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Biomedical subjects

Y S Shim

Publications and source records attributed to Y S Shim.

At least 37 records · Page 2Linked to original sources

Genetic susceptibility to chronic obstructive pulmonary disease in Koreans: combined analysis of polymorphic genotypes for microsomal epoxide hydrolase and glutathione S-transferase M1 and T1.

BACKGROUND: Although smoking is the major causal factor in the development of chronic obstructive pulmonary disease (COPD), only 10-20% of chronic heavy cigarette smokers develop symptomatic COPD which suggests the presence of genetic susceptibility. This genetic susceptibility to COPD might depend on variations in enzyme activities that detoxify cigarette smoke products such as microsomal epoxide hydrolase (mEPHX) and glutathione-S transferase (GST). As there is increasing evidence that several genes influence the development of COPD, multiple gene polymorphisms should be investigated to find out the genetic susceptibility to COPD. METHODS: The genotypes of 83 patients with COPD and 76 healthy smoking control subjects were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (PCR-RFLP) for the mEPHX gene, and multiplex PCR for GST M1 and GST T1 genes. The frequencies of polymorphic genotypes of mEPHX, GST M1, and GST T1 genes were compared both individually and in combination in patients with COPD and healthy smokers. RESULTS: No differences were observed in the frequency of polymorphic genotypes in exons 3 and 4 of mEPHX, GST M1, and GST T1 genes between patients with COPD and healthy smokers. The frequencies of any combination of these genotypes also showed no differences between the COPD group and the control group. CONCLUSIONS: Genetic polymorphisms in mEPHX, GST M1, and GST T1 genes are not associated with the development of COPD in Koreans.

Adult↗

Surgery increased the chance of cure in multi-drug resistant pulmonary tuberculosis.

BACKGROUND: Medical treatment of multiple drug resistant (MDR) pulmonary tuberculosis is generally quite unsuccessful. Recently, surgical management is increasing and shows promise. We analyzed our experience to identify the benefits and complications of pulmonary resection in MDR pulmonary tuberculosis. METHODS: A retrospective review was performed in 27 patients undergoing pulmonary resection for MDR pulmonary tuberculosis between January 1994 and March 1998. Their average ages were 40 years and were diagnosed a median of 15 months before surgery. All patients had resistance to an average of 4.4 drugs including isoniazid and rifampin, and had received second line drugs selected according to drug sensitivity test preoperatively. Most patients (92.6%) had cavitary lesions. Bilateral lesions were also identified in 19 patients (70.4%), but the main focus was recognized in one side of the lung. Most patients were indicated to operation for those who could not achieve negative sputum despite adequate medical treatment (n = 16, 59.3%); or for negative patients who had significant pulmonary parenchymal lesion (n = 11, 40.7%) which would have had a high probability of recurrence. Pneumonectomy was done in nine patients, lobectomy in 16 and segmentectomy in two. RESULTS: There was no operative mortality. Morbidity occurred in seven patients (25.9%); prolonged air leakage in three patients, reoperation due to bleeding in two, bronchopleural fistula in one, and reversible blindness in one. The median follow up period was 15 months (range 3-45). Sputum negative conversion was achieved in 22 patients (81.5%) initially. However, continued postoperative chemotherapy could convert to negative in another four patients (14.8%). Only one pneumonectomy patient (3.7%) failed because of considerable contralateral cavity. CONCLUSION: For patients with MDR pulmonary tuberculosis which is localized, and with adequate pulmonary reserve function, surgical pulmonary resection combined with appropriate pre and postoperative anti-tuberculosis chemotherapy can achieve high success rate with acceptable morbidity.

Adult↗

Pulmonary actinomycosis in Korea.

