tbuckley/cabot-search huggingface dataset:
Abstract 5277: MMP-2 suppression abrogates irradiation-induced microtubule formation in endothelial cells by inhibiting αvβ3-mediated SDF-1/CXCR4 signaling
Authors: Dilip Maddirela, Divya Kesanakurti, Chandramu Chetty, Dzung H. Dinh, Jasti S. Rao
Journal: Cancer Research (2012)

Abstract The majority of glioblastoma multiforme (GBM) tumors recur after the radiation (IR) treatment by increasing angiogenesis and IR-induced signaling events in endothelial cells that are involved in tumor neovascularization; these signaling events have yet to be well characterized. We observed that IR (8 Gy) significantly elevated MMP-2 expression and gelatinolytic activity in 4910 and 5310 human GBM xenograft cells. In addition, endothelial cells treated with tumor conditioned media (CM) obtained from IR-treated 4910 and 5310 cells showed increased microtubule formation. Thus, we investigated the possible anti-angiogenic effects of MMP-2 downregulation using siRNA (pMMP-2.si) in IR-treated cells and further determined the effect of CM obtained from mock, pSV (scrambled vector) and pMMP-2.si on endothelial cell growth and vessel formation. pMMP-2.si-CM-treated endothelial cells showed inhibited IR-CM-induced αvβ3, SDF-1, CXCR4, phospho-PI3K and phospho-AKT expression levels. In vitro angiogenesis assay showed that the pMMP-2.si+IR decreased the IR-induced vessel formation in endothelial cells. Immunofluorescence and immunoprecipitation experiments indicated the abrogation of αvβ3-SDF1 interaction in pMMP-2.si-CM-treated endothelial cells when compared to mock or pSV treatments. External supplementation of either rhMMP-2 or rhSDF-1 counteracted and noticeably reversed the pMMP-2.si-inhibited SDF-1, CXCR4, phospho-PI3K and phospho-AKT expression levels and angiogenesis, thereby confirming the role of MMP-2 in the regulation of αvβ3-mediated SDF-1/CXCR4 signaling. In corroboration with the in vitro results, the in vivo mouse dorsal air sac model also showed reduced angiogenesis with the injection of pMMP-2.si-treated xenograft cells whereas injection of mock or pSV-treated cells resulted in robust formation of characteristic neovascularization. Collectively, our data indicate the role of MMP-2 in the regulation of SDF-1/CXCR4 signaling-mediated angiogenesis in endothelial cells and demonstrates the anti-angiogenic efficacy of combining MMP-2 downregulation and IR when treating GBM in the future. 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 5277. doi:1538-7445.AM2012-5277
OC-053 Results Of The Uk Multi-regional Audit Of Blood Component Use In Cirrhosis
Authors: V Jairath, M Desborough, B Hockley, M Sekhar, A Burroughs
Journal: Gut (2014)

<h3>Introduction</h3> Cirrhosis is a complex acquired disorder of coagulation with a recent paradigm shift in understanding to consider cirrhosis as a pro-thrombotic disorder. It is a frequent indication for transfusion of blood components, both for prophylaxis and for treatment of bleeding, although indications and patterns of blood use are poorly characterised. <h3>Methods</h3> All NHS trusts with representation on the BSG membership list were invited to take part in a national audit. Data were collected prospectively on conseutive admissions with a confirmed diagnosis of liver cirrhosis over a 4 week period, with follow up to discharge/death/day 28. Specific information was requested on use of blood components, including indication, type of component and laboratory indices prior to transfusion. Standards were defined against guidelines on the use of red blood cells (RBCs), fresh frozen plasma (FFP), platelets and cryoprecipitate. <h3>Results</h3> Data on 1313 consecutive patients with cirrhosis (mean age 58 years, 65% male) were collected from 85 hospitals. The predominant aetiology was alcohol (70%; 921/1313); 74% of admissions were for features of decompensation; and 21% (275/1313) cases had a positive septic screen. 30% (391/1313) of all admissions were transfused a blood component; in 61% (238/391) this was for treatment of bleeding and in 39% (153/391) for prophylaxis. In patients transfused for bleeding (81%, 192/238 for gastrointestinal bleeding), 92% (220/238) received RBCs, 32% (77/238) FFP, 14% (34/238) platelets and 4% (10/238) cryoprecipitate; in patients with bleeding who received RBCs, the Hb threshold was &gt;8 g/dL prior to RBC transfusion in 31% (69/220) cases. For prophylaxis the majority (61%, 94/153) received transfusion in the absence of a planned procedure. In patients transfused for prophylaxis prior to a procedure (59/153): 19% (3/16) received FFP at an INR ≤1.5 for high risk procedures and 33% (6/18) received FFP at an INR ≤2 for low risk procedures; 36% (9/25) received platelet transfusion at a platelet count &gt;50 prior to a procedure. The most frequent procedures resulting in prophylactic transfusion were paracentesis (18/59), surgery (15/59) and endoscopy (10/59). In-hospital venous thromboembolism was documented in 2% (29/1313) cases. Case fatality during follow up was 10% overall (128/1313) with decompensated cirrhosis (41%; 52/128) as the most frequent cause of death. <h3>Conclusion</h3> Patients with cirrhosis are frequently transfused during hospitalisation. This audit highlights areas where greater scrutiny of blood component use is required, particularly in the group transfused for prophylaxis of bleeding. Further work is needed to improve patterns of blood use in cirrhosis to ensure patients are not exposed to unnecessary transfusion and its attendant harms. <h3>Disclosure of Interest</h3> None Declared.
Intrauterine Accumulation of F-18 FDG During Menstruation
Authors: SEIEI YASUDA, MICHIRU IDE, SHIGEHARU TAKAGI, AKIRA SHOHTSU
Journal: Clinical Nuclear Medicine (1997)

