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Find video protocols related to scientific articles indexed in Pubmed.
Effect of Indirect Neural Decompression Through Oblique Lateral Interbody Fusion (OLIF) for Degenerative Lumbar Disease.
Spine
PUBLISHED: 11-14-2014
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Study Design. Prospective consecutive clinical study to assess the decompressive benefit and outcome of OLIF for lumbar degenerative diseases.Objective. To evaluate radiologically the effect of interbody distraction upon neuroformal patency via an anterolateral retroperitoneal approach for the treatment of lumbar degenerative diseases.Summary of Background Data. Traditional treatment for symptomatic lumbar stenosis uses direct posterior decompression with or without fusion. Symptoms of radiculopathy and neurological claudication may also be alleviated indirectly through restoration of intervertebral and foraminal heights and correction of spinal alignment.Methods. Twenty-eight consecutive patients presenting with degenerative conditions that included concomitant lumbar stenosis underwent OLIF combined with percutaneous pedicle screw fixation at 52 lumbar levels without neuromonitoring. Magnetic resonance imaging (MRI) was obtained successfully for 48 of 52 levels. The cross-sectional area of the thecal sac (CSA) was measured preoperatively and postoperatively on T2-weighted axial MRI images. Differences in CSA were compared, and the relationship between the ratio of CSA extension to the preoperative CSA was assessed. The change in disc height (DH) and segmental disc angle (SDA) were measured. The relationships between CSA, DH, SDA, and clinical results were assessed by correlational analysis.Results. Twenty-eight OLIFs were performed successfully without neural complications. There was clinical improvement in all cases. The mean CSA increased from 99.6 mm preoperatively to 134.3 mm postoperatively (P < 0.001). The median CSA extension ratio was 30.2% and this correlated inversely with preoperative CSA. DH, SDA, and clinical results improved significantly. Multivariate regression analysis demonstrated that the preoperative CSA was the only independent factor that correlated inversely with the CSA extension ratio (corrected R = 0.361; P < 0.001).Conclusion. Spinal stenosis was resolved successfully by indirect decompression through a mini-open anterolateral retroperitoneal approach without the need for neuromonitoring.
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Inflammasome Activation by Mitochondrial Oxidative Stress in Macrophages Leads to the Development of Angiotensin II-Induced Aortic Aneurysm.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 11-08-2014
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Abdominal aortic aneurysm (AAA) is considered a chronic inflammatory disease; however, the molecular basis underlying the sterile inflammatory response involved in the process of AAA remains unclear. We previously showed that the inflammasome, which regulates the caspase-1-dependent interleukin-1? production, mediates the sterile cardiovascular inflammatory responses. Therefore, we hypothesized that the inflammasome is a key mediator of initial inflammation in AAA formation.
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Outcomes and complications of reconstruction using tumor-bearing frozen autografts in patients with metastatic bone tumors.
Anticancer Res.
PUBLISHED: 10-03-2014
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Tumor-bearing frozen autografts have been used for reconstruction of bone defects after resection of bone tumors. In the present study, outcomes and complications of reconstruction using frozen autografts were assessed to determine indications for this procedure in patients with metastatic bone lesions.
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Tumor-targeting Salmonella typhimurium A1-R prevents experimental human breast cancer bone metastasis in nude mice.
Oncotarget
PUBLISHED: 09-13-2014
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Bone metastasis is a lethal and morbid late stage of breast cancer that is currently treatment resistant. More effective mouse models and treatment are necessary. High bone-metastatic variants of human breast cancer cells were selected in nude mice by cardiac injection. After cardiac injection of a high bone-metastatic variant of breast cancer, all untreated mice had bone metastases compared to only 20% with parental cells. Treatment with tumor-targeting Salmonella typhimurium A1-R completely prevented the appearance of bone metastasis of the high metastatic variant in nude mice (P < 0.001). After injection of the highly bone-metastatic breast cancer variant to the tibia of nude mice, S. typhimurium A1-R treatment significantly reduced tumor growth in the bone (P < 0.001). These data indicated that S. typhimurium A1-R is useful to prevent and inhibit breast cancer bone metastasis and should be of future clinical use for breast cancer in the adjuvant setting.
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Nanosilica-induced placental inflammation and pregnancy complications: Different roles of the inflammasome components NLRP3 and ASC.
Nanotoxicology
PUBLISHED: 09-12-2014
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Abstract Despite the increasing commercial use of nanoparticles, little is known about their effects on placental inflammation and pregnancy complications. In this study, nanosilica (NS) particles upregulated the inflammasome component nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) and induced placental inflammation and reactive oxygen species (ROS) generation, resulting in pregnancy complications. Furthermore, NS-induced pregnancy complications were markedly improved in Nlrp3(-/-) mice but not in component apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-deficient (Asc(-/-)) mice, indicating the independence of NLRP3 inflammasomes. Pregnancy complications in Nlrp3(-/-) and Asc(-/-) mice phenotypes were dependent on the balance between interleukin (IL)-1? and IL-10. NS-induced pregnancy complications were completely prevented by either inhibition of ROS generation or forced expression of IL-10. Our findings provide important information about NS-induced placental inflammation and pregnancy complications and the novel pathophysiological roles of NLRP3 and ASC in pregnancy.
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Fluorescence-guided surgery improves outcome in an orthotopic osteosarcoma nude-mouse model.
J. Orthop. Res.
PUBLISHED: 08-19-2014
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In order to develop a model for fluorescence-guided surgery (FGS), 143B human osteosarcoma cells expressing red fluorescent protein (RFP) were injected into the intramedullary cavity of the tibia in nude mice. The fluorescent areas of residual tumors after bright-light surgery (BLS) and FGS were 10.2?±?2.4?mm(2) and 0.1?±?0.1?mm(2) , respectively (p?
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Diffuse idiopathic skeletal hyperostosis (DISH) is a risk factor for further surgery in short-segment lumbar interbody fusion.
Eur Spine J
PUBLISHED: 07-03-2014
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To elucidate the effect of diffuse idiopathic skeletal hyperostosis (DISH) on the clinical results of short-segment lumbar interbody fusion (LIF) for the treatment of degenerative lumbar spinal diseases.
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Synovial sarcoma in knee joint, mimicking low-grade sarcoma confirmed by molecular detection of SYT gene split.
Anticancer Res.
PUBLISHED: 06-13-2014
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A 10-year-old boy underwent arthroscopic curettage for an intra-articular mass in knee joint. The tumor was diagnosed as low-grade fibrous sarcoma. Five years later, the patient presented with a recurrent tumor. The patient underwent a marginal excision with knee joint preservation and without adjuvant therapy. Two years after the last surgery, the patient is thriving with no evidence of recurrent or metastatic disease. The final diagnosis was synovial sarcoma confirmed via a SYT gene split performed with fluorescent in situ hybridization (FISH), although the tumor appeared as a low-grade fibrous type in a hematoxylin-eosin section. The first curetted specimen was also confirmed to bear a SYT gene split. Synovial sarcoma has been conventionally recognized as a high-grade sarcoma. Our patient had a tumor that exhibited the characteristics of both a histologically and clinically low-grade tumor. From the present case, we consider that low-grade variants of synovial sarcoma do exist although their existence remains controversial.
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The effect of anti-gravity treadmill training for prosthetic rehabilitation of a case with below-knee amputation.
Prosthet Orthot Int
PUBLISHED: 05-14-2014
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Background:The aim of this case study was to verify the efficacy and safety of anti-gravity treadmill training for prosthetic rehabilitation following below-knee amputation.Case description and methods:The patient underwent left below-knee amputation as a result of diabetic foot gangrene. Since his physical strength and vitality had declined during the perioperative period, anti-gravity treadmill training was introduced for his outpatient prosthetic rehabilitation.Findings and outcomes:Stable prosthetic gait exercise could be carried out under guidance on the anti-gravity treadmill, quickly resulting in improved gait. Furthermore, the patient's self-efficacy and exercise tolerance were elevated after the period of anti-gravity treadmill training. At the final evaluation following 6 weeks of rehabilitation with the anti-gravity treadmill, he had acquired prosthetic gait with the assistance of a T-cane.Conclusion:The anti-gravity treadmill was found to be a useful instrument for prosthetic rehabilitation following below-knee amputation.Clinical relevanceAnti-gravity treadmill training has the potential to support the prosthetic rehabilitation of below-knee amputees, especially for patients whose physical strength and vitality are decreased.
