tbuckley/cabot-search huggingface dataset:
Abstract 5172: Whole exome mutation landscape of 70 commonly used colorectal cancer cell lines
Authors: Oliver Sieber, Dmitri Mouradov, Clare Sloggett, Robert Jorissen, Chris Love, Shan Li, Antony Burgess, Diego Arango, Robert Strausberg, Daniel Buchanan, Samuel Wormald, Liam O'Connor, Jenny Wilding, David Bicknell, Ian Tomlinson, Walter Bodmer, John Mariadason
Journal: Cancer Research (2014)

Abstract Human colorectal cancer (CRC) cell lines are an important model system for studying the biology of this malignancy as well as therapeutic and biomarker discovery. However, data on the degree to which established CRC cell lines reflect the somatic diversity of primary cancers at the genome level are limited. Using whole exome sequencing and SNP microarray analysis we show that the profile of mutations and DNA copy-number alterations in 70 widely-used CRC cell lines closely resembles that of primary colorectal tumors published by The Cancer Genome Atlas Network. We demonstrate presence of at least two hypermutation phenotypes, consistent with defective DNA mismatch repair and DNA polymerase epsilon (POLE) proof-reading deficiency, and similar mutation signatures in the WNT, MAPK, PI3K, TGF-beta and TP53 pathways. Paired cell lines derived from the same tumor are found to exhibit substantial mutation and DNA copy-number differences, with in silico simulations suggesting that these largely reflect pre-existing tumor cell heterogeneity, but these differences do not obscure known driver genes. Our genome level data indicate that CRC cell lines are representative models of the main molecular subtypes of primary tumors, and will facilitate informed selection of molecularly-defined models for preclinical investigations. Citation Format: Oliver Sieber, Dmitri Mouradov, Clare Sloggett, Robert Jorissen, Chris Love, Shan Li, Antony Burgess, Diego Arango, Robert Strausberg, Daniel Buchanan, Samuel Wormald, Liam O'Connor, Jenny Wilding, David Bicknell, Ian Tomlinson, Walter Bodmer, John Mariadason. Whole exome mutation landscape of 70 commonly used colorectal cancer cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5172. doi:10.1158/1538-7445.AM2014-5172
Multiply Attenuated, Self-Inactivating Lentiviral Vectors Efficiently Deliver and Express Genes for Extended Periods of Time in Adult Rat Cardiomyocytes In Vivo
Authors: Sylvain Fleury, Eleonora Simeoni, Christian Zuppinger, Nicole Déglon, Ludwig K. von Segesser, Lukas Kappenberger, Giuseppe Vassalli
Journal: Circulation (2003)

Among retroviral vectors, lentiviral vectors are unique in that they transduce genes into both dividing and nondividing cells. However, their ability to provide sustained myocardial transgene expression has not been evaluated.Multiply attenuated, self-inactivating lentivectors based on human immunodeficiency virus-1 contained the enhanced green fluorescent protein (EGFP) gene under the transcriptional control of either the cytomegalovirus (CMV) immediate-early enhancer/promoter, the elongation factor-1alpha (EF-1alpha) promoter, or the phosphoglycerate-kinase (PGK) promoter. Lentivectors transduced adult rat cardiomyocytes in a dose-dependent manner (transduction rates, >90%; multiplicity of infection, approximately 5). The CMV promoter achieved higher EGFP expression levels than the EF-1alpha and PGK promoters. Insertion of the central polypurine tract pol sequence improved gene transfer efficiency by approximately 2-fold. In vivo gene transfer kinetics was studied by measuring the copy number of integrated lentivirus DNA and EGFP concentrations in cardiac extracts by real-time polymerase chain reaction and ELISA, respectively. With CMV promoter-containing lentivectors, vector DNA peaked at day 3, declined by approximately 4-fold at day 14, but then remained stable up to week 10. Similarly, EGFP expression peaked at day 7, decreased by approximately 7-fold at day 14, but was essentially stable thereafter. In contrast, vector DNA and EGFP expression declined rapidly with EF-1alpha promoter-containing lentivectors. Peak EGFP expression with titer-matched adenovectors was approximately 35% higher than with CMV lentivectors but was lost rapidly over time.Lentivectors efficiently transduce and express genes for extended periods of time in cardiomyocytes in vivo. Lentivectors provide a useful tool for studying myocardial biology and a potential system for gene heart therapy.
Effect of eradication ofHelicobacter pylori on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura: A controlled trial
Authors: Nematollah Rostami, Maryam Keshtkar‐Jahromi, Mohammad Rahnavardi, Marzieh Keshtkar‐Jahromi, Fatemeh Soghra Esfahani
Journal: American Journal of Hematology (2008)