A 45-year-old woman underwent a whole-body FDG PET study during her menstrual cycle. On PET images, a focal area of increased F-18 FDG accumulation resembling a solitary pelvic tumor was noticed above the urinary bladder. MR imaging confirmed that the focal area was within the uterine cavity. After the PET study, a gynecologic examination including cytology was performed, and it revealed no pathologic lesion in the uterus. Fourteen months later, a second PET study was performed in the absence of menstruation. The PET result was normal. It is considered that during menstruation, high F-18 FDG accumulation can be observed in the uterus, probably due to intrauterine hemorrhage.
Asthma Caused by a Cathedral Wall
Authors: Alicia Armentia, Borja Bartolomé, Francisco-Javier Martín-Gil, Ana Callejo, Juan-Andrés Asturias, José María Vega, José Manuel Martín-Santos, María Luisa Arranz
Journal: New England Journal of Medicine (2001)

To the Editor: Accurate identification of phenotype is critical for precise genetic characterization.Standard textbooks define the Wolff-Parkinson-White syndrome as the combination of a short PR interval, an increased duration of the QRS complex caused by an initial slow deflection (delta wave), and supraventricular tachyarrhythmias. 1,2 The phenotype identified by Gollob et al. (June 14 issue) 3 is based on "a short PR interval (<120 msec) with a widened QRS complex (>110 msec) or an abnormal initial QRS vector (a delta wave)."Failure to specify that the widened QRS complex must be due to the slow initial delta wave and failure to require the presence of supraventricular arrhythmias result in a much looser definition.No data on the sensitivity or specificity of this definition are provided.Ventricular preexcitation may be intermittent; therefore, the sensitivity is less than 100 percent.The specificity is likely to be very low in this study because of the unusually high incidence of disorders that cause QRS abnormalities in the two families.In contrast, observations in a previous study of familial Wolff-Parkinson-White syndrome showed that structural changes were rare. 4 Most surprising is the fact that complete atrioventricular block, which would require loss of conduction over both normal and accessory pathways, developed in several affected persons.Finally, electrophysiological studies were performed in only eight patients, and several of these studies demonstrated atypical features. 2Therefore, the accuracy of the Wolff-Parkinson-White syndrome phenotype in this study is uncertain, and this may account for the difficulty in linking the physiological function of the identified gene product with the development of the Wolff-Parkinson-White syndrome.
Abstract 1094: Breast cancer metastatic competency in the hepatic niche is driven by E-cadherin re-expression.
Authors: Donald P. Taylor
Journal: Cancer Research (2013)