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NLRP3 regulates neutrophil functions and contributes to hepatic ischemia-reperfusion injury independently of inflammasomes.
J. Immunol.
PUBLISHED: 04-02-2014
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Inflammation plays a key role in the pathophysiology of hepatic ischemia-reperfusion (I/R) injury. However, the mechanism by which hepatic I/R induces inflammatory responses remains unclear. Recent evidence indicates that a sterile inflammatory response triggered by I/R is mediated through a multiple-protein complex called the inflammasome. Therefore, we investigated the role of the inflammasome in hepatic I/R injury and found that hepatic I/R stimuli upregulated the inflammasome-component molecule, nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), but not apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). NLRP3(-/-) mice, but not ASC(-/-) and caspase-1(-/-) mice, had significantly less liver injury after hepatic I/R. NLRP3(-/-) mice showed reduced inflammatory responses, reactive oxygen species production, and apoptosis in I/R liver. Notably, infiltration of neutrophils, but not macrophages, was markedly inhibited in the I/R liver of NLRP3(-/-) mice. Bone marrow transplantation experiments showed that NLRP3 not only in bone marrow-derived cells, but also in non-bone marrow-derived cells contributed to liver injury after I/R. In vitro experiments revealed that keratinocyte-derived chemokine-induced activation of heterotrimeric G proteins was markedly diminished. Furthermore, NLRP3(-/-) neutrophils decreased keratinocyte-derived chemokine-induced concentrations of intracellular calcium elevation, Rac activation, and actin assembly formation, thereby resulting in impaired migration activity. Taken together, NLRP3 regulates chemokine-mediated functions and recruitment of neutrophils, and thereby contributes to hepatic I/R injury independently of inflammasomes. These findings identify a novel role of NLRP3 in the pathophysiology of hepatic I/R injury.
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Anterior corpectomy and fusion to C2 for cervical myelopathy: clinical results and complications.
Eur Spine J
PUBLISHED: 02-18-2014
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Anterior cervical corpectomy and fusion (ACCF) to C2 (ACCF-C2) for multilevel lesions is a challenging procedure that is indicated for massive ossification of the posterior longitudinal ligament (OPLL) extending to C2 or stenosis at the upper cervical region accompanied by kyphosis. However, there is little information on the effectiveness of and complications related to ACCF-C2. The purpose of this study was to investigate the overall surgical results and postoperative complications of ACCF-C2 for cervical myelopathy.
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Fluorescence-guided surgery of prostate cancer bone metastasis.
J. Surg. Res.
PUBLISHED: 02-12-2014
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The aim of this study is to investigate the effectiveness of fluorescence-guided surgery (FGS) of prostate cancer experimental skeletal metastasis.
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New soft X-ray beamline BL07LSU at SPring-8.
J Synchrotron Radiat
PUBLISHED: 02-08-2014
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A new soft X-ray beamline, BL07LSU, has been constructed at SPring-8 to perform advanced soft X-ray spectroscopy for materials science. The beamline is designed to achieve high energy resolution (E/?E> 10000) and high photon flux [>10(12)?photons s(-1) (0.01% bandwidth)(-1)] in the photon energy range 250-2000?eV with controllable polarization. To realise this state-of-the-art performance, a novel segmented cross undulator was developed and adopted as a light source. The details of the undulator light source and beamline monochromator design are described. The achieved performance of the beamline, such as the photon flux, energy resolution and the state of polarization, is reported.
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ASC in renal collecting duct epithelial cells contributes to inflammation and injury after unilateral ureteral obstruction.
Am. J. Pathol.
PUBLISHED: 01-07-2014
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Inflammation plays a crucial role in the pathophysiological characteristics of chronic kidney disease; however, the inflammatory mechanisms underlying the chronic kidney disease process remain unclear. Recent evidence indicates that sterile inflammation triggered by tissue injury is mediated through a multiprotein complex called the inflammasome. Therefore, we investigated the role of the inflammasome in the development of chronic kidney disease using a murine unilateral ureteral obstruction (UUO) model. Inflammasome-related molecules were up-regulated in the kidney after UUO. Apoptosis-associated speck-like protein containing a caspase recruitment domain deficiency significantly reduced inflammatory responses, such as inflammatory cell infiltration and cytokine expression, and improved subsequent renal injury and fibrosis. Furthermore, apoptosis-associated speck-like protein containing a caspase recruitment domain was specifically up-regulated in collecting duct (CD) epithelial cells of the UUO-treated kidney. In vitro experiments showed that extracellular adenosine triphosphate (ATP) induced inflammasome activation in CD epithelial cells through P2X7-potassium efflux and reactive oxygen species-dependent pathways. These results demonstrate the molecular basis for the inflammatory response in the process of chronic kidney disease and suggest the CD inflammasome as a potential therapeutic target for preventing chronic kidney disease progression.
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Flexor tendon rupture of the little finger caused by calcium pyrophosphate dihydrate crystal deposition disease of the pisotriquetrum joint.
Hand Surg
PUBLISHED: 10-26-2013
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We report a case of closed rupture of the flexor tendons of the little finger caused by calcium pyrophosphate dihydrate crystal deposition disease of the pisotriquetrum joint. The patient could not flex the little finger and did not have wrist pain. Plain radiographs of the affected wrist joint showed severe arthritic changes of the pisotriquetrum joint and calcification around the joint. At operation, the pisotriquetrum joint capsule was ruptured and involved the flexor tendon of the little finger. The distal stump of the flexor tendon was transferred to the flexor tendon of the ring finger, and the pisiform was resected. Histological examination with polarized light microscopy revealed crystals showing weakly positive birefringence in the calcification.
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High lung-metastatic variant of human osteosarcoma cells, selected by passage of lung metastasis in nude mice, is associated with increased expression of ?(v)?(3) integrin.
Anticancer Res.
PUBLISHED: 09-12-2013
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Altered expression of ?v?3 integrin is associated with tumor progression and metastasis in several types of cancer, including metastatic osteosarcoma. In this study, we demonstrate that in vivo passaging of lung metastasis in nude mice can generate an aggressive variant of human osteosarcoma cells. Experimental metastases were established by injecting 143B human osteosarcoma cells, expressing green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm, in the tail vein of nude mice. Lung metastases were harvested under fluorescence microscopy from nude mice to establish cell lines which were then injected via the tail vein of additional nude mice. This procedure was repeated for four passages in order to isolate highly metastatic variant sublines. When the parental and metastatic variants were transplanted orthotopically into the tibia of nude mice, the 143B-LM4 variant had the highest metastatic rate, approximately 18-fold higher than the parent (p<0.01). ?v?3 integrin expression was increased approximately 5.6-fold in 143B-LM4 compared to parental cells (p<0.05). Thus, serial passage of lung metastases created a highly metastatic variant of human osteosarcoma cells which had increased expression of ?v?3 integrin, suggesting that ?v?3 integrin plays an essential role in osteosarcoma metastasis. With this highly metastatic variant overexpressing ?v?3 integrin, it will now be possible to further investigate the mechanism by which ?v?3 integrin facilitates metastasis.
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Diagnosis and treatment of low-grade osteosarcoma: experience with nine cases.
Int. J. Clin. Oncol.
PUBLISHED: 06-26-2013
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Low-grade osteosarcoma, including low-grade central osteosarcoma and parosteal osteosarcoma, is an extremely rare variant, and the diagnosis is occasionally difficult. In this article we present cases of low-grade osteosarcomas that should be reviewed by a clinical oncologist.
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Imaging the efficacy of UVC irradiation on superficial brain tumors and metastasis in live mice at the subcellular level.
J. Cell. Biochem.
PUBLISHED: 06-05-2013
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The effect of UVC irradiation was investigated on a model of brain cancer and a model of experimental brain metastasis. For the brain cancer model, brain cancer cells were injected stereotactically into the brain. For the brain metastasis model, lung cancer cells were injected intra-carotidally or stereotactically. The U87 human glioma cell line was used for the brain cancer model, and the Lewis lung carcinoma (LLC) was used for the experimental brain metastasis model. Both cancer cell types were labeled with GFP in the nucleus and RFP in the cytoplasm. A craniotomy open window was used to image single cancer cells in the brain. This double labeling of the cancer cells with GFP and RFP enabled apoptosis of single cells to be imaged at the subcellular level through the craniotomy open window. UVC irradiation, beamed through the craniotomy open window, induced apoptosis in the cancer cells. UVC irradiation was effective on LLC and significantly extended survival of the mice with experimental brain metastasis. In contrast, the U87 glioma was relatively resistant to UVC irradiation. The results of this study suggest the use of UVC for treatment of superficial brain cancer or metastasis.
