Activation and Recruitment of Regulatory T Cells via Chemokine Receptor Activation in Trichinella spiralis-Infected Mice

As most infections by the helminth parasite elicit the recruitment of CD4+CD25+Foxp3+ T (T(reg)) cells, many scientists have suggested that these cells could be used for the treatment of immune-mediated inflammation and associated diseases. In order to investigate the distribution and alteration of activated T(reg) cells, we compared the expression levels of T(reg) cell activation markers in the ileum and gastrocnemius tissues 1, 2, and 4 weeks after infection. The number of T(reg) cells was monitored using GFP-coded Foxp3 transgenic mice. In mice at 1 week after Trichinella spiralis infection, the number of activated T(reg) cells was higher than in the control group. In mice at 2 weeks after infection, there was a significant increase in the number of cells expressing Foxp3 and CTLA-4 when compared to the control group and mice at 1 week after infection. At 4 weeks after infection, T. spiralis was easily identifiable in nurse cells in mouse muscles. In the intestine, the expression of Gzmb and Klrg1 decreased over time and that of Capg remained unchanged for the first and second week, then decreased in the 4th week. However, in the muscles, the expression of most chemokine genes was increased due to T. spiralis infection, in particular the expression levels of Gzmb, OX40, and CTLA-4 increased until week 4. In addition, increased gene expression of all chemokine receptors in muscle, CXCR3, CCR4, CCR5, CCR9, and CCR10, was observed up until the 4th week. In conclusion, various chemokine receptors showed increased expressions combined with recruitment of T(reg) cells in the muscle tissue.

Negligible Egg Positive Rate of Enterobius vermicularis and No Detection of Head Lice among Orphanage Children in Busan and Ulsan, Korea (2014)

To determine whether pinworm infections and head lice infestations spread among children in orphanages, 117 children from 4 orphanages in Busan-si and Ulsan-si, Korea, were examined for enterobiasis and head lice infestation between January and February 2014. The overall rate of Enterobius vermicularis egg positivity was 0.85%, whereas none of the children had head lice infestations. The rate of pinworm infection was much lower among the orphanage children compared to the rates observed in previous studies among kindergarten and primary school students. Moreover, the risk factors for enterobiasis were less frequent among these subjects than previously reported. The personal hygiene and health of the orphanage children were supervised by a regular, employed nurse through a health education program. In conclusion, pinworm infection was efficiently controlled among the children in orphanages, and this might be related to good personal hygiene practices in Korea.

Environmental Factors Related to Enterobiasis in a Southeast Region of Korea

Pinworm infection can occur through contact with contaminated surfaces followed by ingestion or even through inhalation of infective eggs. We have limited information regarding environmental contamination by eggs of Enterobius vermicularis. In order to determine environmental risk factors associated with the rate of E. vermicularis infection, we investigated possible environmental risk factors using a questionnaire from 46 kindergartens in 3 different cities of the southeast area of Korea. In total, using the cellotape anal swab technique, 3,422 children were examined for E. vermicularis infection. We evaluated E. vermicularis egg of books, educational materials, toys, room door handles, dusts of window edges, desks, chairs, tables, and dusts of classrooms. The overall egg-positive rate for E. vermicularis was 6.0%, and the prevalence of enterobiasis in each kindergarten ranged between 0% and 16.9%. We found that 78.9% of egg positive kindergartens were managed by private foundations, which was significantly higher, compared with kindergartens managed by public foundations or the nation. Compared with public or national kindergartens, most private kindergartens were located in residential areas and the number of children in these areas was significantly higher. In conclusion, numbers of children in kindergartens was found to be an environmental risk factor associated with transmission of enterobiasis in Korea.

Alteration of Cytokine Production during Visceral Larva Migrans by Toxascaris leonina in Mice

To determine alteration of immune responses during visceral larva migrans (VLM) caused by Toxascaris leonina at several time points, we experimentally infected mice with embryonated eggs of T. leonina and measured T-helper (Th) cell-related serial cytokine production after infection. At day 5 post infection (PI), most larvae were detected from the lungs, spleen, intestine, and muscle. Expression of thymic stromal lymphopoietin (TSLP) and CCL11 (eotaxin) showed a significant increase in most infected organs, except the intestine. However, expression of the CXCL1 (Gro-alpha) gene was most highly enhanced in the intestine at day 14 PI. Th1-related cytokine secretion of splenocytes showed increases at day 28 PI, and the level showed a decrease at day 42 PI. Th2-related cytokine secretion of splenocytes also showed an increase after infection; in particular, IL-5 level showed a significant increase at day 14 PI, and the level showed a decrease at day 28 PI. However, levels of Th17-related cytokines, IL-6 and IL-17A, showed gradual increases until day 42 PI. In conclusion, Th1, Th2, and Th17-related cytokine production might be important in immune responses against T. leonina VLM in experimental mice.

