Hepatocyte toll-like receptor 4 mediates lipopolysaccharide-induced hepcidin expression

Hepcidin expression is induced by inflammatory molecules such as lipopolysaccharide (LPS) via a macrophage-mediated pathway. Although hepatocytes directly respond to LPS, the molecular mechanism underlying toll-like receptor (TLR)-dependent hepcidin expression by hepatocytes is mostly unknown. Here we show that LPS can directly induce the mRNA expression and secretion of hepcidin by hepatocytes via TLR4 activation. Using hepatocytes deficient in TLR4, myeloid differentiation factor 88 (MyD88) and TIR domain-containing adaptor inducing interferon-β (TRIF), we demonstrated that LPS-induced hepcidin expression by hepatocytes is regulated by its specific receptor, TLR4, via a MyD88-dependent signaling pathway. Hepcidin promoter activity was significantly increased by MyD88-dependent downstream signaling molecules (interleukin-1 receptor-associated kinase (IRAK) and tumor necrosis factor receptor-associated factor 6 (TRAF6), which activate c-Jun N-terminal kinase (JNK) and activator protein-1 (AP-1). We then confirmed that LPS stimulation induced the phosphorylation of JNK and c-Jun, and observed strong occupancy of the hepcidin promoter by c-Jun. Promoter mutation analysis also identified the AP-1-binding site on the hepcidin promoter. Finally, bone marrow transplantation between wild-type and TLR4 knockout mice revealed that hepatic TLR4-dependent hepcidin expression was comparable to macrophage TLR4-dependent hepcidin expression induced by LPS. Taken together, these results suggest that TLR4 expressed by hepatocytes regulates hepcidin expression via the IRAK–TRAF6–JNK–AP-1 axis.

Antigenic characterization of classical swine fever virus YC11WB isolates from wild boar

Classical swine fever (CSF), a highly contagious disease that affects domestic pigs and wild boar, has serious economic implications. The present study examined the virulence and transmission of CSF virus strain YC11WB (isolated from a wild boar in 2011) in breeding wild boar. Virulence of strain YC11WB in domestic pigs was also examined. Based on the severe clinical signs and high mortality observed among breeding wild boar, the pathogenicity of strain YC11WB resembled that of typical acute CSF. Surprisingly, in contrast to strain SW03 (isolated from breeding pigs in 2003), strain YC11WB showed both acute and strong virulence in breeding pigs. None of three specific monoclonal antibodies (7F2, 7F83, and 6F65) raised against the B/C domain of the SW03 E2 protein bound to the B/C domain of strain YC11WB due to amino acid mutations (⁷²⁰K→R and ⁷²³N→S) in the YC11WB E2 protein. Although strains YC11WB and SW03 belong to subgroup 2.1b, they had different mortality rates in breeding pigs. Thus, if breeding pigs have not developed protective immunity against CSF virus, they may be susceptible to strain YC11WB transmitted by wild boar, resulting in severe economic losses for the pig industry.

Expression and roles of NUPR1 in cholangiocarcinoma cells / 대한해부학회지

Nuclear protein-1 (NUPR1) is a small nuclear protein that is responsive to various stress stimuli. Although NUPR1 has been associated with cancer development, its expression and roles in cholangiocarcinoma have not yet been described. In the present study, we found that NUPR1 was over-expressed in human cholangiocarcinoma tissues, using immunohistochemistry. The role of NUPR1 in cholangiocarcinoma was examined by its specific siRNA. NUPR1 siRNA decreased proliferation, migration and invasion of human cholangiocarcinoma cell lines (HuCCT1 and SNU1196 cells). From these results, we conclude that NUPR1 is over-expressed in cholangiocarcinoma and regulates the proliferation and motility of cancer cells.

The Use of an Implantable Loop Recorder in Patients With Syncope of Unknown Origin

BACKGROUND AND OBJECTIVES: Possible mechanisms of syncope often remain unknown despite the performance of extensive cardiological and neurological tests. An implantable loop recorder (ILR) has been introduced to monitor the heart rhythm continuously over a year. We evaluated the diagnostic value of the use of the ILR for unexplained syncope. SUBJECTS AND METHODS: Between 2006 and 2007, an ILR was implanted in 9 patients (7 male, 2 female, mean age 55+/-17 years) where syncope remained unexplained after extensive diagnostic tests. We analyzed the recorded electrocardiogram signal in the memory of the ILR. RESULTS: During a follow-up period of 8.8+/-7.3 months, arrhythmia was detected in five patients. Two patients had a sinus pause and received a permanent pacemaker, and one patient had sustained ventricular tachycardia and fibrillation and received an implantable cardioverter defibrillator. One patient had micturition syncope with sinus pause and is waiting for permanent pacemaker implantation, and one patient had symptomatic paroxysmal atrial fibrillation and was administered anticoagulation therapy. Inappropriate auto-activations such as a pseudopause or a decreasing signal were also noted. CONCLUSION: ILR monitoring seems to be a useful diagnostic tool to identify the arrhythmic cause in patients with unexplained syncope.