Abstract Nearly half of breast cancer metastases will become clinically evident 5 or more years after the cancer was seemingly ablated. This implies that metastatic cancer cells survived over this extended timeframe without emerging as detectable nodules. Breast cancer metastatic dormancy has yet to be universally defined, and is not well understood as a potential means by which clinically evident metastases emerge after being undetected for years (or decades) from the primary tumor diagnosis. Various mechanistic and microenvironmental factors may work independently, collaboratively (or both) in order to allow a dormant metastatic breast cancer cell (or small cluster) to survive long term. At least one tumor dormancy hallmark is likely required: that of E-cadherin re-expression in order to form heterotypic connections between the carcinoma cells and the liver parenchyma. This re-expression is known as the mesenchymal-to-epithelial-reverting-transition (MErT). This re-expression provides not only survival signals to the breast cancer cells but may also establish cell polarity and protection from autocrine signaling (or extracellular factors) that otherwise may prompt the breast cancer cells to initiate metastatic outgrowth. The purpose of this study is to determine E-cadherin's function in the establishment of breast cancer metastases to the liver. The MDA-MB-231 human breast cancer cell line, that can undergo induced MErT ex vivo, was transfected with either exogenously expressing E-cadherin or shRNA to E-cadherin. Xenograft splenic injections of these cell line variants into mice were performed and tumors allowed to grow for 30-60 days until sacrifice. Immunohistochemistry was performed on the liver and splenic tissue sections in order to assess the number and size of metastatic depostis. Preliminary data demonstrate that cells expressing exogenously encoded E-cadherin developed large splenic tumors with fewer to no liver metastases. MDA-MB-231 wild type cells spawned liver metastases about half the time. In order to more fully probe E-cadherin's role in metastatic competency experiments are underway to develop a doxycycline-inducible E-cadherin bicistronic vector allowing for the down-regulation of E-cadherin in the primary tumor and the re-expression in the metastatic niche. Subsequent immunohistochemistry will determine the metastatic E-cadherin status across these MDA-MB-231 cell variants. These results will provide insights into the role of MErT in metastatic establishment. Citation Format: Donald P. Taylor. Breast cancer metastatic competency in the hepatic niche is driven by E-cadherin re-expression. [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 1094. doi:10.1158/1538-7445.AM2013-1094
68Ga DOTATATE PET/CT Imaging of a Solitary Fibrous Tumor of the Nasopharynx
Authors: Rahul Vithalrao Parghane, Kanhaiyalal Agrawal, Bhagwant Rai Mittal, Jaya Shukla, Anish Bhattacharya, Ashok Gupta
Journal: Clinical Nuclear Medicine (2013)

Solitary fibrous tumors (SFTs) are rare group of mesenchymal tumors that occurs predominantly in the pleura. The role of PET/CT imaging in characterizing the SFT is not well reported. Mesenchymal tumors may express somatostatin receptors. We hereby report a rare case of SFT of the nasopharynx showing Ga DOTATATE avidity.
ONE-WIRE-TECHNIQUE: FIRST EXPERIENCES WITH A NOVEL TECHNIQUE FOR ENDOVASCULAR REPAIR OF THE ASCENDING AORTA IN ACUTE TYPE A AORTIC DISSECTIONS USING A COMBINED TRANSAPICAL AND TRANSFEMORAL APPROACH
Authors: Philippe Grieshaber, Nadine Nink, Dursun Guenduez, Peter Roth, Coskun Orhan, Meshal Elzien, Bernd Niemann, Andreas Böning, Ahmed Koshty
Journal: Journal of the American College of Cardiology (2016)
High Frequency of the R117H Cystic Fibrosis Mutation in Patients with Congenital Absence of the Vas Deferens
Authors: Radj Gervais, Viviane Dumur, Jean-Marc Rigot, Jean-Jacques Lafitte, Philippe Roussel, Mireille Claustres, Jacques Demaille
Journal: New England Journal of Medicine (1993)

