BACKGROUND: The appearance of multiple-drug-resistant Mycobacterium tuberculosis strains has been seriously compromising successful control of tuberculosis. Rifampin-resistance, caused by mutations in the rpoB gene, can be indicative of multiple-drug-resistance, and its detection is of great importance. The present study aimed to develop an oligonucleotide chip for accurate and convenient screening of drug-resistance. METHODS: In order to detect point mutations in the rpoB gene, an oligonucleotide chip was prepared by immobilizing specific probe DNA to a microscopic slide glass by a chemical reaction. The probe DNA that was selected from the 81 bp core region of the rpoB gene was designed to have mutation sites at the center. A total of 17 mutant probes related to rifampin-resistance including 8 rifabutin-sensitive mutant probes were used in this study. For accurate determination, wild type probes were prepared for each mutation position with an equal length, which enabled a direct comparison of the hybridization intensities between the mutant and wild type. RESULTS: Mycobacterial genomic DNA from clinical samples was tested with the oligonucleotide chip and the results were compared with those of the drug-susceptibility test in addition to sequencing and INNO-LiPA Rif. TB kit test in some cases. Out of 15 samples, the oligonucleotide chip results of 13 samples showed good agreement with the rifabutin-sensitivity results. The two samples with conflicting result also showed a discrepancy between the other tests, suggesting such possibilities as existence of mixed strains and difference in drug-sensitivity. Further verification of these samples in addition to more case studies are required before the final evaluation of the oligonucleotide chip can be made. CONCLUSION: An oligonucleotide chip was developed for the detection of rpoB gene mutations related to drug-susceptibility. The results to date show the potential for using the oligonucleotide chip for accurate and convenient screening of drug-resistance to provide useful information in antituberculosis drug therapy.
DNA ; Drug Therapy ; Glass ; Mass Screening ; Mycobacterium tuberculosis* ; Mycobacterium* ; Point Mutation* ; Rifabutin ; Rifampin ; Tuberculosis

The objective of this study is to report on a case of a huge epidermoid cyst in the conus medullaris and cauda equina in a 43 year-old lady with the characteristic MRI and histologic findings. She suffered from low back pain, hypoesthesia around the anus and urinary incontinence for over 20 years. Since 15 years previously, she gradually developed right foot drop and muscle atrophy. She underwent surgery and unfortunately, she developed complete paralysis below T12 after complete tumor excision. At postoperative 4 weeks, evidence of partial neurological recovery down to the L3 roots was observed, but as yet there has been no further neurological recovery. Although total surgical excision is thought to be the only radical treatment, we recommend partial tumor excision to avoid damaging the spinal cord and cauda equina during the surgical procedure, than the radical excision, because this cyst is a very slowly growing benign tumor.
Adult ; Anal Canal ; Cauda Equina* ; Conus Snail* ; Epidermal Cyst* ; Foot ; Humans ; Hypesthesia ; Low Back Pain ; Magnetic Resonance Imaging ; Muscular Atrophy ; Paralysis ; Spinal Cord ; Urinary Incontinence

No abstract available.
Tumor Necrosis Factor-alpha*

Amiodarone is a potent antiarrhythmic agent and can cause potentially life-threatening pulmonary fibrosis. Of the numerous side effects associated with amiodarone therapy, lugn toxicity is one of the most serious adverse reactions. Recently, we experienced a case of amiodarone-induced pulmonary toxicity (APT), which induced severe dyspnea and productive coughing, confirmed by cytologic and electron microscopic examination of the bronchoalveolar lavage (BAL). The symptoms and abnormalities in the chest X-ray were improved after the withdrawal of amiodarone. Cytologic examination of the BAL revealed numerous foam cells with cytoplasmic vacuoles or small particles. Ultrastructurally, the foam cells demonstrated characteristic lysosomal inclusions, which were electron-dense multilamellated bodies, crystalloid bodies, and mixed forms with small lipid vacuoles. It is strongly suggested that only cytologic and electron microscopic examination of the BAL without open lung biopsy is enough for diagnosis of APT, when APT is clinically suspected in a patient who has a history or ingestation of amiodarone.
Amiodarone ; Biopsy ; Bronchoalveolar Lavage* ; Cough ; Cytoplasm ; Diagnosis ; Dyspnea ; Foam Cells ; Humans ; Lung ; Microscopy, Electron ; Pulmonary Fibrosis ; Thorax ; Vacuoles

