PURPOSE: T cell-mediated immune responses, and particularly activation of polyfunctional T cells that simultaneously produce multiple cytokines, are necessary for the control of Mycobacterium tuberculosis. In the present study, we examined if DNA immunization of Mycobacterium tuberculosis resuscitation-promoting factor B (RpfB) elicits polyfunctional T cell responses in mice. MATERIALS AND METHODS: C57BL/6 mice were immunized intramuscularly three times, at 3-week intervals, with RpfB-expressing plasmid DNA. For comparison, protein immunization was performed with recombinant RpfB in control mice. After immunization, RpfB-specific T cell responses were assessed by interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assay and intracellular cytokine staining (ICS), and T cell polyfunctionality was assessed from the ICS data. RESULTS: RpfB DNA immunization induced not only humoral immune responses, but also CD8+ and CD4+ T cell responses. Immunodominant T-cell epitopes were identified within RpfB by assays with overlapping peptides. RpfB DNA immunization elicited a polyfunctional CD8+ T cell response that was dominated by a functional phenotype of IFN-gamma+/TNF-alpha+/IL-2-/CD107a+. CONCLUSION: RpfB DNA immunization elicits polyfunctional CD8+ T cell responses, suggesting that RpfB DNA immunization might induce protective immunity against tuberculosis.
Animals ; Complement Factor B* ; Cytokines ; DNA* ; Epitopes, T-Lymphocyte ; Immunity, Humoral ; Immunization* ; Interferon-gamma ; Mice ; Mycobacterium tuberculosis* ; Peptides ; Phenotype ; Plasmids ; T-Lymphocytes ; Tuberculosis ; Vaccines, DNA

Objectives: This study identifies the socioeconomic characteristics and attitudes toward suicide (ATTS) of gatekeepers participating in a suicide prevention project in Gyeongsangbuk-do. Through this study we hope to increase the understanding required to prevent suicide in the community. Methods: We conducted a survey from October 11 to November 4, 2022, with 1,284 individuals from private organizations who participated in the suicide prevention project between September 23 and November 30, 2022. The survey established demographic characteristics, experience in participating in suicide prevention projects, awareness and need for suicide prevention and mental health services, and ATTS. The study conducted cross-analysis and chi-square tests to identify differences in responses according to demographics. An independent sample t-test, one-way analysis of variance, and Scheffe’s post hoc test were performed to analyze the comparisons between each measurement factor. SPSS 21.0 was used to process data and the level of statistical significance was set to p<0.05. Results: The gatekeepers’ ATTS were moderate, with an average of 3.11 out of 5. Specifically, preventability obtained the highest score (4.07), followed by preparedness to prevent (3.96), incomprehensibility (3.74), and noncommunication (3.34). Conversely, resignation obtained the lowest score (2.05), followed by tabooing (2.32) and relation-caused (2.51). The scores for preventability and preparedness to prevent increased with sustained participation in the suicide prevention program, while those for suicidal process decreased. Conclusions Gatekeepers’ ATTS may improve as a result of participation in the suicide prevention project, with better results with continued participation. Thus, actively recruiting more gatekeepers and keeping them engaged in the program may help prevent suicide.

Dysfunction of the virus-specific T cells is a cardinal feature in chronic persistent viral infections such as one caused by hepatitis C virus (HCV). In chronic HCV infection, virus-specific dysfunctional CD8 T cells often overexpress various inhibitory receptors. Programmed cell death 1 (PD-1) was the first among these inhibitory receptors that were identified to be overexpressed in functionally impaired T cells. The roles of other inhibitory receptors such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) have also been demonstrated in T-cell dysfunctions that occur in chronic HCV patients. Blocking these inhibitory receptors in vitro restores the functions of HCV-specific CD8 T cells and allows enhanced proliferation, cytolytic activity and cytokine production. Therefore, the blockade of the inhibitory receptors is considered as a novel strategy for the treatment of chronic HCV infection.
Cell Death ; Hepacivirus ; Hepatitis ; Hepatitis C ; Humans ; Immunoglobulins ; Mucins ; T-Lymphocytes

PURPOSE: Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines. MATERIALS AND METHODS: Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels. RESULTS: Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level. CONCLUSION: We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis.
Acute Disease ; Adult ; Alanine Transaminase/blood ; Biomarkers/blood ; Cytokines/*blood ; Enzyme-Linked Immunosorbent Assay ; Fas Ligand Protein/blood ; Female ; Hepatitis A/blood/virology ; Hepatitis A virus/*genetics/immunology ; Hepatitis B/blood/virology ; Hepatitis B virus/*genetics/immunology ; Humans ; Interleukin-6/blood ; Interleukin-8/blood ; Interleukins/blood ; Liver Failure/immunology/metabolism/*pathology ; Male ; Middle Aged ; T-Lymphocytes, Cytotoxic/immunology/*metabolism

