• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제25권5호
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• pp.422-431
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• 2022

Purpose: At the beginning of the Coronavirus disease (COVID-19) epidemic, physicians paid close attention to children with chronic diseases to prevent transmission or a severe course of infection. We aimed to measure the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels in children with chronic gastrointestinal and liver diseases to analyze the risk factors for infection and its interaction with their primary disease. Methods: This cross-sectional study analyzed SARS-CoV-2 antibody levels in patients with gastrointestinal and liver diseases (n=141) and in healthy children (n=48) between January and February 2021. Results: During the pandemic, 10 patients (7%) and 1 child (2%) had confirmed COVID-19 infection (p=0.2). The SARS-CoV-2 antibody test was positive in 36 patients (25.5%) and 11 children (22.9%) (p=0.7). SARS-CoV-2 antibody positivity was found in 20.4%, 26.6%, 33.3%, and 33.3% of patients with chronic liver diseases, chronic gastrointestinal tract diseases, cystic fibrosis, and liver transplantation recipients, respectively (p>0.05, patients vs. healthy children). Risk factors for SARS-CoV-2 antibody positivity were COVID-19-related symptoms (47.2% vs. 14.2%, p=0.00004) and close contact with SARS-CoV-2 polymerase chain reaction-positive patients (69.4% vs. 9%, p<0.00001). The use, number, and type of immunosuppressants and primary diagnosis were not associated with SARS-CoV-2 antibody positivity. The frequency of disease activation/flare was not significant in patients with (8.3%) or without (14.2%) antibody positivity (p=0.35). Conclusion: SARS-CoV-2 antibodies in children with chronic gastrointestinal and liver diseases are similar to that in healthy children. Close follow-up is important to understand the long-term effects of past COVID-19 infection in these children.

• The Korean Journal of Physiology and Pharmacology
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• 제28권5호
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• pp.435-447
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• 2024

Secretory proteins, including plasma membrane proteins, are generally known to be transported to the plasma membrane through the endoplasmic reticulum-to-Golgi pathway. However, recent studies have revealed that several plasma membrane proteins and cytosolic proteins lacking a signal peptide are released via an unconventional protein secretion (UcPS) route, bypassing the Golgi during their journey to the cell surface. For instance, transmembrane proteins such as the misfolded cystic fibrosis transmembrane conductance regulator (CFTR) protein and the Spike protein of coronaviruses have been observed to reach the cell surface through a UcPS pathway under cell stress conditions. Nevertheless, the precise mechanisms of the UcPS pathway, particularly the molecular machineries involving cytosolic motor proteins, remain largely unknown. In this study, we identified specific kinesins, namely KIF1A and KIF5A, along with cytoplasmic dynein, as critical players in the unconventional trafficking of CFTR and the SARS-CoV-2 Spike protein. Gene silencing results demonstrated that knockdown of KIF1A, KIF5A, and the KIF-associated adaptor protein SKIP, FYCO1 significantly reduced the UcPS of △F508-CFTR. Moreover, gene silencing of these motor proteins impeded the UcPS of the SARS-CoV-2 Spike protein. However, the same gene silencing did not affect the conventional Golgi-mediated cell surface trafficking of wild-type CFTR and Spike protein. These findings suggest that specific motor proteins, distinct from those involved in conventional trafficking, are implicated in the stress-induced UcPS of transmembrane proteins.

