Aeromonas hydrophila에 의해 생산되는 세포외 효소와 백서 복강내 비만세포의 histamine 유리

박석돈,고정운,전병득,오선희,송창호,고명옥 ( Seok Don Park,Jung Woon Ko,Byung Deuk Jeon,Seon Hee Oh,Chang Ho Song,Myoung Ok Koh ) 대한피부과학회 1991 대한피부과학회지 Vol.29 No.6

N/A Aeromonas hydrophila is a facultatively anaerobic, gram-negative rod which has been often regarded as an opportunistic pathogen in hosts with compromised defense mechanisms. A. hydrophila can produce septicemia with skin lesions such as necrosis, edema, and blisters. Therefore, it is necessary to investigate what kinds of exocellular ?oxic or pathogenic factors are produced by A. hydrophila for elucidation of pathogenesis and effective treatment. This study was designed to determine the extracellular enzymes produced by two strains of A. hydrophila which were isolated from the blood and wound of patients with septicemia and osteomyelitis, respectively. Histamine release from rat peritoneal mast cells evoked by A. hydrophila culture supernatant was assayed. The morphologica changes of rat peritoneal mast cells treated with A. hydrophila culture supernatant were observed by electron microscopy. A. hydrophila produced elastease, protease DNase, hemolysin(alpha and beta), lipase, lecithinase, and gelatinase but it did not produce coagulase, hyaluron dase, chondroitin sulfatase or mucinase. The culture supernatant fluid of A. hydrophila induced aistamine release from rat peritoneal mast cells. Transmission electron microscopic studies of mast cells treated with the culture supernatant revealed microvesicles of various size in the cytoplasm and around the cell membrane. These findings suggest that A. hydrophila culture supernatant induces histamine release from rat peritoneal mast cells by a process that may involve a resicular transport mechanism, namely, piecemeal secretion.

흰쥐에 대한 생옻의 생물학적 효과

원태혁 ( Tai Hyok Won ),서필승 ( Phil Seung Seo ),박석돈 ( Seok Don Park ) 대한피부과학회 2009 大韓皮膚科學會誌 Vol.47 No.3

Background: Exposure to Rhus (Japanese lacquer) can cause many adverse effects such as contact dermatitis, pruritus, rash and even hepatitis in human, and these effects can be caused by contact or ingestion of Japanese lacquer. Many Koreans currently eat Japanese lacquer boiled with chicken although it has many side effects. Koreans believe that Rhus will improve their health. However, they don`t known its adverse effects, and there is no experimental report on this topic. Objective: The principle objective of this study was to gather evidence on the toxicity and negative effects of Japanese lacquer through an experimental study with rats. Methods: A total of 60 Sprague-Dawley rats were included in the study; 30 rats (experimental group) were given 0.1 ml of Japanese lacquer sap extract, water and food, and 30 rats (control group) were given only food and water. The WBC, the Hgb, ALT, AST, BUN and creatinine levels, the presence of pruritis and skin eruption, the skin biopsy findings and the liver biopsy findings were all checked at 5, 10, and 15 days. Results: The rats that were given Japanese lacquer sap showed a higher WBC and higher ALT and AST levels and only these rats demonstrated erythroderma (5th day: 30%, 10th day: 40%, 15th day: 70%). In addition, they exhibited frequently scratching behavior. On histological examination of the skin of the rats given Rhus, dermal edema and mild inflammatory cell infiltration were found. On histological examination of the liver of the rats given Rhus, there was no significant change as compared with the rats that weren`t given lacquer. Conclusion: In this experimental study, it was proven that Rhus could induce pruritis, erythroderma, skin inflammation and hepatotoxicity. (Korean J Dermatol 2009;47(3):251∼258)

Vibrio vulnificus cytolysin에 의하여 유발된 전신 Shwartzman 반응에 있어서 cytokines(IL-12, IFN- )의 역할

박석돈(Seok Don Park),김동림(Dong Lim Kim),이상원(Sang Won Lee),전재훈(Jae Hoon Chun),차승훈(Seung Hoon Cha) 대한피부과학회 2000 大韓皮膚科學會誌 Vol.38 No.5

