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HMGB1 Switches Alkylating DNA Damage-Induced Apoptosis to Necrosis (HMGB1에 의한 alkylating DNA 손상에 의해 유도된 세포사멸의 세포괴사로의 전환)

  • Lee, Su-Yeon;Jeong, Eui-Kyong;Jeon, Hyun-Min;Ju, Min-Kyung;Kim, Cho-Hee;Park, Hye-Gyeong;Kang, Ho-Sung
    • Journal of Life Science
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    • v.21 no.7
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    • pp.953-960
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    • 2011
  • Necrosis is characterized by the cell membrane rupture and release of the cellular contents, including high-mobility group box 1 protein (HMGB1), into the extracellular microenvironment. HMGB1 acts as a transcriptional regulator in nuclei, but exerts a pro-inflammatory and tumor-promoting cytokine activity when released into the extracellular space. Its overexpression is associated with tumor progression and chemoresistance. Thus, HMGB1 acts as a clinically important molecule in tumor biology. In this study, we examined whether HMGB1 affects cell death induced by anti-cancer drugs. Here we show that HMGB1 prevented cisplatin (alkylating agent)-induced apoptosis and switched the cell fate to necrosis in MCF-7, MDA-MB231, and MDA-MB361 cells. Similar apoptosis-to-necrosis switch effects of HMGB1 were observed in cells treated with 4-HC, another alkylating agent. In contrast, HMGB1 did not exert any significant effects on docetaxel (DOC)-induced apoptosis in MCF-7 cells. We also show that cisplatin-induced apoptosis was switched to necrosis in MCF-7 multicellular tumor spheroids (MTS) that were cultured for 8 days and had necrotic cores, but DOC-induced apoptosis was prevented without the apoptosis-to-necrosis switch. Finally, the levels of RAGE, a receptor of HMGB1, were increased with extended culture of MTS. These findings demonstrate that HMGB1 switches alkylating agent-induced apoptosis to necrosis, suggesting that the strategy to prevent necrosis occurring as an undesirable action of alkylating agent-based chemotherapy should be delineated to improve the efficacy of chemotherapy for cancer.

Cranial Irradiation in the Management of Childhood Leukemic Hyperleukocytosis (극심한 백혈구 증가증을 보이는 소아 백혈병 환자에서 전두개 방사선치료)

  • Hong, Se-Mie;Kim, Il-Han
    • Radiation Oncology Journal
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    • v.19 no.2
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    • pp.142-145
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    • 2001
  • Purpose : Acute leukemia with hyperleukocytosis (more than $10^5/mm^3$) is at high risk of early sudden death, usually from intracerebral hemorrhage. Emergency cranial irradiation is a relatively simple approach to solve this the problem. We summarized our experience of cranial irradiation in 24 leukemic children who presented with hyperleukocytosis. Methods and Materials : Between 1990 and 1998, 40 children with acute leukemia presenting with hyperleukocytosis were referred for emergency cranial irradiation. Among these patients, 24 children were evaluable. There were 16 boys and eight girls, their ages ranged from 2 to 13 years (median 9.5 years). The initial leukocyte counts ranged $109,910/mm^3\;to\;501,000/mm^3$. Peripheral blood smear was peformed in all patients and noted the morphology of the blast. Introduction of emergency cranial irradiation was determined by the leukocyte counts (more than 100,000/mm) and the existence of the blast in peripheral blood smear. All patients were treated with intravenous hydration with alkaline fluid and oral allopurinol. Cranial irradiation started on the day of diagnosis. With 2 Gy in one fraction in 4 patients, 4 Gy in two fractions in 20 patients. Results : The WBC count had fallen in 19 patients (83%) and no intracerebral hemorrhage occurred after irradiation. There were five cases of early deaths. Four patients died of metabolic complications, and one patient with intracerebral hemorrhage. He died 5 hours after cranial irradiation. No patient had any immediate side effect from cranial irradiation. Conclusion : Our data suggest, that emergency cranial irradiation can be safely chosen and effective in childhood leukemic patients presenting with high leukocyte counts.