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Imaging UVC-induced DNA damage response in models of minimal cancer.
J. Cell. Biochem.
PUBLISHED: 05-09-2013
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We have previously demonstrated that the ultraviolet (UV) light is effective against a variety of cancer cells in vivo as well as in vitro. In the present report, we imaged the DNA damage repair response of minimal cancer after UVC irradiation. DNA-damage repair response to UV irradiation was imaged on tumors growing in 3D culture and in superficial tumors grown in vivo. UV-induced DNA damage repair was imaged with GFP fused to the DNA damage response (DDR)-related chromatin-binding protein 53BP1 in MiaPaCa-2 human pancreatic cancer cells. Three-dimensional Gelfoam® histocultures and confocal imaging enabled 53BP1-GFP nuclear foci to be observed within 1?h after UVC irradiation, indicating the onset of DNA damage repair response. A clonogenic assay showed that UVC inhibited MiaPaCa-2 cell proliferation in a dose-dependent manner, while UVA and UVB showed little effect on cell proliferation. Induction of UV-induced 53BP1-GFP focus formation was limited up to a depth of 40?µm in 3D-culture of MiaPaCa-2 cells. The MiaPaCa-2 cells irradiated by UVC light in a skin-flap mouse model had a significant decrease of tumor growth compared to untreated controls. Our results also demonstrate that 53BP1-GFP is an imageable marker of UV-induced DNA damage repair response of minimal cancer and that UVC is a useful tool for the treatment of residual cancer since UVC can kill superficial cancer cells without damage to deep tissue.
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Complete necrosis of a giant cell tumor with high expression of PPAR?: a case report.
Anticancer Res.
PUBLISHED: 05-07-2013
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Giant cell tumor of the bone (GCTB) is a common primary benign tumor, but in some cases, it behaves aggressively, resulting in tumor recurrence. The standard treatment for GCT is thorough curettage with adjuvant treatment such as phenol, liquid nitrogen, high-speed burr, or methylmethacrylate cement. This article presents the case of a 30-year-old male with GCT of the right distal femur, which demonstrated a complete necrosis of GCTB. Interestingly, the specimen also showed adipocytic lineage, and strong expression of apoptotic markers by [terminal deoxynucleotidyl-transferase dUTP nick-end labelling (TUNEL) and caspase-3] and peroxisome proliferator-activated receptor gamma (PPAR?). To the Authors knowledge, this is the first reported case of complete necrosis of GCTB concurrent with adipocytic lineage and high expression of PPAR?. PPAR? is a master regulator of fat differentiation. PPAR? possesses antitumor activity through suppression of tumor proliferation and invasion and induction of differentiation and apoptosis. Although we could not conclude on the exact cause of complete necrosis and high expression of PPAR? in this case, we focused on the medical history, where this patient took zaltoprofen (240 mg/day) for four weeks before the biopsy to alleviate his pain. Zaltoprofen is a propionic-acid derivative non-steroidal anti-inflammatory drug, and it is reported to act as a direct ligand for PPAR?. We speculated that one of the possible mechanisms of PPAR? activation in this case was induction by zaltoprofen, at least in part. Although further analysis using cultured tumor cells with ligands specific to the receptor is necessary, PPAR? may be a novel therapeutic target in GCTB.
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Single cell time-lapse imaging of focus formation by the DNA damage-response protein 53BP1 after UVC irradiation of human pancreatic cancer cells.
Anticancer Res.
PUBLISHED: 04-09-2013
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We have previously demonstrated that ultraviolet (UV) light treatment is effective against various types of cancer cells expressing fluorescent proteins. In order to further understand the efficacy of UV treatment of cancer cells, we determined the kinetics of focus formation by imaging of a DNA damage-response (DDR) protein after UVC irradiation of human pancreatic cancer cells. A fusion protein consisting of the DDR protein 53BP1 and green fluorescent protein (GFP) (GFP-53BP1) was used as a live-cell imaging marker for cellular response after UVC irradiation. GFP-53BP1 foci were observed after UVC irradiation of MiaPaCa-2 human pancreatic cancer cells. During live-cell imaging, GFP-53BP1 foci were observed in the cells within 15 min after UVC irradiation, and some of the foci remained stable for at least three hours. GFP-53BP1 focus formation was observed in the pancreatic-cancer cells irradiated by 25-200 J/m(2) UVC. Our results indicate that an early response to DNA damage caused by UVC irradiation can be visualized by increased GFP-53BP1 focus formation by pancreatic cancer cells.
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Dynamic subcellular imaging of cancer cell mitosis in the brain of live mice.
Anticancer Res.
PUBLISHED: 04-09-2013
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The ability to visualize cancer cell mitosis and apoptosis in the brain in real time would be of great utility in testing novel therapies. In order to achieve this goal, the cancer cells were labeled with green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm, such that mitosis and apoptosis could be clearly imaged. A craniotomy open window was made in athymic nude mice for real-time fluorescence imaging of implanted cancer cells growing in the brain. The craniotomy window was reversibly closed with a skin flap. Mitosis of the individual cancer cells were imaged dynamically in real time through the craniotomy-open window. This model can be used to evaluate brain metastasis and brain cancer at the subcellular level.
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Characteristics of patients with severe heart failure exhibiting exercise oscillatory ventilation.
Clin. Exp. Hypertens.
PUBLISHED: 03-28-2013
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This study aims to elucidate the characteristics of patients with severe nonischemic heart failure exhibiting exercise oscillatory ventilation (EOV) and the association of these characteristics with the subjective dyspnea. Forty-six patients with nonischemic heart failure who were classified into the New York Heart Association (NYHA) functional class III underwent cardiopulmonary exercise testing (CPX) and were divided into two groups according to the presence or absence of EOV. We evaluated the patients by using the Specific Activity Scale (SAS), biochemical examination, echocardiographic evaluation, results of CPX and symptoms during CPX (Borg scale), and reasons for exercise termination. EOV was observed in 20 of 46 patients. The following characteristics were observed in patients with EOV as compared with those without EOV with statistically significant differences: more patients complaining dyspnea as the reason for exercise termination, lower SAS score, higher N-terminal pro-brain natriuretic peptide level, larger left atrial dimension and volume, left ventricular end-diastolic volume, higher Borg scale score at rest and at the anerobic threshold, higher respiratory rate at rest and at peak exercise, and higher slope of the minute ventilation-to-CO? output ratio, and lower end-tidal CO? pressure at peak exercise. Among the subjects with NYHA III nonischemic heart failure, more patients with EOV had a stronger feeling of dyspnea during exercise as compared with those without EOV, and the subjective dyspnea was an exercise-limiting factor in many cases.
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Dynamic color-coded fluorescence imaging of the cell-cycle phase, mitosis, and apoptosis demonstrates how caffeine modulates cisplatinum efficacy.
J. Cell. Biochem.
PUBLISHED: 03-21-2013
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Caffeine enhances the effect of certain anticancer drugs, but the mechanism of modulation is poorly understood. In this study, modulation of cisplatinum efficacy induced by caffeine was visualized at the subcellular level by real-time fluorescent-protein imaging. Mitotic and apoptotic changes were observed by imaging 143B human osteosarcoma dual-color cells, in which GFP is expressed in the nucleus and RFP is expressed in the cytoplasm. Modulation of the cell cycle was imaged using time-lapse imaging of HeLa cells expressing a fluorescent ubiquitination-based cell cycle indicator (FUCCI) in the nucleus. Clonogenic assays showed that caffeine increased the inhibition by cisplatinum on cell proliferation. Subcellular imaging demonstrated that cisplatinum decreased mitosis and induced apoptosis in 143B cells. The combination of cisplatinum and caffeine enhanced mitosis and subsequently increased apoptosis. Time-lapse imaging showed that cisplatinum strongly induced cell-cycle arrest in the S/G2 phase in HeLa-FUCCI cells. Caffeine overcame the cell-cycle arrest induced by cisplatinum, thereby increasing its efficacy, since cisplatinum is ineffective against quiescent cells. The data in this report indicate that caffeine modulates the cell cycle in cancer cells, thereby enhancing efficacy of cell-cycle-dependent anticancer drugs such as cisplatinum.
