PURPOSE: To investigate the growth inhibitory effects, and the underlying mechanism of human colon cancer cell (HT-29) death, induced by a new synthetic bile acid derivative (HS-1200). MATERIALS AND METHODS: Human colon cancer cells (HT-29), in exponential growth phase, were treated with various concentrations of a new synthetic bile acid derivative (HS-1200). The growth inhibitory effects on HT-29 cells were examined using a trypan blue exclusion assay. The extent of apoptosis was determined using agarose gel electrophoresis, TUNEL assays and Hoechst staining. The apoptotic cell death was also confirmed by Western blotting of PARP, caspase-3 and DNA fragmentation factor (DFF) analysis. To investigate the involvement of mitochondria, we employed immunofluorescent staining of cytochrome c and mitochondrial membrane potential analyses. RESULTS: The dose required for the half maximal inhibition (IC50) of the HT-29 cell growth was 100~150 micro M of HS-1200. Several changes, associated with the apoptosis of the HT-29 cells, were reveal by the agarose gel eletrophoresis, TUNEL assays and Hoechst staining, following their treatment with 100 micro M of HS-1200. HS-1200 treatment also induced caspase-3, PARP and DFF degradations, and the western blotting showed the processed caspase-3 p20, PARP p85 and DFF p30 and p11 cleaved products. Mitochondrial events were also demonstrated. The cytochrome c staining indicated that cytochrome c had been released from the mitochondria in the HS-1200 treated cells. The mitochondrial membrane potential (deltaxm) was also prominently decreased in the HS-1200 treated cells. CONCLUSION: These findings suggest that the HS-1200 - induced apoptosis of human colon cancer cells (HT-29) is mediated via caspase and mitochondrial pathways.
Apoptosis* ; Bile ; Bile Acids and Salts ; Blotting, Western ; Caspase 3 ; Cell Death ; Colon* ; Colonic Neoplasms* ; Cytochromes c ; DNA Fragmentation ; Electrophoresis, Agar Gel ; HT29 Cells ; Humans* ; In Situ Nick-End Labeling ; Membrane Potential, Mitochondrial ; Mitochondria ; Sepharose ; Trypan Blue

PURPOSE: This study aimed to examine levels of stress and professionalism of nurses who provided nursing care during the 2015 Middle East respiratory syndrome outbreak based on their experience, to investigate the nurses' intention to respond to possible future outbreaks in relation to their experience during the outbreak, and to determine the relationship between the outbreak experience and nursing intention considering stress and professionalism. METHODS: A self-administered questionnairewas designed based on modifications of related questionnaires, and used to assess levels of stress, professionalism, and nursing intention according to participants' experiences during the outbreak. Multiple regression analysiswas used to examine the relationship between the outbreak nursing experience and nursing intention considering stress and nursing professionalism. RESULTS: The overall stress, professionalism, and nursing intention scores for the firsthand experience group were 33.72, 103.00, and 16.92, respectively, whereas those of the secondhand experience group were 32.25, 98.99, and 15.60, respectively. There were significant differences in professionalism and nursing intention scores between the groups (p = .001 and p < .001, respectively). The regression analysis revealed that the regression estimate between stress and nursing intention was B(SE) = −0.08(0.02), beta = −0.21, p < .001 and the regression estimate between professionalism in nursing and nursing intention was B(SE) = 0.05(0.01), beta = 0.23, p < .001. CONCLUSIONS: Prior outbreak nursing experience was importantly associated with intention to provide care for patients with a newly emerging infectious disease in the future considering stress and professionalism. Gathering information about nurses' experience of epidemics and regular assessment of job stress and professionalism are required.
