tbuckley/cabot-search huggingface dataset:
Cancer Immunologists and Cancer Biologists: Why We Didn't Talk Then but Need to Now
Authors: George C. Prendergast, Elizabeth M. Jaffee
Journal: Cancer Research (2007)

Abstract What is cancer? Cancer is a disease initiated by a series of cumulative genetic and epigenetic changes that occur in a normal cell. However, in addition to the malignant cell itself, cancer is a disease of microenvironment and immunity. Although genetic and epigenetic alterations drive cellular transformation, genomic plasticity, and evolution, it has become increasingly apparent that multiple signals delivered within the tumor microenvironment by modifier genes, stromal and endothelial cells, and immune cells are critical factors in determining the progression versus dormancy or destruction of an initiated lesion and also whether metastasis may occur. With regard to the important roles of immune cells in cancer, a chasm exists between immunologists and biologists: although sharing a common disease interest, there is little history for workers to draw on based on shared perspectives or understanding. How did this disconnect arise? Here, we look at how these workers became separated in the past and address why it has now become critical to spur greater cross-fertilization. In particular, we highlight three ideas that we believe are important for discussion and debate. The first idea is that therapeutic strategies that fail to harness the immune system will always be defeated by tumor resistance, due to the large “genomic space” that genetically plastic tumor cells can readily access to evolve resistance mechanisms. Because all therapies drive tumor progression by imposing a selection for resistant cells, harnessing the adaptivity of the immune system will be indispensable to ultimately stanching the deadly adaptability of the tumor cell. The second idea is that using molecular targeted agents to reverse tumoral immune suppression may offer a powerful method to leverage the efficacy of most if not all therapeutic agents. We suggest that the mechanisms that support evolution of a “smoldering” inflammatory environment in cancer overlap with those that support evolution of tumoral immune escape. If true, relieving immune suppression will switch the inflammatory state from supportive to destructive for the tumor. The third idea is that by ablating immunosuppression mechanisms, cytotoxic chemotherapy might synergize with, rather than antagonize, active immunotherapy. Provocative preclinical studies in this area prompt clinical attention. We believe that increased efforts to intermingle the perspectives and work of cancer immunologists with cancer biologists and pharmacologists will be needed to realize the National Cancer Institute's goal of managing cancer in the clinic by 2015. [Cancer Res 2007;67(8):3500–4]
The Genetics of Splicing in Neuroblastoma
Authors: Justin Chen, Christopher S. Hackett, Shile Zhang, Young K. Song, Robert J.A. Bell, Annette M. Molinaro, David A. Quigley, Allan Balmain, Jun S. Song, Joseph F. Costello, W. Clay Gustafson, Terry Van Dyke, Pui-Yan Kwok, Javed Khan, William A. Weiss
Journal: Cancer Discovery (2015)

Regulation of mRNA splicing, a critical and tightly regulated cellular function, underlies the majority of proteomic diversity and is frequently disrupted in disease. Using an integrative genomics approach, we combined both genomic data and exon-level transcriptome data in two somatic tissues (cerebella and peripheral ganglia) from a transgenic mouse model of neuroblastoma, a tumor that arises from the peripheral neural crest. Here, we describe splicing quantitative trait loci associated with differential splicing across the genome that we use to identify genes with previously unknown functions within the splicing pathway and to define de novo intronic splicing motifs that influence splicing from hundreds of bases away. Our results show that these splicing motifs represent sites for functional recurrent mutations and highlight novel candidate genes in human cancers, including childhood neuroblastoma.
Proximity to Pollution Sources and Risk of Amphibian Limb Malformation
Authors: Brynn Taylor, David Skelly, Livia K. Demarchis, Martin D. Slade, Deron Galusha, Peter M. Rabinowitz
Journal: Environmental Health Perspectives (2005)