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Pedicle versus free frozen autograft for reconstruction in malignant bone and soft tissue tumors of the lower extremities.
J Orthop Sci
PUBLISHED: 03-06-2013
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Of the biological reconstruction methods for malignant bone and soft tissue tumors, reconstruction with liquid nitrogen has the advantage of maintaining continuity on the distal side of the tumor bone site (pedicle freezing procedure; PFP). This method is expected to result in early blood flow recovery, with early union and low complication rate. The purpose of this study was to compare the outcomes of the PFP and free freezing procedure (FFP) in the lower extremities.
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Hemodialysis patients born with a low birth weight should have a different time course of kidney diseases than those born with a normal birth weight.
Ther Apher Dial
PUBLISHED: 01-21-2013
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Low birth weight (LBW) is thought to be one of the risk factors for the progression of kidney diseases. This study hypothesized that the onset age of kidney disease, the rate of progression of kidney disease, or the age at the time of hemodialysis (HD) induction among HD patients that were born with LBW is different from those without a history of LBW. A questionnaire survey in nine dialysis units in Japan was performed and 427 answer sheets were collected. There were statistically significant differences in the present age, the age of kidney disease onset, and the age of HD induction between LBW group and normal birth weight group (NBW). An analysis limited to participants whose underlying disease was diabetic nephropathy revealed that the duration from the onset of nephropathy to HD induction was much shorter in HD patients with a history of LBW than those with a NBW history. In addition, the Pearsons correlation coefficient between the birth weight and the period from onset of diabetic nephropathy to HD induction was 0.283. Although these results might partly support the primary hypothesis, the necessity to perform other clinical studies is also emphasized.
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Development of a clinically-precise mouse model of rectal cancer.
PLoS ONE
PUBLISHED: 01-01-2013
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Currently-used rodent tumor models, including transgenic tumor models, or subcutaneously growing tumors in mice, do not sufficiently represent clinical cancer. We report here development of methods to obtain a highly clinically-accurate rectal cancer model. This model was established by intrarectal transplantation of mouse rectal cancer cells, stably expressing green fluorescent protein (GFP), followed by disrupting the epithelial cell layer of the rectal mucosa by instilling an acetic acid solution. Early-stage tumor was detected in the rectal mucosa by 6 days after transplantation. The tumor then became invasive into the submucosal tissue. The tumor incidence was 100% and mean volume (±SD) was 1232.4 ± 994.7 mm(3) at 4 weeks after transplantation detected by fluorescence imaging. Spontaneous lymph node metastasis and lung metastasis were also found approximately 4 weeks after transplantation in over 90% of mice. This rectal tumor model precisely mimics the natural history of rectal cancer and can be used to study early tumor development, metastasis, and discovery and evaluation of novel therapeutics for this treatment-resistant disease.
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Prognostic value of histological response to chemotherapy in osteosarcoma patients receiving tumor-bearing frozen autograft.
PLoS ONE
PUBLISHED: 01-01-2013
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A variety of surgical procedures are now available for tissue reconstruction after osteosarcoma excision, and an important prognostic factor is the evaluation of response to chemotherapy using histology. Although tumor-bearing autografts are useful tools for reconstruction, re-use of the primary tumor may make it difficult to assess the histological response to chemotherapy, since the entire tumor cannot be analyzed. Here, we analyzed the prognostic value of the histological response in the patients who received frozen tumor-bearing autografts for reconstruction.
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In vivo fluorescence imaging reveals the promotion of mammary tumorigenesis by mesenchymal stromal cells.
PLoS ONE
PUBLISHED: 01-01-2013
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Mesenchymal stromal cells (MSCs) are multipotent adult stem cells which are recruited to the tumor microenvironment (TME) and influence tumor progression through multiple mechanisms. In this study, we examined the effects of MSCs on the tunmorigenic capacity of 4T1 murine mammary cancer cells. It was found that MSC-conditioned medium increased the proliferation, migration, and efficiency of mammosphere formation of 4T1 cells in vitro. When co-injected with MSCs into the mouse mammary fat pad, 4T1 cells showed enhanced tumor growth and generated increased spontaneous lung metastasis. Using in vivo fluorescence color-coded imaging, the interaction between GFP-expressing MSCs and RFP-expressing 4T1 cells was monitored. As few as five 4T1 cells could give rise to tumor formation when co-injected with MSCs into the mouse mammary fat pad, but no tumor was formed when five or ten 4T1 cells were implanted alone. The elevation of tumorigenic potential was further supported by gene expression analysis, which showed that when 4T1 cells were in contact with MSCs, several oncogenes, cancer markers, and tumor promoters were upregulated. Moreover, in vivo longitudinal fluorescence imaging of tumorigenesis revealed that MSCs created a vascularized environment which enhances the ability of 4T1 cells to colonize and proliferate. In conclusion, this study demonstrates that the promotion of mammary cancer progression by MSCs was achieved through the generation of a cancer-enhancing microenvironment to increase tumorigenic potential. These findings also suggest the potential risk of enhancing tumor progression in clinical cell therapy using MSCs. Attention has to be paid to patients with high risk of breast cancer when considering cell therapy with MSCs.
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Prognostic value of radiological response to chemotherapy in patients with osteosarcoma.
PLoS ONE
PUBLISHED: 01-01-2013
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Chemotherapy is essential to improve the prognosis of the patients with osteosarcoma, and the response to chemotherapy is an important prognostic factor. In this study, the impact of various radiological examinations on overall survival (OS) and event-free survival (EFS) was evaluated.
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Utility of fluorescence in situ hybridization to detect MDM2 amplification in liposarcomas and their morphological mimics.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2013
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The atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLS) and the de-differentiated liposarcoma (DDLS) represent the most common category of liposarcomas. ALT/WDLSs and DDLSs are often difficult to distinguish from other tumors with similar morphological characteristics. In this study, we investigated whether the detection of amplified or overexpressed murine double-minute 2 (MDM2) can be a useful diagnostic ancillary aid. We used fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) to detect MDM2 amplification and protein overexpression, respectively, in 49 WDLSs, 5 DDLSs, 23 myxoid liposarcomas, 25 benign lipomatous tumors, and 75 spindle and pleomorphic sarcomas. MDM2 amplification was detected in 48 of 49 WDLSs, 5 of 5 DDLSs, 2 of 9 malignant peripheral nerve sheath tumors, and 2 of 10 myxofibrosarcomas. We did not detect MDM2 amplification in any of the benign lipomatous tumors. FISH-mediated detection of MDM2 amplification was the most valuable diagnostic aid for ALT/WDLS, as determined by using the Fisher exact test to compare two different diagnoses of 19 biopsies. On the contrary, unequivocal nuclear overexpression of MDM2 was found in only 10 of 50 ALT/WDLSs. The sensitivity and specificity of MDM2 amplification in distinguishing a DDLS from spindle and pleomorphic sarcomas were 100% and 95%, respectively, while those of MDM2 overexpression were 100% and 87%, respectively. In conclusion, our results indicate that FISH-mediated detection of MDM2 amplification is the most useful adjunct in the diagnosis of both ALT/WDLS and DDLS. However, IHC-mediated detection of MDM2 protein is useful only for the diagnosis of DDLS.
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Comparison of cancer-cell seeding, viability and deformation in the lung, muscle and liver, visualized by subcellular real-time imaging in the live mouse.
Anticancer Res.
PUBLISHED: 11-24-2011
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The comparison of cancer cell seeding, deformation and viability in the lung, muscle and liver of nude mice in real-time is reported here. The mice were intubated to support ventilation with positive end-respiratory pressure (PEEP) for imaging on the lung. Human fibrosarcoma cells with green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm (dual-color HT-1080 cells) were injected into the tail vein for lung imaging, the portal vein for liver imaging or the abdominal aorta for muscle imaging which was performed with an Olympus OV100 Small Animal Imaging System. The length of the cytoplasm and nuclei in 20 seeded cancer cells were measured. A large number of cells initially arrested in the lung capillaries and many cells formed aggregates. The cell number decreased rapidly at 6 and 24 h. There was no significant difference in cancer cell survival when immunocompetent C57BL/6 mice were used in place of the nude mice, suggesting that T cell reaction is not very important in the first 24 h after seeding of cancer cells in the lung. In the lung and liver, little cancer cell deformation occurred. In contrast in the muscle, the cytoplasm and nuclei of the seeded cells were highly deformed and many fragmented cells were observed. The rate of cancer cell death was highest in the lung and lowest in the muscle. In each organ, single disseminated cells tended to die earlier than aggregated cells. The results of this study suggest that the early steps of metastasis are different in the lung, liver and muscle.
