Because tuberculosis (TB) causes two - three million deaths annually, development of a vaccine to control and eradicate the infection is an important unmet medical need. Analysis of the mechanisms of protective immunity in mouse models has indicated that both MHC class I- and class II-restricted T cells contribute to immunity against TB. MHC class II-restricted CD4+ T cells release lymphokines such as IFN-gamma and tumor necrosis factor-alpha that result in macrophage activation. More importantly, beta(2)-microglobulin (beta(2)m)-deficient mice are unable to develop MHC class I-restricted cytotoxic T lymphocytes (CTL) and rapidly succumb to Mycobacterium tuberculosis (MTB) infection. This pathway of protective immunity appears to involve CD8+ T cells and transporters associated with antigen processing (TAP)-dependent presentation of peptide antigen. Thus, studies of mouse models of tuberculosis (TB) infection have indicated a central role for MHC class I-restricted CD8+ T cells in protective immunity. Furthermore, CD8+ T cells not only are able to lyse MTB infected cells but also can simultaneously kill intracellular bacteria by the release of the antimicrobial peptide granulysin. To define antigens and epitopes of Mycobacterium tuberculosis (MTB) proteins that are presented by infected cells to CD8+ T cells, we screened 40 MTB proteins for HLA class I A(*)0201-binding motifs. Peptides that bound with high affinity to purified HLA molecules were subsequently analyzed for recognition by CD8+ cytotoxic T lymphocytes. We identified three epitopes recognized by CD8+ T cells from patients recovering from TB infection. Those three epitopes were derived from three different antigens: thymidylate synthase (ThyA(30-38)), RNA polymerase beta-subunit (RpoB(127-135)), and a putative phosphate transport system permease protein A-1 (PstA1(75-83)). In addition, CD8+ T cell lines specific for three peptides (ThyA(30-38), PstA1(75-83), and 85B(15-23)) were generated from peripheral blood mononuclear cells of normal HLA-Al(*)0201 donors. These CD8+ T cell lines specifically recognized MTB-infected macrophages, as demonstrated by production of IFN-gamma and lysis of the infected target cells. Finally, CD8+ cytotoxic T lymphocytes reduced the viability of the intracellular MTB, providing evidence that CD8+ T cell recognition of MHC class I-restricted epitopes of these MTB antigens can contribute to effective immunity against tuberculosis. Currently, the frequencies of circulating CD8+ T cells specific for each epitope peptide are being investigated in TB patients, normal PPD+ and PPD- donors in order to evaluate the relationship of epitope-specific CD8+ T cell population to the immune responses to MTB infection.
Animals ; Antigen Presentation ; Bacteria ; Cell Line ; DNA-Directed RNA Polymerases ; Epitopes ; Humans ; Lymphokines ; Macrophage Activation ; Macrophages ; Mice ; Mycobacterium tuberculosis ; Peptides ; T-Lymphocytes ; T-Lymphocytes, Cytotoxic ; Thymidylate Synthase ; Tissue Donors ; Tuberculosis* ; Tumor Necrosis Factor-alpha

Endoscopic epinephrine injection is a safe and easy treatment for non-variceal gastrointestinal bleeding. It has low complication rates and is used widely. Ischemic gastric necrosis occurs rarely because of the rich vascular supply of the stomach and the vascular reserve of the intramural anastomosis. Endoscopic injection therapy, smoking, hypertension, and atherosclerosis are risk factors for gastric ischemia. There have been a few case reports of gastric ischemia after endoscopic injection therapy. We report a case of gastric ischemia after submucosal epinephrine injection in a 29-year-old woman with anemia.
Adult ; Anemia* ; Atherosclerosis ; Epinephrine* ; Female ; Hemorrhage ; Humans ; Hypertension ; Ischemia ; Necrosis* ; Risk Factors ; Smoke ; Smoking ; Stomach

