tbuckley/cabot-search huggingface dataset:
A8.10 Human memory t cells from the bone marrow are resting and maintain long-lasting memory
Authors: Anna Okhrimenko, Joachim R. Grün, Kerstin Westendorf, Zhuo Fang, Simon Reinke, Philipp von Roth, Georgi Wassilew, Anja A. Kühl, Robert Kudernatsch, Sonya Demski, Carmen Scheibenbogen, Koji Tokoyoda, Mairi A McGrath, Martin Raftery, Alessandro Serra, Hyun-Dong Chang, Andreas Radbruch, Jun Dong
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Memory T cells are essential components of immunological memory, but little is known about their maintenance. Recirculating memory T cells of blood and secondary lymphoid organs slowly decay in numbers. In mice, we have recently identified professional resting memory CD4<sup>+</sup> T cells located in the BM and stably maintained in dedicated survival niches. The cells are resting, despite expression of CD69. Here we analyse and compare paired human peripheral blood (PB) and BM samples for phenotype, specificity and cytokine profiles of memory CD4<sup>+</sup> and CD8<sup>+</sup> T cells. <h3>Material and Methods</h3> Mononuclear cells were isolated from paired PB and BM samples from individuals undergoing hip replacement surgery. Phenotypic analysis and cytokine profile of memory T-cells in response to CMV pp65, tetanus toxoid and measles were measured by flow cytometry. Proliferation and cell cycle status were analysed using Ki-67 and propidium iodide staining, respectively. Global transcription of cells was assessed by microarray analysis. <h3>Results</h3> Significantly higher numbers of memory T cells were found in BM than in PB. BM memory T cells displayed polyfunctionality, secreted a multitude of cytokines, and specificities for all recall antigens tested. They maintained long-lasting memory, even when it was not detectable in blood. CD69-expressing memory T cells were detected in BM but not in PB. Ki-67- and propidium iodide-positive cells were significantly lower in CD69<sup>+</sup> memory T cells from BM compared to PB. BM CD69<sup>+</sup> memory T cells showed a resting global gene expression profile. <h3>Conclusions</h3> BM is home to resting, professional memory CD4<sup>+</sup> and CD8<sup>+</sup>T cells, providing systemic, stable longterm memory.
AB1187 Autoantibodies recognizing carbamylated proteins (anti-carp) in sera of patients with JIA
Authors: P.C. Hissink Muller, J. Anink, J. Shi, N. Levarht, T.H. Reinards, M.H. Otten, M.J. van Tol, C. Jol-van der Zijde, C.F. Allaart, E.P. Hoppenreijs, Y. Koopman-Keemink, K. Dolman, J.M. van den Berg, M.A. van Rossum, L.W. van Suijlekom-Smit, M.W. Schilham, R. Ten Cate, R.E. Toes, L.A. Trouw
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anti-citrullinated protein antibodies (ACPA) have a low prevalence in Juvenile Idiopathic Arthritis (JIA). Autoantibodies recognizing carbamylated protein (anti-CarP) are a promising new serological marker for ACPA negative Rheumatoid Arthritis and are associated with a more severe clinical course (Shi et al, 2011). <h3>Objectives</h3> To determine the presence of anti-CarP antibodies in sera of JIA patients and to investigate their prognostic value. <h3>Methods</h3> Samples of 249 patients with all subgroups of JIA, taken at different time points in their disease course and 107 healthy partially age matched controls were analyzed for the presence of anti-CarP antibodies as well as ACPA (commercial CCP2 ELISA). Cut-off for positivity was determined in the sera of the healthy controls as the mean plus two times standard deviation. <h3>Results</h3> The serum samples came from patients with all different subtypes of JIA (median age 12,1 years, IQR 8,1-15,7 median disease duration 2,2 years IQR 0,7-6,4) including 19 polyarticular rheumatoid factor positive patients. IgG antibodies recognizing carbamylated antigens were present in sera of 12,9% (32/249) of all JIA patients vs 2,8% (3/107) in the controls (p=0,002). Anti-CarP antibodies were detected in 58% (11/19) of the rheumatoid factor positive polyarticular JIA patients (p&lt;0,001) vs 10% (9/90) in the rheumatoid factor negative polyarticular JIA patients. <h3>Conclusions</h3> Anti-CarP antibodies can be detected in sera of patients with JIA, mainly in the rheumatoid factor positive polyarticular subgroup, which is the JIA subtype that shows the most resemblance with RA in adults. Correlations between anti-CarP antibodies and disease characteristics are currently under investigation. <h3>References</h3> Shi J et al. Autoantibodies recognizing carbamylated protein are present in sera of patients with rheumatoid arthritis and predict joint damage. PNAS, October 2011;108(42):17372-7 <h3>Disclosure of Interest</h3> P. Hissink Muller Grant/Research support from: Pfizer and the Dutch League against Rheumatism, J. Anink: None Declared, J. Shi: None Declared, N. Levarht: None Declared, T. Reinards: None Declared, M. Otten: None Declared, M. van Tol: None Declared, C. Jol-van der Zijde: None Declared, C. Allaart: None Declared, E. Hoppenreijs: None Declared, Y. Koopman-Keemink: None Declared, K. Dolman: None Declared, J. van den Berg: None Declared, M. van Rossum: None Declared, L. van Suijlekom-Smit: None Declared, M. Schilham: None Declared, R. ten Cate: None Declared, R. Toes: None Declared, L. Trouw: None Declared
Challenges in endoscopy and histological diagnosis of celiac disease
Authors: K. Rostami, R. Kasturi, V. Villanacci, G. Bassotti, A. Zambelli
Journal: Endoscopy (2011)

