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The Adjuvant Effect of Subcutaneous Interferon-gamma in the Treatment of Refractory Multidrug-resistant Pulmonary Tuberculosis (난치성 다제내성 폐결핵에서 피하주사 Interferon-gamma 치료의 효과: 예비연구)

  • Kim, Eun Kyung;Shim, Tae Sun;Lee, Jung Yeon;Oh, Yeon-Mok;Lim, Chae-Man;Lee, Sang Do;Koh, Younsuck;Kim, Dong Soon;Kim, Won Dong;Kim, Woo Sung
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.3
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    • pp.226-233
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    • 2004
  • Background : Interferon-gamma (IFN-${\gamma}$) is a critical cytokine in the defense against a Mycobacterium tuberculosis infection. Even though IFN-${\gamma}$ has occasionally been used in the treatment of refractory multidrug-resistant tuberculosis (MDR-TB) with some promising results, there is still some controversy regarding the therapeutic efficacy of IFN-${\gamma}$. This study was performed to examine the effect of subcutaneous IFN-${\gamma}$ in the treatment of MDR-TB patients. Methods : Six patients with refractory MDR-TB were enrolled in this study. Two million IU of IFN-${\gamma}$ was administered subcutaneously three times a week with the concomitant administration of antituberculous drugs for at least for 28 weeks. During the IFN-${\gamma}$ therapy, the sputum smear and culture, radiological and clinical evaluations were performed every 4 weeks throughout the study period. Results : The mean age of the 6 patients was 37 years (ranges, 15-61 years). The drug susceptibility test to standard antituberculous drugs revealed resistance to an average of 6.8 (${\pm}1.2$) agents including isoniazid and rifampicin. An average of 10.8 (${\pm}1.3$) antituberculous drugs were prescribed before IFN-${\gamma}$ therapy. The culture became negative in 2 patients (33%) after initiating IFN-${\gamma}$ therapy; one at 8 weeks, and the other at 24 weeks. Finally, after stopping the IFN-${\gamma}$ therapy after 28 weeks, the culture became positive again in the two patients who were culture-negative. The other 4 patients who failed in the culture conversion are still on antituberculous treatment except for one who died of tuberculosis. Conclusion : Even though 28 weeks of subcutaneous IFN-${\gamma}$ therapy in combination with antituberculous drugs was successful in inducing the culture-negative conversion in some patients with refractory MDR-TB, the culture became positive again after stopping the IFN-${\gamma}$ therapy. This suggests that subcutaneous IFN-${\gamma}$ therapy may have suppressive effect on tuberculosis only during the IFN-${\gamma}$ therapy period in some patients. Further studies will be needed to determine the optimum dose, the administration route, the duration of therapy, and the predicting factors of the response to adjuvant IFN-${\gamma}$ therapy.

Clinical Characteristics of Tuberculosis in North Korean Refugees (북한이탈주민에서의 결핵의 임상적 고찰)

  • Choi, Chang-Min;Jeong, Woo-Kyoung;Kang, Cheol-In;Kim, Doh-Hyung;Kim, Young-Keun;Heo, Sang-Taek;Kim, Hee-Jin
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.3
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    • pp.285-289
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    • 2006
  • Background : North Korea's economic and public health problems began in the early 1990s as a result of the gradual loss of economic support from its communist allies, combined with an inordinate number of natural disasters. The decline in public health has increased the incidence of tuberculosis in North Koreans and refugees. This study investigated tuberculosis situation in North Korean refugees in order to prepare for the future impact of tuberculosis control in Korea. Material and Methods : From 2001 to 2005, tuberculosis patients among North Korean refugees who were diagnosed before or after arriving in South Korea, based on the official records of OO hospital, were enrolled in this study. The demographic and clinical data of the cases were evaluated retrospectively. Results : A total of 42 TB cases were reviewed during the study period. Of these, 37 (88.1%) cases were pulmonary TB. based on the cases identified among the number of North Korean refugees' arriving each year, the annual incidence of pulmonary TB were 900 per 100,000 in 2004, 700 in 2003, The number of smear-positive patients was 20 (47.6%) and the number of culture-positive patients was 18 (42.9%). Of the M. tuberculosis isolates, 2 cases were found to be susceptible to all anti-TB drugs available, 4 were resistant to isoniazid, and 3 were multi-drug resistant. Conclusion : The prevalence of pulmonary TB in North Korean Refugees is high. In addition, North Korean refugees suffer from more severe tuberculosis in bacteriological and radiological aspects.

