Differential involvement of LUBAC‐mediated linear ubiquitination in intestinal epithelial cells and macrophages during intestinal inflammation

Disruption of the intestinal epithelial barrier and dysregulation of macrophages are major factors contributing to the pathogenesis of inflammatory bowel diseases (IBDs). Activation of NF-κB and cell death are involved in maintaining intestinal homeostasis in a cell type-dependent manner. Although both are regulated by linear ubiquitin chain assembly complex (LUBAC)-mediated linear ubiquitination, the physiological relevance of linear ubiquitination to intestinal inflammation remains unexplored. Here, we used two experimental mouse models of IBD (intraperitoneal LPS and oral dextran sodium sulfate [DSS] administration) to examine the role of linear ubiquitination in intestinal epithelial cells (IECs) and macrophages during intestinal inflammation. We did this by deleting the linear ubiquitination activity of LUBAC specifically from IECs or macrophages. Upon LPS administration, loss of ligase activity in IECs induced mucosal inflammation and augmented IEC death. LPS-mediated death of LUBAC-defective IECs was triggered by TNF. IEC death was rescued by an anti-TNF antibody, and TNF (but not LPS) induced apoptosis of organoids derived from LUBAC-defective IECs. However, augmented TNF-mediated IEC death did not overtly affect the severity of colitis after DSS administration. By contrast, defective LUBAC ligase activity in macrophages ameliorated DSS-induced colitis by attenuating both infiltration of macrophages and expression of inflammatory cytokines. Decreased production of macrophage chemoattractant MCP-1/CCL2, as well as pro-inflammatory IL-6 and TNF, occurred through impaired activation of NF-κB and ERK via loss of ligase activity in macrophages. Taken together, these results indicate that both intraperitoneal LPS and oral DSS administrations are beneficial for evaluating epithelial integrity under inflammatory conditions, as well as macrophage functions in the event of an epithelial barrier breach. The data clarify the cell-specific roles of linear ubiquitination as a critical regulator of TNF-mediated epithelial integrity and macrophage pro-inflammatory responses during intestinal inflammation

The diagnostic ability of SPECT/CT fusion imaging for gastrointestinal bleeding : a retrospective study

Background Blood loss from the gastrointestinal tract can be an acute and life-threatening event. For the treatment of gastrointestinal bleeding, it is important to accurately detect gastrointestinal bleeding and to localize the sites of bleeding. The purpose of this study was to retrospectively assess the capabilities of SPECT/CT in the diagnosis of gastrointestinal bleeding by a comparison with planar imaging alone as well as planar and SPECT. Methods We conducted a retrospective analysis of 20 patients (21 examinations) who underwent gastrointestinal bleeding scintigraphy in the past 7 years and in whom the bleeding site was identified by endoscopy or capsule endoscopy, or in whom no evidence of gastrointestinal bleeding was identified during the clinical course. Five patients (5 examinations) were diagnosed by planar imaging (planar group). Eight patients (9 examinations) were diagnosed by planar imaging and SPECT (planar + SPECT group). Seven patients (7 examinations) were diagnosed by planar imaging and SPECT/CT (planar + SPECT/CT group). We calculated the diagnostic ability of each method in detecting the presence of bleeding, as well as the ability of each method to identify the sites of bleeding. The sensitivity, specificity, and accuracy of the methods were compared. Results The diagnostic ability of the three imaging methods in detecting the presence of gastrointestinal bleeding was as follows. Planar imaging showed 100% sensitivity (3/3), 100% specificity (2/2), and 100% accuracy (5/5). Planar + SPECT imaging showed 85.7% sensitivity (6/7), 100% specificity (2/2), and 88.9% accuracy (8/9). Planar + SPECT/CT imaging showed 100% sensitivity (6/6), 100% specificity (1/1), and 100% accuracy (7/7). The diagnostic ability of the three modalities in detecting the site of bleeding was as follows: planar, 33.3% (1/3); planar + SPECT, 71.4% (5/7); and planar + SPECT/CT, 100% (6/6). Conclusions All 3 imaging methods showed good accuracy in detecting the presence of gastrointestinal bleeding. The addition of SPECT or SPECT/CT made the anatomical position of the uptake clear and contributed to the localization of the site of gastrointestinal bleeding. Planar + SPECT/CT imaging therefore showed the highest diagnostic ability for detecting the site of gastrointestinal bleeding

