tbuckley/cabot-search huggingface dataset:
P591Transplantation of adipose tissue mesenchymal cells conjugated with functionalized PLGA microspheres promotes revascularization and tissue repair in a murine model of acute myocardial infarction
Authors: R Madonna, L Petrov, MA Teberino, J-P Karam, C Montero-Menei, FV Renna, S Yla-Hertualla, R De Caterina
Journal: Cardiovascular Research (2014)

Rationale: Adipose tissue-derived mesenchymal stromal cells (AT-MSCs) may contribute repairing ischemic cardiovascular tissue. The engraftment and survival of transplanted cells in the harmful microenvironment of host tissue may be improved by combining stem cells with scaffolds to delay apoptosis and enhance their regenerative properties. Objectives: We examined whether poly (lactide-co-glycolide) (PLGA) microspheres functionalized with vascular endothelial growth factor (VEGF) enhance survival, growth, and differentiation of AT-MSCs, and the therapeutic efficacy of transplanted AT-MSCs conjugated with VEGF-microspheres or injection of conditioned medium from AT-MSCs in a murine model of acute myocardial infarction (AMI). Methods: Non-functionalized (empty) or VEGF-releasing microspheres were produced and coated with murine AT-MSCs. Twelve month-old male C57BL/6 mice underwent coronary artery ligation, followed by randomization into 7 groups (n=5/group): Sham operation, AMI control (saline 20 μl), intramyocardial injection with AT-MSCs only (2.5x105 cells/20 μl), or concentrated medium from AT-MSCs (CM, 20 μl), or AT-MSCs (2.5x105 cells/20 μl) conjugated with empty microspheres or VEGF-releasing microspheres. Results: Growth-curve and differentiation assays showed that VEGF-releasing microspheres do not impact proliferation or osteogenic and adipogenic differentiation of AT-MSCs. Conversely, H2O2-induced apoptosis was inhibited in AT-MSCs conjugated with VEGF-releasing microspheres, and this effect was dependent on the VEGF/Akt axis, since reverted by pre-incubation with the Akt inhibitor LY294002 or an anti-VEGF receptor antibody. In a Matrigel assay, AT-MSCs conjugated with VEGF-releasing microspheres were more pro-angiogenic than AT-MSCs alone. Finally, when compared with AT-MSCs alone, AT-MSCs conjugated with VEGF-releasing microspheres decreased the area of fibrosis and increased myogenic marker expression, arteriogenesis, number of cardiac-resident c-Kit positive cells and fractional shortening when transplanted into the infarcted hearts of C57 mice, effects that were paralleled by the injection of CM (p<0.01 vs AMI control by ANOVA) . Conclusions: The delivery of the AT-MSCs conjugated with VEGF-releasing microspheres or injection of CM may have therapeutic applications for enhancing arteriogenesis and survival of AT-MSCs and for improving left ventricular function after AMI.
Results of Trans-Sphenoidal Cryohypophysectomy for Carcinoma of the Breast
Authors: Louis W. Conway, William F. Collins
Journal: New England Journal of Medicine (1969)

In 100 cases of widespread, disseminated carcinoma of the breast, with a follow-up between 14 and 40 months, overall remission rate after cryohypophysectomy was 40 per cent. Eighty-five of the patients are now dead, 25 after remission and all 60 who did not respond to hypophysectomy. The mean survival time of those who responded was 20.3 months as compared with four and four-tenths months for those who did not respond. A previous objective remission to either castration or hormone therapy or both was associated with an increased remission rate. Extensive previous chemotherapy was associated with a less favorable remission rate, regardless of prior history of hormone dependence of the tumor.
All that is red is not blood!
Authors: A. Soloman, M. Merheb, D. Ferguson
Journal: Endoscopy (2010)

A 62-year-old woman presented for screening colonoscopy after a 24-hour clear-liquid diet and Colyte preparation. Frank blood was noted from the point of colonoscope insertion up to the terminal ileum ([Fig. 1 a]). Aspirate tested negative with the hemoccult card. Using narrow-band imaging (NBI) the “red liquid” appeared cyan blue ([Fig. 1 b]). Upon further questioning during recovery, the patient reported eating red jello.
ET-13 * RETROVIRAL REPLICATING VECTOR (RRV)-MEDIATED PRODRUG ACTIVATOR GENE THERAPY WITH CODON-OPTIMIZED NITROREDUCTASE IN EXPERIMENTAL GLIOMA
Authors: S. Collins, C. Logg, A. Inagaki, S. Kamijima, P. Lehouritis, P. Searle, M. Tangney, N. Kasahara
Journal: Neuro-Oncology (2014)