• Journal of Microbiology and Biotechnology
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• 제34권8호
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• pp.1609-1616
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• 2024

The Burkholderia cepacia complex (Bcc) consists of opportunistic pathogens known to cause pneumonia in immunocompromised individuals, especially those with cystic fibrosis. Treating Bcc pneumonia is challenging due to the pathogens' high multidrug resistance. Therefore, inhalation therapy with tobramycin powder, which can achieve high antibiotic concentrations in the lungs, is a promising treatment option. In this study, we investigated potential mechanisms that could compromise the effectiveness of tobramycin therapy. By selecting for B. cenocepacia survivors against tobramycin, we identified three spontaneous mutations that disrupt a gene encoding a key enzyme in the biosynthesis of cobalamin (Vitamin B₁₂). This disruption may affect the production of succinyl-CoA by methylmalonyl-CoA mutase, which requires adenosylcobalamin as a cofactor. The depletion of cellular succinyl-CoA may impact the tricarboxylic acid (TCA) cycle, which becomes metabolically overloaded upon exposure to tobramycin. Consequently, the mutants exhibited significantly reduced reactive oxygen species (ROS) production. Both the wild-type and mutants showed tolerance to tobramycin and various other bactericidal antibiotics under microaerobic conditions. This suggests that compromised ROS-mediated killing, due to the impacted TCA cycle, underlies the mutants' tolerance to bactericidal antibiotics. The importance of ROS-mediated killing and the potential emergence of mutants that evade it through the depletion of cobalamin (Vitamin B₁₂) provide valuable insights for developing strategies to enhance antibiotic treatments of Bcc pneumonia.

• Tuberculosis and Respiratory Diseases
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• 제64권1호
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• pp.33-38
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• 2008

A. xylosoxidans는 면역저하 상태에서 기회감염을 일으키며 호흡기 감염은 매우 드문 균으로 알려져 있다. 저자들은 최근 면역저하가 없는 환자에서 발생한 A. xylosoxidans에 의한 호흡기 감염증을 2예 경험하였기에 문헌 고찰과 함께 보고한다. 본 증례를 통해 정상면역을 가진 환자에서 A. xylosoxidans가 호흡기 감염의 원인일 수 있으며, 이와 같은 경우 세균학적 검사결과에 따른 적절한 치료가 필수적이라는 것을 경험하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제24권4호
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• pp.329-338
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• 2020

Rhinorrhea in allergic rhinitis (AR) is characterized by the secretion of electrolytes in the nasal discharge. The secretion of Cl^- and HCO₃^- is mainly regulated by cystic fibrosis transmembrane conductance regulator (CFTR) or via the calcium-activated Cl^- channel anoctamin-1 (ANO1) in nasal gland serous cells. Interleukin-4 (IL-4), which is crucial in the development of allergic inflammation, increases the expression and activity of ANO1 by stimulating histamine receptors. In this study, we investigated ANO1 as a potential therapeutic target for rhinorrhea in AR using an ANO1 inhibitor derived from a natural herb. Ethanolic extracts (30%) of Spirodela polyrhiza (SP_EtOH) and its five major flavonoids constituents were prepared. To elucidate whether the activity of human ANO1 (hANO1) was modulated by SP_EtOH and its chemical constituents, a patch clamp experiment was performed in hANO1-HEK293T cells. Luteolin, one of the major chemical constituents in SP_EtOH, significantly inhibited hANO1 activity in hANO1-HEK293T cells. Further, SP_EtOH and luteolin specifically inhibited the calcium-activated chloride current, but not CFTR current in human airway epithelial Calu-3 cells. Calu-3 cells were cultured to confluency on transwell inserts in the presence of IL-4 to measure the electrolyte transport by Ussing chamber. Luteolin also significantly inhibited the ATP-induced increase in electrolyte transport, which was increased in IL-4 sensitized Calu-3 cells. Our findings indicate that SP_EtOH and luteolin may be suitable candidates for the prevention and treatment of allergic rhinitis. SP_EtOH^- and luteolin-mediated ANO1 regulation provides a basis for the development of novel approaches for the treatment of allergic rhinitis-induced rhinorrhea.