Communicable Diseases* ; Communicable Diseases, Emerging ; Coronavirus ; Coronavirus Infections ; Disease Outbreaks ; Emergencies* ; Hospitals, Public* ; Humans ; Intention* ; Korea* ; Nursing Care ; Nursing* ; Professionalism* ; Stress, Psychological

PURPOSE: The presence of C4d in peritubular capillaries (C4d (PTC)) as a diagnostic in-situ marker of acute humoral rejection and CD20 as marker of B-cell deposition in graft kidney has been reported to be related to steroid resistance and poor outcome. In this retrospective study, we evaluated the clinical significance of C4d and CD20 in allograft renal biopsies by immunohistochemistry technique. And we also evaluated the relationships between C4d and CD20 positive B lymphocytes. METHODS: We studied 22 patients who had been biopsied for suspected acute rejection. Biopsies were classified by updated Banff 97 criteria. Of the 22 cases, borderline rejection and Banff 1A were 11 cases respectively and no case had a vascular lesion. Paraffin sections were stained with monoclonal antibodies (anti-C4d and -CD20) using an immunohistochemistry technique and the results of immunohistochemistry were analyzed by clinical data. RESULTS: Of the 22 cases, 22.7% (5/22) showed diffuse and 40.9% (9/22) showed focal C4d positivity in peritubular capillaries. The grafts failed to survive in 20% (1/5) of the diffuse (P), 44.4% (4/9) of the focal, and 0% (0/8) of the negative group for 2 years since postbiopsies, however, the C4d staining was not statistically related to graft loss and graft survival rates (P=0.091, P=0.106 respectively). The C4d positivity was significantly related to the level of serum creatinine (P=0.042) and to steroid pulsing therapy resistance (P=0.030). However C4d deposition was not associated with recipient gender, age, type of donor (living vs deceased), HLA matching, induction, and Banff classification. On the CD20 immunostaining, 50.0% (11/22) showed negative reactivity, 9.1% (2/22) one nodule, 40.9% (9/22) 2 nodules. The presence and the number of CD20 positive nodules were not correlated to the C4d clinical data. But, the degree of C4d staining was statistically related with the presence of CD20 positive nodules (P=0.029). CONCLUSION: The peritubular capillary C4d is clinically important however, not likely a significant predictor of grafts survival rates in mild rejection. The clinical implication of CD20 positive B lymphocyte nodules in acute rejection was not demonstrated in this study. But, CD20 positive B lymphocyte may be a positive linkage with C4d and participate in humoral rejection.
Antibodies, Monoclonal ; B-Lymphocytes ; Biopsy ; Capillaries ; Creatinine ; Graft Survival ; Humans ; Immunohistochemistry ; Kidney ; Lymphocytes ; Paraffin ; Rejection (Psychology) ; Retrospective Studies ; Survival Rate ; Tissue Donors ; Transplantation, Homologous ; Transplants

PURPOSE: To investigate whether changes in plasma concentrations of transforming growth factor-beta1 (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) could be used to identify the development of radiation-induced pneumonitis in the lung cancer patients. METHODS AND MATERIALS: Seventeen patients with lung cancer (11 NSCLC, 6 SCLC) were enrolled in a prospective study designed to evaluate clinical and molecular biologic correlation of radiation-induced pneumonitis. The study began in May 1998 and completed in July 1999. All patients were treated with radiotherapy with curative intent : 1.8 Gy per day, 5 fractions per week. Serial measurements of plasma TGF-beta1, TNF-alpha and IL-6 were obtained in all patients before, weekly during radiotherapy and at each follow-up visits after completion of treatment. These measurements were quantified using enzyme linked immunosorbent assay (ELISA). All patients were evaluated for signs and symptoms of pneumonitis at each follow-up visit after completion of radiotherapy. High resolution CT (HRCT) scans were obtained when signs and symptoms of pneumonitis were developed after completion of radiotherapy. RESULTS: Thirteen patients eventually developed signs and symptoms of clinical pneumonitis while four patients did not. TGF-beta1 levels were elevated in all 13 patients with pneumonitis, which showed characteristic pattern of elevation (38.45 ng/ml at pretreatment, 13.66 ng/ml during radiotherapy, then 60.63 ng/ml at 2-4 weeks after completion of radiotherapy). The levels of TNF-alpha and IL-6 were also elevated in the group of patients who developed pneumonitis but the pattern was not characteristic. CONCLUSIONS: Changes in plasma TGFbeta-1 levels before, during and after radiotherapy appears to be a useful means by which to identify patients at risk for the development of symptomatic pneumonitis. Other cytokines like TNF-alpha and IL-6 shows no meaningful changes in association with radiation pneumonitis.
