• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.497-505
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• 2002

Background : INF-${\gamma}$ plays an important role in the host response to a mycobacterial infection. A complete IFN-${\gamma}$ receptor 1 deficiency is a life threatening condition because it renders patients highly susceptible to a mycobacterial infection. Several mutations in the IFN-${\gamma}$ receptor and STAT1 gene have been identified in the rare mycobacterial infections. These mutations have partial function of the IFN-${\gamma}$ receptor and similar pathologic features to clinical tuberculosis. Materials and Methods : The function of the IFN-${\gamma}$ receptor was evaluated in the patients with clinical tuberculosis. In addition, the DNA coding sequence of the IFNgR1 and STAT1 gene was also analyzed in disseminated tuberculosis patients who might have a defective IFN-${\gamma}$ receptor. Results : The cell surface expression levels of HLA-DR and CD64 in the PMBC after being stimulation with IFN-${\gamma}$ (100IU/ml, 1000IU/ml) were increased in both controls and patients. However, the rate of increase in both groups was similar. The production of TNF-${\alpha}$ in the response to stimulation with LPS was higher in the both groups ($850.7{\pm}687.8$ vs. $836.7{\pm}564.3$ pg/ml). Pretreatment with IFN-${\gamma}$ prior to LPS stimulation resulted in further increase in TNF-${\alpha}$ production between both groups ($2203.5{\pm}242.5$ vs. $2227.5{\pm}560.4$ pg/ml). However, the rate of the increase in TNF-${\alpha}$ production in the both groups was similar. The known mutations in the IFNgR1 and STAT1 coding sequences were not found in the genomic DNA of patients with disseminated tuberculosis. Conclusion : The functional and genetic defects of the IFN-${\gamma}$ receptor were not identified in clinical tuberculosis. This suggests the defective IFN-${\gamma}$ receptor that predispoe patients to a BCG or NTM infection can not alone account for the cases of clinical tuberculosis.

• Restorative Dentistry and Endodontics
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• v.30 no.5
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• pp.409-422
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• 2005

The aim of this study was to identify the bacteria isolated from acute endodontic lesions by cell culture and 16S rDNA sequencing. The necrotic pulpal tissue was collected from 17 infected root canals, which were diagnosed as being either an acute pulpitis or acute periapical abscess. Samples were collected aseptically from the infected pulpal tissue of the infected root canals using a barbed broach and a paper point. The cut barbed broaches and paper points were transferred to an eppendorf tube containing 500 ul of 1 XPBS. The sample solution was briefly mixed and plated onto a BHI-agar plate containing $5\%$ sheep blood. The agar plates were incubated in a $37^{\circ}C$ anaerobic chamber for 7 days. The bacteria growing on the agar plate were identified by 16S rRNA coding gene (rDNA) cloning and sequencing at the species level. Among the 71 colonies grown on the agar plates, 56 strains survived and were identified. In dental caries involving the root canals, Streptococcus spp. were mainly isolated. Actinomyces, Clostridia, Bacteroides and Fusobacteria were isolated in the periapical lesion without dental caries. Interestingly, two new Actinomyces spp. (ChDC B639 and ChDC B631) were isolated in this study. These results showed that there was diversity among the species in endodontic lesions, This suggests that an endodontic infection is a mixed infection with a polymicrobial etiology. These results may offer the bacterial strains for pathogenesis studies related to an endodontic infection.

• Childhood Kidney Diseases
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• v.17 no.2
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• pp.65-72
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• 2013

Purpose: Urinary tract infection (UTI) caused by gram-positive uropathogens is usually hospital-acquired and associated with predisposing conditions. However, the incidence of gram-positive bacteria in community-acquired UTIs has recently increased worldwide. We aimed to investigate the clinical significance of UTI and associated genitourinary malformations in young children with febrile UTIs caused by gram-positive bacteria. Methods: We retrospectively reviewed the medical records of 566 patients (age, <1 year) who visited the Korea University Medical Center for febrile UTIs between January 2008 and May 2013. We classified the patients into the following two groups: gram-positive (P group) and gram-negative (N group), according to the results of urine culture. The fever duration; white blood cell (WBC) counts and C-reactive protein (CRP) levels in peripheral blood; and the presence of hydronephrosis, cortical defects, vesicoureteral reflux (VUR), and renal scarring were compared between the two groups. Results: The number of patients with gram-positive bacteria was 23 (4.1%) and with gram-negative bacteria was 543 (95.9%). The most common pathogen was Escherichia coli, and Enterococcus faecalis showed the highest incidence among gram-positive uropathogens. Patients with gram-positive bacteria showed longer fever duration compared to that in patients with gram-negative bacteria (P vs. N, $3.4{\pm}1.2$ vs. $2.9{\pm}1.6$ days, P <0.05). The incidence of VUR was increased in the gram-positive group compared to that in the gram-negative group (P vs. N, 55.6 vs. 17.8%, P<0.05). However, there were no significant differences in other laboratory and radiologic findings. Conclusion: The findings of our study show that community-acquired UTIs in patients younger than 1 year of age, caused by gram-positive uropathogens, can be associated with prolonged fever duration and the presence of VUR.

