Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Purpose: Natural killer (NK) cells are innate immune cells with antitumor activity. NKG2D is the most important activating receptor expressed on the NK cell surface; this receptor binds to the ligands MICA/B and ULBPs to activate NK cells. The current study aimed to evaluate the expression of NKG2D by NK cells, and to the evaluate expression of its ligands in ovarian carcinomas; it also examined the clinical relevance of NK receptor/ligand expression by analyzing the relationship between expression, clinicopathological parameters, and prognosis. Materials and Methods: Formalin-fixed paraffin-embedded archival ovarian high-grade serous carcinoma (HGSC, n=79) tissue samples were used for tissue microarray analysis. The expressions of NK cell markers (CD56 and NKG2D) and NKG2D ligands (MICA/B, ULBP1, ULBP3, and ULBP2/5/6) in carcinoma tissues were evaluated by immunohistochemical staining, and the association between these results and clinical prognostic parameters was analyzed statistically. Results: ULBP1 was highly expressed in 51 cases (64.6%), and ULBP2/5/6 was highly expressed in 56 cases (70.9%) of HGSC. High expression of ULBP1 and ULBP2/5/6 was significantly associated with lower recurrence of HGSC, whereas high expression of ULBP3 was significantly associated with higher recurrence. Multivariate Cox regression analysis revealed that high expression of ULBP1 was associated with increased overall survival and a decreased hazard ratio (0.150, p=0.044), suggesting that it is an independent predictor of better survival. Conclusion High expression of ULBP1 predicts a better prognosis for HGSC, suggesting that ULBP1 expression could be a novel prognostic indicator in this subset of carcinomas.

OBJECTIVES: To identify various factors that might affect the empowerment of outpatients with schizophrenia. METHODS: Of patients who had been receiving outpatient treatments at the department of psychiatry in Dong-A university hospital, 116 patients with a DSM-IV-TR diagnosis of stable schizophrenia were enrolled in this study. The empowerment, psychiatric symptoms, social functions, insight, family attitude, social support and self-esteem were assessed through an interview or self-report measures. Overall, multiple regression analyses were performed in consideration of 11 factors (age, sex, level of education, age of onset, frequency of hospitalization, symptoms, social functions, insight, family attitude, social support, self-esteem) as explanatory variables for the empowerment. RESULTS: Multiple regression analyses using a backward elimination revealed that the following four factors were found to be significant explanatory variables for the empowerment: age of onset, social functions, family attitude and self-esteem. A coefficient of determination for these four explanatory variables was 0.65. CONCLUSION: In conclusion, the results showed that four factors, such as age of onset, social functions, family attitude and self-esteem, were found to be significant explanatory variables for the empowerment of outpatients with schizophrenia. Since these four variables accounted for 65% of total empowerment, however, further studies in a larger group of patients are warranted to identify other potential factors for the empowerment.
Age of Onset ; Diagnosis ; Education ; Hospitalization ; Humans ; Outpatients ; Power (Psychology) ; Schizophrenia

PURPOSE: To investigate the surgical, perfusion, and molecular characteristics of glioblastomas which influence long-term survival after treatment, and to explore the association between MR perfusion parameters and the presence of MGMT methylation and 1p/19q deletions. MATERIALS AND METHODS: This retrospective study was approved by our institutional review board. A total 43 patients were included, all with pathologic diagnosis of glioblastoma with known MGMT methylation and 1p/19q deletion statuses. We divided these patients into long-term (≥ 60 months, n = 7) and short-term (< 60 months, n = 36) survivors, then compared surgical extent, molecular status, and rCBV parameters between the two groups using Fisher's exact test or Mann-Whitney test. The rCBV parameters were analyzed according to the presence of MGMT methylation and 1p/19q deletions. We investigated the relationship between the mean rCBV and overall survival using linear correlation. Multivariable linear regression was performed in order to find the variables related to overall survival. RESULTS: Long-term survivors (100% [7 of 7]) demonstrated a greater percentage of gross total or near total resection than short-term survivors (54.5% [18 of 33]). A higher prevalence of 1p/19q deletions was also noted among the long-term survivors (42.9% [3 of 7]) than the short-term survivors (0.0% [0 of 36]). The rCBV parameters did not differ between the long-term and short-term survivors. The rCBV values were marginally lower in patients with MGMT methylation and 1p/19q deletions. Despite no correlation found between overall survival and rCBV in the whole group, the short-term survivor group showed negative correlation (R2 = 0.181, P = 0.025). Multivariable linear regression revealed that surgical extent and 1p/19q deletions, but not rCBV values, were associated with prolonged overall survival. CONCLUSION: While preoperative rCBV and 1p/19q deletion status are related to each other, only surgical extent and the presence of 1p/19q deletion in GBM patients may predict long-term survival.
Diagnosis ; Ethics Committees, Research ; Glioblastoma ; Humans ; Linear Models ; Methylation ; Perfusion Imaging ; Perfusion ; Prevalence ; Retrospective Studies ; Survivors