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Characteristics of mushroom Phellinus baumii extracts with enzyme pretreatment (효소 전처리에 의한 상황버섯 β-glucan 추출물의 특성)

  • Son, Eun Ji;Ryu, Eun-Ah;Lee, Sang-Han;Kim, Young-Chan;Hwang, In-Wook;Chung, Shin-Kyo
    • Journal of Applied Biological Chemistry
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    • v.61 no.1
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    • pp.101-108
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    • 2018
  • This study was conducted to establish optimized ${\beta}-glucan$ extraction method through enzymatic hydrolysis from Phellinus baumii and investigate ${\beta}-glucan$ contents and physicochemical properties. The optimal condition was obtained with the enzyme concentration of 0.66% (v/v), reaction time of 6.08 h ($R^2=0.9245$) and the ${\beta}-glucan$ contents from the Phellinus baumii extracts under the optimized condition was 1.9594 g/100 g. ${\beta}-Glucan$ yield (0.76-16.40%) of enzyme beta-glucan extract (EBE) was three fold higher than that of non-enzyme beta-glucan extract (NEBE). ${\beta}-Glucan$ purity (11.15-59.05%) of non-enzyme beta-glucan (NEB) and that of enzyme beta-glucan (EB) were higher than that of NEBE and that of EBE. ${\beta}-Glucan$ purity of EB (59.05%) and ${\beta}-glucan$ contents of EB (3.38 g/100 g) showed higher than those of others. Total sugar contents (0.61-1.17 mg/mL) showed that NEB and EB were higher than that of NEBE and EBE, EB had the highest total sugar content as 1.17 mg/mL, respectively. Protein contents (0.44-11.73 mg/mL) of NEBE and that of EBE were higher than that of NEB, that of EB. In FT-IR spectrum, the band at $890cm^{-1}$ of microcapsule was attributed to a ${\beta}-1,3-glucan$. The toxicities of ${\beta}-glucan$ from Phellinus baumii in both melanoma cell lines was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoli um bromide assay and ${\beta}-glucan$ from Phellinus baumii has no toxicity until $30{\mu}g/mL$. The effects of ${\beta}-glucan$ from Phellinus baumii on inhibition of cancer cell proliferation were detected by using a wound healing assay. The effect of NEB and EB were higher than NEBE and EBE, especially $30{\mu}g/mL$ of EB had the highest in both melanoma cell lines.

Analysis by Delphi Survey of a Performance Evaluation Index for a Salt Reduction Project (델파이 조사를 통한 저염화사업 성과평가 지표 분석)

  • Kim, Hyun-Hee;Shin, Eun-Kyung;Lee, Hye-Jin;Lee, Nan-Hee;Chun, Byung-Yeol;Ahn, Moon-Young;Lee, Yeon-Kyung
    • Journal of Nutrition and Health
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    • v.42 no.5
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    • pp.486-495
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    • 2009
  • The purpose of this study was to analyze the performance evaluation index for a salt reduction project. Questionnaires were developed in order to investigate salt reduction programs nationwide. The evaluation index and programs were analyzed through the case study of a salt reduction program in public health centers. The validity of the salt reduction program's evaluation index was determined based on study of the Delphi survey and on discussion with nutrition and health care professionals. The Delphi survey showed that daily salt intake was the most valid nutritional evaluation index. Stroke mortality and stomach cancer mortality were good health care evaluation indexes. The method for measuring salt intake that had the greatest validity was a 24-hour urine collection. However, 24-hour urine collection had the lowest score for ease of performance. The combined scores of validity and ease of performance showed that the survey method for dietary attitude and dietary behavior, dietary frequency analysis (DFQ 15), and a salty taste assessment, in that order, were proper methods. The high reliability of the salty taste assessment indicated that the percentage of the population that exhibits proper salt intake (2,000 mg sodium or less daily) and the percentage of the population that consumes low-salt diets as nutritional evaluation indexes also will be helpful to evaluate performance of salt reduction programs.

Comparative Analysis of Community Health Practitioner's Activities and Primary Health Post Management Before and After Officialization of Community Health practitioner (보건진료원의 정규직화 전과 후의 보건진료원 활동 및 보건진료소 관리운영체계의 비교 분석)