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Activity of bone morphogenetic protein-7 after treatment at various temperatures: freezing vs. pasteurization vs. allograft.
Cryobiology
PUBLISHED: 05-15-2011
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Insufficient bone union is the occasional complication of biomechanical reconstruction after malignant bone tumor resection using temperature treated tumor bearing bone; freezing, pasteurization, and autoclaving. Since bone morphogenetic protein (BMP) plays an important role in bone formation, we assessed the amount and activity of BMP preserved after several temperature treatments, including -196 and -73°C for 20 min, 60 and 100°C for 30 min, 60°C for 10h following -80°C for 12h as an allograft model, and 4°C as the control. The material extracted from the human femoral bone was treated, and the amount of BMP-7 was analyzed using an enzyme-linked immunosorbent assay. Then, the activity of recombinant human BMP-7 after the treatment was assessed using a bioassay with NIH3T3 cells and immunoblotting analysis to measure the amount of phospho-Smad, one of the signaling substrates that reflect the intracellular reaction of BMPs. Both experiments revealed that BMP-7 was significantly better preserved in the hypothermia groups. The percentages of the amount of BMP-7 in which the control group was set at 100% were 114%, 108%, 70%, 49%, and 53% in the -196, -73, 60, 100°C, and the allograft-model group, respectively. The percentages of the amount of phospho-Smad were 89%, 87%, 24%, 4.9%, and 14% in the -196, -73, 60, 100°C, and the allograft-model group, respectively. These results suggested that freezing possibly preserves osteoinductive ability than hyperthermia treatment.
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Functional outcomes after total scapulectomy for malignant bone or soft tissue tumors in the shoulder girdle.
Int. J. Clin. Oncol.
PUBLISHED: 03-17-2011
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The shoulder girdle is a common site for malignant bone and soft tissue tumors. Total scapulectomy represents an attractive alternative to amputation when the whole scapula is invaded with tumor and the neurovascular bundle can be preserved during tumor resection. The purpose of this study was to investigate functional outcomes after total scapulectomy.
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Inhibition of Fas ligand in NOD mice unmasks a protective role for IL-10 against insulitis development.
Am. J. Pathol.
PUBLISHED: 03-10-2011
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Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by the destruction of pancreatic insulin-producing ? cells by autoreactive T cells early in life. Despite daily insulin injections, patients typically develop cardiovascular and other complications; and intensive efforts are being directed toward identifying therapeutic targets to prevent the disease without directly impinging on the host defense. Fas ligand (FasL) is one potential target. Fas-FasL interactions primarily regulate T-cell homeostasis, not activation. Nevertheless, spontaneous gene mutation of Fas (called lpr mutation) or FasL (called the gld mutation) prevents autoimmune diabetes in nonobese diabetic (NOD) mice, the widely used model for T1D. Furthermore, although homozygous gld mutations cause age-dependent lymphoproliferation, limiting the gld mutation to one allele (NOD-gld/+) or treating NOD-wild-type mice with FasL-neutralizing monoclonal antibody completely prevents the disease development without causing lymphoproliferation or immune suppression. Herein, we show that the heterozygous gld mutation inhibits the accumulation of diabetogenic T cells in the pancreas, without interfering with their proliferation and expansion in the draining pancreatic lymph nodes. Pancreata from NOD-gld/+ mice contained B cells that expressed CD5 and produced IL-10, which was critical for maintenance of the disease resistance because its neutralization with an IL-10 receptor-blocking monoclonal antibody allowed accumulation of CD4 T cells in the pancreas and led to insulitis development. The results provide novel insights into the pathogenesis of T1D that could have important therapeutic implications.
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Role of thyroglobulin on negative feedback autoregulation of thyroid follicular function and growth.
J. Endocrinol.
PUBLISHED: 03-04-2011
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Thyroid function is tightly regulated by TSH. Although individual follicles are exposed to the same blood supply of TSH and express relatively homogenous levels of the TSH receptor, the function of individual follicles is variable. It was shown that thyroglobulin (Tg), stored in the follicular lumen, is a potent negative feedback regulator of follicular function. Thus, physiological concentrations of Tg significantly suppress thyroid-specific gene expression and antagonize the TSH-mediated stimulation that induces expression of thyroid-specific genes. Tg coordinately regulates both basal and apical iodide transporters in thyroid follicular cells. Recently, it was also reported that Tg could induce thyroid cell growth in the absence of TSH. These results indicate that Tg is an essential autocrine regulator of physiological thyroid follicular function that counteracts the effects of TSH.
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The bulge area is the major hair follicle source of nestin-expressing pluripotent stem cells which can repair the spinal cord compared to the dermal papilla.
Cell Cycle
PUBLISHED: 03-01-2011
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Nestin has been shown to be expressed in the hair follicle, both in the bulge area (BA) as well as the dermal papilla (DP). Nestin-expressing stem cells of both the BA and DP have been previously shown to be pluripotent and be able to form neurons and other non-follicle cell types. The nestin-expressing pluripotent stem cells from the DP have been termed skin precursor or SKP cells. The objective of the present study was to determine the major source of nestin-expressing pluripotent stem cells in the hair follicle and to compare the ability of the nestin-expressing pluripotent stem cells from the BA and DP to repair spinal cord injury. Transgenic mice in which the nestin promoter drives GFP (ND-GFP) were used in order to observe nestin expression in the BA and DP. Nestin-expressing DP cells were found in early and middle anagen. The BA had nestin expression throughout the hair cycle and to a greater extent than the DP. The cells from both regions had very long processes extending from them as shown by two-photon confocal microscopy. Nestin-expressing stem cells from both areas differentiated into neuronal cells at high frequency in vitro. Both nestin-expressing DP and BA cells differentiated into neuronal and glial cells after transplantation to the injured spinal cord and enhanced injury repair and locomotor recovery within four weeks. Nestin-expressing pluripotent stem cells from both the BA and DP have potential for spinal cord regeneration, with the BA being the greater and more constant source.
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Fragments of genomic DNA released by injured cells activate innate immunity and suppress endocrine function in the thyroid.
Endocrinology
PUBLISHED: 02-08-2011
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Activation of innate and acquired immune responses, which can be induced by infection, inflammation, or tissue injury, may impact the development of autoimmunity. Although stimulation of cells by double-stranded DNA (dsDNA) has been shown to activate immune responses, the role of self-genomic DNA fragments released in the context of sterile cellular injury is not well understood. Using cultured thyroid cells, we show that cell injury prompts the release of genomic DNA into the cytosol, which is associated with the production of type I interferons, inflammatory cytokines, and chemokines. Molecules necessary for antigen processing and presentation to lymphocytes are also induced in thyroid cells by injury. dsDNA strongly suppressed the expression of sodium/iodide symporter and radioiodine uptake. To identify molecules responsible for sensing cytosolic dsDNA, we directly identified the cellular proteins that bound a dsDNA Sepharose column by mass spectrometry. Our analysis identified histone H2B, which was previously demonstrated to be an essential factor that mediates the activation of innate immunity induced by dsDNA. Knockdown of histone H2B using specific small interfering RNA abolished cell injury-induced innate immune activation and increased sodium/iodide symporter expression. These results indicate that genomic DNA fragments released by cell injury are recognized by extrachromosomal histone H2B, which results in the activation of genes involved in both innate and acquired immune responses in thyroid cells and suppression of thyroid function. These results suggest that sterile thyroid injury, in the absence of infection, may be sufficient to trigger autoimmune reaction and to induce thyroid dysfunction.
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GFP-fluorescence-guided UVC irradiation inhibits melanoma growth and angiogenesis in nude mice.
Anticancer Res.
