tbuckley/cabot-search huggingface dataset:
Treatment of High-Risk Acute Leukemia with T-Cell–Depleted Stem Cells from Related Donors with One Fully Mismatched HLA Haplotype
Authors: Franco Aversa, Antonio Tabilio, Andrea Velardi, Isabel Cunningham, Adelmo Terenzi, Franca Falzetti, Loredana Ruggeri, Giuliana Barbabietola, Cynthia Aristei, Paolo Latini, Yair Reisner, Massimo F. Martelli, Rita Felicini, Flavio Falcinelli, Alessandra Carotti, Katia Perruccio, Stelvio Ballanti, Antonella Santucci, Cesare Gambelunghe
Journal: New England Journal of Medicine (1998)

In this study we tried to achieve successful transplantation in patients with acute leukemia with the use of hematopoietic stem cells from donors who shared only one HLA haplotype with the recipient (a “full-haplotype mismatch”). To prevent graft failure, large doses of T-cell–depleted hematopoietic stem cells were transplanted after a conditioning regimen of enhanced myeloablation and immunosuppression was administered to the recipient.
PWE-288 Spontaneous bacterial peritonitis: prevalence on admission to a tertiary centre and subsequent outcome
Authors: T Bugeja, W T Gelson, W J H Griffiths
Journal: Gut (2012)

<h3>Introduction</h3> Spontaneous bacterial peritonitis (SBP) is a sinister complication of cirrhosis associated with poor survival (approximately 38% at 1 year<sup>1</sup>). However, a diagnosis of SBP does not represent, in its own right, an indication for liver transplantation in the UK under current listing criteria. <h3>Methods</h3> We sought to investigate the prevalence and subsequent mortality in patients with an admission diagnosis of SBP. We retrospectively identified 366 consecutive cases admitted with ascites to our liver unit during the calendar year 2009. Of these 271 (74%) patients underwent diagnostic paracentesis at time of admission and were included for further analysis. <h3>Results</h3> Of the 271 cases, 26 (9.6%) were diagnosed with SBP at admission on the basis of an ascitic fluid white cell count above 250 cells/mm<sup>3</sup> (25 cases). Patients with positive cultures but no white cell response were only included if symptomatic (one case). Alcohol was the underlying aetiology in 17 cases (65.4%) and clinical presentations were as follows: routine paracentesis (14 cases), associated pleural effusion (four cases), variceal haemorrhage (three cases), abdominal pain (two cases), jaundice (two cases), encephalopathy (one case). Ascitic culture on two patients grew gram-negative bacilli, both resistant to quinolones being used for prophylaxis. One ascitic culture grew <i>Lactobacillus</i> spp. and one a mixed growth of <i>Enterococcus faecalis</i> and gram-positive cocci. Three patients (11.5%) died during the index admission. Three patients (11.5%) had successfully undergone liver transplantation and were alive 6 months after admission. Overall mortality at 6 months from an admission diagnosis of SBP was 50%. <h3>Conclusion</h3> SBP is not uncommon in cirrhotic patients with ascites, can often present silently and is associated with high mortality. Resistance to standard quinolone prophylaxis and isolation of gram-positive bacteria are more recent phenomena in this group of patients. All cirrhotics admitted with significant ascites should undergo diagnostic paracentesis to exclude SBP and assessment for liver transplantation must be an urgent consideration in appropriate candidates. Listing criteria may need to be revised to include SBP as a standard indication. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Tito L</b>, <i>et al.</i> Recurrence of spontaneous bacterial peritonitis in cirrhosis: frequency and predictive factors. <i>Hepatology</i> 1988;<b>8</b>:27–31.
A SIMPLE-TO-USE NOMOGRAM FOR PREDICTING 5-, 10- AND 15-YEAR SURVIVAL FOR ASYMPTOMATIC INDIVIDUALS UNDERGOING CORONARY ARTERY CALCIUM SCORING
Authors: Briain O Hartaigh, Heidi Gransar, Tracy Callister, Leslee Shaw, Joshua Schulman-Marcus, Valentina Valenti, Iksung Cho, Quynh Truong, Jackie Szymonifka, James Min
Journal: Journal of the American College of Cardiology (2015)
TCT-804 The Impact Of Triple Anti-Platelet Therapy For Endothelialization And Inflammatory Response At Overlapping Bioabsorbable Polymer Coated Drug-Eluting Stents In A Porcine Coronary Model
Authors: Keun-Ho Park, Youngkeun Ahn, Young Joon Hong, Myung Ho Jeong, Young Wook Jeong, Hae Chang Jeong, Dong Goo Kang, Sung Soo Kim, Ju Han Kim, Si Hyun Rhew, Doo Sun Sim
Journal: Journal of the American College of Cardiology (2013)
Hydroxychloroquine and Surfactant Protein C Deficiency
Authors: Dennis M. Rosen, David A. Waltz
Journal: New England Journal of Medicine (2005)