Pulmonary actinomycosis is a chronic pulmonary infection caused by Actinomyces, a Gram-positive, microaerophilic bacterium. Pulmonary involvement, other than cervicofacially or abdominopelvically, is uncommon and often leads to a misdiagnosis of pulmonary tuberculosis or lung cancer. In order to investigate the clinical, radiological, diagnostic and therapeutic characteristics of pulmonary actinomycosis, we reviewed a total of 25 cases reported in Korea. Thirteen were diagnosed at our hospital between 1985 and 1997 and 12 were reported in Korean publications. The condition occurred most frequently in middle-aged males, the most common symptom being haemoptysis, followed by cough and sputum. The main radiological features were peripherally located mass or nodule and consolidation, with central low attenuation. Complications such as empyema, sinus fistula or mediastinitis did not occur. Diagnosis was confirmed by percutaneous needle aspiration (n = 8), bronchoscopic biopsy (n = 3) or thoracotomy (n = 13). Eleven of 25 cases were treated medically and in nine others, surgical resection was followed by treatment with antibiotics. In conclusion, when a middle-aged male patient presents with haemoptysis and cough, together with radiologic findings of a peripheral mass or nodule with/without central low attenuation, pulmonary actinomycosis should be suspected.

Actinomycosis↗

Bronchoscopic findings of endobronchial vascular lesions in patients with haemoptysis.

Cases of endobronchial vascular lesions observed with bronchoscope are presented. These lesions tend to be diagnosed erroneously as true endobronchial tumours so that biopsies are tried frequently. Consequently, a catastrophic accident of massive bleeding can complicate the condition if endobronchial vascular lesions are injured during bronchoscopic biopsy or brushing. We present three types of endobronchial vascular lesion: tubular bulging type, mass-like type and haemangioma type. Because bronchoscopic findings of submucosal tubular structure and visible pulsation are highly suggestive of endobronchial vascular lesion, there must be extreme caution to prevent fatal bleeding.

Adult↗

Pulmonary lymphangioleiomyomatosis in Korea.

BACKGROUND: Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease occurring in women of reproductive age and leading to progressive respiratory failure in spite of treatment. In Korea the first case was reported in 1984 and by 1997 a total of 23 cases had been reported. The clinical findings of these Korean cases are reviewed. METHODS: The details of 10 cases of LAM on file at Seoul National University Hospital were reviewed together with those of 13 cases previously reported from other Korean institutes. Two, including the only one to be reported in a man, were excluded after reviewing the clinical, radiological, and pathological findings, leaving a total of 21 cases in the present study. RESULTS: All 21 patients were women and in all cases the disease was proven pathologically. The mean (SD) age at onset of symptoms was 32 (8.6) years. The most common symptoms were dyspnoea and pneumothorax which were seen in 19 (90%) and 13 (76%) patients, respectively. Pulmonary function tests showed decreased transfer factor (TLCO) (100%) and airflow limitation (67%). All the cases had characteristic cysts on high resolution computed tomographic (HRCT) scanning. The overall severity score based on HRCT scans correlated with the percentage predicted TLCO/VA (p = 0.03) and FEV1/FVC (p = 0.02). The patients were all treated with medroxyprogesterone and/or tamoxifen. Follow up was possible in 10 cases. Two of these patients appeared to stabilise with no appreciable change clinically or in lung function on medroxyprogesterone and/or tamoxifen, but the remaining patients all deteriorated with two dying of respiratory insufficiency and one of infection following lung transplantation. CONCLUSIONS: As in other countries, in Korea LAM occurs exclusively in women and progresses despite hormonal treatment.

Adult↗

Association of HLA class I antigens with diffuse panbronchiolitis in Korean patients.

Diffuse panbronchiolitis (DPB) is a chronic obstructive pulmonary disease of unknown etiology. Observations of significantly increased frequency of human leukocyte antigen (HLA)-B54 in Japanese patients and occurrence of familial cases suggest possible genetic predisposition to the disease susceptibility. To evaluate the possible association of HLA with the disease in Koreans, we have analyzed 30 patients for HLA class I (A, B, C) and class II (DR) antigens by the serologic and DNA typing methods, respectively. The most significant change in the patients compared to the control subjects was increased frequency of HLA-A11 (53.3% versus 17.5%, corrected p [pc] = 1.2 x 10(-)4, odds ratio [OR] = 5.4). In addition, B55 showed significant positive association (16.7% versus 3.5%, pc = 0.05, OR = 5.5), and B62 and Cw4 showed rather weak association with the disease. Certain A11-associated haplotypes showed much stronger positive association with the disease, compared to A11 antigen itself. Observations of a strong association of HLA-A11 in Koreans and B54 in Japanese with DPB suggest that the candidate gene(s) responsible for the disease susceptibility is located within the HLA class I region, most probably between HLA-A and HLA-B loci.

