tbuckley/cabot-search huggingface dataset:
Repeated FcεRI triggering reveals modified mast cell function related to chronic allergic responses in tissue
Authors: Jolien Suurmond, Kim L.L. Habets, Zuotian Tatum, Joris J. Schonkeren, Peter A.C.'t Hoen, Tom W.J. Huizinga, Jeroen F.J. Laros, René E.M. Toes, Fina Kurreeman
Journal: Journal of Allergy and Clinical Immunology (2016)
S53 Nanoparticles cause pulmonary inflammation through IL-1 and partial activation of the NLRP3 inflammasome
Authors: N. R. Riteau, A. Y. Yazdi, L. B. Baron, A. G. Gombault, G. G. Guarda, J. T. Tschopp, I. C. Couillin
Journal: Thorax (2010)

Nanoparticles are increasingly used in various fields, including biomedicine and electronics. Their size and physical characteristics allow them to easily access the cytosol of tissue or immune cells. Although inorganic metal oxide nano-TiO<sub>2</sub> is believed to be biologically inert, an emerging literature reports increased incidence of respiratory diseases in exposed people. Here, we show that instillation of nano-TiO<sub>2</sub> induces lung inflammation which is strongly suppressed in IL-1R- and IL-1α-deficient mice. They have drastically reduced neutrophil recruitments in the alveolar space, together with lung inflammatory cytokine productions. Surprisingly, the NLRP3 inflammasome complex seems to be only partially involved. Nlrp3-, ASC- or Casp-1-deficient mice show only a slight reduction in pulmonary inflammatory response. IL-1β-deficient mice exhibit decreased inflammation parameters that are less pronounced than IL-1α-deficient mice. <i>In vitro</i> experiments show that primary pulmonary epithelial cells cultured in presence of nano-TiO<sub>2</sub> are able to produce KC and IL-1α, but not IL-1β, to initiate inflammation. In conclusion, it appears that nanoparticles-mediated inflammation is highly dependent on IL-1α and to a less extend on the NLRP3 inflammasome/IL-1β axis. Collectively, these data demonstrate that the expending use of nano-TiO<sub>2</sub>, e.g. in cosmetics, may present a health hazard and should be taken under consideration, a situation reminiscent of inflammation provoked by asbestos exposure.
Gastric liposarcoma presenting as a huge pedunculated polyp
Authors: Min Kim, Mi Gu, Joon Choi, Se Kim, Kyeong Kim
Journal: Endoscopy (2014)

A 46-year-old woman was admitted to a local medical center with abdominal pain and discomfort, which she had experienced for 6 months. Her medical history was unremarkable. Esophagogastroduodenoscopy (EGD) showed a huge pedunculated polyp located in the stomach body. The patient was referred to our hospital for endoscopic submucosal dissection (ESD) with the working diagnosis of hyperplastic polyp.
