tbuckley/cabot-search huggingface dataset:
Lymphoscintigraphic Evaluation of Congenital Lymphedema of the Newborn
Authors: Carlo Bellini, Cesare Arioni, Massimo Mazzella, Corradino Campisi, Gioconda Taddei, Francesco Boccardo, Giovanni Serra
Journal: Clinical Nuclear Medicine (2002)

BELLINI, CARLO M.D., Ph.D.; ARIONI, CESARE M.D.; MAZZELLA, MASSIMO M.D.; CAMPISI, CORRADINO M.D.; TADDEI, GIOCONDA M.D.; BOCCARDO, FRANCESCO M.D.; SERRA, GIOVANNI M.D. Author Information
Azd9291, a Third Generation EGFR Inhibitor, Versus Gefitinib or Erlotinib in Treatment-Naïve Patients (PTS) with Advanced Non-Small Cell Lung Cancer (NSCLC) Harbouring an Egfr-Tki-Sensitising Mutation (EGFRM): a Randomised, Phase Iii Study (FLAURA)
Authors: S.S. Ramalingam, Y. Rukazenkov, K. Thomas, J.-C. Soria
Journal: Annals of Oncology (2015)
Abstract 2208: High-resolution analysis of insertional mutagenesis screens to study genetic interactions in heterogeneous tumors
Authors: Marco J. Koudijs, Jaap Kool, Daoud Sie, Pramudita Prasetyanti, Edwin Cuppen, Anton Berns, John Hilkens, Maarten van Lohuizen, David Adams, Jos Jonkers
Journal: Cancer Research (2010)

Abstract Insertional mutagenesis (IM) screens in genetically engineered mouse models of cancer are a powerful tool to identify genes or regions in the genome contributing to tumorigenesis. Current methods to identify the integration sites are not quantitative and do not give information about the clonality of a given insertion in a tumor. Consequently, the results of IM screens are hard to interpret since the obtained data are incomplete and highly biased due to technical variation. We have developed and optimized a next-generation sequencing-based method for ultra high-throughput analysis of insertional mutations in a less biased and quantitative manner. Integration sites of retroviral or transposon based insertional mutagens are amplified using Splinkerette-mediated PCR and subsequent 454 sequencing. In contrast to current protocols, based on restriction enzyme (RE) fragmentation, we randomly shear gDNA, which allows a random ligation of the Splinkerette. This enables us to generate randomly sized amplicons per integration, which reduces amplification- and sequencing bias compared to amplicons with a fixed length per integration using RE based methods. Since Splinkerette ligation can occur at every base pair, we can determine the amount of cells containing the given insertion by counting unique ligation points, each representing a unique chromosome, and thereby a cell, in the tumor. This latter feature, addressing clonality of an insertional mutagen, will allow the identification of both clonal and sub-clonal mutations in genetically heterogeneous tumors. More importantly, we are now able to study co-occurring mutations, e.g. underlying synthetic lethality, which cannot be performed reliably using the current method. The insertional mutagenesis data obtained with the improved method will represent the biological situation of a given integration within a tumor, thereby facilitating subsequent validation experiments. Additionally, data obtained from our retroviral- and transposon-based screens in various mouse models of cancer will serve as a catalogue of cancer-relevant mutations that can be used for cross-species comparative analysis of the large numbers of mutations found in human breast cancer. 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 2208.
Discrepancy Between 24-Hour I-131 and 30-Minute Tc-99m Tetrofosmin Thyroid Imaging in Thyroiditis
Authors: CHIA-HUNG KAO, YEH-YOU SHEN, JONG-KANG LEE, SHYH-JEN WANG
Journal: Clinical Nuclear Medicine (1997)

I-131 and Tc-99m tetrofosmin thyroid imaging were performed in two patients with thyroiditis. One patient had subacute thyroiditis and the other had Hashimato's thyroiditis. I-131 imaging showed no thyroid visualization in the patient with subacute thyroiditis and poor visualization in the patient with Hashimato's thyroiditis. Thyroid imaging with Tc-99m tetrofosmin was successful in both cases.
Differential Alterations of Dopamine Transporter in the Striatum and Midbrain in Patients With Parkinsonian Syndrome
Authors: Manuela C. Matesan, Donna J. Cross, David H. Lewis, Satoshi Minoshima
Journal: Clinical Nuclear Medicine (2014)