• Applied Microscopy
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• 제27권4호
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• pp.433-452
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• 1997

Mongolian gerbil (Meriones unguiculatus) has been as an animal model for studing the neurological diseases such as stroke and epilepsy because of the congenital incompleteries in Willis circle, as well as the investigation of water metabolism because of the long time-survival in the condition of water-deprived desert condition, compared with other species animals. In order to accomplish the this research, first of all another divided the laboratory animals 5 groups of which each group include the 5 animals. In this study were investigated the histological structure in the kidney, measured the plasma osmolalities at the time of sacrifice of indivisual animals, and the body weights every day during water-deprived. The results obtained in this study were summarized as followings: 1. The body weights and decreasing rates of the body weight in water-deprived mongolian gerbil groups were continuosly decreased. 2. The plasma osmolalities were increased from the 5th water-deprived day, after then the gradually increasing reached nearly its equilibrium state at the 10th water-deprived day. 3. The urine volumes were abruptly decreased from the 2th water-deprived day, after then the gradually decreasing patterns were reached nearly its equilibrium state at the 10th day, and stopped the 11th day. 4. In the light microscopical observation of the kidney, glomerular capillary loop thickening, mesangial matrix increasing, sclerosis, glomerular cystic atrophy, interstitial fibrosis, tubular dilatation, mononuclear interstitial inflammation, interstitial mineralization, and hyperplasia of the collecting duct epithelium in the cortex area, were observed from the 10th water deprived day, and the lesions were gradually severe changed as the time lapse. 5. In the electron microscopical findings of the kidney, the degenerative changes of endothelial cell, podocyte and mesangial cell in glomeruli were initially observed on the 10th water-deprived day as well as the degeneration of microvilli and intracellular organelle in the renal tubules.

• Advances in pediatric surgery
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• 제8권2호
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• pp.113-118
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• 2002

The etiology of several motility disorders, including persistent megacolon after definitive surgery for Hirschsprung's disease, meconium ileus which is not associated with cystic fibrosis and idiopathic megacolon, is still unclear. Interstitial cells of Cajal (ICC) are thought to modulate gut motility as gastrointestinal pace maker cells. The aim of this study was to evaluate the role of ICC in the bowel walls of the patients (n=15) who had variable motility disorders. The ICC were identified by immunohistochemical staining using an anti-C-Kit antibody and the results were compared with control specimens (n=2). The control group (G1) showed evenly distributed ICC in their bowel walls. The second group (G2, n=5) who had normal bowel movements after Duhamel procedures and the third group (G3, n=4) who had persistent megacolon after Duhamel procedures showed absent or scarcely distributed ICC in their aganglionic bowels. The ICC were immunohistochemical staining using an anti-C-Kit antibody and the results were compared with control specimens (n=2). The control group (G1) showed evenly distributed ICC in their bowel walls. The second group (G2, n=5) who had normal bowel movements after Duhamel procedures and the third group (G3, n=4) who had persistent megacolon after Duhamel procedures showed absent or scarcely distributed ICC in their aganglionic bowels. Whereas ICC were evenly distributed in the ganglionic bowels of G2, they were not seen or scarecely distributed in the ganglionic bowels of G3. Two patients (G4) who suffered from idiopathic megacolon showed absence or decrease of ICC in spite of presence of ganglion cells in their colons. Four neonates (G5) who underwent ileostomy because of meconium obstruction showed absent or markedly decreased ICC in the the colon at the time of ileostomy and the distribution of ICC was changed to a normal pattern at the time of ileostomy closure between 39-104 days of age and their bowel motility were restored after that. The results suggest that lack of ICC caused reduce motility in the ganglionic colons and it may be responsible for the development of various motility disorders. Delayed maturity of ICC may also playa role in the meconium obstruction of neinates.