We herein describe a 70-year-old woman who presented with respiratory failure due to extensive lung adenocarcinoma. Despite advanced disease, care in the intensive care unit with ventilator support was performed because she was a newly diagnosed patient and was considered to have the potential to recover after cancer treatment. Because prompt control of the cancer was needed to treat the respiratory failure, empirical treatment with an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor was initiated before confirmation of EGFR-mutant adenocarcinoma, and the patient was successfully treated. Later, EGFR-mutant adenocarcinoma was confirmed.
Adenocarcinoma* ; Aged ; Female ; Humans ; Intensive Care Units ; Lung* ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Respiration, Artificial ; Respiratory Insufficiency* ; Ventilators, Mechanical ; Erlotinib Hydrochloride

We herein describe a 70-year-old woman who presented with respiratory failure due to extensive lung adenocarcinoma. Despite advanced disease, care in the intensive care unit with ventilator support was performed because she was a newly diagnosed patient and was considered to have the potential to recover after cancer treatment. Because prompt control of the cancer was needed to treat the respiratory failure, empirical treatment with an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor was initiated before confirmation of EGFR-mutant adenocarcinoma, and the patient was successfully treated. Later, EGFR-mutant adenocarcinoma was confirmed.
Adenocarcinoma ; Aged ; Female ; Humans ; Intensive Care Units ; Lung ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Respiration, Artificial ; Respiratory Insufficiency ; Ventilators, Mechanical ; Erlotinib Hydrochloride

OBJECTIVES: The shape of the flow-volume (F-V) curve is known to change to showing a prominent plateau as stenosis progresses in patients with tracheal stenosis. However, no study has evaluated changes in the F-V curve according to the degree of bronchial stenosis in patients with unilateral main bronchial stenosis. METHODS: We performed an analysis of F-V curves in 29 patients with unilateral bronchial stenosis with the aid of a graphic digitizer between January 2005 and December 2011. RESULTS: The primary diseases causing unilateral main bronchial stenosis were endobronchial tuberculosis (86%), followed by benign bronchial tumor (10%), and carcinoid (3%). All unilateral main bronchial stenoses were classified into one of five grades (I, < or =25%; II, 26%-50%; III, 51%-75%; IV, 76%-90%; V, >90% to near-complete obstruction without ipsilateral lung collapse). A monophasic F-V curve was observed in patients with grade I stenosis and biphasic curves were observed for grade II-IV stenosis. Both monophasic (81%) and biphasic shapes (18%) were observed in grade V stenosis. After standardization of the biphasic shape of the F-V curve, the breakpoints of the biphasic curve moved in the direction of high volume (x-axis) and low flow (y-axis) according to the progression of stenosis. CONCLUSION: In unilateral bronchial stenosis, a biphasic F-V curve appeared when bronchial stenosis was >25% and disappeared when obstruction was near complete. In addition, the breakpoint moved in the direction of high volume and low flow with the progression of stenosis.
Bronchi ; Carcinoid Tumor ; Constriction, Pathologic* ; Humans ; Lung ; Maximal Expiratory Flow-Volume Curves ; Spirometry ; Tracheal Stenosis ; Tuberculosis

Fanconi syndrome (FS) is a rare condition that is characterized by defects in the proximal tubular function. A 48-year-old woman was admitted for evaluation of proteinuria. The patient showed normal anion gap acidosis, normoglycemic glycosuria, hypophosphatemia, and hypouricemia. Thus, her condition was compatible with FS. The M peak was found behind the beta globulin region in urine protein electrophoresis. Upon bone marrow examination, we found that 24% of cells were CD138+ plasma cells with kappa restriction. From a kidney biopsy, we found crystalline inclusions within proximal tubular epithelial cells. Thereafter, she was diagnosed with FS accompanied by multiple myeloma. The patient received chemotherapy and autologous stem cell transplantation, and obtained very good partial hematologic response. However, proximal tubular dysfunction was persistent until 1 year after autologous stem cell transplantation. In short, we report a case of FS accompanied by multiple myeloma, demonstrating crystalline inclusion in proximal tubular cells on kidney biopsy.
Acid-Base Equilibrium ; Acidosis ; Beta-Globulins ; Biopsy ; Bone Marrow Examination ; Crystallins ; Drug Therapy ; Electrophoresis ; Epithelial Cells ; Fanconi Syndrome* ; Female ; Glycosuria ; Humans ; Hypophosphatemia ; Immunoglobulin kappa-Chains ; Kidney ; Middle Aged ; Multiple Myeloma* ; Plasma Cells ; Proteinuria ; Stem Cell Transplantation