  • Yun, Suk-Ok;Jung, Moon-Sook
    • Journal of agricultural medicine and community health
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    • v.19 no.2
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    • pp.141-158
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    • 1994
  • To provide better health care services to the rural population, the government has made the Community Health Practitioner(CHP) a regular government official from April 1, 1992. This study was carried out to study the impact of officialization of CHP on the activities and management system of Primary Health Post(PHP). Fifty PHPs were selected by two stage sampling, cluster and simple random, from 595 PHPs in Kyungnam and Kyungpook provinces. Data were collected by a personal interview with CHPs and review of records and reports kept in the PHPs. The study was done for the periods of January 1-March 31, 1992 (before officialization) and January 1-March 31, 1993 (after officialization). Ninety-six percent of the CHPs wanted to become a regular government official in the hope of better job security and higher salary. The proportion of CHPs who were proud of their iob was increased from 24% to 46% after officialization. Those CHPs who felt insecure for their job decreased from 30% to 10%. Monthly salary was increased by 34% from 802,600 Won to 1,076,000 Won and 90% of the CHPs were satisfied with their salary, also more CHPs responded that they have autonomy in their work planning, implementation of plan, management of the post, and evaluation of their activity. There were no appreciable changes in such CHPs' activities as assessment of local health resources, drawing map for the catchment area, utilization of community organization, grasping the current population structure in the catchment area, keeping the family health records, individual and group health education, and school health service. However, the number of home visits was increased from 13.6 times on the average per month per CHP to 27.5 times. More mothers and children were referred to other medical facilities for the immunization and family planning services. Average number of patients of hypertension, cancer, and diabetes in three months period was decreased from 12.7 to 11.6, from 1.5 to 1.2, and 4.3 to 3.4, respectively. Records for the patient care, drug management, and equipment were well kept but not for other records. The level of record keeping was not changed after officialization. The proportion of PHPs which had support from the health center was increased for drug supply from 14.0% to 30.0%, for consumable commodities from 22.0% to 52.0%, for maintenance of PHP from 54.0% to 68.0%, for supply of health education materials from 34.0% to 44.0%, and supply of equipment from 54.0% to 58.0%. Total monthly revenue of a PHP was increased by about 50,000 Won; increased by 22,000 Won in patient care and 34,700 Won in the government subsidy but decreased in the membership due and donation. However, there was no remarkable changes in the expenditure. The proportion of PHPs which had received official notes from the health center for the purpose of guidance and supervision of the CHPs was increased from 20% to 38% during three months period and the average number of telephone call for supervision from the health center per PHP was increased from 1.8 to 2.1 times(p<0.01). However, the proportion of PHPs that had supervisory visit and conference was reduced from 79% to 62%, and from 88% to 74%, respectively. The proportion of CHPs who maintained a cooperative relationship with Myun Health Workers was reduced from 42% to 36%, that with the director of health center from 46% to 24%, that with the chief of public health administration section from 56% to 36%, and that with the chairman of PHP management council from 62% to 38%. Most of the CHPs (92% before and 82% after officialization) stated that the PHP management council is not helpful for the PHP. CHPs who considered the PHP management council unnecessary increased from 4% to 16%(p<0.05). Suggestions made by the CHPs for the improvement of CHP program included emphasis on health education, assurance of autonomy for PHP management, increase of the kind of drugs that can be dispensed by CHPs, and appointment of an experienced CHP in the health center as the supervisor of CHPs. The results of this study revealed that the role and function of CHPs as reflected in their activities have not been changed after officialization. However, satisfaction in job security and salary was improved as well as the autonomy. Support of health center to the PHP was improved but more official notes were sent to the PHPs which required the CHPs more paper works. Number of telephone calls for supervision was increased but there was little administrative and technical guidance for the CHP activities.

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Curriculum Development for Hospice and Palliative Care Nurses (간호사를 위한 호스피스 완화의료 교육과정 개발)

  • Choi, Eun-Sook;Kim, Hyun-Sook;Lee, So-Woo;Yoo, Yang-Sook
    • Journal of Hospice and Palliative Care
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    • v.9 no.2
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    • pp.77-85
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    • 2006
  • Purpose: The purpose of this study is to develop the basic curriculum for the nurses who work at hospice and palliative care settings. Methods: Seven curricula of hospice and palliative care for the nurses in Korea and other countries were reviewed, and Education Need for hospice and palliative care was surveyed from 162 nurses by mailing the questionnaires to hospice palliative care settings. Results: 1. The curricula of hospice and palliative care for the nurses in Korea and other countries in common include 'understanding of hospice and palliative care', 'understanding of lift and death', 'pain and symptom management for person with terminal disease', 'on-the-spot study and practical training', 'management of hospice and palliative ward', 'hospice and palliative care at home', 'physical assessment', 'therapeutic communication skills', 'children's hospice', 'administration and management of hospice and palliative care', 'interdisciplinary team of hospice and palliative care', 'ethics and laws in hospice and palliative care', 'psychological, social and spiritual care', 'care of the dying', 'bereavement care', etc. 2. The scores above 3.3 were marked for 34 items in education Need Survey. The highest scores were given in the order for the items 'understanding of death and dying', 'attitude and response to death and dying', 'understanding and assessment of pain' etc. respondents marked that they have been trained for 'pain and symptom management', 'ethics and laws in hospice and palliative care', 'building the system for cooperation and publicity activities in hospice' etc. 3. The basic curriculum of hospice and palliative care for the nurses requires 78 studying hours for 17 subjects, comprising 48 hours of theory education and 30 hours of practical training. The education methods are lectures, discussions, and case studies. Conclusion: The efforts of developed basic curriculum should be evaluated after educating nurses. It is necessary to develop the standard curriculum and regularly update it based on the result of education Need Survey for actively working nurses in hospice and palliative care settings.

