• Journal of Life Science
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• v.31 no.5
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• pp.527-535
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• 2021

Lysosomes are organelles surrounded by membranes that contain acid hydrolases; they degrade proteins, macromolecules, and lipids. According to nutrient conditions, lysosomes act as signaling hubs that regulate intracellular signaling pathways and are involved in the homeostasis of cells. Therefore, the lysosomal dysfunction occurs in various diseases, such as lysosomal storage disease, neurodegenerative diseases, and cancers. Multiple forms of stress can increase lysosomal membrane permeabilization (LMP), resulting in the induction of lysosome-mediated cell death through the release of lysosomal enzymes, including cathepsin, into the cytosol. Here we review the molecular mechanisms of LMP-mediated cell death and the enhancement of sensitivity to anticancer drugs. Induction of partial LMP increases apoptosis by releasing some cathepsins, whereas massive LMP and rupture induce non-apoptotic cell death through release of many cathepsins and generation of ROS and iron. Cancer cells have many drug-accumulating lysosomes that are more resistant to lysosome-sequestered drugs, suggesting a model of drug-induced lysosome-mediated chemoresistance. Lysosomal sequestration of hydrophobic weak base anticancer drugs can have a significant impact on their subcellular distribution. Lysosome membrane damage by LMP can overcome resistance to anticancer drugs by freeing captured hydrophobic weak base drugs from lysosomes. Therefore, LMP inducers or lysosomotropic agents can regulate lysosomal integrity and are novel strategies for cancer therapy.

• Journal of Chest Surgery
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• v.35 no.2
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• pp.118-126
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• 2002

배경: 체외순환에 의해 생성되는 염증매개체는 소아 환자에서 술 후 다기관 기능부전과 연관이 있다. 본 연구에서는 선천성 신장질환 소아환자에서 체외순환에 의한 전염증성 사이토카인과 케모카인의 유전자 발현 특성에 대해 알아보고자 하였다. 대상 및 방법: 개심술을 시행한 18명의 소아 환자의 요골 동맥에서 마취유도 후(기준치), 체외순환(0시간), 체외순환 2시간 후 24시간 후, 48시간 후에 혈액을 채취하였다. 모든 환자에서 인터루킨-1알파, 인터루킨-1베타 인터루킨-6, 인터루킨-8, 종양괴사자인자-알파, 인터루킨-15,인터페론 감마의 mRNA의 유전자 발현 정도를 반정량적으로 역전사 중합효소 연쇄반응으로 측정하였다. 6명의 환자에서 인터루킨-6단백치는효소결합면역흡착검사로 측정하였다. 결과: 전신적인 인터루킨-6 mRNA와 비슷한 양상을 보였으나 최고치는 인터루킨-6보다 낮은 값을 보였다. 인터루킨-1알파와 인터루킨-1베타의 mRNA의 발현은 체외순환 2시간 후에 최고치를 나타내었고 체외순환 2시간 후에 최고치를 나타내었고 체외순환 48시간 후에 감소하였다. 종양괴사자인자-알파는 체외 순환 24시간 후에 최고치를 나타내었고 체외순환 48시간 후에 감소하였다. 인터루킨-15 mRNA 발현은 체외순환 전후와 비교하여 유의한 변화가 없었다. 인터페론-감마는 시간이 지남에 따라 감소하였다. 결론: 선천성 심장질환으로 개심술을 시행한 소아환자의 혈청 내 인터루킨-6, 인터루킨-8, 인터루킨-1알파, 인터루킨-베타, 종양괴사자인자-알파의 유전자 발현은 체외 순환 전후로 유의한 변화를 보였다. 인터루킨-15는 유의한 변화가 없었고 인터페론-감마는 반대 양상의 변화를 보였다. 체외순환 후 전염증성 사이토카인과 케모카인의 높은 혈중 농도는 술 후 조직 손상과 연관되리라 생각한다.

• Childhood Kidney Diseases
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• v.16 no.2
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• pp.126-131
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• 2012

Sj$\ddot{o}$gren's syndrome (SS) is an autoimmune disorder primarily affecting the salivary and lacrimal glands. In addition, extra-glandular manifestations involving the lungs, liver, kidneys, pancreas, skin and central nervous system were reported in patients with SS. These extra-glandular manifestations are not rare in adult patient, but are very rare in pediatric SS. Renal manifestations are relatively common in adult SS, but are rarely reported in childhood SS. We experienced a girl with primary SS manifested with nephrogenic diabetes insipidus and renal tubular acidosis.