The cause of limb deformities in wild amphibian populations remains unclear, even though the apparent increase in prevalence of this condition may have implications for human health. Few studies have simultaneously assessed the effect of multiple exposures on the risk of limb deformities. In a cross-sectional survey of 5,264 hylid and ranid metamorphs in 42 Vermont wetlands, we assessed independent risk factors for nontraumatic limb malformation. The rate of nontraumatic limb malformation varied by location from 0 to 10.2%. Analysis of a subsample did not demonstrate any evidence of infection with the parasite Ribeiroia. We used geographic information system (GIS) land-use/land-cover data to validate field observations of land use in the proximity of study wetlands. In a multiple logistic regression model that included land use as well as developmental stage, genus, and water-quality measures, proximity to agricultural land use was associated with an increased risk of limb malformation (odds ratio = 2.26; 95% confidence interval, 1.42-3.58; p < 0.001). The overall discriminant power of the statistical model was high (C = 0.79). These findings from one of the largest systematic surveys to date provide support for the role of chemical toxicants in the development of amphibian limb malformation and demonstrate the value of an epidemiologic approach to this problem.
Colon Cancer Metastatic to a Urachus Diagnosed by PET/CT
Authors: Robert Percarpio, Alan Siegel, Marc Seltzer
Journal: Clinical Nuclear Medicine (2012)

A 50-year-old man presented with a mass in the transverse colon diagnosed by colonoscopy. He underwent a left hemicolectomy and was diagnosed with a moderately differentiated adenocarcinoma penetrating into the pericolic adipose but no lymph node metastases. His course was uneventful with enrollment in a monoclonal antibody research treatment protocol. Eight years later, he presented with hematuria. A PET/CT demonstrated a hypermetabolic right external iliac lymph node and a hypermetabolic mass within a urachal remnant. The mass was excised and pathologically proven to represent a metastasis from the original primary tumor.
Transmission of Glomerular Permeability Factor from a Mother to Her Child
Authors: Markus J. Kemper, Gunter Wolf, Dirk E. Müller-Wiefel
Journal: New England Journal of Medicine (2001)

To the Editor: In the idiopathic nephrotic syndrome, including focal segmental glomerulosclerosis, a glomerular permeability factor may be responsible for the development of proteinuria and the rec...
Defining radiographic incidence and progression of knee osteoarthritis: suggested modifications of the Kellgren and Lawrence scale
Authors: D. T. Felson, J. Niu, A. Guermazi, B. Sack, P. Aliabadi
Journal: Annals of the Rheumatic Diseases (2011)

In the 1950s, Kellgren and Lawrence carried out the first large-scale epidemiological studies of osteoarthritis. Obtaining x-rays on multiple subjects from the populations of various communities in England, they defined a grading scale for osteoarthritis that is still widely used and called by their names, the Kellgren and Lawrence (K&L) scale.1 This osteophyte-based scale is used in most large and small-scale clinical and epidemiological studies to define whether osteoarthritis is present or absent on the radiograph.

Unfortunately, neither Kellgren and Lawrence nor subsequent users of their scale were consistent in how they described each of their grades. Importantly, for grade 2, which usually defines whether osteoarthritis is present, it has been labelled as ‘definite osteophyte’ to ‘definite osteophyte with possible narrowing of the joint space’. As noted by Schiphof and colleagues,2 3 as investigators have come up with various descriptions of K&L grade 2, each of these studies may have identified a somewhat different group of persons with radiographic knee osteoarthritis.

