The increasing prevalence of Toxoplasma gondii infection in the human population in the Republic of Korea (= Korea) is due to various reasons such as an increase in meat consumption. However, the importance of cats in transmitting T. gondii infection through oocysts to humans has seldom been assessed. A total of 300 fecal samples of stray cats captured around Seoul from June to August 2013 were examined for T. gondii B1 gene (indicating the presence of oocysts) using nested-PCR. Fourteen (4.7%) of 300 cats examined were positive for B1 gene. Female cats (7.5%) showed a higher prevalence than male cats (1.4%). Cats younger than 3 months (5.5%) showed a higher prevalence than cats (1.5%) older than 3 months. For laboratory passage of the positive samples, the fecal suspension (0.2 ml) of B1 gene positive cats was orally inoculated into experimental mice. Brain tissues of the mice were obtained after 40 days and examined for the presence of tissue cysts. Two isolates were successfully passaged (designated KNIH-1 and KNIH-2) and were molecularly analyzed using the SAG5D and SAG5E gene sequences. The SAG5D and SAG5E gene sequences showed high homologies with the ME49 strain (less virulent strain). The results indicated the importance of stray cats in transmitting T. gondii to humans in Korea, as revealed by detection of B1 gene in fecal samples. T. gondii isolates from cats were successfully passaged in the laboratory for the first time in Korea.
Animals ; Cat Diseases/diagnosis/epidemiology/*parasitology ; Cats ; Feces/*parasitology ; Female ; Genotype ; Humans ; Male ; Mice ; Protozoan Proteins/genetics ; Seoul/epidemiology ; Toxoplasma/genetics/*isolation & purification ; Toxoplasmosis/epidemiology/parasitology/transmission ; Toxoplasmosis, Animal/diagnosis/epidemiology/*parasitology

Immunogenicity of dendritic cell-derived exosomes stimulated with Toxoplasma gondii lysates (TLA exo), mixed with cholera toxin as an adjuvant, was investigated in mice immunized via 2 mucosal routes (ocular vs intranasal). BALB/c mice were injected 3 times with TLA exo vaccine at 2 week interval, and the levels of IgG in serum and IgA in tear, saliva, feces, and vaginal wash were measured. To observe the expression of T. gondii-specific B1 gene, mice infected with ME49 T. gondii cysts were immunized with TLA exo or PBS exo (not stimulated with TLA), and their brain tissues were examined. The mice vaccinated via intranasal route elicited significantly higher humoral and mucosal immune responses compared with mice treated with PBS alone. Also, mice immunized via ocular route (by eyedrop) induced significantly higher T. gondii-specific IgG in serum and IgA in tear and feces in comparison with PBS controls. B1 gene expression was significantly lower in TLA exo vaccinated mice than in PBS or PBS exo vaccinated mice. These results demonstrated that ocular immunization of mice with TLA exo vaccine has the potential to stimulate systemic or local antibody responses. This study also highlighted an advantage of an eyedrop vaccine as an alternative for T. gondii intranasal vaccines.

BACKGROUND: Time to first cigarette after waking is an indicator of nicotine dependence. We aimed to identify the association between time to first cigarette and spirometry-proven obstructive respiratory impairment, especially chronic obstructive pulmonary disease, in current smokers. METHODS: We included 392 subjects who visited the comprehensive medical examination center of Hallym University Sacred Heart Hospital between July 2014 and September 2015. Subjects with lung disease or anemia were excluded. Obstructive pulmonary impairment was defined as < 70% of the predicted value of forced expiratory volume in 1 second/forced vital capacity. Subjects were classified into the early (≤30 minutes) and late (>30 minutes) groups based on the time to first cigarette. Logistic regression and linear regression analyses were used for data analysis. RESULTS: Ninety-eight subjects (25%) were classified into the early group. After adjusting for smoking behaviors (cigarettes per day and smoking duration), socioeconomic status (education and income), age, and physical activity, an early time to first cigarette was found to be associated with an increased risk of obstructive pulmonary impairment measured using spirometry (adjusted odds ratio, 2.84; 95% confidence interval, 1.22–6.61). CONCLUSION: Compared to current smokers with a late time to first cigarette, those with an early time to first cigarette had a higher risk of obstructive pulmonary impairment, especially chronic obstructive pulmonary disease. Classifying smoking-related behaviors, especially time to first cigarette, may help target clinical screening for chronic obstructive pulmonary disease.
Anemia ; Forced Expiratory Volume ; Heart ; Linear Models ; Logistic Models ; Lung Diseases ; Mass Screening ; Motor Activity ; Odds Ratio ; Pulmonary Disease, Chronic Obstructive* ; Respiratory Function Tests ; Smoke ; Smoking ; Social Class ; Spirometry* ; Statistics as Topic ; Tobacco Products* ; Tobacco Use Disorder ; Vital Capacity

