Histiocytic neoplasms are rare diseases involving macrophages, dendritic cells, and monocytes. They include Langer‑ hans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), and histiocytic sarcoma. Histiocytic neoplasms are characterized by varied clinical courses and prognoses, necessitating a nuanced understanding of their classification, epidemiology, and clinical manifestations. Genetic studies have revealed somatic mutations, predominantly in the MAPK pathway, suggesting a clonal neoplastic nature.This review covers the current understanding of histiocytic neoplasms, molecular pathophysiology, with a particular focus on mutations in genes such as BRAF, MAP2K1, and the PI3K-AKT signaling pathways, and evolving treatment strategies, especially focusing on LCH, ECD, RDD, and JXG. The treatment landscape has evolved with advancements in targeted therapies. BRAF inhibitors, such as vemurafenib and dabrafenib, have shown efficacy, especially in highrisk LCH cases; however, challenges remain, including relapse post-treatment discontinuation, and adverse effects.MEK inhibitors have also demonstrated effectiveness, and cobimetinib has recently been approved for use in adults.Further research is required to determine the optimal treatment duration and strategies for managing therapy inter‑ ruptions. Advancements in molecular genetics and targeted therapies have revolutionized the management of histio‑ cytic neoplasms. However, ongoing research is crucial for optimizing patient outcomes.

Histiocytic neoplasms are rare diseases involving macrophages, dendritic cells, and monocytes. They include Langer‑ hans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), and histiocytic sarcoma. Histiocytic neoplasms are characterized by varied clinical courses and prognoses, necessitating a nuanced understanding of their classification, epidemiology, and clinical manifestations. Genetic studies have revealed somatic mutations, predominantly in the MAPK pathway, suggesting a clonal neoplastic nature.This review covers the current understanding of histiocytic neoplasms, molecular pathophysiology, with a particular focus on mutations in genes such as BRAF, MAP2K1, and the PI3K-AKT signaling pathways, and evolving treatment strategies, especially focusing on LCH, ECD, RDD, and JXG. The treatment landscape has evolved with advancements in targeted therapies. BRAF inhibitors, such as vemurafenib and dabrafenib, have shown efficacy, especially in highrisk LCH cases; however, challenges remain, including relapse post-treatment discontinuation, and adverse effects.MEK inhibitors have also demonstrated effectiveness, and cobimetinib has recently been approved for use in adults.Further research is required to determine the optimal treatment duration and strategies for managing therapy inter‑ ruptions. Advancements in molecular genetics and targeted therapies have revolutionized the management of histio‑ cytic neoplasms. However, ongoing research is crucial for optimizing patient outcomes.

Histiocytic neoplasms are rare diseases involving macrophages, dendritic cells, and monocytes. They include Langer‑ hans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), and histiocytic sarcoma. Histiocytic neoplasms are characterized by varied clinical courses and prognoses, necessitating a nuanced understanding of their classification, epidemiology, and clinical manifestations. Genetic studies have revealed somatic mutations, predominantly in the MAPK pathway, suggesting a clonal neoplastic nature.This review covers the current understanding of histiocytic neoplasms, molecular pathophysiology, with a particular focus on mutations in genes such as BRAF, MAP2K1, and the PI3K-AKT signaling pathways, and evolving treatment strategies, especially focusing on LCH, ECD, RDD, and JXG. The treatment landscape has evolved with advancements in targeted therapies. BRAF inhibitors, such as vemurafenib and dabrafenib, have shown efficacy, especially in highrisk LCH cases; however, challenges remain, including relapse post-treatment discontinuation, and adverse effects.MEK inhibitors have also demonstrated effectiveness, and cobimetinib has recently been approved for use in adults.Further research is required to determine the optimal treatment duration and strategies for managing therapy inter‑ ruptions. Advancements in molecular genetics and targeted therapies have revolutionized the management of histio‑ cytic neoplasms. However, ongoing research is crucial for optimizing patient outcomes.

Hepatobiliary scintigraphy has been widely used for the differential diagnosis of neonatal cholestasis. Relatively good hepatic uptake with no evidence of excretion into the bowel for up to 24 h is a representative finding of biliary atresia. Hepatobiliary scintigraphy has very high sensitivity and moderate specificity. Here, we report a false-positive case of hepatobiliary scintigraphy in a child with a choledochal cyst, which mimicked biliary atresia.

Purpose: The purpose of this study was to determine the lowest Tl-201 dose that does not reduce the image quality of myocardial perfusion SPECT (MPS) by Poisson resampling simulation. Methods: One hundred and twelve consecutive MPS data from patients with suspected or known coronary artery disease were collected retrospectively. Stress and rest MPS data were resampled using the Poisson method with 33%, 50%, 67%, and 100% count settings. Two nuclear medicine physicians assessed the image quality of reconstructed data visually by giving grades from − 2 to + 2. The summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) were obtained on the workstation. Image quality grades and semi-quantitative scores were then compared among these resampled images. Results: The proportions of “adequate” image quality were 0.48, 0.75, 0.92, and 0.96 for the groups of images with 33%, 50%, 67%, and 100% data, respectively. The quality of the resampled images was significantly degraded at 50% and 33% count settings, while the image quality was not different between 67 and 100% count settings. We also found that high body mass index further decreased image quality at 33% count setting. Among the semi-quantitative parameters, SSS and SRS showed a tendency to increase with a decline in count. Conclusion Based on the simulation results, Tl-201 dose for MPS can be reduced to 74 MBq without significant loss of image quality. However, the SSS and SRS can be changed significantly, and it needs to be further verified under the different conditions.

