[Show abstract][Hide abstract] ABSTRACT: Botulinum neurotoxin type A (BoNT/A) is the most potent protein toxin and causes fatal flaccid muscle paralysis by blocking neurotransmission. Application of BoNT/A has been extended to the fields of therapeutics and biodefense. Nevertheless, the global response of host immune cells to authentic BoNT/A has not been reported. Employing microarray analysis, we performed global transcriptional profiling of RAW264.7 cells, a murine alveolar macrophage cell line. We identified 70 genes that were modulated following 1 nM BoNT/A treatment. The altered genes were mainly involved in signal transduction, immunity and defense, protein metabolism and modification, neuronal activities, intracellular protein trafficking, and muscle contraction. Microarray data were validated with real-time RT-PCR for seven selected genes including tlr2, tnf, inos, ccl4, slpi, stx11, and irg1. Proinflammatory mediators such as nitric oxide (NO) and tumor necrosis factor alpha (TNFα) were induced in a dose-dependent manner in BoNT/A-stimulated RAW264.7 cells. Increased expression of these factors was inhibited by monoclonal anti-Toll-like receptor 2 (TLR2) and inhibitors specific to intracellular proteins such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase (MAPK). BoNT/A also suppressed lipopolysaccharide-induced NO and TNFα production from RAW264.7 macrophages at the transcription level by blocking activation of JNK, ERK, and p38 MAPK. As confirmed by TLR2-/- knock out experiments, these results suggest that BoNT/A induces global gene expression changes in host immune cells and that host responses to BoNT/A proceed through a TLR2-dependent pathway, which is modulated by JNK, ERK, and p38 MAPK.
PLoS ONE 04/2015; 10(4):e0120840. DOI:10.1371/journal.pone.0120840 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate whether laughter therapy lowers total mood disturbance scores and improves self-esteem scores in patients with cancer.
Randomized controlled trial in a radio-oncology outpatient setting.
Sixty-two patients were enrolled and randomly assigned to the experimental group (n=33) or the wait list control group (n=29).
Three laughter therapy sessions lasting 60 minutes each.
Mood state and self-esteem.
The intention-to-treat analysis revealed a significant main effect of group: Experimental group participants reported a 14.12-point reduction in total mood disturbance, while the wait list control group showed a 1.21-point reduction (p=0.001). The per-protocol analysis showed a significant main effect of group: The experimental group reported a 18.86-point decrease in total mood disturbance, while controls showed a 0.19-point reduction (p<0.001). The self-esteem of experimental group was significantly greater than that of the wait list control group (p=0.044).
These results indicate that laughter therapy can improve mood state and self-esteem and can be a beneficial, noninvasive intervention for patients with cancer in clinical settings.
Journal of alternative and complementary medicine (New York, N.Y.) 04/2015; 21(4):217-22. DOI:10.1089/acm.2014.0152 · 1.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epignathus is an extremely rare type of congenital teratoma arising in the oral cavity. Although it is a benign tumor, it is associated with high mortality and morbidity rates because of severe airway obstruction and other malformations. We present a case of epignathus affecting one fetus in a twin pregnancy. The tumor was associated with multiple congenital malformations including cleft palate, bifid tongue, bifid uvula, congenital heart defect, and bilateral inguinal hernias. The diagnostic value of three-dimensional ultrasonography and magnetic resonance imaging was explored with respect to antenatal counseling and peripartum management.
