• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.304-310
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• 1999

Background: IFN-$\gamma$ plays an important role in host response to intracellular organisms such as mycobacterium. Human infection with mycobacterium leads to a wide variety of outcomes, ranging from asymptomatic infection to widespread and rapidly fatal disease. Recent reports suggest that alteration of the function of IFN-$\gamma$ caused by a defective IFN-$\gamma$ receptor gene can explain different host response to mycobacterium. In this study, we investigated the role of IFN-$\gamma$ in the development of chronic refractory tuberculosis. Methods: The LPS-induced TNF-$\alpha$ production with or without IFN-$\gamma$ priming was compared by using monocytes taken from recently diagnosed tuberculosis, chronic refractory tuberculosis patients and controls. And the IFN-$\gamma$ receptor was measured by indirect fluorescent antibody technique to know whether change in the priming effect of IFN-$\gamma$ is related to IFN-$\gamma$ receptor deficiency or not. Results: The ratio of TNF-$\alpha$ produced in response to stimulation with INF-$\gamma$ and LPS to LPS alone was $13.5{\pm}7.6$ in controls, $10.8{\pm}6.4$ in recently diagnosed tuberculosis patients and $6.7{\pm}3.9$ in chronic refractory tuberculosis patients. The priming effect of IFN-$\gamma$ significantly decreased in chronic refractory tuberculosis patients compared with that in controls(p=0.002). However, IFN-$\gamma$ receptor deficiency was detected in one of chronic refractory tuberculosis patients. Conclusion: The decrease of the priming effect of IFN-$\gamma$ may play an important role in the development of chronic refractory tuberculosis, and in some patients, this may be related to the IFN-$\gamma$ receptor deficiency.

• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.497-509
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• 2002

Background : The mechanisms through which cellular activation results in intracellular mycobacterial killing is only partially understood. However, in vitro studies of human immunity to Mycobacterium tuberculosis have been largely modeled on the work reported by Crowle, which is complicated by several factors. The whole blood culture is simple and allows the simultaneous analysis of the relationship between bacterial killing and the effect of effector cells and humoral factors. In this study, we attempted to determine the extent to which M. tuberculosis is killed in a human whole blood culture and to explore the role of the host and microbial factor in this process. Methods : The PPD positive subject were compared to the umbilical cord blood and patients with tuberculosis, diabetes and lung cancer. The culture is performed using heparinized whole blood diluted with a culture medium and infected with a low number of M. avium or M. tuberculosis $H_{37}Ra$ for 4 days by rotating the culture in a $37^{\circ}C$, 5% $CO_2$ incubator. In some experiments, methlprednisolone- or pentoxifyline were used to inhibit the immune response. To assess the role of the T-cell subsets, CD4+, CD8+ T-cells or both were removed from the blood using magnetic beads. The ${\Delta}$ log killing ratio was defined using a CFU assay as the difference in the log number of viable organisms in the completed culture compared to the inoculum. Results : 1. A trend was noted toward the improved killing of mycobacteria in PPD+ subjects comparing to the umbilical cord blood but there was no specific difference in the patients with tuberculosis, diabetes and lung cancer. 2. Methylprednisolone and pentoxifyline adversely affected the killing in the PPD+ subjects umbilical cord blood and patients with tuberculosis. 3. The deletion of CD4+ or CD8+ T-lymphocytes adversely affected the killing of M. avium and M. tuberculosis $H_{37}Ra$ by PPD+ subjects. Deletion of both cell types had an additive effect, particularly in M. tuberculosis $H_{37}Ra$. 4. A significantly improved mycobacterial killing was noted after chemotherapy in patients with tuberculosis and the ${\Delta}$ logKR continuously decreased in a 3 and 4 days of whole blood culture. Conclusion : The in vitro bactericidal assay by human whole blood culture model was settled using a CFU assay. However, the host immunity to M. tuberculosis was not apparent in the human whole blood culture bactericidal assay, and patients with tuberculosis showed markedly improved bacterial killing after anti-tuberculous chemotherapy compared to before. The simplicity of a whole blood culture facilitates its inclusion in a clinical trial and it may have a potential role as a surrogate marker in a TB vaccine trial.

• The Korean Journal of Nuclear Medicine
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• v.28 no.3
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• pp.343-349
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• 1994

