tbuckley/cabot-search huggingface dataset:
AB0572 Additional Role of FDG Pet/Ct in the Assessment of Disease Activity in Takayasu Arteritis
Authors: E. Tombetti, E. Incerti, A. Salerno, S. Sartorelli, M.C. Di Chio, P. Alongi, F. Fallanca, M. Papa, L. Gianolli, M.G. Sabbadini, A.A. Manfredi, M. Picchio, F. De Cobelli, E.M. Baldissera
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Takayasu arteritis (TA) is an inflammatory vasculitis, typically affecting young women with important morbidity and mortality and a largely unknown pathogenesis. Disease activity (DA) evaluation is still a major unresolved issue, currently defined according to NIH criteria. <h3>Objectives</h3> Evaluation of the additional role of PET/CT with FDG (PET/CT) in the assessment of DA status. <h3>Methods</h3> A cross-sectional analysis of 19 patients (pts) with definite TA was performed. DA was evaluated with NIH criteria, and all pts underwent PET/CT and magnetic resonance angiography (MRA) examinations, with a median interval of 60 days. All vascular lesions uptake in PET/CT was evaluated both with a qualitative and a quantitative (SUV max) method. The capability of MRA and PET/CT in detecting active vascular inflammation was compared in all the lesions evaluable for dimensions with PET/CT. DA as assessed by MRA and PET/CT was compared with DA by NIH criteria. <h3>Results</h3> In 11/19 pts PET/CT was positive with a median SUVmax of 3.5 (range: 2.7-9.8). Of the 89 vascular lesions evidenced by MRI and evaluable with PET/CT, 24 (27%) showed a positive uptake. Three out of 6 pts with active disease at the time of MRA showed vascular enhancement in at least one lesion, while vascular enhancement was observed in 4/13 pts with inactive disease. Two out of 5 pts with active disease at the time of PET/CT showed vascular uptake in at least one vascular lesion, while vascular uptake was observed 9/14 pts with inactive disease. Five out of 11 pts with evidence of uptake on PET/CT showed vascular enhancement at MRI, while 3/8 pts with a negative PET/CT showed vascular enhancement at MRI. <h3>Conclusions</h3> NIH criteria, MRI, and PET/CT are non-redundant modalities of addressing DA in TA, possibly giving complementary information. Prospective evaluation of these preliminary results is needed to define the precise role of a multi-modality assessment of DA in TA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5497
Dumbbell-Shaped Activity on Meckel’s Scintigraphy Caused by Hiatal Hernia
Authors: Xia Bai, Victor M. Ho-Fung, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2015)

A 13-month-old underwent Meckel’s scintigraphy to evaluate a cause of melena. The images revealed a dumbbell-shaped activity. One side of dumbbell was located in the midline lower chest, whereas another side with similar intensity was in the normal location of the stomach. A subsequent contrast CT demonstrated a large hiatal hernia.
Abstract 3369: The importance of dose schedule with Hsp90 inhibitors: Results from a Phase II study in dogs with mast cell tumors.