To the Editor: We wish to report initial success in treating a boy with surfactant protein C deficiency. The patient was first admitted to the hospital at five months of age with severe respiratory distress that followed a viral respiratory infection. Open-lung biopsy revealed nonspecific interstitial pneumonitis, and DNA analysis revealed that the gene encoding surfactant protein C had a C-to-A substitution leading to an alanine-to-aspartate substitution at amino acid 116 in exon 4. The patient was discharged home in moderate respiratory distress; he was breathing oxygen at a rate of 2 to 3 liters per minute by nasal cannula . . .
UK hospitals need a proper seven day system, consensus conference concludes
Authors: B. Christie
Journal: BMJ (2013)

A 56-year-old Hispanic male with solo risk factor of uncontrolled diabetes mellitus presented with recurrent haemoptysis. Initial concern was for malignancy with postobstructive pneumonia; however, invasive testing and biopsy confirmed infectious mass of fungal aetiology requiring surgical resection followed by a prolonged course of anti-fungal therapy. Discussion centred on approach to, progression of and course of action in the management of pulmonary abscess due to mucormycosis.
Catabolic Defect of Branched-Chain Amino Acids Promotes Heart Failure
Authors: Haipeng Sun, Kristine C. Olson, Chen Gao, Domenick A. Prosdocimo, Meiyi Zhou, Zhihua Wang, Darwin Jeyaraj, Ji-Youn Youn, Shuxun Ren, Yunxia Liu, Christoph D. Rau, Svati Shah, Olga Ilkayeva, Wen-Jun Gui, Noelle S. William, R. Max Wynn, Christopher B. Newgard, Hua Cai, Xinshu Xiao, David T. Chuang, Paul Christian Schulze, Christopher Lynch, Mukesh K. Jain, Yibin Wang
Journal: Circulation (2016)

Although metabolic reprogramming is critical in the pathogenesis of heart failure, studies to date have focused principally on fatty acid and glucose metabolism. Contribution of amino acid metabolic regulation in the disease remains understudied.Transcriptomic and metabolomic analyses were performed in mouse failing heart induced by pressure overload. Suppression of branched-chain amino acid (BCAA) catabolic gene expression along with concomitant tissue accumulation of branched-chain α-keto acids was identified as a significant signature of metabolic reprogramming in mouse failing hearts and validated to be shared in human cardiomyopathy hearts. Molecular and genetic evidence identified the transcription factor Krüppel-like factor 15 as a key upstream regulator of the BCAA catabolic regulation in the heart. Studies using a genetic mouse model revealed that BCAA catabolic defect promoted heart failure associated with induced oxidative stress and metabolic disturbance in response to mechanical overload. Mechanistically, elevated branched-chain α-keto acids directly suppressed respiration and induced superoxide production in isolated mitochondria. Finally, pharmacological enhancement of branched-chain α-keto acid dehydrogenase activity significantly blunted cardiac dysfunction after pressure overload.BCAA catabolic defect is a metabolic hallmark of failing heart resulting from Krüppel-like factor 15-mediated transcriptional reprogramming. BCAA catabolic defect imposes a previously unappreciated significant contribution to heart failure.
Reply to Manno et al.
Authors: A. May
Journal: Endoscopy (2012)

We agree that the experience using single-balloon enteroscopy (SBE) for investigation of the small bowel is much less in the study of Takano et al. compared with the experience using double-balloon enteroscopy (DBE). However, both techniques are push-and-pull techniques, which means that the principle of pleating the small bowel is similar. In the paper of Mehdizadeh et al., a learning period of 10 DBEs was calculated, but this was for endoscopists with no experience in any kind of balloon-assisted enteroscopy [1]. The lack of skill, especially for the SBE technique, might be the reason for a 0 % rate of complete enteroscopy for SBE in the Takano study [2]. Nevertheless, the results of the Takano study confirmed the results of our own comparative trial, which showed a three-fold higher complete rate of enteroscopy for DBE compared with SBE [3].
Case 36-2007
Authors: Marc S. Sabatine, Kian-Keong Poh, Jessica L. Mega, Jo-Anne O. Shepard, James R. Stone, Matthew P. Frosch
Journal: New England Journal of Medicine (2007)