OC-157 Physiological changes in matrix stiffness modulate hepatic progenitor cell morphology, proliferation and differentiation
Authors: T T Gordon-Walker, J Schrader, L Boulter, A J Robson, S J Forbes, R G Wells, J P Iredale
Journal: Gut (2012)

<h3>Introduction</h3> Liver injury is associated with changes in the biochemical and physical properties of the extracellular matrix (ECM). Hepatic progenitor cell (HPC) activation occurs in the context of severe liver injury. ECM stiffness has been shown to direct differentiation in mesenchymal stem cells. However, the effect of mechanical factors, such as ECM stiffness on HPC responses is poorly characterised. We examined the effect of ECM stiffness on HPC proliferation and differentiation. <h3>Methods</h3> Experiments were undertaken using a murine HPC line (BMOL) and primary murine HPCs. Cell culture experiments were performed using a system of laminin-coated polyacrylamide (PA) gel supports of variable stiffness. The stiffness of the PA supports (expressed as shear modulus) was altered across a physiological range (1–12 kPa) corresponding to values encountered in normal and fibrotic livers. <h3>Results</h3> Increasing matrix stiffness is associated with enhanced cell spreading. BMOL cells cultured on stiff (12kPa) supports develop prominent actin stress fibres. The projected surface area (mean±SEM) of BMOL cells culture on soft (1kPa) supports was 378±21 μm<sup>2</sup> compared to 687±47 μm<sup>2</sup> for BMOL cells cultured on stiff (12 kPa) supports (p&lt;0.001). Cell proliferation (Ki67 positivity) increased as a function of increasing matrix stiffness. The proliferative index (PI) of BMOL cells cultured on 2.5 kPa and 12 kPa supports was 7.1-fold (p&lt;0.01) and 11.8-fold higher (p&lt;0.001), respectively, than cells cultured on 1kPa supports. Similarly, in experiments with primary cells, the PI of murine HPCs was 1.7-fold higher (p&lt;0.05) when cells were cultured on stiff (12 kPa) vs soft (1 kPa) supports. Quantitative PCR revealed that BMOL cells cultured on soft (1 kPa) supports up-regulate hepatocyte markers, including; albumin (1.5-fold, p&lt;0.01) and CYP7A1 (1.6-fold, p&lt;0.01), and down-regulate the HPC/biliary marker cytokeratin-19 (0.6-fold, p&lt;0.01), relative to cells on stiff (12kPa) supports. There was no significant change in expression of the biliary epithelial cell markers aquaporin-1 and γ-glutamyl-transferase. <h3>Conclusion</h3> Physiological changes in ECM stiffness lead to alterations in HPC morphology, proliferation and differentiation. Increased ECM stiffness (as would be encountered in an injured or fibrotic liver) promotes HPC proliferation and expression of the HPC/biliary marker cytokeratin-19. In contrast, a low-stiffness environment is associated with a reduction in cell proliferation and up-regulation of hepatocyte-specific markers. These results suggest that mechanical factors, such as ECM stiffness might regulate HPC responses following liver injury. <h3>Competing interests</h3> None declared.
OSTEOPONTIN AND BRAIN DERIVED NEUROTROPHIC FACTOR: BIOMARKERS OF CARDIOVASCULAR DISEASE IN DUCHENNE MUSCULAR DYSTROPHY
Authors: Jonathan Soslow, Cristi L. Galindo, Holly Smith, Bruce M. Damon, Joe N. Kornegay, W. Bryan Burnette, Douglas Sawyer, Larry Markham
Journal: Journal of the American College of Cardiology (2016)
Life-threatening air embolism during ERCP
Authors: Clotilde Duburque, Erick Beaujard, Jean-Baptiste Landel, Riadh Rihani, Karim Merouani, Wissam Yassine, Olivier Lucidarme, Damien Lucidarme
Journal: Endoscopy (2014)

Patient #1, a 45-year-old man who was being monitored because of chronic pancreatitis, had anicteric cholestasis and pain caused by double-duct stricture. Endoscopic retrograde cholangiopancreatography (ERCP) was undertaken using air, with the patient under general anesthesia with intubation ([Fig. 1]). After short sphincterotomies had been done, self-expanding metal stents were inserted (10 mm diameter for the common bile duct [CBD], and 6 mm diameter for the pancreatic duct, both 60 mm length;). At 1 hour after the procedure was started, the patient became hypocapnic. An inferolateral ST segment elevation mandated coronary angiography. Gas bubbles were visualized in the heart cavities ([Fig. 2]), and echocardiography showed a patent foramen ovale. Administration of pure oxygen and aspiration of bubbles improved the patient's hemodynamic status. Brain magnetic resonance imaging revealed ischemic lesions. The patient was transferred quickly for initiation of hyperbaric oxygen therapy (HBOT). He was referred, 1 month later, to a rehabilitation unit because of nonregressing tetraparesis.
AB0805 Educational programs for patients with osteoporosis in clinical practice.