Our studies to date have demonstrated dramatic survival benefit when tumor-selective retroviral replicating vectors (RRV) are employed for prodrug activator gene therapy in a variety of preclinical cancer models. RRV-mediated gene therapy using yeast cytosine deaminase (CD) is under investigation in multi-center ascending dose trials in patients with recurrent high grade glioma in the United States. We have further developed an RRV encoding E.coli nitroreductase (NTR), a prodrug activator enzyme which converts CB1954 to a potent bifunctional alkylating agent. We constructed RRV encoding wild-type E.coli NTR genes (RRV-NfsA, RRV-NfsB) as well as NTR variants extensively modified to optimize human codon usage and vector stability (RRV-NAO, RRV-NBO). NTR transgene insertion did not affect vector replication, which resulted in increasing NTR expression over time in U87 human glioma cultures for all vectors, but sequence optimisation significantly increased genomic stability of the RRV-NAO and RRV-NBO vectors over serial passage. U87 cells fully transduced with the optimized vectors showed higher levels of NTR protein and increased levels of enzymatic activity compared with cells transduced with wild-type vectors. In vitro cytotoxicity was examined by MTS assay after CB1954 treatment of fully transduced U87 cells. Viability was reduced by >80% within 48 hrs in cells transduced with RRV-NAO, which showed the most potent cell killing efficiency and bystander effect among all vectors tested. Significant reduction in luminescence and inhibition of tumor growth was observed in subcutaneous U87-FLuc2 tumors initiated with 2% RRV-NAO transduction followed by intraperitoneal administration of CB1954. In intracerebral U87-FLuc2 orthotopic tumor models, stereotactic intratumoral injection of RRV-NAO and repeated cycles of prodrug treatment also resulted in significant luminescence reduction, and achieved prolonged survival benefit. These data indicate that we have been successful in developing an improved prodrug activator gene with therapeutic efficacy when delivered by RRV in experimental models of human glioma.
AB0474 Comparison of drug retention rates between anti-tumor necrosis factor agents in rheumatoid arthritis and ankylosing spondylitis in daily clinical practice:
Authors: J.M. Senabre-Gallego, J. Rosas, G. Santos-Soler, C. Santos-Ramírez, M. Sánchez-Barrioluengo, X. Barber, E. Salas-Heredia, C. Cano, N. Llahí
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The efficacy of different anti-tumor necrosis factor alpha (anti-TNF) agents in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) has not been directly compared in clinical trials, and meta-analysis showed no differences between them<sup>1,2</sup>. Drug retention rates obtained in observational studies are indicators of treatment success<sup>3</sup>. <h3>Objectives</h3> To analyze the retention rates and causes of discontinuation among anti-TNF agents in our local cohort of RA and AS patients. <h3>Methods</h3> We conducted an observational prospective study. Patients treated with infliximab (INF), etanercept (ETN) and adalimumab (ADA) since January 2001 to November 2011 were included. The causes of discontinuation were categorized as: inefficacy, adverse events, clinical remission and loss of follow up. Kaplan-Meier survival function was estimated. Factors that could determine the time to discontinuation were analyzed using a Cox proportional hazard ratio model. <h3>Results</h3> A total of 318 treatments were started: 97 INF, 105 ETN and 116 ADA. Total exposure to TNF inhibitors was 589 patient-years. Discontinuations due to adverse events were: 49% INF, 34% ADA and 33% ETN. ETN retention curves were higher than INF or ADA. Cox regression analysis showed higher risk of discontinuation for INF than ETN (Table 1) in both RA and AS patients, but comparison between ETN and ADA do not showed statistical differences. <h3>Conclusions</h3> ETN estimated retention curves were higher than INF or ADA. The risk of INF discontinuation is more than double compared with ETN in both RA and AS. Comparison between ETN and ADA do not showed statistically significant differences. <h3>References</h3> Gartlehner G, Hansen RA, Jonas BL, Thieda P, Lohr KN. The comparative efficacy and safety of biologics for the treatment of rheumatoid arthritis: a systematic review and metaanalysis. J Rheumatol. 2006;33:2398–408. McLeod C, Bagust A, Boland A, Dagenais P, Dickson R, Dundar Y, et al. Adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis: a systematic review and economic evaluation. Health Technol Assess. 2007;11:1–158, iii-iv. Wolfe F. The epidemiology of drug treatment failure in rheumatoid arthritis. Baillieres Clin Rheumatol 1995;9:619–32. <h3>Disclosure of Interest</h3> J. Senabre-Gallego Grant/Research support from: Asociaciόn para la Investigaciόn en Reumatología Marina Baixa (AIRE-MB), J. Rosas: None Declared, G. Santos-Soler: None Declared, C. Santos-Ramírez: None Declared, M. Sánchez-Barrioluengo: None Declared, X. Barber: None Declared, E. Salas-Heredia: None Declared, C. Cano: None Declared, N. Llahí: None Declared
P476SREBF1, SREBF2 and their target genes expression is different in wistar and SHR rats under high cholesterol treatment conditions
Authors: HV Portnichenko, SV Goncharov, LV Tumanovska, DO Stroy, OS Moibenko, MO Kuzmenko, OO Moibenko, VE Dosenko
Journal: Cardiovascular Research (2014)

