Activation Pattern of Langerhans Cells in the Afferent and Efferent Phases of Contact Hypersensitivity

Langerhans cells are MHC class II (Ia) positive antigen- presenting cells that play a crucial role in the induction of contact hypersensitivity (CHS). The topical application of a hapten modifies the cell surface moieties of Langerhans cells, and activates Langerhans cells to increase their size and Ia intensity. The haptenated and activated Langerhans cells emigrate from the epidermis and thus the in situ density of Langerhans cells usually decreases during 24-48h after the hapten application in CHS. To determine whether the early activation pattern of Langerhans cells is different between the afferent phase and the efferent phase of CHS, we compared the density and morphologic changes of Langerhans cells in CHS to trinitrochlorobenzene using nonsensitized and sensitized mice. We found that the application of a hapten induces more significant enlargement of Langerhans cell size in the afferent phase than in the efferent phase, whereas the reduction of Langerhans cell density is more marked in the efferent than in the afferent phase of CHS. Moreover, topical immunosuppressive drugs inhibit the in situ activation of Langerhans cells

Hyperhomocysteinemia induced by excessive methionine intake promotes rupture of cerebral aneurysms in ovariectomized rats.

BackgroundHyperhomocysteinemia (HHcy) is associated with inflammation and a rise in the expression of matrix metalloproteinase-9 (MMP-9) in the vascular wall. However, the role of HHcy in the growth and rupture of cerebral aneurysms remains unclear.MethodsThirteen-week-old female Sprague-Dawley rats were subject to bilateral ovariectomy and ligation of the right common carotid artery and fed an 8 % high-salt diet to induce cerebral aneurysms. Two weeks later, they underwent ligation of the bilateral posterior renal arteries. They were divided into two groups and methionine (MET) was or was not added to their drinking water. In another set of experiments, the role of folic acid (FA) against cerebral aneurysms was assessed.ResultsDuring a 12-week observation period, subarachnoid hemorrhage due to aneurysm rupture was observed at the anterior communicating artery (AcomA) or the posterior half of the circle of Willis. HHcy induced by excessive MET intake significantly increased the incidence of ruptured aneurysms at 6-8 weeks. At the AcomA of rats treated with MET, we observed the promotion of aneurysmal growth and infiltration by M1 macrophages. Furthermore, the mRNA level of MMP-9, the ratio of MMP-9 to the tissue inhibitor of metalloproteinase-2, and the level of interleukin-6 were higher in these rats. Treatment with FA abolished the effect of MET, suggesting that the inflammatory response and vascular degradation at the AcomA is attributable to HHcy due to excessive MET intake.ConclusionsWe first demonstrate that in hypertensive ovariectomized rats, HHcy induced by excessive MET intake may be associated with the propensity of the aneurysm wall to rupture

A Case of Metastatic Extramammary Paget's Disease Responding to Trastuzumab plus Paclitaxel Combination Therapy

There is no effective treatment for advanced extramammary Paget's disease (EMPD). The human epidermal growth factor receptor 2 (HER2) protein is often overexpressed in EMPD. Trastuzumab is a humanized monoclonal antibody against HER2 used in the treatment of breast cancers in which HER2 is overexpressed. We report a case of advanced EMPD in which trastuzumab and paclitaxel combination therapy was effective. The patient was a 70-year-old Japanese woman who presented with EMPD on the vulva and multiple metastatic lymph nodes. Immunohistochemical staining revealed strong HER2 protein expression in the primary tumor and metastatic lymph nodes. The patient received trastuzumab and paclitaxel. After 4 courses of this regimen, the mass on the vulva and the metastatic lymph nodes regressed. Our findings may imply that trastuzumab plus paclitaxel combination therapy is useful for the treatment of advanced EMPD overexpressing HER2

Perforator Vessels in Ischiorectal Fossa

Background: Perforator flaps based on the ischiorectal fossa (IRF) (ie, internal pudendal artery perforator flaps) are useful for perineal reconstruction. The three-dimensional characterization of perforator arteries in the IRF remains unclear, as the IRF contains thick adipose tissue as well as organs, such as the rectum, vagina, and urethra. This study aimed to evaluate perforators in the IRF to guide the safe elevation of skin flaps designed based on the IRF. Methods: IRF vessels were examined in 200 bilateral computed tomography angiography scans performed in 100 patients. We examined branching patterns arising from the internal iliac artery and the origins of the skin perforators in the IRF. Results: The branching patterns of the internal iliac artery were divided into three groups: perforators derived exclusively from the internal pudendal artery (78%), perforators derived from the internal pudendal artery and the inferior gluteal artery (18%), and perforators derived exclusively from the inferior gluteal artery (4%). The average number of perforators in the IRF was 1.5 ± 0.7. The number of perforators was significantly higher in women than in men. The perforator arteries were found exclusively around the medial and dorsal sides of the ischial tuberosity. Conclusions: We found that perforators in the IRF were stable. All cases had more than one skin perforator, which was mainly derived from the internal pudendal artery. Although perforators cannot be identified during flap elevation because the fatty tissue in the IRF is very thick, physicians must focus on preserving the perforator-containing fatty tissue around the ischial tuberosity

Effects of Acid Soils on Plant Growth and Successful Revegetation in the Case of Mine Site