Authors: L. Myasoutova, A. Vasiliev, S. Lapshina
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> An effective and long-term treatment of osteoporosis is not possible without the active, regular participation of the patient in the process, which requires educational programs. <h3>Objectives</h3> To evaluate the effectiveness of educational activities (schools) for patients with osteoporosis (OP). <h3>Methods</h3> 48 patients with OP from primary group were trained in the schools (5 sessions per year), 40 patients with OP were in control group, which only visited rheumatologist 4-5 times a year. The groups were matched by sex, age, structure (primary and secondary) and the severity of OP, the presence of fractures, received therapy. At baseline and after 6 months pain intensity on VAS back pain, adherence to treatment were determined. At baseline and after 12 months determination of bone mineral density (BMD) was measured by dual energy X-ray absorptiometry <h3>Results</h3> After 6 months of training intensity of back pain was significantly (p &lt;0.01) decreased by 2.5 times in the primary group and by 1.5 times fold in control, 52% of patients from the primary group, and 37.5% - in the control wore an orthopedic corset. 95.8% of patients who visited schools and 90% of patients in the control group were continuously taking calcium and vitamin D during 6 months, after 12 months - 93.7% and 85% respectively. Pathogenetic therapy was applied to all patients, initially these drugs began to take 97.9% of the study group and 92.5% of the control group patients, after 6 months of continuous administration of drugs 89.5% from group trained patients and 67.5% - the control group continued treatment, after 12 months commitment to therapy was 87.5% and 42.5% in the test and control groups, respectively. Densitometry results in dynamics after 12 months showed that the increase in BMD was significantly (p &lt;0.05) higher in the group that has been schooled for the patients and was 5,6 ± 6,2% at the spine, 4,2 ± 4,5% at the femoral neck in the main group, 3,1 ± 4,8% and 1,9 ± 3,2% respectively in the control group. <h3>Conclusions</h3> Educational programs improve functional status and quality of patients life, remain high compliance of therapy, increase commitment to treatment. <h3>Disclosure of Interest</h3> None Declared
FRI0283 Progression of early arthritis to spondyloarthritis after a 10-year follow-up
Authors: D. Guellec, D. Cornec, J. Morvan, J.-M. Berthelot, Y. Maugars, C. Le henaff, S. Hoang, T. Marhadour, G. Chales, A. Martin, A. Khoreichi, S. Jousse-Joulin, V. Devauchelle-Pensec, A. Saraux
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Early arthritis is often undifferentiated and may resolve spontaneously, remain undifferentiated, or progress to rheumatoid arthritis or to another chronic joint disease such as SpA. There is a need for improving the early diagnosis of ankylosing spondylitis (AS) and other spondyloarthritis (SpAs). <h3>Objectives</h3> To 1- assess the level of agreement between a SpA at baseline and 10 years later in a cohort of patients with recent-onset arthritis and 2- evaluate the ability of baseline clinical, laboratory, and radiographic features to predict a final diagnosis of SpA. <h3>Methods</h3> Patients with swelling of at least one joint between 1995 and 1997 were included. Ten years later, the physicians of each patient were contacted to determine the final diagnosis. Baseline pelvic radiographs were subjected to centralized blinded review. The statistical analysis used the chi-square test, Mann-Whitney test, and Cohen’s kappa coefficient. <h3>Results</h3> The diagnosis at baseline and 10 years later was known for 164 patients. At baseline, a diagnosis of SpA was suggested in 25 (15.2%) patients, of whom only 10 had a diagnosis of SpA 10 years later, in addition to 10 patients not diagnosed with SpA at baseline (20/164, 12.2%, Kappa=0.36±0.1). The 10-year diagnoses were ankylosing spondylitis (n=3), psoriatic arthritis (n=7), reactive arthritis (n=4), undifferentiated SpA (n=4), SAPHO syndrome, and Crohn’s disease (n=1). Of the 20 patients with a 10-year diagnosis of SpA, only 4 had inflammatory back pain at baseline (versus 11/144 non-SpA patients, <i>p</i>=0.72), 5 had psoriasis (versus 9/144 non-SpA patients, <i>p</i>=0.005), and 1 had uveitis (<i>p</i>=0.12); 10 of the 20 SpA patients were HLA-B27-positive versus 8/144 non-SpA patients (<i>p</i>&lt;0.0001). Blinded review of baseline pelvic radiographs in 12 patients with a 10-year SpA diagnosis showed sacroiliitis in only 2 patients. <h3>Conclusions</h3> SpA is relatively rare and extremely challenging to diagnose in patients with early peripheral arthritis. <h3>Disclosure of Interest</h3> None Declared