PUBLISHED: 10-15-2010
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Melanoma cell lines that stably express green fluorescent protein (GFP) and nude mice that ubiquitously express red fluorescent protein (RFP) have previously been developed to study tumor-host interaction by color-coded imaging. In the present study, the efficacy of fluorescence-guided ultraviolet C (UVC) irradiation on the growth of murine melanoma expressing GFP in the ear of RFP mice was determined using a non-invasive ear-tumor imaging model developed previously. The GFP-expressing melanoma and RFP-expressing blood vessels from the transgenic mice expressing RFP used as hosts were readily visible using non-invasive imaging. The melanoma was treated under fluorescence guidance with UVC at 650 J/m2/minute for 3 minutes. The ears of the mice were observed before and 24 hours after irradiation with UVC. UVC inhibited melanoma growth and also damaged blood vessels in the tumor. Thus, UVC irradiation has a direct effect on melanoma growth as well as an anti-angiogenesis effect. This color-coded tumor-host model is useful for evaluation of treatment efficacy on melanoma growth and angiogenesis, which are readily discernable with non-invasive color-coded fluorescent protein imaging. These results suggest that fluorescence-guided UVC irradiation is a promising therapeutic strategy for melanoma.
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Induction of experimental autoimmune hypophysitis in SJL mice.
J Vis Exp
PUBLISHED: 10-13-2010
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Autoimmune hypophysitis can be reproduced experimentally by the injection of pituitary proteins mixed with an adjuvant into susceptible mice(1). Mouse models allow us to study how diseases unfold, often providing a good replica of the same processes occurring in humans. For some autoimmune diseases, like type 1A diabetes, there are models (the NOD mouse) that spontaneously develop a disease similar to the human counterpart. For many other autoimmune diseases, however, the model needs to be induced experimentally. A common approach in this regard is to inject the mouse with a dominant antigen derived from the organ being studied. For example, investigators interested in autoimmune thyroiditis inject mice with thyroglobulin(2), and those interested in myasthenia gravis inject them with the acetylcholine receptor(3). If the autoantigen for a particular autoimmune disease is not known, investigators inject a crude protein extract from the organ targeted by the autoimmune reaction. For autoimmune hypophysitis, the pathogenic autoantigen(s) remain to be identified(4), and thus a crude pituitary protein preparation is used. In this video article we demonstrate how to induce experimental autoimmune hypophysitis in SJL mice.
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Preparation of mouse pituitary immunogen for the induction of experimental autoimmune hypophysitis.
J Vis Exp
PUBLISHED: 10-13-2010
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Autoimmune hypophysitis is a chronic inflammation of the pituitary gland caused or accompanied by autoimmunity(1). It has traditionally been considered a rare disease but reporting has increased markedly in recent years. Hypophysitis, in fact, develops not uncommonly as a "side effect" in cancer patients treated with antibodies that block inhibitory receptors expressed on T lymphocytes, such as CTLA-4(2) and PD-1 receptors. Autoimmune hypophysitis can be induced experimentally by injecting mice with pituitary proteins mixed with an adjuvant(3). In this video article we demonstrate how to extract proteins from mouse pituitary glands and how to prepare them in a form suitable for inducing autoimmune hypophysitis in SJL mice.
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UV/thermally driven rewritable wettability patterns on TiO2-PDMS composite films.
ACS Appl Mater Interfaces
PUBLISHED: 08-18-2010
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Composite films of TiO2 and polydimethylsiloxane (PDMS) are prepared by a sol-gel method, cured with UV irradiation, and then treated in hot water to crystallize the TiO2 in the film. The presence of anatase TiO2 contributes to the photoinduced superhydrophilicity of the film under UV irradiation. Contact angle studies reveal that the TiO2-PDMS composite film recovers its original hydrophobic state. Hydrophobic-superhydrophilic patterns are successfully formed on the films. The wettability patterns can be erased by UV irradiation and thermal treatment. New wettability patterns can be reconstructed, demonstrating that the film exhibits rewritable wettability without the need for organic chemicals.
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Long-working-distance fluorescence microscope with high-numerical-aperture objectives for variable-magnification imaging in live mice from macro- to subcellular.
J Biomed Opt
PUBLISHED: 08-09-2010
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We demonstrate the development of a long-working-distance fluorescence microscope with high-numerical-aperture objectives for variable-magnification imaging in live mice from macro- to subcellular. To observe cytoplasmic and nuclear dynamics of cancer cells in the living mouse, 143B human osteosarcoma cells are labeled with green fluorescent protein in the nucleus and red fluorescent protein in the cytoplasm. These dual-color cells are injected by a vascular route in an abdominal skin flap in nude mice. The mice are then imaged with the Olympus MVX10 macroview fluorescence microscope. With the MVX10, the nuclear and cytoplasmic behavior of cancer cells trafficking in blood vessels of live mice is observed. We also image lung metastases in live mice from the macro- to the subcellular level by opening the chest wall and imaging the exposed lung in live mice. Injected splenocytes, expressing cyan fluorescent protein, could also be imaged on the lung of live mice. We demonstrate that the MVX10 microscope offers the possibility of full-range in vivo fluorescence imaging from macro- to subcellular and should enable widespread use of powerful imaging technologies enabled by genetic reporters and other fluorophores.
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UV light killing efficacy of fluorescent protein-expressing cancer cells in vitro and in vivo.
J. Cell. Biochem.
PUBLISHED: 05-28-2010
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We investigated the cell-killing efficacy of UV light on cancer cells expressing GFP in the nucleus and RFP in the cytoplasm (dual-color cells). After exposure to various doses of UVA, UVB, or UVC, apoptotic and viable cells were quantitated under fluorescence microscopy using dual-color 143B human osteosarcoma cells, HT-1080 human fibrosarcoma cells, Lewis lung carcinoma (LLC), and XPA-1 human pancreatic cancer cells in vitro. UV-induced cancer cell death was wave-length and dose dependent, as well as cell-line dependent. After UVA exposure, most cells were viable even when the UV dose was increased up to 200 J/m(2). With UVB irradiation, cell death was observed with irradiation at 50 J/m(2). For UVC, as little as 25 J/m(2) UVC irradiation killed approximately 70% of the 143B dual-color cells. This dose of UVB or UVA had almost no effect on the cancer cells. UV-induced cancer cell death varied among the cell lines. Cell death began about 4 h after irradiation and continued until 10 h after irradiation. UVC exposure also suppressed cancer cell growth in nude mice in a model of minimal residual cancer (MRC). No apparent side effects of UVC exposure were observed. This study opens up the possibility of UVC treatment for MRC after surgical resection.
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Response-time improved hydrothermal-method-grown ZnO scintillator for soft x-ray free-electron laser timing-observation.
Rev Sci Instrum
PUBLISHED: 04-08-2010
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For pump and probe experiments in x-ray free-electron laser (XFEL) facilities, accurate timing synchronization between short-wavelength femtosecond pulses from XFELs and short optical pulses from other light sources is required. For this purpose, the response time of a hydrothermal-method-grown ZnO is improved by over one order of magnitude via intentional iron ion doping. The fluorescence rise- and decay-time constants are measured to be less than 10 and 100 ps, respectively. Owing to its intense fluorescence even for single pulse XFEL excitation, the timing jitter of the soft x-ray pulse and timing electronics are evaluated to be less than 70 ps.
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Prestroke anticoagulation and paroxysmal type are correlated with favorable outcome in ischemic stroke patients with atrial fibrillation.
J Stroke Cerebrovasc Dis
PUBLISHED: 02-27-2010
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Paroxysmal atrial fibrillation (AF), which often precedes permanent AF, is reported to be a risk factor for milder ischemic stroke. We assessed whether the type of AF and prestroke treatment with an anticoagulant were associated with physical disabilities in patients with AF-related acute ischemic stroke. We identified 162 consecutive acute ischemic stroke patients with AF who were admitted to our hospital over a 3-year period. Disability was measured using the modified Rankin Scale (mRS) at the time of discharge and was categorized according to favorable clinical outcome (mRS score 0-2). Of the 162 patients, 71 (43.8%) had paroxysmal AF and 91 had permanent AF. Fifty-six patients (34.6%) had been treated with a prophylactic anticoagulant. A total of 103 patients (63.6%) had a favorable outcome. Multivariate logistic analysis revealed that paroxysmal AF (odds ratio [OR], 1.58; P = .0187), prestroke anticoagulation treatment (OR, 1.95; P = .0019), and noncardiogenic embolism (OR, 2.20; P = .0073) were independent factors associated with a favorable clinical outcome. Our data indicate that paroxysmal AF and prestroke anticoagulation treatment are independently associated with favorable clinical outcome at the time of hospital discharge in patients with AF.
