BACKGROUND/AIMS: The aim of this study was to determine the risk factors of multiple gastric polyps according to the histological classification of gastric polyps. METHODS: Subjects with multiple gastric polyps (at least three) during endoscopy were enrolled prospectively. They were assigned to a fundic gland polyp (FGP) group and hyperplastic polyp (HP) group based on a histological classification of gastric polyps. Helicobacter pylori (H. pylori) was confirmed by its histology. Serum gastrin was measured using the radioimmunoassay method. A questionnaire was taken regarding the intake of proton pump inhibitor and nonsteroidal anti-inflammatory drugs, alcohol, smoking history, and diet. RESULTS: Among the 60 subjects enrolled from 2015 to 2018 at Seoul National University Bungdang Hospital, 47 and 13 subjects were assigned to the FGP and HP groups, respectively. The H. pylori infection rate was 12.8% in the FGP group, which is lower than that in the HP group (69.2%, p<0.001). The gastrin level was higher in the HP group (194.7 pg/dL, range 50.6–387.8 pg/dL) than in the FGP group (57.4 pg/dL, range 24.8–79.0 pg/dL) (p=0.007). Histologically, neutrophil infiltration in the antrum and body of the stomach were higher in the HP group than in the FGP group (p=0.022 and p=0.030, respectively). In contrast, monocyte infiltration in the antrum and body of the stomach were higher in the FGP group than in the HP group (p=0.018 and p<0.001, respectively). CONCLUSIONS: HPs arise from inflammation caused by H. pylori. On the other hand, the FGP was not associated with H. pylori or environmental factors.
Classification ; Cohort Studies ; Diet ; Endoscopy ; Gastrins ; Hand ; Helicobacter pylori ; Inflammation ; Methods ; Monocytes ; Neutrophil Infiltration ; Polyps ; Prospective Studies ; Proton Pump Inhibitors ; Proton Pumps ; Radioimmunoassay ; Risk Factors ; Seoul ; Smoke ; Smoking ; Stomach

PURPOSE: Atopic dermatitis (AD) is the most common chronic and relapsing inflammatory skin disease with skin barrier defects and altered immune responses. Chronic inflammation leads to irreversible fibrosis in the skin and there is no treatment to completely abolish the inflammation and fibrosis. To prevent or treat the chronic process of AD, it is necessary to develop a murine model of AD that reflects the chronic process to identify the mechanism. The aims of this study were to develop a chronic AD model with a crude extract Aspergillus fumigatus (Af) antigen. METHODS: We applied Af extract (40 µg) epicutaneously to the dorsal skin of BALB/c mice for 5 consecutive days per week during a period of 5 weeks for a chronic AD model, and 5 consecutive days repeatedly with 2 weeks interval for an acute AD model. RESULTS: The clinical score and transepidermal water loss were more increased in the chronic AD model than in the acute AD model. Histologic findings showed that more increased epidermal thickness, neutrophil infiltration and hyperkeratosis in the chronic model than in the acute model. Skin fibrosis was more prominent in the chronic model than in the acute model. The mRNA expression levels of transforming growth factor (TGF)-β, thymic stromal lymphopoietin, and interleukin-33 were increased in the skin of the chronic model compared to the acute model. The levels of total IgE, Af-specific IgE, IgG1, and IgG2a were significantly increased in the chronic model compared to controls. CONCLUSION: The Af-induced chronic AD model showed prominent fibrosis and increased TGF-β expression in the skin, which suggests that these models may be useful in the research for the mechanism of the chronic process in AD.
Animals ; Aspergillus fumigatus ; Aspergillus ; Dermatitis, Atopic ; Fibrosis ; Immunoglobulin E ; Immunoglobulin G ; Inflammation ; Interleukin-33 ; Mice ; Neutrophil Infiltration ; RNA, Messenger ; Skin ; Skin Diseases ; Transforming Growth Factors ; Water