PURPOSE: Guinea pig is one of the most suitable animal models for Mycobacterium tuberculosis (M. tb) infection since it shows similarities to pulmonary infection in humans. Although guinea pig shows hematogenous spread of M. tb infection into the whole body, immunological studies have mainly focused on granulomatous tissues in lungs and spleens. In order to investigate the time-course of disease pathogenesis and immunological profiles in each infected organ, we performed the following approaches with guinea pigs experimentally infected with M. tb over a 22-week post-infection period. MATERIALS AND METHODS: We examined body weight changes, M. tb growth curve, cytokine gene expression (IFN-gamma and TNF-alpha), and histopathology in liver, spleen, lungs and lymph nodes of infected guinea pigs. RESULTS: The body weights of infected guinea pigs did not increase as much as uninfected ones and the number of M. tb bacilli in their organs increased except bronchotracheal lymph node during the experimental period. The gene expression of IFN-gamma and TNF-alpha was induced between 3 and 6 weeks of infection; however, kinetic profiles of cytokine gene expression showed heterogeneity among organs over the study period. Histophathologically granulomatous lesions were developed in all four organs of infected guinea pigs. CONCLUSION: Although IFN-gamma and TNF-alpha gene expression profiles showed heterogeneity, the granuloma formation was clearly observed in every organ regardless of whether the number of bacilli increased or decreased. However, this protective immunity was accompanied with severe tissue damage in all four organs, which may lead to the death of guinea pigs.
Animals ; Body Weight ; *Disease Progression ; Female ; Gene Expression ; Gene Expression Regulation ; Guinea Pigs ; Interferon-gamma/genetics/*metabolism ; Kinetics ; Liver/metabolism/pathology ; Lung/metabolism/pathology ; Lymph Nodes/metabolism/pathology ; Mycobacterium tuberculosis ; Spleen/metabolism/pathology ; Tuberculosis/*genetics/pathology ; Tumor Necrosis Factor-alpha/genetics/*metabolism

Leiomyosarcoma(LMS) is a malignant tumor from smooth muscle origin that arises most commonly in the gastrointestinal tract and uterus, but rarely in the oral and maxillofacial area which lacks smooth muscles. 63 cases of oral LMS have been reported, especially LMS that occurred in the mandibular gingiva is only 2 cases. Major symptom of oral LMS is painful or painless swelling. Besides it, oral LMS has no specific characteristics. So it is difficult to diagnose the case as LMS of the oral cavity. Certain cases report that LMS of the oral cavity was misdiagnosed as periodontitis and the patients were treated with unnecessary procedures. Conventional treatment of LMS is the radical surgical excision. LMS that is infiltrative and very malignant has poor prognosis despite of well-circumscribed boundary. LMS of the oral cavity is often recurred, has high rate of distant metastasis and 5-year-survival rate is as low as 23%. This article reports LMS of the mandibular gingiva that treated with surgical intervention, had local recurrence and metastasis to the lymph node after 16-month's follow-up examination.
Follow-Up Studies ; Gastrointestinal Tract ; Gingiva* ; Humans ; Leiomyosarcoma* ; Lymph Nodes ; Mouth ; Muscle, Smooth ; Neoplasm Metastasis ; Periodontitis ; Prognosis ; Recurrence ; Unnecessary Procedures ; Uterus

Head ; Lipoma ; Neck Muscles ; Neck ; Recurrence ; Shoulder ; Subcutaneous Tissue

