70 research outputs found
HSP70 and HSP90 Differentially Regulate Translocation of Extracellular Antigen to the Cytosol for Cross-Presentation
Antigens (Ag) from cancer or virus-infected cells must be internalized by dendritic cells (DCs) to be presented to CD8+ T cells, which eventually differentiate into Ag-specific cytotoxic T lymphocytes (CTLs) that destroy cancer cells and infected cells. This pathway is termed cross-presentation and is also implicated as an essential step in triggering autoimmune diseases such as Type I diabetes. Internalized Ag locates within endosomes, followed by translocation through a putative pore structure spanning endosomal membranes into the cytosol, where it is degraded by the proteasome to generate antigen peptides. During translocation, Ag is believed to be unfolded since the pore size is too narrow to accept native Ag structure. Here, we show that paraformaldehyde-fixed, structurally inflexible Ag is less efficient in cross-presentation because of diminished translocation into the cytosol, supporting the “unfolded Ag” theory. We also show that HSP70 inhibitors block both endogenous and cross-presentation. ImageStream analysis revealed that the inhibition in cross-presentation is not due to blocking of Ag translocation because a HSP70 inhibitor rather facilitates the translocation, which is in marked contrast to the effect of an HSP90 inhibitor that blocks Ag translocation. Our results indicate that Ag translocation to the cytosol in cross-presentation is differentially regulated by HSP70 and HSP90
Development of Pancreatic Acinar Cell Metaplasia During Gastric Repair in a Rat Duodenal Contents Reflux Model.
Background: We previously reported the development of pancreatic acinar cell metaplasia (PACM) in the glandular stomach of a duodenal contents reflux model (reflux model).Aims: We aimed to investigate the characteristics and histogenesis of PACM using a reflux model.Methods: A reflux model was created using 8-week-old male Wistar rats, which were killed up to 30 weeks postoperatively. Histological examination was performed to analyze the glandular stomach-jejunal anastomosis. Furthermore, electron microscopic images of PACM samples were compared with pancreatic and gastric glands removed from rats that had not undergone surgery. Immunostaining for α-amylase, HIK1083, TFF2, and Ki-67 was performed, and double fluorescent staining was carried out using antibodies against α-amylase and HIK1083, or α-amylase and TFF2.Results: In all reflux model rats, PACM was observed proximal to the glandular stomach-jejunal anastomosis, surrounded by pseudopyloric metaplasia. The number of chief cells was decreased in the deep part of the gland, where PACM occurred. Electron microscopy showed that PACM cells had greater numbers of rough endoplasmic reticulum tubules than chief cells, and exhibited pancreatic acinar cell morphology. Upon immunochemical staining, the regenerative foveolar epithelium and part of the pseudopyloric glands stained strongly positive for TFF2, whereas PACM cells were only weakly positive. Double fluorescent staining identified early lesions of PACM in the neck, which were double positive for α-amylase and TFF2, but negative for HIK1083.Conclusions:PACM could be induced by duodenal contents reflux. PACM originates from stem cells located in the neck of oxyntic glands during gastric mucosal regeneration
Alveolar rhabdomyosarcoma in the skin of the abdominal wall in an elderly patient: A case report
Alveolar rhabdomyosarcoma (ARMS) is a type of primitive round cell tumor that mainly develops in adolescents and young adults. Immunohistochemically, the expression of myogenic markers is a key clue for pathological diagnosis, and an aberrant expression of neuroendocrine markers and/or cytokeratin has also been reported. Therefore, an unusual clinical course complicated with aberrant neuroendocrine expression may make the diagnosis of ARMS difficult. In this report, we present a case of ARMS that developed in the skin of the abdominal wall in an elderly patient; the tumor cells expressed neuroendocrine markers. ARMS should be considered as a differential diagnosis of primitive round cell tumors in elderly patients and it is essential to confirm concurrent myogenic differentiation and PAX3/PAX7–FOXO1 fusion gene expression to make a pathological diagnosis. Keywords: Alveolar rhabdomyosarcoma, Primitive round cell tumor, Neuroendocrine marker, PAX3/PAX7–FOXO1 fusion gene, High-sensitivity RT-PC