Apoptosis, including the programmed cell death, is important event in normal cell turnover and maintenance of adult tissues. Apoptosis exerts a homeostatic function in relation to tissues dynamics, as the steady state of continuously renewing tissues achieved by a balance between cell replication and cell death. This study was undertaken to investigate the association between apoptosis and development of the cervical neoplasia. Archival cervical samples from normal epithelium (n 10), low-grade squamous intraepithelial lesions (LSIL, n = 10), high-grade squamous intraepithelial lesions (HSIL, n 10), microinvasive squamous cell carcinomas (n 10), and invasive squamous cell carcinomas (n = 10) were evaluated for apoptosis. We used in situ end-labeling of DNA strand breaks by terminal deoxynucleotidyltransferase incorporation of biotinylated deoxyuridine to 3-OH ends of DNA, identified by nickel-avidine-peroxidase. The apoptotic index (sum of apoptotic bodies divided by the total nuclei times 100) significantly decreased (P<0.05) as the degree of neoplasia increased: 3.1 + 0.9 % in normal epithelium, 5.5 +/- 1.4 % in LSIL, 1.6 +/- 0.4 % in HSIL, 1.9 +/- 0.5 % in microinvasive carcinomas, and 0.6 +/- 0.3 % in invasive carcinomas. Compared to normal epithelium, the total cell number per 200x field increased significantly (P<0,05): 379 +/- 47 in normal epithelium, 462 +/- 228 in LSIL, 670+/-293 in HSIL, 1035 +/- 254 in microinvasive carcinomas, and 1389 +/- 247 in invasive carcinomas. Consequently, these results suggest that progession of cervical carcinogenesis is associated with a decrease in apoptotic index and an increase in the number of the total cell.
Adult ; Apoptosis* ; Carcinogenesis ; Carcinoma, Squamous Cell ; Cell Count ; Cell Death ; Deoxyuridine ; DNA ; DNA Nucleotidylexotransferase ; Epithelium ; Humans

BACKGROUND/AIMS: Nontuberculous mycobacteria (NTM) infection has been increasing worldwide in both general population and immunocompromised patients, which has also been reported in rheumatoid arthritis (RA) patients. This study aimed to identify the incidence and clinical characteristics of NTM infection in RA patients living in tuberculosis (TB) infection endemic area. METHODS: We performed a retrospective analysis of NTM infection cases in our RA registry at a tertiary referral center from January 1995 to December 2013. The clinical features of them were compared to those of 52 TB infection patients from same registry. RESULTS: Among 1,397 patients with RA, NTM infection was newly developed in 26 patients and the incidence of NTM infection was 164.8 per 100,000 patient-years. The Mycobacterium avium complex was the most frequent isolate (76.9%). None of the NTM infections had extrapulmonary involvement, which was rather common in TB infection (26.9%). Patients with NTM infection were older, received higher cumulative steroid doses, and had higher rates of past TB infection history and concomitant interstitial lung disease (ILD) than cases with TB infection. CONCLUSIONS: In South Korea, NTM infection is not rare in RA patients, and infection rates are growing. Physicians should be cautious about NTM infection in patients with a history of TB infection or concomitant ILD, even living in TB endemic area.
Arthritis, Rheumatoid* ; Humans ; Immunocompromised Host ; Incidence ; Korea* ; Lung Diseases, Interstitial ; Mycobacterium avium Complex ; Mycobacterium tuberculosis ; Nontuberculous Mycobacteria ; Retrospective Studies ; Tertiary Care Centers ; Tuberculosis

