• Clinical and Experimental Pediatrics
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• v.49 no.4
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• pp.439-445
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• 2006

Purpose : ${\alpha}$-Galactosylceramide (${\alpha}$-GalCer)-stimulated human $V{\alpha}24$ natural killer T (NKT) cells exert antitumor activity against some leukemia in a CD1d dependent and TCR-mediated manner, but could not kill CD1d - negative neuroblastoma (NB) cells. There are few reports about the direct antitumor effect of highly secreted cytokines by these cells on activation. In this study, using a cell-free supernatant (SPN) collected from plate bound hCD1d/${\alpha}$ GalCer tetramers-stimulated NKT cells, we examined whether they could be helpful in the immunotherapeutic treatment of NB. Methods : Cells were cultured in IMDM. The cytokines produced by NKT cells were measured with Cytometric Bead Array (CBA) analysis. Cell viability was evaluated by calcein-AM fluorescence with digital image microscopy scanning (DIMSCAN). The percentage of specific apoptosis was calculated by flow cytometric detection of apoptosis using annexin V and 7-AAD. Results : The activated NKT cells secreted high levels of IL-2, INF-${\gamma}$, TNF-${\alpha}$. The SPN was significantly cytotoxic against four out of eight tested NB cell lines, through mainly apoptosis as evidenced by annexin-V staining and inhibition with the pretreatment of pancaspase blocker. This apoptosis was significantly inhibited when anti-TNF-${\alpha}$ and anti-IFN-${\gamma}$ neutralizing mAbs were used separately and it was completely abolished when the two mAbs were combined. Conclusion : IFN-${\gamma}$ and TNF-${\alpha}$ produced by NKT cells could exert synergistically direct antitumor activity through apoptosis on some NB cell lines.

• Journal of Oral Medicine and Pain
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• v.34 no.3
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• pp.261-276
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• 2009

Lactacystin, a microbial natural product synthesized by Streptomyces, has been commonly used as a selective proteasome inhibitor in many studies. Proteasome inhibitors is known to be preventing the proliferation of cancer cells in vivo as well as in vitro. Furthermore, proteasome inhibitors, as single or combined with other anticancer agents, are suggested as a new class of potential anticancer agents. This study was undertaken to examine in vitro effects of cytotoxicity and growth inhibition, and the molecular mechanism underlying induction of apoptosis in SCC25 human tongue sqaumous cell carcinoma cell line treated with lactacystin. The viability of SCC25 cells, human normal keratinocytes (HaCaT cells) and human gingiva fibroblasts (HGF-1 cells), and the growth inhibition of SCC25 cells were assessed by MTT assay and clonogenic assay respectively. The hoechst staining, hemacolor staining and TUNEL staining were conducted to observe SCC25 cells undergoing apoptosis. SCC25 cells were treated with lactacystin, and Western blotting, immunocytochemistry, confocal microscopy, FAScan flow cytometry, MMP activity, and proteasome activity were performed. Lactacystin treatment of SCC25 cells resulted in a time- and does-dependent decrease of cell viability and a does-dependent inhibition of cell growth, and induced apoptotic cell death. Interestingly, lactacytin remarkably revealed cytotoxicity in SCC25 cells but not normal cells. And tested SCC25 cells showed several lines of apoptotic manifestation such as nuclear condensation, DNA fragmentation, the reduction of MMP and proteasome activity, the decrease of DNA contents, the release of cytochrome c into cytosol, the translocation of AIF and DFF40 (CAD) onto nuclei, the up-regulation of Bax, and the activation of caspase-7, caspase-3, PARP, lamin A/C and DFF45 (ICAD). Flow cytometric analysis revealed that lactacystin resulted in G1 arrest in cell cycle progression which was associated with up-regulation in the protein expression of CDK inhibitors, $p21^{WAF1/CIP1}$ and $p27^{KIP1}$. We presented data indicating that lactacystin induces G1 cell cycle arrest and apoptois via proteasome, mitochondria and caspase pathway in SCC25 cells. Therefore our data provide the possibility that lactacystin could be as a novel therapeutic strategy for human tongue squamous cell carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.356-364
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• 1999