Causative Organisms of Community Acquired Urinary Tract Infection and Their Antibiotic Susceptibility at a Secondary hospital in Korea (2차 병원에서의 지역 사회 획득 요로 감염의 원인균 및 항생제 감수성 분석)

  • Jo, Yun Ju;Lee, Eun Jeong;Choi, Kyong Min;Eun, Young Min;Yoo, Hwang Jae;Kim, Cheol Hong;Lee, Hyun Hee;Kim, Pyung Kil
    • Pediatric Infection and Vaccine
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    • v.17 no.1
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    • pp.30-35
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    • 2010
  • Purpose : We investigated the causative organism and its antibiotic susceptibility of community acquired urinary tract infection (UTI) in children at a secondary hospital to test the adequacy of the current guidelines. Methods : Children diagnosed with UTI at the Department of Pediatrics, Kwandong University MyMyongji Hospital by pyuria and bacterial growth of greater than $1.0{\times}10^5CFU/mL$ on clean catch midstream urine from January 2005 to December 2008 were studied retrospectively. The epidemiologic data, causative organism, and the antibiotic susceptibility were analyzed. Results : Sixty two children were diagnosed with sixty four cases of UTI's. Two bacteria were isolated in one case and thus data on 65 urine cultures were analyzed. The male:female ratio was 1.6:1 and 78.1% were less than 12 months of age. Escherichia coli was the predominant cause consisting of 53 cases (82.8%) of the cases. K. pneumoniae (5), Enterobacter (4), Enterococcus (1), $\beta$-streptococcus (1), Diphtheroides (1) were isolated. The antibiotic resistance of E. coli were as follows; ampicillin 69.8%, cefotaxime 1.9%, gentamicin 15.1%, amikacin 0.0%, levofloxacin 1.9%, and trimethoprim/sulfamethoxazole 26.4 %. Only one case of the E. coli was extended spectrum $\beta$-lactamase (ESBL) positive. Conclusion : Compared to prior reports from other tertiary hospitals in Korea, E. coli was the predominant cause in childhood UTI and the rate of ESBL positivity was low. The antibiotic resistance was also different compared to prior reports. We conclude that a difference in the cause and antibiotic resistance of childhood UTI exists between centers and this should be taken into consideration when prescribing antibiotics for childhood UTIs.

Risk factors associated with complicated methicillin-resistant Staphylococcus aureus bacteremia in neonates (신생아의 MRSA 균혈증에서 합병증 발생과 연관된 위험인자)

  • Lee, Young Jin;Kim, Hyen Jin;Byun, Shin Yun;Park, Su Eun;Park, Hee Ju
    • Clinical and Experimental Pediatrics
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    • v.53 no.2
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    • pp.173-177
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    • 2010
  • Purpose : Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen that causes nosocomial infection in NICU. It contributes to neonatal morbidity and mortality with variable complications. This study was conducted to identify the risk factors associated with complicated MRSA bacteremia in neonates. Methods : We reviewed the medical records of 44 neonates with positive blood culture for MRSA who were admitted to the NICU of Pusan National University Hospital from January 2002 to December 2007. We compared various factors of the complicated and uncomplicated MRSA bacteremia cases. Results : Of the 44 neonates, 31 were male and 13, female. The mean gestational age and birth weight were $33.2{\pm}4.9$ weeks and $1,859.9{\pm}962.2g$, respectively. Twenty-one of infants were treated with a mechanical ventilator during a mean of $8.8{\pm}13.8$ days. There were 13 cases of complicated and 31 cases of uncomplicated MRSA bacteremia. Between the 2 groups, we compared the following variables: gestational age, birth weight, ventilator use, umbilical catheter use and central catheter insertion, $O_2$ inhalation, first oral feeding day after birth, underlying disease, transfusion, and initial vancomycin use. The underlying disease and transfusion were the risk factors related to complicated MRSA bacteremia. Conclusion : Complicated MRSA bacteremia is related to underlying disease and transfusion. Since this was a retrospective study with a small sample size, it offered limited capacity to compare complicated and uncomplicated MRSA bacteremia. A prospective study with a larger population is needed to determine the exact characteristics of MRSA bacteremia in NICU.