Purpose: Investigate pathophysiological changes in cardiovascular system and discover the role of SREBP related system in this process under conditions of essential hypertension and high cholesterol diet in rats.

Methods: 6 month old male Wistar rats and spontaneously hypertensive rats (SHR) were taken as the objects of research. They were fed with standard rodent's food enriched with 3% cholesterol for 8 weeks. Registration of cardiac function using pressure-volume conductance catheter, lipid profile measurements, histological examinations, reverse transcription and real-time PCR were performed.

Results: After cholesterol diet, hemodynamic parameters worsened in Wistar rats, but in SHR rats no significant changes in these parameters were found. Lipids profile researches has shown 27% higher levels of HDL in SHR rats before and after high cholesterol diet, in contrast to Wistar. Histological researches revealed considerable changes in cardiac and aortic tissues morphology and histological parameters after cholesterol diet in SHR unlike the Wistar rats. Our study indicates that levels of SREBF and their target genes expression are significantly different in Wistar and SHR rats. We have firstly described that levels of SREBF1 and SREBF2 mRNA in heart are lower in SHR than in Wistar rats. After cholesterol diet expression of SREBF1 and SREBF2 was increased only in SHR, but not in Wistar. In liver, another interrelation was observed - significant response on high cholesterol diet appeared only in Wistar rats. Expression of SREBF1 and SREBF2 target genes (Insig-1, HMGCoAr) was not associated with changes of SREBF expression.

Conclusions: We have identified two different reactions. The first is cardiac functions and lipid profile levels deterioration, and changes in SREBF mRNA expression, but without any histological changes in aorta tissues in healthy Wistar rats after 8 weeks of 3% cholesterol diet. The second is characterized with absence of significant changes in cardiac function, similar lipid profile levels alteration, quite different profile of SREBF mRNA expression, and histological changes typical to first stages of atherosclerosis. These results confirm our hypothesis that SREBP-related system is involved in cardiac failure development and is affected by high arterial pressure and high cholesterol diet. Therefore it is potential target for further investigations in cardiac failure development, especially complicated by metabolic syndrome disorders like lipid profile deterioration and arterial hypertension.
Les adénomes iléaux dans les polyposes adénomateuses familiales colectomisées
Authors: E Pommaret, Y Parc, A Vienne, J Lefevre, S Chaussade, C Florent, B Desaint
Journal: Endoscopy (2010)

Introduction: Le risque élevé de cancer colo-rectal dans les polyposes adénomateuses familiales justifie la réalisation d'une colectomie à visée prophylactique avec anastomose iléo-rectale, iléo-anale avec réservoir en J ou une iléostomie définitive. Cette étude a pour but de déterminer l'incidence, la prévalence et les facteurs de risque de développement d'adénomes sur les différents segments iléaux après colectomie.
1401 THE PREVALENCE OF TYPE 2 DIABETES MELLITUS IN PATIENTS WITH COMPOUND HETEROZYGOUS HAEMOCHROMATOSIS
Authors: M. Smyth, M. Azhar, C. Kiat, M. Scarry, M. Bohan Keane, A. Moore, A. Lyons, C. Minihan, J.M. Lee
Journal: Journal of Hepatology (2013)
ANG-1005 in Patients with Brain Metastases from Breast Cancer: Correlative Imaging with 18F-FLT-PET/CT
Authors: S. Bates, M. Lindenberg, C. Bryla, N. Patronas, L. Amiri-Kordestani, T. Fojo, S. Balasubramaniam, P. Choyke
Journal: Annals of Oncology (2015)
Aseptic Loosening of a Knee Prosthesis as Imaged on FDG Positron Emission Tomography
Authors: F De Winter, C Van De Wiele, D De Clercq, D Vogelaers, P De Bondt, R A Dierckx
Journal: Clinical Nuclear Medicine (2000)