Authors: Cheryl A. London, Misty D. Bear, David A. Proia
Journal: Cancer Research (2013)

Abstract Purpose: STA-1474 is the prodrug of ganetespib, currently the most advanced Hsp90 inhibitor in human clinical trials. In a Phase I clinical trial, STA-1474 demonstrated biologic activity in dogs with spontaneous tumors. Data from this trial suggested that longer drug infusion times (8 hours versus 1 hour) were potentially associated with greater biologic activity. The purpose of the following study was to extend these observations and identify the optimum dosing schedule of STA-1474 in dogs with spontaneous mast cell tumors (MCT). Experimental Design: This was a Phase 2 trial in which dogs with spontaneous MCT received STA-1474 (6 mg/kg, per week) under one of four different dosing schedules: once weekly with a 1 hour infusion (cohort A) or 8 hour infusion (cohort B), or twice weekly with a 1 hour infusion given 24 hour (cohort C) or 72 hour (cohort D) between doses. Toxicities, biomarker changes from pre- and two post-treatment biopsies, and tumor responses were assessed. Results: Twenty-four chemotherapy and radiation naïve dogs with MCT were enrolled. Toxicities were mild and primarily gastrointestinal in nature consisting of diarrhea, vomiting, inappetence and lethargy. Measurable responses were observed from dogs in cohort A (SD=5, PD=1), cohort B (PR=2, SD=4), cohort C (PR=3, SD=3) and cohort D (PR=2, SD=1, PD=1). Biopsies are currently being evaluated by reverse phase protein array and results will be presented. Conclusions: This study provides further evidence that prolonged exposure to STA-1474 improves biological activity. Dosing STA-1474 on two consecutive days yielded the greatest objective responses (50%) and a disease control rate of 100%. Given the similarities of canine and human cancers with respect to tumor biology and HSP90 synthesis following its inhibition, it is likely that more frequent exposure to ganetespib will demonstrate comparable anti-cancer activity in human patients and is currently being evaluated in a Phase I study. Citation Format: Cheryl A. London, Misty D. Bear, David A. Proia. The importance of dose schedule with Hsp90 inhibitors: Results from a Phase II study in dogs with mast cell tumors. [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 3369. doi:10.1158/1538-7445.AM2013-3369
Laparoscopic versus Open Appendectomy
Authors: Robert W. Ikard, Charles F. Federspiel
Journal: New England Journal of Medicine (1995)

To the Editor: Bravo to Dr. Gottlieb for her Sounding Board article.The silence of organized medicine in the face of two decades of terrorist assaults on women, physicians who perform abortions, and personnel assisting in abortions has been nothing less than scandalous.Were such murderous rage and harassment unleashed against physicians who perform vasectomies, their patients, and their staffs, it is not far-fetched to believe that the American Medical Association and the American College of Surgeons would long since have voiced their outrage publicly.But in the face of the terrorist campaign against women and abortion providers by right-wing fanatics and religious bigots, organized medicine has responded with craven silence.
AB0088 Activity of Cationic Proteins in Neutrophils, Complement Activity Fnd Circulating Immune Complexes in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Systemic Sleroderma:
Authors: V.I. Shishkin, G.V. Kudriavtseva
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Cationic proteins (CP) of neutrophils are characteristically detected in patients with rheumatoid arthritis (RA), and growing evidence suggest that they are involved in disease pathogenesis. <h3>Objectives</h3> We investigated the concentration of the cationic proteins (CP) in lysosomes of neutrophils in systemic lupus erythematosus (SLE), RA, systemic scleroderma (SSd), activity of the blood complement system (CH50) and concentration of immune complexes (CIC) in the blood serum. <h3>Methods</h3> The study group included 105 patients with RA, SLE 158, 45 patients with SSd, and 78 healthy controls. CP content of neutrophils were assayed by fluorescent cytochemical method (lysosomal cationic test)/Neutrophils were stained with fast blue and asur II. Hemolytic complement activity was determined by the standard method using sheep red blood cells in units of 50% hemolysis (CH50). Circulating immune complexes were measured using polyethylene glycol 6000. <h3>Results</h3> CP in SLE, RA and SS significantly fall in all diseases. Decrease in CP followed by increased levels of the CIC in SLE and RA. Correlation of reduced complement activity with the CEC was marked in SLE and RA but not in SSc. At the same time, CH, increased levels of CIC complexes significantly correlated with the activity of SLE and, to a lesser extent RA. In systemic sclerosis increase levels of circulating immune complexes found only in severe Raynaud9s syndrome and progressive lung disease <h3>Conclusions</h3> These findings suggest that peripheral blood neutrophils are involved in the pathogenesis of RA, SLE and SSc. In SLE and RA with great confidence we can assume the relationship of these changes with CIC. Significant decrease in complement activity in patients with SLE and RA confirms this hypothesis. Lower levels of complement in SLE may also indicate in favor of the rapid depletion of the complement system, genetically inherent in this disease. Data obtained in patients with scleroderma show significant differences from SLE and RA, and therefore evidence in favor of special pathogenesis of this disease. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5724