Narrow-band imaging (NBI) is an interesting endoscopic imaging technique that helps in visualizing some mucosal changes consistent with celiac disease. The technique seems to be more effective than conventional light endoscopy and the paper of Singh et al. opens up a new prospect in the endoscopic aspects of celiac disease [1].
Percutaneous Catheter Drainage of Abdominal Abscesses
Authors: Stephen G. Gerzof, Alan H. Robbins, Willard C. Johnson, Desmond H. Birkett, Donald C. Nabseth
Journal: New England Journal of Medicine (1981)

We used computed tomography (CT) and ultrasonography for detection and localization of intra-abdominal abscesses. On the basis of these images, safe routes for diagnostic aspiration and percutaneous drainage were planned. Over these routes indwelling catheters were inserted to provide immediate decompression, evacuation, and continuous drainage until the abscess resolved. All patients received concomitant intravenous antibiotics. The treatment was used for 71 abscesses in 67 patients. Sixty-one abscesses (86 per cent) were satisfactorily drained. There were 11 complications (15 per cent). Six deaths were attributable to sepsis, three of which (4 per cent) were related to inadequate drainage. There was one recurrence (1 per cent) during a follow-up period ranging from one month to five years (mean, 22.3 months). The mean duration of treatment was 20.2 days (range, five to 120 days). We conclude that percutaneous drainage is an effective method for treatment of abdominal abscesses and is indicated when sectional imaging demonstrates an accessible unilocular lesion. (N Engl J Med. 1981; 305:653–7.)
Abstract SY12-02: Computational cancer genomics: Biological discovery and translation.
Authors: Nikolaus Schultz, Chris Sander
Journal: Cancer Research (2013)