• Tuberculosis and Respiratory Diseases
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• 제43권4호
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• pp.547-557
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• 1996

연구배경 : 호중구는 성인형 호흡곤란증후군, 폐기종 및 원발성 폐섬유화증 등 여러 폐질환에서 과도하게 폐에 침착되어 여러 가지 독설 물질을 분비하여 조직 손상을 일으키는 것으로 알려져 있어, 말초혈액 호중구가 폐포나 간질조직으로 이동하는 기전을 이해하는 것은 매우 중요하다. 저자들은 급성 폐손상의 동물실험모델로 흰쥐에 고농도 산소를 추여하여 급성 폐손상을 일으킨 후 기관지폐포세척액내 호중구 및 호중구에 대한 화학주성능이 증가하였는지 그리고 이러한 변화가 고농도산소 노출 시간에 따라 차이가 있는지를 관찰하였으며, 또한 호중구 화학주성인자의 분자량 및 물리적 특성을 알아보았다. 방법 : 고농도산소를 투여할수 있는 기구(hyperoxic chamber)를 만들어 95%이상의 산소를 흰쥐에 24, 48, 60, 72시간 투여하였으며 각군의 쥐에서 기관지폐포세척을 실시하여 얻은 세척액내 호중구의 증가여부를 관찰하였고 호중구의 화학주성능은 정상인의 말초혈액내 호중구를 대상으로 Neuroprobe 48 well chemotactic chamber를 이용하여 계산하였다. 또한 기관지 폐포세척액을 열처리하거나 cellulose membrane에 filter 시켰을 때 화학주성능의 변화여부를 관찰하였고 FPLC(Fast performance liquid chromatography)로 분자량을 측정하였다. 결과 : 1) 기관지폐포세척액내 호중구는 대조군에 비해 고농도 산소 노출 48시간에서부터 증가하여 노출 시간이 길수록 유의하게 증가하였다. 2) 기관지폐포세척액의 호중구 화학주성능 (chemotactic index)도 대조군에 비해 고농도 산소 노출 48시간에부터 유의하게 증가하기 시작하여 노출 시간이 길수록 유의하게 증가되었다. 3) 흰쥐는 48시간까지는 한마리도 사망하지 않았으나 60시간에 33.3 %, 72시간에 81.3 %의 사망률로 현저히 증가하였다. 4) FPLC를 이용하여 호중구 화학주성인자를 분석하였을 때 chemotactic index는 분자량이 104,000과 12,000 dalton에서 peak를 나타냈다. 5) 48시간과 60시간 및 72시간 노출군에서 기관지폐포세척액을 $56^{\circ}C$에서 30분과 $100^{\circ}C$에서 10된 열처리 후 chemotactic index는 열처리 전보다 모두 유의하게 감소하였으며, 48시간과 60시간 노출군에서 12,000 dalton 이하의 물질을 dialysis 후 chemotactic index도 dialysid 전에 비해 유의하게 감소하였다. 결론 : 이상의 결과로서 흰쥐에 고농도의 산소를 40시간 이상 노출시키면 기관지폐포세척액에 호중구 화학주성인자가 증가되고 그에 따라 호중구가 폐에 증가하여 급성 폐손상을 일으키고, 이때 나타나는 호중구 화학주성인자는 분자량이 작은 것 뿐 아니라 큰 것까지 다양하며, 열에 대해 약한 것 뿐 아니라 강한 성분 등 여러가지가 있음을 관찰하였으며 앞으로 이들 성분에 대한 연구가 더욱 진행되어야 할 것으로 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제64권2호
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• pp.102-108
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• 2008