To the Editor: We have previously described an increased frequency of the δF508 mutation of the cystic fibrosis gene in a group of patients with congenital absence of the vas deferens1. This sugges...
Crosstalk between nitrosative stress and altered Ca2<sup>+</sup>handling in arthritis-induced skeletal muscle dysfunction
Authors: Joseph Bruton, Takashi Yamada, Niklas Ivarsson, Cecilia Grundtman, Shi-Jin Zhang, Helena Erlandsson-Harris, Ingrid E Lundberg, Johana T Lanner, Arthur J Cheng, Håkan Westerblad
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background and objective</h3> Muscle weakness is a common symptom in patients with rheumatoid arthritis. In mice with collagen-induced arthritis, (CIA, a mouse model of rheumatoid arthritis) the authors demonstrated that muscle weakness is overwhelmingly due to nitric oxide (NO)-derived radicals modifying myofibrillar proteins (nitrosative stress) in skeletal muscle from mice. Here, the authors investigate whether this nitrosative stress might result from altered sarcoplasmic reticulum Ca<sup>2+</sup> handling properties <h3>Materials and methods.</h3> Myoplasmic free Ca<sup>2+</sup> concentration ((Ca<sup>2+</sup>)<sub>i</sub>) was measured in intact, single muscle fibres from flexor digitrum brevis (FDB) and soleus muscles. Mechanisms underlying changes in Ca<sup>2+</sup> handling were assessed using immunoprecipitation and Western blotting to investigate the ryanodine receptor (RyR) macromolecular complex in FDB, extensor digitorum longus (EDL) and soleus muscles. <h3>Results</h3> Increased tetanic (Ca<sup>2+</sup>)<sub>i</sub> was observed in FDB and soleus fibers from mice with CIA compare to those from control mice. The neuronal isoform of nitric oxide synthase (nNOS) co-localisation with RyR was greatly increased in soleus, FDB, and EDL muscles from CIA compared to control mice. In addition, there was an increased content of 3-nitrotyrosine in RyR macromolecular complex in CIA muscles compared to control muscles. <h3>Conclusions</h3> The increased presence of nNOS-RyR complexes results in NO-modifications of the RyR macromolecular complex which in turn increases tetanic (Ca<sup>2+</sup>)<sub>i</sub> in CIA skeletal muscles. This results in a positive feedback loop to enhance NO-derived radical production since increased tetanic (Ca<sup>2+</sup>)<sub>i</sub> will in turn increase activation of the Ca<sup>2+</sup>-dependent nNOS. Pharmacological intervention targeting nNOS may be useful to protect against arthritis-induced muscle weakness and wasting.
SP0124 Osteoporosis and Bone Diseases
Authors: W.F. Lems
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> In the field of osteo-immunology, the crosstalk between cytokines and bone, new data have elucidated that activated inflammatory cells at the site of inflammation produce a wide spectrum of cytokines which not only upregulate RANKl and stimulate local and generalized bone resorption, but also interfere with the Wnt-signaling pathway, with an inhibiting effect on bone formation. Obviously, this may lead to rapid bone loss and decreased bone quality in patients with systemic inflammatory rheumatic diseases, such as RA, PMR and SLE. As a consequence, both generalised and local bone loss (erosions) in RA may be limited in patients with adequate suppression of disease activity. This has been demonstrated in RA-patients treated with low dose glucocorticoids, but also in a longterm observational study in SLE. In contrast, bone loss at the spine and hips is much larger in glucocorticoid-treated patients after heart or liver transplantation. For primary osteoporosis, implementation is still the major challenge for the coming years. Unfortunately, no diagnostic procedures and/or therapeutic interventions are done in the majority of fracture patients 50 years and over! The first step is to perform a DXA-measurement, preferably followed by a VFA (Vertebral Fracture Assesment), a fall-risk evaluation, and a screening for (underlying) secondary osteoporosis. While earlier data have shown that adherence to treatment was around 50% in osteoporotic patients 1 year after starting treatment, recent data have elucidated that adherence to therapy in fracture patients could be above 85%! How should osteoporotic patients be treated? – lifestyle measures are still very important: adequate supply of calcium and vitamin D, stop smoking, limit alcohol intake, fall-prevention, regular weigh-bearing exercises; – oral bisphosphonates are first choice of treatment, zoledronic acid and denosumab are attractive alternatives for those who do not intolerate these drugs; – teriparatide is a unique osteo-anabolic drug, since it not only more or less preserves the BMD, by blocking osteoclast activity (such as bisphosphonates), but by building up new bone; – new exciting drugs are under development: odanacatib, a cathepsin K inhibitor, which seems to uncouple bone metabolism, since bone resorption is depressed, while bone formation is unchanged, and monoclonal antibodies against sclerostin, which seem to have a stronger bone formation stimulating effect than the currently available drugs. <h3>Disclosure of Interest</h3> W. Lems Conflict with: Merck, Takeda, Eli Lily, Novartis, Will Pharma, Servier, Amgen <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6204
Virus Particles in Tissue Cultures of a Human Liposarcoma
Authors: William T. Hall, Donald L. Morton, Richard A. Malmgren
Journal: JNCI Journal of the National Cancer Institute (1970)