N/A Background:Knowledge of the pathogenetic mechanism for the activation of the coagulation system (disseminated intravascular coagulation, DIC) associated with V. vulnificus infection is important for the development of improved modalities for prevention and treatment. The use of experimental model of DIC (generalized Shwartzman reaction, GSR) induced by toxins and cytokines in mice has partly elucidated the pathogenetic pathways that are involved in the development of DIC in septic patients Objective:The purpose of this study was to investigate the role of cytokines (IL-12, IFN-γ) in the pathogenesis of the GSR induced by V. vulnificus cytolysin. Methods:Generally the GSR was elicited by two consecutive injections of V. vulnificus cytolysin. The priming cytolysin intradermal injection was replaced with recombinant murine IL-12 (0.25 or 0.5㎍) and recombinant murine IFN-γ (5 or 10㎍), respectively and was followed by 24 hr later by the cytolysin (1-3 hemolytic units) intravenous challenge injection. The occurrence of GSR was evaluated by mortality rate within 3 days. The death time measured. The gross and histopathological findings of various vital organs were examined shortly after death. Results:When mice were primed with 0.5㎍ IL-12 and challenged 24 hr later with cytolysin, they died completely within 13 hr. This priming effect of IL-12 and provocative effect of cytolysin were dose-dependent. All the mice primed intradermally with IFN-γ(10㎍) died within 9 hr. The priming effect of IFN-γ was dose-dependent. In the gross and histopathologic examinations of various organs in dead mice, pathologic changes were observed mainly in the lungs.Conclusion:These results suggest that the pathomechanisms of V. vulnificus cytolysin-induced lethal GSR in mice is dependent upon IFN-γ synthesis triggered by cytolysin-induced IL-12 production. (Korean J Dermatol 2000;38(5):622~628)

Vibrio vulnificus 패혈증의 역학적 연구

박석돈 ( Seok Don Park ),김현대 ( Hyun Dai Kim ),원태혁 ( Tai Hyok Won ),서필승 ( Phil Seung Seo ) 대한피부과학회 2008 대한피부과학회지 Vol.46 No.2

Background: Vibrio vulnificus is an estuarine bacterium which is capable of causing rapidly fatal infections in humans following either ingestion of raw seafoods or entry from seawater into wounds. Although V. vulnificus sepsis (called as Vibrio sepsis) has been well known in Korea since 1982 and was designated as a legal communicable disease (group III) since August 2000, many patients occurr annually. Objective: We investigated the epidemiological features of Vibrio sepsis to offer basic data such as correlation among disease occurrence, seawater temperature, salinity and pH, amount of rainfall, incidence rate and consumed seafoods, in order to further prevent this disease. Methods: We reviewed the epidemiologic data on monthly disease occurrence, history of raw seafood consumption and kinds of consumed seafoods in 141 patients with Vibrio sepsis obtained from 105 admitted patients in hospitals and 36 case reports published in the Korean medical journals between 1982 and 2004. Environmental data on seawater temperature, salinity and pH were obtained from the National Fisheries Research & Development Institute. The monthly amount of rainfall was obtained from the Korea Meteorological Administration. The yearly occurrence of Vibrio vulnificus regional areas was obtained from the Korea Center for Disease Control & Prevention. Population data were obtained from the Korea National Statistical Office. Results: Patients began to develop in June when mean seawater temperature was over 18.9oC, and with a peak from July to September when seawater temperature was over 22oC. The majority of the patients were found in the southern and western coastal areas of Korea, especially, estuaries, where sea mud is abundant. Also disease occurrence was positively correlated with the amount of rainfall which can lower the salt concentration of seawater. Yearly occurrence of patients by regional area was the highest in the Jellanam-do during the 5 years since August 2000. The incidence rates per 100,000 population were highest in the Jellanam-do (0.69), lowest in the Jeju-do (0.01) and 0.10 in the whole areas. Seventy two percent of patients ingested 38 kinds of seafoods raw such as blue crab, goby, blood ark shell and many kinds of fishes and shellfishes. 9% of patients had not eaten seafood and 17% had either no records or unknown. 2% developed sepsis resulted from exposure of wounds to seawater. Conclusion: Vibrio sepsis develops in summer months with much rain and mostly in the estuaries. These results suggest that Vibrio vulnificus multiply well in the warm and in relatively low salt seawater. We think that weather, environmental and geographic factors are important for the outbreak of Vibrio sepsis. (Korean J Dermatol 2008; 46(2):171∼180)