Abstract Several recent studies have suggested that an association exists between Helicobacter pylori (HP) eradication and improvement in platelet count in a significant proportion of patients with idiopathic thrombocytopenic purpura (ITP). In this controlled study, we prospectively examined adult patients with chronic ITP for HP infection, and assessed the effect of HP eradication on platelet count. One hundred forty‐two consecutive Iranian patients with chronic ITP were assessed. Those who met the criteria and had platelet counts &gt;30 × 10 9 /L within the medication‐free screening month were enrolled ( n = 129; 66 females; mean age, 29.2 ± 7.0 years). HP‐positive patients received a 2‐week course of triple HP eradication therapy (i.e., amoxicillin, clarithromycin, and omeprazole) and were followed for 48 weeks. An ITP response was defined as a platelet count of &gt;100 × 10 9 /L 24 weeks after treatment, together with an increase in the platelet count &gt;30 × 10 9 /L over the baseline value. HP infection was detected in 79 (61%) patients. HP‐positive patients were significantly older than HP‐negative subjects ( P = 0.018). HP eradication was successful in 87% (62/71) of those who completed the eradication therapy. Whereas 48% (30/62) of HP‐eradicated patients showed an ITP response, no HP‐negative patient had an ITP response. The ITP response persisted for 48 weeks in 93% (28/30) of the responders. The ITP responders had a shorter disease duration than the nonresponders ( P = 0.002). The management of mild‐to‐moderate chronic ITP in Iranian patients, especially those with a recent onset of disease, should include an investigation for and eradication of infection with HP. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.
Energy thresholds that determine membrane integrity and injury in a renal epithelial cell line (LLC-PK1). Relationships to phospholipid degradation and unesterified fatty acid accumulation.
Authors: M A Venkatachalam, Y J Patel, J I Kreisberg, J M Weinberg
Journal: Journal of Clinical Investigation (1988)

This study related ATP levels with membrane damage, lipid abnormalities, and cell death in energy-depleted LLC-PK1 cells. Oxidative phosphorylation was inhibited by antimycin A, and glycolysis was regulated by graded glucose deprivation to achieve stepwise ATP depletion. Over a range of ATP levels down to approximately equal to 5% of normal, over 5 h, cells were altered only minimally, or injured reversibly. Such cells maintained mitochondrial potential, and retained more K+ than cells without an energy source. Over the same duration, cells without an energy source were lethally injured. Treatment with antimycin induced increments of triglycerides and decreases of phospholipids. With severe ATP depletion (approximately equal to 5-10% of normal after 5 h), decrease of phospholipids was marked. Cells in which ATP was not measurable (or was less than 5% of normal) showed comparable phospholipid declines but, in addition, showed massive and progressive increase of unesterified fatty acids. The results identified a low threshold of ATP, at best 5-10% of normal, which preserved viability in LLC-PK1 cells despite major loss of membrane phospholipids. This threshold also determined the ability of cells to maintain their normally low levels of unesterified fatty acids. Failure of energy-dependent mechanisms that normally metabolize unesterified fatty acids may be a correlate of the extent of energy depletion that determines lethal injury.
Risk vs Risk: Tradeoffs in Protecting Health and the Environment
Authors: Arthur L. Frank
Journal: JAMA (1996)

The somewhat catchy and promising title for this book unfortunately covers a generally simplistic and superficial series of case studies involving risks, and overall the book has little to recommend it. The positives are best found in the opening and closing sections, rather than in the case studies, which outline the basic issues of risk and alternative risks when changes are made and could serve as a useful introduction for those with little experience in these areas. There is also an extensive reference section for each chapter, which some might find useful. The book, in fact, has many failings. It picks off easy targets but does not address some of the more clear, if complex, issues in our society, such as tobacco use. Issues worthy of review might have included local and global environmental equity, trade-offs for developing countries in establishing their own manufacturing base, and other similar issues. In
Production of antikeratin autoantibodies by hybrid spleen cells of naive mice
Authors: K. IWATSUKI, S. IMAIZUMI, H. HASHIZUME, K. SUGAYA, M. TAKIGAWA, M. YAMADA
Journal: British Journal of Dermatology (1990)