A study of serotyping of Streptococcus pneumoniae by multibead assay (다중구슬 분석법에 의한 폐구균 혈청형 결정 연구)

  • Cho, Ky Young;Lee, Jung Ah;Cho, Sung Eun;Kim, Nam Hee;Lee, Jin A;Hong, Ki Sook;Lee, Hoan Jong;Kim, Kyung Hyo
    • Clinical and Experimental Pediatrics
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    • v.50 no.2
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    • pp.151-156
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    • 2007
  • Purpose : Streptococcus pneumoniae is a major etiologic agent for pneumonia, meningitis, otitis media, and sepsis among young children. Multi-drug resistant strains have raised great concern worldwide, thus the importance of prevention with vaccines has been emphasized. However, vaccines may force the appearance of pneumococcal infections by nonvaccine serotypes. Thus, distribution of pneumococcal serotypes should be monitored to estimate vaccine efficacy. We used a new and efficient multibead assay in determining pnemococcal serotypes. Methods : From January to February 2005, 643 children were recruited from ten day care centers to isolate pneumococci from their oropharynx. Pneumococcal serotyping was performed on 62 pneumococcal isolates from 60 children by multibead assay. This immunoassay required two sets of latex particles coated with pneumococcal polysaccharides and serotype-specific antibodies. Twenty four newly developed monoclonal antibodies specific for common serotypes and a pool of polyclonal rabbit sera for some of the less common serotypes were used. Results : The most prevalent pneumococcal serotypes were serotype 6A, 19A, 19F, 23F, and 11A/D/F which accounted more than 50 precent of all the 62 pneumococcal isolates. We found that multibead assay can be performed very rapidly and objectively. Conclusion : This multibead immunoassay was very useful in serotyping clinical isolates of S. pneumoniae because it was simple, reliable and fast.

Chlorophyll Fluorescence and $CO_2$ Fixation Capacity in Leaves of Camellia sinensis, Camellia japonica, and Citrus unshiu (차나무, 동백나무, 귤나무 잎에서 엽록소 형광 및 $CO_2$ 흡수능의 비교 분석)

  • Oh, Soonja;Lee, Jin-Ho;Ko, Kwang-Sup;Koh, Seok Chan
    • Korean Journal of Environmental Biology
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    • v.30 no.2
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    • pp.98-106
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    • 2012
  • The chlorophyll fluorescence and photosynthetic $CO_2$ fixation capacity of leaves from three major crop trees found on Jeju Island, Camellia sinensis L., Camellia japonica L., and Citrus unshiu M., were analyzed. The photosynthetic $CO_2$ fixation rate of C. sinensis was similar to that of C. unshiu, and much higher than that of C. japonica which belongs to the same genus. Stomatal conductance in the three species was high at dawn and low during daytime. The intercellular $CO_2$ concentration of the three species was also high at dawn and decreased at midday. The transpiration rate showed an opposite trend from the intercellular $CO_2$ concentration. The photochemical efficiencies of PSII (Fv/Fm) in C. sinensis were slightly lower at midday compared to the level at dawn and/or dusk. The decline in Fv/Fm of C. sinensis at midday was much smaller than that of C. japonica. These results indicate that C. sinensis is better acclimated to high levels of radiation under natural conditions in late summer, although its PSII reaction center was inhibited by strong radiation. Of the chlorophyll fluorescence parameters in the species, the RC/CS decreased significantly while the ABS/RC, TRo/RC, ETo/RC, and DIo/RC increased significantly at midday in late summer. However, C. unshiu did not show significant changes in these values depending on the time of day. Among the three species, the daily $CO_2$ fixation rate in C. sinensis ($320.1mmol\;m^{-2}d^{-1}$) was the highest, followed by that of C. unshiu ($292.5mmol\;m^{-2}d^{-1}$) and C. japonica ($244.8mmol\;m^{-2}d^{-1}$). Thus, C. sinensis may be a valuable crop tree in terms of the uptake of $CO_2$ under natural field conditions.