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Effects of Dietary Addition of Wormwood (Artemisia sp.) on the Growth Performance, Nutrients Utilization, and Abdominal Fat Deposition of Broiler Chickens (사료내 쑥 첨가가 육계의 성장률, 영양소 이용률, 복강내 지방에 미치는 영향)

  • Lee, Sung-Jin;Song, Ki-Duk;Ko, Yung-Du;Kim, Chang-Hyun
    • Korean Journal of Organic Agriculture
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    • v.18 no.3
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    • pp.347-361
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    • 2010
  • This study was carried out to investigate the effects of wormwood (Artemisia sp.) addition on the growth performance, nutrients utilization and abdominal fat deposition of broiler chickens. Two hundred twenty five and two-day old Arboracre strain male commercial broiler chicks were distributed to 5 treatments with wormwood supplementation levels; C(O%), $T_1$ (1%), $T_2$ (3%), $T_3$ (5%), and $T_4$ (10%) and with 3 replications each with 5 birds for five weeks. Body weight gain during the experiment was improved in $T_1$ (1723.0g) compared with that of $T_3$ (1557.7g) and $T_4$ (1450.7g) (P<0.05). Feed intake was significantly (P<0.05) increased as the levels of wormwood addition increased (C: 2653.8g, T1: 2852.0, $T_2$: 2900.3, $T_3$: 2900.7g, T4: 2954.7g). Feed conversion rate (feed/gain) was significantly (P<0.05) increased as the levels of wormwood addition increased (C: 1.55, $T_1$: 1.66, $T_2$: 1.70, $T_3$: 1.86, $T_4$: 2.04). The days reaching to 2.0kg of body weight were expected to be 43.2 days in control, whereas those of group T1 were reduced to 42.6 days by 0.6 day from control. Nutrient utilization and abdominal fat deposition in the experiment were significantly decreased (P<0.05) and small intestine contents in the broilers was significantly increased (P<0.05) as the levels of wormwood addition increased. Therefore, although there was no significant improvement for the performance of broiler chickens with the dietary supplementation of wormwood meal, less than 1% addition of wormwood to broiler diets might have beneficial for human health by reducing the abdominal fat deposition of the broiler chicknens.

Estimating the Likelihood of Malignancy in Solitary Pulmonary Nodules by Bayesian Approach (Bayes식 접근법에 의한 고립성 폐결절의 악성도 예측)

  • Shin, Kyeong-Cheol;Chung, Jin-Hong;Lee, Kwan-Ho;Kim, Chang-Ho;Park, Jae-Yong;Jung, Tae-Hoon;Han, Sung-Beom;Jeon, Young-Jun
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.4
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    • pp.498-506
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    • 1999
  • Background : The causes of solitary pulmonary nodule are many, but the main concern is whether the nodule is benign or malignant. Because a solitary pulmonary nodule is the initial manifestation of the majority of lung cancer, accurate clinical and radiologic interpretation is important. Bayes' theorem is a simple method of combining clinical and radiologic findings to estimate the probability that a nodule in an individual patients is malignant. We estimated the probability of malignancy of solitary pulmonary nodules with a specific combination of features by Bayesian approach. Method : One hundred and eighty patients with solitary pulmonary nodules were identified from multi-center analysis. The hospital records of these patients were reviewed and patient age, smoking history, original radiologic findings, and diagnosis of the solitary pulmonary nodules were recorded. The diagnosis of solitary pulmonary nodule was established pathologically in all patients. We used to Bayes' theorem to devise a simple scheme for estimating the likelihood that a solitary pulmonary nodule is malignant based on radiological and clinical characteristics. Results : In patients characteristics, the probability of malignancy increases with advancing age, peaking in patients older than 66 year of age(LR : 3.64), and higher in patients with smoking history more than 46 pack years(LR : 8.38). In radiological features, the likelihood ratios were increased with increasing size of the nodule and nodule with lobulated or spiculated margin. Conclusion : In conclusion, the likelihood ratios of malignancy may improve the accuracy of the probability of malignancy, and can be a guide of management of solitary pulmonary nodule.

