• Journal of Life Science
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• v.18 no.11
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• pp.1471-1478
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• 2008

In this study, nitric oxide (NO) production in a macrophage-lymphocyte co-culture system was used to assess the cytokine producing capability of cells during endotoxin tolerance in mice. Incubation of peritoneal macrophages with interferon-$\tau$ (IFN-$\tau$) in the presence of lipopolysaccharide (LPS) augmented NO synthesis. Exogenous tumor necrosis factor-$\alpha$(TNF-$\alpha$) could also replace LPS for the stimulation of NO production. Macrophages co-cultured with splenic lymphocytes showed augmented NO synthesis by LPS alone. However, pretreatment of mice with 2.5 mg/kg LPS completely prevented the lethality and the increase of blood TNF-$\alpha$ and IFN-$\tau$ after the second challenge with a lethal dose of LPS. In addition, when macrophages prepared from LPS-tolerant mice were co-cultured with normal splenocytes, LPS also could not induce the production of NO, even in the presence of exogenous TNF-$\alpha$. Moreover, when normal macrophages were co-cultured with splenocytes obtained from LPS-tolerant mice, stimulation with LPS could not evoke the NO production enhancement. However, this down-regulation was able to reverse by exogenous IFN-$\tau$ or concanavalin A (ConA), a stimulator of IFN-$\tau$ production. Our results indicate that not only macrophages but also lymphocytes contribute to LPS tolerance. As INF-$\tau$ can enhance the expression of TNF-$\alpha$, the decrease of INF-$\tau$synthesis from lymphocytes may orchestrate with the decrease of TNF-$\alpha$ synthesis from LPS-tolerant macrophages for the production of tolerant state and the prevention of excessive inflammation. Therefore, LPS tolerance may be exploited for prophylaxis of severe sepsis in patients at risk.

• Clinical and Experimental Pediatrics
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• v.57 no.1
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• pp.50-53
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• 2014

Hemophagocytic lymphohistiocytosis (HLH) occurs in the primary form (genetic or familial) or secondary form (acquired). The familial form of HLH (FHL) is a potentially fatal autosomal recessive disorder that occurs because of constitutional defects in cell-mediated cytotoxicity. Here, we report a fatal neonatal case of type 2 FHL (FHL2) that involved a novel frameshift mutation. Clinically, the newborn presented with severe sepsis-like features and required mechanical ventilation and continuous venovenous hemodiafiltration. Flow cytometry analysis showed marked HLH and complete absence of intracytoplasmic perforin expression in cytotoxic cells; therefore, we performed molecular genetic analyses for PRF1 mutations, which showed that the patient had a compound heterozygous mutation in PRF1, that is, c.65delC ($p.Pro22Argfs^*2$) and c.1090_1091delCT ($p.Leu364Glufs^*93$). Clinical and genetic assessments for FHL are required for neonates with refractory fever and progressive multiple organ failure, particularly when there is no evidence of microbiological or metabolic cause.

• Clinical and Experimental Pediatrics
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• v.51 no.11
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• pp.1236-1240
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• 2008

Smith-Lemli-Opitz syndrome (SLOS) is a rare, autosomal recessive disease caused by an inborn error in cholesterol synthesis. Patients with this disease suffer from multiple malformations due to reduced activity of 7-dehydrocholesterol reductase (DHCR7), which increases 7-dehydrocholesterol (7DHC) and 8-dehydrocholesterol (8DHC) concentrations and decreases cholesterol concentration in body fluids and tissue. The SLOS phenotypic spectrum ranges from a mild disorder with behavioral and learning problems to a lethal disease characterized by multiple malformations. Here, we describe a newborn male with ambiguous genitalia who was diagnosed to have type II SLOS during the neonatal period. A clinical examination revealed low levels of unconjugated estriol in the maternal serum, and a variety of fetal ultrasound anomalies, including prenatal growth retardation. After birth, the infant was diagnosed to have congenital heart disease (Tetralogy of Fallot with severe pulmonary artery stenosis), cleft lip and palate, micrognathia, postaxial polydactyly, ambiguous genitalia, and cataracts. Clinical investigation revealed extremely low plasma cholesterol levels and the presence of mutation (homozygote of p.Arg352Gln) in the DHCR7 gene. The patient underwent palliative heart surgery (to widen the pulmonary artery) and received intravenous lipid supplementation. Cholesterol levels increased slightly, but not to normal values. The patient died from cardiopulmonary failure and sepsis 72 days after birth. This report provides the first description of a Korean patient with SLOS confirmed by verification of DHCR7 gene mutation and illustrates the need for early recognition and appropriate diagnosis of this disease.