Combined Effects of Gamma-irradiation and Hyperthermia on the Human Cell Lines for Various Temperatures and Time Sequences (감마선과 온열치료 병용시 세포 치사 능력 증강에 관한 실험적 연구)

  • Koh Kyung Hwan;Cho Chul Koo;Park Woo Yoon;Yoo Seong Yul;Yun Hyong Geun;Shim Jae Won;Lee Mi Jung
    • Radiation Oncology Journal
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    • v.11 no.1
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    • pp.51-58
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    • 1993
  • We tried to establish the theoretical basis of clinical use of combined modality of hyperthermia and radiation therapy. For this purpose, we made an in vitro experiment in order to get the synergistic and/or additive effects on the cell killing of hyperthermia combined with radiation therapy by using the microwave-hyperthermia machine already installed at our department. In our experiment, we use two human cell lines: MKN-45 (adenocarcinoma of stomach) and K-562 (leukemia cell lines). In cases of combined treatments of hyperthermia and gamma-irradiation, the therapeutic effect was the highest in the simultaneous trial. Hyperthermia after gamma irradiation showed slightly higher therapeutic effect than that before irradiation without significant difference, but its effect was the same in the interval of 6 hours between hyperthermia and irradiation. The higher temperature and the longer treatment time were applied, the higher therapeutic effects were observed. We could observe the thermoresistance by time elapse at $43^{\circ}C$. When hyperthermia was done for 30 minutes at the same temperature, thermal enhancement ratio (TER) at DO. 01 (dose required surviving fraction of 0.01) were $2.5{\pm}0.08,\;3.75{\pm}0.18$, and $5.0{\pm}0.15\;at\;436{\circ}C,\;44^{\circ}C,\;and\;45^{\circ}C$ respectively in K-562 leukemia cell lines. Our experimental data showed that more cell killing effect can be obtained in the leukemia cell lines, although they usually are known to be radiosensitive, when treated with combined hyperthermia and radiation therapy. Furthermore, our data show that leukemia cell lines may have various intrinsic radiosensitivity, especially in vitro experiments. The magnitude of cell killing effect, however, will be less than that of MKN-45.

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Identification of multiple key genes involved in pathogen defense and multi-stress tolerance using microarray and network analysis (Microarray와 Network 분석을 통한 병원균 및 스트레스 저항성 관련 주요 유전자의 대량 발굴)

  • Kim, Hyeongmin;Moon, Suyun;Lee, Jinsu;Bae, Wonsil;Won, Kyungho;Kim, Yoon-Kyeong;Kang, Kwon Kyoo;Ryu, Hojin
    • Journal of Plant Biotechnology
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    • v.43 no.3
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    • pp.347-358
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    • 2016
  • Brassinosteroid (BR), a plant steroid hormone, plays key roles in numerous growth and developmental processes as well as tolerance to both abiotic and biotic stress. To understand the biological networks involved in BR-mediated signaling pathways and stress tolerance, we performed comparative genome-wide transcriptome analysis of a constitutively activated BR bes1-D mutant with an Agilent Arabidopsis $4{\times}44K$ oligo chip. As a result, we newly identified 1,091 (562 up-regulated and 529 down-regulated) significant differentially expressed genes (DEGs). The combination of GO enrichment and protein network analysis revealed that stress-related processes, such as metabolism, development, abiotic/biotic stress, immunity, and defense, were critically linked to BR signaling pathways. Among the identified gene sets, we confirmed more than a 6-fold up-regulation of NB-ARC and FLS2 in bes1-D plants. However, some genes, including TIR1, TSA1 and OCP3, were down-regulated. Consistently, BR-activated plants showed higher tolerance to drought stress and pathogen infection compared to wild-type controls. In this study, we newly developed a useful, comprehensive method for large-scale identification of critical network and gene sets with global transcriptome analysis using a microarray. This study also showed that gain of function in the bes1-D gene can regulate the adaptive response of plants to various stressful conditions.