• Korean Journal of Clinical Laboratory Science
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• v.56 no.3
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• pp.236-247
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• 2024

The human leukocyte antigen (HLA) system, which is part of the major histocompatibility complex (MHC) plays a vital role in immune responses by differentiating between itself and foreign cells and antigens. The significant diversity of alleles affects disease susceptibility and immune responses within different populations. Specifically, the HLA-A and HLA-DRB1 alleles are associated with various immune-related diseases, and understanding the frequency and haplotype associations of these alleles is vital for genetic and immunological research. To investigate the distribution of these characteristics in Koreans, we isolated peripheral blood mononuclear cells (PBMCs) from blood samples donated by volunteers at the Seoul Central Blood Bank and performed HLA typing on 790 samples. Our study found that the HLA-A and HLA-DRB1 alleles are widely distributed within the Korean population, with HLA-A^*24:02 (21.7%) and HLA-DRB1*09:01 (9.9%) being the most frequent. Significant haplotype associations between specific HLA-A and HLA-DRB1 alleles were identified using the Chi-square test, suggesting that certain genetic combinations may influence disease onset. This insight could contribute to the development of predictive and preventative strategies for various diseases. The unique genetic characteristics of the Korean population highlight the importance of studying the HLA allele and the haplotype distributions in this group as key indicators for understanding disease susceptibility.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.135-143
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• 1994

Background: The cell mediated immunity has an important role in the pathogenesis of tuberculosis. sIL-2R has been known as a sensitive marker of T lymphocyte activation Elevated serum levels of sIL-2R have been found in patients with lymphoproliferative disorders, organ transplantation, autoimmune diseases, and various granulomatous diseases. Elevated levels of sIL-2R have been also found in the serum and pleural fluid of the patients with tuberculosis. To evaluate the diagnostic value of sIL-2R in the differentiation of tuberculous pleurisy and nontuberculous pleurisy. We measured the level of sIL-2R in the sera and pleural fluids of 12 patients with tuberculous pleurisy and 32 patients with nontuberculous pleurisy. Method: Samples of pleural fluid and serum were centrifuged at 2500 rpm for 10 min to remove cell pellets. Soluble IL-2R was measured with a sandwitch enzyme immunoassay using the Cellfree(r) Interleukin-2 Receptor Test kit(T-cell science,Inc. Cambridge, MA). Results: The results obtained were as follows: 1) The sIL-2R level in pleural fluid of the patients with tuberculous pleurisy was higher than that of patients with nontuberculous pleurisy(P<0.005). 2) When the sIL-2R level above 5,000 u/ml in pleural fluid was used as the cut-off value to diagnose tuberculous pleurisy, it had a sensitivity of 84.6% and a specificity of 90.9%. 3) The sIL-2R level in the sera of the patients with tuberculous pleurisy was higher than that of patients with bacterial pleural effusions and normal control group(P<0.05) and there was no difference of levels compared with malignant pleural effusions and transudative pleural effusions(P>0.05). 4) In patients with tuberculous pleurisy, the mean concentration of sIL-2R in pleural fluid was higher than that in serum(P<0.005). Conclusion: These findings suggest that the measurement of elevated levels of pleural fluid sIL-2R in tuberculous pleurisy may be useful in the differential diagnosis between patients with tuberculous pleurisy and nontuberculous pleurisy.

• Clinical and Experimental Pediatrics
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• v.53 no.4
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• pp.548-553
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• 2010

Purpose : IgA nephropathy (IgAN) is the most commonly occurring form of chronic glomerulonephritis in pediatric cases. Human leukocyte antigen (HLA) genes have been implicated in various inflammatory and autoimmune diseases. The present study was conducted to investigate the association between 2 single nucleotide polymorphisms (SNPs) of the HLA-G gene and childhood IgAN. Methods : The authors analyzed and compared $HLA-G$ gene SNPs (rs1736936 and rs2735022) in 174 patients with childhood IgAN and in 438 healthy controls. In addition, IgAN patients were dichotomized and compared with respect to proteinuria (< and >$4mg/m^2/hour$), the presence or absence of podocyte foot process effacement, and the presence of pathologically early and advanced disease markers such as interstitial fibrosis, tubular atrophy, or global sclerosis. Results : No significant SNP frequency differences were observed for the $HLA-G$ gene between IgAN patients and the control group. Moreover, no significantly associated SNP was observed with the presence of proteinuria, podocyte foot process effacement, or pathologically advanced markers. However, the haplotype, composed of rs1736936 and rs2735022, showed a significant association with the susceptibility to develop childhood IgAN (haplotype T/C: dominant model, $P$=0.049; haplotype C/T: recessive model, $P$=0.030). Conclusion : Our results indicate that rs1736936 and rs2735022 as the $HLA-G$ gene promoter haplotype might be associated with the susceptibility to develop childhood IgAN in the Korean population.

• Pediatric Infection and Vaccine
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• v.29 no.2
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• pp.96-104
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• 2022

Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory bone disorder presenting with sterile osteomyelitis, most often presenting in childhood. Although the etiology is understood incompletely, its association with other auto-inflammatory diseases including inflammatory bowel disease (IBD); psoriasis; Wegener's disease; arthritis; and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome suggests that dysregulated innate immunity may play an important role in the pathogenesis. We report a case of a 13-year-old boy with CRMO associated with Crohn's disease (CD) successfully treated with infliximab after failure of non-steroidal anti-inflammatory drug (NSAID) treatment. He initially was diagnosed with CRMO based on symmetric and aseptic bone lesions with no fever, lack of response to antibiotic treatment, vertebral involvement, and normal blood cell counts. Despite five months of NSAID treatment, his musculoskeletal symptoms were aggravated, and he developed gastrointestinal symptoms. Finally, he was diagnosed with CRMO associated with CD. Due to the severity of symptoms, infliximab was initiated and produced symptom improvement. This case supports infliximab as another choice for treatment of bowel symptoms in addition to the bone and joint symptoms of CRMO when other first-line treatments are ineffective.