Abstract 3034: Hsp90-dependent stabilization of active NPM-ALK kinase: Structural insights by mutagenesis of the ALK catalytic domain
Authors: Paolo Bonvini, Lara Mussolin, Giorgio Cozza, Stefano Moro, Angelo Rosolen
Journal: Cancer Research (2012)

Abstract Background. Among the posttranslational modifications occurring in eukaryotic cells, phosphorylation is the most critical for proteins, as phosphate-mediated conformational switching of catalytic and non-catalytic motifs impacts expression and activity through changes in structure stability. Activation by phosphorylation is the rule for protein kinases, including oncogenic protein tyrosine kinase NPM-ALK (nucleophosmin-anaplastic lymphoma kinase) in Anaplastic Large Cell Lymphomas, though it renders the kinase prone to degradation. For several of them, however, the maintenance of functional stability is provided by the molecular chaperone Hsp90, through the recognition of specific motifs within the catalytic domain. Objectives. Herein, we determined whether NPM-ALK kinase activity facilitates Hsp90 binding, and whether structural motifs within NPM-ALK catalytic domain favor or impair Hsp90 interaction. Design/Methods. To test this hypothesis we prepared a series of N- and C-terminal deletion mutants of wild-type NPM-ALK, as well as inactive point mutants by site-directed mutagenesis of the NPM-ALK ATP-binding site and activation loop. Results. Using NPM-ALK constructs in COS7 and 293T cells, we showed that Hsp90 strongly interacts with wild-type NPM-ALK, but fails to co-adsorb with inactive point mutants and with deletion mutants lacking the entire kinase domain. By comparison, binding to Hsp90 family members Hsc70 and Hsp70 is independent of NPM-ALK activity, suggesting a greater dependence of active NPM-ALK on Hsp90 function. Accordingly, phosphorylated NPM-ALK associated with Hsp90 and co-chaperone cdc37, and pharmacological inhibition of NPM-ALK prevented the interaction of NPM-ALK with both proteins. Of note, mutants unmasking the αC-helix motif in the N-terminal lobe of the catalytic domain maintained the ability to bind Hsp90, whereas mutants lacking αC-helix did not. Conclusions. Our findings, therefore, suggest a model in which, in addition to a role in folding nascent NPM-ALK, Hsp90 provides an “ongoing folding support” to activated NPM-ALK kinase, by protecting self-phosphorylated NPM-ALK from ubiquitination through recognition of specific unstable motifs within its catalytic domain. 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 3034. doi:1538-7445.AM2012-3034
A1.35 Adiponectin isoform-mediated effects on P38 MAPK and AMPK pathways in rheumatoid arthritis synovial fibroblasts
Authors: K Khawaja, KW Frommer, M Bausch, S Rehart, U Müller-Ladner, E Neumann
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Adiponectin, a C1q/tumour necrosis factor homologue, was previously described to be secreted by adipocytes. Adiponectin levels were found to be increased in the synovial fluid of rheumatoid arthritis (RA) patients as compared to osteoarthritis patients, hence suggesting a role of adiponectin in the pathophysiology of the disease. RA synovial fibroblasts (SF) in addition to adipocytes are able to secrete adiponectin in the synovium <i>in vivo</i>. At present, four different adiponectin isoforms are known, namely globular, low-molecular-weight (LMW), middle-molecular-weight (MMW) and high-molecular-weight (HMW) adiponectin. Adiponectin acts by binding to its receptors AdipoR1, AdipoR2, and potentially PAQR3 and PAQR10. This leads to the activation of signalling cascades involving key signalling molecules like AMPK and p38 MAPK. The aim of the present study was to verify which signalling molecules are involved in the adiponectin-induced signalling in RASF and to analyse potential differences in the adiponectin isoform-mediated signalling. <h3>Methods</h3> RASF were preincubated with serum-free medium for 30 min with or without signalling inhibitors. Stimulation of RASF was performed using the respective adiponectin isoforms: WT (wild type containing all isoforms), globular, LMW, and MMW/HMW-enriched adiponectin (each 10 µg/ml) for 10 min. Subsequently, phosphorylation of p38, AMPK, and FAK was analysed by Western blotting. <h3>Results</h3> Phosphorylation of p38 was increased by all adiponectin isoforms, with the strongest induction by the MMW/HMW-enriched adiponectin (2-fold increase). Similarly, the phosphorylation of AMPK was increased in response to all adiponectin isoforms and the effect was again stronger with the MMW/HMW-enriched adiponectin (5-fold increase). On the contrary, although FAK was detectable in RASF, no alteration in FAK phosphorylation was observed in response to adiponectin isoform stimulation indicating that FAK does not play a role here. The adiponectin-mediated increase in phosphorylation of AMPK was further enhanced by the addition of the AMPK activator AICAR (e.g. 6-fold increase for WT adiponectin) and was reduced by the AMPK inhibitor compound C (e.g. 2-fold decrease for LMW adiponectin). Compound C caused an additional increase in the adiponectin isoform-induced phosphorylation of p38 (e.g. 2-fold increase for globular adiponectin), whereas pre-treatment with the p38 inhibitor SB203580 did not have any effect on the phosphorylation of AMPK. <h3>Conclusions</h3> Adiponectin signalling in RASF is mediated via the p38 MAPK and AMPK pathway but not FAK, and the effect is adiponectin isoform-dependent. The data suggest that the p38 MAPK pathway is a compensatory pathway for the AMPK pathway but not <i>vice versa</i>. <h3>Funding</h3> This work was supported by the German Research Foundation (DFG) (NE1174/8-1).