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Study for Reliability of Interpretation of the Three Phase Bone Scintigraphy in Patients with Post-traumatic Complex Regional Pain Syndrome (외상 후 복합부위통증증후군 환자에서 시행한 삼상 뼈 스캔의 판독 신뢰도에 관한 연구)

  • Park, Jung-Mi;Kim, Seon-Jung;Chung, Seung-Hyun;Lee, Yong-Taek
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.1
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    • pp.44-51
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    • 2008
  • Purpose: We performed this study to evaluate reliability on interpretation of three phase bone scintigraphy (TPBS) in patients with post-traumatic complex regional pain syndrome (PT-CRPS). Methods: Based on International Association for the Study of Pain guideline in 1994, 34 patients with PT-CRPS were selected for this study. Two nuclear medicine physicians evaluated identical TPBS according to the uptake pattern, extent and intensity of the lesion, and their agreements (kappa values) were analysed. The final diagnosis based on arbitrary criteria of each physician were compared with those obtained by the criteria for PT-CRPS established in this study, which are hyperactivity on all phases (criteria 1), hyperactivity of whole joints on delayed phase (criteria 2), and hyperactivity of either whole or FDGal joints on delayed phase (criteria 3). Results: Intra-observer agreements were good for uptake pattern, intensity, and extent on TPBS. Inter-observer agreements were also good, except extent on blood pool phase (0.55). The inter-observer agreements on final diagnosis improved when criteria 1-3 were applied (0.77-0.88), compared to when physician's own criteria were used (0.63). Those also improved from 0.29 to 0.47-0.82 for acute stage, and from 0.37 to 1.0 for chronic stage. The sensitivities of chronic stage were relatively lower to those of acute stage. Conclusions: Inter-observer's variations in diagnosis of the patients with PT-CRPS using TPBS were observed. These results were attributed to different criteria set by observers. In order to improve agreement on interpretation of TPBS, common positive criteria should be established, especially considering uptake pattern and clinical stages.

Hepatitis Complicated with Mycoplasma pneumoniae Infection (Mycoplasma pneumoniae 폐렴에 합병된 간염)

  • Lee, Jin-Tae;Kim, Hee-Sup;Tchah, Hann
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.4 no.2
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    • pp.207-212
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    • 2001
  • Purpose: Mycoplasma pneumoniae infection is relatively common in childhood. Its extrapulmonary manifestations have been reported so much, but hepatitis associated with it has not been studied yet until now in Korea. Methods: We performed the prospective study of 19 cases that had AST and ALT>50 IU/L respectively without evidence of hepatitis A, B, C, cytomegalovirus, and Ebstein-Barr virus infections amongst 143 patients with M. pneumoniae pneumonia who were admitted to the Department of Pediatrics, Seoul Red Cross Hospital from Jan. 1999 to Dec. 2000. Results: 1) Hepatitis occurred in 13.3% of Mycoplasma pneumoniae infection, especially in fall and winter times. The average age was 4.86 years and male to female ratio was 2.2:1. 2) Vomiting was developed in 21.1%, diarrhea in 36.8%, and hepatomegaly in 21.1%, respectively. And leukocytosis was noted in 21.1%, eosinophilia in 15.4%, anemia in 10.5%, and thrombocytosis in 5.3%, respectively. The average level of C-reactive protein was $6.34{\pm}4.82$ mg/dl. 3) There was no hyperbilirubinemia, but hypoalbuminemia was detected in 42.1%. The average serum levels of AST and ALT were $214.05{\pm}183.22$ IU/L and $284.16{\pm}286.84$ IU/L, respectively. 4) Chest radiology showed lobar or lobular consolidation in 73.7%, bronchial infiltration in 26.3%, and pleural effusion in 31.6%. 5) The average length of hospitalization was 7.9 days, and the average length of normalization of serum transaminases was 8.8 days. All patients recovered within 2 weeks completely. Conclusion: The prognosis of M. pneumoniae hepatitis is good. However, its incidence is not so low that liver function should be considerately checked in case of M. pneumoniae infection.

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