Differential vulnerabilities of subregional dopamine neurons have been suggested in movement disorders such as idiopathic Parkinson disease. In this study, we examined dopamine transporter (DaT) density in the striatum versus midbrain (MB) in patients with nigrostriatal denervation.Brain SPECT was performed in 39 patients with parkinsonian syndrome (age 61 ± 15 years, 18 male patients) 4 hours after IV injection of 3 to 5 mCi 123I ioflupane using SPECT-CT acquisition. Images were reconstructed using OSEM with resolution recovery and correction for scatter and attenuation based on a low-dose CT. Peak pixel counts within the caudate head (CA), mid putamen (PT), and MB localized by sagittal CT, as well as averaged counts around the calcarine fissure as reference, were determined by region-of-interest analysis. Semiquantitative DaT values were expressed as CA, PT, or MB uptake relative to the reference. We then assessed the relationship between the MB measurements and independent clinical evaluation of motor symptoms in these patients.Averaged striatal DaT values for both hemispheres ranged from 1.67 to 6.59 for CA, 1.50 to 5.33 for PT, and 1.08 to 2.24 for MB. Within the high striatal DaT group (mean, 4.76 [SD, 0.55]) and low DaT group (mean, 2.71 [SD, 0.58]; dichotomy defined as a threshold of 4), mean DaT values in MB were 1.68 (SD, 0.32) and 1.53 (SD, 0.29), respectively, indicating nonsignificant 9% decrease (P > 0.15) in comparison to 43% decrease in the averaged striatal uptake. Within the high striatal DaT group, Pearson correlations between DaT values of CA and PT versus MB were highly significant at 0.81 and 0.82 (P ≤ 0.001), respectively, but those correlations were not significant, 0.35 (P > 0.05) and 0.06 (P > 0.75), in the low striatal DaT group. Midbrain uptake measurements did not correlate with motor symptoms (bradykinesia, tremor, rigidity, and postural instability).These findings indicate that reductions in DaT values in the striatum and MB are not necessarily simultaneous with the process of nigrostriatal denervation, and correlation of DaT values among CA/PT and MB becomes weaker as the denervation becomes more severe. Differential regional DaT loss may indicate differential vulnerability of DaT-containing neurons in these structures or could be in part related to tracer binding to non-DaT targets.
Endoscopic appearance of sclerosing mesenteritis in the colon
Authors: M. Cravo, P. Sousa, I. Tavora, N. Zozimo, J. Velosa
Journal: Endoscopy (2012)

A 46-year-old man presented with a 1-month history of back pain, vague abdominal discomfort in the lower quadrants, change of bowel habit with constipation alternating with liquid, nonbloody stools, and a suprapubic mass about the size of his fist that he had noticed 1 week previously. Physical examination showed a suprapubic mass of 6 – 8 cm, which was tender on deep palpation. A computed tomography (CT) scan showed a thickening of the sigmoid and descending colonic wall with increased opacification of the adjacent mesentery. Colonoscopy showed an edematous mucosa with pseudonodular areas and a total absence of normal motility in the rectum, sigmoid and descending colon ([Fig. 1]), with a normal appearing colonic mucosa proximal to the splenic flexure. Multiple biopsies were performed, which showed congestion and an inflammatory infiltrate, insufficient for a definite diagnosis.
Bacterial Stimulation and Granulocyte Inhibition of Granulopoietic Factor Production
Authors: William A. Robinson, Maureen A. Entringer, Rex W. Bolin, O. Gordon Stonington
Journal: New England Journal of Medicine (1977)