With the emergence of large longitudinal studies of osteoarthritis have come questions about how to define new-onset disease and progressive disease, questions that the K&L scale was never designed to address. Even so, many studies, especially large epidemiological investigations, have used the K&L scale to identify knees with new-onset disease or progressive disease. In the Framingham and Rotterdam Studies,4 5 for example, investigators have defined new-onset disease as the emergence of K&L grade 2 disease in knees that had previously been graded as either K&L grades 0 or 1. Rotterdam Study investigators have alternatively used as disease incidence the new onset of K&L grade 1 in knees previously graded as grade 0.5 Progression of extant disease has also been characterised using K&L grades with progression by one grade or more often listed as one criterion …
Unrecognized Chronic Lithium Neurotoxic Reactions
Authors: David A. Lewis
Journal: JAMA (1983)

PREVIOUS investigators have reported the occurrence of lithium neurotoxic reactions in the presence of therapeutic serum lithium levels.<sup>1,2</sup>These reports have been criticized because the time interval between the last dose of lithium and the serum lithium level determination was not specified and because complicating factors, such as organic brain damage or other psychotropic drug use, were present.<sup>3</sup> The following case report describes a patient who experienced lithium neurotoxic reactions in the presence of consistently normal 12- to 16-hour serum lithium levels and in the absence of major complicating factors. It also illustrates that lithium neurotoxic reactions can occur chronically and still resolve after the discontinuation of lithium therapy. <h3>Report of a Case</h3> A 58-year-old man had a 26-year history of bipolar affective disorder. He had been treated with maintenance lithium carbonate, 300 mg twice daily, and desipramine hydrochloride, 75 mg at bedtime, for two years. The patient
Coronary vasodilation after a single ventricular extra-activation in the conscious dog.
Authors: G G Schwartz, P A McHale, J C Greenfield
Journal: Circulation Research (1982)

This study was undertaken to determine if coronary blood flow can be regulated in response to a transient increase in cardiac metabolic demand. Eight conscious dogs with experimentally produced complete heart block, a chronically implanted electromagnetic flow probe on the left circumflex coronary artery, and fluid-filled catheters for measurement of left ventricular and aortic pressures were studied. At a paced heart rate of 60 beats/min, a single ventricular extra-stimulus was introduced with a delay of 150-200 msec from the preceding R-wave. The extra-stimulus produced a ventricular extra-activation, but not a discrete mechanical extra-systole. The ensuing beats exhibited systolic potentiation, manifest by a 50 +/- 8% increase from control in maximum left ventricular dp/dt in the first potentiated beat, presumably accompanied by increased myocardial oxygen demand. In the diastole immediately following the first potentiated systole, the coronary vascular resistance index (mean aortic pressure/mean coronary flow in that diastole) fell significantly from control by 12 +/- 2%. The results indicate that a transient increase in cardiac metabolic demand is followed immediately by a compensatory coronary vasodilation that occurs within the same cardiac cycle.
Inflammation, Apoptosis, and Necrosis Induced by Neoadjuvant Fas Ligand Gene Therapy Improves Survival of Dogs With Spontaneous Bone Cancer
Authors: Jaime F Modiano, Donald Bellgrau, Gary R Cutter, Susan E Lana, Nicole P Ehrhart, EJ Ehrhart, Vicki L Wilke, J Brad Charles, Sibyl Munson, Milcah C Scott, John Pozniak, Cathy S Carlson, Jerome Schaack, Richard C Duke
Journal: Molecular Therapy (2012)