EARLY (1-10 DAYS) READMISSION IS ASSOCIATED WITH A SIGNIFICANTLY LOWER 2-12 MONTHS POST-DISCHARGE ALL-CAUSE MORTALITY AMONG OLDER MEDICARE BENEFICIARIES HOSPITALIZED FOR HEART FAILURE WITH 30-DAY ALL-CAUSE READMISSIONS
Authors: Phillip Hong Lam, Cherinne Arundel, Rahul Khosla, Charity Morgan, Sijian Zhang, Charles Faselis, Wen-Chih Wu, Marc Blackman, Ross Fletcher, Gregg Fonarow, Prakash Deedwania, Javed Butler, Wilbert Aronow, Maciej Banach, John Parissis, Stefan Anker, Richard Allman, Ali Ahmed
Journal: Journal of the American College of Cardiology (2016)
Frequency of Extracranial Cerebrovascular Disease in Patients with Chronic Psychosis
Authors: Lester R. Bryant, Ben Eiseman, Frank C. Spencer, Arthur Lieber
Journal: New England Journal of Medicine (1965)

THE concept that significant Central-nervous-system dysfunction may result from occlusive disease of the extracranial cerebral arteries is now well established. The entire spectrum, ranging from mental depression and confusion1 to frank stroke,2 3 4 5 has been found due to cerebral arterial insufficiency. Hunt4 called attention to the role of occlusive lesions of the carotid arteries in producing strokes, and Fisher2 noted the episodic nature of cerebral symptoms in association with advanced atherosclerotic narrowing of the extracranial cerebral vessels. The latter author also found premonitory mental and emotional changes in some patients in whom the stroke syndrome subsequently developed.The frequency of atherosclerotic . . .
S45 Sleep Disordered Breathing (SDB) in Patients of Type 2 Diabetes Mellitus(DM) with and Without Retinopathy- A Hospital Based Study
Authors: S Mehta, D Chaudhry, SV Singh, A Atreja, V Sangwan
Journal: Thorax (2012)

<h3>Background</h3> Higher incidence of SDB has been reported from West in patients having sight threatening retinopathy with limited information from South Asia. <h3>Methods</h3> It was a prospective, observational study carried out on 80 patients of type 2 DM presented to Vitreo-retinal clinic. Patients with coronary artery disease, acute and chronic Heart Failure, concurrent hypothyroidism, known Obstructive sleep apnea (OSA) with DM and of any known respiratory disorder were excluded. On the basis of fundus and fluorescein angiography they were divided into two Groups, Group I without retinopathy (n=30) and Group II with retinopathy (n=50). Latter had 30 and 20 patients of Non Proliferative Diabetic retinopathy (NPDR) and Proliferative Diabetic retinopathy (PDR) respectively. All patients underwent whole night attended polysomnography in the hospital. <h3>Results</h3> The patients having diabetic retinopathy had higher age, BMI, waist circumference, Serum creatinine, HbA1c and Apnea Hypoapnea index (AHI) (p&lt;0.05). PDR sub-group had a higher waist and neck circumference however NPDR patients had a higher HbA1c (p&lt;0.05). OSA was observed in 66% and 40% of patients with &amp; without diabetic retinopathy (12/30 vs. 33/50) respectively. On subgroup analysis, 90% of patients having PDR had OSA as compared to 50% in NPDR group. Severity of OSA was proportional to the presence of retinopathy (AHI=24.35±27.72 vs. 13.09±20.3 in Gp II &amp; Gp.I respectively). It was nearly twice as severe in PDR Group than NPDR Group ((34.91±30.61 vs 17.3±23.94) with significantly higher desaturation (5.37±5.09% vs. 11.53±6.82%). On multivariate regression analysis only HbA1c levels correlated with presence of SDB in Diabetics. <h3>Conclusion</h3> In a selective hospital based population of type 2 DM, prevalence and severity of SDB correlated with severity of retinopathy. A larger longitudinal study is need of the hour to predict factors responsible for OSA and find correlation between SDB with diabetic retinopathy. <h3>Key words</h3> sleep disordered breathing, type 2 Diabetes Mellitus, NPDR, PDR, Apnea Hypoapnea Index.
