배 경 :FQ계 약제는 다제내성 결핵환자들의 치료를 위한 주용 2차 항결핵약제의 하나이다. 그러나 FQ계 여러 약제들 간 교차내성정도와 내성관련 유전자인 gyrA의 돌연변이간 관련성을 조사하게 되었다.방 법 :결핵균 중에서 OFX 내성인 63균주와 감수성인 10균주를 대상으로 Lowenstein-Jensen 배지에 CIP, LVX, MXF, GAT, SPX 등에 대한 교차내성을 조사하였다. 퀴놀론계 각 약제를 0.5-3g/ml 농도로 첨가한 배지에서, 2g/ml 이상에서 균이 발육한 경우를 내성으로 판정하였다. OFX 내성인 균주의 gyrA 및 gyrB 유전자의 돌연변이가 잘 발생하는 곳을 염기서열 분석하여 약제별로 그 교차내성 양상을 비교하였다.
Background : Fluoroquinolone drugs are an important anti-tuberculous agent for the treatment of multi-drug resistant tuberculosis. However, many drugs belonging to the fluoroquinolones have different cross resistance to each other. Methods : Sixty-three ofloxacin (OFX) resistant and 10 pan-susceptible M. tuberculosis isolates were selected, and compared for their cross resistance using a proportion method on Lowenstein-Jensen media, containing ofloxacin (OFX), ciprofloxacin (CIP), levofloxacin (LVX), moxifloxacin (MXF), gatifloxacin (GAT) and sparfloxacin (SPX), at concentrations ranging from 0.5 to 3µg/ml. DNA extracted from the isolates was directly sequenced after amplifying from the gyrA and gyrB genes. Results : The 63 OFX resistant M. tuberculosis isolates showed complete cross resistance to CIP, but only 90.5, 44.4, 36.5 and 46.0% to LVX, MXF, GAT, and to SPX, respectively. Fifty-one of the isolates (81.0%) had point mutations in codons 88, 90, 91 and 94 in gyrA, which are known to be correlated with OFX resistance. The Gly88Ala, Ala90Valand Asp94Ala mutations in gyrA showed a tendency to be susceptible to MXF, GAT and SPX. Only 4 isolates had mutations in the gyrB gene, which did not affect the OFX resistance. Conclusion : About 60% of the OFX resistant M. tuberculosis isolates were susceptible to GAT, SPX and MXF. These fluoroquinolones may be useful in the treatment of TB patients showing OFX resistance. (Tuberc Respir Dis 2005; 59: 250-256)
배 경 : 에탐부톨은 6개월 단기요법 중에 사용되는 1차 항결핵약제 중 하나이다. embB 유전자의 돌연변이는 에탐부톨의 내성과 관련이 있은 것으로 추측 되어 왔다. 그러나 최근에 embB 유전자의 돌연변이는 에탐부톨 감수성인 균에서도 발견되어 이 유전자의 돌연변이가 에탐부톨 내성과 관련이 있는 것인지에 대한 논란이 있는 바, 이에 대한 이해를 높이고자 본 실험을 하게 되었다.방 법 : 약제감수성검사에서 에탐부톨은 감수성이지만 타 항결핵약제에 내성을 보인 36균주를 선택하였다. 이 균주들에서 embB 유전자에 대하여 중합효소연쇄반응를 실시한 후에 염기서열분석을 통해 돌연변이 여부를 조사하였다. 돌연변이가 있는 균주에 대하여 과거의 항결핵약제 감수성검사 결과를 비교하였다.