A 31-year-old woman was admitted to this hospital because of rash, fever, and facial swelling that developed after the administration of modafinil for the treatment of fatigue associated with multiple sclerosis. Several hours after admission, chest discomfort and hypotension developed, ST-segment elevation was present on the electrocardiogram, and biomarkers of cardiac necrosis were elevated. Echocardiography disclosed a pericardial effusion and left ventricular dysfunction. A diagnostic procedure was performed.
FOOTPRINT PATTERNS AND FACTURES IN BIORESORBABLE STENTS IMPLANTED IN STEP-DOWN BIFURCATIONS
Authors: Camilla Fox Maule, Jo Simonsen, Emil Holck, Jouke Dijkstra, Lene Andreasen, AnneMarie Brüel, Jesper Skovhus Thomsen, Jens Lassen, Shengxian Tu, Hans Erik Boetker, Evald Christiansen, Niels Holm
Journal: Journal of the American College of Cardiology (2016)
THU0184 Identification of biomarkers in SLE pregnancies using urinary proteomics
Authors: K. Schreiber, K. Bramham, H. Mistry, O. Barrutia-Ateka, S. Lynham, A. Weston, M.A. Ward, L.M. Bertolaccini, L.C. Chappell, M.A. Khamashta
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pre-eclampsia affects 2-7% of all pregnancies (1), is a leading cause of maternal morbidity and mortality and increases perinatal mortality five-fold (2). Women with Systemic Lupus Erythematosus (SLE) have a particularly high risk of developing pre-eclampsia (3) and patients with specific organ involvement (i.e. lupus nephritis) are at higher risk of developing pre-eclampsia earlier in their pregnancy (4). <h3>Objectives</h3> This study aims to identify human pregnancy biomarkers in the urinary proteome to improve the diagnosis and/or prediction of pre-eclampsia in patients with SLE. <h3>Methods</h3> Second trimester urine samples were collected from 3 women with SLE and lupus nephritis who subsequently developed pre-eclampsia, 5 SLE gestation-matched patients who did not develop pre-eclampsia and 6 healthy controls. Samples were prepared following our optimized workflow using in-gel trypsin digestion followed by LC-MS/MS. Spectral abundance of differentially expressed proteins was analysed using minimal stringency settings in Scaffold software. <h3>Results</h3> Our preliminary data suggest that pre-eclampsia results in a distinctive urinary proteome in women with lupus nephritis, but also in controls compared to women without pre-eclampsia (Figure 1a and b). One hundred and sixteen proteins were identified; of these, 6 proteins were found to be present only in the SLE pre-eclampsia urine samples (arrow). Furthermore, two proteins were found to be present in SLE pre-eclampsia (arrow), but showed a difference in SLE non-pre-eclampsia urinary samples and were absent in the samples from women with SLE without pre-eclampsia (circled in black) (Figure 1b). <h3>Conclusions</h3> Previous work in this group involving pre-eclamptic samples has used targeted mass spectrometry for relative quantitation in a validation sample set. Our study shows differentially expressed proteins, representing potential biomarker candidates of pre-eclampsia in patients with SLE/APS and hence warrant further investigation. <h3>References</h3> Sibai B et al., Lancet 2005;365:785-99. Roberts J.M.; Placenta 2002;23:359-72. Salmon JE et al., PLoS Med. 2011;8:e1001013. Bramham K et al., J Rheumatol 2011 Jun 1. <h3>Disclosure of Interest</h3> K. Schreiber Grant/Research support from: ESF - Biolupus, K. Bramham: None Declared, H. Mistry: None Declared, O. Barrutia-Ateka: None Declared, S. Lynham: None Declared, A. Weston: None Declared, M. Ward: None Declared, L. M. Bertolaccini: None Declared, L. C. Chappell: None Declared, M. Khamashta: None Declared
Interferon Alfa-2b Alone or in Combination with Ribavirin as Initial Treatment for Chronic Hepatitis C
Authors: John G. McHutchison, Stuart C. Gordon, Eugene R. Schiff, Mitchell L. Shiffman, William M. Lee, Vinod K. Rustgi, Zachary D. Goodman, Mei-Hsiu Ling, Susannah Cort, Janice K. Albrecht
Journal: New England Journal of Medicine (1998)

Only 15 to 20 percent of patients with chronic hepatitis C have a sustained virologic response to interferon therapy. We compared the efficacy and safety of recombinant interferon alfa-2b alone with those of a combination of interferon alfa-2b and ribavirin for the initial treatment of patients with chronic hepatitis C.
Assessing Acid-Base Status in Circulatory Failure
Authors: Horacio J. Adrogué, M. Nabil Rashad, Arnold B. Gorin, Joseph Yacoub, Nicolaos E. Madias
Journal: New England Journal of Medicine (1989)