短時間の造影ダイナミック灌流画像を用いた脳腫瘍の質的診断について

This study sought to determine the diagnostic utility of perfusion parameters derived from dynamic contrast-enhanced (DCE) perfusion MRI with a short acquisition time (approximately 3.5 min) in patients with glioma, brain metastasis, and primary CNS lymphoma (PCNSL). Twenty-six patients with 29 lesions (4 low-grade glioma, 13 high-grade glioma, 7 metastasis, and 5 PCNSL) underwent DCE-MRI in a 3 T scanner. A ROI was placed on the hotspot of each tumor in maps for volume transfer contrast Ktrans, extravascular extracellular volume Ve, and fractional plasma volume Vp. We analyzed differences in parameters between tumors using the Mann–Whitney U test. We calculated sensitivity and specificity using receiver operating characteristics analysis. Mean K trans values of LGG, HGG, metastasis and PCNSL were 0.034, 0.31, 0.38, 0.44, respectively. Mean Ve values of each tumors was 0.036, 0.57, 0.47, 0.96, and mean Vp value of each tumors was 0.070, 0.086, 0.26, 0.17, respectively. Compared with other tumor types, low-grade glioma showed lower Ktrans (P < 0.01, sensitivity = 88%, specificity = 100%) and lower Ve (P < 0.01, sensitivity = 96%, specificity = 100%). PCNSL showed higher Ve (P < 0.01, sensitivity = 100%, specificity = 88%), but the other perfusion parameters overlapped with those of different histology. Kinetic parameters derived from DCE-MRI with short acquisition time provide useful information for the differential diagnosis of brain tumors

The diagnostic ability of SPECT/CT fusion imaging for gastrointestinal bleeding: a retrospective study

Abstract Background Blood loss from the gastrointestinal tract can be an acute and life-threatening event. For the treatment of gastrointestinal bleeding, it is important to accurately detect gastrointestinal bleeding and to localize the sites of bleeding. The purpose of this study was to retrospectively assess the capabilities of SPECT/CT in the diagnosis of gastrointestinal bleeding by a comparison with planar imaging alone as well as planar and SPECT. Methods We conducted a retrospective analysis of 20 patients (21 examinations) who underwent gastrointestinal bleeding scintigraphy in the past 7 years and in whom the bleeding site was identified by endoscopy or capsule endoscopy, or in whom no evidence of gastrointestinal bleeding was identified during the clinical course. Five patients (5 examinations) were diagnosed by planar imaging (planar group). Eight patients (9 examinations) were diagnosed by planar imaging and SPECT (planar + SPECT group). Seven patients (7 examinations) were diagnosed by planar imaging and SPECT/CT (planar + SPECT/CT group). We calculated the diagnostic ability of each method in detecting the presence of bleeding, as well as the ability of each method to identify the sites of bleeding. The sensitivity, specificity, and accuracy of the methods were compared. Results The diagnostic ability of the three imaging methods in detecting the presence of gastrointestinal bleeding was as follows. Planar imaging showed 100% sensitivity (3/3), 100% specificity (2/2), and 100% accuracy (5/5). Planar + SPECT imaging showed 85.7% sensitivity (6/7), 100% specificity (2/2), and 88.9% accuracy (8/9). Planar + SPECT/CT imaging showed 100% sensitivity (6/6), 100% specificity (1/1), and 100% accuracy (7/7). The diagnostic ability of the three modalities in detecting the site of bleeding was as follows: planar, 33.3% (1/3); planar + SPECT, 71.4% (5/7); and planar + SPECT/CT, 100% (6/6). Conclusions All 3 imaging methods showed good accuracy in detecting the presence of gastrointestinal bleeding. The addition of SPECT or SPECT/CT made the anatomical position of the uptake clear and contributed to the localization of the site of gastrointestinal bleeding. Planar + SPECT/CT imaging therefore showed the highest diagnostic ability for detecting the site of gastrointestinal bleeding

カンゴシ ノ シュウロウ ゴ ニ ショウジル カシ フシュ ニ タイスル ガショウ ト ヨウシュテキ リンパドレナージ デノ カシ シュウイケイ ヘンカ ノ ヒカク

The purpose of this study was to clarify outcomes on the lower limbs in cases of lying and taking Manual Lymph Drainage (MLD) for nurses after an 8-hour shift. The participants were eight females who were not pregnant, over 35 years old and had not had any operations on their bodies. We measured circumference of seven points on their lower limbs by two times on different days. It meant that we measured before and after at the time of lying in bed or taking MLD for 30 minutes. By the lying in bed, four points of the left side and one point of the right side decreased significantly the lower limb’s circumference. However, the circumference of the inguinal region and popliteal fossa did not change. By taking MLD, six points of on the left side and three points of right side decreased significantly the lower limb’s circumference. We found that the circumference of the lower limbs, including the inguinal region and popliteal fossa, were decreased. This result suggested MLD was a useful skill for to hasten blood circulation. To decrease the circumference of the lower limbs, we suggest that it is not only lying, but also add to MLD on their lower limbs