Abstract The analysis of genes and cellular pathways that are altered in different cancers can lead to biological discoveries and potential patient-specific and subtype-specific therapeutic hypotheses. Several large-scale studies, including those from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), aim to survey the landscape of genomic and molecular profiles of thousands of tumor samples in tens of different tumor types from generous patients. We analyze these informative genetic and molecular profiles to better understand the processes of oncogenesis, vulnerabilities to therapeutic interventions and tumor-subtype specific differences. Hypotheses can then be tested in focussed cell line and mouse model experiments and, if validated, advanced to clinical trials. To assist the general community of cancer biologists, we make available a generally useful feature map of essential information in the Cancer Genome Atlas via the information service cbioportal.org. Analysis and information services reported are based on the work of Niki Schultz, Giovanni Ciriello, Nils Weinhold, William Lee, Jian Jiong Gao, Rileen Sinha, Anders Jacobsen, Erik Larsson, Arman Aksoy, Gideon Dresdner, Benjamin Gross, several clinical research collaborators and the TCGA network. Citation Format: Nikolaus Schultz, Chris Sander. Computational cancer genomics: Biological discovery and translation. [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 SY12-02. doi:10.1158/1538-7445.AM2013-SY12-02
Value of Thin-Layer Chromatography in Two Fatal Cases of Intoxication Due to Lidocaine and Mepivacaine
Authors: Irving Sunshine, Winston W. Fike
Journal: New England Journal of Medicine (1964)

AN adverse reaction to local anesthetics has long been recognized as a calculated risk in the use of these drugs.1 If such a reaction occurs characteristic clinical signs and symptoms signal the patient's deteriorating condition, but proper therapy, promptly instituted, usually ameliorates this condition. Although occasional deaths due to local anesthetics have been reported2 no such reports have heretofore been published on lidocaine or mepivacaine. Two fatal cases resulting from the use of these agents are the subject of this paper.Chemically and physically these two drugs are so similar that a new technic for their separation, thin-layer chromatography, was . . .
Abstract 623: CLU inhibition using OGX-011 is a new adjuvant therapeutic strategy for HSP90 inhibition in prostate cancer
Authors: Francois Lamoureux, Min-Jean Yin, Amina Zoubeidi, Martin E. Gleave
Journal: Cancer Research (2011)

Abstract Introduction and Objective: Prostate cancer (PCa) responds initially to anti-androgen therapies, however, progression to castration resistant disease (CRPC) frequently occurs. Several small molecule inhibitors of HSP90 show promise in CRPC and other cancers. However, most HSP90 inhibitors (17-AAG or PF-04928473 and its prodrug PF-04929113) trigger the elevation of HSPs (HSP90, 70, 27 and clusterin), which lead to tumor cell survival and treatment resistance. We hypothesized that targeting clusterin (CLU) using siRNA or the antisense drug, OGX-011, may enhance HSP90 inhibitors-induced cell death in PCa. Methods: Inducible and constitutive CLU and other HSP mRNA and protein levels were measured by real-time RT-PCR and immunoblot assays. The combination of OGX-011 with PF-04928473 or 17-AAG was evaluated in vitro on LNCaP and PC3 cells growth and apoptosis. The HSP90 inhibitor PF-04929113 was evaluated in combination with OGX-011 in vivo in athymic mice bearing castration resistant LNCaP xenografts, while the combination of OGX-011 with 17-AAG was evaluated in PC3 xenografts. Results: In prostate tumor cell lines, PF-04928473 and 17-AAG induced expression of HSPs in a dose and time dependent manner, and especially CLU at RNA and protein level, by increasing HSF-1 nuclear translocation and transcription activity. In vitro, OGX-011 synergistically enhanced the activity of HSP90 inhibitors on cell growth and apoptosis with increased sub-G1 fraction and PARP cleavage. These biologic events were accompanied by decreased expression of HSPs, Akt, AR and PSA, and HSF-1 transcriptional activity. In vivo, OGX-011, administered 3 times a week (IP, 15mg/kg), potentiated the effect of orally administered HSP90 inhibitors (PF-04929113: 25mg/kg; 17-AAG: 50mg/kg), significantly inhibiting tumor growth by 80% and prolonging survival in PC3 and castrate resistant LNCaP xenograft model compared to the HSP90 inhibitors alone. Conclusions: These results indicate that HSP90 inhibitor-mediated induction of CLU expression can be attenuated by OGX-011, with synergistic effects on delaying progression of CRPC. This work was supported by the Canadian Institutes of Health Research fellowship and Association pour la Recherche sur le Cancer, France. 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 623. doi:10.1158/1538-7445.AM2011-623
UTILIDAD DE LA VIDEOCAPSULA ENDOSCOPICA (VCE) EN HEMORRAGIA DIGESTIVA DE ORIGEN OSCURO (HDOO)
Authors: M Navajas-Laboa, A Orive-Calzada, M Durán-Rigueira, S Torres-Burgos, M Aguirresarobe, M López-López, JA Arévalo-Serna, L Bridet, A Bernal-Martínez, JL Cabriada-Nuño
Journal: Endoscopy (2011)