BACKGROUND/OBJECTIVES: Inflammatory Bowel Disease (IBD) has rapidly escalated in Asia (including Korea) due to increasing westernized diet patterns subsequent to industrialization. Factors associated with endoplasmic reticulum (ER) stress are demonstrated to be one of the major causes of IBD. This study was conducted to investigate the effect of Lycium barbarum (L. barbarum) on ER stress. MATERIALS/METHODS: Mouse embryonic fibroblast (MEF) cell line and polarized Caco-2 human intestinal epithelial cells were treated with crude extract of the L. chinense fruit (LF). Paracellular permeability was measured to examine the effect of tight junction (TJ) integrity. The regulatory pathways of ER stress were evaluated in MEF knockout (KO) cell lines by qPCR for interleukin (IL) 6, IL8 and XBP1 spliced form (XBP1s). Immunoglobulin binding protein (BiP), XBP1s and CCAAT/enhancer-binding homologous protein (CHOP) expressions were measured by RT-PCR. Scanning Ion Conductance Microscopy (SICM) at high resolution was applied to observe morphological changes after treatments. RESULTS: Exposure to LF extract strengthened the TJ, both in the presence and absence of inflammation. In polarized Caco-2 pretreated with LF, induction in the expression of proinflammatory marker IL8 was not significant, whereas ER stress marker XBP1s expression was significantly increased. In wild type (wt) MEF cells, IL6, CHOP and XBP1 spliced form were dose-dependently induced when exposed to 12.5–50 µg/mL extract. However, absence of XBP1 or IRE1α in MEF cells abolished this effect. CONCLUSION: Results of this study show that LF treatment enhances the barrier function and reduces inflammation and ER stress in an IRE1α-XBP1-dependent manner. These results suggest the preventive effect of LF on healthy intestine, and the possibility of reducing the degree of inflammatory symptoms in IBD patients.
Animals ; Asia ; Carrier Proteins ; Cell Line ; Diet ; Endoplasmic Reticulum ; Epithelial Cells ; Fibroblasts ; Fruit ; Humans ; Immunoglobulins ; Inflammation ; Inflammatory Bowel Diseases ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Intestines ; Lycium ; Mice ; Microscopy ; Permeability ; Tight Junctions

PURPOSE: Bone single-photon emission computed tomography/computed tomography (SPECT/CT) has been widely used for evaluation of femoral head viability in patients with femoral neck fracture. The current study aimed to investigate utility of standardized uptake value (SUV) from quantitative bone SPECT/CT for assessment of femoral head viability.METHODS: From March 2015 to November 2018, quantitative bone SPECT/CT was performed in 9 patients with non-viable femoral head post femoral neck fracture and in 31 controls. Maximum (SUV(max)), mean (SUVmean), and minimum standardized uptake values (SUVmin) were measured over femoral head and neck. Mann-Whitney U test with Bonferroni correction was used to compare SUVs of ipsilateral and contralateral femurs from femoral neck fracture patients with those of control femurs.RESULTS: As for femoral head viability, SUV(max) and SUVmean were not significantly decreased in non-viable femoral heads compared to those in controls. Only the SUVmin was significantly reduced in non-viable femoral heads (mean ± standard deviation, 0.57 ± 0.38) than in controls (0.95 ± 0.26, p = 0.006) and contralateral femoral heads (1.36 ± 0.59, p = 0.008). The cutoff SUVmin of 0.61 (g/mL) yielded a sensitivity of 77.8% and specificity of 87.1% for detection of non-viable femoral heads (p = 0.006). Contralateral femoral necks of the femoral neck fracture patients showed significantly higher SUVmean and SUVmin (3.17 ± 1.20 and 1.64 ± 0.63) than those of controls (2.32 ± 0.53 and 1.04 ± 0.27; p = 0.021 and p = 0.002, respectively), which seemed to reflect weight bearing effect or metabolic derangement.CONCLUSIONS: The non-viable femoral heads from the femoral neck fracture showed significantly reduced SUVmin. Quantitative bone SPECT/CT holds promise for objective evaluation of femoral head viability.
Femoral Neck Fractures ; Femur ; Femur Neck ; Head ; Humans ; Neck ; Sensitivity and Specificity ; Weight-Bearing