• Journal of Trauma and Injury
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• v.22 no.2
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• pp.193-198
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• 2009

Purpose: This study evaluated the characteristics and the prognosis of multiple intraabdominal solid organ injuries, including those to the liver, spleen, and kidney, after blunt trauma. Methods: From January 2001 to March 2009, 39 patients with multiple intraabdominal solid organ injuries, which had been confirmed by contrast-enhanced computed tomography after blunt trauma, were included in this retrospective study. The injury severity score (ISS), abbreviated injury scale (AIS), revised trauma score (RTS), American Association for the Surgery of Trauma (AAST) injury grade of solid organs, initial hemodynamic status, blood gas analysis, blood transfusion, and the mortality were the main outcome measurements. Results: Injured groups were classified into liver/kidney (n=17), liver/spleen (n=4), spleen/kidney (n=13), and liver/kidney/spleen (n=5) groups. Patients were older in the liver/kidney group than in the liver/kidney/spleen group (43 vs 18 years, p=0.023). The initial systolic blood pressures tended to be lower in the liver/kidney group than in the other groups (84 vs 105, 112, and 114 mmHg, p=0.087). The amounts of 24-hour packed RBC transfusion were 32 units in the liver/kidney group and 4 units in the liver/kidney/spleen group, but the difference was not statistically significant. Differences were found in neither the RTS, ISS, and AIS for head, chest, abdominal, and pelvic injuries nor the AAST injury grade for solid organ, but injuries to the chest were more severe in the liver/spleen group than in the spleen/kidney group (AIS 4.0 vs 2.8, p=0.028). Conservative treatment was the most frequent applied treatment in all groups. There were 6 mortalities : 3 due to hypovolemia, 2 to sepsis, and 1 to brain injury. Mortalities occurred only in the liver/kidney group. Conclusion: Patients who had intraabdominal solid organ injuries of the liver and the kidney simultaneously, tended to be transfused more at an early time after trauma, to have lower initial systolic blood pressures, and to have a higher mortality.

• Pediatric Infection and Vaccine
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• v.11 no.1
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• pp.126-130
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• 2004

Neisseria meningitidis is a leading cause of meningitis and septicemia in children and young adults. Meningococcemia, the most severe form of infection, represents a part of the various spectrum of the illness, and its clinical manifestations varied from mild fever and occult bacteriemia to fulminant catastrophic events(e.g., sepsis, shock, and death) within a few hours after onset of symptoms. Complement deficiencies, either congenital or acqired, increase the risk for invasive meningococcal disease. Since C3 plays a critical role in the complement cascade, congenital C3 deficiency or conditions that decrease C3(e.g., systemic lupus erythematosus, cirrhosis, nephritis, C3 nephritic factor) increase the risk for invasive disease due to pyogenic bacteria including N. meningitidis. We had experienced a case of meningococcemia and meningococcal meningitis presenting with mild fever, petechiae, and purpura. The patient was a 7-year old male. He had mild fever, vomiting, headache, nuchal rigidity, petechiae and purpura on both lower extremities, which spreaded to the whole body. His blood culture grew Neisseria meningitidis. The diagnosis of meningococcal meningitis was confirmed by examination of cerebrospinal fluid. The clinical symptoms of the illness were improved after treatment of antibiotics(cefotaxime) for 12 days. However the patient had developed generalized edema, microscopic hematuria & proteinuria on the third day after admission. High ASO titer and low serum C3 level were also noted. The microscopic hematuria returned to normal about 2 months after discharge. The C3 level returned to normal range about 3~4 months after discharge. we report a case of combined acute poststreptococcal glomerulonephritis and acute invasive meningococcal disease with reference review.

• Korean Journal of Food Science and Technology
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• v.40 no.1
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• pp.101-105
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• 2008