Background : Ethambutol(EMB) is one of the first-line drugs included in short-course anti-tuberculosis therapy. The point mutations in embB gene have been speculated to be associated EMB resistance. However, detection of embB mutations at these positions have been observed in both EMB-susceptible isolates; thus, it remains controversial whether these mutations are associated with EMB resistance Methods : The 36 M. tuberculosis isolates were selected from clinical isolates which tested susceptible to EMB and resistant to at least one drug. DNA extracted from the isolates was analyzed by amplifying embB gene. The PCR products were purified and directly sequenced. We reviewed the history of past drug susceptibility test results. Results : Out of 36 EMB-susceptible strains, 3 strains (8.3%) had a mutation in codon 306 or 406 of the embB gene. These three strains had at least isoniazid resistance. They grew at 1.0 mcg/ml of EMB in Lowenstein-Jensen media. The patients of the strains were continuously smear-positive for over 3 years despite taking TB therapy. One strain had been EMB-resistant in past drug susceptibility tests. Conclusion : EMB-susceptible strains containing embB mutation may be caused by decreased viability in vitro test not by itself. (Tuberc Respir Dis 2005; 59: 266-271)
배 경 : 결핵의 보호면역 반응에서 CD8+T 세포에 의한 여러 기전이 중요한 역할을 한다는 사실이 최근에 보고되고 있다. IFN-γ 분비 외에도 결핵균으로 감염된 세포에 독성을 나타내어 직접 결핵균으로 감염된 세포를 제거하는 독성능 또한 그 역할이 중요하다고 알려지고 있는데, BCG 예방접종을 받은 개체에서도 이러한 균체항원에 특정한 CD8+T 세포의 독성능이 유도되어 있어서 보호면역 반응에서의 역할을 하는지 연구하였다.대상 및 방법 : HLA-A*0201 과 A*0206를 표현하며 BCG 예방접종을 한 개체들의 혈액에서 백혈구를 분리하고 균체항원의 항원결정기 (ThyA30-38) 에 대한 독성능과 ex vivo IFN-γ 분비능을 유도하였다.
Background : The immune responses mediated by CD8+T cells are known to be significant in controlling M. tuberculosis infections. In order to determine the role of cytotoxic CD8+T cells in the protective immune mechanism in latently infected subjects, this study examined whether or not the cytotoxic immune responses of CD8+T cells specific to the M. tuberculosis somatic antigens are induced in BCG vaccinated healthy subjects. Methods : Cytotoxicity and IFN-γ elispot assays were used to investigate the activities of CD8+T cells specific for the thyA30-38 peptide epitope in circulating peripheral blood mononuclear cells (PBMC) from BCG-vaccinated HLA-A*0201 and A*0206 subjects. Results : The results indicate the cytotoxic and IFN-γ immune responses of CD8+T cells specific for thyA30-38 were induced in BCG vaccinated healthy subjects. Conclusion : The cytotoxic and IFN-γ responses by CD8+T cells specific for the M. tuberculosis somatic antigens are induced in BCG-vaccinated subjects, and appear to be involved in the protective immune mechanism in latently infected people against a M. tuberculosis infection. (Tuberc Respir Dis 2005; 59: 272-278)
연구배경 : 폐쇄성 수면무호흡증후군은 다양한 원인에 의해 발생하게 된다. 주된 위험요소로는 비만과 좁은 상기도, 비정상적인 머리-얼굴 구조 등이 알려져 있으며 유전적 요인 또한 가족내 집단적 발생하였다는 보고들에 의해 뒷받침되고 있다. 본 연구에서 저자들은 HLA검사를 통하여 폐쇄성 수면무호흡증후군에서 유전학적인 배경을 규명하고자 하였다.방 법 : 철야 수면다원검사로 진단한 25명의 폐쇄성 수면무호흡증후군 환자 (여자 1명과 남자 24명, 연령 30- 66세)를 대상으로 하였으며 대조군은 200명의 건강한 한국인으로 하였다. HLA-A와 B 대립유전자의 검사는 미세세포독성검사로 시행하였고 HLA-DRB1 유전자의 두번째 엑손의 다형성에 대한 분석은 PCR- SSOP방법을 이용하여 시행하였다.
Background : Obstructive sleep apnea syndrome (OSAS) is believed to have multifactorial causes. The major risk factors for OSAS are obesity, narrowed upper airways, and abnormal cranial-facial structures. A genetic basis for OSAS has been also suggested by reports of families with many members affected. This study analyzed the HLA typing in patients with OSAS to determine the possible role of genetics in OSAS. Methods : Twenty-five Korean patients with OSAS (1 woman and 24 men; age range 30-66 years) were enrolled in this study. A diagnosis of OSAS was made using full-night polysomnography. The control group consisted of 200 healthy Korean people. Serologic typing of the HLA-A and B alleles was performed in all patients using a standard lymphocyte microcytotoxicity test. Analysis of the polymorphic second exons of the HLA-DRB1 gene was performed using a polymerase chain reaction-sequence specific oligonucleotide probe. Results : The allele frequency of HLA-A11 was significantly lower in patients with OSAS compared with the controls (p<0.05). The HLA-B allele frequencies in the patients and controls had a similar distribution. Analysis of the HLA- DRB1 gene polymorphisms showed an increased frequency of DRB1*09 in the OSA patients compared with the controls (p<0.05). When the analysis was performed after dividing the OSAS patients according to the severity of apnea, the allele frequency of HLA-DRB1*08 was significantly higher in the severe OSA patients (apnea index >45) than in the controls (p<0.05). Conclusion : This study revealed an association between OSAS and the HLA-A11 and DRB1*09 alleles as well as association between the disease severity and the HLA-DRB1*08 allele in Korean patients. These results suggest that genetics plays an important role in both the development and the disease severity of OSAS. (Tuberc Respir Dis 2005; 59: 298-305)
저자들은 결핵성 뇌수막염을 가진 31세 남자환자에서 심한 다뇨와 저나트륨혈증, 저혈압, 요중 염분 소실이 동반되어 있어 CSWS로 진단하고 항결핵제 투여와 식염수, 염류코르티코이드의 투여 후 임상적 호전을 보인 증례 1예를 경험하였기에 보고하는 바이다.