PURPOSE: We evaluated the characteristics of and treatment outcomes in patients with benign tracheobronchial tumors. MATERIALS AND METHODS: We reviewed the records of patients with benign tracheobronchial tumors who underwent bronchoscopic intervention with mechanical removal and Nd: YAG laser cauterization, and evaluated the characteristics and treatment outcomes of 55 patients with hamartomas, leiomyomas, papillomas, typical carcinoids, or schwannomas seen between April 1999 and July 2012. RESULTS: The most common tumors were hamartoma (n=24), leiomyoma (n=16), papilloma (n=7), typical carcinoid (n=5), and schwannoma (n=3). Forty-one patients (75%) had symptoms. On chest computed tomography, 35 patients (64%) had round or ovoid lesions, accompanied by atelectasis (n=26, 47%) or obstructive pneumonia (n=17, 31%). Fatty components (n=9, 16%) and calcifications (n=7, 13%) were observed only in hamartomas, leiomyomas, and typical carcinoids. At bronchoscopy, the typical findings were categorized according to tumor shape, surface, color, and visible vessels. Fifty (91%) patients underwent complete resection. Forty patients (73%) achieved successful bronchoscopic removal defined as complete resection without complications or recurrence. Recurrences occurred in four papillomas, one leiomyoma, and one typical carcinoid. The proportions of tumor types (p=0.029) differed between the successful and unsuccessful removal groups, and a pedunculated base (p<0.001) and no spontaneous bleeding (p=0.037) were more frequent in the successful removal group. CONCLUSION: We described clinical, radiological, and typical bronchoscopic findings in patients with benign tracheobronchial tumors; these findings might help to differentiate such tumors. Bronchoscopic intervention was a useful treatment modality, and tumor type, pedunculated base, and vascularity may influence successful tumor removal.
Adolescent ; Adult ; Aged ; Bronchi/pathology/*surgery ; Bronchoscopy ; Carcinoid Tumor/pathology/surgery ; Female ; Hamartoma/pathology/surgery ; Humans ; Leiomyoma/pathology/surgery ; Male ; Middle Aged ; Neurilemmoma/pathology/surgery ; Papilloma/pathology/surgery ; Young Adult

We evaluated whether sonographic findings can provide additional diagnostic yield in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), and can more accurately predict nodal metastasis than chest computed tomography (CT) or positron emission tomography (PET)/CT scans. EBUS-TBNA was performed in 146 prospectively recruited patients with suspected thoracic lymph node involvement on chest CT and PET/CT from June 2012 to January 2013. Diagnostic yields of EBUS finding categories as a prediction model for metastasis were evaluated and compared with findings of chest CT, PET/CT, and EBUS-TBNA. In total, 172 lymph nodes were included in the analysis: of them, 120 were malignant and 52 were benign. The following four EBUS findings were predictive of metastasis: nodal size > or =10 mm, round shape, heterogeneous echogenicity, and absence of central hilar structure. A single EBUS finding did not have sufficient diagnostic yield; however, when the lymph node had any one of the predictive factors on EBUS, the diagnostic yields for metastasis were higher than for chest CT and PET/CT, with a sensitivity of 99.1% and negative predictive value of 83.3%. When any one of predictive factors is observed on EBUS, subsequent TBNA should be considered, which may provide a higher diagnostic yield than chest CT or PET/CT.
Aged ; Bronchi ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/*methods ; Endosonography/*methods ; Female ; Humans ; Lymph Nodes/*pathology/ultrasonography ; Lymphatic Diseases/*pathology/ultrasonography ; Lymphatic Metastasis ; Male ; Middle Aged ; Prospective Studies ; Reproducibility of Results ; Sensitivity and Specificity ; Thoracic Neoplasms/*pathology/*secondary/ultrasonography