Enterobacter sakazakii is implicated in severe forms of neonatal infections such as meningitis and sepsis. This organism has been isolated from a wide range of foods, including cheese, vegetables, grains, herbs, and spices, but its primary environment is still unknown. Generally, dried infant milk formula has been epidemiologically identified as the source of E. sakazakii. Sunsik (a powdered mixture of roasted grains and other foodstuffs) is widely consumed in Korea as a side dish or energy supplement. Sunsik is consumed without heat treatment; thus, lacking an additional opportunity to inactivate foodborne pathogens. Therefore, its microbiological safety should be guaranteed. In this study, the prevalence of E. sakazakii was monitored in 23 different sunsik component flours, using FDA recommended methods; but E. sakazakii medium (Neogen) and Chromogenic E. sakazakii medium (Oxoid) were used as the selective media. In total, presumptive E. sakazakii strains were isolated from 8 different sunsik powders. Subsequently, an API 20E test was conducted, and 15 strains from 5 different sunsik flours (sea tangle, brown rice, non-glutinous rice, cheonggukjang, dried anchovy) were confirmed as E. sakazakii. Fifteen strains were again confirmed by PCR amplification, using three different primer sets (tDNA sequence, ITS sequence, 16S rRNA sequence), and compared to ATCC strains (12868, 29004, 29544, 51329). They were once again confirmed by their enzyme production profiles using an API ZYM kit. Finally, RAPD (random amplified polymorphic DNA)-genotyping was carried out as a monitoring tool to determine the contamination route of E. sakazakii during processing.

• Advances in pediatric surgery
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• v.16 no.2
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• pp.154-161
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• 2010

Pulmonary sequestration (PS) is a rare congenital malformation of the lower respiratory tract. The anomaly is characterized by absence of communication with the tracheobronchial tree and isolated blood supply from an anomalous systemic vessels. With the utilization of antenatal ultrasound, the diagnosis of asymptomatic neonatal PS has increased. Treatment options include observation, arterial embolization and surgical resection. The aim of the present study is to review the clinical course of PS and to share our experience with thoracoscopic resection. A total of 96 patients with PS were treated at Asan Children's Hospital between 1999 and 2010. The diagnosis of PS was established by CT in the cases managed by observation or embolization, and by tissue pathology in the surgical cases. Medical records and radiographic images were retrospectively reviewed. Thirty-nine patients were managed by embolization and 30 patients by surgery. The remaining 27 patients have been under observation without any procedures. Among 27 observation patients, 1 patient regressed completely and 10 patients were lost to follow up. Of the 39 embolizations patients, 2 had their lesion regress and sepsis was suspected after embolization. In 1 patient, the microcoil migrated to the iliac artery during the embolization procedure, and another patient developed renal abscess caused by renal artery embolization. Among 30 surgical cases, resection by thoracotomy was performed in 27 at the Department of Thoracic Surgery, and thoracoscopic resection in 3 at the Division of Pediatric Sugery. Only one wound complication ocurred. We conclud that surgical excision should be recommended for pulmonary sequestration, whether the sequestration is symptomatic or not because of the risk of infection, the low rate of natural regress, poor compliance, severe complications after embolization, and to exclude other pathology. In summary, thoracoscopic resection of the pulmonary sequestration is feasible, efficacious, safe and cosmetically superior even in neonatal period.

• Korean Journal of Clinical Laboratory Science
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• v.56 no.1
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• pp.52-58
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• 2024

Photodynamic therapy (PDT) activates intracellular oxygen using a photosensitizer activated by light of a specific wavelength and is a potential means of treating wound infections caused by antibiotic-resistant bacteria. Pseudomonas aeruginosa (P. aeruginosa) is typically non-pathogenic in healthy individuals but can induce severe illnesses like sepsis in the immunocompromised. Antibiotics have been conventionally used to treat P. aeruginosa infections, but increasing antibiotic resistance caused by drug misuse poses a growing challenge to the management of these infections. This study aimed to investigate the ability of PDT using photosensitizers (PhotoMed, Methyl pheophorbide A, or Radachlorin^®) and a diode laser to inhibit P. aeruginosa. Suspensions of P. aeruginosa and a photosensitizer were inoculated into Petri dishes and incubated for 30 minutes. Samples were then irradiated with the laser at 3 J/cm², and after incubation, colony areas were measured. P. aeruginosa killing rates were 79.65% for PhotoMed, 47.36% for Methyl pheophorbide A, and 40.91% for Radachlorin^®. This study shows that PDT using a diode laser and a photosensitizer constitutes an effective practical therapeutic approach for inhibiting P. aeruginosa.