PURPOSE: Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid and BRAFV600E mutation is the most frequent genetic alteration in PTC. BRAFV600E mutation has been demonstrated as a prognostic biomarker for prediction of poor clinicopathological outcomes, such as increased incidence of extrathyroidal extension, lymph node metastasis, and advanced stage. However, there is conflicting literature regarding the association of BRAFV600E mutation and aggressive clinicopathological features. In this study, we investigated the prevalence of BRAFV600E mutation in PTC and determined the association of BRAF mutation with indicators of poor prognosis for PTC. METHODS: We reviewed 1009 patients with PTC, who underwent thyroid surgery at Kyungpook National University Hospital between January 2013 and March 2014. BRAFV600E mutation analysis was performed using real-time polymerase chain reaction based amplification of DNA extracted from paraffin-embedded tumor specimens. RESULTS: BRAFV600E mutation was detected in 863 (85.5%) patients. In univariate analysis, histologic subtype, extrathyroidal extension, and advanced stage showed significant association with BRAFV600E mutation. In addition, concurrent Hashimoto's thyroiditis showed an association with low prevalence of BRAFV600E mutation. However, no statistically significant association was observed for age, gender, multifocal or bilateral tumor, and lymph node metastasis. Multivariate analysis showed an independent association of extrathyroidal extension with BRAFV600E mutation. CONCLUSION: In this study, extrathyroidal extension of PTC is an independent prognostic factor associated with BRAFV600E mutation status. However, conduct of further large scale studies with long term follow up is required before the BRAF mutation can be conclusively recommended as a prognostic biomarker.
DNA ; Gyeongsangbuk-do ; Humans ; Incidence ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Prevalence ; Prognosis ; Real-Time Polymerase Chain Reaction ; Thyroid Gland ; Thyroid Neoplasms* ; Thyroiditis

PURPOSE: To investigate the effects of radiation dose-escalation on the treatment outcome, complications and the other prognostic variables for glioblastoma patients treated with 3D-conformal radiotherapy (3D-CRT). MATERIALS AND METHODS: Between Jan 1997 and July 2002, a total of 75 patients with histologically proven diagnosis of glioblastoma were analyzed. The patients who had a Karnofsky Performance Score (KPS) of 60 or higher, and received at least 50 Gy of radiation to the tumor bed were eligible. All the patients were divided into two arms; Arm 1, the high-dose group was enrolled prospectively, and Arm 2, the low-dose group served as a retrospective control. Arm 1 patients received 63~70 Gy (Median 66 Gy, fraction size 1.8~2 Gy) with 3D-conformal radiotherapy, and Arm 2 received 59.4 Gy or less (Median 59.4 Gy, fraction size 1.8 Gy) with 2D-conventional radiotherapy. The Gross Tumor Volume (GTV) was defined by the surgical margin and the residual gross tumor on a contrast enhanced MRI. Surrounding edema was not included in the Clinical Target Volume (CTV) in Arm 1, so as to reduce the risk of late radiation associated complications; whereas as in Arm 2 it was included. The overall survival and progression free survival times were calculated from the date of surgery using the Kaplan-Meier method. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group neurotoxicity scores. RESULTS: During the relatively short follow up period of 14 months, the median overall survival and progression free survival times were 15+/-1.65 and 11+/-0.95 months, respectively. There was a significantly longer survival time for the Arm 1 patients compared to those in Arm 2 (p=0.028). For Arm 1 patients, the median survival and progression free survival times were 21+/-5.03 and 12+/-1.59 months, respectively, while for Arm 2 patients they were 14+/-0.94 and 10+/-1.63 months, respectively. Especially in terms of the 2-year survival rate, the high-dose group showed a much better survival time than the low-dose group; 44.7% versus 19.2%. Upon univariate analyses, age, performance status, location of tumor, extent of surgery, tumor volume and radiation dose group were significant factors for survival. Multivariate analyses confirmed that the impact of radiation dose on survival was independent of age, performance status, extent of surgery and target volume. During the follow-up period, complications related directly with radiation, such as radionecrosis, has not been identified. CONCLUSION: Using 3D-conformal radiotherapy, which is able to reduce the radiation dose to normal tissues compared to 2D-conventional treatment, up to 70 Gy of radiation could be delivered to the GTV without significant toxicity. As an approach to intensify local treatment, the radiation dose escalation through 3D-CRT can be expected to increase the overall and progression free survival times for patients with glioblastomas.
Arm ; Diagnosis ; Disease-Free Survival ; Edema ; Follow-Up Studies ; Glioblastoma* ; Humans ; Magnetic Resonance Imaging ; Multivariate Analysis ; Neurologic Examination ; Prospective Studies ; Radiotherapy* ; Retrospective Studies ; Survival Rate ; Tomography, X-Ray Computed ; Treatment Outcome ; Tumor Burden