The mechanism of the occurrence of natural antikeratin antibodies in human sera was studied using hybrid spleen cells obtained from experimentally naive or from immunized mice. Antikeratin antibodies were detected by enzyme-linked immunosorbent assay (ELISA) in 5.9-9.5% of the culture supernatants of fused spleen cells taken from naive mice. When mice were immunized with keratins, the number of supernatants containing antikeratin antibodies was increased to eight out of 51 (15.7%). When immunized with non-keratin materials such as activated human T cells, adult T-cell leukaemia cell lysates, and human T-cell lymphotropic virus type-I (HTLV-I), 16.7-20.8% of the supernatants were found to contain antikeratin antibodies by ELISA. The antikeratin antibodies in the supernatants showed cytoplasmic staining of keratinocytes in human as well as mouse skin by indirect immunofluorescence. The antibodies reacted with extracted human epidermal keratins by dot-blot and Western blot analysis. Most antikeratin antibodies in the supernatants did not show cross-reactivity with exogenous antigens used for immunization and vimentin-type intermediate-sized filaments. These findings demonstrate that B cells producing antikeratin antibodies are common in naive mice, and produce various types of antikeratin antibodies following specific activation with epidermal keratins and non-specific immunological stimuli.
731 CHANGES OF SERUM APOPTOTIC CASPASE ACTIVITY IN HBEAG-NEGATIVE CHRONIC HEPATITIS B (CHB) PATIENTS UNDER ORAL ANTIVIRAL THERAPY
Authors: G.V. Papatheodoridis, J. Giannousis, S. Manolakopoulos, E. Hadziyannis, A. Georgiou, A.J. Archimandritis
Journal: Journal of Hepatology (2010)
Endoscopic ultrasound (EUS)-guided ethanol injection in hepatic metastatic carcinoma: a case report
Authors: Y.-H. Hu, X.-P. Tuo, Z.-D. Jin, Y. Liu, Y. Guo, L. Luo
Journal: Endoscopy (2010)

Endoscopic ultrasound (EUS)-guided ethanol injection is used as palliative treatment for localized pancreatic tumorous lesions such as pancreatic cysts [1]. However, there have been few reports of its use in hepatic metastatic carcinoma. Here we report the use of EUS-guided ethanol injection for treatment of hepatic metastatic carcinoma following pancreatoduodenectomy in a patient with pancreatic cancer, which was successful in obtaining local control.
UN investigators call for inquiry into possible war crimes during Israel's attack on Gaza
Authors: J. Zarocostas
Journal: BMJ (2009)

United Nations investigators have called for an independent inquiry to be conducted into allegations of war crimes during Israel’s recent 22 day onslaught on the Gaza Strip.

They say that the targeting of ambulances, hospitals, and other healthcare facilities, attacks on densely populated civilian areas, and obstructions of people fleeing the conflict all warrant investigation.

“Considering that the attacks were directed at densely populated areas, it was to some extent inevitable and certainly foreseeable that hospitals, religious, and educational sites and United Nations facilities would be hit and that extensive civilian casualties would result,” said Richard Falk, the UN’s special rapporteur on the …
FRI0320 Radiographic features, better than clinical features, represent actual joint degeneration and inflammation: Considerations for total knee replacement surgery
Authors: T.N. De Boer, S.C. Mastbergen, A.M. Huisman, A.A. Polak, W.H. Noort-vanderLaan, J.W. Bijlsma, F.P. Lafeber
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Clinically, osteoarthritis (OA) is characterized by joint pain, tenderness, limitation of movement, crepitus, occasional effusion, and local inflammation. Pain, joint deformation, and stiffness of the joint capsule may lead to severe restriction of function, and in the long term to disability. In end-stage disease total knee replacement (TKR) surgery might become a treatment option. Indication for TKR is primarily based on persistent pain and functional disability despite conservative therapy. Unfortunately, specific indications for timing of TKR are not clearly defined. Radiographic joint damage adds to decision-making, but is not leading. <h3>Objectives</h3> The aim of this study is to evaluate whether radiographic characteristics and/or clinical characteristics prior to TKR predict actual cartilage damage and/or synovial inflammation. <h3>Methods</h3> Demographics, radiographic features of OA (K&amp;L and Altman grade) and clinical symptoms (WOMAC-pain, -stiffness, and -physical function) of 172 knee OA patients were assessed shortly before TKR. NSAIDs and acetaminophen use was registered. During surgery, cartilage and synovial tissue were obtained and evaluated by macroscopy, histology, and biochemistry. To examine the relationship of radiographic features as well as clinical features with the actual cartilage damage and synovial inflammation, binary logistic regression modeling was used. All analyses were performed with and without adjustment for demographics age, gender, and BMI. <h3>Results</h3> The average K&amp;L score of this population was 3.1 (range 1-4). The average Altman scores for this population were 2.5 (range 0-3) for joint space narrowing and 3.2 (range 0.8-6) for the osteophytes. Both the K&amp;L score and the Altman osteophyte score were associated with the actual macroscopic cartilage damage [2.375, p=0.006/2.229, p=0.005, respectively]. Joint space narrowing also showed an association with macroscopic cartilage damage [1.619, p=0.067]. Additionally, osteophyte score was associated with macroscopical synovial inflammation [1.593, p=0.029] and histological synovial inflammation [1.454, p=0.039], suggesting synovial inflammation to be involved in osteophyte formation. No clinical parameter related to any of the actual structural cartilage damage of synovial inflammation parameters. <h3>Conclusions</h3> Radiographic OA characteristics correlate better with actual cartilage damage and synovial inflammation parameters in patients undergoing TKR than clinical parameters do. As such, it is important to include radiographic OA characteristics when selecting patients for TKR. <h3>Disclosure of Interest</h3> None Declared
Cardiovascular Control Mechanisms in the Conscious State
Authors: Stephen F. Vatner, Eugene Braunwald
Journal: New England Journal of Medicine (1975)