Anisakiasis is a zoonotic disease induced by anisakid nematodes, and endoscopic inspection is used for a diagnosis or remedy for it. Anisakis simplex, Anisakis physeteris, and Pseudoterranova decipiens had been reported to be the major species causing human infections, particularly, in Japan. However, in Korea, recent studies strongly suggested that Anisakis pegreffii is the major species of human infections. To support this suggestion, we collected anisakid larvae (n=20) from 20 human patients who were undergone gastrointestinal endoscopy at a health check-up center in Korea, and molecular identification was performed on the larvae using PCR-RFLP analysis and gene sequencing of rDNA ITS regions and mtDNA cox2. In addition, anisakid larvae (n=53) collected from the sea eel (Astroconger myriaster) were also examined for comparison with those extracted from humans. The results showed that all human samples (100%) were identified as A. pegreffii, whereas 90.7% of the samples from the sea eel were A. pegreffii with the remaining 9.3% being Hysterothylacium aduncum. Our study confirmed that A. pegreffii is the predominant species causing human anisakiasis in Korea, and this seems to be due to the predominance of this larval type in the fish (sea eels) popularly consumed by the Korean people. The possibility of human infection with H. aduncum in Korea is also suggested.
Anisakiasis ; Anisakis ; Diagnosis ; DNA, Mitochondrial ; DNA, Ribosomal ; Eels ; Endoscopy, Gastrointestinal ; Humans ; Japan ; Korea ; Larva ; Zoonoses

With the increase in human immunodeficiency virus (HIV) infection, the incidence of syphilis also increased worldwide presenting with diverse clinical manifestations. We experienced a case of symptomatic early neurosyphilis manifesting as optic neuritis and trochlear nerve palsy with typical skin lesions of secondary syphilis in an HIV-Infected patient. Intravenous penicillin and oral steroid were administered for 2 weeks. Skin lesions improved after a week, and ocular lesions resolved completely after eight weeks of treatment.
HIV ; Humans ; Incidence ; Male ; Neurosyphilis ; Optic Neuritis ; Penicillins ; Skin ; Syphilis ; Trochlear Nerve ; Trochlear Nerve Diseases

Toxoplasma gondii is an intracellular protozoan that can modulate the environment of the infected host. An unfavorable environment modulated by T. gondii in the brain includes tumor microenvironment. Literature has suggested that T. gondii infection is associated with development of brain tumors. However, in Korea, epidemiological data regarding this correlation have been scarce. In this study, in order to investigate the relationship between T. gondii infection and brain tumor development, we investigated the seroprevalence of T. gondii among 93 confirmed brain tumor patients (various histological types, including meningioma and astrocytoma) in Korea using ELISA. The results revealed that T. gondii seropositivity among brain tumor patients (18.3%) was significantly (P<0.05) higher compared with that of healthy controls (8.6%). The seropositivity of brain tumor patients showed a significant age-tendency, i.e., higher in younger age group, compared with age-matched healthy controls (P<0.05). In conclusion, this study supports the close relationship between T. gondii infection and incidence of brain tumors.
Brain Neoplasms* ; Brain* ; Enzyme-Linked Immunosorbent Assay ; Humans ; Incidence ; Korea* ; Meningioma ; Seroepidemiologic Studies ; Toxoplasma* ; Tumor Microenvironment

Toxoplasma gondii infection induces alteration of the host cell cycle and cell proliferation. These changes are not only seen in directly invaded host cells but also in neighboring cells. We tried to identify whether this alteration can be mediated by exosomes secreted by T. gondii-infected host cells. L6 cells, a rat myoblast cell line, and RH strain of T. gondii were selected for this study. L6 cells were infected with or without T. gondii to isolate exosomes. The cellular growth patterns were identified by cell counting with trypan blue under confocal microscopy, and cell cycle changes were investigated by flow cytometry. L6 cells infected with T. gondii showed decreased proliferation compared to uninfected L6 cells and revealed a tendency to stay at S or G2/M cell phase. The treatment of exosomes isolated from T. gondii-infected cells showed attenuation of cell proliferation and slight enhancement of S phase in L6 cells. The cell cycle alteration was not as obvious as reduction of the cell proliferation by the exosome treatment. These changes were transient and disappeared at 48 hr after the exosome treatment. Microarray analysis and web-based tools indicated that various exosomal miRNAs were crucial for the regulation of target genes related to cell proliferation. Collectively, our study demonstrated that the exosomes originating from T. gondii could change the host cell proliferation and alter the host cell cycle.
Animals ; Cell Count ; Cell Cycle* ; Cell Line ; Cell Proliferation* ; Exosomes* ; Flow Cytometry ; Microarray Analysis ; MicroRNAs ; Microscopy, Confocal ; Myoblasts ; Rats ; S Phase ; Toxoplasma* ; Toxoplasmosis ; Trypan Blue