[Show abstract][Hide abstract] ABSTRACT: Background Bacillus anthracis is the etiological agent of anthrax. Lethal toxin (LT) produced by B. anthracis is a well-known key virulence factor for anthrax because of its strong cytotoxic activity. However, little is known about the role of B. anthracis genomic DNA (BAG) in anthrax pathogenesis.ResultsWe examined the effect of BAG on TNF-¿ production and LT-mediated cytotoxicity during B. anthracis spore infection in mouse macrophage cell lines (RAW264.7 cells and J774A.1) and BALB/c mice. Infection of RAW264.7 cells with B. anthracis spores induced TNF-¿ expression in a multiplicity of infection (MOI)-dependent manner, and this enhancement was attenuated by the toll-like receptor (TLR) 9 inhibitor oligodeoxynucleotide (ODN)2088. BAG led to TNF-¿ expression in a dose- and time-dependent manner when applied to RAW264.7 cells. TNF-¿ expression induced by BAG was reduced by either pretreatment with TLR9 inhibitors (ODN2088 and chloroquine (CQ)) or transfection with TLR9 siRNA. Furthermore, BAG-induced TNF-¿ production in TLR9+/+ macrophages was completely abrogated in TLR9¿/¿ macrophages. BAG enhanced the phosphorylation of mitogen-activated protein kinases (MAPK), and BAG-induced TNF-¿ expression was attenuated by pretreatment with MAPK inhibitors. A reporter gene assay and confocal microscopy demonstrated that BAG increased NF-¿B activation, which is responsible for TNF-¿ expression. Treatment with BAG alone showed no cytotoxic activity on the macrophage cell line J774A.1, whereas LT-mediated cytotoxicity was enhanced by treatment with BAG or TNF-¿. Enhanced LT-induced lethality was also confirmed by BAG administration in mice. Furthermore, LT plus BAG-mediated lethality was significantly recovered by administration of Infliximab, an anti-TNF-¿ monoclonal antibody.Conclusions
Our results suggest that B. anthracis DNA may contribute to anthrax pathogenesis by enhancing LT activity via TLR9-mediated TNF-¿ production.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Cervical cancer is caused by persistent infection with high-risk types of human papillomavirus (HPV). The aim of this study was to investigate the potential of Raman spectroscopy as a stand-alone analytical tool for clinical diagnosis of HPV infection using human cervical fluids.
A drop-coating deposition surface-enhanced Raman scattering (DCD-SERS) method was identified as the most effective method of biochemical analysis in cervical biofluids.
Using a 2-µL sample, the proposed DCD-SERS method yielded Raman spectra with high reproducibility, noise-independence, and uniformity. Additionally, the produced spectra were independent of the volume of fluid used and detection zone analyzed within the central and the ring zones. The optical detection of HPV infection in cervical fluids could be detected accurately in the central zone. Different Raman spectra were obtained according to HPV type. In particular, HPV-16 and HPV-18, which are the major risk factors for cervical cancer, showed a distinct spectral difference in cervical fluids, with a similar pattern for high Raman bands at >1,000 cm(-1) but a different pattern for low Raman bands at <1,000 cm(-1) . Therefore, all ranges of HPV-gated DCD-SERS could be used to detect the presence of HPV infection.
Raman spectroscopy provides a good alternative method for early clinical diagnosis of HPV infection, and we are hopeful that this proposed method of HPV assessment will be approved for use in obstetrics and gynecology clinics.
Microscopy Research and Technique 12/2014; 78(3). DOI:10.1002/jemt.22461 · 1.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Surgical scars are crucial cosmetic problem, especially when in exposed areas such as the anterior neck following thyroidectomy.
To evaluate the impact of post-thyroidectomy scars on quality of life (QoL) of thyroid cancer patients and identify the relationship between scar characteristics and QoL.
Patients with post-thyroidectomy scars on the neck were recruited. QoL was measured using the Dermatology Life Quality Index (DLQI). Scar characteristics were graded according to Vancouver scar scale (VSS) score.
Ninety-seven patients completed a battery of questions at the time of enrollment. Post-thyroidectomy scars were classified according to morphology as linear flat scars, linear bulging scars, hypertrophic scars or adhesive scars. There were 32 patients (33.0%), 9 patients (9.3%), 41 patients (42.3%) and 15 patients (15.5%), respectively, in each group. The mean total DLQI score was 9.02. Domain 2 (daily activities, 2.87 points), which includes questions about clothing, was the most greatly impacted among patients. The total DLQI scores of patients who have experienced scar-related symptoms were significantly higher than those of patients without symptoms (p<0.05). The VSS scores were 3.09 for linear flat scars, 6.89 for linear bulging scars, 6.29 for hypertrophic scars and 5.60 for adhesive scars. However, the DLQI scores did not significantly differ among scar types or VSS scores.
Post-thyroidectomy scars on the neck affect the QoL of thyroid cancer patients regardless of scar type. Therefore, clinicians should pay attention to the psychological effects of scars on patients and take care to minimize post-thyroidectomy scar.