Comparison of Functional Gene Annotation of Toxascaris leonina and Toxocara canis using CLC Genomics Workbench

The ascarids, Toxocara canis and Toxascaris leonina, are probably the most common gastrointestinal helminths encountered in dogs. In order to understand biological differences of 2 ascarids, we analyzed gene expression profiles of female adults of T. canis and T. leonina using CLC Genomics Workbench, and the results were compared with those of free-living nematode Caenorhabditis elegans. A total of 2,880 and 7,949 ESTs were collected from T. leonina and T. canis, respectively. The length of ESTs ranged from 106 to 4,637 bp with an average insert size of 820 bp. Overall, our results showed that most functional gene annotations of 2 ascarids were quite similar to each other in 3 major categories, i.e., cellular component, biological process, and molecular function. Although some different transcript expression categories were found, the distance was short and it was not enough to explain their different lifestyles. However, we found distinguished transcript differences between ascarid parasites and free-living nematodes. Understanding evolutionary genetic changes might be helpful for studies of the lifestyle and evolution of parasites.

Trichinella spiralis Infection Suppressed Gut Inflammation with CD4+CD25+Foxp3+ T Cell Recruitment

In order to know the effect of pre-existing Trichinella spiralis infection on experimentally induced intestinal inflammation and immune responses, we induced colitis in T. spiralis-infected mice and observed the severity of colitis and the levels of Th1, Th2, and regulatory cytokines and recruitment of CD4+CD25+Foxp3+ T (regulatory T; Treg) cells. Female C57BL/6 mice were infected with 250 muscle larvae; after 4 weeks, induction of experimental colitis was performed using 3% dextran sulfate sodium (DSS). During the induction period, we observed severity of colitis, including weight loss and status of stool, and evaluated the disease activity index (DAI). A significantly low DAI and degree of weight loss were observed in infected mice, compared with uninfected mice. In addition, colon length in infected mice was not contracted, compared with uninfected mice. We also observed a significant increase in production of pro-inflammatory cytokines, IL-6 and IFN-gamma, in spleen lymphocytes treated with DSS; however, such an increase was not observed in infected mice treated with DSS. Of particular interest, production of regulatory cytokines, IL-10 and transforming growth factor (TGF)-beta, in spleen lymphocytes showed a significant increase in mice infected with T. spiralis. A similar result was observed in mesenteric lymph nodes (MLN). Subsets of the population of Treg cells in MLN and spleen showed significant increases in mice infected with T. spiralis. In conclusion, T. spiralis infection can inhibit the DSS-induced colitis in mice by enhancing the regulatory cytokine and Treg cells recruitment.

Serum Cystatin C Reflects the Progress of Albuminuria

BACKGROUND: Research on the relationship between urinary albumin excretion and serum cystatin C in diabetes is restricted to cross-sectional studies. In this study, we investigated how well serial measurements of serum cystatin C level reflect changes in the urinary albumin excretion rate. METHODS: We enrolled and retrospectively collected data on 1,058 participants with type 2 diabetes who were older than 18 years and who had more than 3 years of follow-up with serial measurements of albuminuria and serum cystatin C at an outpatient clinic. RESULTS: With the use of a linear mixed model, we found that the albuminuria level for each patient over time corresponded with the annual change in serum cystatin C-based estimated glomerular filtration rate (cysC-eGFR) but did not correspond with the creatinine-based eGFR calculated by the modification of diet in renal disease formula (MDRD-eGFR). The discrepancy in the direction of the trend was smaller with cysC-eGFR than with MDRD-eGFR. CONCLUSION: Serum cystatin C level reflects the trend in albuminuria level more accurately than serum creatinine level in Korean type 2 diabetes mellitus patients.

A 24 kDa Excretory-Secretory Protein of Anisakis simplex Larvae Could Elicit Allergic Airway Inflammation in Mice

We have reported that a 24 kDa protein (22U homologous; As22U) of Anisakis simplex larvae could elicit several Th2-related chemokine gene expressions in the intestinal epithelial cell line which means that As22U may play a role as an allergen. In order to determine the contribution of As22U to allergic reactions, we treated mice with 6 times intra-nasal application of recombinant As22U (rAs22U). In the group challenged with rAs22U and ovalbumin (OVA), the number of eosinophils in the bronchial alveolar lavage fluid (BALF) was significantly increased, as compared to the group receiving only OVA. In addition, mice treated with rAs22U and OVA showed significantly increased airway hyperresponsiveness. Thus, severe inflammation around the airway and immune cell recruitment was observed in mice treated with rAs22U plus OVA. The levels of IL-4, IL-5, and IL-13 cytokines in the BALF increased significantly after treatment with rAs22U and OVA. Similarly, the levels of anti-OVA specific IgE and IgG1 increased in mice treated with rAs22U and OVA, compared to those treated only with OVA. The Gro-alpha (CXCL1) gene expression in mouse lung epithelial cells increased instantly after treatment with rAs22U, and allergy-specific chemokines eotaxin (CCL11) and thymus-and-activation-regulated-chemokine (CCL17) gene expressions significantly increased at 6 hr after treatment. In conclusion, rAs22U may induce airway allergic inflammation, as the result of enhanced Th2 and Th17 responses.