Pilot study to introduce a notification card for partner notification of sexually transmitted infections in Catalonia, Spain, June 2010 to June 2011
Authors: M J Tuneu, X Vallès, D Carnicer-Pont, M J Barberá, P Godoy, A Avecilla-Palau, B Jordà, E Lopez-Grado, D Rivero, A Vives, A Acera, R Almirall, N Crespo, J Casabona, collective the Partner Notification Study Group
Journal: Eurosurveillance (2013)

We conducted a cross-sectional study in 10 primary care centres in Catalonia, to determine applicability, acceptability and effectiveness of partner notification cards used by patients diagnosed of a sexually transmitted infection (STI) and to characterise these and their sexual partners. Statutorily notifiable STIs included Chlamydia infection, gonorrhoea, syphilis, human immunodeficiency virus (HIV) infection or other STIs as deemed necessary by the treating physician. Between June 2010 and June 2011, 219 index cases were enrolled, of whom 130 were men (59.4%), 71 of them men who have sex with men (54.6%). Chlamydia infection (41.1%), gonorrhoea (17.8%) and syphilis (16.0%) were the STIs most frequently diagnosed. HIV infection accounted for 4% of cases. A total of 687 sexual partners were reported, and 300 of these were traceable through the notification card (45.7%). Those who did not report traceable contacts were older (mean age: 34 years versus 31 years, p=0.03). The main reason for not distributing the card was anonymous sexual intercourse (38%). Patient referral notification cards can reach a high percentage of sexual partners at risk. However, only few notified sexual partners attended participating health centres. Internet-based partner notification may be considered in order to reach those partners not otherwise traceable.
Abstract 5425: Epidermal respiratory uncoupling blocks skin carcinogenesis by inhibiting Akt.
Authors: Sara M. Nowinski, Joyce E. Rundhaug, Okkyung Rho, Cory U. Lago, Susan M. Fischer, John DiGiovanni, Edward M. Mills
Journal: Cancer Research (2013)

Abstract Metabolic reprogramming, characterized by increased glycolysis and decreased oxygen consumption, is now considered a hallmark of malignancy. Mitochondrial uncoupling proteins oppose this phenotype by driving futile mitochondrial respiration that is uncoupled from ATP synthesis, and mice expressing a keratin 5 - uncoupling protein 3 (K5-UCP3) transgene in the epidermis are completely protected from the formation of chemically induced skin carcinomas. We crossed these mice with Tg.AC mice that express a cutaneous oncogenic v-Ha-Ras transgene, bypassing tumor initiation. Bi-transgenic Tg.AC/K5-UCP3 mice were still remarkably resistant to 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumorigenesis, indicating that UCP3 likely inhibits tumor promotion. Accordingly, K5-UCP3 mice exhibited striking resistance to epidermal proliferation induced by TPA as measured using a bromodeoxyuridine (BrdU) based labeling assay. In agreement with these data, K5-UCP3 epidermis failed to show activation of Akt (Ser473 &amp; Thr308 phosphorylation) and phosphorylation of downstream signaling molecules in response to TPA treatment. This effect corresponded to decreased expression of cyclins D1 and A, and increased expression of the cell cycle inhibitory proteins p21 and p27. Decreased Akt activation was also observed in vitro in response to epidermal growth factor (EGF) treatment of serum starved, isolated K5-UCP3 primary keratinocytes. To test the notion that the lack of Akt signaling was responsible for the lack of TPA induced proliferation and tumorigenesis, we bred bi-transgenic K5-UCP3/K5-Akt mice, and found that over-expression of wild type Akt recovered proliferation following TPA treatment. Future experiments will elucidate the mechanism underlying UCP3-induced inhibition of Akt activation and signaling. Citation Format: Sara M. Nowinski, Joyce E. Rundhaug, Okkyung Rho, Cory U. Lago, Susan M. Fischer, John DiGiovanni, Edward M. Mills. Epidermal respiratory uncoupling blocks skin carcinogenesis by inhibiting Akt. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5425. doi:10.1158/1538-7445.AM2013-5425