CLINICIANS and clinical physiologists would prefer to base an understanding of the function and regulation of the cardiovascular system on observations carried out in man. However, both ethical considerations and limitations in instrumentation mandate the study of laboratory animals, in which appropriate controls and interventions can be introduced. Whereas extremely important hemodynamic information has been obtained from studies of man, most of the knowledge of cardiovascular physiology and pharmacology is based on findings obtained in animal experiments, which have been conducted most frequently on animals in the anesthetized state, often with an open chest. The conclusions derived from these experiments . . .
A Severe Response to Substances Released From Cotton
Authors: Stanley S. Lefkowitz
Journal: JAMA (1984)

To the Editor.—  Cotton dust has been implicated in the etiology of byssinosis as well as other important respiratory diseases. 1 It also has been reported that inhalation of cotton dust can result in antibody-independent complement activation causing histamine release resulting in airway changes. 2,3   Report of a Case.—  A 39-year-old woman with a history of asthma was having continual respiratory problems. Initially she had laryngeal edema coupled with headaches and frequent lethargy. These symptoms seemed to be somewhat cyclic, with remissions in the evenings and on Sundays. Because of the time of the year, it was suggested that her symptoms could relate to cotton ginning, which is of considerable importance in this area. It was subsequently noted that when she left the cotton ginning and growing area, her symptoms would disappear. These severe manifestations, however, would recur after she returned to the area.  A number of radioallergosorbent tests as
High incidence of amiodarone-induced photosensitivity in North-west England.
Authors: R J Chalmers, H L Muston, V Srinivas, D H Bennett
Journal: BMJ (1982)

High incidence of amiodaroneinduced photosensitivity in North-west England Amiodarone is a potent cardiac antiarrhythmic agent which has been used in Europe for more than a decade but which has only recently become available in Britain.Facial pigmentation and photosensitivity are well recognised side effects,'-4 but their incidence is disputed.We report the incidence of photosensitivity in a large group of patients receiving amiodarone at a regional cardiothoracic centre.
What carbohydrate foods should diabetics eat?
Authors: D Freed
Journal: BMJ (1984)

Disorders, and Pain in the Neck.These are free and can be sent in bulk to general practitioners and hospital doctors or individually to patients.Special booklets for the parents and teachers of children with juvenile arthritis, When Your Child Has Arthritis and When A Young Person Has Arthritis, have also been produced.Other booklets-Your Home and Your Rheumatism, Marriage, Sex and Arthritis, and Are You Sitting Comfortably?-are available at a modest cost.
Induction of cytotoxic T lymphocytes by dendritic cells pulsed with murine leukemic cell RNA
Authors: Chul Won Jung, Jung Hye Kwon, Jae Goo Seol, Woo Hyun Park, Jung Mi Hyun, Eun Shil Kim, Seung Taik Kim, Sang Jae Lee, Byoung Kook Kim, Young Yiul Lee
Journal: American Journal of Hematology (2004)