Fas ligand (FasL) gene therapy for cancer has shown promise in rodents; however, its efficacy in higher mammals remains unknown. Here, we used intratumoral FasL gene therapy delivered in an adenovirus vector (Ad-FasL) as neoadjuvant to standard of care in 56 dogs with osteosarcoma. Tumors from treated dogs had greater inflammation, necrosis, apoptosis, and fibrosis at day 10 (amputation) compared to pretreatment biopsies or to tumors from dogs that did not receive Ad-FasL. Survival improvement was apparent in dogs with inflammation or lymphocyte-infiltration scores >1 (in a 3-point scale), as well as in dogs that had apoptosis scores in the top 50th percentile (determined by cleaved caspase-3). Survival was no different than that expected from standard of care alone in dogs with inflammation scores ≤1 or apoptosis scores in the bottom 50th percentile. Reduced Fas expression by tumor cells was associated with prognostically advantageous inflammation, and this was seen only in dogs that received Ad-FasL. Together, the data suggest that Ad-FasL gene therapy improves survival in a subset of large animals with naturally occurring tumors, and that at least in some tumor types like osteosarcoma, it is most effective when tumor cells fail to express Fas. Fas ligand (FasL) gene therapy for cancer has shown promise in rodents; however, its efficacy in higher mammals remains unknown. Here, we used intratumoral FasL gene therapy delivered in an adenovirus vector (Ad-FasL) as neoadjuvant to standard of care in 56 dogs with osteosarcoma. Tumors from treated dogs had greater inflammation, necrosis, apoptosis, and fibrosis at day 10 (amputation) compared to pretreatment biopsies or to tumors from dogs that did not receive Ad-FasL. Survival improvement was apparent in dogs with inflammation or lymphocyte-infiltration scores >1 (in a 3-point scale), as well as in dogs that had apoptosis scores in the top 50th percentile (determined by cleaved caspase-3). Survival was no different than that expected from standard of care alone in dogs with inflammation scores ≤1 or apoptosis scores in the bottom 50th percentile. Reduced Fas expression by tumor cells was associated with prognostically advantageous inflammation, and this was seen only in dogs that received Ad-FasL. Together, the data suggest that Ad-FasL gene therapy improves survival in a subset of large animals with naturally occurring tumors, and that at least in some tumor types like osteosarcoma, it is most effective when tumor cells fail to express Fas.
Diamine Oxidase-Gold Ultrastructural Localization of Histamine in Human Skin Biopsies Containing Mast Cells Stimulated to Degranulate In Vivo by Exposure to Recombinant Human Stem Cell Factor
Authors: Ann M. Dvorak, John J. Costa, Ellen S. Morgan, Rita A. Monahan-Earley, Stephen J. Galli
Journal: Blood (1997)
Sera from children with active Henoch-Schonlein purpura can enhance the production of interleukin 8 by human umbilical venous endothelial cells
Authors: Y H Yang
Journal: Annals of the Rheumatic Diseases (2004)

To investigate the ability of sera from children with active Henoch-Schonlein purpura (HSP) to enhance endothelial interleukin (IL) 8 production and intercellular adhesion molecule (ICAM)-1 expression.Nine children with active HSP and nine normal healthy children were enrolled. IL8 serum levels of patients and controls at different stages were analysed. Production of IL8 and expression of ICAM-1 by human umbilical venous endothelial cells were detected (ELISA for IL8, flow cytometry for ICAM-1) and compared under various stimuli, including sera of patients at different stages, sera of controls, and medium alone.Serum levels of IL8 were increased at the acute stage. Levels of IL8 in supernatants from human umbilical venous endothelial cells (HUVEC) co-cultured with sera from children with active HSP were significantly higher than those from HUVEC without any treatment (p = 0.001), HUVEC treated with inactive sera (p = 0.004), and HUVEC treated with sera from healthy controls (p = 0.004). Sera from patients and from controls did not enhance the expression of ICAM-1 on HUVEC.Some factors may be present in sera from children with active HSP that could activate endothelial cells to produce IL8. This process may account, in part, for the mechanisms of perivascular neutrophil infiltration and leucocytosis in HSP.
Radiation-Mediated Up-Regulation of Gene Expression from Replication-Defective Adenoviral Vectors: Implications for Sodium Iodide Symporter Gene Therapy
Authors: Mohan Hingorani, Christine L. White, Shane Zaidi, Andrew Merron, Inge Peerlinck, Martin E. Gore, Christopher M. Nutting, Hardev S. Pandha, Alan A. Melcher, Richard G. Vile, Georges Vassaux, Kevin J. Harrington
Journal: Clinical Cancer Research (2008)