Risk of Cancer among Offspring of Childhood-Cancer Survivors
Authors: Risto Sankila, Jørgen H. Olsen, Harald Anderson, Stanislaw Garwicz, Eystein Glattre, Henrik Hertz, Frøydis Langmark, Marjatta Lanning, Torgil Møller, Hrafn Tulinius
Journal: New England Journal of Medicine (1998)

Increasing numbers of children with cancer survive and reach reproductive age. However, the risk of cancer (other than retinoblastoma) in the offspring of survivors of childhood and adolescent cancer is uncertain.Using data from national cancer and birth registries, we assessed the risk of cancer among 5847 offspring of 14,652 survivors of cancer in childhood or adolescence diagnosed since the 1940s and 1950s in Denmark, Finland, Iceland, Norway, and Sweden. The offspring were followed up for a diagnosis of cancer for 86,780 person-years, and standardized incidence ratios were calculated.Among the 5847 offspring, 44 malignant neoplasms were diagnosed (standardized incidence ratio, 2.6; 95 percent confidence interval, 1.9 to 3.5). There were 17 retinoblastomas, yielding a standardized incidence ratio of 37. There were 27 neoplasms other than retinoblastoma (standardized incidence ratio, 1.6; 95 percent confidence interval, 1.1 to 2.4). The second most common primary site of cancer among the offspring was the brain and nervous system, in which eight tumors were observed (standardized incidence ratio, 2.0; 95 percent confidence interval, 0.9 to 3.9.) There were between zero and four apparently sporadic cases of cancer in other primary sites among the offspring. Excluding 4 likely cases of hereditary cancer and 2 subsequent cancers among the offspring with hereditary retinoblastoma, there were 22 sporadic cancers, for a standardized incidence ratio of 1.3 (95 percent confidence interval, 0.8 to 2.0).There is no evidence of a significantly increased risk of nonhereditary cancer among the offspring of survivors of cancer in childhood.
Abstract 5180: MUC4 mucin upregulates N-cadherin: A novel mechanism for human ovarian tumor metastasis
Authors: Moorthy Palanimuthu Ponnusamy, Imayavaramban Lakshmanan, Maneesh Jain, Surinder K. Batra
Journal: Cancer Research (2010)

Abstract The human MUC4 protein is a high molecular weight transmembrane glycoprotein which is over-expressed in ovarian tumors and plays a role in increasing the cellular motility of the ovarian cancer cells. Previous reports have indicated that gain of expression of N-cadherin in tumor cells is associated with increased motility and metastasis. We hypothesize that MUC4 upregulates N-cadherin and plays a major role in metastasis of ovarian cancer. The aim of the present study was to analyze the mechanism of MUC4 induced cellular motility, invasion and metastasis in ovarian cancer cells. For this we have used a MUC4 gene construct (entire coding sequence along with 10% of the central tandem repeat region) for ectopic expression to determine the metastatic function of MUC4 in human ovarian cancer cells (SKOV3). Interestingly, we observed that N-cadherin was up-regulated in MUC4 overexpressing ovarian cancer cells (SKOV3-MUC4) compared to control (vector transfected) cells. We further discovered that N-cadherin upstream pathways such as FAK, MKK7, JNK and c-Jun are activated in the MUC4 expressing SKOV3 cells. Additionally, inhibition of pFAK led to the downregulation of N-cadherin by inhibiting the activation of MKK7, JNK and c-Jun in MUC4 overexpressing SKOV3 cells. On other hand, knockdown of N-cadherin decreased the activation of ERK, AKT and MMP9 in the MUC4 expressing SKOV3 cells. Inhibition of pFAK, pJNK and knockdown of N-cadherin in the MUC4 overexpressing cells further led to a significant decrease in cellular motility. Upon tumorigenisis and metastasis analysis with NOD-SCID mice, the SKOV3-MUC4 cells produced significantly larger tumors and demonstrated a higher incidence of metastasis to distant organs (peritoneal wall, colon, intestine, stomach, lymph nodes, liver and diaphragm) than the SKOV3-vector cells. Taken together, our result suggests that MUC4 mediated upregulation of N-cadherin plays a major role in promoting the metastatic property of ovarian cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5180.