We attempted to determine the effect of live bacteria (Staphylococcus epidermidis) on granulocyte colony-stimulating-factor production by human peripheral blood mononuclear cells (monocytes and lymphocytes) in vitro. Addition of bacteria to mononuclear-cell cultures enhanced colonystimulating-factor production by these cells, as assayed on both human and mouse bone marrow. Addition of peripheral blood granulocytes to parallel cultures eliminated this enhancement effect, presumably by bacterial removal or inactivation. These data suggest that micro-organisms may have a pivotal role in granulocyte production and maturation by serving as a stimulus to increase colony-stimulating-factor production and also as negative control through their removal by the newly formed granulocytes. (N Engl J Med 297:1129–1134, 1977)
Anti–Interleukin-17 Monoclonal Antibody Ixekizumab in Chronic Plaque Psoriasis
Authors: Craig Leonardi, Robert Matheson, Claus Zachariae, Gregory Cameron, Linda Li, Emily Edson-Heredia, Daniel Braun, Subhashis Banerjee
Journal: New England Journal of Medicine (2012)

Type 17 helper T cells have been suggested to play a pathological role in psoriasis. They secrete several proinflammatory cytokines, including interleukin-17A (also known as interleukin-17). We evaluated the safety and efficacy of ixekizumab (LY2439821), a humanized anti–interleukin-17 monoclonal antibody, for psoriasis treatment.
METHOD AND RESULTS OF ELECTRIC CONVULSIVE THERAPY DURING COMPLETE CURARIZATION
Authors: JACQUES S. GOTTLIEB, LUCIEN E. MORRIS
Journal: American Journal of Psychiatry (1953)

1. Six elderly depressed patients with severe osteoporosis of the spine and other physical disabilities were treated by electric convulsive therapy during complete curarization. The method of complete curarization allowed the administration of electric convulsive therapy without danger of producing further injury to diseased skeletal structures, and thus extended the usefulness of this therapy to patients who otherwise would be unable to receive it. 2. The results of experiences with Tensilon indicate its limitations and its usefulness as an adjunct to bag, mask, and oxygen in the maintenance of the proper ventilation of the patient when the patient had been completely curarized.
Trends in the Incidence of Myocardial Infarction and in Associated Mortality and Morbidity in a Large Employed Population, 1957–1983
Authors: Sidney Pell, William E. Fayerweather
Journal: New England Journal of Medicine (1985)

We analyzed long-term trends in the incidence of a first acute myocardial infarction and in case-fatality rates among employees of the Du Pont Company from 1957 through 1983. A steady decline in Incidence was observed among male employees. The annual age-adjusted rate in the 1957–1959 period was 3.19 per 1000, as compared with 2.29 per 1000 in the 1981 -1983 period — a decline of 28.2 per cent. The rate of decline was higher among salaried (white-collar) employees than among production workers receiving hourly wages. No trend was seen among female employees, but the number of cases may have been too small to detect a decline. Beginning in 1969, the 24-hour case-fatality rate showed a moderate decline, but after 1975, there was a sharp drop in the 30-day case-fatality rate among persons who survived 24 hours after the attack. These declines did not begin until several years after the decline in incidence had begun. This study and others suggest that improved medical care probably made some contribution to the decline in mortality associated with coronary heart disease, but the major source of the decline has been a reduction in the incidence of the disease. (N Engl J Med 1985; 312: 1005–11.)
Myasthenia Gravis: A Clinical and Pathological Study of a Case Associated with a Primary Mediastinal Thymoma and a Solitary Secondary Intrapulmonary Thymoma
Authors: Harry A. Derow, Monroe J. Schlesinger, Lester Persky
Journal: New England Journal of Medicine (1950)

THE tumor of the thymus occurring in about a sixth of the patients presenting the symptoms of myasthenia gravis is usually encapsulated and slowly growing and is generally regarded as a benign neoplasm. It has been called a thymoma.1 Ten per cent or less of such thymomas encroach upon and extend by continuity into the adjacent pleura, lungs, pericardium or superior vena cava. Separate, discrete, secondary deposits of such thymomas occasionally found at a distance on the pleura have been interpreted as implants and not as true metastases.1 , 2 Separate, discrete, secondary metastases from such thymomas in other organs have not . . .
PWE-109 Measurement of Infliximab and Anti-Infliximab Antibodies - Analytical Aspects and Clinical Implications: Abstract PWE-109 Table
Authors: N Unsworth, Z Arkir, P Irving, M G Ward, G Richards
Journal: Gut (2013)