To assess arteriovenous differences in acid-base status, we measured the pH and partial pressure of carbon dioxide (PCO2) in blood drawn simultaneously from the arterial and central venous circulations in 26 patients with normal cardiac output, 36 patients with moderate and 5 patients with severe circulatory failure, and 38 patients with cardiac or cardiorespiratory arrest. The patients with normal cardiac output had the expected arteriovenous differences: venous pH was lower by 0.03 unit, and venous PCO2 was higher by 0.8 kPa (5.7 mm Hg). These differences widened only slightly in those with moderate cardiac failure. Additional simultaneous determinations in mixed venous blood from pulmonary arterial catheters were nearly identical to those in central venous blood. In the five hypotensive patients with severe circulatory failure there were substantial differences between the mean arterial and central venous pH (7.31 vs. 7.21) and PCO2 (5.8 vs. 9.0 kPa [44 vs. 68 mm Hg]). Large arteriovenous differences were present during cardiac arrest in patients whose ventilation was mechanically sustained, whether sodium bicarbonate had been administered (pH, 7.27 vs. 7.07; PCO2, 5.8 vs. 8.6 kPa [44 vs. 65 mm Hg]) or not (pH, 7.36 vs. 7.01; PCO2, 3.7 vs. 10.2 kPa [28 vs. 76 mm Hg]). By contrast, in patients with cardiorespiratory arrest, large arteriovenous differences were noted only when sodium bicarbonate had been given (pH, 7.24 vs. 7.01; PCO2, 9.5 vs. 16.9 kPa [71 vs. 127 mm Hg]). We conclude that both arterial and central venous blood samples are needed to assess acid–base status in patients with critical hemodynamic compromise. Although information about arterial blood gases is needed to assess pulmonary gas exchange, in the presence of severe hypoperfusion, the hypercapnia and acidemia at the level of the tissues are detected better in central venous blood. (N Engl J Med 1989; 320:1312–6.)
Abstract 4203: Analysis of the association of Notch pathway genes with ID4 and Ikaros gene expression in leukemia
Authors: Nejat Dalay, Orkun Gurbuz
Journal: Cancer Research (2012)

Abstract The Notch signal pathway plays an important role in several cellular processes in a variety of tissues. In the hematopoiesis Notch expression is involved in various aspects of cellular regulation and aberrant Notch signaling components have been associated with malignant transformation. Hes1 (hairy/enhancer of split 1) gene is a Notch target gene coding for a transcriptional repressor that is necessary to maintain progenitor cell populations. HES1 can bind promoter regions of the cyclin-dependent kinase inhibitors and repress their expression. Hes-1 expression can be stimulated by growth factors The Hey family of transcriptional repressors are canonical direct targets of Notch and function as downstream effectors of Notch signaling. Expression of HES1 and HEY proteins can vary in different cell types suggesting an additional mechanism of transcription regulation. Ikaros is a member of the Kruppel transcription factor family. Expression of Ikaros down-regulates expression of the Notch target genes. Deregulation of Ikaros and Notch signalling cooperate to promote leukemogenesis, providing evidence that they function in converging pathways. The ID4 (inhibitor of differentiation 4) gene is a member of the family of ID helix-loop-helix proteins that function as dominant negative regulators of basic transcription factors. In certain cancer types downregulation of the ID4 gene has been reported resulting in low or no expression of the ID4 protein. In the current study the expression of the Hes1, Hey1, Ikaros and ID4 genes was investigated in 110 patients with acute and chronic leukemias and 32 healthy controls by real time PCR using the ΔΔCt method. Both Hes1 and Hey1 expression levels were significantly increased in the patients in all disease groups. ID4 expression was significantly decreased in % 86.4 of the patients. Expression of these genes was strongly associated. Expression of the Ikaros gene decreased only in the subgroup of patients with CML while it increased in patients with acute leukemias and CLL. Our data suggest that the Notch pathway genes Hes1 and Hey1 are activated in leukemias and may contribute to the disease development while the ID4 gene is supressed, possibly by methylation. 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 4203. doi:1538-7445.AM2012-4203
Abstract 2088: NVP-BKM120 decreases cell survival and antagonizes resistance signals derived from protective tissue microenvironment by interfering with the Akt/FoxO3a/Bim axis in CLL cells.
Authors: Laia Rosich, Ifigenia Saborit-Vilarroya, Monica Lopez-Guerra, Silvia Xargay-Torrent, Arnau Montraveta, Marta Aymerich, Neus Villamor, Elias Campo, Patricia Perez-Galan, Gael Roue, Dolors Colomer
Journal: Cancer Research (2013)