Cytokines* ; Enzyme-Linked Immunosorbent Assay ; Follow-Up Studies ; Humans ; Interleukin-6 ; Lung Neoplasms* ; Lung* ; Plasma* ; Pneumonia* ; Prospective Studies ; Radiation Pneumonitis ; Radiotherapy ; Transforming Growth Factor beta1 ; Tumor Necrosis Factor-alpha

PURPOSE: To assess the tolerance, complete response rate, bladder preservation rate and survival rate in patients with muscle-invading bladder cancer treated with selective bladder preservation protocol. METHOD AND MATERIALS: From October 1990 to June 1998, twenty six patients with muscle-invading bladder cancer (clinical stage T2-4, N0-3, M0) were enrolled for the treatment protocol of bladder preservation. They were treated with maximal TURBT (transurethral resection of bladder tumor) and 2 cycles of MCV chemotherapy (methotrexate, crisplatin, and vinblastine) followed by 39.6~45 Gy pelvic irradiation with concomitant cisplatin. After complete urologic evaluation (biopsy or cytology), the patients who achieved complete response were planed for bladder preservation treatment and treated with consolidation cisplatin and radiotherapy (19.8 Gy). The patients who had incomplete response were planed to immediate radical cystectomy. If they refused radical cystectomy, they were treated either with TURBT followed by MCV or cisplatin chemotherapy and radiotherapy. The median follow-up duration is 49.5 months. RESULT: The patients with stage T2-3a and T3b-4a underwent complete removal of tumor or gross tumor removal by TURBT, respectively. Twenty one out of 26 patients (81%) successfully completed the protocol of the planned chemo-radiotherapy. Seven patients had documented complete response. Six of them were treated with additional consolidation cisplatin and radiotherapy. One patient was treated with 2 cycles of MCV chemotherapy due to refusal of chemo-radiotherapy. Five of 7 complete responders had functioning tumor-free bladder. Fourteen patients of incomplete responders were further treated with one of the followings : radical cystectomy (1 patient), or TURBT and 2 cycles of MCV chemotherapy (3 patients), or cisplatin and radiotherapy (10 patients). Thirteen patients of them were not treated with planned radical cystectomy due to patients' refusal (9 patients) or underlying medical problems (4 patients). Among twenty one patients, 12 patients (58%) were alive with their preserved bladder, 8 patients died with the disease, 1 patient died of intercurrent disease. The 5 years actuarial survival rates according to CR and PR after MCV chemotherapy and cisplatin chemoradiotherapy were 80% and 14%, respectively (p=0.001). CONCLUSION: In selected patients with muscle-invading bladder cancer, the bladder preservation could be achieved by MCV chemotherapy and cisplatin chemo-radiotherapy. All patients tolerated well this bladder preservation protoco. The availability of complete TURBT and the responsibility of neoadjuvant chemotherapy and chemoradiotherapy were important predictors for bladder preservation and survival. The patients who had not achieved complete response after neoadjuvant chemotherapy and chemoradiotherapy should be immediate radical cystectomy. A randomized prospective trial might be essential to determine more accurate indications between cystectomy or bladder preservation.