Hyponatremia which is due to excessive sodium loss in the urine and decrease in extracellular fluid volume following an acute or chronic central nervous system injury, has been conjunctively described as cerebral salt wasting syndrome (CSWS). This syndrome is often confused with dilutional hyponatremia due to inappropriate secretion of antidiuretic hormone. Accurate diagnosis and management are mandatory for improvement of the course of the disease. This report describes a case of a 31-year-old male patient with CSWS associated with tuberculous meningitis. The patient exhibited hyponatremia, polyuria, excessive natriuresis, volume depletion, and hypotension. He was diagnosed to manifest CSWS and was treated by administration of fluids, salt, and fludrocortisone. After the respective treatments, symptoms of polyuria and hypotension were gradually resolved and hyponatremia was corrected. (Tuberc Respir Dis 2005; 59: 306-310)
저자들은 좌상엽 기관지를 막아 종양을 형성하여 폐암으로 오인된 기관지내 아스페르길루스증 1예를 경험하였기에 보고하는 바이다.
Pulmonary aspergillosis may present with three different features, according to the immune status of the host. These forms are invasive aspergillosis, allergic bronchopulmonary aspergillosis (ABPA) or aspergilloma. Bronchial involvement is an uncommon type of invasive pulmonary aspergillosis. We encountered an unusual case of an endobronchial aspergillosis that completely obstructed the left upper lobe, which was initially thought to be lung cancer. We report this case along with a review of the relevant literature. (Tuberc Respir Dis 2005; 59: 311-314)
저자들은 좌상엽 기관지를 막아 종양을 형성하여 폐암으로 오인된 기관지내 아스페르길루스증 1예를 경험하였기에 보고하는 바이다.
Pulmonary aspergillosis may present with three different features, according to the immune status of the host. These forms are invasive aspergillosis, allergic bronchopulmonary aspergillosis (ABPA) or aspergilloma. Bronchial involvement is an uncommon type of invasive pulmonary aspergillosis. We encountered an unusual case of an endobronchial aspergillosis that completely obstructed the left upper lobe, which was initially thought to be lung cancer. We report this case along with a review of the relevant literature. (Tuberc Respir Dis 2005; 59: 311-314)
저자들은 복수나 심낭액, 심부전의 소견 없이 갑상선기능저하증에 의해 발생한 일측성 흉막액을 진단하고, levothyroxine sodium 치료로 호전을 보인 환자 1예를 경험하였기에 문헌 고찰과 함께 보고하는 바이다.
Serous effusions have been most commonly associated with ascites, pericardial effusion, and heart failure. But, they have been considered to be an unusual form of complication in hypothyroidism and pleural effusion, which has been observed as an isolated finding in hypothyroidism is apparently rare and complete analysis of these types of hypothyroid-associated pleural effusions has yet not been described. We report a case of hypothyroidism associated with unilateral pleural effusion in a 77 year-old male patient who was improved through levothyroxine sodium with brief review of the literature. (Tuberc Respir Dis 2005; 59: 321-325)
A case of 51-year-old woman with a malignant solitary pulmonary nodule (SPN) that exhibited no growth over a period of 4 years is reported. Surgical wedge resection revealed an adenocarcinoma upon intra-operative frozen examination. The operation was completed with a right upper lobectomy and complete lymphadenectomy. The authors recommend an early surgical procedure for any SPNs due to risk factors for developing lung cancer. (Tuberc Respir Dis 2005; 59: 326-329)