• Pediatric Infection and Vaccine
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• v.30 no.2
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• pp.73-83
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• 2023

Purpose: This study aimed to investigate the viral load dynamics in children with underlying malignancies diagnosed with symptomatic coronavirus disease 2019 (COVID-19). Methods: This was a retrospective longitudinal cohort study of patients <19 years old with underlying hemato-oncologic malignancies that were diagnosed with their first symptomatic severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR)-confirmed COVID-19 infection during March 1 to August 30, 2022. Review of electronic medical records and telephone surveys were undertaken to assess the clinical presentations and transmission route of the patients. Thresholds of negligible likelihood of infectious virus was defined as E gene reverse transcription (RT)-PCR cycle threshold (Ct) value ≥25. Results: During the 6-month study period, a total of 43 children with 44 episodes of COVID-19 were included. Of the 44 episodes, the median age of the patients included was 8 years old (interquartile range [IQR], 4.9-10.5), and the most common underlying disease was acute lymphoid leukemia (n=30, 68.2%), followed by patients post-hematopoietic stem cell transplantation (n=8, 18.2%). Majority of the patients had mild COVID-19 (n=32, 72.7%), and three patients (7.0%) had severe/critical COVID-19. Furthermore, 2.3% (n=1) died of COVID-19 associated acute respiratory distress syndrome. The largest percentage of the patients showed E gene RT-PCR Ct value ≥25 between 15-21 days (n=13, 39.4%), followed by 22-28 days (n=10, 30.3%). In 15.2% (n=5), E gene RT-PCR Ct value remained <25 beyond 28 days after initial positive PCR. Refractory malignancy status (β, 67.0; 95% confidence interval, 7.0-17.0; P=0.030) was significantly associated with prolonged duration of E gene RT-PCR <25. A patient with prolonged duration of E gene RT-PCR Ct value <25 was suspected to have infectivity shown by the transmission of the virus to his mother at day 86 after his initial positive test. Conclusions: Children that acquire symptomatic COVID-19 during refractory malignancy state are at a high risk for prolonged shedding warranting PCR-based transmission precautions in this cohort of patients.

• Pediatric Infection and Vaccine
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• v.30 no.3
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• pp.129-138
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• 2023

Purpose: Cancer incidence is known to be higher in patients with inborn errors of immunity (IEI) compared to the general population in addition to traditionally well-known infection susceptibility. We aimed to investigate cancer occurrence in patients with IEI in a single center. Methods: Medical records of IEI patients treated at Samsung Medical Center, Seoul, Korea were retrospectively reviewed from November 1994 to September 2023. Patients with IEI and cancer were identified. Results: Among 194 patients with IEI, seven patients (3.6%) were diagnosed with cancer. Five cases were lymphomas, 4 of which were Epstein-Barr virus (EBV)-associated lymphomas. The remaining cases included gastric cancer and multiple myeloma. The median age at cancer diagnosis was 18 years (range, 1-75 years). Among patients with cancer, underlying IEIs included X-linked lymphoproliferative disease-1 (XLP-1, n=3), activated phosphoinositide 3-kinase delta syndrome (APDS, n=2), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) haploinsufficiency (n=2). Seventy-five percent (3/4) of XLP-1 patients, 40.0% (2/5) of APDS patients, and 50.0% (2/4) of CTLA-4 haplo-insufficiency patients developed cancer. Patients with XLP-1 developed cancer at earlier age (median age 5 years) compared to those with APDS and CTLA-4 (P<0.001). One patient with APDS died during hematopoietic cell transplantation. Conclusions: Cancer occurred in 3.6% of IEI patients at a single center in Korea. In addition to infectious complications and inflammation, physicians caring for IEI patients should be aware of the potential risk of cancer, especially in association with EBV infection.