Introducción: El 5% de los pacientes con hemorragia digestiva presenta una HDOO, que se define como aquella hemorragia gastrointestinal de etiología desconocida que persiste o recidiva tras una gastroscopia y colonoscopia inicial negativa. Hasta un 75% de las HDOO tienen su origen en el Intestino Delgado. Las HDOO se clasifican en: -HDOO Oculta (HDOOO): se presenta como SOH positivo y/o anemia ferropénica sin pérdida de sangre visible o evidente. -HDOO Manifiesta (HDOOM): Hematemesis, melena o hematoquecia. La VCE se recomienda como la primera prueba a realizar ante una HDOO.
Aortic Embolism Complicating Mitral Stenosis
Authors: William W. L. Glenn, Thomas M. McNeill
Journal: New England Journal of Medicine (1957)

AMONG the most serious complications of mitral stenosis is the formation of a thrombus in the left atrium and the discharge of the thrombus or a part of it as an embolus into the arterial circulation. When, in the presence of mitral stenosis, an embolus lodges at the aortic bifurcation the state of compensation of the heart is of major importance in the survival of the patient after embolectomy. When there is severe cardiac decompensation, the risk of operation for removal of the aortic embolus may be so great as to contraindicate operation. At the same time, the failure to . . .
Tc-99m MAG3 Scintigraphy in a Newborn With Acute Renal Vein Thrombosis
Authors: VICENTE IZQUIERDO, DIEGO GÓMEZ, ELENA MACÍAS, JOSEFA GELLIDA, ROSA SIURANA, JOSE MORALEJO, CARMEN M. de VÍRGALA
Journal: Clinical Nuclear Medicine (1999)

After removal of central venous and umbilical catheters from a premature infant, the patient went into sudden peripheral vascular collapse with hematuria and hypertension. The hematuria appeared to be associated with a right renal vein thrombosis secondary to the venous catheter, and the acute nephropathy was suggested by ultrasound. This was confirmed with Tc-99m DMSA and Tc-99m MAG3 imaging.
Liver Disease in Alpha<sub>1</sub>-Antitrypsin Deficiency Detected by Screening of 200,000 Infants
Authors: Tomas Sveger
Journal: New England Journal of Medicine (1976)

We prosepctively studied 200,000 newborns to determine the frequency and clinical characteristics of alpha1-antitrypsin deficiency. One hundred and twenty Pi Z, 48 Pi SZ, two PI Z-and one Pi S-infants were identified and followed to the age of six months. Fourteen of 120 Pi Z infants had prolonged obstructive jaundice, nine with severe clinical and laboratory evidence of liver disease. Five had only laboratory evidence of liver disease. Eight other Pi Z infants had minimal abnormalities in serum bilirubin and hepatic enzyme activity and variable hepatosplenomegaly. All 22 Pi Z infants with hepatic abnormalities, two thirds of whom were made, appeared healthy at six months of age. Ninety-eight Pi Z infants did not have clinical liver disease, but liver-function tests gave abnormal results in 44 of 84 at three months, and in 36 of 60 at six months of age. The number of small-for-gestational-age infants was greater (P less than 0.001) among those with clinical liver disease. None of the 48 Pi SZ infants had clinical liver disease, but 10 of 42 at three months and one of 22 at six months of age had abnormal liver function. The Pi Z and Pi SZ phenotypes are associated with covert or readily apparent hepatic dysfunction in the first three months of life.
P239 A role for polycystins in airway mucociliary clearance?
Authors: L Adams, M Loebinger, A Shoemark
Journal: Thorax (2013)