Backgrounds: Previous reports have revealed a high morbidity and mortality in fatal asthma patients, especially those treated in the medical intensive care unit(MICU). But it has not been well known about the predictable factors for the mortality of fatal asthma(F A) with acute respiratory failure. In order to define the predictable factors for the mortality of FA at the admission to MICU, we analyzed the relationship between the clinical parameters and the prognosis of FA patients. Methods: A retrospective analysis of all medical records of 59 patients who had admitted for FA to MICU at a tertiary care MICU from January 1992 to March 1997 was performed. Results: Over all mortality rate was 32.2% and 43 patients were mechanically ventilated. In uni-variate analysis, the death group had significantly older age ($66.2{\pm}10.5$ vs. $51.0{\pm}18.8$ year), lower FVC($59.2{\pm}21.1$ vs. $77.6{\pm}23.3%$) and lower $FEV_1$($41.4{\pm}18.8$ vs. $61.l{\pm}23.30%$), and longer total ventilation time ($255.0{\pm}236.3$ vs. $98.1{\pm}120.4$ hour) (p<0.05) compared with the survival group (PFT: best value of recent 1 year). At MICU admission, there were no significant differences in vital signs, $PaCO_2$, $PaO_2/FiO_2$, and $AaDO_2$, in both groups. However, on the second day of MICU, the death group had significantly more rapid pulse rate ($121.6{\pm}22.3$ vs. $105.2{\pm}19.4$ rate/min), elevated $PaCO_2$ ($50.1{\pm}16.5$ vs. $41.8{\pm}12.2 mm Hg$), lower $PaO_2/FiO_2$, ($160.8{\pm}59.8$ vs. $256.6{\pm}78.3 mm Hg$), higher $AaDO_2$ ($181.5{\pm}79.7$ vs. $98.6{\pm}47.9 mm Hg$), and higher APACHE III score ($57.6{\pm}21.1$ vs. $20.3{\pm}13.2$) than survival group (p<0.05). The death group had more frequently associated with pneumonia and anoxic brain damage at admission, and had more frequently developed sepsis during disease progression than the survival group (p<0.05). Multi-variate analysis using APACHE III score and $PaO_2/FiO_2$, ratio on first and second day, age, sex, and pneumonia combined at admission revealed that APACHE III score (40) and $PaO_2/FiO_2$ ratio (<200) on second day were regarded as predictive factors for the mortality of fatal asthma (p<0.05). Conclusions: APACHE III score ($\geq$40) and $PaO_2/FiO_2$ ratio (<200) on the second day of MICU, which might reflect the response of treatment, rather than initially presented clinical parameters would be more important predictable factors of mortality in patients with FA.

• Clinical and Experimental Pediatrics
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• v.48 no.7
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• pp.737-744
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• 2005

Purpose : Infants and children with cardiovascular diseases often present with respiratory symptoms. However, missed or delayed evaluation for potential airway problem may complicate overall prognosis. The aim of this study is to determine the clinical characteristics of these patients and explore the cause of airway problem. Methods : We reviewed the medical records of 64 patients(M : F=33:31, mean age : $6.3{\pm}7.5$ months) whose airway problems were proven by computed tomography or bronchoscopy in perioperative periods at the Asan Medical Center from January 1997 to June 2004. Patients were divided into two groups based on the duration of ventilator care : ${\leq}7$ days(group 1 : 23 cases, M : F=10 : 13) and >7 days(group 2 : 41 cases, M : F=23 : 18). Results : The patients in group 2 significantly developed more post-operative respiratory symptoms than group 1(P<0.001) and had more airway problems including extrinsic obstruction, intrinsic anomaly, and combined problem than group 1 although not significantly different(P=0.082). Among underlying diseases, the most common diseases were vascular anomaly(26.2 percent) and aortic arch anomaly(26.2 percent) in group 1 and pulmonary atresia with ventricular septal defect(22.4 percent) in group 2. The most frequent respiratory symptoms were recurrent wheezing pre-operatively and failure of ventilator weaning post-operatively. The major types of airway anomaly were tracheomalacia and tracheal stenosis(in each case 18.2 percent). Nineteen patients with persistent airway problems underwent aortopexy or other vascular correction. Of the 19 patients, 13(68.4 percent) were improved, but 2 failed in weaning ventilator and 4 died of non-airway problems. Conclusion : Early evaluation and treatment for potential airway problems may affect natural or surgical prognosis in patients with cardiovascular diseases presenting with respiratory symptoms.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.126-132
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• 2009