<h3>Introduction</h3> Commercial assays for monitoring Infliximab (IFX) and anti-drug antibodies (ADAb) are currently available. The heterogeneity of these assays and lack of standardisation of ADAb may cause difficulties in interpretation, in particular comparing bridging ELISA and radioimmunoassay (RIA). Bridging ELISAs have high specificity but are more prone to inhibition by drug hence may underestimate ADAb, whereas false positive results can be seen with RIA. <b>Aims</b>Evaluation of (i) the effect of common interferents in the LISA-Tracker Premium ELISA assay (Theradiag). (ii) the inhibitory effect of IFX on the detection of ADAb. <h3>Methods</h3> The LISA-Tracker kit was used for the quantitative determination of free drug and ADAb by indirect and bridging assay principles respectively. The measurement range was 0.1 to 5 μg/mL for IFX and 10 to 200 ng/mL for ADAb (&gt; 10 ng/mL considered positive). Interference studies were carried out using samples with known levels of haemolysis, icterus, rheumatoid factor (RF) and paraprotein (IgG kappa = 17 g/L). All patients had no history of exposure to biologics. Samples were run neat and diluted with samples of known IFX and ADAb concentration to assess recovery. Samples with known levels of ADAb were spiked with aqueous solutions of IFX (2.4, 1.2 and 0.3 µg/mL) at a ratio of 1:2. Predicted ADAb concentrations were calculated by sample dilution in drug-free diluent. <h3>Results</h3> No interference was observed from haemolysis (up to 0.6 g/dL haemoglobin equivalent), icterus (up to 349 μmol/L bilirubin), RF (up to 885 U/mL) and paraprotein as confirmed by recoveries of 93–113% for drug and ADAb. Spiking experiments The inhibitory effect of IFX on ADAb detection was observed in both low and high level ADAb samples with ADAb only detectable in sample 2 i.e. as free, not complex form. Comparing expected with measured concentrations of IFX in the spiked samples indicated a difference in recovery between the low and high ADAb positive samples suggesting decreased availability of free IFX in the presence of ADAb. <h3>Conclusion</h3> This study shows that the LISA-Tracker kit is not affected by tested interferents. Results from spiking experiments highlight the importance of measuring trough levels and also indicate that the presence of ADAb (detectable or undetectable) can limit the availability of free IFX, leading to sub-therapeutic levels. LISA-Tracker is a simple, robust assay which has been implemented in our hospital and is routinely used as a personalised approach to prescribing and optimising anti-TNFα therapies in IBD. <h3>Disclosure of Interest</h3> None Declared.
Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome
Journal: New England Journal of Medicine (2014)

In the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS.We conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure-free days to day 14.The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P=0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P=0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P=0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P=0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range.Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction. (Funded by the National Heart, Lung, and Blood Institute and the Investigator-Sponsored Study Program of AstraZeneca; ClinicalTrials.gov number, NCT00979121.).
Case 48-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, N.G. Pandian, J.F. Southern
Journal: New England Journal of Medicine (1991)

Presentation of CaseA 75-year-old man was admitted to the hospital because of the recent onset of congestive heart failure and the finding of a left atrial mass. The patient was well until three or four weeks earlier, when he began to experience exertional dyspnea, easy fatigability, and rises in the temperature as high as 37.2°C.During the two or three weeks before admission, peripheral edema and orthopnea developed and increased, and the patient felt lightheaded on two occasions. Two weeks before admission an x-ray film of the chest, obtained elsewhere, was reported to show evidence of congestive heart failure, . . .
Abstract 4202: Genetic re-programming of the AML cell line HL-60 during differentiation: Roles of the EGR/NAB and NR4A transcription factors
Authors: Michael Roberts, Nicole Briceno, Jamie Bugel, Catherine Campbell, Mary Dickinson, Trevor McCarthy, Phoebe Oldach, Natalie Stanley, Jeffrey Forrester
Journal: Cancer Research (2012)