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Excess iodide decreases transcription of NIS and VEGF genes in rat FRTL-5 thyroid cells.
Biochem. Biophys. Res. Commun.
PUBLISHED: 01-23-2010
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Although it is well known that an excess of iodide suppresses thyroid function and blood flow in vivo, the underlying molecular mechanisms are not fully known. The functional effect of iodide occurs at multiple steps, which include inhibition of sodium/iodide symporter (NIS) expression, transient block of organification, and inhibition of hormonal release. The vascular effect likely involves suppression of the vascular endothelial growth factor (VEGF) gene. In this report, we show that excess iodide coordinately suppresses the expression of the NIS and VEGF genes in FRTL-5 thyroid cells. We also demonstrate that the mechanism of iodide suppression of NIS gene expression is transcriptional, which is synergized by the addition of thyroglobulin. Based on the findings of reporter gene assays and electrophoretic gel mobility shift analysis, we also report two novel DNA binding proteins that responded specifically to iodide and modulated NIS promoter activity. The results suggest that excess iodide affects thyroid vascular function in addition to iodide uptake. This study provides additional insights into the mechanism of action of excess iodide on thyroid function.
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Interleukin-12 induces salivary gland dysfunction in transgenic mice, providing a new model of Sjögrens syndrome.
Arthritis Rheum.
PUBLISHED: 12-02-2009
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Interleukin-12 (IL-12) is a pleiotropic cytokine that is elevated in the affected organs of patients with Sjögrens syndrome (SS). We have previously reported that overexpression of IL-12 in CBA mice leads to mononuclear infiltration of salivary and lacrimal glands, as well as to expansion of bronchial lymphoid tissue and decreased mucociliary clearance. Because xerostomia is one of the most important clinical features in SS patients, our main objective in the current study was to evaluate salivary gland function in IL-12-transgenic mice. Our secondary objective was to further characterize this animal model and to determine if the changes observed in these mice are representative of those observed in patients with SS overall.
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Immunoproteasome overexpression underlies the pathogenesis of thyroid oncocytes and primary hypothyroidism: studies in humans and mice.
PLoS ONE
PUBLISHED: 07-27-2009
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Oncocytes of the thyroid gland (Hürthle cells) are found in tumors and autoimmune diseases. They have a unique appearance characterized by abundant granular eosinophilic cytoplasm and hyperchromatic nucleus. Their pathogenesis has remained, thus far, unknown.
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Pregnancy, postpartum autoimmune thyroiditis, and autoimmune hypophysitis: intimate relationships.
Autoimmun Rev
PUBLISHED: 05-03-2009
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Autoimmune diseases comprise a group of about 85 heterogeneous conditions that can affect virtually any organ and tissue in the body. Many autoimmune diseases change significantly during pregnancy: some ameliorate, some worsen, and others are unaffected. Two autoimmune diseases present prominently in relation to pregnancy: postpartum autoimmune thyroiditis and autoimmune hypophysitis. This article will review the current state of knowledge of the immunological changes that occur during normal pregnancy, and will explore the striking temporal association with pregnancy observed in thyroiditis and hypophysitis.
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Caffeine-potentiated chemotherapy for metastatic osteosarcoma.
J Orthop Sci
PUBLISHED: 04-15-2009
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The prognosis for patients with metastatic osteosarcoma is still poor despite the development of effective adjuvant and neoadjuvant chemotherapy regimens. We have developed caffeine-potentiated chemotherapy for treatment of high-grade bone and soft tissue sarcomas based on the ability of caffeine to enhance the cytocidal effects of anticancer drugs. We report results of caffeine-potentiated chemotherapy for patients with osteosarcoma with pulmonary metastases.
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Ultra-fast switching of light by absorption saturation in vacuum ultra-violet region.
Opt Express
PUBLISHED: 04-03-2009
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Advances in free electron lasers producing high energy photons [Nat. Photonics 2(9), 555-559 (2008)] are expected to open up a new science of nonlinear optics of high energy photons. Specifically, lasers of photon energy higher than the plasma frequency of a metal can show new interaction features because they can penetrate deeply into metals without strong reflection. Here we show the observation of ultra-fast switching of vacuum ultra-violet (VUV) light caused by saturable absorption of a solid metal target. A strong gating is observed at energy fluences above 6J/cm2 at wavelength of 51 nm with tin metal thin layers. The ratio of the transmission at high intensity to low intensity is typically greater than 100:1. This means we can design new nonlinear photonic devices such as auto-correlator and pulse slicer for the VUV region.
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Influence of signal transducer and activator of transcription-1 signaling on thyroid morphology and function.
Endocrinology
PUBLISHED: 03-26-2009
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Interferon (IFN)-gamma has been involved in the pathogenesis of Hashimoto thyroiditis. It is a cytokine released by infiltrating mononuclear cells that mediates its actions mainly through signal transducer and activator of transcription-1 (STAT1) but also through other transcription factors. To dissect the effect of IFN gamma on thyroid morphology and function, we crossed transgenic mice that express IFN gamma specifically in the thyroid gland to mice deficient in STAT1. Lack of STAT1 ameliorated the abnormal thyroid morphology and the primary hypothyroidism typical of IFN gamma transgenic mice but not the suppressed iodine accumulation. Interestingly, lack of STAT1 alone decreased iodine accumulation, seemingly through expression of TGFbeta. These results indicate that STAT1 is required to mediate some but not all of the phenotypic changes induced by IFN gamma and that it also regulates iodine accumulation via TGFbeta signaling.
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Development of the transgenic cyan fluorescent protein (CFP)-expressing nude mouse for "Technicolor" cancer imaging.
J. Cell. Biochem.
PUBLISHED: 03-24-2009
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A major goal for in vivo biology is to develop models which can express multiple colors of fluorescent proteins in order to image many processes simultaneously in real time. Towards this goal, the cyan fluorescent protein (CFP) nude mouse was developed by crossing non-transgenic nude mice with the transgenic CK/ECFP mouse in which the beta-actin promoter drives expression of CFP in almost all tissues. In crosses between nu/nu CFP male mice and nu/+ CFP female mice, approximately 50% of the embryos fluoresced blue. In the CFP nude mice, the pancreas and reproductive organs displayed the strongest fluorescent signals of all internal organs which vary in intensity. Orthotopic implantation of XPA-1 human pancreatic cancer cells expressing red fluorescent protein (RFP); or green fluorescent protein (GFP) in the nucleus and RFP in the cytoplasm, was performed in female nude CFP mice. Color-coded fluorescence imaging of these human pancreatic cancer cells implanted into the bright blue fluorescent pancreas of the CFP nude mouse afforded novel insight into the interaction of the pancreatic tumor and the normal pancreas, in particular the strong desmoplastic reaction of the tumor. The naturally enhanced blue fluorescence of the pancreas in the CFP mouse serves as an ideal background for color-coded imaging of the interaction of implanted cancer cells and the host. The CFP nude mouse will provide unique understanding of the critical interplay between the cancer cells and their microenvironment.
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The cyan fluorescent protein (CFP) transgenic mouse as a model for imaging pancreatic exocrine cells.
JOP
PUBLISHED: 03-17-2009
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The use of fluorescent proteins for in vivo imaging has opened many new areas of research. Among the important advances in the field have been the development of transgenic mice expressing various fluorescent proteins.
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Regenerative potentials of the murine thyroid in experimental autoimmune thyroiditis: role of CD24.
Endocrinology
PUBLISHED: 03-13-2009
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Hashimoto thyroiditis can be partially reproduced in mice by immunization with thyroglobulin or, more recently, thyroperoxidase. This experimental autoimmune thyroiditis (EAT) model has been extensively characterized during early disease phases (up to d 35 after immunization). By extending the analysis of EAT to 100 d after immunization, we noted a remarkable regenerative capacity of the thyroid and the expression of Oct-4, suggesting in vivo the existence of adult thyroid stem cells. After an almost complete destruction of the follicular architecture, occurring between d 21 and 28, the thyroid was capable of restoring its follicles and reducing the mononuclear infiltration, so that by d 100 after immunization, it regained its normal morphology and function. During this regeneration process, thyrocytes expressed high levels of CD24. We therefore assessed the role of CD24 in thyroid regeneration by inducing EAT in mice lacking CD24. Regeneration was faster in the absence of CD24, likely a consequence of the effect of CD24 on the infiltrating lymphocytes. The study suggests that the EAT model can also be used as a tool to investigate adult thyroid stem cells.
