• Applied Microscopy
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• 제12권1호
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• pp.49-56
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• 1982

전신성 Cryptococcosis로 판명된 4세 남아의 피부 생검조직에서 발견된C. neoformans의 미세구조를 광학현미경 관찰과 함께 보고 하였다. 광학현미경 관찰에서는 각종 만성 염증 세포의 침윤과 함께 다수의 구형의 organism을 관찰할 수 있었다. 전자현미경적으로도 난원형의 세포가 gelatinous 또는 filamentous한 capsular material에 둘러 싸여 단세포 혹은 여러개의 세포가 모여 있는 상태로 관찰되었으며 budding중인 상태의 것도 관찰되었다. 세포막은 고전사 밀도의 여러층으로 구성되어 있었으며 한개의 핵과 핵인이 관찰되었고 세포질내에는 mitochondria, ribosome, lipid bodies, vacuole등과 함께 plasma membrane의 infolding으로 형성된 mesosome-like structure도 관찰되었다.

• Journal of Yeungnam Medical Science
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• 제5권2호
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• pp.175-181
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• 1988

임상적으로 뇌압 항진 소견을 보여서 시행한 뇌전산화 단층 촬영상 뇌수두증이 확인되어 뇌실 복막간 단락술을 시행하였으나, 단락 도관 기능 부전증이 크립토코스 뇌실염에 의해 초래된 것이 조직학적 검사로 확인된 한 예를 문헌 고찰과 함께 보고하는 바이다.

• Pediatric Infection and Vaccine
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• 제3권2호
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• pp.194-199
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• 1996

Cryptococcosis is a rare in normal child and the majority of cases usually occur in patients with defective cell-mediated immunity. Infection is acquired by inhalation of organisms from the environment and disseminated via the blood stream to any organ of the body. We experienced a 7 year old girl who presented with fever, both cervical lymphadenopathy, hepatomegaly under the impression of lymphoma. However lymph node biopsy revealed cryptococcal budding and culture of lymph nodes yielded cryptococcus neoformans. The radiologic finding showed huge, multiple cervical lymph node enlargement spreading to mediastinum and abdomen. The immune fuction in term of T cell, B cell, serum immunoglobulin, complement and neutrophil function tests was normal. The patient was treated with amphotericin B and flucytosine for 6 weeks and responded to the treatment well. We report this case with brief review of the related literatures.

• Mycobiology
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• 제37권3호
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• pp.161-170
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• 2009

Cryptococcus neoformans is a basidiomycete human fungal pathogen that causes meningoencephalitis in both immunocompromised and immunocompetent individuals. The ability to sense and respond to diverse extracellular signals is essential for the pathogen to infect and cause disease in the host. Four major stress-activated signaling (SAS) pathways have been characterized in C. neoformans, including the HOG (high osmolarity glycerol response), PKC/Mpk1 MAPK (mitogen-activated protein kinase), calcium-dependent calcineurin, and RAS signaling pathways. The HOG pathway in C. neoformans not only controls responses to diverse environmental stresses, including osmotic shock, UV irradiation, oxidative stress, heavy metal stress, antifungal drugs, toxic metabolites, and high temperature, but also regulates ergosterol biosynthesis. The PKC(protein kinase C)/Mpk1 pathway in C. neoformans is involved in a variety of stress responses, including osmotic, oxidative, and nitrosative stresses and breaches of cell wall integrity. The $Ca^{2+}$/calmodulin- and Ras-signaling pathways also play critical roles in adaptation to certain environmental stresses, such as high temperature and sexual differentiation. Perturbation of the SAS pathways not only impairs the ability of C. neoformans to resist a variety of environmental stresses during host infection, but also affects production of virulence factors, such as capsule and melanin. A drug(s) capable of targeting signaling components of the SAS pathway will be effective for treatment of cryptococcosis.

• Journal of Chest Surgery
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• 제51권5호
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• pp.350-355
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• 2018

Background: The complication rate of fungal disease is higher among patients with hematological malignancies. We investigated the clinicobacteriological outcomes of resected pulmonary fungal infections complicating hematological malignancies. Methods: Between 2001 and 2017, 21 patients with pulmonary fungal infections complicating hematological malignancies underwent resection, and their clinical records and survival were retrospectively reviewed. Results: The median age of the patients was 47 years, and 13 were male. The histological diagnoses were pulmonary aspergillosis (19 cases), mucormycosis (1 case), and cryptococcosis (1 case). The indications for surgery were resistance to antifungal therapy and the necessity of surgery before hematopoietic stem cell transplantation in 13 and 8 cases, respectively. The diagnoses of the hematological malignancies were acute myelogenous leukemia (10 cases), acute lymphocytic leukemia (5 cases), myelodysplastic syndrome (3 cases), and chronic myelogenous leukemia, malignant lymphoma, and extramedullary plasmacytoma (1 case each). The surgical procedures were partial resection (11 cases), segmentectomy (5 cases), lobectomy (4 cases), and cavernostomy (1 case). The size of the lesions was 0.9-8.5 cm. Fourteen cases had cavitation. There were no surgical-related deaths or fungal progression. Conclusion: Pulmonary fungal infections are resistant to treatments for hematological malignancies. Since the treatment of the underlying disease is extended and these infections often recur and are exacerbated, surgery should be considered when possible.