Abstract HL-60 cells represent an established line of human acute myeloid leukemia cells that can be induced to differentiate along several distinct myeloid lineages. Phorbol esters activate a signaling network, which includes the protein kinase C (PKC) pathway, causing the leukemia cells to differentiate into macrophage-like cells. As the leukemia genetic program is converted to the macrophage program, the cells exit the cell cycle, undergo morphological changes, become adherent, display other macrophage properties, and ultimately initiate apoptosis. This study provides a detailed DNA microarray analysis with qRT-PCR validation of the genetic network of the leukemia cell during first 24 hours post-induction of differentiation. We present data describing the global changes in gene expression at the RNA-level at 0.5, 1, 3, 6, 12, and 24 hours post-PMA treatment and information about specific genes with regard to their RNA and protein expression levels. Approximately 2,000 genes were identified that exhibit significant changes in mRNA levels from the leukemia expression program. A cluster analysis was performed to group these genes by their pattern of expression resulting in a collection of distinct expression profiles and associated functional profiles. These genes encode transcription factors, intracellular signal transducers, receptors, cytokines and a variety of other proteins. Of particular interest in understanding the genetic re-programming of the leukemic cells is the transcription factor expression profile. In addition to the established roles of the NF-kappa-B and AP-1 transcription factors in HL-60 cell differentiation, we present possible roles for the EGR/NAB and NR4A transcription factor families in both differentiation and initiation of apoptosis. A variety of biological analysis strategies using the expression data to define regulatory groupings that characterize the changing genetic network in these cells, including interaction networks and pathway activations have been carried out. Taken together, we seek to better understand the genetic program defining leukemia cells and the mechanisms by which oncogenic mutations can be overridden to achieve cell cycle arrest, differentiation and apoptosis. 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 4202. doi:1538-7445.AM2012-4202
Abstract A5: Characterization of signaling pathways related to resistance of breast cancer cells against irreversible EGFR/HER/ErbB kinase inhibitors
Authors: Caroline Bruenner-Kubath, Waheed Shabbir, Victoria Saferding, Renate Wagner, Christian F. Singer, Peter Valent, Walter Berger, Brigitte Marian, Christoph C. Zielinski, Michael Grusch, Thomas W. Grunt
Journal: Clinical Cancer Research (2010)

Abstract Epidermal growth factor (EGF) receptor-related antigens (EGFR, ErbB1-4, HER1-4) represent emerging drug targets in oncology. However, resistance against ErbB-targeting drugs occurs frequently in cancer patients. Drug-resistant cells may exhibit drug-refractory phosphatidylinositol 3-kinase (PI3K) or mitogen-activated protein kinase (MAPK) signaling, but the relative impact and contribution of these two downstream pathways to drug resistance are still controversially discussed. We examined the effects of the two very potent, irreversibly binding ErbB receptor tyrosine kinase inhibitors (RTKIs) pelitinib (EKB-569) and canertinib (CI-1033) on PI3K- and MAPK activity in ErbB RTKI-sensitive and ErbB RTKI-resistant breast and ovarian cancer cells. Western blot analysis revealed that ErbB phosphorylation was abrogated by the inhibitors in both drug-sensitive and drug-resistant cells, whereas AKT- and GSK3β phosphorylation were drug-dependently downregulated only in drug-sensitive cells. ErbB RTKI sensitivity did not correlate with expression of wildtype PTEN or PIK3CA, nor was it associated with drug-dependent silencing of ERK1,2 in the breast and ovarian cancer cell lines examined. Moreover, exogenous AKT, but not MEK, significantly induced drug resistance. Our data demonstrate that blocking AKT phosphorylation is essential and sufficient, whereas abrogation of ERK phosphorylation is not required for ErbB RTKI anticancer efficacy. AKT phosphorylation may thus be a useful biomarker of ErbB RTKI sensitivity in breast and ovarian cancer cells. Supported by ‘MedizinischWissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien’ (#08037) and ‘Initiative Krebsforschung’, Medical Univ. Vienna. Citation Information: Clin Cancer Res 2010;16(7 Suppl):A5