tbuckley/cabot-search huggingface dataset:
Brain Dopamine–Serotonin Vesicular Transport Disease and Its Treatment
Authors: Jennifer J. Rilstone, Reem A. Alkhater, Berge A. Minassian
Journal: New England Journal of Medicine (2013)

We describe a disease encompassing infantile-onset movement disorder (including severe parkinsonism and nonambulation), mood disturbance, autonomic instability, and developmental delay, and we describe evidence supporting its causation by a mutation in SLC18A2 (which encodes vesicular monoamine transporter 2 [VMAT2]). VMAT2 translocates dopamine and serotonin into synaptic vesicles and is essential for motor control, stable mood, and autonomic function. Treatment with levodopa was associated with worsening, whereas treatment with direct dopamine agonists was followed by immediate ambulation, near-complete correction of the movement disorder, and resumption of development.
Case 40-2014
Authors: Rajesh T. Gandhi, Tarik K. Alkasab, Valentina Nardi, John A. Branda
Journal: New England Journal of Medicine (2014)

A 57-year-old man with HIV infection was seen in the emergency department because of pain in the left inguinal region. CT of the abdomen and pelvis revealed enlarged lymph nodes with areas of necrosis. A diagnostic test was performed.
Lupus Cystitis on Ga-67 Scans
Authors: W Y Lin, J L Lan, S J Wang
Journal: Clinical Nuclear Medicine (2000)

A 46-year-old woman with systemic lupus erythematosus had hematuria, fever, and proteinuria. She was transferred to the nuclear medicine department for evaluation of the disease activity of lupus nephritis. A Ga-67 scan showed increased radioactivity in both kidneys. Active nephritis was suggested. Furthermore, increased Ga-67 uptake in the wall of the urinary bladder was also noted. Lupus cystitis was indicated. A bladder biopsy confirmed the diagnosis.
Left Ventricular Function and Rapid Release of Creatine Kinase MB in Acute Myocardial Infarction
Authors: Lawrence Ong, Peter Reiser, James Coromilas, Lawrence Scherr, John Morrison
Journal: New England Journal of Medicine (1983)

Intracoronary thrombolysis during acute myocardial infarction in human beings is associated with rapid release of creatine kinase and improvement of the cardiac ejection fraction. To examine the phenomenon of spontaneous coronary-artery recanalization, we studied the release of creatine kinase MB and sequential radionuclide ventriculograms in 52 patients with transmural myocardial infarction. Patients were divided into two groups according to whether the release of creatine kinase MB (time from base-line to peak serum level) was rapid (n = 24) or slow (n = 28). Patients with slow release had no significant change in global or regional ejection fraction from the time of admission to discharge. However, global ejection fraction in patients with rapid release improved from 0.38 +/- 0.09 (mean +/- S.D.) to 0.48 +/- 0.08 (P less than 0.001). The regional ejection fraction of Q-wave regions also improved, from 0.33 +/- 0.11 to 0.43 +/- 0.13 (P less than 0.001). A negative correlation (r = -0.52, P less than 0.001) existed between time to peak enzyme level and degree of improvement in ejection fraction. With increasing left ventricular damage, patients with rapid release had greater increments in creatine kinase MB than comparable patients with slow release (P = 0.03), suggesting enzyme washout. These data are consistent with the idea that spontaneous reperfusion, leading to altered enzyme release and improvement in ventricular function, is not uncommon after acute myocardial infarction.
Abstract B26: The role of G alpha12 and thromboxane receptor beta interaction in bladder cancer progression
Authors: Julie Ann Woolworth, Mohamed Desouki, Perry Halushka, Dennis Watson, Michael T. Smith, Omar Moussa
Journal: Clinical Cancer Research (2010)