Abstract IA18: Oncogene regulation of the autophagy machinery
Authors: Beth C. Levine
Journal: Cancer Research (2011)

Abstract It is well-established that many oncogenic growth signaling pathways negative regulate autophagy through a mechanism that has been presumed to be via activation of mTOR. However, it has been unknown whether oncogenes directly suppress the autophagy machinery and whether autophagy suppression contributes to oncogene-mediated tumorigenesis. We will discuss new findings indicating direct regulation of the Beclin 1 autophagy protein by the Akt oncoprotein and a role for Beclin 1 inactivation in Akt-driven tumorigenesis. The results presented will provide support for the concept that autophagy functions in tumor suppression and will demonstrate a specific biochemical mechanism by which autophagy is suppressed in human cancers with aberrant activation of the oncogenic Class I phosphatidylinositol 3-kinase/Akt signaling axis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr IA18.
Abstract 4999: Glutamate receptors in cancer: Stable expression of GluR6 induces growth arrest and senescence in hepatocellular carcinoma HCC 7703 cells
Authors: Gurpreet Kaur, Konstantinos G. Pilidis, Vikramjit K. Zhawar, Gursurinder P. Kaur, Raghbir S. Athwal
Journal: Cancer Research (2010)

Abstract Applying a functional strategy, we identified a gene, SEN6A, located at 6q21, which restores senescence in breast tumor cells. Human genome database search identified SEN6A as GluR6, a kainate type - ionotropic glutamate receptor gene. Kainate receptors constitute a family of ionotropic glutamate receptors that plays a role in the rapid synaptic transmission in the central nervous system. Glutamate receptors have been implicated in several pathophysiological conditions including Epilepsy, Schizophrenia and Parkinson's disease. We cloned the GluR6 gene by RT-PCR and investigated the structure, splicing pattern and its role in the cell senescence and cancer. We show that GluR6A, a splice variant is specifically expressed in brain, and four other variants; namely, GluR6B, GluR6C, GluR6D and GluR6E are expressed in other tissues and fibroblast cell lines. Genomic analysis and cloning of the sequence preceding the transcribed region led to the identification of two tissue specific promoters designated as neuronal promoter Pn and non-neuronal promoter Pnn. GluR6 is expressed in most tissues and its expression is elevated in late passage cells, relative to young human cells. The gene is either turned off or expressed at a reduced level in a large number of tumor cell lines. The chromosomal location of GluR6 at 6q21, a LOH hot spot in multiple cancers, points to its potential role in the etiology of cancer. The analysis for mutations in 22 cancer cell lines revealed a point mutation in exon 15 and deletion of exon 6 in two hepatoma cell lines. Open reading frame of GluR6 was cloned in a retroviral expression vector, in frame with EGFP tag, where EGFP is added after the signal peptide. In this vector GluR6-EGFP gene is expressed as a single transcript, from a CMV promoter, along with puromycin gene for selection. Ecotopic expression of GluR6 (variants A-E) induces growth arrest and senescence in hepatoma HCC7703 cells, and induce premature senescence in normal fibroblasts. Clones of GluR6 transfer cells display doubling time of 72-96 hours that gradually increases to 3-4 days ending in complete growth arrest and senescence. In contrast the transfer of empty vector or a construct carrying truncated GluR6 gene did not affect the growth of HCC7703 or normal cells. These result show that GluR6 is involved in the cascade of signaling circuits that govern cell growth and differentiation. Future studies are designed to investigate signaling pathways responsive to the expression of GluR6 gene. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 4999.