Vibrio vulnificus 감염증

박석돈 (Seok Don Park) 대한피부과학회 1993 대한피부과학회지 Vol.31 No.3

Vibrio vulntficus is a halophilic, gram-negative, motile, marine rod tha is capable of causing rapidly progressing, life-threatening infection in human. The illnesses associated with this organism can be categorized clinically as four groups such as wound infection, primary sept cemia, gastrointestinal illness, and other infection. The clinica1 manifestation of patients with primarys pticemia can vary from fever and chills alone to a more severe illness including secondary skin lesions, multisystem organ failure and shock. Several skin lesions are found in patients with this septicemia, including edema, blister, gangrene, localized swelling, and papura and, less comrnonly, cyanosis, maule and patch, papule, wheal, and pustule. The cutaneous lesions appear mostly on the legs. The hist pathologic findings differ according to the clinieal stage(inflammatory, bullous, and gangrenous) of the lesions. Mortality is very high. The organism is isolated mostly from skin lesion and/or blood. Vibrio vulnifices is sensitive to chloramphenicol, gentamicin, tubramycin, tetracycline, and 3rd generation cephalosporins. Most cases occur during the summer montlis, in men and in person 40 or more year of age. The illness begin with septicemia, often within 2 days of the consumption of various kinds of raw seafood such as fish, shell- fish, and brown seaweed. Patierts frequently have preexisting liver diseae and/or alcohol abuse. For prevention of Vibrio vulni ficus infections, persons with liver diseases or alcohol abuse should avoid consuming or handling raw seafood. Clinicians should start appropriate therapy promptly in patients with chronic underlying disease and a recent history of raw seafood con umption who present with unexplained febrile illness. (Kor J Dermatol 1993; 31(3): 289-304)

Vibrio vulnificus 패혈증의 임상적 연구

박석돈 ( Seok Don Park ),이재영 ( Jae Young Lee ),김현대 ( Hyun Dai Kim ),윤녕훈 ( Nyung Hoon Yoon ) 대한피부과학회 2006 대한피부과학회지 Vol.44 No.6

Background: Vibrio (V.) vulnificus is a pathogenic marine bacterium that can cause rapid progression of a life-threatening infection. Although V. vulnificus sepsis is well-known to Koreans and was designated as a legal communicable disease in August 2000, many people still become infected each year. Objective: The purpose of this study was to investigate the clinical features of V. vulnificus sepsis, in order to offer basic data for the treatment and prevention of this disease. Methods: We reviewed the available data of 141 patients with V. vulnificus sepsis, which were obtained from 105 patients admitted to hospital and 36 case reports published in the Korean medical journals between 1982 and 2004. Results: Eighty-five percent of patients were 40 to 60 years old. Men were affected 10.5 times more often than women. Patients with underlying chronic diseases (94%) such as alcohol abuse and liver diseases displayed primary sepsis starting with fever, chills, and/or diarrhea, often within 2.3 days of consumption of various kinds of raw seafood. Skin lesions appeared initially as a painful, localized swelling like a bee-sting, followed by edema, blisters, purpura, necrosis and, less commonly, maculopatch, cyanosis, papules, wheals, pustules or erythema multiforme-like lesions. The cutaneous lesions that were present in 91.5% of patients on admission, appeared on the lower extremities in 88.9% of the cases. Of the 141 patients, 88 patients (62.4%) died. The mortality rate increased as initiation of treatment was delayed. Laboratory findings revealed thrombocytopenia and elevated levels of liver enzymes in many tested cases. V. vulnificus was cultivated more easily from the skin lesion (95%) than blood (69%). There were significant differences in systolic blood pressure, leukocyte count and creatinine between survivors and nonsurvivors (p<0.05). V. vulnificus was highly susceptible to several kinds of antibiotics such as ampicillin, ciprofloxacin, and 3rd generation cephalosporins. Mortality rate increased as the delay from the onset of illness to the initiation of treatment was prolonged. Conclusion: Clinicians should promptly initiate appropriate therapy for patients with underlying chronic disease if they exhibit unexplained fever and diarrhea after ingesting raw seafood. (Korean J Dermatol 2006;44(6):696~707)

Vibrio Vulnificus 세포용해소에 의한 마우스 독혈증시 Cytokine ( TNF - α , IL - β , IL - 6 ) 의 변화

박석돈 ( Seok Don Park ),김주섭 ( Ju Seob Kim ),차승훈 ( Seung Hoon Cha ) 대한피부과학회 1998 大韓皮膚科學會誌 Vol.36 No.1

Background: Cytokines such as TNF-a, and IL-1, 6, 8 are thought to mediate many host responses in patients with sepsis through the release of many kinds of inflammatory mediators. Vibrio vulnificus is a virulent, halophilic, marine, and Gram-negative bacterium causing wound infections or primary sepsis with fulminant course. It has been known to produce many exocellular factors, such as cytolysin and exozymes, which are possible causes of shock and tissue damage. Objective : Our purpose was to investigate the changes of cytokines(TNF-a, Il-l p, and IL-6) after intravenous administration of V. vulnificus cytolysin which have known to be a major virulent factor for elucidating pathogenesis of septic shock. Methods : After administration of V. vulnificus cytolysin(20 hemolytic units) and physiologic saline through a mouse tail vein, we obtained blood samples from the heart according to a time course(0, 30, 60, 90, 120, 240, and 360 minutes). We measured serum concentrations of circulating TNF- a, IL-1 p, and IL-6 using commercially available immunoassay kits. Results . The serum concentration of TNF- a peaked at 60 min (1894 pg/ml, as compared with 829 pg/ml after saline administration), began to decrease at 90 min and fell to baseline at 360min. Concentration of IL-6 rose significantly at 90 min(>3,839 pg/ml) and began to decrease at 120 min, whereas the level of IL-1 0 increased slightly and the peaked around 90min(117 pg/ml) after the cytolysin injection. Conclusion: We conclude that the host response to cytolysin is associated with a brief pulse of circulating cytokines in the early stage of sepsis caused by V. vulnipcus infection. (Korean J Dermatol 1998;36(1): 23-29)