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Pituitary and systemic autoimmunity in a case of intrasellar germinoma.
Pituitary
PUBLISHED: 02-03-2009
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Germinomas arising in the sella turcica are difficult to differentiate from autoimmune hypophysitis because of similar clinical and pathological features. This differentiation, nevertheless, is critical for patient care due to different treatments of the two diseases. We report the case of an 11-year-old girl who presented with diabetes insipidus and growth retardation, and was found to have an intra- and supra-sellar mass. Initial examination of the pituitary biopsy showed diffuse lymphocytic infiltration of the adenohypophysis and absent placental alkaline phosphatase expression, leading to a diagnosis of hypophysitis and glucocorticoid treatment. Because of the lack of clinical and radiological response, the pituitary specimen was re-examined, revealing this time the presence of scattered c-kit and Oct4 positive germinoma cells. The revised diagnosis prompted the initiation of radiotherapy, which induced disappearance of the pituitary mass. Immunological studies showed that the patients serum recognized antigens expressed by the patients own germinoma cells, as well as pituitary antigens like growth hormone and systemic antigens like the Sjögren syndrome antigen B and alpha-enolase. The study first reports the presence of pituitary and systemic antibodies in a patient with intrasellar germinoma, and reminds us that diffuse lymphocytic infiltration of the pituitary gland and pituitary antibodies does not always indicate a diagnosis of autoimmune hypophysitis.
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Monopolar surface electromyography: a better tool to assess motoneuron excitability upon passive muscle stretching.
J Physiol Sci
PUBLISHED: 02-01-2009
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Bipolar and monopolar surface electromyography (sEMG) are known procedures to measure the H-reflex. However, signal cancellation is a potential experimental problem of bipolar sEMG. The results of our study show that monopolar sEMG was the more sensitive procedure to differentiate motoneuron excitability at different passive muscle stretching speeds as it overcame signal cancellation.
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TNF-? and tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors.
PLoS ONE
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Dendritic cells (DCs) play a pivotal role in the immune system. There are many reports concerning DC-based immunotherapy. The differentiation and maturation of DCs is a critical part of DC-based immunotherapy. We investigated the differentiation and maturation of DCs in response to various stimuli.
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[Research update on pathogenesis of autoimmune thyroid diseases].
Nippon Rinsho
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Autoimmune thyroid disease (AITD) is the typical organ-specific autoimmune disorder. However, the underlying molecular mechanisms by which immune reactions against specific thyroid proteins are induced are still largely unknown. Accumulated evidence from animal models has generated new insights into the pathogenesis of AITD. Recent studies have indicated that innate immune responses induced by both exogenous and endogenous factors affect the phenotype and severity of autoimmune reactions. One of the recent topics is the effect of self genomic DNA fragments on immune activation. Here we review by focusing on the possible role of innate immune activation in the development of AITD.
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Fluorescent proteins enhance UVC PDT of cancer cells.
Anticancer Res.
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Cancer cells, with and without fluorescent protein expression, were irradiated with various doses of UVC (100, 400, and 600 J/m(2)). Dual-color Lewis lung carcinoma cells (LLC) and U87 human glioma cells, expressing GFP in the nucleus and RFP in the cytoplasm and non-colored LLC and U87 cells were cultured in 96-well plates. Eight hours after seeding, the cells were irradiated with the various doses of UVC. The resulting cell number was determined after 24 hours. Compared to non-colored LLC cells, the number of dual-color LLC cells decreased significantly due to UVC irradiation with 100 J/m(2) (p=0.003). Although there was no significant difference in the number of dual-color and non-colored U87 cells after 100 J/m(2) UVC irradiation (p=0.852), the number of dual-color U87 cells decreased significantly with respect to non-colored cells due to UVC irradiation with 400 J/m(2) and 600 J/m(2) (p=0.011 and p=0.009, respectively). Thus, both dual-color LLC and dual-color U87 cells were more sensitive to UVC light than non-colored LLC and U87 cells. These results suggest that the expression of fluorescent proteins in cancer cells can enhance photodynamic therapy (PDT) using UVC and possibly with other wavelengths of light as well.
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Reconstruction of the sacral region using the lumbo-gluteal sensory flap.
J Plast Reconstr Aesthet Surg
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Local skin flaps are used for reconstruction of sacral decubitus ulcers because of their structural endurance against the patients weight. However, a major concern is associated with decubitus recurrence after repair. Sensory flaps are one choice to prevent recurrence. Thus, we reconstructed sacral decubitus ulcers using Nakajimas lumbo-gluteal flap as a sensory flap.
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Caffeine induces apoptosis of osteosarcoma cells by inhibiting AKT/mTOR/S6K, NF-?B and MAPK pathways.
Anticancer Res.
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We previously reported that caffeine-assisted chemotherapy improved the treatment of malignant bone and soft tissue tumours such as osteosarcoma. Caffeine affects tumour cells through various pathways, including phosphatase and tensin homolog deleted on chromosome 10 (PTEN), AKT, Bcl-2-associated X protein (BAX), caspase-3 and p53, and has therefore been indicated as being useful for the treatment of malignant tumours. Here, the effects of caffeine on the proliferation of HOS osteosarcoma cells were assessed by WST-8 assay, and the effects on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B), mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) pathways were assessed by western blot analyses. Caffeine inhibited proliferation of HOS cells and suppressed NF-?B, AKT, mTOR/S6K and ERK activities. Our results support those from previous studies relating to the use of caffeine in the treatment of osteosarcoma.
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Critical role of caspase-1 in vascular inflammation and development of atherosclerosis in Western diet-fed apolipoprotein E-deficient mice.
Biochem. Biophys. Res. Commun.
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Recent investigations have suggested that the inflammasome plays a role in the development of vascular inflammation and atherosclerosis; however, its precise role remains controversial. We produced double-deficient mice for apolipoprotien E (Apoe) and caspase-1 (Casp1), a key component molecule of the inflammasome, and investigated the effect of caspase-1 deficiency on vascular inflammation and atherosclerosis.
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Hürthle cells predict hypothyroidism in interferon-? transgenic mice of different genetic backgrounds.
Endocrinology
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Hürthle cells have long been described in Hashimoto thyroiditis but remain of undetermined significance. We have previously shown that Hürthle cells and hypothyroidism develop in C57BL/6J mice expressing interferon-? (IFN?) in the thyroid. To assess the influence of genetic backgrounds on Hürthle cell development, we crossed C57BL/6J IFN? transgenic mice to 14 strains and analyzed thyroid histopathology and function in a cohort of 389 mice (225 transgenic and 164 wild type) using a multiple linear regression model that also included strain, sex, genotype, and major histocompatibility complex haplotype. We then queried the Johns Hopkins surgical pathology electronic archive for "Hashimoto" and/or "thyroiditis" keywords, reviewed the reports, and reexamined the Hashimoto slides. Hürthle cells were markedly affected by the genetic background: they were prominent and associated with hypothyroidism in the C57BL/6J, C57BL/6ByJ, C57BL/10J, C57BLKS/J, C57L/J, C58/J, and BPN/3J IFN? transgenic strains, whereas they are mild or absent in the BPH/2J, BPL/1J, LP/J, CBA/J, Balb/cJ, DBA/1J, and NOD/ShiLtJ strains. Hürthle cells were the strongest predictor of hypothyroidism after adjusting for all the other covariates in the regression model. Interestingly, transgenic mice of the BPL/1J, DBA/1J, and NOD/ShiLtJ strains developed a marked accumulation of intrathyroidal brown adipocytes that was significantly associated with improved thyroid function. Hürthle cells were mentioned in 23% of the Hashimoto reports but increased to 79% upon our slide review. This study reports a novel association of Hürhtle cells and brown adipocytes on thyroid function that should prompt a reconsideration of their significance and role in pathogenesis of autoimmune thyroiditis.
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Progressive thoracic myelopathy caused by spinal calcium pyrophosphate crystal deposition because of proximal junctional vertebral compression fracture after lumbopelvic fusion.
Eur Spine J
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We describe cases presenting with progressive thoracic myelopathy after lumbopelvic fusion attributed to proximal junctional vertebral compression fracture (PJF) followed by spinal calcium pyrophosphate dehydrate (CPPD) crystal deposition.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.