BACKGROUND: IgE is closely related to the development of allergies. However, the poor relationship between the specific IgE level and the severity of allergic diseases suggests the possibility of functionally different IgE isoforms. With this in mind, rat basophilic leukemia (RBL)-2H3 activation was analyzed with each type of rat IgE for two parameters, exocytosis and IL-4 mRNA production. RBL-2H3 has been well documented in the rat mucosal mast cell line. METHODS: RBL-2H3 cells sensitized with each kind of rat IgE was activated by cross-linking FcRI with B5 (monoclonal anti-rat IgE mouse IgG antibodies). The RBL-2H3 exocytosis was measured by analyzing the beta-hexosaminidase level, and the level of IL-4 mRNA synthesis was analyzed using semi- quantitative RT-PCR. Rat IgE, which was produced by a parasite infection (REP), was prepared using either Paragonimus westermani metacercariae (REP-PW) or Anisakis simplex third stage larvae (REP-AS). A rat IgE prototype of IR162 was prepared by a peritoneal injection of immunocytoma. RESULTS: The level of exocytosis showed a linear relationship with the rat IgE concentration when REP-PW or REP-AS was applied. However, it exhibited a biphasic response with IR162. In addition, the time course of heating at 56oC illustrated the similarity between REP-PW and REP-AS, which differed from that of IR162. In contrast, the level of IL-4 mRNA synthesis in the RBL-2H3 cells with IR162 was comparable to that of either REP-PW or REP-AS. CONCLUSION: These results suggest that functionally different rat IgE isoforms exists in RBL-2H3 exocytosis.
Animals ; Anisakis ; Basophils ; beta-N-Acetylhexosaminidases ; Exocytosis* ; Heating ; Hot Temperature ; Hypersensitivity ; Immunoglobulin E* ; Immunoglobulin G ; Interleukin-4 ; Larva ; Leukemia ; Mast Cells ; Metacercariae ; Mice ; Paragonimus westermani ; Parasites ; Protein Isoforms ; Rats* ; RNA, Messenger

BACKGROUND: Diagnosis of tuberculous pleurisy is sometimes difficult using conventional diagnostic methods. We have investigated the utility of pleural fluid cell IFN-gamma production assay in the diagnosis of tuberculous pleurisy. METHODS: We prospectively performed pleural fluid cell IFN-gamma production assay in 39 patients with tuberculous pleural effusions (TPE) and in 26 patients with nontuberculous pleural effusions (NTPE) (13 malignant pleural effusions and 13 parapneumonic effusions). Pleural fluid cells were cultured in DMEM media and stimulated with purified protein derivatives (PPD), and phytohemagglutinin (PHA) for 24 hr. The amount of IFN-gamma released in the culture supernatant was quantitated by IFN-gamma ELISA assay. We have also measured adenosine deaminase (ADA) activities and IFN-gamma concentrations in the pleural fluid. RESULTS: 1) The pleural fluid levels of ADA activity and IFN-gamma concentrations were significantly higher in TPE than NTPE (p<0.01). 2) IFN-gamma production in TPE cells stimulated by PPD (755,266+/-886,636 pg/ml) was significantly higher than NTPE cells (3,509+/-6,980 pg/ml) (p<0.01). By considering the fact that IFN-gamma concentrations over 10,000 pg/ml is a criteria for the diagnosis of TBE, sensitivity and specificity of the test were 97.4 and 92.3%, respectively. 3) The ratios of IFN-gamma production by the stimulation with PPD and PHA (PPD/PHA) were significantly higher in TPE cells (59+/-85) than NTPE cells (5+/-18)(p<0.01). Considering the criteria for the diagnosis of TBE as PPD/PHA ratio over 5, sensitivity and specificity of the test were 76.9 and 92.3%, respectively. CONCLUSION: Pleural fluid cell IFN-gamma production assay may be useful for the diagnosis of tuberculous pleurisy.
Adenosine Deaminase ; Diagnosis* ; Enzyme-Linked Immunosorbent Assay ; Humans ; Pleural Effusion ; Pleural Effusion, Malignant ; Pleurisy ; Prospective Studies ; Tuberculosis ; Tuberculosis, Pleural*