Wischnewski spots (WS) are multiple black spots observed in the gastric mucosa at autopsy that are considered a reliable and important feature of hypothermia. Nonetheless, the frequency of WS varies widely. WS were discovered in 20 cases out of 3,493 autopsies (0.57%) conducted between 2001 and 2017 in the Department of Forensic Medicine of the School of Medicine, Kyungpook National University in Korea. This study aimed to investigate the distribution and size of WS in these cases and analyze the respective causes of death. Nine cases that occurred in winter were the same as the nine cases with hypothermia as the cause of death or contributory cause. The post-mortem blood alcohol test was positive in eight cases, with acute or chronic alcoholism determined as the cause of death in two of these cases. There were two cases of acute poisoning by pesticides. Putrefaction was noted in six cases (30%). WS presented in various sizes ranging from pinpoint to more than 5 mm in diameter, and the number of WS varied from 5 to 100. WS distribution was diffuse in four cases (20%) and localized in 13 cases (65%). Microscopic examination showed brown to black pigmentation but no neutrophil infiltration or vital reactions in the WS. Thus, WS are associated with hypothermia and are considered post-mortem alterations with variable appearance, size, and distribution. Hypothermia is an exclusive diagnosis at autopsy that should result from a combined assessment of toxicological tests, circumstance of death, and autopsy findings.
Alcoholism ; Autopsy ; Cause of Death ; Diagnosis ; Forensic Medicine ; Gastric Mucosa ; Gyeongsangbuk-do ; Humans ; Hypothermia ; Korea ; Neutrophil Infiltration ; Pesticides ; Pigmentation ; Poisoning

BACKGROUND/AIMS: The aim of this study was to determine the risk factors of multiple gastric polyps according to the histological classification of gastric polyps.METHODS: Subjects with multiple gastric polyps (at least three) during endoscopy were enrolled prospectively. They were assigned to a fundic gland polyp (FGP) group and hyperplastic polyp (HP) group based on a histological classification of gastric polyps. Helicobacter pylori (H. pylori) was confirmed by its histology. Serum gastrin was measured using the radioimmunoassay method. A questionnaire was taken regarding the intake of proton pump inhibitor and nonsteroidal anti-inflammatory drugs, alcohol, smoking history, and diet.RESULTS: Among the 60 subjects enrolled from 2015 to 2018 at Seoul National University Bungdang Hospital, 47 and 13 subjects were assigned to the FGP and HP groups, respectively. The H. pylori infection rate was 12.8% in the FGP group, which is lower than that in the HP group (69.2%, p<0.001). The gastrin level was higher in the HP group (194.7 pg/dL, range 50.6–387.8 pg/dL) than in the FGP group (57.4 pg/dL, range 24.8–79.0 pg/dL) (p=0.007). Histologically, neutrophil infiltration in the antrum and body of the stomach were higher in the HP group than in the FGP group (p=0.022 and p=0.030, respectively). In contrast, monocyte infiltration in the antrum and body of the stomach were higher in the FGP group than in the HP group (p=0.018 and p<0.001, respectively).CONCLUSIONS: HPs arise from inflammation caused by H. pylori. On the other hand, the FGP was not associated with H. pylori or environmental factors.
Classification ; Cohort Studies ; Diet ; Endoscopy ; Gastrins ; Hand ; Helicobacter pylori ; Inflammation ; Methods ; Monocytes ; Neutrophil Infiltration ; Polyps ; Prospective Studies ; Proton Pump Inhibitors ; Proton Pumps ; Radioimmunoassay ; Risk Factors ; Seoul ; Smoke ; Smoking ; Stomach

Objective To explore the application of neutrophil migration distance for wound age estimation of skeletal muscles in rats, and to provide methodological basis for follow-up study in future. Methods The skeletal muscle contusion model was established in rats, and the control group and the 2, 4, 6 h post-traumatic groups were set. The law of response of neutrophils that participated in the inflammation after injury was detected by immunohistochemical staining, and the relationship between neutrophil migration distance and injury time was detected by TissueFAXS PLUS software. Results The skeletal muscle was obviously infiltrated with neutrophils 2-6 h after injury. The positive rate of neutrophil was （28.75±0.94）% at 2 h post-traumatic, and reached the peak （45.50±3.63）% at 4 h post-traumatic, then decreased to （31.92±1.56）% at 6 h post-traumatic. The neutrophil migration distances increased with the progress of inflammation, and reached （124.80±12.32） μm, （229.03±21.45） μm and （335.04±16.75） μm at 2 h, 4 h and 6 h, respectively. Conclusion There is a relationship of neutrophil infiltrated number and migration distance and wound age within the 2-6 h after skeletal muscle injury, which could be used for the inference of skeletal muscle wound age.
Animals ; Contusions/metabolism* ; Follow-Up Studies ; Muscle, Skeletal/pathology* ; Neutrophil Infiltration ; Neutrophils ; Rats ; Rats, Sprague-Dawley ; Time Factors