Liposarcoma cells from a malignant pleural effusion of a 60-year-old man with a liposarcoma on his right thigh were grown in vitro in medium RPMI-1640. Fifty-seven days after the initiation of the culture, multilayered foci of tightly packed, lipid-containing cells were scattered throughout most flasks. By electron microscopic investigation, virus particles were found budding into intracytoplasmic vesicles of cells in all foci observed, but in none of the cells between foci or in cultures before foci had formed. The particles, which acquired their outer membrane from the membrane of the vesicle, measured about 85–100 mμ in diameter and were morphologically similar to C-type viruses in various animal neoplasms. Although particles did not bud from the plasma membrane, mature virions were seen extracellularly. There were no particles found in thin sections of the original liposarcoma and infectivit of the particles could not be demonstrated.
Pomalidomide reverses γ-globin silencing through the transcriptional reprogramming of adult hematopoietic progenitors
Authors: Brian M. Dulmovits, Abena O. Appiah-Kubi, Julien Papoin, John Hale, Mingzhu He, Yousef Al-Abed, Sebastien Didier, Michael Gould, Sehba Husain-Krautter, Sharon A. Singh, Kyle W. H. Chan, Adrianna Vlachos, Steven L. Allen, Naomi Taylor, Philippe Marambaud, Xiuli An, Patrick G. Gallagher, Narla Mohandas, Jeffrey M. Lipton, Johnson M. Liu, Lionel Blanc
Journal: Blood (2015)
The Value of Federalism in Defining Essential Health Benefits
Authors: Alan Weil
Journal: New England Journal of Medicine (2012)

Interview with Alan Weil on the states’ role in the implementation of the Affordable Care Act. (22:46)Download In December, it was announced that rather than the federal government's defining a single set of essential health benefits, each state will choose from among 10 options. This decision is sound public policy and capitalizes on the strengths of American federalism.
Tc-99m Ethylcysteinate Dimer Brain SPECT Perfusion Imaging in Ictal Nonepileptic Visual Hallucinations
Authors: Mordechai Lorberboym, Yair Lampl, Ronit Gilad, Menahem Sadeh
Journal: Clinical Nuclear Medicine (2002)

Visual hallucinations can occur within the central nervous system and may be associated with a lesion anywhere in the visual pathway. The purpose of this study was to assess "ictal" regional cerebral blood flow with Tc-99m ethylcysteinate dimer (ECD) SPECT in patients having acute hallucinations, and to compare the findings to the "interictal" state.A prospective study was performed to evaluate patients admitted to the neurology department with nonpsychiatric and nonepileptic visual hallucinations. The nine patients included in the study underwent thorough neurologic and psychiatric evaluations. A computed tomographic (CT) scan was performed when each patient was admitted, and electroencephalographic (EEG) recordings were made during their hallucinations. All patients underwent a brain SPECT while having acute hallucinations (ictal SPECT), and a follow-up scan was obtained 2 to 3 weeks later.All patients had normal ictal EEG findings during the hallucinations. Seven of nine patients had increased perfusion on the SPECT studies in one or more regions, with a mean lesion-to-contralateral ratio of 2.1 (range, 1.5 to 2.7). Three of the seven patients had findings consistent with a cerebrovascular accident. After treatment, the hallucinations disappeared in two patients and the motor deficit improved dramatically. The follow-up SPECT study showed significant improvement in all patients 1 week later. Charles Bonnet syndrome, frontal lobe dementia, and Anton syndrome were diagnosed in three other patients, and the last one had no identifiable background disease, all with normal findings of EEG, CT, and magnetic resonance examinations. They all responded readily to carbamazepine therapy, and the follow-up SPECT study showed resolution of the findings. Two of nine patients showed posterior cortical hypoperfusion, and eventually Lewy body disease was diagnosed. The SPECT showed no evidence of regional hyperperfusion.This prospective preliminary study suggests that brain imaging using SPECT may be useful in identifying the mechanisms and evolution of blood flow abnormalities in certain subgroups of patients who have visual hallucinations and may assist in the selection of specific therapy.
P477Myeloid PHD-2 deficiency leads to enlarged and fibrotic atherosclerotic plaques in mice
Authors: T L Theelen, E Marsch, J Demandt, C Dinjens, JP Cleutjens, MJ Gijbels, P Carmeliet, MJAP Daemen, JC Sluimer
Journal: Cardiovascular Research (2014)

Purpose: Macrophage specific knockout of PHD-2 prolylhydroxylase domain protein 2 (PHD-2-/-), the crucial cellular oxygen sensor, increased anti-inflammatory M2 macrophages, angiogenesis and arteriogenesis in mice. As macrophages and angiogenesis are known to enhance progression of atherosclerotic plaques, we hypothesized that macrophage PHD-2-/- would increase plaque size and progression.