• Journal of Periodontal and Implant Science
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• v.33 no.4
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• pp.739-745
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• 2003

Interleukine-1(IL-1)은 여러 가지 기능을 가진 싸이토카인으로써 미생물에 대한 면역반응을 일으킨다. IL-1의 유전자 다형성과 치주질환과의 관련성에 대한 많은 연구가 있어왔지만, 대부분이 백인을 대상으로 한 연구였다. 이후 중국인과 일본인을 대상으로 한 연구에서 IL-1의 유전자 다형성의 분포가 인종간에 차이를 보인다는 점이 발견되었다. 이번 연구에서는 치주적으로 건강한 한국인에서 IL-1${\beta}$-511, IL-1${\beta}$+3954, IL-1RN에 대한 유전자형의 분포를 조사하고자 하였다. 서울대학교 치과병원에 근무하는 치과의사, 치과위생사, 간호조무사 및 서울대학교 치과대학 4학년 학생 중 치주낭 깊이와 부착소실이 4mm 이하인 치주적으로 건강한 한국인 65명을 대상으로 하였다. IL-1${\beta}$-511, IL-1${\beta}$+3954, IL-1RN의 유전자 다형성은 분리한 DNA에 각 대립유전자에 특이성을 지닌 primer를 넣고 PCR(Polymerase Chain Reaction)법을 이용하여 증폭시킨후 전기영동법을 이용하여 각 대립유전자의 존재를 확인함으로써 결정하였다. IL-1${\beta}$-511 대립유전자 11, 대립유전자 12, 대립유전자 22의 유전자형에 대하여 각각 23.1%, 49.2%, 26.2%의 분포를 보였다. IL-1${\beta}$+3954의 유전자 다형성은 대립유전자 11, 대립유전자 12의 유전자형에 대하여 각각 89.2%, 10.8%의 분포를 보였으며, 대립유전자 22의 유전자형을 갖는 사람은 한명도 발견되지 않았다. IL-1RN의 유전자형은 5가지의 대립유전자 중에서 1, 대립유전자 2, 대립유전자 4만일 발견되었으며, 대립유전자 11, 대립유전자 12, 대립유전자 14의 유전자형이 86.2%, 12.3%, 1.5%로 분포하였다. 이를 바탕으로 각 대립유전자의 발생빈도 계산한 결과 IL-1${\beta}$-511에서는 대립유전자 1과 2의 비율이 거의 유사하였으나 (47.7%, 52.3%), IL-1${\beta}$+3954, IL-1RN에서는 대립유전자 1이 90%이상 발견되었으며, 또한 대립유전자 1외의 다른 대립유전자가 발견된 경우, 모두 이형접합체였다. 이 연구는 IL-1${\beta}$-511, IL-1${\beta}$+3954, IL-1RN에 대한 유전자형의 분포를 조사한 것으로 한국인에서 이들 유전자의 유전자형의 분포는 백인에서의 분포와 차이를 보이고 있었다. 이후 치주질환자의 유전자형 분포와의 비교로 치주질환과 IL-1${\beta}$-511, IL-1${\beta}$+3954, IL-1RN의 유전자다형성과의 관련성에 관한 추가적인 연구가 필요할 것으로 여겨진다.

• The Journal of the Korean bone and joint tumor society
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• v.13 no.1
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• pp.43-47
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• 2007

Sj$\"{o}$gren's syndrome is a systemic, autoimmune disorder of the exocrine glands with associated lymphocytic infiltrates of the affected glands and characteristic of dry eye and mouth. We report a case of Sj$\"{o}$gren's syndrome in which the patient presented systemic symptoms without sicca symptoms and had radiologic findings mimicking multiple skeletal metastasis and was finally confirmed with Sj$\"{o}$gren's syndrome with renal tubualr acidosis.

• Journal of the Korean Society of Radiology
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• v.84 no.5
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• pp.1146-1151
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• 2023

Medullary thyroid carcinoma (MTC) is a rare malignancy that originates from the parafollicular cells of the thyroid gland. Hashimoto's thyroiditis (HT) is an autoimmune thyroid disease and is the most common cause of hypothyroidism. Previous studies have frequently discussed the association among HT, papillary thyroid carcinoma, and thyroid lymphoma. However, there have been few reports on the ultrasonographic findings of concomitant HT and MTC. In the present case, a heterogeneous hypoechoic background parenchymal echogenicity, with intraglandular echogenic strands, and increased vascularity were observed. A concurrent, ill-defined, parallel-oriented, heterogeneous hypoechoic mass with central microcalcifications was located at the left thyroid gland, consistent with reported US findings of medullary thyroid carcinoma except for an ill-defined margin in our case.