BACKGROUND: Residual pleural thickening(RPT) develops in about 50% of tuberculous pleurisy(PLTB). Some reports have suggested that elevated TNF-α and impaired fibrinolysis could be the cause of RPT, but until now, the mechanism and predictors of RPT have not been well known. TGF-β has been known to promote fibrogenesis and is increased in tuberculous pleural fluid(PF). PLTB and malignant pleurisy(PLMAL) manifest lymphocyte-dominant exudative pleural effusion, and it has clinical implications in the differentiation of the two diseases, based on the findings of pleural effusion. We performed this study to compare pleural fluid TNF-α, TGF-β, and fibrinolytic parameters between PLTB and PLMAL, and to find the predictors of RPT in PLTB. METHODS: Thirty-five PLTB and 14 PLMAL patients who were admitted to the Asan Medical Center from February 1997 to August 1999 were enrolled. All PLTB patients were prescribed a primary, short-course, anti-tuberculosis regimen. TNF-α, tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), plasminogen, α2-antiplasmin, and D-dimer were measured in both PF and PB, TGF-β was measured only in PF. Clinical characteristics, TNF-α, TGF-β, and fibrinolytic parameters were compared between patients with RPT less than 2 mm and patients with more than 2 mm of the thirty patients who completed the anti-tuberculosis treatment. RESULTS: The levels of TNF-α, tPA, PAI-1, plasminogen, α2-antiplasmin, and D-dimer in PF were higher than those in peripheral blood (PB) in PLTB, whereas only plasminogen, α2-antiplasmin, and D-dimer were higher in PF than in PB in PLMAL. Pleural fluid TNF-α, TGF-β, PAI-1, plasminogen, α2-antiplasmin were increased in PLTB compared with PLMAL, but these factors did not show any further advantages over ADA in differentiation between PLTB and PLMAL. TNF-α, TGF-β, and fibrinolytic parameters did not show any differences between patients with RPT less than 2 mm and patients with RPT more than 2 mm. CONCLUSION: Our data suggest that TNF-α, TGF-β, and fibrinolytic parameters may play some role for the development of RPT in PLTB, but they failed to predict the occurrence of RPT in PLTB. Also these parameters did not seem to have any advantages over ADA in differentiating between two diseases.
Chungcheongnam-do ; Fibrinolysis ; Humans ; Plasminogen ; Plasminogen Activator Inhibitor 1 ; Pleural Effusion ; Pleural Effusion, Malignant* ; Tissue Plasminogen Activator ; Transforming Growth Factor beta* ; Tuberculosis, Pleural ; Tumor Necrosis Factor-alpha*

Serum amyloid A (SAA) has been regarded as an important mediator of inflammatory responses. The effect of several formyl peptide receptor-like 1 (FPRL1) ligands on the production of IL-8 by SAA was investigated in human neutrophils. Among the ligands tested, LL-37 was found to specifically inhibit SAA-induced IL-8 production in transcriptional and post-transcriptional levels. Since SAA stimulated IL-8 production via ERK and p38 MAPK in human neutrophils, we tested the effect of LL-37 on SAA induction for these two MAPKs. LL-37 caused a dramatic inhibition of ERK and p38 MAPK activity, which is induced by SAA. LL-37 was also found to inhibit SAA-stimulated neutrophil chemotactic migration. Further, the LL-37-induced inhibitory effect was mediated by FPRL1. Our findings indicate that LL-37 is expected to be useful in the inhibition of SAA signaling and for the development of drugs against SAA-related inflammatory diseases.
Animals ; Antimicrobial Cationic Peptides/*pharmacology ; Cell Line, Tumor ; Cell Movement ; Chemotaxis, Leukocyte ; Humans ; Interleukin-8/*biosynthesis ; MAP Kinase Kinase Kinases/metabolism ; Neutrophils/drug effects/*immunology ; Proto-Oncogene Proteins/metabolism ; Rats ; Receptors, Formyl Peptide/metabolism ; Receptors, Lipoxin/metabolism ; Serum Amyloid A Protein/*antagonists & inhibitors ; Signal Transduction ; Transcription, Genetic