Ectopic breast tissue can occur anywhere along the incompletely regressed mammary ridge. Among the various types of breast choristoma, ectopic breast tissue, which has only glandular tissue without a nipple or areola, is most commonly detected in axillary areas. However, ectopic breast cancer is often not detected until significant clinical symptoms have been revealed, or diagnosis is delayed. Furthermore, an examination of ectopic breast tissue tends to be omitted from a screening mammography. Especially, the microcalcifications of ectopic breast tissue are difficult to delineate on mammography. Herein, the authors report a case of ectopic breast carcinoma that showed clustered microcalcifications on screening mammography, and discuss the interpretation and implications of microcalcification in ectopic breast tissue.
Breast Neoplasms ; Breast* ; Carcinoma, Ductal* ; Choristoma ; Diagnosis ; Mammography* ; Mass Screening* ; Nipples

PURPOSE: Firstly, to analyze factors in terms of radiation treatment that might potentially cause subfrontal relapse in two patients who had been treated by craniospinal irradiation (CSI) for medulloblastoma. Secondly, to explore an effective salvage treatment for these relapses. MATERIALS AND METHODS: Two patients who had high-risk disease (T3bM1, T3bM3) were treated with combined chemoradiotherapy. CT-simulation based radiation-treatment planning (RTP) was performed. One patient who experienced relapse at 16 months after CSI was treated with salvage surgery followed by a 30.6 Gy IMRT (intensity modulated radiotherapy). The other patient whose tumor relapsed at 12 months after CSI was treated by surgery alone for the recurrence. To investigate factors that might potentially cause subfrontal relapse, we evaluated thoroughly the charts and treatment planning process including portal films, and tried to find out a method to give help for placing blocks appropriately between subfrotal-cribrifrom plate region and both eyes. To salvage subfrontal relapse in a patient, re-irradiation was planned after subtotal tumor removal. We have decided to treat this patient with IMRT because of the proximity of critical normal tissues and large burden of re-irradiation. With seven beam directions, the prescribed mean dose to PTV was 30.6 Gy (1.8 Gy fraction) and the doses to the optic nerves and eyes were limited to 25 Gy and 10 Gy, respectively. RESULTS: Review of radiotherapy portals clearly indicated that the subfrontal-cribriform plate region was excluded from the therapy beam by eye blocks in both cases, resulting in cold spot within the target volume. When the whole brain was rendered in 3-D after organ drawing in each slice, it was easier to judge appropriateness of the blocks in port film. IMRT planning showed excellent dose distributions (Mean doses to PTV, right and left optic nerves, right and left eyes: 31.1 Gy, 14.7 Gy, 13.9 Gy, 6.9 Gy, and 5.5 Gy, respectively. Maximum dose to PTV: 36 Gy). The patient who received IMRT is still alive with no evidence of recurrence and any neurologic complications for 1 year. CONCLUSION: To prevent recurrence of medulloblastoma in subfrontal-cribriform plate region, we need to pay close attention to the placement of eye blocks during the treatment. Once subfrontal recurrence has happened, IMRT may be a good choice for re-irradiation as a salvage treatment to maximize the differences of dose distributions between the normal tissues and target volume.
Brain ; Chemoradiotherapy ; Craniospinal Irradiation ; Humans ; Medulloblastoma* ; Optic Nerve ; Radiotherapy ; Recurrence*

Background: Although rhythm control could be the best for symptomatic atrial fibrillation (AF), some patients fail to achieve sinus rhythm (SR). This study aimed to identify clinical risk factors of failed electrical cardioversion (ECV). Methods: A total of 248 patients who received ECV for persistent AF or atrial flutter (AFL) were retrospectivelyreviewed. Patients were divided into three groups: Group 1 maintained SR for > 1 year, group 2 maintained SR ≤ 1 yearafter ECV, and group 3 failed ECV. SR maintenance was assessed using regular electrocardiography or Holter monitoring. Results: Patients were divided into group 1 (73, 29%), group 2 (146, 59%), and group 3 (29, 12%). The mean ageof patients was 60 ± 10 years, and 197 (79%) were male. Age, sex, and baseline characteristics were similar amonggroups. However, increased cardiac size, digoxin use, heart failure (HF), and decreased left ventricular ejection frac‑ tion (LVEF) were more common in group 3. Univariate analysis of clinical risk factors for failed ECV was increasedcardiac size [hazard ratio (HR) 2.14 (95% confidence interval [CI], 1.06–4.34, p = 0.030)], digoxin use [HR 2.66 (95% CI, 1.15–6.14), p = 0.027], HF [HR 2.60 (95% CI, 1.32–5.09), p = 0.005], LVEF < 40% [HR 3.45 (95% CI, 1.00–11.85), p = 0.038], and decreased LVEF [HR 2.49 (95% CI, 1.18–5.25), p = 0.012]. Among them, HF showed clinical significance only by multivariate analysis [HR 3.01 (95% CI, 1.13–7.99), p = 0.027]. Conclusions Increased cardiac size, digoxin use, HF, LVEF < 40%, and decreased LVEF were related to failed ECV for persistent AF or AFL. Among these, HF was the most important risk factor. Further multi-center studies including greater number of participants are planned.