Effects of Halothane and Fentanyl Anesthesia on Coronary Endothelial Endothelin-1 Production During Myocardial Ischemia-Reperfusion in Dogs / 대한마취과학회지

Endothelin(ET), is the most potent endogenous vasoconstrictor. Myocardial ischemia and chemical stimuli including calcium ionophores are known to release ET-1. Recently, halothane has been shown to block calcium channel. Thus, halothane might attenuate coronary endothelial ET-1 production during myocardial ischemia-reperfusion. To test this hypothesis, we measured plasma ET-1 level continuously in open chest dogs subjected to 15 min of left anterior coronary arterial occlusion and 1 hour of reperfusion during fentanly(n=8) or halothane(n=7) anesthesia. The results were as follows. I) Baseline ET-1 levels of both femoral artery and great cardiac vein in the halothane group were lower than in the fentanly group(NS). 2) ET-1 level of femoral artery and great coronary vein in both halothane and fentanyl group remained unchanged 10 min into ischemia. 3) Coronary blood flow increased by 325, 250% in the halothane group and by 315, 258% in the fentanly group 2, 5 min into reperfusion, respectively. 4) ET-1 production increased from baseline of -2.9+/-1.7 pg/min to 66.0+/-21.5(p<0.05), 20.8+/-5.1 (p<0.01), 13.2+/-6.2(p<0.05) pg/min 5, 15, 30 min into reperfusion, respectively in the fentanyl group, but it remained unchanged from baseline of 0.8+/-3.1 pg/min in the halothane group. These findings suggest that ET-1 production or release is diminished by halothane during myocardial ischemia-reperfusion. Thus, halothane provides an advantage over fentanyl in patients with myocarial ischemic episodes.

Effects of Intravenous Verapamil on Hemodynamics and Pulmonary Gas Exchanges in Isoflurane-N2O-O2 Anesthetized Man / 대한마취과학회지

The purpose of this study was to evaluate the effects of verapamil on hemodynamics and pulmonary gas exchanges during isoflurane-N2O-O2(FIO2, 50%) anesthesia. Hemodynamic measurements and arterial and mixed venous blood gas analyses were made in thirteen healthy patients immediately before (control) and at 1, 5,10min after 5mg of intravenous verapamil administration as single bolus. 1) Verapamil produced a rapid and transient reduction of 15% in mean arterial pressure resulting from a decrease in systemic vascular resistance. 2) Heart rate and cardiac index increased by 14%, 9% respectively only immediately after i.v. verapamil injection and restored thereafter toward control values. 3) SVI, MPAP, PCWP, PVR and CVP revealed only minor changes. 4) Verapamil did not cause any significant changes in intrapulmonary shunt. These findings suggest that during isoflurane-N2O-O2(50%) anesthesia verapamil might safely be used, even in the presence of ventilation/perfusion inequalities, (i.e. lung disease, one lung anesthesia) provided patient has good cardiovascular reserve.

Psychological Study of Leprosy Patients: III . Ambulatory Patients / 대한피부과학회지

Many factors including social rejection, family problems, loss of educational opportunity, fear, prejudice and ignorance, compound the inherent paychologicaI stress of leprosy. In ligh.t of these problems this present study was undertaken to evaluate the psychologica.l status of 1cprosy patients. The subjects of the present study were 220 patients staying at home and 304 control people living in similar isolated areas to resettlemert villages. A self reprort symptom inventory,, SCL--90 symptom check list 90) was used and the group", were analysed and compand by many factors. The results of this study are follows. -countinue-