• Clinical and Experimental Pediatrics
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• v.46 no.2
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• pp.143-153
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• 2003

Purpose : Infection with Shiga-like toxin (SLT)-producing Escherichia coli, an emerging human pathogen found particularly in young children under 5 years of age, causes a spectrum of illnesses with high morbidity and mortality, ranging from diarrhea to hemorrhagic colitis and hemolytic uremic syndrome. Host mediators play an important role in the pathogenesis of SLT-I toxicity. The experiments described here were designed to investigate the effect of SLT-I on TNF-${\alpha}$ production and to understand the effect of TNF-${\alpha}$ on GB3 expression. We also further examine the relationship between the Gb3 level and the differential susceptibility of cells to the cytotoxic action of SLT-I. Methods : The effect of purified SLT-1 from E. coli O157 : H7 (ATCC 43890) on tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) production in Raw264.7 cells was investigated. Many mediators regulate endothelial cell membrane expression of the glycolipid globotriaosyleramide (Gb3), which serves as the toxin receptor, suggesting that the host response to the toxin or other bacterial products may contribute to pathogenesis by regulating target cell sensitivity to the toxins. Therefore, the relationships between Gb3 expression and cytotoxicity against SLT-I on three types of cells were evaluated. Results : Detectable levels of TNF-${\alpha}$ were produced as early as six hours after induction and continued to increase during 48 hours by SLT-I. It was also found that Vero cells and dendritic cells (DC2.4 cells) expressed high levels of Gb3, 83% and 68%, respectively, and that Raw264.7 cells had a low level of Gb3 (29%) and appeared refractory to cytotoxicity against SLT-I. Vero cells and DC2.4 cells expressing high levels of Gb3 were highly susceptible to SLT-I. Furthermore, macrophages showed a resistance to SLT-I cytotoxicity, despite the fact that Gb3 expression was enhanced. Conclusion : These results strongly suggest that the expression of Gb3 is necessary but not sufficient to confer sensitivity of macrophages to SLT-I and further underpin the important role of SLT-I and its Gb3 receptors in the pathogenesis of E. coli O157 infection.

• Pediatric Infection and Vaccine
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• v.12 no.2
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• pp.101-107
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• 2005

Purpose : We evaluated the C-reactive protein(CRP), white blood cell(WBC) and neutrophil levels in the various infectious diseases in a single hospital. Methods : A total of 640 medical records of children with infectious diseases such as bacterial meningitis(19 cases), acute pyelonephritis(55 cases), measles(253 cases), chicken pox (38 cases), mycoplasma pneumonia(160 cases), tsutsugamushi disease(39 cases) and Kawasaki disease(152 cases) admitted to The Catholic University of Korea, Daejeon St. Mary's hospital from 1996 to 2002 were retrospectively analyzed. Results : The mean CRP level was $17.9{\pm}6.4mg/dL$ in bacterial meningitis, $9.1{\pm}5.6mg/dL$ in Kawasaki disease, and $8.1{\pm}3.3mg/dL$ in acute pyelonephritis. In the mycoplasma pneumonia and tsutsugamush disease group(atypical bacterial group), the CRP level was $3.2{\pm}2.5mg/dL$, and $1.0{\pm}0.8mg/dL$ in the viral diseases group(measles and chicken pox). There were also significant differences for the WBC count and neutrophil differential between the 3 infectious groups with higher level in the bacterial infections group($15,600{\pm}6,100/mm^3$, $62{\pm}21%$) than in the atypical bacterial infections and in the viral infections group($9,600{\pm}3,300mm^3$, $57{\pm}11%$ and $7,300{\pm}2,900/mm^3$, $49{\pm}16%$, respectively). The inflammatory indices in Kawasaki disease were like those of bacterial infections. There was a correlation between CRP level and WBC or neutrophil count in the bacterial infections and Kawasaki disease groups. Conclusion : The CRP, WBC and neutrophil levels showed a clear difference between the infectious diseases according to causative agents. The WBC and neutrophil level was different according to age in measles and mycoplasma pneumonia. There was a correlation between CRP level and WBC or neutrophil count in the bacterial infections and Kawasaki disease groups.

• Applied Microscopy
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• v.38 no.1
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• pp.11-19
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• 2008

To examine the effect of the electrolyzed alkaline reduced water (ERW) on animal immunity, by employing Echinostoma hortense that is a parasite in the small intestine, the immune response of C57BL/6 was examined. To C57BL/6 mice, Echinostoma hortense metacercaria 15 per animal was in oculate dorsally, the worm was collected after 2 weeks, and the change of goblet cells and mast cells in the mucosa of small intestine was examined, and by using a protein chip, the change of cytokines in the serum was compared and observed. As a result, average 8.3 worms were collected from the C57BL/6 mice infected with E. hortense, and in the group fed with the ERW, average 10 worms were collected. In regard to the examination of the change of goblet cells, in the experimental group infected with E. hortense and fed with the ERW, average 4.3 worms per villus were detected, hence, it was found that the expression of goblet cells was low (p<0.001). Regarding the examination of the change of mast cells, similarly, in the group infected with E. hortense and fed with the ERW, average 11 worms per villus were detected, and it appears to be less than control group (p<0.001). Regarding the expression of cytokines in mouse serum, in comparison of the experiment group infected with E. hortense and control group, in the expression of the Th1 cytokines IL-6, IL-$1{\beta}$, IFN-${\gamma}$, TNF-${\alpha}$, and IL-2, and the Th2 cytokines IL-4, IL-5, IL-10, and IL-13, a significant difference was not detected. In our study, it was found that in the infection of E. hortense, the ERW mediates its effect on the number of goblet cells and mast cells in the intestinal mucosa, and simultaneously, the worm expulsion was delayed, and thus the conclusion that the ERW mediated its effect on the intestinal immunity of mice was obtained.