Adult↗

The clinical characteristics of pulmonary alveolar proteinosis: experience at Seoul National University Hospital, and review of the literature.

Pulmonary alveolar proteinosis is such an extremely rare disease in Korea, that only a few cases have been reported. Meanwhile five cases were experienced at Seoul National University Hospital over ten years since 1987. We summarized the clinical characteristics and courses of them. Seven cases reported in the literature were included to add data about clinical characteristics and courses although only a few case reports mentioned patient's course. Middle aged male patients were mainly affected. No association with particular environmental or occupational exposure was identified. Dyspnea on exertion was the main symptom. Bilateral crackles were consistent, and bilateral parahilar hazy infiltrations on plain chest radiograph and ground glass opacity on high-resolution CT were characteristic. Superimposed infection was not identified in any patient at the time of diagnosis. Decreased diffusing capacity and hypoxia were present in almost every case. Whole lung lavage proved to be an effective therapeutic measure. The response to treatment was good. Long-term course of the disease, e.g. recurrence rate, is not yet known.

Adult↗

The effects of transferring tumor suppressor gene p16INK4A to p16INK4A-deleted cancer cells.

OBJECTIVES: p16 is known to be an important tumor suppressor gene and is also called MTS1 (multiple tumor suppressive gene 1). Especially in the case of non-small cell lung cancer, it was not expressed in more than 70% of cell lines examined. To determine changes in cell-cycle related proteins and the tumorigenic effect, we, therefore, transfected p16INK4A gene into lung cancer cell lines. METHODS: We transfected p16INK4A gene into lung cancer cell lines which do not express p16 protein. We evaluated the effect by clonogenic assay and observed the changes of cell-cycle related proteins. RESULTS: The newly-expressed p16 formed a complex with cdk4, and phosphorylated pRB was decreased, although cyclin D1 and pRB:cyclin D1 complex were unchanged. Clonogenic assay after selection with G418 showed that, in the cell lines transfected with p16, tumorigenicity was significantly less than in the control. CONCLUSION: These results suggest that the p16INK4A gene can be a candidate for gene therapy in cases of NSCLC in which p16INK4A gene is inactivated.

Carcinoma, Non-Small-Cell Lung↗

Sequence variation of EBNA2 of Epstein-Barr virus isolates from Korea.

To reveal sequence variations in the Epstein-Barr virus nuclear antigen 2 (EBNA2) genes of Epstein-Barr virus (EBV) strains circulating in the Korean population, the EBNA2 divergent region was amplified and sequenced from 13 EBV-1 isolates, 2 EBNA2 type 1 intertypic EBV isolates, and two EBV-2 isolates, all derived from Korean cancer patients. Comparative sequence analysis revealed that type 1 and type 2 EBNA2 divergent regions of Korean EBV isolates were almost identical to the respective regions of the B95-8 EBV-1 and AG876 EBV-2 strains. Two of the nucleotide changes found in the type 1 divergent regions of all Korean isolates, G-to-T and C-to-A at B95-8 EBV positions 48,991 and 48,998, respectively, are also present in all EBV-1 strains of non-Asian origins, indicating that these two sites might be mutational hot sites. Besides these two mutations, EBV-1 strains from Papua New Guinea or European Caucasians and Africa show unique patterns of identical sequence variations from B95-8, which were not found in type 1 isolates from Korea, suggesting that Korean type 1 are evolving as a lineage distinct from isolates from Papua New Guinea or European Caucasian and Africa.

Africa↗

Isolation and characterization of hrp1+, a new member of the SNF2/SWI2 gene family from the fission yeast Schizosaccharomyces pombe.