Abstract In the United States, it is predicted that there will be over 70,000 new cases of bladder cancer this year. Bladder cancer is the fourth most common cancer in men and eighth in women. Our lab has previously identified Thromboxane receptor-β (TP-β) as potentially playing a role in bladder cancer progression. TP-β is a G-protein coupled receptor that is over-expressed in bladder cancer tumors and high levels of TP-β in bladder cancer patients correlate with decreased survival. G-proteins are involved in second messenger cascades that influence a variety of cellular functions, including transcription and motility. In multiple cellular systems TP-β has been found to interact with multiple G proteins such as Gαi, Gαs, Gα12, and Gα13. We found high levels of mRNA and protein expression of the G-protein, Gα12, in bladder cancer cell lines. We also observe high levels of Gα12 expression in human bladder cancer tissues. Studies using a constitutively active Gα12 mutant, suggest that signaling through Gα12 can contribute to oncogenic transformation. In this study we aim to elucidate the TP-β associated Gα12 dependent pathways that contribute to bladder cancer progression. We found that TP agonist U46619 increases cell migration and that treatment with TP antagonist blocks this increase in cell migration induced by U46619. TP agonist stimulation also increases the phosphorylation of extracellular regulated kinase (ERK) and U46619-induced phosphorylation of ERK is blocked with TP agonist treatment. Using a shRNA to knockdown Gα12 we observe a reduction in U46619-induced cell migration and ERK phosphorylation. Together our results suggest that TP-β mediated cell migration and the MAPK signaling pathway is in part regulated through Gα12. This work could have clinical implications by targeting the TP-β and Gα12 interaction as a potential therapeutic approach for bladder cancer treatment. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B26
FRI0138 Characterization of non-hodgkin lymphomas in rheumatic diseases
Authors: V. Vasilyev, V. Gorodetskiy, O. Logvinenko, S. Sedishev, E. Rodionova, T. Safonova, E. Nasonov, N. Probatova, N. Kokosadze, A. Kovrigina, A. Pavlovskaya
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Non-Hodgkin lymphomas (NHL) are 3 to 45 times more common in rheumatic diseases (RD) than in the general population. The spectrum of NHL varies in different studies. <h3>Objectives</h3> To describe the most common types of NHL diagnosed in rheumatic patients from 2008 to 2010 in the Institute of Rheumatology of RAMS, Moscow. <h3>Methods</h3> 185 patients (female-148, male-27) aged 19 to 80 years old (median-52 years old) with various RD and predictors of NHL development (massive enlargement of lacrimal and salivary glands, cytopenia, lymphadenopathy, splenomegaly, monoclonalsecretionIg) were conducted an oncohematological survey, including incisional biopsies with subsequent immunomorphological study, trephine biopsies and myelograms, T-and B-cell clonality determination by PCR in peripheral blood and tissue samples. <h3>Results</h3> One hundred and ten (65.5%) patients (primary Sjögren's syndrome (pSS) - 58, rheumatoid arthritis (RA)–25, systemic scleroderma (SSD)-4 and chronic hepatobiliary diseases (CHD)-6) were diagnosed with NHL. The diagnosis of RD was withdrawn with subsequent identification of primary NHL in 8 cases, myeloproliferative diseases in 5 cases and primary AL-amyloidosis in 4 patients. B-cell NHL were found in 97 (88%) and T-cell in 13 (12%) patients respectively. Immunoglobulin-secreting variant of lymphoma was observed in 30 (29.7%) patients with NHL. In RA B-cell (48%) and T-cell (52%) lymphomas were represented in equal proportions. Marginal zone lymphoma (MZL) was most frequently detected in pSS, SSD and CHD, whereas T-cell leukemia of large granular lymphocytes was more often diagnosed in RA (n=9). Plasma cell dyscrasia (PD) ranked second more frequent in pSS (n=5) and RA (n=5). T-cell splenic lymphoma (RA - 4), chronic lymphocytic leukemia (pSS - 1, RA - 2) and diffuse large B-cell lymphoma (RA-1, pSS-2) were diagnosed less frequently. Seventeen (76.5%) of the 22 examined patients with RA, SSD and CHD had associated Sjögren's syndrome. Three patients simultaneously developed two types of NHL. <h3>Conclusions</h3> A prospective study has shown that low-grade MZL, PD, T-cell leukemia of large granular lymphocytes and γδ-T-cell splenic lymphoma are the most common in RD. Primary NHL, PD, AL-amyloidosis and myeloproliferative disorders often have clinical features similar to rheumatic diseases. <h3>Disclosure of Interest</h3> None Declared
SAT0310 Use of Low Dose Aspirin is Associated with Reduced Medial Tibial Cartilage Loss in Symptomatic Osteoarthritis: Data from a Cohort Study
Authors: A. Wluka, C. Ding, Y. Wang, G. Jones, F. M. Cicuttini
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Inflammation and vascular disease have recently been shown to play a role in the pathogenesis of osteoarthritis (OA). Low dose aspirin is commonly used in the prevention of cardiovascular disease. Its effects have been attributed to a variety of actions, including anti-inflammatory effects and effects on platelet function (both anti-thrombotic and anti-inflammatory) and lipids. However whether it affects human joints has not been studied. <h3>Objectives</h3> The aim of this study was to examine whether the use of low dose aspirin affects change in knee cartilage volume over 2 years. <h3>Methods</h3> 117 people with symptomatic knee OA underwent magnetic resonance imasging of the knee at baseline and 2 years later. Medial and lateral tibial cartilage volumes were measured using validated methods. Annual absolute change and annual percentage change in cartilage volume were calculated. Information about regular low dose aspirin use was collected at baseline, 6, 12 and 24 months. Participants who reported taking regular low dose aspirin (≤ 150 mg per day) at more than 1 time point were defined as being aspirin users. <h3>Results</h3> Twenty six participants reported taking aspirin at more than one visit, with 91 not taking aspirin. At baseline, the only significant difference between the 2 groups was that those taking aspirin were older than those who did not (p = 0.03). In those taking aspirin, annual change in medial tibial cartilage volume and annual percentage change in cartilage volume was approximately half that seen in those not taking aspirin (-50 vs. -102 mm<sup>3</sup> and -2.5% vs. -5.5%, respectively, P=0.04 for both). These differences became more significant after adjusting for age, gender, body mass index, initial cartilage volume and severity of radiographic change in the medial compartment. The annual change in medial tibial cartilage volume was -40 mm<sup>3</sup> (95% confidence interval (CI) -83, 1.3) in aspirin users vs. -105 mm<sup>3</sup> (95% CI -127, -82) in non-aspirin users (P = 0.009 for difference). The annual percentage change in medial tibial cartilage volume was -2.0% (95% CI -4.6, 0.53) in aspirin users vs. -5.6% (95% CI -6.9, -4.0) in non-aspirin users (P=0.02 for difference). There were no significant differences observed in change in lateral tibial cartilage volume. <h3>Conclusions</h3> This study showed that in people with knee OA, the use of low dose aspirin was associated with reduced medial tibial cartilage loss over 2 years. This requires confirmation in a randomised controlled trial. If this hypothesis were proven, aspirin may provide a cost effective disease modifying therapy for OA as it is a cheap medication that is already in common use and known to be well tolerated. <h3>Disclosure of Interest</h3> None Declared
Jejunal ectopic pancreas: a rare cause of gastrointestinal bleeding diagnosed using balloon enteroscopy
Authors: Teresa Pinto-Pais, Rolando Pinho, Adélia Rodrigues, Germano Boas, Carlos Fernandes, Iolanda Ribeiro, Olinda Lima, Alexandre Costa, João Carvalho
Journal: Endoscopy (2014)