A Study of Finger Prints in Normal Korean People / 대한피부과학회지

The skin in the palmar and plantar surface of the human hand and foot is corrugated with narrow ridges; the ridges form definite local designs o the terminal segments of digits and in consistant sites on the palm and sole. Dermatoglyphics collectively means the features of epidermal ridges and the study of these ridges as well as the pattems formed by them, and is useful in personal identification, twin identification, human biology, syudies of genetics and diagnosis of some diseases. Two thougand normal Koreans(1,000 males and 1,000 females) were examined forpattem type of finger prints to establish the dermatoglyphics of the Korean perple, and the following results were obtained. Men had whorls 49.89%, ulnar loops 44.53%, radial loops 3.10%, arches 2.49%; women had whorls 43.42%, ulnar loops 51.16% radial loops 2.24%, arches 3.20%. On the average, whorls were present 46.65%, ulnar loops 47.83%, radial loops. 2.68% and arches 2.84. Pattem intensity (the number of triadii per individual) was 14.381. Of all the men and women examined, 16.65% and 14.89% respectively had pattems of the same type(whorls, loops, arches) on all ten fingers. Of those men. 10.55% had only whorls, 6.0% only loops. In my test group, 15,78% had 10 pattems of the same type, 16.01% had 9 pattems of the same type and 20.57% had 9 pattems of the same type. Only 8.17% bore pattems of all main 3 types. Monomorphic hands of which all 5 fingers bore the same pattem type were 27.79% of Rt hands and 26.93% of Lt hands. In compatison of couplets composed of homologous fingers, the approximate incidences of symmetry in single figers ranged from 73% to 82%. Symmetry in individuals was complete in 32.99% and the diminishing frequencies of unlike pattem types on one, two, three, four and five digital couplets were, respectively:37.29%, 21.02%, 7.57%, 1.07% and 0.05%

Evaluation of Effectiveness of Low-dose-Longterm Vibramycin on Acne Vulgaris with Double-blind Study / 대한피부과학회지

In order to evaluate the the effectiveness of low-dose longterm Vibramycin (Doxycycline) treatment on Acne Vulgaris, a double-blind study was performed on fifty two patients with Acne Vulgaris. The patients were classified as to the severi.ty of their disease before treatment according to Wand. et al. The degree of the effcctiveness of the treatment was evaluated every other week for 12 weeks on the grounds of clinical improvement. The therapeutic results obtaincd were as follovs: araong the 19 patients who received 50 mg per day for 12 weeks, 13 cases (72.2%) showed excellent improverrent after 6 weeks; whereas in thc placebo group only 4 out of 15 patients (26. 7%) showed good response, Statistical analysis of the data revealed that there was a significant difference (p<0.05) in effectiveness between the Vibrarzycin 50mg per day group and the placebo group. Among the 19 patient who received a 100mg capsile orally per day for 4 weeks (subsequently this group received 50mg per day for 8 weeks) 13 cases.(68.4%) showed excellent improvement in 4 weeks; whereas in the placebo group only 4 cases(26, 7%) showed good respnnse Statistical analysis of this data revealed that there was a significant difference (p<0. 05) in efectivencess the Vibramycin 100mg per day group and the placebo group, It was noted that 44 out of 52 patients (83%) had a distinct family history of the disease, suggesting that there might be a predisposing hereditary factor involvcd in the manifestation of Acne Vulgaris It is concluded f rom this study that Vibramycin, when administrated in a dose of 50mg per day for more than 6 weeks is effective in the treatment of Acne Vulgaris.

Studies in Etiological Organisms of Mycotic Infection of the Feet : 1 . Dermatophytes infection of the feet / 대한피부과학회지

Dermatophytosis of the feet, i.e. tinea pedis, is one of the most frequent fungal infections and is caused by a dermatophyte. There are many predisposing factors to the disease such as living or environmental conditions; underlying endocrine or metabolic diseases, complicated individual immune mechanisms, long-term use of adrenocorticosteroids, antibiotics or other drugs and feet, per se, succeptable to infection of the organism by physio-anatomical condition. The authors performed clinical and mycological studies on 225 outpatients visiting the dermatological clinic of Chonnam University Hospital from April to September in 1977, who had clinical evidence of tinea pedis, dermatophytes infection of the feet. The incidence of tinea pedis was 8.9% of the whole 2531 out-patients who visited our clinic during that time. Of the 225 patients, the male patients were53%, the female patients 47%, and patients living in urban areas were affected about 2 times more frequently than those living in rural areas. The age distribution of the patients varied from 5 to 68 years old, but the most of them were in their third decade, at an actively working age. Concurreat infection with tinea pedis and other dermatophytosis was noted in 106 patients (47.1%). The patients with T. pedis and manus were most commonly observed, and the incidence of concurrent infection with T. pedis and T. manus was 31%;, T. cruris 19.8%, onychomycosis 17.0%, and with T. corporis 10.4% respectively. Id reaction or autoeczemation to the disease itself and inadequate or over treatment dermatitis developed in 19 patient*8.4%). It happened more in patients with tinea pedis alone than in thos with concurrent infection, but there was no difference between sexes. The positive rate of 10%. KOH mount was 59% in 173 preparations. The culture rate was about 7 times higher in the KOH positive group than in the negative group. Among the 39 strains of dermatophytes isolated by Sabouraud's dextrose agermedia from 111 patients and identified by 1% dextrose com meal agar media, bloo3 agar media and hair culture method, T. rubrum were 28 strains (71.l%) and T. mentagrophytes were 11 strains (28. 2%) The straivs of all noted hair perforation did not produce the pigmentation on 1% dextrose com meal agar media, and the strains which produced pigmentation on 1% dextrose com meal agar media did not perforate hair in hair culture. We cultured fungi from each lesion of 3 patients with concurrent infection of T.pedis, T.cruris, T.corporis, and dbtained T.rubrum only in all lesions of each patient. Upon making this observation, we presumed concurrent infection generally to be autoinoculation from one to another part.