Protease-Activated Receptor 2 Is Involved in Th2 Responses against Trichinella spiralis Infection

In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection.

Parasitic Helminth Cystatin Inhibits DSS-Induced Intestinal Inflammation Via IL-10+F4/80+ Macrophage Recruitment

Many immune down-regulatory molecules have been isolated from parasites, including cystatin (cystain protease inhibitor). In a previous study, we isolated and characterized Type I cystatin (CsStefin-1) of the liver fluke, Clonorchis sinensis. To investigate whether the CsStefin-1 might be a new host immune modulator, we induced intestinal inflammation in mice by dextran sodium sulfate (DSS) and treated them with recombinant CsStefin-1 (rCsStefin-1). The disease activity index (DAI) increased in DSS only-treated mice. In contrast, the DAI value was significantly reduced in rCsStefin-1-treated mice than DSS only-treated mice. In addition, the colon length of DSS only-treated mice was shorter than that of rCsStefin-1 treated mice. The secretion levels of IFN-gamma and TNF-alpha in the spleen and mesenteric lymph nodes (MLNs) were significantly increased by DSS treatment, but the level of TNF-alpha in MLNs was significantly decreased by rCsStefin-1 treatment. IL-10 production in both spleen and MLNs was significantly increased, and IL-10+F4/80+ macrophage cells were significantly increased in the spleen and MLNs of rCsStefin-1 treated mice after DSS treatment. In conclusion, rCsStefin-1 could reduce the intestinal inflammation occurring after DSS treatment, these effects might be related with recruitment of IL-10 secreting macrophages.

Clinical Fate of Reversible Non-Ischemic Left Ventricular Systolic Dysfunction and Its Influencing Factors

BACKGROUND AND OBJECTIVES: About 25% of the patients with non-ischemic left ventricular (LV) systolic dysfunction will improve spontaneously. However, little has been known about the fate of the patients stricken with heart failure after recovery from LV dysfunction. We hypothesized that the patients who recovered from non-ischemic LV dysfunction have a substantial risk for recurrent heart failure. SUBJECTS AND METHODS: Fifty patients (32 males, mean age: 54.9+/-12.4 years) who recovered from systolic heart failure (LV ejection fraction; an EF of 28.8+/-7.2% at the initial presentation) to near-normal (LVEF > 40% and a 10% or more increase in the absolute value) were monitored for the recurrence of heart failure. Patients with significant coronary artery disease were excluded. The etiologies of heart failure were idiopathic dilated cardiomyopathy (n=39), alcoholic cardiomyopathy (n=7), adriamycin-induced cardiomyopathy (n=2), and tachycardia-induced cardiomyopathy (n=2). After recovery of LV dysfunction, the patients were followed up for a mean of 41.0+/-26.3 months. RESULTS: In 9 patients (18%), the LV systolic dysfunction recurred during follow-up (LVEF 32.6+/-7.3%). There was no significant difference in the baseline clinical and echocardiographic variables between the patients with and without recurrent heart failure. However, cessation of anti-heart failure medication was more frequently observed in the patients with recurrent LV systolic dysfunction (55.6% vs 4.9%, respectively, p<0.05). CONCLUSION: Recurrent heart failure may ensue in the patients with reversible non-ischemic LV systolic dysfunction. The maintenance of anti-heart failure medication in these patients may be a significant influencing factor for their clinical prognosis.

A Case of HIV Infection with Progressive Cerebellar Dysfunction as Initial Manifestation

Human immunodeficiency virus (HIV) is known to affect the nervous system at all levels. Neurological complications of HIV occur at all stage of HIV infection, but cerebellar degeneration associated with HIV infection in the absence of cognitive impairment is exceedingly rare. We report a case of HIV infection, in which cerebellar degeneration was the first clinical manifestation. The brain MRI showed marked isolated cerebellar atrophy with severe cerebellar degeneration, but the patient did not have cognitive dysfunction. She was diagnosed as cerebellar form of progressive multifocal leukoencephalopathy with HIV infection. HIV infection should be considered in the diagnosis of any patient with cerebellar dysfunction of unclear origin.