A 42-year-old man with arterial hypertension and human immunodeficiency virus (HIV) infection was admitted for investigation of melena. Blood tests revealed iron deficiency anemia (hemoglobin concentration was 4.9 g/dL). On further questioning, the patient acknowledged having experienced several months of intermittent melena and recurrent episodes of abdominal pain. He denied weight loss or other gastrointestinal symptoms. Esophagogastroduodenoscopy and colonoscopy failed to identify a source of bleeding. To complete the evaluation, video capsule endoscopy was performed, which disclosed a subepithelial tumor located in the jejunum ([Fig. 1]), without other relevant findings in the small bowel. Subsequent single-balloon enteroscopy (SIF-Q180; Olympus Medical Systems, Tokyo, Japan) was carried out through the oral insertion route. A 20-mm caterpillar-like subepithelial tumor was observed within the topography of the lesion previously described ([Video 1]), with a smooth surface and focal erythema in the mucosa ([Fig. 2]). Endoscopic tattooing was performed and the patient was referred for surgical resection. Pathologic examination revealed pancreatic acinar cells, prominent secretory ducts, and islet cells in the jejunal submucosa ([Fig. 3]), consistent with ectopic pancreas (type I, Heinrich's classification). At 6-month follow-up, the patient remains asymptomatic.
SAT0320 Return to Work After Total Knee and Hip Arthroplasty: a Systematic Review
Authors: C. Tilbury, W. Schaasberg, J. W. Plevier, M. Fiocco, T. P. Vliet-Vlieland, R. G. Nelissen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The number of people undergoing Total Knee Arthroplasty (TKA) and Total Hip Arthroplasty (THA) surgery is rising, with a substantial proportion of patients being of working age. <h3>Objectives</h3> To describe the duration of return to work in patients undergoing TKA or THA and to determine which factors are associated with returning to work. <h3>Methods</h3> A systematic review was performed using a search strategy in various databases until April 2012. All clinical studies concerning patients undergoing TKA and/or THA providing quantitative information on work status before and after surgery were eligible for inclusion. Extracted data included study characteristics, patient characteristics, work status prior to surgery and after surgery and determinants of return to work. Selection of papers and data extraction were done by two investigators independently. <h3>Results</h3> The literature search yielded 514 titles and abstracts, with finally 18 studies, published between 1986 and 2011 being selected (4 on TKA, 13 on THA and 1 on both TKA and THA). These studies included 649 patients with TKA and 3633 with THA. Seven studies had a prospective cohort design and 11 a retrospective cohort design. There was a large variety concerning the definition of work status before and after surgery. In the studies describing return to work, the proportions of patients returning to work ranged between 71% and 83% at 3 to 6 months after TKA (n=2 studies) and between 25% and 95% at 1 to 12 months after THA (n= 6 studies). The duration of return to work in patients who were working pre-operatively varied from 8.0 to 12.0 weeks after TKA (n=4 studies) and from 1.1-10.5 weeks after THA (n=6 studies). Studies reporting on the determinants of (a faster) return to work after surgery varied largely with respect to their methodology. For TKA determinants were: not receiving a worker's compensation, having a sense of urgency and positive motivation to return to work, working in a handicap accessible workplace, being female, being self-employed, and having better physical and mental functioning scores (n=1 study). In THA the following factors were associated with (faster) return to work: working pre-operatively, a short duration of sick leave pre-operatively, younger age, doing mental work, having a higher educational level and being male (n=10 studies). <h3>Conclusions</h3> This systematic review of the literature shows that the majority of patients who are employed before TKA and THA return to work postoperatively. The rate and speed of return to work appear to be more favorable in THA than in TKA, however comparisons are hampered by large variations in patient selection and measurement methods. Standardization of the selection op patients and measurement of work status in patients undergoing total hip and knee surgery is needed. <h3>Disclosure of Interest</h3> None Declared
P375 SORTILIN DEFICIENCY ABOLISHES DUCTULAR REACTION AND REDUCES HEPATOCYTE APOPTOSIS AND LIVER FIBROSIS IN BILE DUCT LIGATION-INDUCED CHOLESTASIS
Authors: I. Zvibel, E. Hubel, J. Dranoff, W.J. Park, E. Lavoie, N. Erez, S. Fishman, R. Bruck
Journal: Journal of Hepatology (2014)
Predictive coding? Yes, but from what source?
Authors: Gregory Hickok
Journal: Behavioral and Brain Sciences (2013)