Annals of Dermatology 12/2014; 26(6):693-699. DOI:10.5021/ad.2014.26.6.693 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The impact and outcomes of the implementation of a pain management guideline and pain assessment standard operating procedure (SOP) in a cancer-specific emergency department are evaluated in this article. After implementation of the SOP, the number of pain assessments conducted per patient during hospitalization increased, as did the percentage of patients who underwent a pain assessment at admission, within one hour after analgesic medication was administered, and at regular intervals.
[Show abstract][Hide abstract] ABSTRACT: Anthrax is caused by the spore-forming bacterium Bacillus anthracis-, which has been used as a weapon for bioterrorism. Although current vaccines are effective, they involve prolonged dose regimens and often cause adverse reactions. High rates of mortality associated with anthrax have made the development of an improved vaccine a top priority. To identify novel vaccine candidates, we applied an immunoproteomics approach. Using sera from convalescent guinea pigs or from human patients with anthrax, we identified 34 immunogenic proteins from the virulent B. anthracis H9401. To evaluate vaccine candidates, six were expressed as recombinant proteins and tested in vivo. Two proteins, rGBAA_0345 (Alkyl hydroperoxide reductase subunit C) and rGBAA_3990 (Malonyl CoA-acyl carrier protein transacylase), have afforded guinea pigs partial protection from a subsequent virulent-spore challenge. Moreover, combined vaccination with rGBAA_0345 and rPA (Protective antigen) exhibited an enhanced ability to protect against anthrax mortality. Finally, we demonstrated that GBAA_0345 localizes to anthrax spores and bacilli. Our results indicate that rGBAA_0345 may be a potential component of a multivalent anthrax vaccine, as it enhances the efficacy of rPA vaccination. This is the first time that sera from patients with anthrax have been used to interrogate the proteome of virulent B. anthracis vegetative cells. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to compare job satisfaction, quality of life (QOL), incident report rate and overtime hours for 12-hour shifts and for 8-hour shifts in a pediatric intensive care unit (PICU).
[Show abstract][Hide abstract] ABSTRACT: To investigate the effects of meditation on anxiety, depression, fatigue, and quality of life in women who are receiving radiation therapy for breast cancer.
Randomized, non-program controlled, parallel intervention clinical trial.
The ASAN Cancer Center located in Seoul, Korea.
The subjects of this study included 102 female breast cancer patients who had undergone breast-conserving surgery; these female patients were randomized into equally assigned meditation control groups, with each group consisting of 51 patients. The test group received a total of 12 meditation therapy sessions during their 6-week radiation therapy period, and the control group underwent only a conventional radiation therapy.
The tools used to evaluate the effects of meditation were Hospital Anxiety and Depression scale, Revised Piper Fatigue scale, and European Organization for Research and Treatment of Cancer-Quality of Life Core-30. The results were analyzed based on the principles of intention-to-treat analysis, and, as a corollary analysis, per-protocol analysis was conducted.
The breast cancer patients who received meditation therapy compared with the non-intervention group saw improvements in reduction of anxiety (p=.032), fatigue (p=.030), and improvement in global quality of life (p=.028).
Based on the results of this study, an affirmation can be made that meditation can be used as a non-invasive intervention treatment for improving fatigue, anxiety, quality of life, and emotional faculties of women with breast cancer.
Complementary therapies in medicine 08/2013; 21(4):379-87. DOI:10.1016/j.ctim.2013.06.005 · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Anthrax is an acute infectious disease caused by Bacillus anthracis. We previously reported that the adjuvant CIA06B, which consists of TLR4 agonist CIA05 and aluminum hydroxide (alum), enhanced the immune response to anthrax protective antigen (PA) in mice. This study was carried out to determine whether CIA06B can enhance long-term immune responses to PA in mice. BALB/c mice were immunized intramuscularly three times at 2-week intervals with recombinant PA alone or PA combined with alum or CIA06B. At 8 and 24 weeks post-immunization, the immunological responses including serum anti-PA IgG antibody titer, toxin-neutralizing antibody titer, splenic cytokine secretion and the frequency of PA-specific memory B cells were assessed. Compared with mice injected with PA alone or PA plus alum, mice injected with PA plus CIA06B had higher titers of serum anti-PA IgG antibodies, and higher frequencies of PA-specific memory B cells and interferon-γ secreting cells. Furthermore, anti-PA antibodies induced by CIA06B were more effective in neutralizing anthrax toxin. These results demonstrated that CIA06B is capable of providing long-term immunity when used as an adjuvant in a PA-based anthrax vaccine.