Triptolide (TP) induces severe liver injury, but its hepatotoxicity mechanisms are still unclear. Inflammatory responses may be involved in the pathophysiology. Neutrophils are the first-line immune effectors for sterile and non-sterile inflammatory responses. Thus, the aim of the present study was to investigate the neutrophilic inflammatory response in TP-induced liver injury in C57BL/6 mice. Our results showed that neutrophils were recruited and accumulated in the liver, which was parallel to or slightly after the development of liver injury. Neutrophils induced release of myeloperoxidase and up-regulation of CD11b, which caused cytotoxicity and hepatocyte death. Hepatic expressions of CXL1, TNF-α, IL-6, and MCP1 were increased significantly to regulate neutrophils recruitment and activation. Up-regulation of toll like receptors 4 and 9 also facilitated neutrophils infiltration. Moreover, neutrophils depletion using an anti-Gr1 antibody showed mild protection against TP overdose. These results indicated that neutrophils accumulation might be the secondary response, not the cause of TP-induced liver injury. In conclusion, the inflammatory response including neutrophil infiltration may play a role in TP-induced hepatotoxicity, but may not be severe enough to cause additional liver injury.
Animals ; Chemical and Drug Induced Liver Injury ; etiology ; immunology ; Chemokine CCL2 ; genetics ; immunology ; Diterpenes ; adverse effects ; Drugs, Chinese Herbal ; adverse effects ; Epoxy Compounds ; adverse effects ; Female ; Humans ; Interleukin-6 ; genetics ; immunology ; Intracellular Signaling Peptides and Proteins ; genetics ; immunology ; Liver ; drug effects ; immunology ; Mice ; Mice, Inbred C57BL ; Neutrophil Infiltration ; drug effects ; Neutrophils ; drug effects ; immunology ; Phenanthrenes ; adverse effects ; Tripterygium ; adverse effects ; chemistry ; Tumor Necrosis Factor-alpha ; genetics ; immunology

Neutrophilic myositis is a very rare disease histologically characterized by neutrophil infiltration of muscle tissues. We report a case of a 47-year-old man who presented with acute onset of severe swelling and pain on his left shoulder with high fever. He was initially suspected of having cellulitis, but intravenous antibiotics did not improve his symptoms. Similar swelling and pain then developed on both calves. Investigations with magnetic resonance imaging of the lower legs and muscle biopsy led to a diagnosis of neutrophilic myositis. High dose glucocorticoid dramatically improved his symptoms within days. Clinicians need to be aware of this rare disease as a cause of acute febrile myositis mimicking infection.
Anti-Bacterial Agents ; Biopsy ; Cellulitis ; Diagnosis ; Fever ; Humans ; Leg ; Magnetic Resonance Imaging ; Middle Aged ; Myositis* ; Neutrophil Infiltration ; Neutrophils* ; Rare Diseases ; Shoulder ; Sweet Syndrome

BACKGROUND/AIMS: Recent findings have demonstrated the occurrence of neutrophil transendothelial migration in the reverse direction (reverse TEM) and that endothelial junctional adhesion molecule C (JAM-C) is a negative regulator of reverse TEM. In this study, we tested the effects of a JAM-C blocking antibody on the resolution of kidney injuries and inflammation in a mouse model of cisplatin-induced acute kidney injury (AKI). METHODS: Cisplatin was administered via intraperitoneal injection. A JAM-C blocking antibody or a control immunoglobulin G was administered intraperitoneal at 1.5 mg/kg, with the injection being delayed until day 4 following cisplatin administration to restrict the effect of antibodies on recovery. RESULTS: After cisplatin injection, serum creatinine and histologic injuries peaked on day 4. Treatment with a JAM-C blocking antibody on days 4 and 5 promoted the functional and histologic recovery of cisplatin-induced AKI on days 5 and 6. Facilitating recovery with a JAM-C blocking antibody correlated with significantly increased circulating intercellular adhesion molecule 1+ Tamm-Horsfall protein+ neutrophils and significantly decreased renal neutrophil infiltration, indicating that facilitating reverse the TEM of neutrophils from the kidney to the peripheral circulation partially mediated the resolution of inflammation and recovery. CONCLUSIONS: These results demonstrated that reverse TEM is involved in the resolution of neutrophilic inflammation in cisplatin-induced AKI and that JAM-C is an important regulator of this process.
Acute Kidney Injury* ; Animals ; Antibodies ; Cisplatin ; Creatinine ; Immunoglobulin G ; Inflammation ; Injections, Intraperitoneal ; Junctional Adhesion Molecule C* ; Junctional Adhesion Molecules* ; Kidney ; Mice ; Neutrophil Infiltration ; Neutrophils ; Transendothelial and Transepithelial Migration

