• 제목/요약/키워드: Conversion to resistant

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Src Family Kinase Inhibitor PP2 Induces LC3 Conversion in a Manner That is Uncoupled from Autophagy and Increases Apoptosis in Multidrug-Resistant Cells

  • Kim, Yun-Ki;Ahn, Jun-Ho;Lee, Mi-Chael
    • Biomolecules & Therapeutics
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    • 제20권4호
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    • pp.393-398
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    • 2012
  • Recently, we reported that defective autophagy may contribute to the inhibition of the growth in response to PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), a selective SFK inhibitor, in multidrug-resistant v-Ha-ras-transformed NIH 3T3 cells (Ras-NIH 3T3/Mdr). In this study, we demonstrated that PP2 induces LC3 conversion via a mechanism that is uncoupled from autophagy and increases apoptosis in Ras-NIH 3T3/Mdr cells. PP2 preferentially induced autophagy in Ras-NIH 3T3 cells rather than in Ras-NIH 3T3/Mdr cells as determined by LC3-I to LC3-II conversion and GFP-LC3 fluorescence microscopy. Beclin 1 knockdown experiments showed that, regardless of drug resistance, PP2 induces autophagy via a Beclin 1-dependent mechanism. PP2 induced a conformational change in Beclin 1, resulting in the enhancement of the pro-autophagic activity of Beclin 1, in Ras-NIH 3T3 cells. Further, PI3K inhibition induced by wortmannin caused a significant increase in apoptosis in Ras-NIH 3T3 cells, as demonstrated by flow cytometric analysis of Annexin V staining, implying that autophagy inhibition through PI3K increases apoptosis in response to PP2 in Ras-NIH 3T3 cells. However, despite the fact that wortmannin abrogates PP2-induced GFP-LC3 punctae formation, some LC3 conversion remains in Ras-NIH 3T3/Mdr cells, suggesting that LC3 conversion may occur in an autophagy-independent manner. Taken together, these results suggest that PP2 induces LC3 conversion independent of PI3K, concomitant with the uncoupling of LC3 conversion from autophagy, in multidrug-resistant cells.

결핵균의 항결핵제 내성 전환 패턴 (The Patterns of Conversion to Anti-Tuberculosis Drug Resistance in Mycobacterium tuberculosis)

  • 정무상;이규택
    • 대한임상검사과학회지
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    • 제54권2호
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    • pp.125-132
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    • 2022
  • 다제내성결핵과 광범위내성결핵은 결핵 치료의 문제가 되고 있으며 발생빈도 역시 증가하고 있다. 본 연구는 2010년 1월부터 2019년 12월까지 녹십자의료재단 의뢰된 환자를 대상으로 Löwenstein-Jensen 고체배지와 pyrazinamide for pyrazinamidase를 이용하여 약물감수성시험(DST)을 시행하여 내성으로 전환되는 항결핵제 패턴과 평균 추적 기간을 분석하였다. 항결핵제 중 1개 이상의 항결핵제 내성을 보인 증례들에서 초기 의뢰 시 INH 항결핵제에 내성인 경우가 55명(33.1%)으로 가장 높은 비율로 나타났으며, 내성으로 전환된 항결핵제는 EMB 17명(26.6%), RFP 14명(21.9%), QUI 14명(21.9%), PZA 12명(10.9%) 순으로 조사되었다. 10개의 항결핵제에 모두 감수성인 증례들에서는 INH 항결핵제에 대한 내성 전환은 43명(7.2%)으로 가장 빈도가 높았으며, 평균 추적 기간은435.6일로 조사되었으며, 내성으로 전환되는 항결핵제의 내성전환율은 INH 43명(7.2%), RFP 23명(3.9%), SM 11명(1.9%), QUI 4명(0.7%), AMK 3명(0.5%), EMB 3명(0.5%)이었다. 이에 본 연구는 항결핵제에 대한 감수성에서 내성으로의 전환은 특히 다제내성결핵과 광범위 내성결핵의 전환되는 환자에게 매우 중요한 자료가 될 것으로 보이며, 결핵 치료에서 환자 치료에 도움이 될 것으로 사료된다.