Archives of Pharmacal Research 02/2013; 36(4). DOI:10.1007/s12272-013-0034-5 · 2.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:: Since 2003, the Accreditation Council for Graduate Medical Education requires residency programs to restrict to 80 hrs/wk, averaged over 4 wks to improve patient safety. These restrictions force training programs with night call responsibilities to either maintain a traditional program with alternative night float schedules or adopt a "shift" model, both with increased handoffs. OBJECTIVE:: To assess whether a 65 hrs/wk shift-work schedule combined with structured sign-out curriculum is equivalent to a 65 hrs/wk traditional day coverage with night call schedule, as measured by multiple assessments. DESIGN:: Eight-month trial of shift-work schedule with structured sign-out curriculum (intervention) vs. traditional call schedule without curriculum (control) in alternating 1-2 month periods. SETTING:: A mixed medical-surgical intensive care unit at a tertiary care academic center. SUBJECTS:: Primary subjects: 19 fellows in a Multidisciplinary Critical Care Training Program; Secondary subjects: intensive care unit nurses and attending physicians, families of intensive care unit patients. INTERVENTIONS:: Implementation of shift-work schedule, combined with structured sign-out curriculum. MEASUREMENTS:: Workplace perception assessment through Continuity of Care Survey evaluation by faculty, fellows, and nurses through structured surveys; family assessment by the Critical Care Family Needs Index survey; clinical assessment through intensive care unit mortality, intensive care unit length of stay, and intensive care unit readmission within 48 hrs; and educational impact assessment by rate of fellow didactic lecture attendance. MAIN RESULTS:: There were no statistically significant differences in surveyed perceptions of continuity of care, intensive care unit mortality (8.5% vs. 6.0%, p = .20), lecture attendance (43% vs. 42%), or family satisfaction (Critical Care Family Needs Index score 24 vs. 22) between control and intervention periods. There was a significant decrease in intensive care unit length of stay (8.4 vs. 5.7 days, p = .04) with the shift model. Readmissions within 48 hrs were not different (3.6% vs. 4.9%, p = .39). Nurses preferred the intervention period (7% control vs. 73% intervention, n = 30, p = .00), and attending faculty preferred the intervention period and felt continuity of care was maintained (15% control vs. 54% intervention, n = 11, p = .15). CONCLUSIONS:: A shift-work schedule with structured sign-out curriculum is a viable alternative to traditional work schedules for the intensive care unit in training programs.
Critical care medicine 10/2012; 40(12). DOI:10.1097/CCM.0b013e3182657b5d · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to identify the adipocyte-specific gene expression patterns in chorion-derived mesenchymal stem cells during adipogenic differentiation.
Chorionic cells were isolated from the third trimester chorions from human placenta at birth and identified morphologically and by fluorescence-activated cell sorting analysis. After inducing adipogenic differentiation for 28 days, cells at days 3, 10, 21 and 28 were analyzed by Oil red O staining and RNA extraction in order to assess the expression levels of adipocyte marker genes, including CCAAT-enhancer binding protein α (C/EBPα), peroxisome proliferator- activated receptor γ (PPARγ), fatty acid binding protein 4 (FABP4) and Glycerol-3-phosphate dehydrogenase (GPD2). Cells not induced for differentiation were compared with the induced cells as a control group.
Chorion-derived cells showed the same pattern as fibroblasts, and expressed CD73, CD105, and CD166 antigens, but not CD45, CD34, and HLA-DR antigens. On day 3 after differentiation, cells began to stain positively upon Oil red O staining, and continuously increased in lipid granules for 4 weeks. The expression level of C/EBPα increased 4.6 fold on day 3 after induction, and continued to increase for 4 weeks. PPARγ was expressed at a maximum of 2.9 fold on day 21. FABP4 and GPD2 were significantly expressed at 4.7- and 3.0-fold, respectively, on day 21, compared to controls, and further increased thereafter.
Human chorion-derived mesenchymal stem cells exhibited the sequential expression pattern of adipocyte marker genes during differentiation, corresponding to adipogenesis.
Yonsei medical journal 09/2012; 53(5):1036-44. DOI:10.3349/ymj.2012.53.5.1036 · 1.29 Impact Factor