PURPOSE: Lipopolysaccharide (LPS) is a cell wall component of Gram-negative bacteria and important for pro-inflammatory mediators. This study aimed to establish a rhinitis model using ovalbumin (OVA) and LPS in order to evaluate the role of interleukin (IL)-17 in the pathogenesis of an LPS-induced non-eosionophilic rhinitis model. METHODS: Mice were divided into 4 groups and each group consisted of 10 mice (negative control group, allergic rhinitis model group, 1-µg LPS treatment group, and 10-µg LPS treatment group). BALB/c mice were sensitized with OVA and 1 or 10 µg of LPS, and challenged intranasally with OVA. Multiple parameters of rhinitis were also evaluated to establish the LPS-induced rhinitis model. IL-17 knockout mice were used to check if the LPS-induced rhinitis model were dependent on IL-17. Eosinophil and neutrophil infiltration, and mRNA and protein expression profiles of cytokine in nasal mucosa or spleen cell culture were evaluated using molecular, biochemical, histopathological, and immunohistological methods. RESULTS: In the LPS-induced rhinitis model, neutrophil infiltration increased in the nasal mucosa, and systemic and nasal IL-17 and interferon-gamma (IFN-γ) levels also increased as compared with the OVA-induced allergic rhinitis model. These findings were LPS-dose-dependent. In IL-17 knockout mice, those phenotypes (neutrophil infiltration, IL-17, and IFN-γ) were reversed, showing IL-17 dependency of LPS-induced rhinitis. The expression of vascular endothelial growth factor (VEGF), an important mediator for inflammation and angiogenesis, decreased in IL-17 knockout mice, showing the relationship between IL-17 and VEGF. CONCLUSIONS: This study established an LPS-induced rhinitis model dependent on IL-17, characterized by neutrophil infiltration and increased expression of IL-17.
Animals ; Cell Culture Techniques ; Cell Wall ; Eosinophils ; Gram-Negative Bacteria ; Inflammation ; Interferon-gamma ; Interleukin-17* ; Interleukins ; Mice ; Mice, Knockout ; Nasal Mucosa ; Neutrophil Infiltration ; Ovalbumin ; Ovum ; Phenotype ; Rhinitis* ; Rhinitis, Allergic ; RNA, Messenger ; Spleen ; Vascular Endothelial Growth Factor A

Interleukin (IL)-17 plays an important role in rhinitis and the level thereof correlates with the severity of disease. However, no mouse model for IL-17-dominant rhinitis has yet been developed. Our objective was to establish a mouse model of IL-17-dominant rhinitis via intranasal application of polyinosinic-polycytidylic acid (abbreviated as Poly(I:C)). Mice were divided into 6 groups (n=8 for each group); 1) 1 negative control group, 2) 1 positive control group (OVA/alum model), 3) 2 Poly(I:C) groups (10 or 100 µg), and 4) 2 OVA/Poly(I:C) groups (10 or 100 µg). The positive control group was treated with the conventional OVA/alum protocol. In the Poly(I:C) and OVA/Poly(I:C) groups, phosphate-buffered saline or an OVA solution plus Poly(I:C) were administered. The OVA/Poly(I:C) groups exhibited significantly greater neutrophil infiltration and increased IL-17/interferon γ expression compared with the other groups. However, the levels of total immunoglobulin E (IgE), OVA-specific IgE, eosinophil infiltration, IL-4, IL-5, IL-6, and IL-10 were significantly lower in the OVA/Poly(I:C) groups than in mice subjected to conventional Th2-dominant OVA/alum treatment (the positive control group). IL-17 and neutrophil measurement, chemokine (C-X-C motif) ligand 1 immunohistochemistry, and confocal microscopy revealed increased numbers of IL-17-secreting cells in the nasal mucosa of the OVA/Poly(I:C) groups, which included natural killer cells, CD4 T cells, and neutrophils. In conclusion, we developed a mouse model of IL-17-dominant rhinitis using OVA together with Poly(I:C). This model will be useful in research on neutrophil- or IL-17-dominant rhinitis.
Animals ; Chemokine CXCL1 ; Eosinophils ; Immunoglobulin E ; Immunoglobulins ; Immunohistochemistry ; Interleukin-10 ; Interleukin-17 ; Interleukin-4 ; Interleukin-5 ; Interleukin-6 ; Interleukins ; Killer Cells, Natural ; Mice* ; Microscopy, Confocal ; Nasal Mucosa ; Neutrophil Infiltration ; Neutrophils ; Ovum ; Poly I-C* ; Rhinitis* ; T-Lymphocytes