Abstract Phosphatidylinositol-3-kinase (PI3K) pathway is a key component of many cancers survival. Particularly, PI3K is constitutively activated in chronic lymphocytic leukemia (CLL) due to microenvironment signals, including stromal cell interaction, CXCR4 activation and B-cell receptor (BCR) triggering. Because of the importance of PI3K for CLL-microenvironment cross-talk and chemotherapy resistance, we investigated the activity of the NVP-BKM120, an orally available pan class I PI3K inhibitor. Here, we show that NVP-BKM120 promoted mitochondrial apoptosis in primary CLL cells independently of common prognostic markers. At the molecular level, NVP-BKM120 blocked PI3K signalling, resulting in decreased phosphorylation of Akt and FoxO3a while downregulating Mcl-1 and inducing Bim. Importantly, selective knockdown of BIM rescued cells from NVP-BKM120-induced apoptosis. Moreover, NVP-BKM120 enhanced the activity of the BH3-mimetic ABT263 in CLL cells, leading to synergistic apoptosis induction. We also found that NVP-BKM120 inhibited BCR- and stromal-induced Akt activation as well as induced Bim in presence of BCR-derived and stromal survival signals. In stromal cocultures, NVP-BKM120 sensitized CLL cells towards bendamustine and fludarabine. Furthermore, NVP-BKM120 downregulated secretion of chemokines after BCR triggering and inhibited CLL cell chemotaxis and actin polymerization toward CXCL12. Altogether, our data suggest that NVP-BKM120 displays a dual mechanism of action, directly decreasing cell survival and antagonizing survival and drug-resistance signals derived from protective tissue microenvironment. Citation Format: Laia Rosich, Ifigenia Saborit-Vilarroya, Monica Lopez-Guerra, Silvia Xargay-Torrent, Arnau Montraveta, Marta Aymerich, Neus Villamor, Elias Campo, Patricia Perez-Galan, Gael Roue, Dolors Colomer. NVP-BKM120 decreases cell survival and antagonizes resistance signals derived from protective tissue microenvironment by interfering with the Akt/FoxO3a/Bim axis in CLL cells. [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 2088. doi:10.1158/1538-7445.AM2013-2088
Abstract 4955: TIMP-1 inhibits apoptosis in lung adenocarcinoma cells via Bcl-2 interaction
Authors: Srilatha Nalluri, Sitaram Gayatri, Juhi Ohja, Amyn M. Rojiani, Mumtaz V. Rojiani
Journal: Cancer Research (2012)

Abstract Tissue inhibitors of matrix metalloproteinases have multifunctional properties, orchestrating diverse biological activities. Previous studies revealed a novel function of TIMP-1 as an inhibitor of apoptosis in mammalian cells. However, the mechanisms by which TIMP-1 exerts its anti-apoptotic effect are not completely understood. The antiapoptotic effect has been correlated with higher levels of Bcl-Xl. Our earlier studies in a CNS model of metastasis, using HB-1, a TIMP-1 overexpressing lung adenocarcinoma cell line (H2009), resulted in more aggressive tumor kinetics and increased vasculature. The present study was undertaken to elucidate the role of TIMP-1 in apoptosis in our model. Utilizing an apoptosis -specific gene array, we found that TIMP-1 overexpression results in 3-fold increased expression of Bcl-2. H2009 and the TIMP1 over-expressing clone - HB1 were treated with staurosporine to induce apoptosis, followed by analysis for poly ADP-ribose polymerase (PARP) cleavage. HB1 showed marked reduction in PARP cleavage in comparison to the controls. Treatment of HB1 cells with ABT737, an inhibitor of Bcl-2, restored apoptosis resulting in PARP cleavage in this clone. To further confirm this mechanism, we induced transient inhibition of Bcl-2 with siRNA, which also restored PARP cleavage in the HB-1 clone. Thus both chemical and biological inhibition resulted in increased apoptosis. Additionally, immunoprecipitation of Bcl-2 from cell lysate co-immunoprecipitated TIMP-1 suggesting a direct interaction between TIMP-1 and Bcl-2. These investigations identify a relationship between TIMP-1 and Bcl-2 in apoptosis inhibition, contributing to aggressive tumor kinetics, utilizing non-MMP dependent mechanisms. 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 4955. doi:1538-7445.AM2012-4955