폐결핵 수술: 163례 보고 (The Surgery of Pulmonary Tuberculosis: 163 cases experience)

  • 박창권
    • Journal of Chest Surgery
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    • 제21권1호
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    • pp.109-115
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    • 1988
  • With the decreasing incidence of new cases and the highly effective results with antituberculous drug therapy, there is a marked decline in the need for surgery which was formerly such an important part in the successful program of management of this disease. During the period of two years and a half from Jun. 1984 to Dec. 1986, this study represents an analysis of 163 cases of several surgical management for eventual control of pulmonary tuberculosis at National Kon-ju tuberculosis Hospital. 1. Mode of surgical treatment was: Resection; 123 cases [Pneumonectomy: 83, lobectomy: 35, lobectomy plus segmentectomy; 4 segmentectomy: 1], thoracoplasty: 20 and others: 20. 2. Age distribution ranged 16and 68 with average of 34 years. Male and female ratio was 1.2: 1. 3. Surgical indications were: totally destroyed lung; 64, Destroyed lobe of segment; 13, cavity positive sputum; 10, cavity c negative Sputum; 6, Bronchostenosis c atelectasis; 2, empyema c or s BPF; 46, Aspergilloma; 8, Questions of Associated tumor; 4 and other 5. 4. Incidence of Complications was 10.4% and the mortality was 5.5 percent. The cause of mortality were analyzed. The main causes of death were respiratory insufficiency; 4, fulminant hepatitis; 1, hemorrhage; 1 and unknown; 1 in pneumonectomy, and asphyxia; 1 in lobectomy and sepsis; 1 in other procedure. 5. Conversion rare of positive sputum to negative state related to resectional surgery was 91.5%. In pneumonectomy, drug resistant group preoperatively showed 88.1% conversion rate postoperatively and drug sensitive group showed that 100% conversion rate. In lobectomy, both drug resistant and sensitive groups showed that 100% conversion rate postoperatively.

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Para-aminosalicylic acid(PAS)가 포함된 처방으로 치료한 다제내성 결핵환자에서 치료경과 중 균음전 후 PAS 중단시 재발율에 관한 조사 (A Retrospective Study for Relapse Rate According to the Discontinuance of Para-aminosalicylic acid(PAS) after Bacteriological Conversion during the Course of Chemotherapy for Multidrug- Resistant Tuberculosis(MDR-TB))

  • 박승규;김병주;신동옥;전병률
    • Tuberculosis and Respiratory Diseases
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    • 제60권2호
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    • pp.180-186
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    • 2006
  • 배경: 다제내성 결핵환자에서 이차약제로 구성된 처방 복약시 특히 PAS는 심한 위장장애 등의 부작용으로 환자의 치료순응도 저하에 중요한 요인이 되므로 균음전 후 PAS를 처방에서 제외한 경우의 치료경과 특히, 치료종결 후 재발율에 대한 조사를 통해 치료경과 중에 적절한 시점에 처방에서 PAS제외 가능성에 대하여 평가하고자 하였다. 방법: 2000년 1월 1일부터 2001년 12월 31일 동안에 국립마산결핵병원에서 입원 혹은 외래치료를 받았던 452명의 다제내성 결핵환자 중에서 처방에 PAS가 포함된 194명 중 심한 위장장애 등의 부작용 때문에 PAS를 중단한 환자 중 균음전 후 PAS를 제외한 처방을 12개월 이상 유지할 수 있었던 42명을 대상으로 임상적 특성 및 치료종결 후 재발율을 분석하였다. 결과: 대상환자의 남녀성비는 2.5:1, 평균나이는 56.2세였다. 1.2회의 과거치료력이 있었으며, 사용한 약제는 평균 3.9제였다. 내성약제수는 평균 4.3제였으며 처방에 포함된 감수성약제수는 평균 3.9제였다. 치료가 시작된 후 균음전시기는 평균 2.3개월째였으며, PAS 중단 시기는 균음전 후 평균 6개월째였다. 31.6개월의 추구관찰 기간 중 재발환자는 없었다. 결론: 새로운 항결핵제의 개발이 요원하고, 다제내성 결핵에 사용가능한 약제가 제한된 현 상황에서 치료순응도 개선방안을 강구하는 것은 치료효율을 높일 수 있는 최선의 방법 중 하나라고 생각되며, 다제내성 결핵환자에서 PAS가 포함된 처방으로 균음전이 되고 환자가 PAS복약에 따른 부작용을 호소하여 치료순응도가 나빠질 것으로 염려가 되면 균음전 후 6개월 즈음에는 PAS를 처방에서 제외할 수 있을 것으로 판단되었다.