연구배경: 최근 다제내성 A. baumannii에 의한 폐렴이 중환자실 환자에서 매우 빈번하게 발생하고 있으며, 이탈 지연, 중환자실 재원기간 및 사망률의 증가가 초래되기도 한다. 수 년 전부터 colistin이 치료제로 다시 주목받고 있으나 병원획득폐렴에 대한 치료 경험은 많지 않으며, 분무치료의 효과에 대해서는 근거가 매우 부족하다. 이에 저자들은 한 대학병원 중환자실에서 발생한 다제내성 A. baumannii에 의한 병원획득폐렴에서 colistin 분무치료의 적용 가능성을 평가해보고자 하였다. 방법: 다제내성 A. baumannii에 의한 병원획득폐렴의 발생이 확인되어 colistin 분무치료를 시행한 환자 10명을 대상으로 후향적 분석을 시행하였다. 결과: Colistin 분무치료 기간은 평균 $12.7{\pm}2.4$일이었다. 10명의 대상환자 중 9명(90.0%)의 환자에서 효과적인 치료 반응을 나타내었다. 치료 종료 후 추적한 객담 배양 검사에서 다제내성 A. baumannii는 단 한 명도 분리되지 않았다. 1명의 환자에서 기관지연축이 발생하였으나 기관지확장제 치료 후 호전되었다. 결론: 다제내성 A. baumannii에 의한 병원획득폐렴에서 colistin 분무치료는 매우 효과적일 가능성이 있으며, 향후 전향적인 연구를 진행할 가치가 있을 것으로 판단된다.

• Journal of Chest Surgery
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• 제31권2호
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• pp.108-112
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• 1998

\ulcorner연구자들은 순차적으로 양측폐를 이식하는 수술수기를 익힘으로서 사람에서 양측 폐이식이 필요로 하는 경우를 대비하고자 본 실험을 계획하였다. 몸무게 25kg 내외의 황견 14마리 준비하였으며 1회 실험에 2마리의 황견이 사용되었으며 이중 1마리는 정중흉골절개하여 폐동맥을 통해 Prostaglandin E1을 20mg/kg을 투여하고 4$^{\circ}C$로 냉각된 Euro-Collin's (E-C) preservation 용액을 70cc/kg 양으로 30 cmH2O의 압력으로 신속히 주입하여 심장-폐를 절제한 후 나머지 1마리를 좌측 흉부절개하여 폐동맥, 상, 하 폐정맥 및 기관지를 노출시킨 후 전폐절제술을 시행하였다. 수술중에 혈압을 계속 측정하면서 출혈이 된 만큼의 피를 수혈하면서 정상혈압을 유지시켰으며 수술후 1시간 간격으로 대퇴동맥압, 폐동맥압과 각각의 산소분압을 측정하였다. 첫번째 실험은 좌측폐를 먼저 이식하여 우측폐이식시 폐동맥압이 증가하여 심장마비로 사망하였는데 이는 좌측폐가 체순환 모두를 감당하기에는 너무적어 폐동맥 고혈압이 온 것으로 생각되고 두번째 실험에서는 우측폐이식후 좌측폐 이식시 수술시야 확보 부족으로 폐동맥 결찰부위에서 출혈이 발생하여 중도에 실험을 종료 할 수밖에 없었다. 다섯번째 실험에서는 우측폐이식후 재관류손상으로 좌측 폐이식이 불가능 하였다. 세번째 실험은 우측폐이식후 좌측폐 이식시 폐동맥압이 증가하였으나 양측 모두 이식후 정상으로 돌아왔다. 그러나 네 번째, 여섯 번째와 일곱 번째 실험은 특별한 문제가 없었다. 이식직전, 일측폐이식후 및 양측폐이식후의 산소 분압차 및 폐동맥압을 비교해보면 산소분압은 수술전에 119.56$\pm$35.728 mmHg에서 86.5$\pm$32, 88.67$\pm$10.22 mmHg로 감소하였고 폐동맥압의 평균은 수술전에 11.4$\pm$5.68 mmHg에서 25.94$\pm$11.53, 29.67$\pm$9.31 mmHg로 증가 하였으나 모두 통계적 의의는 없었다(p>0.05). 양측 폐이식수술에서인 폐동정맥문합부위의 파열, 협착, 뒤틀림 등의 수술수기상의 문제점을 예방하면서 우측폐를 먼저 이식하면서, 폐수술시야를 충분히 확보하고, 재관류손상을 방지하는 경우 cystic fibrosis, pulmonary hypertention, emphysema와 같은 심한 호흡부전증 환자의 치료방법으로 적합하리라 사료된다.