TLR4, 5, and 9 Agonists Inhibit Murine Airway Invariant Natural Killer T Cells in an IL-12-Dependent Manner

Jae-Uoong Shim,Joon Haeng Rhee,Young-Il Koh 대한천식알레르기학회 2012 Allergy, Asthma & Immunology Research Vol.4 No.5

Purpose: Invariant natural killer T (iNKT) cells may play an important role in the pathogenesis of asthma in mice and humans. Thus, an agent that modulates the function of iNKT cells may have therapeutic potential to control asthma. We hypothesized that lipopolysaccharide (LPS)-, flagellin-, or CpG-induced changes in the cytokine milieu may modify and even inhibit the function of airway iNKT cells in asthma. Methods: Because increased α-galactosylceramide (GalCer)-induced airway hyperreactivity (AHR) reflects the presence of airway iNKT cells, α-GalCer-induced AHR, as well as inflammatory cells and cytokines in bronchoalveolar lavage (BAL) fluid, were determined 24 hours after in vivo treatment with LPS, flagellin, or CpG in naïve BALB/c mice. Intracellular IL-4 and IFN-γ were measured in spleen iNKT cells after in vitro treatment with LPS, flagellin, or CpG. A role for IL-12 following the treatments was determined. Results: Intranasal administration of LPS, flagellin, or CpG reduced development of α-GalCer-induced AHR, eosinophilic airway inflammation, and Th1 and Th2 cytokine responses in BAL fluid, while producing IL-12 in BAL fluid. Intraperitoneal administration of IL-12 mAb blocked the suppressive effect of LPS, flagellin, or CpG. In vitro treatment with LPS, flagellin, or CpG reduced production of IL-4 and IFN-γ from α-GalCer-stimulated spleen iNKT cells; these effects were ameliorated by addition of anti-IL-12 mAb. Conclusions: TLR4, 5,and 9 agonists may suppress the function of airway and spleen iNKT cells via IL-12-dependent mechanisms. Anergy of iNKT cells by IL-12 might play a role in suppression by these TLR agonists.

급성 A형 간염에 병발한 급성신부전 2 례

홍수민;박경식;박일권;손형래;구호석;고행일 인제대학교 2011 仁濟醫學 Vol.32 No.-

Hepatitis A is a mild, self-limiting disease of the liver, critical complications of which, such as acute kidney injury, are rare. Two cases of patients with acute hepatitis A who had an acute renal failure complication are reported herein. The first case is that of a 30-year-old man who showed up at the author’s hospital complaining of fever and myalgia. His laboratory tests upon his admission showed 9,520 lU/L of aspartate transaminase, 5,600 lU/L of alanine transaminase, 31.9 mg/dL of blood urea nitrogen, and 5.5 mg/dL of creatinine, and he was positive for the Anti-HAV IgM antibody. Upon his admission, supportive treatment was started, which included fluid therapy. The laboratory tests on the next day showed 53 mg/dL of blood urea nitrogen, 9.9 mg/dL of creatinine, and lower urine output per day. Renal replacement therapy was performed only once. A renal biopsy was performed and the result was Acute Tubular Necrosis (ATN). The patient recovered from acute renal failure without sequela. In the second case, a 35-year-old man complained of fever and abdominal pain. His laboratory tests upon his admission showed 8,570 lU/L of aspartate transaminase, 4,510 lU/L of alanine transaminase, 16 mg/dL of blood urea nitrogen, and 1.19 mg/dL of creatinine, and he was positive for the Anti-HAV IgM antibody. He experienced acute renal failure and recovered after two-time renal replacement therapy. The result of the renal biopsy was Acute Tubular Necrosis and C1q nephropathy.