FDG positron emission tomography (PET) has been presented as a highly accurate technique (n = 51; accuracy 96%, no false-positive results) for diagnosing chronic osteomyelitis. The authors report a case of high FDG uptake in aseptic loosening of a knee prosthesis. The FDG uptake mechanism in infection is related to increased tracer accumulation in activated macrophages, leukocytes, and fibroblasts. Macrophages and fibroblasts also play a role in aseptic loosening. This may be reflected in an elevated FDG uptake. Although promising, FDG PET probably will not be able to distinguish infection from inflammation. Further investigation is needed to determine its value in loosened prostheses.
ISO Research M.D.s: Clinical Scientists Needed for Biomedical Boom
Authors: F. X. Mahaney
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article ISO Research M.D.s: Clinical Scientists Needed for Biomedical Boom Get access Francis X. Mahaney, Jr. Francis X. Mahaney, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 3, 2 February 1994, Pages 171–172, https://doi.org/10.1093/jnci/86.3.171 Published: 02 February 1994
Abstract 862: Pre-clinical and molecular analysis of Crizotinib in c-Met positive uveal melanoma
Authors: Mark J. de Lange, Mieke Versluis, Gre P.M. Luyten, Martine J. Jager, Pieter A. van der Velden
Journal: Cancer Research (2012)

Abstract Uveal melanoma (UM) is an intraocular neoplasm with an annual incidence of 7 per million. UM originates from melanocytes just like cutaneous melanoma (CM) and similar to CM, the RAS/RAF/MEK/ERK pathway is involved in the development of UM. However, not all UM seem to depend on the activation of this pathway. Loss of ERK signalling may be correlated with progression as the ERK negative cells are derived from UM metastasis. In these tumours, cells apparently use a different pathway to proliferate and survive. In order to identify treatment targets for metastasis patients we set out to identify the pathway which stimulates proliferation in the ERK negative UM cells. Growth factor receptor screening revealed that activation of c-Met or HGF receptor, is inversely correlated with ERK activation leaving the metastatic UM, halfway progression to metastasis, with both c-Met and ERK activated. In this study, we tested the efficacy of c-Met inhibitor Crizotinib and investigated primary and downstream targets to delineate the role of c-Met signalling in UM progression. Crizotinib was shown to specifically inhibit c-Met positive UM and this was most clear when cells were grown anchorage independent, in line with a role in dissemination for c-Met. With phospho-proteomics we showed that c-Met is the primary target of Crizotinib in UM while FAK emerges as the prime downstream target. Moreover, Src was shown to be the downstream kinase that transmits the c-Met signal to both FAK and ERK in metastatic UM. In UM metastasis, lacking active ERK, Src is absent and FAK is directly activated by c-Met. Combined, our data support the use of Crizotinib in late stage UM and reveals altered c-Met signalling in uveal melanoma progression. 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 862. doi:1538-7445.AM2012-862
The clinical application of tricyclic antidepressant pharmacokinetics and plasma levels
Authors: J Amsterdam, D Brunswick, J Mendels
Journal: American Journal of Psychiatry (1980)

The authors present a clinical approach for predicting and using plasma concentrations of tricyclic antidepressants in the treatment of depressed patients. They review the pharmacokinetics of this group of drugs and their side effects and toxicity. There is a suggested therapeutic range for plasma concentrations of imipramine, amitriptyline, and nortriptyline; more definitive studies are needed to determine the necessary plasma levels for achieving clinical response with the other tricyclic antidepressants (desmethylimipramine, protriptyline, doxepin, clomipramine, impiramine N-oxide, and butriptyline). A more thorough knowledge of the clinical pharmacokinetics of tricyclic antidepressants should lead to more rational use of these drugs, with a higher response rate and fewer adverse reactions.
Ontogeny of human IgE-expressing B cells and plasma cells
Authors: F. Ramadani, H. Bowen, N. Upton, P. S. Hobson, Y.-C. Chan, J.-B. Chen, T. W. Chang, J. M. McDonnell, B. J. Sutton, D. J. Fear, H. J. Gould
Journal: Allergy (2016)