The study was taken to analyze the laboratory findings of the 161 patients with autoimmune thyroiditis treated at Kyungpook University Hospital from January 1992 to July 1993. They were all female and mean age was 33 years ranging from 10 to 73 years. Mean radioactive iodine uptake(RAIU) of the thyroid was $30.90{\pm}21.80(mean{\pm}SD)%$ at 6 hours and $37.97{\pm}23.25%$ at 24 hours. Mean serum levels of thyroid hormones were $1.41{\pm}0.48$(ng/ml) of T3, $7.26{\pm}3.23$(ug/dl) of T4, and $1.11{\pm}0.66$(ng/dl) of free T4, while mean serum level of TSH was $17.99{\pm}30.72$(uIU/ml). Mean levels of serum autoantibodies were 24. $43{\pm}31.91$(U/ml) of antithyroglobulin antibody and $55.32{\pm}41.97$(U/ml) of antimicrosomal antibody. The correlation between RAIU and serum thyroid hormone levels was significantly negative, but the positive correlation between RAIU and serum TSH was noted. The correlation between thyroid hormones and TSH was significantly negative, but the positive correlation between RAIU and serum TSH was noted. The correlation between thyroid hormones and TSH was significantly negative, while antimicrosomal antibody titer revealed significantly positive correlation with TSH. The RAIU and free T4 showed negatively correlated with the increasing age. The Initial clinical findings of the patients with autoimmune thyroiditis revealed euthyroidism in 83.2%, hypothyroidism in 14.9%, and hyperthyroidism in 1.9%. The incidence of abnormally increased serum thyroglobulin, antithyroglobulin antibody, and antimicrosomal antibody were 21.3%, 97.5%, and 87.6%, respectively and these abnormalities were more frequent in the patients with documented clinical thyroid functional disturbances.

• Tuberculosis and Respiratory Diseases
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• v.66 no.6
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• pp.463-466
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• 2009

Streptococcus constellatus (S. constellatus) is a commensal microorganism belonging to the "Streptococcus milleri" group, but may cause infections in different locations in immunocompromised patients. The infection of S. constellatus has high mortality and morbidity due to its tendency to cause abscesses in infected patients, which require immediate surgical drainage for effective treatment. We report on a 72-year-old woman with end stage renal disease, who suffered from dyspnea and general weakness that had developed over 7 days. Chest CT showed loculated pleural effusion. S. constellatus was cultured from exudative pleural effusions and confirmed by an analysis of 16S rRNA sequence. The patient was treated with drainage of pleural effusion and piperacillin/tazobactam for 5 weeks.

• Pediatric Infection and Vaccine
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• v.13 no.2
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• pp.180-185
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• 2006

Invasive Pseudomonas infections most often occur in the immunocompromised patients and are associated with high mortality rate. Rarely this disease may develop in healthy infants and children. We report two cases of invasive Pseudomonas aeruginosa infections that were diagnosed in otherwise healthy infants. The first case was a previously healthy 5-month-old infant with ecthyma gangrenosum and septicemia. She presented with fever, swelling of left periorbital area and multiple erythronodular skin lesions. Each skin lesion formed a black eschar surrounded by an erythematous areola over time. Cultures of blood, urine and discharge from skin lesions grew P. aeruginosa. On the day of visit, she showed pancytopenia which was normalized after 10 days. The patient responded well to the management with ceftazidime and tobramycin. The other case was a previously healthy 9-month-old infant with community-acquired pneumonia. He was referred from an outside hospital with fever and cough. Chest x-ray revealed pneumonic infiltrations on both lower lungs with pleural effusion on the right side. Cultures of blood and pleural fluid grew P. aeruginosa. Chest CT performed on the ninth day demonstrated pneumatoceles, lung abscess and necrosis of lung parenchyma. He was managed with ceftazidime and amikacin for 50 days. No residual pulmonary complications were noted during the three month follow-up. Laboratory results to evaluate immunologic defects of phagocytic cells, complement components and T- and B-lymphocytes were all within normal range in both patients. It should be kept in mind that Pseudomonas can be, though uncommon, a cause of community-acquired invasive infections in the previously healthy infants.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.294-308
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• 2002

Background : The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under the influence of IFN-$\gamma$ with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-$\gamma$ and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. Methods : The serum sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. Results : 1) the serum sIL-2R and IFN-$\gamma$ levels were elevated in patients with tuberculosis when compared to those of healthy subjects (p>0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis($2967{\pm}2132.8$ pg/ml) than in healthy controls($4949{\pm}1242.1$ pg/ml)(p<0.05). 2) In the pulmonary tuberculosis group, the serum sIL-2R and IFN-$\gamma$ levels were higher in patients with severe disease than those in patients with mild and moderate disease. However, the neopterin levels declined as the pulmonary tuberculosis became more severe (p<0.01). 3) The mean serum sIL-2R and IFN-$\gamma$ levels declined from $1071{\pm}1139.4$ U/ml to $1023{\pm}1920.9$ U/ml(p>0.05), $41{\pm}52.8$ pg/ml to $22{\pm}23.9$ gm/ml(p<0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from $3158{\pm}2272.6$ pg/ml to $3737{\pm}2307.5$ pg/ml(p>0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. Conclusion : On the basis of this study, sIL-2R, IFN-$\gamma$ and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.