• Journal of Microbiology and Biotechnology
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• 제30권8호
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• pp.1142-1148
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• 2020

Mitochondria play a vital role in iron uptake and metabolism in pathogenic fungi, and also influence virulence and drug tolerance. However, the regulation of iron transport within the mitochondria of Cryptococcus neoformans, a causative agent of fungal meningoencephalitis in immunocompromised individuals, remains largely uncharacterized. In this study, we identified and functionally characterized Mrs3/4, a homolog of the Saccharomyces cerevisiae mitochondrial iron transporter, in C. neoformans var. grubii. A strain expressing an Mrs3/4-GFP fusion protein was generated, and the mitochondrial localization of the fusion protein was confirmed. Moreover, a mutant lacking the MRS3/4 gene was constructed; this mutant displayed significantly reduced mitochondrial iron and cellular heme accumulation. In addition, impaired mitochondrial iron-sulfur cluster metabolism and altered expression of genes required for iron uptake at the plasma membrane were observed in the mrs3/4 mutant, suggesting that Mrs3/4 is involved in iron import and metabolism in the mitochondria of C. neoformans. Using a murine model of cryptococcosis, we demonstrated that an mrs3/4 mutant is defective in survival and virulence. Taken together, our study suggests that Mrs3/4 is responsible for iron import in mitochondria and reveals a link between mitochondrial iron metabolism and the virulence of C. neoformans.

• 대한의생명과학회지
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• 제24권3호
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• pp.183-195
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• 2018

Cryptococcosis, which is caused by the Cryptococcus species complex (including Cryptococcus neoformans and Cryptococcus gattii), is well known as one of the most important medical problems. However, the of the Cryptococcus species complex is still limited to pneumonia and meningitis. In particular, the differences in virulence among the five major serotypes of the Cryptococcus species complex are not fully understood. To elucidate the virulence of the Cryptococcus species complex when it is disseminated hematogenously, rats were infected by different strains of the Cryptococcus species serotype, and their histopathological characteristics were compared after infection. The cumulative mortality ratio of rats infected with serotype B strain was slightly higher than in the other experimental groups. In addition, the average recovery of the Cryptococcus species complex from rats infected with serotype B strain was significantly higher than in the other groups in almost all organ samples except spleen. The recovery of the Cryptococcus species complex was associated with the severity of histopathological lesions, including bleeding, inflammation, and tissue damage in all organs. In rats infected with serotype B strain, the virulence was the most severe, especially in the lungs and liver. These results indicate that the pathophysiology of the Cryptococcus species complex infection differs according to serotype.

• Tuberculosis and Respiratory Diseases
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• 제55권6호
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• pp.589-596
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• 2003

연구배경 : 고립성 폐 결절의 양성과 악성의 감별은 치료와 예후를 결정하는데 중요하지만 결핵성 육아종의 빈도가 높은 국내에서는 감별진단이 쉽지가 않다. 이에 저자들은 최근 고립성 폐 결절의 진단에 정확성이 높다고 알려진 PET의 유용성과 혈당농도와 결절의 표준섭취계수의 차이를 알아보고자 하였다. 방 법 : 2001년 1월부터 2002년 6월까지 전남대학교 의과대학병원에서 시행한 단순 흉부사진상 발견된 고립성 폐 결절과 타 병원에서 이를 주소로 내원한 환자들 중 FDG-PET 및 조직학적인 검사로 진단된 61명의 환자를 대상으로 하였다. 결 과 : 조직학적으로 진단된 61례에서 악성 결절은 48례(편평상피세포폐암 23례, 선암 16례, 소세포폐암 9례), 양성 결절은 13례(염증성 육아종 9례, 결핵종 3례, cryptococcosis 증 l례) 이었다. 침상형을 가진 경우는 모두 악성 결절을 보였으나 분엽성과 침상형을 모두 갖지 않은 경우에서도 악성 결절을 보여 이러한 결절의 변연으로 악성과 양성 결절을 명확히 구분할 수 없었다. PET의 경우 SUV cut-off value를 3.0으로 하였을 때 13례의 양성 결절 중 10례에서 3.0 이하의 수치를 보였으며 3례에서 SUV가 3.0 이상으로 증가되었다. 악성 결절 48례는 모두 SUV가 3.0 이상의 값을 보였다. 악성 결절의 평균 SUV는 $9.52{\pm}5.20$, 양성 결절은 $1.61{\pm}3.60$으로 두 군간에 의의 있게 차이를 보였다. 폐암 환자에서 당뇨병을 가진 환자 군과 당뇨병이 없는 군의 평균 SUV에선 $9.10{\pm}4.51$, $9.65{\pm}5.46$으로 두 군 사이에 차이를 보이지 않았다. FDG-PET 검사의 민감도, 특이도, 양성 예측치 및 음성 예측치는 100%, 77%, 94% 및 100%의 결과를 보여 다른 검사에 비하여 진단적 정확성은 높았으나 상대적으로 특이도는 낮았다. 결 론 : 고립성 폐 결절에 대해 FDG-PET 진단검사는 비침습적인 검사로 다른 검사에 비하여 높은 정확도를 보여 주고 있으며 혈중 포도당 농도에 영향을 받지 않는 것으로 생각되고 있다. 특이도가 낮은점은 결핵종 등이 많은 우리나라에서 더 많은 연구가 이루어져야 할 것으로 생각된다.

