum with fistula formation of the adjacent lung and esophagus.

Purpose: To determine the CT findings of an acute pulmonary thromboembolism for the prediction of response to anticoagulant therapy. Materials and Methods: Forty-eight patients diagnosed with a pulmonary embolism underwent anticoagulant therapy, and underwent pre- and post-treatment CT scans, were selected to be part of the study. Pre-treatment CT scans were retrospectively reviewed for the number and degree of emboli, right ventricular to left ventricular (RV/LV) diameter ratio, pulmonary arterial to aorta (PA/aorta) diameter ratio, ventricular septal bowing, consolidation, mosaic perfusion, and pleural effusion. The response to anticoagulant therapy was assessed by a change in embolic burden on pre-and post-treatment CT scans. The 48 patients were divided into two groups: good responder and poor responder. The pre-treatment CT findings were compared by group to determine if there were any differences in the CT findings. Results: Thirty patients were categorized as good responders (62.5%) and eighteen patients as poor responders (37.5%). A pleura-based wedge-shaped consolidation was observed in 9 of 18 cases (50%) from the poor responder group and one of 30 (3%) cases from the good responder group. The comparison of the finding by group was found to be significantly different (p

Purpose: This study was designed to investigate the pattern, distribution and extent of pulmonary abnormalities in relation to the amount of ingested paraquat as determined with the use of high resolution computed tomography (HRCT). Materials and Methods: The study included 15 patients exposed to paraquat based on a positive urine assay and the presence of pulmonary abnormalities as detected on HRCT scans. The pattern, distribution and extent of pulmonary abnormalities in relation to the amount of ingested paraquat was evaluated. Patients were classified into five groups based on the amount of paraquat that was ingested. The groups were designated as indirect exposure, minimum exposure (the patient spat out the agent after swallowing), low exposure ( 30 cc), medium exposure (31-60 cc) and high exposure (61-100 cc). Results: Abnormal lung parenchymal patterns as depicted on HRCT images consisted of ground glass opacity (n = 9), consolidation (n = 9), irregular lines (n = 9) and the presence of nodules (n = 2). The most common distribution was in the lower and subpleural lung zone with no relation to the amount of ingestion. The most common patterns were the presence of irregular lines in the indirect exposure group and ground glass opacity in the high exposure group. The mean number of involved lobes increased in relation to the amount of ingestion. Conclusion: For paraquat poisoning, the pattern and extent of pulmonary abnormalities were related to the amount of ingestion, but the distribution of pulmonary abnormalities was not related to the amount of ingestion.

There are several respiratory diseases that show chronic granulomatous inflammation for the histologic finding. Among them, sarcoidosis and tuberculosis are not easy to differentiate when the clinical and radiological features present similar patterns. The increasing incidence of nontuberculous mycobacteria pulmonary disease is making it more difficult for clinicians to arrive at a proper diagnosis. A 69 year old male patient visited our hospital with chronic cough as his chief compliant. His radiologic findings w ere multiple enlarged mediastinal lymphadenpathies with innumerable micronodules and multiple patch infiltrations. The spleen biopsy finding showed chronic granulomatous inflammation, and Mycobacterium avium was identified on the bronchoscopic culture. Because of these findings, we treated him with drugs for nontuberculous my cobacteria disease other than sarcoidosis. However, during the treatment, his symptoms and radiological features became aggravated. Thus, we reviewed the radiologic and pathologic findings and decided to treat him with steroid, which relieved his symptoms and improved the radiologic findings. We report here on a case of sarcoidosis that was initially misdiagnosed as nontuberculous mycobacteria pulmonary disease.Key Words: Sarcoidosis, Nontuberculous mycobacteria pulmonary disease, Chronic granulomatous inflammation

Purpose: Currently MRI (Magnetic Resonance Imaging) is widely used for the preoperative staging of breast cancer. In this study, we assessed the impact of preoperative breast MRI on the surgical management of breast cancer in women. Methods: From March 2004 to October 2006, 162 cases were enrolled for preoperative MRI for the staging of breast cancer. The MRI findings and clinicopathological results were investigated and the accuracy of breast MRI was analyzed with respect to the detection of multiplicity, nipple involvement and bilaterality of the breast cancers. Results: For detecting multifocal lesions, the sensitivity and specificity of breast MRI were 100% and 48.5%, respectively, and the results of bresat ultrasound were 100% and 63.4%, respectively. For detecting nipple invasion, the sensitivity and specificity of breast MRI was 80% and 74.6%, and for ultrasound was 33.3% and 86.4%. In 27 cases (16.7%) the type of surgery was changed according to the preoperative MRI findings; however, in only 6 cases were the MRI findings in concordance with the pathological findings of the mastectomy specimen. Conclusion: In clinical application of breast MRI for preoperative staging, the decision to undertake surgery for breast cancer based on a MRI findings should be prudent due to its low specificity. (J Breast Cancer 2006;9: 343-348)

Hemangioendothelioma is a rare vascular tumor characterized by endothelial tumor cells and variable malignant behavior, and it's not common for this lesion to involve the bone. Although there are a few reports of cranial involvement by hemangioendothelioma, only rare cases arising in temporal bone have been published. We present the radiologic findings of a 7-year-old boy who had a high grade hemangioendothelioma involving the temporal bone with intracranial extension. Evidence of flow voids on MR images suggested a tumor of vascular origin, and the ill-defined margins, cortical destruction and intracranial extension on the CT and MR images were correlated with the tumor's high histologic grade.