• Childhood Kidney Diseases
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• v.8 no.2
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• pp.176-185
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• 2004

Purpose: Rapidly progressive glomerulonephritis (RPGN) is a clinicopathologic entity characterized by extensive crescent formation and rapid deterioration of renal function within few months. For better understanding of its clinical course and designing better treatment strategies, a clinicopathological study of childhood RPGN was performed. Methods: The clinical manifestations and pathological findings were reviewed retrospectively in 12 children who were diagnosed as having RPGN by clinical manifestations and renal biopsy during a period from 1991 to 2003. Several clinicopathological parameters were analyzed as prognostic factors. Results: Among a total of 12 patients, 4 were male and 8 were female. The median onset age was 11.5 years(range 5.5-14.6 years), and the median period of follow-up was 25 months(range 7 months-6.6 years). According to the pathological classification, 10 patients (83%) were type II RPGN(immune-complex mediated glomerulonephritis), 2 patients were type III RPGN(pauci-immune glomerulonephritis), and none was type I RPGN(anti-glomerular basement membrane nephritis). All patients were treated with oral steroid in various combinations with methylprednisolone pulse therapy(10 patients, 83%), cyclophosphamide(8 patients, 67%), or plasmapheresis(4 patients, 33%). Clinical outcomes of 12 patients were complete remission in 1(8%), end-stage renal disease in 2(17%), chronic renal insufficiency with persistent proteinuria in 2(17%), and normal renal function with persistent proteinuria in 7(58%) at the last follow-up. Poor prognosis is associated with increased serum creatinine level, severe anemia and younger age at the time of diagnosis. Conclusion: Immune-complex mediated glomerulonephritis is the major cause RPGN in children and most cases showed improvement of renal function with aggressive management. For better understanding of this rare disease, a prospective multicenter study should be done.

• Tuberculosis and Respiratory Diseases
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• v.61 no.3
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• pp.239-247
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• 2006

Background: Culture filtrate proteins secreted by mycobacteria are thought to play an important role in inducing protective immunity and to develop new methods for diagnosing tuberculosis. Methods: A culture filtrate protein of M. avium that was strongly reactive with goat antiserum against M. intracellulare was constructed. Its homologous protein (TB-14) in M. tuberculosis was cloned, expressed and purified. The inductions of IFN-${\gamma}$ stimulated with $10{\mu}g$ of TB-14 recombinant protein and $10{\mu}g$ PPD were estimated by using whole bloods from seven PPD (-) subjects, seven PPD (+) healthy volunteers and nine tuberculosis patients. Results: M. avium culture filtrate protein was confirmed as a hypothetical protein that was termed contig 116. A novel 14-kDa recombinant protein (TB-14) of M. tuberculosis was composed of 148 amino acids, including 30 amino acids of the signal peptide, and it showed 78% homology with M. avium. In the PPD (+) healthy volunteers, recombinant TB-14 protein strongly induced the secretion of IFN-${\gamma}$ in whole blood cultures. Conclusion: These results suggest that TB-14 recombinant protein might play an important role in inducing cell-mediated immunity against tuberculosis. Furthermore, TB-14 protein antigen and its antiserum will be available for the development of new diagnostic tools for tuberculosis.

• Pediatric Infection and Vaccine
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• v.8 no.1
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• pp.101-106
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• 2001

Purpose : The outbreaks of measles in infants and school children have been reported recently, but there are no specific treatment of these patients except symptomatic therapy. This study was performed to evaluate the effectiveness of intravenous gammaglobulin(IVGG) therapy in acute febrile phase of measles. Methods : The 68 cases in measles were treated with single dose of IVGG(400~500 mg/kg), and 44 cases were treated with only symptomatic treatment during the periods of 14 months from Jan. 2000 to Feb. 2001. They were compared to duration of fever, rash, the levels of CRP and days of admission on both groups after treatment. Results : The results obtained follows. The average of age was $7.9{\pm}3.6$ year old, and male to female was 1.0 : 1.6. The duration of fever after admission was $2.4{\pm}1.2$ days in treated group and $5.7{\pm}2.4$ days in control group. The period of disappearance of systemic erythematous maculopapular rash was $4.5{\pm}1.3$ days in treated group, and $6.9{\pm}2.4$ days in control group. The durations of admission day were also shown significantly shorter duration of period in treated group(P<0.05). The levels of CRP were no significant difference between two groups before treatment. However, treated group was significantly shown by improved within 5 days after IVGG therapy(P<0.05). Conclusions : The single dose of IVGG(400~500 mg/kg) therapy is one of rapid and effective therapy for clinical symptoms and signs in acute high febrile phase of measles.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.786-796
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• 1999

Background: It has been anticipated that the amount and composition of mucin are changed in patients with chronic airway diseases. We evaluated whether RTO3(mAb against rat tracheal mucins) could quantify the amount of mucin from the airway in the patients with chronic airway diseases. Methods and results; 1) RTO3 was bound to high molecular weight of mucin based on Western blot in sputum and BALF from patients with chronic airway diseases. 2) The goblet cells and submucosal glands in main bronchus from human were observed by PAS stain. And immunohistochemical stain with RTO3 showed immunoreactivity on some goblet cells. 3) The amount of mucin was more increased in patients with chronic airway diseases compared to those in normal subjects. 4) In the exacerbation of asthmatics, mucin amounts were more increased than stable asthmatics. Conclusion: We suggested that secreted mucin in chronic airway diseases can be quantified by ELISA with RTO3.