<h3></h3> Polycystins 1 and 2 are the gene products of the mutated genes PKD1 and PKD2 in autosomal dominant polycystic kidney disease (ADPKD). They are localised to primary cilia in the kidney and thought to detect fluid flow. Recently patients with ADPKD have been shown to have an increased incidence of radiological findings of bronchiectasis, an abnormal dilatation of the bronchioles involving impaired mucociliary clearance (Driscoll <i>et al</i> 2009). We hypothesise that proteins from the polycystin pathway are present in respiratory epithelium and that this pathway is defective in bronchiectasis. We demonstrate using immunoflourescent antibodies that the extracellular portion of polycystin 1 and the n terminal tail of polycystin 2 consistently localise to cilia of nasal epithelial cells from healthy individuals and that blocking polycystin 1 with antibodies can alter ciliary beat. Contrary to our hypothesis there were no differences in the distribution of these proteins in a group of patients with bronchiectasis (n = 13) In conclusion we have shown that polycystins 1 and 2 are present in the motile cilia of the airways and may be involved in ciliary beat frequency regulation. We did not find any evidence of disruption of the polycystin proteins in a small population of patients with bronchiectasis.
Case 35-1981
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Allan H. Ropper, Elizabeth C. Dooling
Journal: New England Journal of Medicine (1981)

Presentation of CaseA 16-year-old boy was admitted to the hospital because of confusion.He was well until the early hours of the day of entry, when he was observed in a parked car having a seizure. When the police arrived he was wandering on a nearby street. He was taken to another hospital, where he became combative, with occasional choreoathetoid movements. Naloxone hydrochloride, physostigmine, thiamine hydrochloride, and glucose were administered by vein, without response, and he was transferred to this hospital. On arrival in the Emergency Ward he responded only to painful stimuli. Decerebrate posturing developed, followed by a . . .
Case 12-2015
Authors: Ting-Yi Lin, David H. Ebb, Paul A. Boepple, Elizabeth A. Thiele, Sandra P. Rincon, Daniel A. Mordes
Journal: New England Journal of Medicine (2015)

