• Title/Summary/Keyword: 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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    • v.20 no.4
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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.

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

  • Chong, Moo-Sang;Lee, Kyutaeg
    • Korean Journal of Clinical Laboratory Science
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    • v.54 no.2
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    • pp.125-132
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    • 2022
  • The prevalence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) are increasing. We analyzed the patterns of drug resistance and tracking period days of acquiring anti-mycobacterial resistance. From January 2010 to December 2019, drug susceptibility tests (DST) were performed by the absolute concentration method using the Löwenstein-Jensen solid medium and pyrazinamidase activity test (to assess pyrazinamide resistance) in samples from patients who were referred to the Green Cross Laboratories in Yongin. Among the cases that showed resistance to one or more anti-tuberculosis drugs, 55 patients (33.1%) were resistant to isoniazid (INH) at the time of initial referral, and the rates for the development of resistant anti-tuberculosis drugs were ethambutol (EMB) (26.6%), rifampicin (RFP) (21.9%), quinolones (QUI) (21.9%) and pyrazinamide (PZA) (10.9%), in that order. In the cases sensitive to all 10 anti-tuberculosis drugs initially, the development of resistance to INH was the most frequent, seen in 43 patients (7.2%). The average follow-up period was 435.6 days, and the resistance development was observed in the order of INH (7.2%), RFP (3.9%), SM (1.9%), QUI (0.7%), amikacin (AMK) (0.5%), and EMB (0.5%). The conversion of susceptible strains to resistant strains is an important warning sign for the patient, especially in cases of conversion to MDR or XDR. This information would be helpful for improving patient care during TB treatment.

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

  • 박창권
    • Journal of Chest Surgery
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    • v.21 no.1
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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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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) (Para-aminosalicylic acid(PAS)가 포함된 처방으로 치료한 다제내성 결핵환자에서 치료경과 중 균음전 후 PAS 중단시 재발율에 관한 조사)

  • Park, Seung-Kyu;Kim, Byoung-Ju;Shin, Dong-Ohk;Jun, Byung-Yool
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.2
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    • pp.180-186
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    • 2006
  • Background : Para-aminosalicylic acid(PAS) is a 2nd-line drug that can cause severe adverse reactions leading to poor patient compliance. This study evaluated the relapse rate according to the discontinuance of PAS at a certain point after bacteriological conversion during the course of chemotherapy for multidrug-resistant tuberculosis(MDR-TB). Methods : 42 out of 452 MDR-TB patients were enrolled in this study. All subjects were receiving chemotherapy including PAS at National Masan TB Hospital between Jan. 1, 2000 and Dec. 31, 2001. The relapse rate was evaluated after the discontinuance of PAS from their initial regimen as a result of the severe adverse reactions at a certain point after the bacteriological conversion during the course of chemotherapy for MDR-TB. Results : The male to female ratio was 2.5:1, and the mean age was 47.2 years old. The average number of past histories, used drugs and resistant drugs was 1.2, 3.9 and 4.3. The mean number of sensitive drugs included in the inirial regimen was 3.9. The mean time for bacteriological conversion and discontinuance of the PAS was 2.3 months after initiating treatment and 6 months after bacteriological conversion, respectively. There was no relapse after discontinuing PAS during a mean follow up period of 31.6 months. Conclusion : PAS may be discontinued in the cases of serious gastrointestinal problems approximately 6 months after bacteriological conversion without concern about relapse.

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

  • Woojin Jung;Taewook Sung;Ae Jin Kim;Jung-woo Chae;Hwi-yeol Yun
    • Korean Journal of Clinical Pharmacy
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    • v.33 no.4
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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.

Treatment and Management of Conversion Disorder (전환장애의 치료와 관리)

  • Oh, Duck-Won
    • Physical Therapy Korea
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    • v.4 no.2
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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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Improvement of Efficiency about $TiO_2$ Layer Multi-dividing Effect in Dye-sensitized Solar Cell (염료감응형 태양전지의 $TiO_2$ Layer 다분할 효과에 따른 효율 향상 연구)

  • Son, Min-Kyu;Seo, Hyun-Woong;Lee, Kyoung-Jun;Hong, Ji-Tae;Kim, Hee-Je
    • 한국신재생에너지학회:학술대회논문집
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    • 2008.05a
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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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The Patterns of Acquiring Anti-Mycobacterial Drug Resistance by Susceptible Strains of Mycobacterium tuberculosis (항결핵제 감수성 결핵에서의 내성 변화 추이)

  • Lee, Kyutaeg;Chong, Moo-Sang
    • Korean Journal of Clinical Laboratory Science
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    • v.53 no.2
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    • pp.137-142
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    • 2021
  • This study investigated the patterns of acquiring anti-mycobacterial resistance in individuals who were susceptible to all anti-mycobacterial drugs in their initial treatment. From 2010 to 2019, anti-mycobacterial drug susceptibility tests were conducted on patients who were referred to the Green Cross Laboratories. The test results of 594 anti-mycobacterial drug sensitivity tests were collected at 111 medical institutions. The first test results had 594 cases in which all anti-mycobacterial drugs were susceptible. Isoniazid (INH), rifampin (RIF), streptomycin (SM), and quinolone (QUI) showed the highest single-resistant conversion rates. Out of 56 patients, 17 patients (30.4%) showed a high conversion rate of resistance to both INH and RIF. The tracking period was analyzed from a minimum of 98 days to 1,862 days, and an average of 435.6 days for INH, and a minimum of 108 days to 1,673 days, with an average of 457.7 days for RIF. In the case of tuberculosis patients who are susceptible to all anti-mycobacterial drugs, it is considered that the conversion to resistant and multi-drug resistant tuberculosis (MDR-TB) must be confirmed through an anti-mycobacterial susceptibility test after 3 months. It is hoped that this study will help the national tuberculosis management project to improve public health.

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

  • 김헌태;김인수
    • Journal of the Korean institute of surface engineering
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    • v.37 no.4
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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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    • v.26 no.2
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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.