The SNF2/SWI2 ATPase/helicase family comprises proteins from a variety of species, which serve a number of functions, such as transcriptional regulation, maintenance of chromosome stability during mitosis, and various types of DNA repair. Several proteins with unknown functions are also included in this family. The number of genes that belong to this family is rapidly expanding, which makes it easier to analyze the common biological functions of the family members. This study was designed to clone the SNF2/SWI2 helicase-related genes from the fission yeast Schizosaccharomyces pombe in the hope that this would help to elucidate the common functions of the proteins in this family. The hrp1+ (helicase-related gene from S. pombe) gene was initially cloned by PCR amplification using degenerate primers based on conserved SNF2 motifs within the ERCC6 gene, which encodes a protein involved in DNA excision repair. The hrp1+ ORF codes for an 1373-amino acid polypeptide with a molecular mass of 159 kDa. Like other SNF2/SWI2 family proteins, the deduced amino acid sequence of Hrp1 contains DNA-dependent ATPase/7 helicase domains, as well as a chromodomain and a DNA-binding domain. This configuration is similar to that of mCHD1 (mouse chromo-ATPase/helicase-DNA-binding protein 1), suggesting that Hrp1 is a S. pombe homolog of mCHD1, which is thought to function in altering the chromatin structure to facilitate gene expression. Northern blot analysis showed that the hrp1+ gene produces a 4.6-kb transcript, which reaches its maximal level just before the cells enter the exponential growth phase, and then decreases gradually. DNA-damaging agents, such as MMS, MNNG and UV, decrease the rate of transcription of hrp1+. Deletion of the hrp1+ gene resulted in accelerated cell growth. On the other hand, overexpression of Hrp1 caused a reduction in growth rate. These results indicate that hrp1+ may act as a negative regulator of cellular growth.

Adenosine Triphosphatases↗

Telomerase activity in lung cancer cell lines and tissues.

Using TRAP assay, we studied the activity of the telomerase in the lung cancer cell lines, and lung cancer and normal tissues in which expression appears to be related to the immortality of cancer cells. All the human lung cancer cell lines and the majority of human lung cancer tissues (78%) expressed telomerase activity, but this was undetectable in normal human lung tissues. Positivity for telomerase activity in lung cancer cell lines was higher than in lung cancer tissues; this result implies the expression of telomerase activity may play a crucial role in the development or progression of lung cancer, and also suggests that improved method of detection may lead to the higher positivity for telomerase activity in primary lung cancer tissues. To determine whether there is a definite causal relationship between telomerase and cancer, and to develop new anti-cancer agents which inhibit telomerase, further study is needed.

Humans↗

Genetic instability of microsatellite sequences in non-small cell lung cancers.

To evaluate the frequency and pattern of microsatellite instability in NSCLCs, we examined 36 cases of resected NSCLC. The mean age of the patients was 59.9+/-8.4 years. There were 19 cases of squamous cell carcinoma, 15 of adenocarcinoma and two of large cell carcinoma. We observed microsatellite instability at one or more loci in 13 (36%) of 36 tumors analyzed, and this instability ranged from six tumors showing instability in only a single microsatellite to three tumors that had alterations in three of four tested microsatellites. The microsatellite that showed instability most frequently in these tumors was D3S1340 (31%). Microsatellite instability was found in five (26%) of 19 squamous cell carcinomas, six (40%) of 15 adenocarcinomas, and in both large cell carcinomas tested. We found microsatellite instability in four (24%) of 17 cancers at stage I, in one (17%) of six at stage II, in eight (73%) of eleven at stage IIIa, and in neither at stage IIIb. In conclusion, microsatellite instability was noted in at least one third of non-small cell lung cancers, suggesting its possible role in cancer development.

Adenocarcinoma↗

Bronchiolitis obliterans organizing pneumonia in Korea.