PURPOSE: Bone single-photon emission computed tomography/computed tomography (SPECT/CT) has been widely used for evaluation of femoral head viability in patients with femoral neck fracture. The current study aimed to investigate utility of standardized uptake value (SUV) from quantitative bone SPECT/CT for assessment of femoral head viability. METHODS: From March 2015 to November 2018, quantitative bone SPECT/CT was performed in 9 patients with non-viable femoral head post femoral neck fracture and in 31 controls. Maximum (SUV(max)), mean (SUVmean), and minimum standardized uptake values (SUVmin) were measured over femoral head and neck. Mann-Whitney U test with Bonferroni correction was used to compare SUVs of ipsilateral and contralateral femurs from femoral neck fracture patients with those of control femurs. RESULTS: As for femoral head viability, SUV(max) and SUVmean were not significantly decreased in non-viable femoral heads compared to those in controls. Only the SUVmin was significantly reduced in non-viable femoral heads (mean ± standard deviation, 0.57 ± 0.38) than in controls (0.95 ± 0.26, p = 0.006) and contralateral femoral heads (1.36 ± 0.59, p = 0.008). The cutoff SUVmin of 0.61 (g/mL) yielded a sensitivity of 77.8% and specificity of 87.1% for detection of non-viable femoral heads (p = 0.006). Contralateral femoral necks of the femoral neck fracture patients showed significantly higher SUVmean and SUVmin (3.17 ± 1.20 and 1.64 ± 0.63) than those of controls (2.32 ± 0.53 and 1.04 ± 0.27; p = 0.021 and p = 0.002, respectively), which seemed to reflect weight bearing effect or metabolic derangement. CONCLUSIONS The non-viable femoral heads from the femoral neck fracture showed significantly reduced SUVmin. Quantitative bone SPECT/CT holds promise for objective evaluation of femoral head viability.

Remifentanil is commonly used in operating rooms and intensive care units for the purpose of anesthesia and sedation or analgesia. Although remifentanil may significantly affect the bone regeneration process in patients, there have been few studies to date on the effects of remifentanil on bone physiology. The purpose of this study was to investigate the effects of remifentanil on osteoclast differentiation and bone resorption. Bone marrow-derived macrophages (BMMs) were cultured for 4 days in remifentanil concentrations ranging from 0 to 100 ng/ml, macrophage colony-stimulating factor (M-CSF) alone, or in osteoclastogenic medium to induce the production of mature osteoclasts. To determine the degree of osteoclast maturity, tartrate-resistant acid phosphatase (TRAP) staining was performed. RT-PCR and western blotting analyses were used to determine the effect of remifentanil on the signaling pathways involved in osteoclast differentiation and maturation. Bone resorption and migration of BMMs were analyzed to determine the osteoclastic activity. Remifentanil reduced the number and size of osteoclasts and the formation of TRAP-positive multinuclear osteoclasts in a dose-dependent manner. Expression of c-Fos and NFATC1 was most strongly decreased in the presence of RANKL and remifentanil, and the activity of ERK was also inhibited by remifentanil. In the bone resorption assay, remifentanil reduced bone resorption and did not significantly affect cell migration. This study shows that remifentanil inhibits the differentiation and maturation of osteoclasts and reduces bone resorption.
Acid Phosphatase ; Analgesia ; Anesthesia ; Blotting, Western ; Bone Regeneration ; Bone Resorption* ; Cell Movement ; Humans ; Intensive Care Units ; Macrophage Colony-Stimulating Factor ; Macrophages ; Operating Rooms ; Osteoclasts* ; Physiology

BACKGROUND: We aimed to determine the effect of fibronectin (FN)-immobilized microgrooved titanium (Ti) on human gingival fibroblast proliferation, gene expression and protein expression. METHODS: Photolithography was used to fabricate the microgrooved Ti, and amine funtionalization (silanization) was used for FN immobilization on titanium surfaces. Cell proliferation, gene expression and protein expression were analyzed, followed by multiple regression analysis for determining the influential factors on cell proliferation. RESULTS: FN-immobilized microgrooved Ti significantly enhanced the fibroblast proliferation in various timelines of culture, among which a burst of fivefold increase is induced at 96 h of culture compared to that on the control smooth Ti. We suggest a presence of the synergistic promotion effect of microgrooves and FN immobilization on fibroblast proliferation. Through a series of analyses on the expression of various genes and proteins involved in cell adhesion and proliferation, cyclin-dependent kinase 6, cyclin D1, integrin α5, oncogene c-Src, osteonectin, paxillin and talin-2 were determined as influential factors on promoting fibroblast proliferation induced by FN-immobilized microgrooved Ti. CONCLUSION: FN-immobilized microgrooved Ti can act as an effective surface for enhancing fibroblast proliferation, and can be used for promoting soft tissue response on the connective tissue attachment zone of biomaterial surfaces.
Cell Adhesion ; Cell Proliferation* ; Connective Tissue ; Cyclin D1 ; Cyclin-Dependent Kinase 6 ; Fibroblasts* ; Fibronectins ; Gene Expression ; Humans* ; Immobilization ; Oncogenes ; Osteonectin ; Paxillin ; Titanium*