Clinical Courses of Cavitary Lesions in Pulmonary Tuberculosis (폐결핵에서 공동성 병소의 임상적 경과)

  • Park, Seung-Kyu;Kweon, Eun-Soo;Song, Sun-Dae
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.4
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    • pp.484-492
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    • 2001
  • Background : Pulmonary tuberculosis with a remaining cavitary lesion is considered to be a problem with the course of treatment. In particular, re-treatment cases tend to respond poorly to current anti-tuberculosis agents. Therefore the factors that are related with the poor closure of a cavitary lesion in pulmonary tuberculosis during treatment were evaluated. Methods : A retrospective review of the medical records and chest X -ray films of 68 patients who had chemotherapy for the pulmonary tuberculosis with cavitary lesions was made. All the patients had been followed up for more than 12 months at National Masan Tuberculosis Hospital as of Aug. 2000. Results : The male to female ratio was 3.9:1.72.4% of the patients were between 20 to 50 years of age. 66.2% of the cavitary lesions on the chest X-ray films were confined to the upper lung fields : 36.8% in the right upper lung field and 29.4% in the left upper lung field. 82.4% of the cavities were less than 40 mm in their size, and 83.8% were less than 6 mm thick. The cavitary lesions were closed in 48 cases and remained in 20 cases during a follow-up period of more than 12 months. The factors that are thought to affect to the outcomes of the cavities were age, past medication history, the number of unused drugs, and the number of sensitive drugs. Conclusion : In the treatment courses of pulmonary tuberculosis with cavitary lesions, the following factors are associated with less desirable outcome:an age over 45, a past medication history of more than 2 courses of treatment, The number of unused drugs not exceeding average 6 and the number of sensitive drugs not exceeding average 7.

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Targeted Therapies and Radiation for the Treatment of Head and Neck Cancer (두경부 암의 표적 지향적 방사선 치료)

  • Kim, Gwi-Eon
    • Radiation Oncology Journal
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    • v.22 no.2
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    • pp.77-90
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    • 2004
  • Purpose: The purpose of this review Is to provide an update on novel radiation treatments for head and neck cancer Recent Findings: Despite the remarkable advances In chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) Is an appealing target for novel therapies In head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression Is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuxlmab) and tyrosine kinase inhibitors (ZD1839 and 051-774) have been assessed and have been most extensively studied In preclinical models and clinical trials. Additional TKIs In clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted In rapid translation Into the clinic. Results from Initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or In combination with chemotherapy. In this review, we begin with a brief summary of erbB- mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinlcal and clinical data on the role of EGFR antagonists alone or in combination with radiation In the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR biockade and efforts In the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1 ) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2) how to sequence these agents with radiation and/or cytotoxlc compounds, (3) reliable markers for patient selection and verification of effective blockade of signaling in vivo, and (4) mechanisms behind intrinsic or acquired resistance to targeted agents to facilitate rational development of multi-targeted therapy, Other molecuiar-targeted approaches In head and neck cancer were briefly described, Including angloenesis Inhibitors, farnesyl transferase inhibitors, cell cycle regulators, and gene therapy Summary: Novel targeted theraples are highly appealing in advanced head and neck cancer, and the most premising strategy to use them Is a matter of intense Investigation.