Acid soils are caused by mining, potentially causing the death of plants. Although soil pH is one of the useful indicators to evaluate acid soil conditions for successful revegetation, the dissolution of harmful elements under acidic conditions should be considered in addition to the tolerance mechanism of plants in mines. Thus, this study aims to report the current situation of acid soils and plant growth in mine site and to elucidate the effects of acid soils on plant growth over time through field investigation and a vegetation test. The results showed that the dissolution of Al from acid soils which were attributed to the dissolution of sulfides influenced plant growth. Not only soil pH but also the assessment of the dissolution of sulfides over time is crucial for successful revegetation, suggesting that net acid producing potential (NAPP) and net acid generation (NAG) pH, which are used for evaluating the formation of acidic water, are useful to evaluate soil conditions for the revegetation. Furthermore, acid-tolerant plant survived under acidic conditions by increasing the resistance against acidic conditions with the plant growth. Such factors and the proper selection of plant species play an important role in achieving successful revegetation in mines

ユビキリン２は低酸素ストレスに耐性を示すことで骨肉腫の増殖を促進させる

Ubiquilin 2 (UBQLN2), a member of the ubiquitin-like protein family (ubiquilins), maintains protein homeostasis. Although UBQLN2 has been implicated in the pathogenesis of neurodegenerative diseases, it is also associated with mali­gnant tumors. Therefore, we examined whether UBQLN2 plays a role in human osteosarcoma. The human osteosarcoma cell line MG63 was transfected with UBQLN2 siRNA and cultured under hypoxic conditions. The rat osteosarcoma cell line COS1NR was inoculated into Fischer 344 rats, followed by injection of UBQLN2 siRNA with atelocollagen. An immunohistochemical analysis of UBQLN2 was performed using 34 cases of human high-grade osteosarcomas, and metastasis-free survival was estimated by the Kaplan-Meier method. Silencing of UBQLN2 by siRNA transfection under hypoxia led to activation of JNK and p38, resulting in induction of apoptosis in the osteosarcoma cell line MG63. Injection of UBQLN2 siRNA suppressed tumor growth in the rat osteosarcoma model, followed by apoptosis induction. The immunohistochemical examination revealed that high UBQLN2 expression was significantly associated with the unfavorable metastasis-free survival of osteosarcoma patients. UBQLN2 plays an important role in resistance to hypoxic stress and enhances tumor progression in osteosarcoma. UBQLN2 may be a new molecular target for chemotherapeutics and a useful clinicopathological marker in human osteosarcoma.博士（医学）・甲第637号・平成27年5月28日Copyright © Spandidos Publications 2015本文のリンク：http://dx.doi.org/10.3892/or.2015.378

Antineoplastic Effects of Gamma Linolenic Acid on Hepatocellular Carcinoma Cell Lines

The aim of this study was to investigate the effect and the mechanism of gamma linolenic acid (GLA) treatment on human hepatocellular (HCC) cell lines. The human HCC cell line HuH7 was exposed to GLA. Cell proliferation and reactive oxygen species (ROS) generation including lipid peroxidation and apoptosis were compared. We then used a cDNA microarray analysis to investigate the molecular changes induced by GLA. GLA treatment significantly reduced cell proliferation, generated ROS, and induced apoptosis. After 24 h exposure of Huh7 cells to GLA, we identified several genes encoding the antioxidant proteins to be upregulated: heme oxygenase-1 (HO-1), aldo-keto reductase 1 family C1 (AKR1C1), C4 (AKR1C4), and thioredoxin (Trx). The HO-1 protein levels were overexpressed in Huh7 cells after GLA exposure using a Western blot analysis. Furthermore, chromium mesoporphyrin (CrMP), an inhibitor of HO activity, significantly potentiated GLA cytotoxicity. GLA treatment has induced cell growth inhibition, ROS generation including lipid peroxidation, and HO-1 production for antioxidant protection against oxidative stress caused by GLA in Huh7 cells. GLA treatment should be considered as a therapeutic modality in patients with advanced HCC

Alpha-pinene and dizocilpine (MK-801) attenuate kindling development and astrocytosis in an experimental mouse model of epilepsy

Understanding the molecular and cellular mechanisms involved during the onset of epilepsy is crucial for elucidating the overall mechanism of epileptogenesis and therapeutic strategies. Previous studies, using a pentylenetetrazole (PTZ)-induced kindling mouse model, showed that astrocyte activation and an increase in perineuronal nets (PNNs) and extracellular matrix (ECM) molecules occurred within the hippocampus. However, the mechanisms of initiation and suppression of these changes, remain unclear. Herein, we analyzed the attenuation of astrocyte activation caused by dizocilpine (MK-801) administration, as well as the anticonvulsant effect of α-pinene on seizures and production of ECM molecules. Our results showed that MK-801 significantly reduced kindling acquisition, while α-pinene treatment prevented an increase in seizures incidences. Both MK-801 and α-pinene administration attenuated astrocyte activation by PTZ and significantly attenuated the increase in ECM molecules. Our results indicate that astrocyte activation and an increase in ECM may contribute to epileptogenesis and suggest that MK-801 and α-pinene may prevent epileptic seizures by suppressing astrocyte activation and ECM molecule production