• Journal of Gastric Cancer
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• v.5 no.3 s.19
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• pp.191-199
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• 2005

Background: Though infections of Helicobacter pylori (H. pylori) are closely associated with activation of host angiogenesis, the underlying mechanisms, as well as the strategy for its prevention, have not been identified. Here, we investigated a causal role of H. pylori infection in angiogenesis of gastric mucosa and a potent inhibitory effect of a gastric proton pump inhibitor (PPI) on the gastropathy. Materials and Methods: A comparative analysis of CD 34 expression in tissues obtained from 20 H. pylori-associated gastritis and 18 H. pylori-negative gastritis patients was performed. Expression of $HIF-1{\alpha}$ and VEGF were tested by using RT-PCR. To evaluate the direct effect of H. pylori infection on differentiation of endothelial HUVEC cells, we carried out an in vitro angiogenesis assay. Results: H. pyfori-associated gastritis tissues showed significantly higher density of $CD34^+$ blood vessels than did H. pylori-negative gastritis tissues, and the levels were well correlated with expressions of $HIF-1{\alpha}$. Conditioned media from H. pylori-infected gastric mucosal cells stimulated a tubular formation of HUVEC cells. We also found a significant inhibitory effect of PPI, an agent frequently used for H. pylori eradication, on H. pylori-induced angiogenesis. This drug effectively inhibited the phosphorylation of MAP kinase ERK1/2, which is a principal signal for H. pylori-induced angiogenesis. Conclusion: The fact that PPls can down-regulate H. pylori-induced angiogenesis suggest that anti-angiogenic treatment using PPI may be a preventive approach for H. pylori-associated carcinogenesis.

• Parasites, Hosts and Diseases
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• v.26 no.2
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• pp.95-106
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• 1988

Specific or non-specific cytolytic processes of free-living amoebae causing meningoencephalitls have been emphasized and the cytolytic ability related to hydrolases in Entantoeba sp. and Naegleria sp. has also been reported since the latter half of 1970's. However, no information on hydrolase activities in Acanthamoeba sp. is available. Hydrolases in Acanthamoeba culbertsoni, a pathogenic species of free-living amoebae, were assayed and compared with those in a non-pathogenic species, A. royreba. Pathogenicity of these two species was confirmed through experimental infection to BALB/c mice. Hydrolase activities and cytotoxic effects between pathogenic and non.pathogenic species were compared in the trophozoites cultured in CGV media and in CHO cell line, respectively. The results are summarized as follows: 1. The mice infected with A. culbertseni were all dead 15 days after nasal inoculation, and the mean survival time was 8.5 days. Also the mice infected with this pathogenic species manifested typical meningoencephalitis, whereas the mice infected with A. royreba did not. 2. Hydrolases detected both in the cell extracts and culture media were acid phosphatase, ${\beta}-N-acetyl$ galactosaminidase, ${\beta}-N-acetyl$ glucosaminidase, ${\alpha}-mannosidase$, neutral proteinase and acid proteinase, all of which were detected with remarkably higher rate in A. culbertsoni than in A. royreba. 3. A. cuzbertsoni revealed strong cytotoxicity for the target CHO cells, whereas A. royreba did not show any specific cytotoxicity. About 80% of the target cells mixed with A. culbertsoni were dead 48 hours after cultivation, and more than 95% of the target cells were dead 72 hours after cultivation. 4. Hydrolase activities in A. culbertsoni cultured with the target cell line were assayed according to the culture time. The activities of acid phosphatase, ${\beta}-N-acetyl$ galactosaminidase, ${\beta}-N-acetyl$ glucosaminidase, ${\alpha}-mannosidase$ and acid proteinase in this pathogenic amoeba were detected higher in amoeba extracts than in culture media up to 120 hours after cultivation, but after 120 hours of cultivation those activities were detected higher in culture media than in the amoeba Iysates. Neutral proteinase activity in A. culbertsoni increased more in EBSS medium than in the Iysate specimens although the activity in the extracts was generally steady according to the cultivation time. Summarizing the above results, it is concluded that there were differences in hydrolase activities between Pathogenic A. culbertsoni and non-pathogenic A. royreba, and that some hydrolase activities were detected remarkably higher in A. culbertsoni which revealed strong cytotoxicity to the target CHO cell line.