OBJECTIVE: Cell to cell and cell to extracellular matrix interaction are crucial in tumor development and progression. Tight junction proteins such as claudins and zonula occludens-1 (ZO-1) play an important role in these processes. This study was performed to investigate the difference of expressions of claudin-1, claudin-4 and ZO-1 in low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL), and invasive squamous cell carcinoma (ISCC) of the uterine cervix. METHODS: The expressions of claudin-1, claudin-4 and ZO-1 were evaluated using immunohistochemical staining in 78 cervical tissue specimens (LSIL 22 case, HSIL 36 case, and ISCC 20 case). RESULTS: Claudin-1 expression was positive in 40.9% of LSIL, in 94.0% of HSIL and in 20.0% of ISCC. The expression of claudin-1 was significantly high in HSIL (p=0.0001). Claudin-4 expression was positive in 31.8% of LSIL, in 41.7% of HSIL and in 25.0% of ISCC. The expression of claudin-4 was high in HSIL, but it was not statistically different. ZO-1 expression was positive in 13.6% of LSIL, in 41.7% of HSIL, and in 25.5% of ISCC. The expression of ZO-1 was significantly high in HSIL (p=0.011). CONCLUSION: These results indicate increased expressions of claudin-1 and ZO-1 in the HSIL that includes cervical intraepithelial neoplasia (CIN) 2 and 3, which decrease during progression to cervical cancer.
Carcinoma, Squamous Cell* ; Cervical Intraepithelial Neoplasia* ; Cervix Uteri ; Claudin-1* ; Claudin-4* ; Claudins ; Extracellular Matrix ; Female ; Tight Junction Proteins ; Uterine Cervical Neoplasms

OBJECTIVE: To investigate the effects of bisphenol A (BPA) on cell death pattern in neuronal development of chick embryos. MATERIALS AND METHODS: We planned to compare the cytokinetic features in the normal chick embryo and those with BPA. Fifteen eggs were divided into three GROUPS: the control group, BPA 50 microgram/g egg group and BPA 200 microgram/g egg group. Embryos were incubated for 56 hours (Hamburger & Hamilton stage 16) and then we injected BPA into embryos. The embryos were sectioned by 3 micrometer thickness at the level of wing buds and stained at 72 hours after incubation (HH stage 18). We observed cell death in the spinal cord using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. RESULTS: The TUNEL-positivity markedly increased in proportion to the doses of BPA. The number of TUNEL-positive cells per section was 15.2+/-2.14 in the control group, 34.6+/-3.44 in the BPA 50 microgram/g egg group, 87.6+/-4.32 in the BPA 200 g/g egg group. Furthermore the contour of spinal cord was deformed as the doses of BPA raised. CONCLUSION: BPA causes neuronal cell death and exerts cytotoxic effect on early chick embryos. It suggests that BPA might have an effect on cytogenesis during neural tube development.
Animals ; Apoptosis ; Benzhydryl Compounds ; Cell Death ; Chick Embryo ; Eggs ; Embryonic Structures ; Neural Tube ; Neurons ; Ovum ; Phenols ; Spinal Cord ; Wings, Animal

PURPOSE: The present study aimed to evaluate the accuracy of determining the prevalence of atopic dermatitis (AD) with a questionnaire by diagnosing AD with both a questionnaire and pediatricians' physical examinations and to determine the possible risk factors for AD. METHODS: A survey was conducted from December 2008 to February 2009 in four elementary schools. The Korean version of the International Study of Asthma and Allergies in Childhood written questionnaire (WQ) was used to identify AD ever and AD during the last 12 months. Current AD was diagnosed by well-trained pediatricians according to the Hanifin and Rajka's diagnostic criteria. A total of 2,729 children who completed the questionnaire and underwent a physical examination by pediatricians were included in this analysis. RESULTS: According to the WQ, the prevalence of AD in the entire life and in the last 12 months was 18.4% and 12.9%, respectively. The prevalence of clinically diagnosed AD by pediatricians was 8.8%. There was a significant positive relationship between the prevalence of AD diagnosed by physical examination and past history of allergic rhinitis (adjusted odds ratio [aOR], 1.45), allergy history of the mother (aOR, 2.48), and AD history of the mother (aOR, 1.61). According to the WQ, there was also a significant positive relationship between the prevalence of AD in the last 12 months and past history of asthma (aOR, 2.55) and AD history of the mother (aOR, 1.71). CONCLUSION: Prevalence and risk factors of AD were different according to the survey methods. When prevalence of AD is determined with a questionnaire in the future, more careful attention should be used, because the result can be overestimated compared to the actual prevalence.
Asthma ; Child ; Dermatitis, Atopic ; Humans ; Hypersensitivity ; Mothers ; Odds Ratio ; Physical Examination ; Prevalence ; Surveys and Questionnaires ; Rhinitis ; Rhinitis, Allergic, Perennial ; Risk Factors