Abstract There is little doubt that predictive coding is an important mechanism in language processing–indeed, in information processing generally. However, it is less clear whether the action system is the source of such predictions during perception. Here I summarize the computational problem with motor prediction for perceptual processes and argue instead for a dual-stream model of predictive coding.
Massive Splenomegaly in Hairy-Cell Leukemia
Authors: Joanne Monterroso, Sreenivasa Chandana
Journal: New England Journal of Medicine (2012)

A 63-year-old man presented with a 6-month history of fatigue, weight loss, and gingival bleeding. Physical examination suggested the presence of a massively enlarged spleen, a finding confirmed on a reconstructed coronal CT image of the abdomen.
Defective Glucose Transport across the Blood-Brain Barrier as a Cause of Persistent Hypoglycorrhachia, Seizures, and Developmental Delay
Authors: Darryl C. De Vivo, Rosario R. Trifiletti, Ronald I. Jacobson, Gabriel M. Ronen, Ramin A. Behmand, Sami I. Harik
Journal: New England Journal of Medicine (1991)

GLUCOSE (D-glucose) is an essential fuel for the brain and many other tissues. Five glucose-transporter proteins facilitate the diffusion of glucose across lipophilic plasma membranes.1 2 3 This pr...
Abstract 642: Novel EGFR inhibitory antibodies directed against EGFR mutants with potentially reduced toxicity
Authors: Fang Wang, Donna McIntosh, Steve Bottega, Yinghui Zhou, Christina Fleet, Jinwei Jiang, Tin Chen, Solly Weiler, William Winston, Joerg Heyer, Steven Clark, Jeno Gyuris, Sylvie Vincent
Journal: Cancer Research (2011)