• 한국균학회소식:학술대회논문집
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• 한국균학회 2015년도 춘계학술대회 및 임시총회
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• pp.59-59
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• 2015

Cryptococcus neoformans causes life-threatening meningoencephalitis in humans, but the treatment of cryptococcosis remains challenging. To develop novel therapeutic targets and approaches, signaling cascades controlling pathogenicity of C. neoformans have been extensively studied but the underlying biological regulatory circuits remain elusive, particularly due to the presence of an evolutionarily divergent set of transcription factors (TFs) in this basidiomycetous fungus. In this study, we constructed a high-quality of 322 signature-tagged gene deletion strains for 155 putative TF genes, which were previously predicted using the DNA-binding domain TF database (http://www.transcriptionfactor.org/). We tested in vivo and in vitro phenotypic traits under 32 distinct growth conditions using 322 TF gene deletion strains. At least one phenotypic trait was exhibited by 145 out of 155 TF mutants (93%) and approximately 85% of the TFs (132/155) have been functionally characterized for the first time in this study. Through high-coverage phenome analysis, we discovered myriad novel TFs that play critical roles in growth, differentiation, virulence-factor (melanin, capsule, and urease) formation, stress responses, antifungal drug resistance, and virulence. Large-scale virulence and infectivity assays in insect (Galleria mellonella) and mouse host models identified 34 novel TFs that are critical for pathogenicity. The genotypic and phenotypic data for each TF are available in the C. neoformans TF phenome database (http://tf.cryptococcus.org). In conclusion, our phenome-based functional analysis of the C. neoformans TF mutant library provides key insights into transcriptional networks of basidiomycetous fungi and ubiquitous human fungal pathogens.

• Tuberculosis and Respiratory Diseases
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• 제61권6호
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• pp.554-561
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• 2006

배 경: AIDS환자에게서 기회감염은 가장 치명적인 합병증으로 대부분은 폐 감염의 형태로 발현된다. 본 연구는 타 국가에 비해 아직까지는 유병률이 낮아서 상대적으로 자료가 부족한 국내의 현황에서, HIV 감염자 및 AIDS 환자의 임상양상을 살펴보고 특히 AIDS 환자들이 주로 어떤 호흡기 질환으로 발현하며, 호흡기 질환이 발현된 AIDS 환자와 기타 폐외 질환으로 발현하거나, HIV 단순감염자와의 임상상에 어떤 차이가 있는지를 중점적으로 살펴보고자 하였다. 방 법: 2001년부터 2006년 2월까지 중앙대학교 병원에 내원한 HIV 감염자 총28명을 대상으로, 이들 환자의 의무기록을 후향적으로 조사하여 분석하였다. 결 과: 총 28명의 HIV 감염자 중 27명이 남자이었고 평균연령은 40.6세로 30대가 40%로 가장 많은 분포를 보였다. 이 중에서 폐질환을 동반한 경우가 11명이었고, 폐외질환 환자가 16명이었다. 폐질환을 동반환 환자군과 폐외질환자에서 내원시 CD4+림프구수와 HIV RNA 수는 평균 79.5/mm3, 48,903 IU/ml, $400/mm^3$, 60,256 IU/ml을 보여(P value: 0.001, 0.695) 폐감염이 동반된 경우에 더 심한 면역억제 상태가 심하였다. 폐감염의 종류로는 폐결핵, 주폐포자충 폐렴이 가장 많은 빈도를 차지하였으며, 이들의 평균 CD4+림프구 수를 보면, 폐결핵이 $56/mm^3$, 주폐포자충폐렴이 $42/mm^3$이었다. 결 론: HIV에 관련된 폐질환이 동반된 경우 그렇지 않은 경우에 비해 월등히 면역억제가 심하였다. 이 중에서 폐결핵과 주폐포포자충 폐렴이 가장 흔한 형태의 폐감염이었다. 본 연구는 일개 대학병원에서 경험한 HIV 감염자와 특히 폐질환이 발현된 AIDS 환자의 임상상의 특징을 확인할 수 있었고 빠른 조기진단과 치료의 필요성을 다시 한번 확인하였다.