Mycobacterium leprae , M . lepreae Phenolic Glycolipid - 1 및 Cytokine 이 RAW 264 . 7 대식세포의 Nitric Oxide 생성에 미치는 영향

박석돈(Seok Don Park),이재승(Jae Sung Lee),이복수(Bok Soo Lee),전창덕(Chang Duk Jun),정헌택(Hun Taeg Chung),김종구(Jong Gu Kim) 대한피부과학회 1994 대한피부과학회지 Vol.32 No.2

Background: Nitric oxide(NO) has been reproted to play an important role in macrophage-mediated microbicidal capacity for a variety of intracellular pathogens. NO generation is used as an indicator of microbicidal function of macrophages. Objective : Our purpose is to investigate the production of NO rom macrophages phagocytized with Mycobacterium leprae or M. leprae phenolic glycolipid-1(PGL-1) for the purpose of elucidating the pathogenesis of leprosy. Methods : We used a murine macrophage cell line, RAW 264.7. Macrophages were incubated with dead M. leprae or PGL-1, respectively and then treated with interfer n-gamma(IFN-r) and/or tumor necrosis factor-alpha(TNF-a). The release of NO was determined spectrophotometrically by measuring nitrite. Results : M. Leprae and PGL-1 failed to stimulnte NO secretion execept at high bacteria-to-cell rations(50:1)and at the higheat concentrat,ion(100pg/ml) of PGL-1. IFN-r or IFN-r plus TNF-a markedly stimulated macrophages phagocyt,ized with M. leprae or PGL-1 to release NO . Conclusion : Defective IFN-r-dependent NO production of macrophages may be an important factor in the pathogenesis of leprosy. (Kor J Dermatol 1994 ; 32(1), 234-244)

수소이온 농도가 Vibrio vulnificus 성장에 미치는 영향

박석돈(Seok Don Park),손형선(Hyung Sun Sohn),고정운(Jung Woon Ko) 대한피부과학회 1986 대한피부과학회지 Vol.24 No.3

Using the 8 strains of Vibrio vulnificus isolated from the patients with prim- ary sepsis, the viability of Vibrio vulnificus were studied in the various range of hydrogen ion concentration. The opitimal pH range of growth was 7-9, and survived between pH 3. 6 and 12. 5 when incubated at 37C for one hour.

Phenol - Chloroform - Petroleum ether 법을 이용한 Vibrio vulnificus lipopolysaccharide의 추출 및 생물학적 활성 측정

김주섭,박석돈 ( Ju Seob Kim,Seok Don Park ) 대한피부과학회 1997 대한피부과학회지 Vol.35 No.4

Background: Vibrio vulnificus is a pathogenic, marine, halophilic, gram-negative bacillus which causes fulminant infecticn in humans through the ingestion of raw seafood or skin wounds. V. vulnificus produces seveal kinds of virulent factors including cytolysin, endotoxin, exoenzymes, and siderphores. Among these, the lipopolysaccharide(LPS) of V. vulnificus has recently been purified, but the biological activity of this endotoxin is not well clarified as yet. Objective : The purpose of this study was to extract LPS from Vibrio vulnificus and to test the biological activity of extracted LPS for the elucidation of the role in V. vulnificas septicemia. Methods : V. vulnificus LPS was extracted by the Phenol Chloroform-Petroleurn ether(PCP) method. The biological activity of LPS was evaluated with a limulus amebocyte lysate assay and by assessment of lethality to ICR mice. Results : Five hundreds mg of LPS were extracted from 10g of dried V. vulnificus. Lirnulus amebocyte lysate formed a hard gel in response to the extracted LPS. This LPS showed low level of protein contaminatior in SDS-PAGE electophoresis and spectrophotometry. A High dose of LPS(200 mg/ml body weight) was lethal to mice. Conclusion : The PCP extraction yield relatively large amounts of LPS from V. vnlnificus. with out significant protein contamination and e xtrated LPS has endotoxin activity. This extrated LPS can be used for further studies such as making antibody or characterizing pathogenic roles in the V. vulnificus infection. (Kor J Dermatol 1997;35(4): 645-650)