The seroprevalence of human toxoplasmosis has been increasing in Korea, and it is controversial whether cats are an important infection source or not. This study was performed to evaluate the seroprevalence of Toxoplasma gondii infection in a high risk group (cat sitters) and to determine the possible importance of cats as an infection source in Korea. Risk factors, including the age, sex, and diet of cat sitters, their contact experience and contact frequency with stray cats, and origin, number, and outdoor activity of their pet cats, were analyzed using structured questionnaires. A total of 673 serum samples from people who have frequent contact with cats (high risk group) and 1,114 samples from general people (low risk group) were examined for specific IgG antibodies against T. gondii by ELISA. The results revealed that the overall seroprevalence of T. gondii infection was 7.4% (n=1,787). The seroprevalence among low risk group was 8.0% (89/1,114), whereas that among high risk group was rather lower 6.4% (43/673), though this difference was statistically not significant (P=0.211). Among the risk factors, only the outdoor activity of pet cats was important; people having cats with outdoor activities revealed 2 times higher seroprevalence than people having cats with only indoor activities (P=0.027). In conclusion, the seroprevalence of T. gondii was not significantly different between the high risk group and low risk group, and the importance of cats as a source of infection in Korea is questionable.
Animals ; Antibodies ; Cats* ; Diet ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoglobulin G ; Korea* ; Risk Factors* ; Seroepidemiologic Studies* ; Toxoplasma* ; Toxoplasmosis*

PURPOSE: Dry eye syndrome is commonly thought of as an inflammatory disease, and we have previously presented data showing the effectiveness of topical TNF-α blocker agents for the treatment of this condition. The purpose of this study was to investigate the effectiveness of the TNF-α blocking agent HL036337 compared to cyclosporine A for the treatment of dry eye induced inflammation in order to establish whether HL036337 represents a more effective method for suppressing inflammation. The efficacy of HL036337 and cyclosporine A was determined using an experimental murine dry eye model. METHODS: The TNF-α blocker HL036337 is a modified form of TNF receptor I. Using dry eye induced C57BL/6 mice (n = 45), corneal erosion was measured at day 4 and 7 after topical treatment with cyclosporine A or HL036337. To determine the effective treatment dose, 0.25, 0.5, 1, 2.5, and 5 mg/mL of HL036337 were topically administered twice per day to dry eye induced murine corneas for 1 week. RESULTS: The optimal concentration of the TNF-α blocker HL036337 for treatment of dry eye induced corneal erosion was determined to be 1 mg/mL. Dry eye induced corneal erosion was improved after 1 week with topically applied cyclosporine A and HL036337 at 1 mg/mL. CONCLUSIONS: HL036337 administered topically at 1 mg/mL effectively improved corneal erosion induced by dry eye. This finding may also suggest that inhibition of TNF-α can improve dry eye syndrome.
Animals ; Cornea/diagnostic imaging ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Dry Eye Syndromes/diagnosis/*drug therapy ; Female ; Mice ; Mice, Inbred C57BL ; Microscopy, Acoustic ; Ophthalmic Solutions/administration & dosage ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

Anticancer effects of beta-lapachone (beta-lap) are due to generation of ROS and metabolic catastrophes as a result of NAD(P)H:quinone oxidoreductase (NQO1)-mediated futile cycling between the oxidized and reduced forms of beta-lap. It has been shown that NQO1 is also essential for the TNF-induced activation of NF-kappaB and that beta-lap suppresses the TNF-induced NF-kappaB activation. We investigated whether or not NQO1 is involved and beta-lap suppresses the radiation-induced NF-kappaB activation using A549 human lung cancer cells and NQO1-knock down A549 cells (shNQO1 A549 cells). Irradiation with 4 Gy markedly increased the DNA binding activity of NF-kappaB in A549 cells, but not in the shNQO1 A549 cells, thus demonstrating that NQO1 plays a pivotal role in irradiation-induced NF-kappaB activation. Treatment with 10 micrometer beta-lap for 4 h almost completely abrogated the radiation-induced increase in NF-kappaB activation and the transcription of NF-kappaB target genes such as bcl2, gadd45beta and cyclinD1. Moreover, beta-lap markedly suppressed the activation of IkappaB kinase gamma (IKKgamma) and the subsequent phosphorylation of IkappaBalpha, thereby inhibiting NF-kappaB activation. It is concluded that beta-lap suppresses the radiation-induced activation of NF-kappaB by interrupting the involvement of NQO1 in the activation of NF-kappaB, thereby inhibiting the transcription of survival signals. The radiosensitization caused by beta-lap may, in part, be attributed to beta-lap-induced suppression of NF-kappaB activation.