Serum amyloid A (SAA) has been regarded as an important mediator of inflammatory responses. The effect of several formyl peptide receptor-like 1 (FPRL1) ligands on the production of IL-8 by SAA was investigated in human neutrophils. Among the ligands tested, LL-37 was found to specifically inhibit SAA-induced IL-8 production in transcriptional and post-transcriptional levels. Since SAA stimulated IL-8 production via ERK and p38 MAPK in human neutrophils, we tested the effect of LL-37 on SAA induction for these two MAPKs. LL-37 caused a dramatic inhibition of ERK and p38 MAPK activity, which is induced by SAA. LL-37 was also found to inhibit SAA-stimulated neutrophil chemotactic migration. Further, the LL-37-induced inhibitory effect was mediated by FPRL1. Our findings indicate that LL-37 is expected to be useful in the inhibition of SAA signaling and for the development of drugs against SAA-related inflammatory diseases.
Animals ; Antimicrobial Cationic Peptides/*pharmacology ; Cell Line, Tumor ; Cell Movement ; Chemotaxis, Leukocyte ; Humans ; Interleukin-8/*biosynthesis ; MAP Kinase Kinase Kinases/metabolism ; Neutrophils/drug effects/*immunology ; Proto-Oncogene Proteins/metabolism ; Rats ; Receptors, Formyl Peptide/metabolism ; Receptors, Lipoxin/metabolism ; Serum Amyloid A Protein/*antagonists & inhibitors ; Signal Transduction ; Transcription, Genetic

We have previously reported that aqueous extract of gall from Rhus chinensis, known as "Obaeja", inhibited rat intestinal alpha-glucosidase and suppressed postprandial hyperglycemia by delaying digestion and absorption of intestinal carbohydrate (Shim et al., 2003). This led us to speculate that obaeja could be involved in ameliorating beta-cell injury by lowering glucotoxicity. In the present study, we thus examined the protective effect of obaeja on pancreatic beta-cell damage along with its anti-diabetic effect in streptozotocin-induced animal models. Streptozotocin was administered to rat pups (neonate/STZ model), or to adult rats with a lower dose using osmotic pump (osmotic pump/STZ model) for inducing beta cell death and diabetes. Obaeja was given to those rat pups after weaning in neonate/STZ model, or 2 weeks before subcutaneous implantation of osmotic pump to rats of the other latter model. In the diabetic control rats of the neonate/STZ model, which were not fed with obaeja, some pancreatic islets demonstrated a destruction of beta cell mass with insulitis 2 weeks after weaning, while some larger and irregular islets were formed by proliferation of alpha cells. In particular, we found some pancreatic lobules showing a severe inflammation and degeneration of islet and acinar tissues in this model. Islets in these inflammatory lobules were smaller in size with only few cells. In contrast, any inflammatory responses and insulitis were not observed in pancreas of the rats fed obaeja in this model. The islets in those rats maintained their normal profiles and islet cell population. Such anti-cytotoxic effect was also monitored in the diabetic rats of osmotic pump/STZ model. Especially, occurrence of hyperglycemia in the obaeja fed rats was delayed by 25~30 days than that of diabetic control rats in this model. Taken together, these results imply that regulation of postprandial blood glucose level by obaeja feeding may ameliorate a secondary injury caused by glucotoxicity.
Absorption ; Adult ; alpha-Glucosidases ; Animals ; Blood Glucose ; Cell Death ; Digestion ; Humans ; Hyperglycemia ; Inflammation ; Islets of Langerhans ; Models, Animal ; Pancreas ; Rats ; Rhus* ; Streptozocin ; Weaning