An analysis of the clinical features in 23 cases of bronchiolitis obliterans organizing pneumonia (BOOP) in Korea is presented. Six were men and 17 were female, with a male-to-female ratio of 1:2.4. Idiopathic BOOP was present in 18 of these patients, connective tissue disease-associated BOOP in five and all of them were females. The most frequent symptoms were dyspnoea and coughing in both groups; and crackles were the most prominent physical findings. Leukocytosis was observed in seven of the idiopathic BOOP group and all in the connective tissue disease-associated BOOP group. In most cases, FVC, FEV 1, diffusing capacity and arterial O2 pressure were reduced. In roentgenographic study, patchy air space consolidation was the major finding and subpleural predominance was observed in the majority of patients in both groups. Migration of lesions were identified in only two patients with idiopathic BOOP. Steroid treatment was effective in all of idiopathic BOOP. In contrast to previous reports, an analysis of the 23 Korean BOOP patients showed several interesting points. First, a female predominance was observed. Second, migration of lesion was rare. Third, it did not show any different prognosis in patients with reticular pattern on roentgenogram compared with patients with patchy air space consolidation on roentgenogram. Whether these differences were due to ethnic or environmental factors is to be determined.

Adult↗

Hypertrophied bronchial artery at thin-section CT in patients with bronchiectasis: correlation with CT angiographic findings.

PURPOSE: To evaluate hypertrophied bronchial arteries on thin-section computed tomographic (CT) scans in patients with bronchiectasis by using CT angiographic correlation. MATERIALS AND METHODS: Spiral CT angiography was performed prospectively in 14 patients (eight men, six women; age range, 34-71 years) with bronchiectasis who were suspected of having bronchial arterial hypertrophy at thin-section CT (performed without contrast medium). The inclusion criteria were tubular (in six patients) or nodular (in 14 patients) areas of soft-tissue attenuation that had an appearance unlike that of lymph nodes at thin-section CT and that were within the mediastinum and around the central airway. These findings were subsequently correlated with the spiral CT angiographic findings. RESULTS: At comparative analysis of thin-section CT scans and CT angiograms, seven of the eight (88%) tubular lesions and 19 of the 36 (53%) nodular lesions in the mediastinal soft tissue were proved to be hypertrophied bronchial arteries. All of the six (100%) tubular and 19 of the 21 (90%) nodular lesions around the walls of the main (primary) and lobar bronchi were hypertrophied bronchial arteries. In eight (57%) patients, CT angiograms showed 11 intraluminal protrusions caused by hypertrophied bronchial arteries in the main bronchi, lobar bronchi, or both. CONCLUSION: Nodular and tubular structures in the mediastinum and around the central airway on thin-section CT scans in the patients with bronchiectasis are suggestive of hypertrophied bronchial arteries. Recognition of the hypertrophied bronchial artery can be critical for the bronchoscopist.

Adult↗

Clinicopathologic study of basaloid squamous carcinoma of the upper aerodigestive tract.

The clinicopathologic and immunohistochemical characteristics of nine cases of basaloid squamous carcinoma (BSC) of the upper aerodigestive tract are reported, along with the results of an in situ hybridization for human papilloma virus (HPV) DNA. The cases were selected through a review of 237 head and neck carcinomas, and were located in the supraglottic larynx (5), hypopharynx (2), and the base of tongue (2). The patients were 7 males and 2 females with the mean age of 62. BSCs were histologically characterized by lobules and nests of basaloid cells with scanty cytoplasm, comedonecrosis and adenoid features, and by concomitant presence of squamous cell carcinoma. Immunohistochemically, all BSCs showed positivity for high molecular weight cytokeratin (HMW CK) with heterogeneous or diffuse staining pattern, but lacked reactivity for neuroendocrine markers and bcl-2 oncoprotein. No HPV DNA was detected in BSCs. This study reaffirms that BSC is a rare carcinoma with a peculiar topographic distribution and distinct pathologic features.

Aged↗

Summer-type hypersensitivity pneumonitis outside Japan: a case report and the state of the art.

A 61-year-old Korean housewife developed dyspnoea, cough and weight loss in the summer of 1994. The case was diagnosed as definite summer-type hypersensitivity pneumonitis (SHP) according to the criteria proposed for hypersensitivity pneumonitis and for SHP. Her serum antibodies to Trichosporon were positive. Her symptoms were exacerbated after she returned home and Trichosporon was isolated from the patient's home, indicating Trichosporon as the causative antigen. This is the first confirmed case of SHP outside Japan. On the basis of our research in SHP to date, we propose that SHP occurs in other Asian countries and that the assay of anti-Trichosporon antibodies is useful for the diagnosis of the disease.

Alveolitis, Extrinsic Allergic↗