Increase in plasma thrombin-activatable fibrinolysis inhibitor may not contribute to thrombotic tendency in antiphospholipid syndrome because of inhibitory potential of antiphospholipid antibodies toward TAFI activation
Background: The causes of thrombosis in antiphospholipid syndrome (APS) remain unknown, though several hypotheses in regard to hypofibrinolysis have been proposed. Objective: To clarify the mechanism, we measured plasma levels of thrombin-activatable fibrinolysis inhibitor (TAFI) in APS patients. Methods and Results: Both the TAFI antigen (TAFI:Ag) level measured with an ELISA, and thrombin-thrombomodulin-dependent TAFI activity (TAFI:Ac) were elevated in 68 APS patients as compared with those in 66 healthy controls, though they were lower than those in 46 patients with autoimmune diseases. As for the influence of antiphospholipid antibodies (aPL) on TAFI levels, the mean TAFI:Ac level in 39 SLE patients positive for APS was significantly lower than that in 27 SLE patients without APS, whereas there was no difference in TAFI:Ag between those groups. Furthermore, purified IgG from patients positive for aPL, and monoclonal aPL (EY2C9 and 23-1D) inhibited the activation of TAFI in a concentration dependent manner. Conclusion: These results suggest that aPL inhibits TAFI activation by affecting the function of thrombomodulin-thrombin complex through phospholipids. Although TAFI in plasma is elevated in autoimmune diseases including APS, we concluded that an elevated level is not likely a risk factor for thrombosis in APS patients, because of the inhibition of TAFI activation by aPL
Strategy Comparison of Endoscopic Ultrasound-Guided Gallbladder Drainage to Percutaneous Transhepatic Gallbladder Drainage, Following Failed Emergent Endoscopic Transpapillary Gallbladder Drainage
Endoscopic transpapillary gallbladder drainage (ETGBD) is recommended for patients with acute cholecystitis at high risk for surgery/percutaneous transhepatic gallbladder drainage (PTGBD). Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has higher success and mortality rates than ETGBD. Optimal endoscopic drainage remains controversial. Patients with moderate/severe acute cholecystitis and high risk for surgery/PTGBD who underwent ETGBD were enrolled. In the new-ETGBD (N-ETGBD)/traditional-ETGBD (T-ETGBD) strategy, patients in whom the initial ETGBD failed underwent rescue-EUS-GBD in the same endoscopic session/rescue-PTGBD, respectively. Therapeutic outcomes were compared. Patients who could not undergo rescue-EUS-GBD/PTGBD owing to poor general conditions received conservative treatment. Technical success was defined as successful ETGBD or successful rescue-EUS-GBD/PTGBD. Forty-one/forty patients were enrolled in the N-ETGBD/T-ETGBD groups, respectively. The N-ETGBD group had a higher, though non-significant, technical success rate compared to the T-ETGBD group (97.6 vs. 90.0%, p = 0.157). The endoscopic technical success rate was significantly higher in the N-ETGBD than in the T-ETGBD group (97.6 vs. 82.5%, p = 0.023). The clinical success/adverse event rates were similar between both groups. The hospitalization duration was significantly shorter in the N-ETGBD than in the T-ETGBD group (6.6 ± 3.9 vs. 10.1 ± 6.4 days, p < 0.001). ETGBD with EUS-GBD as a rescue backup may be an ideal hybrid drainage for emergency endoscopic gallbladder drainage in high-risk surgical patients
Su1163 Comparing Esomeprazole Based Versus Rabeprazole Based Triple Therapy for the Eradication of Helicobacter pylori in Japan
Adeno-associated virus vector-mediated production of hepatocyte growth factor attenuates liver fibrosis in mice
Tu1249 The Extent of Small Bowel Injury Induced by a Selective Cyclooxygenase-2 Inhibitors Compared With That Induced by Conventional Nonsteroidal Anti-Inflammatory Drugs in Healthy Subjects: a Randomized Cross-Over Study
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