다제내성결핵 환자에서 메타분석을 통한 Linezolid의 효능 및 안전성 평가 (Evaluation of the Efficacy and Safety of Linezolid by Meta-analysis for Multidrug-resistant Tuberculosis Patients)

  • 정우진;성태욱;김애진;채정우;윤휘열
    • 한국임상약학회지
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    • 제33권4호
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    • pp.278-289
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    • 2023
  • Background: Linezolid has been widely used in the treatment for multidrug-resistant tuberculosis. However, there are limitations to use it such as long treatment, because of related side effects, even adequate treatment period has been needed for remission of multidrug-resistant tuberculosis (MDR-TB). Method: The meta-analysis was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. To choose literatures, systematic literature reviews were conducted with databases of PubMed, Web of Science, and EMBASE. Results: Efficacy and safety of Linezolid were determined by 85% (95% CI=79~89%, p<0.05) in the sputum culture conversion and 55% (95% CI=45~64%, p<0.01) in side effects related to linezolid, respectively. In addition, I2 was estimated by 72%. In the subgroup analysis, efficacy and safety by dose and region were analyzed. In the subgroup analysis, compared with the linezolid dose in groups greater than 600 mg/day and less than 600 mg/day, this study showed 85% (95% CI 79~90%, p>0.05) in 206 patients and 82% (95% CI 73~89%, p<0.05) in 297 patients, respectively. Also, in the subgroup analysis, adverse effects caused by linezolid occurred more than 50% of treated patients. Conclusion: Therapeutic efficacy of linezolid for MDR-TB patients was confirmed regardless of the initial dose of linezolid, especially for sputum culture conversion and it was recommended that the dose of linezolid has been more effective below 600 mg/day. However, it should be necessary to closely monitored for safety issues since serious side effects possibly occurred by administration of long period treatment.

전환장애의 치료와 관리 (Treatment and Management of Conversion Disorder)

  • 오덕원
    • 한국전문물리치료학회지
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    • 제4권2호
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    • pp.77-88
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    • 1997
  • Conversion disorder is a psychologically produced alteration or loss of physical functioning suggestive of a physical disorder. Conversion symptoms are often superimposed on organic disease and can be overlooked. Psychological techniques are central to the management include the following: avoiding confrontation with the patients; avoiding reinforcement or trivializing the symptoms; reviewing results of tests and exams and creating an expectation of recovery; educating the patient before a treatment is begun; evaluating the patient's emotional adjustment and considering it at a treatment; using caution in labeling the condition; considering referral for psychotherapy; establishing particularly a treatment plan and making a definite treatment program; adjusting patient' s environment; letting participate a family at appropriate time; developing a reinforcement program for a treatment of chronic symptoms; developing a home program for outpatients. Use behavior therapy reinforcement may be helpful with more chronic or resistant symptoms, especially when there is a history of vague or excessive somatic complaints or significant secondary gain.

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염료감응형 태양전지의 $TiO_2$ Layer 다분할 효과에 따른 효율 향상 연구 (Improvement of Efficiency about $TiO_2$ Layer Multi-dividing Effect in Dye-sensitized Solar Cell)

  • 손민규;서현웅;이경준;홍지태;김희제
    • 한국신재생에너지학회:학술대회논문집
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    • 한국신재생에너지학회 2008년도 춘계학술대회 논문집
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    • pp.425-427
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    • 2008
  • Active area of dye-sensitized solar cell (DSSC) has an effect on the efficiency of DSSC. As the active area increases, the efficiency goes down in a general way. This is caused by the increase of internal resistance in DSSC. The internal resistances are related to various resistant elements. The charge transfer processes at Pt counter electrode and the sheet resistance of TCO are two of these resistant elements. In this study, we try to divide the active area into several small sections in a large sized cell to reduce these two internal resistant elements. As a result, we find out that the fill factor is increased and then the conversion efficiency is improved as the number of dividing active area into several small sections is increased.