Case 6-2005
Authors: Eric L. Krakauer, Andrew X. Zhu, Brenna C. Bounds, Dushyant Sahani, Kevin R. McDonald, Elena F. Brachtel
Journal: New England Journal of Medicine (2005)

A 58-year-old man with esophageal cancer had nausea, spontaneous vomiting, and intractable hiccups. The discussants review the role of palliative care in the management of distressing symptoms in patients with cancer, emphasizing the importance of the differential diagnosis in identifying the cause and selecting appropriate treatment for each symptom.
Abstract 2744: Identification of synergistic effect of autophagy inhibitors and resveratrol on BRCA1 mutant cancer cells
Authors: Guelaguetza Vazquez-Ortiz, Cristine L. Chisholm, Ruili Huang, Cuiling Li, Xiaoling Xu, Wang Rui-Hong, Chuxia Deng
Journal: Cancer Research (2012)

Abstract Over 200,000 new breast cancer cases are diagnosed in the US each year, with 5% of cases caused by mutations in BRCA1 (Breast cancer associated gene 1). Mutation carries have a lifetime risk of up to 80% for developing breast cancer. Current treatment options are limited and often do not lead to cure. We showed previously that treatment with resveratrol, although initially reduced more the tumor size in BRCA1 mutant (mt) tumors, with respect to BRCA1 wild-type (wt) in mice, tumors continued to grow after prolonged treatment. To identify small molecules that can be repurposed and synergize the killing effect of resveratrol in BRCA1-mt tumors, we screened the NCGC Pharmaceutical Collection in which, more than 52% are drugs approved for human or animal use by FDA, and the rest are drugs approved in other countries or in clinical trial. Using a high-throughput cell viability assay by measuring intracellular ATP content, we identified the inhibitory effect of 43 compounds that exhibited synergy with resveratrol (Res) with efficacy&amp;gt;50% and potency &amp;lt;35uM. We further analyzed 4 of them, cantharidin, chloroquine, amodiaquin and colchicine for in vivo study. Utilizing BRCA1-mt breast tumor implant models in aythymic mice reveal that mice treated with combination therapy (Drug + Res) exhibit significantly reduced tumor volumes and increased survival rate compared with mice on monotreatment and this effect was even more significant when compared to wt-BRCA1. Also, some mammary tumors developed in the BRCA1 mammary tissue specific mutant mice exhibited a total regression with combination therapy. In order to identify a shared molecular and biochemical change which make BRCA1-mt cancer cells more susceptible to the combination treatment, we found that these compounds inhibit autophagy at different levels, targeting the mTOR/AKT pathway at different levels and/or inhibiting the fusion between the lysosome and the phagosome producing strong vacuolization in the cytoplasm during treatment, increasing LC3-II in a Beclin independent manner, followed by a faster induction of apoptosis on the BRCA mutant cells. This approach offers the potential to combat breast cancer cells and sensitize BRCA1 deficient cells to more effective treatments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2744. doi:1538-7445.AM2012-2744