Chemoradiotherapy ; Cisplatin ; Clinical Protocols ; Combined Modality Therapy* ; Cystectomy ; Disulfiram ; Drug Therapy ; Follow-Up Studies ; Humans ; Radiotherapy ; Survival Rate ; Urinary Bladder Neoplasms* ; Urinary Bladder*

PURPOSE: The genes involved on the suppression of radiation-induced apoptosis by genistein in K562 leukemia cell line was investigated. MATERIALS AND METHODS: K562 cells in exponential growth phase were irradiated with a linear accelerator at room temperature. Forx-ray irradiation and drug treatment, cultures were prepared at 2x105 cells/mL. The cells were irradiated with 10 Gy (Clinac 1800C, Varian, USA). Stock solutions of herbimycin A (HMA, Calbiochem, UK) and genistein (Calbiochem, UK) were prepared in dimethylsulfoxide (DMSO, Sigma, UK). After incubation at 37degreesC for 24 h, PCR-select cDNA subtractive hybridization, dot hybridization, DNA sequencing and Northern hybridization were examined. RESULTS: Smad6 gene was identified from the differentially expressed genes in K562 cells incubated with genistein which had been selected by PCR-select cDNA subtractive hybridization. The mRNA expression of Smad6 in K562 cells incubated with genistein was also higher than control group by Northern hybridization analysis. CONCLUSION: We have shown that Smad6 involved on the suppression of radiation-induced apoptosis by genistein in K562 leukemia cell line. It is plausible that the relationship between Smad6 and the suppression of radiation-induced apoptosis is essential for treatment development based on molecular targeting designed to modify radiation-induced apoptosis.
Apoptosis* ; Cell Line ; Dimethyl Sulfoxide ; DNA, Complementary ; Genistein* ; K562 Cells* ; Leukemia ; Particle Accelerators ; RNA, Messenger ; Sequence Analysis, DNA

PURPOSE: Buerger's disease (Thromboangiitis obliterans, TAO) is characterized by non- atheromatous inflammatory disease, and segmental inflammatory thrombotic occlusions of the small & middle-sized arteries and veins of the upper or lower extremities. Any epidemiological study of Buerger's disease in Korea has not been carried out until now. This study was undertaken to investigate the incidence of Buerger's disease in Korea among the patients suffering with arterial disease. METHODS: We collected and analyzed the data on 11,128 patients who were admitted to or visited the participating 22 hospitals for chronic arterial diseases throughout the major region of the South Korea from January 1986 to December 2003. The clinical diagnostic inclusion criteria for Buerger's disease were the followings: (1) a history of smoking or tobacco abuse; (2) an age of onset less than 50 years; (3) infrapopliteal, segmental arterial occlusions with sparing of the proximal vasculature; (4) frequent distal upper extremity arterial involvement (Raynaud's syndrome or digital ulceration) or-superficial phlebitis; and (5) the absence of arteriosclerotic risk factors other than smoking. RESULTS: The incidence rate of Buerger's disease among the arterial disease (11,128 patients) was 93 patients (0.83%) when the strict criteria of Shionoya was applied. 699 male-patients (6.55%) and 30 female patients (4.12%) who met the less strict criteria (the extended clinical diagnostic criteria group) were also reviewed. The 4th and 5th decades were the most common ages with-249 patients (34.2%) and 222 patients (30.5%) respectively, being found at these ages. The mean age was 40.4+/-1.6 years (age range: 16~83 years) and this was similar in both the strict criteria group and the less strict criteria group. CONCLUSIONS: This study suggests there was a low incidence of Buerger's disease in Korea among the patients who visited the participating hospitals when the strict diagnostic criteria were used. The incidence was lower than expected even when the less strict criteria were used. The more accurate incidence of Buerger's disease among the general population can be obtained by performing careful prospective study that is participated in by not only vascular surgeons, but also the other medical specialists with utilizing the strict diagnostic criteria.
Age of Onset ; Arteries ; Epidemiologic Studies ; Female ; Humans ; Incidence ; Korea* ; Lower Extremity ; Phlebitis ; Risk Factors ; Smoke ; Smoking ; Specialization ; Thromboangiitis Obliterans* ; Tobacco ; Upper Extremity ; Veins