Respiratory syncytial virus (RSV) infection is recognized by the innate immune system through Toll like receptors (TLRs) and retinoic acid inducible gene I. These pathways lead to the activation of type I interferons and resistance to infection. In contrast to TLRs, very few studies have examined the role of NOD-like receptors in viral recognition and induction of adaptive immune responses to RSV. Caspase-1 plays an essential role in the immune response via the maturation of the proinflammatory cytokines IL-1beta and IL-18. However, the role of caspase-1 in RSV infection in vivo is unknown. We demonstrate that RSV infection induces IL-1beta secretion and that caspase-1 deficiency in bone marrow derived dendritic cells leads to defective IL-1beta production, while normal RSV viral clearance and T cell responses are observed in caspase-1 deficient mice following respiratory infection with RSV. The frequencies of IFN-gamma producing or RSV specific T cells in lungs from caspase-1 deficient mice are not impaired. In addition, we demonstrate that caspase-1 deficient neonatal or young mice also exhibit normal immune responses. Furthermore, we find that IL-1R deficient mice infected with RSV exhibit normal Th1 and cytotoxic T lymphocytes (CTL) immune responses. Collectively, these results demonstrate that in contrast to TLR pathways, caspase-1 might not play a central role in the induction of Th1 and CTL immune responses to RSV.
Adaptive Immunity* ; Animals ; Bone Marrow ; Cytokines ; Dendritic Cells ; Immune System ; Interferon Type I ; Interleukin-18 ; Lung ; Mice ; Respiratory Syncytial Viruses* ; T-Lymphocytes ; T-Lymphocytes, Cytotoxic ; Toll-Like Receptors ; Tretinoin

Hematopoietic stem cells (HSCs) in bone marrow are pluripotent cells that can constitute the hematopoiesis system through self-renewal and differentiation into immune cells and red blood cells. To ensure a competent hematopoietic system for life, the maintenance of HSCs is tightly regulated. Although autophagy, a self-degradation pathway for cell homeostasis, is essential for hematopoiesis, the role of autophagy key protein Atg5 in HSCs has not been thoroughly investigated. In this study, we found that Atg5 deficiency in hematopoietic cells causes survival defects, resulting in severe lymphopenia and anemia in mice. In addition, the absolute numbers of HSCs and multiple-lineage progenitor cells were significantly decreased, and abnormal erythroid development resulted in reduced erythrocytes in blood of Vav_Atg5(−/−) mice. The proliferation of Lin⁻Sca-1⁺c-Kit⁺ HSCs was aberrant in bone marrow of Vav_Atg5(−/−) mice, and mature progenitors and terminally differentiated cells were also significantly altered. Furthermore, the reconstitution ability of HSCs in bone marrow chimeric mice was significantly decreased in the presence of Atg5 deficiency in HSCs. Mechanistically, impairment of autophagy-mediated clearance of damaged mitochondria was the underlying cause of the HSC functional defects. Taken together, these results define the crucial role of Atg5 in the maintenance and the reconstitution ability of HSCs.
Anemia ; Animals ; Autophagy ; Bone Marrow ; Erythrocytes ; Hematopoiesis ; Hematopoietic Stem Cells ; Hematopoietic System ; Homeostasis ; Lymphopenia ; Mice ; Mitochondria ; Stem Cells

PURPOSE: Any battery impacted in the esophagus must be removed urgently because of the possibility of serious complications such as perforation, fistula, and mediastinitis. The use of endoscopic procedures was compared to find the most rapid, effective, and safe method to remove disk batteries. METHODS: The cases of 24 children (9 males, mean age, 1.5 years) that had accidentally ingested disk batteries were reviewed. The patients had visited the Department of Pediatrics, Kyungpook National University Hospital from July 1997 to June 2007 for the removal of disk batteries. Endoscopic removal was attempted using a retrieval net or a magnetic extractor with a balloon (condom). The procedure times for removing the ingested battery were compared. RESULTS: Children that ingested batteries with a larger diameter (20 mm) had a greater chance to have esophageal impaction with serious injury, such as esophageal mucosal necrosis or ulcers, as compared to the ingestion of smaller diameter batteries (10 mm) (p<0.01). Endoscopic removal of disk batteries was attempted either using a retrieval net in 10 children or by using a magnetic extractor with a balloon in 6 children. Endoscopic removal using a retrieval net was more effective (mean procedure time: 1.5 min) as compared to using a magnetic extractor with a balloon (mean procedure time: 3.3 min) (p<0.05). CONCLUSION: Both procedures, either using a retrieval net or a magnetic extractor with a balloon were effective in removing ingested disk batteries. Based on our experience, an endoscopic procedure using a retrieval net was a more effective method for foreign body removal.
Child* ; Eating ; Endoscopy ; Esophagus ; Fistula ; Foreign Bodies ; Gyeongsangbuk-do ; Humans ; Male ; Mediastinitis ; Necrosis ; Pediatrics ; Ulcer

PURPOSE: Any battery impacted in the esophagus must be removed urgently because of the possibility of serious complications such as perforation, fistula, and mediastinitis. The use of endoscopic procedures was compared to find the most rapid, effective, and safe method to remove disk batteries. METHODS: The cases of 24 children (9 males, mean age, 1.5 years) that had accidentally ingested disk batteries were reviewed. The patients had visited the Department of Pediatrics, Kyungpook National University Hospital from July 1997 to June 2007 for the removal of disk batteries. Endoscopic removal was attempted using a retrieval net or a magnetic extractor with a balloon (condom). The procedure times for removing the ingested battery were compared. RESULTS: Children that ingested batteries with a larger diameter (20 mm) had a greater chance to have esophageal impaction with serious injury, such as esophageal mucosal necrosis or ulcers, as compared to the ingestion of smaller diameter batteries (10 mm) (p<0.01). Endoscopic removal of disk batteries was attempted either using a retrieval net in 10 children or by using a magnetic extractor with a balloon in 6 children. Endoscopic removal using a retrieval net was more effective (mean procedure time: 1.5 min) as compared to using a magnetic extractor with a balloon (mean procedure time: 3.3 min) (p<0.05). CONCLUSION: Both procedures, either using a retrieval net or a magnetic extractor with a balloon were effective in removing ingested disk batteries. Based on our experience, an endoscopic procedure using a retrieval net was a more effective method for foreign body removal.
Child* ; Eating ; Endoscopy ; Esophagus ; Fistula ; Foreign Bodies ; Gyeongsangbuk-do ; Humans ; Male ; Mediastinitis ; Necrosis ; Pediatrics ; Ulcer

Purpose: Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients. Conclusion The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Purpose: Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients. Conclusion The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Purpose: Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients. Conclusion The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Purpose: Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients. Conclusion The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.