육안적 혈뇨로 내원한 환자에서 발견된 방광 유전분증 : 증례보고

김은진;성 현;홍수민;정성연;박경식;손형래;박일권;구호석;고행일 인제대학교 백병원 2011 仁濟醫學 Vol.32 No.-

Amyloidosis is a disease resulting in deposition of amyloid in the body. The disease can be either primary or secondary. The amyloidosis of urinary bladder is more usually affected by primary amyloidosis and also very rare. The patient with primary amyloidosis of the bladder usually presents with gross hematuria. The amyloidosis resembles bladder cancer in cystoscopy. It can be confirmed by biopsy. The treatment consists of medication (e.g., steroid, antitumor agent, cholchicine, DMSO) and/or transurethral resection. The standard treatment is mephalan and prednisolone. A 49-year-old man complained of recently developed gross hematuria without abdominal pain. We examined urinary bladder cystoscope for gross hematuria. It revealed small bulging mass on trigone are a of bladder. Therefore we did bladder biopsy. Finally, it revealed bladder amyloidosis. The patient was improved by medication (mephalan 2mg and prednisolone 1 mg/kg po daily). We report an unusual case of amyloidosis involving bladder.

IgA 사구체신염 7예

고행일,남송현,이석호,유원상,이현순,이상국 인제대학교 1980 仁濟醫學 Vol.1 No.2

1979년 7월부터 1980년 6월까지 재발성 혈뇨 및 단백뇨를 갖는 환자를 대상으로 인제의과대학 부속 백병원에서 시행한 43예의 신생검에서 7예가 IgA 사구체 신염으로 증명되었다. 이들은 면역형광학적 검사에서 IgA와 C3가 중등도이상 Mesangium에 침착되었고 전자현미경 검사에서 electron dense deposit가 mesangium에서 발견되는 특징적인 소견을 갖고 있었는데 남녀 비율은 6 : 1로 압도적으로 남자가 많았고 모두 35세 이하의 젊은 사람이었다. 이중 2명은 신증후군과 고혈압을 갖고 있었고 다른 1명은 조직소견상 반월체형을 갖고 있어 예후가 나쁜예는 약 43%에 이르는 것이였고 Mesangium에 침착된 IgA나 C3의 양과 임상경과의 심도와는 관계 없는것 같고 오히려 paramesangium에 보체의 침착이 있는 경우에 신기능의 장해가 있었다. 구치적으로 1예를 제외하고는 모두 광학현미경 소견에서 분절성 혹은 구상 경화증이 있었다. Seven cases of IgA glomerulonephritis were diagnosed by immunopathological criteria during last one year in In-Je Medica1 College with common presentation of persistent or intermmittent hematuria (microscopic or macroscopic) and proteinuria. Immunofluorescent studies of renal biopsy specimens revealed diffuse generalized mesangial deposits of IgA and C3 in all specimens. In four cases diffusemesangial IgG deposits were also seen. Ultrastructural studies of renal biopsy specimens showed accumulation of electron dense material in the mesangium with thickening of its matrix. The fact that seven cases having such glomerular lesions were observed in a period of one year suggests that the condition is not so rare when we have intensive care to it.

원발성 유전분증 1례 보고

고원섭,김용균,전영빈,이윤우,고행일 인제대학교 1990 仁濟醫學 Vol.11 No.3

51세 여자 환자로서 신, 직장조직생검에 의해 원발성 유전분증으로 밝혀진 1례를 문헌 고찰과 함께 보고하는 바이다. A 51-year-old female patient with primary amyloidisis showing huge hepatonegaly & nephrotic syndrome is reported. Amyloidosis was confirmed by renal and biopsy and involvement of heart & liver were suggested clinically.