A newborn boy was admitted to the hospital because of respiratory distress and hypotension. At delivery, meconium was suctioned from the airway. Respiration and blood pressure improved after intervention, but lethargy and myoclonus developed.
AB1242 Role of sonography in the painful shoulder: Analysis of a rheumatological unit cohort of patients
Authors: A. Delle Sedie, L. Carli, E. Sardano, E. Cioffi, S. Bombardieri, L. Riente
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ultrasound (US) emerged as a key diagnostic tool for rheumatologists in the last two decades. It improves clinical diagnosis as well as follow-up of arthritis patients. It is well known the utility of US in the diagnostic assessment of shoulder pain. <h3>Objectives</h3> To evaluate the shoulder findings by musculoskeletal US in the assessment of patients presenting with shoulder pain. <h3>Methods</h3> We examined 209 patients (M:F=60:149), mean age 60±14 years (range 25-82 years), 55.5% of them affected by rheumatologic disorders (24 with rheumatoid arthritis, 12 with polimyalgia rheumatica, 7 with psoriatic arthritis, 4 with undifferentiated spondyloarthritis, 11 with fibromyalgia, 5 with systemic sclerosis, 5 with systemic lupus erythematosus). The other 48 patients complained shoulder pain with no established diagnosis. Ninety per cent of the patients had yet been treated with non steroidal antinflammatory drugs and/or analgesics without efficacy while 40% experienced partial remission by rehabilitative therapy. US examinations were performed with a Logiq9 machine (General Electrics Medical Systems, Milwaukee, WI) using a linear probe at a frequency of 10 MHz. We examined: tendon of the long head of biceps (LHB) muscle, supraspinatus, subscapularis and infraspinatus tendons, subacromiondeltoid and subscapolaris bursae, gleno-humeral and acromion-clavicular (AC) joints. We studied homogeneity, thickness and continuity of fibers of tendons, as well as the presence of effusion into the bursae and the joints. Finally we focused the attention on the cortical bone appearance. <h3>Results</h3> Ninety-four patients (45%) showed tears of rotator cuff tendons usually localized in the supraspinatus tendon (69% of them were ≥65 years old), while long biceps tendon tear was present only in 14 cases (associated to supraspinatus tear). Effusion in the AC joint was observed in 29 patients (in 22 of them it was associated with rotator cuff tendon tear), while tenosynovitis of LHB tendon was shown in 133 patients (in 53 of them it was the only pathologic finding). Hyperechoic spots or linear aggregates were imaged in 56.4% of the patients. Tendinosis was more evident in the supraspinatus tendon (112 cases) while in other tendons only in 14-19% of subjects. <h3>Conclusions</h3> US examination showed high prevalence of abnormal findings in painful shoulders, most of all in the ≥65 years old patients. US provide great help for the clinician for the screening of the painful shoulder, suggesting the need of an MRI in some cases, guiding invasive maneuvers (i.e. arthrocentesis or intrarticular injection) or, finally, in the follow-up. <h3>Disclosure of Interest</h3> None Declared
Abstract 1635: MiR-21/Smad 7 signaling determines TGF-β1-induced cancer associated fibroblast (CAF) formation.
Authors: Qiong Li, Yongbin Wang, Wujun Xiong, Jun Mi
Journal: Cancer Research (2013)

Abstract Tumor-secreted growth factors such as TGF-β1 transform adjacent normal fibroblasts into cancer-associated fibroblasts (CAF) which is a major source of CAF. TGF-β1 has canonical and noncanonical Smad pathway, which pathway mediates TGF-β1 signaling during the CAF formation and how TGF-β1 activates regulatory Smad proteins is not entirely understood. To investigate whether the miR-21/Smad 7 signaling determines TGF-β1-induced CAF formation, the in vitro TGF-β1-induced CAF model was successfully established and the function of fibroblasts knocked down or overexpressed miR-21 or Smad 7 were finally identified in the xenografted mice, with or without TGF-β1 stimulation. Our data showed that the mature miR-21 is increased in fibroblast after TGF-β1 treatment, and miR-21 regulates Smad 7 protein level through the translation inhibition instead of the mRNA decay. Moreover, our data showed Smad 3 was phosphorylated 2 hours early than Smad 2 after TGF-β1 stimulation and Smad 7 knockdown enhanced Smad 2 and 3 phosphorylation; both of their phosphorylations were abolished by the TGFR kinase inhibitor. Most important, both of the over-expression of miR-21 or the knockdown of Smad 7 promoted CAF formation, even without TGF-β1 stimulation while the miR-21 knockdown or the Smad 7 overexpression as well as Smad 2, 3 and Smad 4 knock down blocked the TGF-β1-induced CAF formation. These observations suggest that TGF-β1 induces CAF formation through the canonical pathway, miR-21/Smad 7 is a critical mediator. Citation Format: Qiong Li, Yongbin Wang, Wujun Xiong, Jun Mi. MiR-21/Smad 7 signaling determines TGF-β1-induced cancer associated fibroblast (CAF) formation. [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 1635. doi:10.1158/1538-7445.AM2013-1635 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.