Purpose: We wanted to evaluate the prognostic factors for the pathologic N2 non-small cell lung cancer (NSCLC) patients who were treated by postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 112 pN2 NSCLC patients who underwent surgery and postoperative radiotherapy (PORT) From January 1999 to February 2008. Seventy-five (67%) patients received segmentectomy or lobectomy and 37 (33%) patients received pneumonectomy. The resection margin was negative in 94 patients, and it was positive or close in 18 patients. Chemotherapy was administered to 103 (92%) patients. Nine (8%) patients received PORT alone. The median radiation dose was 54 Gy (range, 45 to 66), and the fraction size was 1.8~2 Gy. Results: The 2-year overall survival (OS) rate was 60.2% and the disease free survival (DFS) rate was 44.7% for all the patients. Univariate analysis showed that the patients with multiple-station N2 disease had significantly reduced OS and DFS (p=0.047, p=0.007) and the patients with an advanced T stage ($\geq$T3) had significantly reduced OS and DFS (p<0.001, p=0.025). A large tumor size ($\geq$5 cm) and positive lymphovascular invasion reduced the OS (p=0.035, 0.034). Using multivariate analysis, we found that multiple-station N2 disease and an advanced T stage ($\geq$T3) significantly reduced the OS and DFS. Seventy one patients (63.4%) had recurrence of disease. The patterns of failure were loco-regional in 23 (20.5%) patients, distant failure in 62 (55.4%) and combined loco-regional and distant failure in 14 (12.5%) patients. Conclusion: Multiple involvement of mediastinal nodal stations for the pN2 NSCLC patients with PORT was a poor prognostic factor in this study. A prospective study is necessary to evaluate the N2 subclassification and to optimize the adjuvant treatment.

• Journal of the Korean Applied Science and Technology
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• v.37 no.4
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• pp.878-892
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• 2020

The purpose of this study is to explore the effects of pregnant women's taking of probiotics and pilates exercise on Postnatal women's body composition, gut-microbiota, obesity hormones, blood lipid, inflammatory cytokine. Overall clinical trial procedures are as follows. First, a total of 15 pregnant women were classified into 3 groups, probiotics intake+exercise group(PEX, n=5), exercise group(EX, n=5), and control group(CON, n=5). The PEX and EX groups participated in the pilates exercise twice a week for eight weeks, with 10 min for warm-up, 30 min for main exercise and 10 min for cool-dawn. The probiotics had to take one capsule a day on its empty stomach every day. The results showed that intestinal harmful bacteria were inhibited after childbirth in PEX group, and body fat, WHR reduction. There were also positive effects on the decrease of leptin hormone in PEX group and on IL-6, TNF-a levels. The caesarean section ratio of CON group compared to PEX and EX group was found to be high. Conclusion pregnant women's probiotics intake and pilates exercise will be effective in women's abdominal fat reduction after childbirth, and will have positive effects on inflammatory levels and appetite control hormones, which will be effective in preventing and treating obesity for after childbirth.

• Journal of Plant Biotechnology
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• v.45 no.3
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• pp.250-256
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• 2018

To determine whether metabolite fingerprinting for whole cell extracts based on Fourier transform infrared spectroscopy (FT-IR) can be used to discriminate and compare metabolic equivalence, standard medicinal parts of Cynanchum wilfordii (Maxim.) Hemsl. and their adventitious roots were subjected to FT-IR. The principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) from FT-IR spectral data showed that whole metabolic pattern from the adventitious root of Cynanchum wilfordii was highly similar to its standard medicinal parts. These results clearly showed that mass proliferation of adventitious roots could be applied for the novel supply of standard medicinal parts of medicinal plants. Furthermore, FT-IR spectroscopy combined with multivariate analysis established in this study could be applied as an alternative tool for discriminating of whole metabolic equivalence from standard medicinal parts. Thus, it is proposed that these metabolic discrimination systems from the adventitious root of Cynanchum wilfordii could be applied for metabolic standardization of in vitro grown Cynanchum wilfordii.

• Journal of Oral Medicine and Pain
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• v.36 no.1
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• pp.71-79
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• 2011