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항결핵제 감수성 결핵에서의 내성 변화 추이 (The Patterns of Acquiring Anti-Mycobacterial Drug Resistance by Susceptible Strains of Mycobacterium tuberculosis)

  • 이규택;정무상
    • 대한임상검사과학회지
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    • 제53권2호
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    • pp.137-142
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    • 2021
  • 본 연구는 결핵환자의 초기 치료에서 모든 항결핵제에 감수성을 보이는 경우, 치료 과정 중 항결핵제에 대한 내성 전환을 조사하였다. 2010년 1월부터 2019년 12월까지 111개 의료기관에서 녹십자의료재단에 항결핵제감수성 검사를 의뢰한 760건의 환자를 대상으로 하였다. 항결핵제에 모두 감수성인 594명중 추적 기간에 감수성에서 내성으로 전환되는 56명을 분석한 결과 INH, RIF, SM, QUI 순으로 단독 내성 전환율이 가장 높게 나타났으며, INH, RIF에 동시에 복합 내성을 보인 경우는 56명중 17명(30.4%)으로 높은 내성 전환율을 보이고 있다. 전환 시기는 INH 항결핵제는 최소 98일부터 1,862일, 평균 435.6일이며, RIF 항결핵제는 최소 108일부터 1,673일, 평균 457.7일로 분석되었다. 이에 본 연구는 결핵 초기 치료 후 모든 항결핵제에 감수성을 보였다면 3개월이 지난 시점에서 반드시 항결핵제 감수성 검사를 통해 내성 전환 및 다제내성결핵을 확인해야만 한다고 사료되며, 국민보건향상과 국민건겅증진을 위한 국가결핵관리 사업에 도움이 되었으면 한다.

전기아연도금 강판의 몰리브데이트 화성처리 (Molybdate Chemical Conversion Coating of Electro-Galvanized Steel)

  • 김헌태;김인수
    • 한국표면공학회지
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    • 제37권4호
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    • pp.200-207
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    • 2004
  • Molybdate chemical conversion coating layer formed on EGI has been studied in view of corrosion resistance, surface morphologies, and phases formed. It was found that coating layer consists of$ MoO_3$, $MoO_2$, Mo oxides having lower valences than 4 and ZnO. It is interesting to note that the coating layer formed at high Mo concentration (30 g/l) in the temperature range of $40-60^{\circ}C$ exhibited relatively high corrosion resistance, although thickness of coating layer is nearly identical with those formed under the other conditions. It was believed that an increase of driving force due to high Mo concentration plays an important role in the formation of corrosion-resistant coating layer, probably due to tile formation of dense coating layer.

Phage Conversion for β-Lactam Antibiotic Resistance of Staphylococcus aureus from Foods

  • Lee, Young-Duck;Park, Jong-Hyun
    • Journal of Microbiology and Biotechnology
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    • 제26권2호
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    • pp.263-269
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    • 2016
  • Temperate phages have been suggested to carry virulence factors and other lysogenic conversion genes that play important roles in pathogenicity. In this study, phage TEM123 in wild-type Staphylococcus aureus from food sources was analyzed with respect to its morphology, genome sequence, and antibiotic resistance conversion ability. Phage TEM123 from a mitomycin C-induced lysate of S. aureus was isolated from foods. Morphological analysis under a transmission electron microscope revealed that it belonged to the family Siphoviridae. The genome of phage TEM123 consisted of a double-stranded DNA of 43,786 bp with a G+C content of 34.06%. A bioinformatics analysis of the phage genome identified 43 putative open reading frames (ORFs). ORF1 encoded a protein that was nearly identical to the metallo-β-lactamase enzymes that degrade β-lactam antibiotics. After transduction to S. aureus with phage TEM123, the metallo-β-lactamase gene was confirmed in the transductant by PCR and sequencing analyses. In a β-lactam antibiotic susceptibility test, the transductant was more highly resistant to β-lactam antibiotics than S. aureus S133. Phage TEM123 might play a role in the transfer of β-lactam antibiotic resistance determinants in S. aureus. Therefore, we suggest that the prophage of S. aureus with its exotoxin is a risk factor for food safety in the food chain through lateral gene transfer.