• Pediatric Infection and Vaccine
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• v.30 no.2
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• pp.84-90
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• 2023

Purpose: Infants aged ≤90 days with fever are susceptible to severe infections. This study aimed to analyze the clinical features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in this particular age group. Methods: Infants aged ≤90 days who were diagnosed with coronavirus disease 2019 (COVID-19) and hospitalized between March 1, 2020, and May 1, 2022 were included. Medical records of patients were retrospectively reviewed. Results: A total of 105 infants with COVID-19 were included; 27 (25.7%) neonates aged <28 days, and 48 (45.7%) and 30 (28.6%) infants aged 28-59 days and 60-90 days, respectively. Five (4.7%) patients remained asymptomatic and 68 (62.8%) were febrile, with a median fever duration of 2 days. The most common symptoms were respiratory including cough (66.6%), nasal stuffiness (51.4%), and rhinorrhea (40.9%). Blood cultures were performed in 10 infants but no organisms were detected. Cultures of bag-collected urine specimens from 8 infants were grown, resulting in positive growth for 2 without pyuria. Nine (8.6%) infants were treated with empirical antibiotics for a median duration of 2.3 days (range, 1-7 days). All 105 infants showed improvement without any complications, and there were no fatal cases. Conclusions: In this study, most infants aged ≤90 days with COVID-19 presented with mild symptoms and none of those evaluated had documented bacterial co-infection. The favorable prognosis among young infants with SARS-CoV-2 may aid clinicians in tailoring their approach to evaluation and management during outbreaks.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.360-378
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• 1997

Background : Severe acute lung injury(ALI), also known as the adult respiratory distress syndrome(ARDS), is a heterogenous nature of dynamic and explosive clinical synrome that exacts a mortality of approximately 50%. Endotoxin(ETX) is an abundant component of the outer membrane of gram-negative bacteria capable of inducing severe lung injury in gram-negative sepsis and gram-negative bacterial pneumonia, which are among the most common predisposing causes of ARDS. The influx of PMNs into airway tissue is a pathological hallmark of LPS-induced lung injury. And there is a substantial evidence suggesting that cytokines are important mediators of lung injury in gram-negative sepsis. However, the kinetics of phagocytes and cytokines by an exact time sequence and their respective pathogenic importance remain to be elucidated. This study was performed to investigate the role of phagocytes and proinflammatory cytokines in ETX-induced ALI through a time course of changes in the concentration of protein, $TNF{\alpha}$ and IL-6, and counts of total and its differential cells in BALF. The consecutive histologic findings were also evaluated. Method : The experimental animals, healthy male Sprague-Dawley, weighted $200{\pm}50g$, were divided into control- and ALI- group. ALI was induced by an intravenous administration of ETX, 5mg/kg. Above mentioned all parameters were examined at 0(control), 3, 6, 24, 72 h after administration of ETX. $TNF{\alpha}$ and IL-6 cone. in BALF were measured by a bioassay. Results : The protein concentration and total leukocyte count(TC) in BALF was significantly increased at 3h compared to controls(p < 0.05). The protein conc. was significantly elavated during observation period, but TC was significantly decreased at 72h(p < 0.05 vs. 24h). There was a close relationship between TC and protein cone. in BALF(r = 0.65, p < 0.001). The PMN and monocyte count was well correlated with TC in BALF, and the correlation of PMN(r = 0.97, p < 0.001) appeared to be more meaningful than that of monocyte(r = 0.61, p < 0.001). There was also a significant correlation between protein cone. and PMN or monocyte count in BALF(PMN vs. monocyte : r = 0.55, p < 0.005 vs. r = 0.64, p < 0.001). The count of monocyte was significantly elavated during observation period though a meaningful reduction of PMN count in BALF at 72h, this observation suggested that monocyte may, at least, partipate in the process of lung injury steadly. In this study, there was no relationship between IL-6 and $TNF{\alpha}$ cone., and $TNF{\alpha}$ but not IL-6 was correlated with TC(r = 0.61, p < 0.05) and monocyte(r = 0.67, p < 0.05) in BALF only at 3, 6h after ETX introduced. In particular, the IL-6 cone. increased earlier and rapidly peaked than $TNF{\alpha}$ cone. in BALF. In histologic findings, the cell counts of lung slices were increased from 3 to 72h(p < 0.001 vs. NC). Alveolar wall-thickness was increased from 6 to 24h(p < 0.001 vs. NC). There was a significant correlation between the cell counts of lung slices and alveolar wall-thickness(r= 0.61, p < 0.001). This result suggested that the cellular infiltrations might be followed by the alterations of interstitium, and the edematous change of alveolar wall might be most rapidly recovered to its normal condition in the process of repair. Conclusion : We concluded that although the role of PMN is partly certain in ETX-induced ALI, it is somewhat inadequate to its known major impact on ALL Alveolar macrophage and/or non-immune cells such as pulmonary endothelial or epithelial cells, may be more importantly contributed to the initiation and perpetual progression of ETX-induced ALI. The IL-6 in ETX-induced ALI was independent to $TNF{\alpha}$, measured by a bioassay in BALF. The early rise in IL-6 in BALF implies multiple origins of the IL-6.