Abstract Non-small cell lung cancers (NSCLC) driven by ligand-independent activating mutations in epidermal growth factor receptor (EGFR) often respond to treatment with EGFR tyrosine kinase inhibitors (TKIs). About half of acquired resistance to EGFR-TKI therapy results from a secondary point mutation in the EGFR tyrosine kinase domain at amino acid position 790 (T790M). T790M mutants also display reduced sensitivity to Cetuximab treatment. We have investigated the molecular mechanism responsible for the reduced Cetuximab sensitivity and found that T790M mutant receptors primarily exist and signal as monomers. We have exploited this characteristic of the T790M mutant to isolate novel EGFR inhibitory antibodies with activities against all EGFR variants. In addition, as opposed to other EGFR inhibitory antibodies, these novel antibodies have reduced ligand binding inhibitory activity and minimal inhibitory effect on EGF induced human primary keratinocyte proliferation, suggesting a potentially reduced skin toxicity profile. The broad activity profile, combined with potentially reduced skin toxicity, suggests that these antibodies will have great potential for combinability with other therapeutic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 642. doi:10.1158/1538-7445.AM2011-642
813 PRIMING BY PROINFLAMMATORY CYTOKINES IS REQUIRED FOR TOLL-LIKE RECEPTORS ON HEPATIC ENDOTHELIUM TO RECRUIT MONOCYTES UNDER CONDITIONS OF FLOW
Authors: R. Sutaria, S.M. Curbishley, C.J. Weston, S.C. Afford, D.H. Adams, K.-K. Li
Journal: Journal of Hepatology (2012)
Through-the-scope transpyloric stent placement improves symptoms and gastric emptying in patients with gastroparesis
Authors: J. Clarke, R. Sharaiha, A. Kord Valeshabad, L. Lee, A. Kalloo, M. Khashab
Journal: Endoscopy (2013)

A 23-year-old woman was evaluated in clinic for diabetic gastroparesis. At the time of our evaluation, she was symptomatic despite a regimen consisting of domperidone, esomeprazole, ondansetron, duloxetine, and promethazine. Previous attempts using erythromycin and metoclopramide were both unsuccessful and limited by side effects. She continued to undergo frequent hospitalization, with four admissions to our facility plus numerous admissions to her local hospital. A 4-hour solid state gastric emptying scintigraphy study revealed only 47 % emptying at 4 hours. Gastric stimulation was declined by her insurance company and she therefore proceeded with transpyloric stent placement ([Fig. 1 a – c]).
Calcification of the Left Atrium
Authors: James J. Leonard, Sol Katz, Donald Nelson
Journal: New England Journal of Medicine (1957)

CALCIFICATION of the left atrium has been identified in two anatomic locations. The more common location is a shell-like calcification in the subendocardial layer of this chamber. Such deposition of calcium may be patchy in distribution throughout the atrial wall or may diffusely envelop the entire atrial endothelium.1 2 3 4 5 6 7 8 9 10 11 12 13 Less commonly the calcification actually lies in the bed of an organized thrombus that is densely adherent to the atrial endothelium.10 , 14 , 15 It is the small thrombi in the atrial appendage that most frequently calcify.10 Large thrombi rarely calcify. If they do, since they usually represent a many-layered clot, the calcification within them . . .
EP-03 * MOLECULAR CLASSIFICATION OF EPENDYMAL TUMORS ACROSS ALL CNS COMPARTMENTS, HISTOPATHOLOGICAL GRADES AND AGE GROUPS
Authors: K. W. Pajtler, H. Witt, M. Sill, D. Jones, V. Hovestadt, P. Johann, J. Reimand, P. Lichter, M. D. Taylor, R. Gilbertson, D. W. Ellison, K. Aldape, A. Korshunov, S. M. Pfister, M. Kool
Journal: Neuro-Oncology (2015)

Ependymal tumors across age groups are currently classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patients' outcome. DNA methylation patterns in tumors have been shown to represent a very stable molecular memory of the respective cell of origin throughout disease course, making them particularly suitable for tumor classification purposes. To attempt a uniform molecular classification for ependymal tumors across all age groups, histopathological grades and all anatomical CNS compartments – spine (SP), posterior fossa (PF), supratentorial region (ST) - we generated genome-wide DNA methylation profiles for 500 ependymal tumors using the Illumina 450k methylation array. Unsupervised hierarchical clustering of the DNA methylation data identified nine distinct molecular subgroups of ependymal tumors, three within each CNS compartment. One of the subgroups within each compartment was enriched with grade I subependymomas (SE) which were labeled as SP-SE, PF-SE and ST-SE. Within the spinal compartment the other molecular subgroups showed a relatively good concordance with the histopathological subtypes myxopapillary ependymoma (SP-MPE) and ependymoma (SP-EPN). The remaining molecular subgroups within the posterior fossa were previously described as posterior fossa Group A and B ependymomas and are now labeled as PF-EPN-A and PF-EPN-B. Two supratentorial subgroups are characterized by prototypic fusion genes involving RELA(ST-EPN-RELA) and YAP1 (ST-EPN-YAP1), respectively. Notably, the vast majority of high-risk patients (mostly children), for whom novel therapeutic concepts are desperately needed, were restricted to just two of the nine molecular subgroups identified, namely PF-EPN-A and ST-EPN-RELA. Regarding clinical associations, the molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next WHO classification of CNS tumors.