A Mycological and Epidemiological Study of Otomycosis / 대한피부과학회지

As increasing numbers of antibiotics, adrenocorticosteroids, and antitumor agents have come into use, so increasing numbars of mycotic diseases have been identified. Qtomycosis, a mycotic infection of the extcrnal ear which is occasionally accompanied by dermatitis of the surrounding skin, is corsidered to be such a disease. While opinion vari.es as to whether otomycosis is caused by a saprophytic or a pathogenic organism, our clinical obs:rvations revealed pathological inflammation of the external auditory canal with profuse fungal elements. During August 1975, l3 specimens of ear wax were taken from patients whv visited the out-patient ENT clinic of this hospital. All patients had had their ears clea,ned at a barber shop prior to visiting the ENT clinic. Because ar cleaning instrumenta (scoops and brushes) are re-used m Korean Sarber shops, 204 of theae in- strum.ent;s were randomly selected from different barber shops and examined. KGH mounts and Lactophenol cot@ten blue stains were used to examine the specimens. Qf the lR ear wax specimens, I2 samples (92. 3%) reveaIed Aspergillus sp. and 1 sample (7. 7%) revealed Penicillium sp. Of the 204 ear cleaning instrumenta tested, l94 colonies grew in culture. Of these cultures, 146 (75. 3 %) were Aspergillus sp., 9 (4. 6%) were Mycelia sterila, 5 (2. 6%) were Fenicillium sp., 4 (2. 1 %) wr Al- terna,ria, 2 (l. 0%) were Stemphylium sp., 1 (0. 5%) was Geotrichum sp., and 27 (13. 9%) were of an unknown species. Of the 146 Aspergillius sp. cultures, 99 (67. 8%) were Asp. terreus, 17 (11.6%) were Asp. glaucus, 5 (3.4%) were Asp. niger, 17 (11. 6%) were Asp. flavus-oryzRC, R (2. 1 %) Were Asp. versicolor, and 5 (3. 4 %) were athers. Beca.use of the close correlation between the fungi cultivated from ear wax apc imens and those cultured from ea,r cleaning instruments, the authors believe that the ear cleaning instruments used in the barber shops could well have been the primary source of infection. In this study the authors also discuss the probable causative factbrs of otomycosis arrd a review of the literature is presented.

Double - Blind Evaluation of the Effectiveness of Vibramycin to Acne Vulgaris / 대한피부과학회지

In order to evaluate the effectiveness of Vibramycin (Doxycycline) to acne vulgaris, a double-blind study was performed in forty three patients of ance vulgaris. The patients were classified as to the severity of the disease before the treatment according to Wand, et al. and the degree of the effectiveness was evaluated weekly by Clinical improvement. The results obtained were as follows: Among 14 patients who received a 100mg capsule orally per day for four weeks, 12 cases (85.7%) showed excellent improvement, whereas in the placebo group only 4 out of 12 patients (33.3%) showed good responses. Statistical analysis of the data revealed that there was a significant difference (P<0.05) in effectiveness between the Vibramycin group (100mg) and the placebo group, and that at the end of the first week of the treatment there was no significant improvement, but at the end of the third week there was a highly significant improvement, p_value between the first-week response and the third-week response among the patients in administering 100mg of Vibramycin being less than 0.01. It was noted that 24 out of 43 patients(55.8%) had a distint familial history of the disease, suggesting that there might be a predisposing factor involved in the manifestation of acne vulgris. It is concluded from this study that Vibramycin, when administered in dose of 100mg per day for more than three weeks, is effective in improving the acne vulgaris.