Background IgE-expressing (IgE+) plasma cells (PCs) provide a continuous source of allergen-specific IgE that is central to allergic responses. The extreme sparsity of IgE+ cells in vivo has confined their study almost entirely to mouse models. Objective To characterize the development pathway of human IgE+ PCs and to determine the ontogeny of human IgE+ PCs. Methods To generate human IgE+ cells, we cultured tonsil B cells with IL-4 and anti-CD40. Using FACS and RT-PCR, we examined the phenotype of generated IgE+ cells, the capacity of tonsil B-cell subsets to generate IgE+ PCs and the class switching pathways involved. Results We have identified three phenotypic stages of IgE+ PC development pathway, namely (i) IgE+germinal centre (GC)-like B cells, (ii) IgE+PC-like 'plasmablasts' and (iii) IgE+PCs. The same phenotypic stages were also observed for IgG1+ cells. Total tonsil B cells give rise to IgE+ PCs by direct and sequential switching, whereas the isolated GC B-cell fraction, the main source of IgE+ PCs, generates IgE+ PCs by sequential switching. PC differentiation of IgE+ cells is accompanied by the down-regulation of surface expression of the short form of membrane IgE (mIgES), which is homologous to mouse mIgE, and the up-regulation of the long form of mIgE (mIgEL), which is associated with an enhanced B-cell survival and expressed in humans, but not in mice. Conclusion Generation of IgE+ PCs from tonsil GC B cells occurs mainly via sequential switching from IgG. The mIgEL/mIgES ratio may be implicated in survival of IgE+ B cells during PC differentiation and allergic disease.
Night of the gatekeeper
Authors: G. Dunea
Journal: BMJ (1997)

The boy had kept nothing down for three days, ever since coming back from his vacation in Mexico. For the past six hours he had been vomiting continuously, and by now he was dehydrated and could no longer sit up. The mother was becoming hysterical, and at 11 pm the father, a professor at the medical school, now thoroughly alarmed, decided to call the health medical organisation (HMO). He had joined this some time earlier when the university had offered coverage at a lower rate than his private insurance. It was understood at the time that the children …
AB1030 Efficiency of Spoken Medical Advice in Quitting Smoking in Patients Smokers with Rheumatoid Arthritis
Authors: A. Gudelj Gračanin, F. Grubišić, I. Marković, I. Milivojem, M.I. Čulo, S. Grazio, J. Morović-Vergles
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Smoking is a big public health problem that represents a risk factor for the onset and progression of rheumatoid arthritis. The physician and the patient are partners in the treatment process in which mutual understanding and cooperation lead to betterment. <h3>Objectives</h3> Assessing patient compliance investigating the efficiency of spoken medical advice in quitting smoking in patients smokers with rheumatoid arthritis. <h3>Type of Research</h3> Observational, multicenter. <h3>Methods</h3> The research included ninety-six patients (82 women, 14 men; average age 60.2 + 11.99) with rheumatoid arthritis diagnosed based on modified criteria of the American College of Rheumatology from 1987. All the patients were from continental Croatia, recruited in cooperation between two rheumatology departments. Out of the total number of patients there were twenty smokers (20.8%) and 76 non-smokers (79.2%). DAS28CRP values of disease activity were analyzed, as well as the patient9s assessment of disease activity on a visual analogue scale (on a 10cm visual analogue scale – VAS) in smokers and non-smokers. Smokers were given short, spoken advice about the harms of smoking, and advice to quit smoking. The results of efficiency of spoken advice to quit smoking in smokers with RA were analyzed after 1 month, and descriptively presented. <h3>Results</h3> Average duration of rheumatoid arthritis was 11.8 + 9.90 years. DAS28CRP and VAS values were analyzed in smokers and non-smokers, and no statistically significant difference was noticed between study groups (p&gt;0.05), although the medial VAS value of pain in non-smokers was 5, and in smokers 6. In 45% of non-smokers and in 30% of smokers the DAS28CRP value was between 3.2 and 5.1. 20% of non-smokers and 30% of smokers had the DAS28CRP value &gt;5.1. After spoken medical advice to quit smoking, two patients (10%) quit smoking in the period of one month. <h3>Conclusions</h3> Spoken medical advice to quit smoking in patients smokers with RA was efficient in a small number of patients, which raises the question about patient compliance in general. KEY WORDS rheumatoid arthritis, smoking, spoken medical advice, patient compliance <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3314