간신 증후군

고행일 한국의학사 1986 診斷과治療 Vol.6 No.6

정상 혈중 마그네슘치를 갖고 있는 입원환자에서의 마그네슘 결핍의 임상적 평가

고행일,강기혁,하근우,이승진,류정임,노승현 인제대학교 1998 仁濟醫學 Vol.19 No.2

마그네슘은 주로 세포질 내의 효소 작용에 조효소로 작용하는 전해질이므로 혈청내의 마그네슘보다는 체내 총마그네슘치가 더 중요하다고 알려져 있으나 실제 임상적으로 이를 측정하기는 어려운 상태이다. 이에 저자들은 정상 혈중 마그네슘치의 입원 환자를 대상으로 마그네슘 부하 검사를 실시하여 체내 마그네슘 결핍여부를 확인하고 이렇게 확인된 마그네슘 결핍 환자에게 충분한 양의 마그네슘(하루 6g)을 정주 후 나타나는 생물학적 효과를 spirometer에 의한 노력성 호흡능을 측정하여 확인하고자 하였다. Magnesium, the second most abundant intracellular cation next to potassium, has several critically important roles in various enzyme reactions producing energy as a co-factor in the cytoplasm. Only 0.3% of total magnesium is in the extracellular fluid compartment. Moreover, magnesium is distributed unevenly with the greatest concentration in tissues having the highest metabolic activity, such as the brain, heart, liver and kidney. So the portion of intracellular is more important than that of extracellular fluid in the biologic function of magnesium. Because of theses reasons, serum magnesium level may not reflect intracellular magnesium content and the intracellular magnesium depletion may exist despite a normal serum magnesium concentration. Especially the magnesium deficiency with normal serum magnesium is frequently encountered in hospitalized patients and is see most often in patients admitted to intensive care units. The detection of magnesium deficiency can be increased by measuring magnesium concentration in the urine or using the parenteral magnesium loading test. So we designed the study to identify that intravenous 6g magnesium infusion can improve the biologic function which is mediated by intracellular magnesium in 7 hospitalized patients with magnesium deficiency having normal serum magnesium level, diagnosed by more than 50% retention of magnesium in loading test. We measured FEVI and FVC by spirometer to evaluate the biologic influence on respiratory muscle power of before and after magnesium infusion and could available below results. 1.The average retention % of magnesium after loading test was 78.9±15.35%. 2.The serum magnesium and potassium levels after intravenous 6g magnesium infusion were not changed significantly, compared to before the infusion(serum magnesium 1.87±0.33mg/dL vs 2.23±0.55mg/4L, p= 0.14, serum potassium 3.34±0.38mEq/L vs 3.50±0.38mEq/L, p = 0.23). 3.There were no significant urine electrolyte changes between before and after intravenous 6gm magnesium infusion(urine Mg++ 4.33±2.96mg/dL vs 8.07±3.21mg/dL, p=0.056, urine K+ 21.9±14.11mEq/L vs 14.47±6.41mSq/L, p=0.2, urine Ca++ 7.94±10.60mg/dL vs 12.35±11.08mg/dL, p=0.087, urine phosphate 12.63±17.35mg/dL vs 10.20±8.00mg/dL, p=0.61, TTKG 4.99±1.73 vs 4.87±1.43. p=0.81). 4.After intravenous 6g magnesium infusion, the predicted % of FEVI and FVC reflecting effort respiratory capacity become improved significantly, compared to before the infusion (FEV1 79.12±17.75% vs 92.26±16.59%, p=0.025, FVC 73.23±19.38% vs 82.55±18.29%, p = 0.017). In conclusion, normal serum magnesium level can be accompanied by the presence of intracellular magnesium depletion, which can be improved the effort respiratory capacity by the repletion of magnesium.