Peptide-pulsed dendritic cells can stimulate T cells showing specific cytotoxicity in chronic myelogenous leukemia. We tried to induce a specific cytotoxic T-cell response stimulated by RNA-pulsed dendritic cells in acute myelogenous leukemia. The total RNA of WEHI-3BD+, a myelomonocytic leukemia cell line derived from BALB/c mice, was transfected into dendritic cells induced from bone marrow nucleated cells of BALB/c mice with granulocyte macrophage colony-stimulating factor (GM-CSF) and lipopolysaccharide (LPS) using liposome. RNA-pulsed dendritic cells were injected into the peritoneal cavity of BALB/c mice, and splenic T cells were isolated for antigen-stimulated proliferation and leukemia-specific cytotoxicity assay. Cultured bone marrow nucleated cells expressed dendritic cell markers including MHC class II antigen, CD80, CD86, and CD11c. T cells stimulated by RNA-pulsed dendritic cells showed enhanced proliferation than those stimulated by unpulsed dendritic cells (P = 0.05) and showed dose-dependent specific cytotoxicity against WEHI-3BD+ cells. We concluded total RNA-pulsed dendritic cells could induce a specific T-cell cytotoxicity in acute myelogenous leukemia.
Evidence That the Human Y Chromosome Does Not Contain Clustered DNA Sequences (Bkm) Associated with Heterogametic Sex Determination in Other Vertebrates
Authors: Karen Kiel-Metzger, Gwynedd Warren, Golder N. Wilson, Robert P. Erickson
Journal: New England Journal of Medicine (1985)

SEX differentiation in mammals, including human beings, is poorly understood. Although the Y chromosome is the usual stimulus for male sexual differentiation, the existence of fertile chromosomally normal XX males in goats demonstrates the importance of autosomal loci.1 It has been popular to consider a male-specific antigen, H-Y, to be the mediator of the Y stimulus for male sexual differentiation, but recent experiments in mice2 , 3 invalidate this hypothesis because normal fertile females exist with normal levels of H-Y and male differentiation can occur in the absence of H-Y. Alternative markers for male sexual differentiation are the banded krait minor satellite . . .
P5-01-17: HER2 Amplification in Primary Tumor: A Potential Marker for Presence of Circulating Tumor Cells in Inflammatory Breast Cancer Patients?
Authors: A Bhattacharyya, S Krishnamurthy, A Lodhi, C Hall, A Anderson, S Jackson, N Ueno, I Bedrosian, H Kuerer, A Lucci
Journal: Cancer Research (2011)

Abstract Background: Inflammatory breast cancer (IBC) is a rare but aggressive form of invasive breast cancer accounting for 3–6% of all cases and have higher rates of distant recurrence. Circulating tumor cells (CTCs) are known to predict outcome in metastatic breast cancer (BC) patients, but little is known about their prognostic significance in non-metastatic BC. We hypothesized that CTCs can be identified in patients with IBCs and may correlate with primary tumor characteristics. Methods: All patients had blood samples collected at the time of primary surgery. CTCs (per 7.5 ml blood) were detected using the Cell Search™ system (Veridex) and were defined as nucleated cells lacking CD45 but expressing cytokeratins (CK) 8, 18, or 19. The presence of ≥ 1 epithelial cells meeting morphologic criteria for malignancy was considered a positive result. Statistical analyses employed Chi square and Fisher's exact tests using STATA IC 11. Results: We prospectively evaluated 41 IBC patients enrolled in an IRB approved protocol undergoing surgery for stage I-III breast cancer. Median follow-up was 30 months. Mean age was 52 years. Thirty five patients (94%) had positive lymph nodes (LNs) at presentation, 30 (75%) had high-grade tumors and 20 (53%) had lymphovascular invasion. Eleven patients (28%) were ER positive, 11 (27%) were PR positive and 18 (44%) were HER2 positive. IBCs were more likely to be high grade (P&amp;lt;0.0001), ER negative (P&amp;lt;0.0001), PR negative (P&amp;lt;0.0001), HER2 positive (P&amp;lt;0.0001), High Ki-67 (P= 0.005) and had a BMI of more than 25kg/m2 (P=0.04). Eleven (27%) patients were CTC positive. CTCs were more likely be found in HER2 positive (8/18; 44%) vs. HER2 negative primary tumors (3/20; 15%) [OR= 4.53; 95% C.I. = 1.02−19.52; P= 0.04]. We found no statistically significant correlations between primary tumor characteristics (ER, PR, LNs, high grade) and presence of CTCs. Conclusions: About a quarter of IBC patients had CTCs at the time of primary surgery. In these patients HER2 overexpression predicted the presence of CTCs. Studies with longer follow-ups is needed to determine if CTCs predicted survival. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-01-17.