Aim: Disc displacement without reduction of the temporomandibular joint (TMJ) has been managed by mandibular manipulation to reduce the displaced disc but with a low success rate. The purpose of this study was to determine whether auriculotemporal nerve block anesthesia had an effect on the reduction of the displaced disc and to analyze the factors that influenced the result. Methods: 112 patients were diagnosed with disc displacement without reduction and treated by mandibular manipulation. Disc was recaptured in 35 patients. Among the 77 patients with whom disc recapture had failed, the auriculotemporal nerve was blocked with a local anesthetic in the 49 patients (mean $age \;{\pm}\; SD\; =\; 34.4\;{\pm}\; 15.1$; male 24, female 25) and then mandibular manipulation was performed again. Factors including age, elapsed time from the onset, and opening amount were analyzed in association with disc reduction rate with the auriculotemporal nerve block. Results: Among 49 patients who did not respond to manipulation only, manual reduction with auriculotemporal nerve block anesthesia was successful in 19 patients (38.8%). Maximum unassisted opening amount significantly increased in the 19 patients with successful recapture of the disc ($mean \;{\pm}\; SD\; =\; 46.1 \;{\pm}\; 4.5\; mm$), in contrast to the limited opening amount of the 49 patients before local anesthesia of the auriculotemporal nerve ($mean \;{\pm}\; SD\; =\; 25.7 \;{\pm}\; 6.0\; mm$). Age, elapsed time after the onset, and preoperative opening amount were not associated with the reduction rate. Conclusion: The results of this study suggest that auriculotemporal nerve block anesthesia increases the reduction rate of the disc displacement without reduction of the TMJ when combined with mandibular manipulation, and such anesthesia should be applied at the first stage of manual treatment of disc displacement without reduction.

• Development and Reproduction
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• v.16 no.4
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• pp.295-300
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• 2012

Manganese ($Mn^{2+}$) is a trace element that is essential for normal physiology, and is predominantly obtained from food. Several lines of evidence, however, demonstrated that overexposure to $MnCl_2$ exerts serious neurotoxicity, immunotoxicity and developmental toxicity, particularly in male. The present study aimed to evaluate the effect of 0, 1.0, 3.3, and 10 mg/kg/day doses of $MnCl_2$ on the reproductive organs in the immature female rats. Rats (PND 22; S.D. strain) were exposed to $MnCl_2$ ($MnCl_2{\cdot}4H_2O$) dissolved in drinking water for 2 weeks. The animals were sacrificed on PND 35, then the tissues were immediately removed and weighed. Histological studies were performed using the uteri tissue samples. Serum LH and FSH levels were measured with the specific ELISA kits. Body weights of the experimental group animals were not significantly different from those of control group animals. However, ovarian tissue weights in 1 mg and 3.3 mg $MnCl_2$ dose groups were significantly lower than those of control animals (p<0.05 and p<0.01, respectively). Uterine tissue weights of 3.3 mg dose $MnCl_2$ groups were significantly lower than those of control animals (p<0.01), while the 1 mg $MnCl_2$ dose and 10 mg $MnCl_2$ dose failed to induce any change in uterine weight. Similarly, only 3.3 mg $MnCl_2$ dose could induce the significant decrease in the oviduct weight compared to the control group (p<0.05). Non-reproductive tissues such as adrenal and kidney failed to respond to all doses of $MnCl_2$ exposure. The uterine histology revealed that the $MnCl_2$ exposure could affect the myometrial cell proliferation particularly in 3.3 mg dose and 10mg dose group. Serum FSH levels were significantly decreased in 1mg $MnCl_2$ dose and 10 $MnCl_2$ mg groups (p<0.05 and p<0.01, respectively). In contrast, treatment with 1 mg $MnCl_2$ dose induced a significant increment of serum LH level (p<0.05). The present study demonstrated that $MnCl_2$ exposure is capable of inducing abnormal development of reproductive tissues, at least to some extent, and altered gonadotropin secretions in immature female rats. Combined with the well-defined actions of this metal on GnRH and prolactin secretion, one can suggest the $Mn^{2+}$ might be a potential environmental mediator which is involved in the female pubertal process.

• Parasites, Hosts and Diseases
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• v.26 no.4
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• pp.255-262
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• 1988

An epidemiological study on brugian filariasis was carried out in endemic areas including Cheju Island in Korea, with a brief review of literatures. The results showed that the incidence among residents has remarkably decreased in Cheju Island, which was the main endemic area. Reviewing available informations on the prevalence of filariasis reported in recent years and also judging from the present socio·economic conditions which enable people to practice personal protection against mosquitos, it can be said with confidence that alariasis has almost disappeared from Cheju Island and inland areas. The disease is considered to remain at a low level of endemicity in Hugsan Islands. Certainly mass diethylcarbamasine (DEC) treatment carried out in Cheju Island in the 1960s and 1970s and remarkable economic growth followed by improved living standard and altered life-style of inhabitants could all have combined effects on the disappearance of this mosquito-borne disease in this island. If the present trends go on, the possibility of resurgence of filariasis in Cheju Island is hardly postulated.