Poster Session:PS 0552 ; Nephrology : Acute Pyelonephritis in a Patient with Kidney Transplantation Misdiagnosed as Having Acute Rejection

( Seo Young Yun ),( Haeng Il Koh ),( Ho Seok Koo ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Regularly treated with immunosuppressants, maintaining the creatinine levels within 1.5 mg%. In the admission battery, the level of creatinine was increased to 7.74 mg%, and metabolic acidosis was suspected. In addition, his body weight was increased by 7 kg within a week and urine output was decreased. He showed urinary frequency for two days, but there was no tenderness on his graft area. Urinalysis showed 3+ protein, and many WBCs and RBCs. Spot urine protein to creatinine ratio was 3.09 g/ g cr. Ultrasonography exhibited that the size of graft was slightly increased. The renal arterial resistive index was increased by 0.84-0.90, and his cyclosporine level was in therapeutic level. Under the impression of acute rejection, steroid pulse therapy was started together with graft biopsy on hospital day 2. By light microscopy, the graft showed the features of acute pyelonephritis with many pus casts and microabscess. E.coli was isolated in his blood and urine culture. After medical treatments (antibiotic ceftriaxone), the creatinine level was decreased to 2.26 mg% within two months.

안정 혈액투석환자에서 영양지표로서 tCO2의 임상적 의의

노승현,고행일,하근우,강기혁 대한신장학회 1999 Kidney Research and Clinical Practice Vol.18 No.2

Metabolic acidosis is a well-recognized complication of chronic hemodialyzed patients. The metabolic acidosis in stable hemodialyzed patients is mainly resulted from the consequences of the inability to excrete nonvolatile acid and the patients' daily protein intake. So severe metabolic acidosis in patients on hemodialysis is known as an independent determinant of protein catabolic rate and high mortality rate but the moderate degree of metabolic acidosis in stable patients on maintenace hemodialysis can be explained by the patients' nutritional status. On the other hand, patients having adequate daily protein intake could have lower total CO2 levels than those of patients having inadequately lower daily protein intake. To identify this relationship, we analyzed correlations between pre-hemodialysis total CO2 and various factors reflecting the patient's nutritional status in 37 patients on stable hemodialysis. The total CO2 was ranged from 15.6 to 26.5mMol/L. Among various factors, total CO2 had negative linear correlation with normalized protein catabolic rate(nPCR) reflecting the patient's daily protein intake indirectly(Y= -0.0371X+1.75, r=-0.1319, P=0.014). Moreover, metabolic acidosis having CO2 lower than 18mMol/L may modulate protein kinetics as showing steeper slope than those of more than 18mMol/L(Y=-0.1321X+3.342, r2=0.1074 vs Y=-0.03373X+1.7543 r2=0.1001, P=0.0001). However other factors including serum albumin, body mass index, pre-hemodialysis BUN, and Kt/V, had no correlation with the total CO2. The result suggested that moderately lower pre- hemodialysis total CO2 ranging from 18 to 26.5 mMol/L was usually resulted from the high intake of the patient's daily protein intake and should be of no concern in stable patients on maintenance hemodialysis and it may use as a parameter of nutritional status. However metabolic acidosis having CO2 lower than 18mMol/L may modulate protein-kinetics, which may make the protein catabolic rate increased and can not reflect the patient's nutritional status. But should be recommended that further studies should be needed to confirm this factor.

Labetalol의 本態性高血壓에 對한 臨床效科

朴賢夏,高行日,劉元相 인제대학교 1982 仁濟醫學 Vol.3 No.1

本態性高血壓患者 33例를 對象으로 Labetalol (TrandateR) 300∼900mg 經口投與로 60.6%의 降壓效果를 보았으며 副作用으로 起立性低血壓을 少數에서 보였다. The clinical trial conducted on 33 patients with essential hypertension using labetalol during a period of six months in Paik Hospital yielded the following results: Their age ranged from 30 to 76 years c￣ mean 52 years. Eighteen cases were male and 15 cases were female. The daily effective dose were ranged from 300mg to 900mg and duration of medication was from four week to 24 weeks (mean 10 weeks). Twenty (60.6%) of 33 cases showed antihypertensive effect. Among them six (18.2%) exhibited excellent effect, while 14(42.4%) revealed good result. In most of them antihypertensive effect was seen within two weeks trial persisting thereafter as well. As to its side effects, 3 cases complained of orthostatic dizziness and 2 cases difficulties in urination and constipation.