A Case of HIV Infection with Progressive Cerebellar Dysfunction as Initial Manifestation

Human immunodeficiency virus (HIV) is known to affect the nervous system at all levels. Neurological complications of HIV occur at all stage of HIV infection, but cerebellar degeneration associated with HIV infection in the absence of cognitive impairment is exceedingly rare. We report a case of HIV infection, in which cerebellar degeneration was the first clinical manifestation. The brain MRI showed marked isolated cerebellar atrophy with severe cerebellar degeneration, but the patient did not have cognitive dysfunction. She was diagnosed as cerebellar form of progressive multifocal leukoencephalopathy with HIV infection. HIV infection should be considered in the diagnosis of any patient with cerebellar dysfunction of unclear origin.

A Case of Benign Metastasizing Pulmonary Leiomyoma / 결핵및호흡기질환

A benign metastasizing pulmonary leiomyoma (BMPL) is a rare disease that usually occurs in women with a prior or coincident history of uterine leiomyoma. Although leiomyoma is histologically benign, it has the potential to metastasize to a distant site such as the lung. A 35 year old woman who had undergone a hysterectomy due to uterine leiomyoma 5 years prior was admitted for an investigation of multiple pulmonary nodules on a routine chest roentgenogram. An open lung biopsy was taken to make a pathological diagnosis. The microscopic finding of the nodules was leiomyoma and was similar to those of the uterine leiomyoma that had been resected 5 years ago. The woman underwent wedge resections of all pulmonary nodules. This is the first case of BMPL in Korea, which was treated with wedge resections of all multiple pulmonary nodules.

A Case of Multiple Endocrine Neoplasia Type 1 with Mutation in MENIN Gene / 대한내분비학회지

Multiple endocrine neoplasia type 1(MEN 1) is an autosomal dominantly inherited syndrome, characterized by the combined occurrence of tumors of the parathyroid glands, endocrine pancreas, and anterior pituitary gland. The MENIN gene, which is a kind of tumor suppressor gene, is located at the chromosomal locus 11q13. It consists of one untranslated exon and nine exons encoding the menin protein. We report a case of a 22-yearss-old woman with MEN type 1, who was proven to have a mutation in the MENIN gene. The patient was admitted because of repeated hypoglycemia. The fasting plasma glucose level was 32mg/dL. Seventy two hours fasting test showed an the insulin/glucose ratio as 0.33. Endoscopic ultrasonography detected multiple masses on the pancreas. The arterial -stimulated venous sampling(ASVS) with calcium showed sudden step up of insulin at the head and tail portions of the pancreas. The sellar MRI showed a pituitary mass that produced prolactin. Instead of a pathologic diagnosis from operational specimen, the genetic analysis revealed a mutation in the MENIN 1 gene(exon 2, 200~201insAGCCC).

A Case of Pheochromocytoma Presented with Cardiogenic Shock / 대한내분비학회지

A pheochromocytoma is a catecholamine secreting tumor, which is often overlooked when cardiovascular complications, such as acute heart failure, myocardial infarction, angina pectoris, arrhythmias, and dilated cardiomyopathy, presented as the initial clinical manifestations. Failure to identify a pheochromocytoma in these situations may be fatal. We report the case of 32-year-old female, who presented with cardiogenic shock. Echocardiography revealed severe global hypokinesia of the dilated left ventricle, with the exception of the apex. Computed tomography of the aorta showed a well-enhanced left adrenal mass, 3.5cm in diameter. A 24 hour urine collection study for catecholamines and a 131I-metaiodobenzylguanidine(MIBG) scan were suggestive of the diagnosis of a single adrenal pheochromocytoma. The patient stabilized after shock management, and recovered with intensive medical treatment. Follow-up echocardiography revealed normalized cardiac function and chamber dimensions. Thereafter, the adrenal mass was successfully removed using laparaoscopic surgery, without complications

A Case of Endoscopic Mucosal Resection for Esophageal Adenocarcinoma Arising from Barrett's Esophagus / 대한소화기내시경학회지

Barrett's esophagus is defined as the replacement of normal squamous epithelium of distal esophagus with metaplastic columnar epithelium. It is a well known risk factor of esophageal adenocarcinoma. If high grade dysplasia or early stage esophageal cancer develops in a patient with Barrett's esophagus, esophagectomy shoud be performed. However, operative procedures have various complications and the patients may suffer resulting in poor quality of life. Therefore, if the cancer is detected at an early stage such as superficial mucosal lesion, it is possible to resect the tumor with the use of endoscopic technique. Furthermore, endoscopic mucosal resection (EMR) also can be performed for the patients with mucosal or submucosal cancer who can not receive esophagectomy due to old age or poor general condition. We experienced a case of esophageal adenocarcinoma from Barrett's esophagus which had been successfully resected endoscopically.