To assess the effects of external beam radiotherapy (EBRT) on adenoviral-mediated transgene expression in vitro and in vivo and to define an optimal strategy for combining sodium iodide symporter (NIS)-mediated (131)I therapy with EBRT.Expression of reporter genes [NIS, green fluorescent protein (GFP), beta-galactosidase (lacZ), and luciferase (Luc)] from replication-deficient adenoviruses was assessed in tumor cell lines under basal conditions and following irradiation. The effects of viral multiplicity of infection (MOI) and EBRT dose on the magnitude and duration of gene expression were determined. In vivo studies were done with Ad-CMV-GFP and Ad-RSV-Luc.EBRT increased NIS, GFP, and beta-galactosidase expression in colorectal, head and neck, and lung cancer cells. Radiation dose and MOI were important determinants of response to EBRT, with greatest effects at higher EBRT doses and lower MOIs. Radiation exerted both transductional (through increased coxsackie-adenoviral receptor and integrin alpha(v)) and nontransductional effects, irrespective of promoter sequence (CMV, RSV, hTR, or hTERT). Analysis of the schedule of EBRT followed by viral infection revealed maximal transduction at 24 hours. Radiation maintained increasing radioiodide uptake from Ad-hTR-NIS over 6 days, in direct contrast to reducing levels in unirradiated cells. The effects of EBRT in increasing and maintaining adenovirus-mediated transgene expression were also seen in vivo using GFP- and luciferase-expressing adenoviral vectors.Radiation increased the magnitude and duration of NIS gene expression from replication-deficient adenoviruses. The transductional effect is maximal at 24 hours, but radioiodide uptake is maintained at an elevated level over 6 days after infection.
Companies that want to charge a higher than basic price for a new drug will have to give evidence that it's worth it
Authors: N. Hawkes
Journal: BMJ (2010)

<h3>AIMS</h3> To evaluate the inferior to temporal neuroretinal rim width ratio and superior to temporal rim width ratio as measures of rim shape for diagnosis of glaucoma. <h3>METHODS</h3> Colour stereo optic disc photographs of 527 normal subjects, 100 ocular hypertensive individuals with normal visual fields, and 202 open angle glaucoma patients with a mean perimetric defect of less than 10 dB were morphometrically evaluated. Eyes with an optic cup area of &lt; 0.2 mm<sup>2</sup> were excluded. <h3>RESULTS</h3> In the normal subjects, inferior to temporal rim width ratio (1.67 (SD 0.53)) was significantly (p&lt;0.0001) higher than superior to temporal rim width ratio (1.56 (0.49)). Both ratios were significantly (p&lt;0.0001) higher the more vertically the optic disc was configured. In the normal eyes, both ratios were statistically independent of disc size, rim area, refractive error, age, and sex. With the differences being more marked for the inferior to temporal ratio than for the superior to temporal ratio, both rim width ratios were significantly (p&lt;0.005) lower in the ocular hypertensive group than in the normal group. Despite the high significance of the differences, diagnostic power of the inferior ratio and the superior ratio was 59% and 58%, respectively, indicating a marked overlap between the groups. <h3>CONCLUSIONS</h3> Abnormally low inferior to temporal and superior to temporal rim width ratios can indicate glaucomatous optic nerve damage in some ocular hypertensive eyes. Being independent of optic disc size and ocular magnification, the rim width ratios may be taken as one among other variables for the ophthalmoscopic optic disc evaluation, taking into account, however, a pronounced overlap between normal eyes and ocular hypertensive eyes.
Relation of prothrombotic platelet polymorphisms to the first manifestation of coronary artery disease in middle-aged males
Authors: Jussi Mikkelsson, Lassi Narhi, Markku Eskola, Elina Ollikainen, Kari Pietila, Kjell Nikus, Kari Niemela, Pekka J Karhunen
Journal: Journal of the American College of Cardiology (2003)
Combining BCR-ABL1 transcript levels at 3 and 6 months in chronic myeloid leukemia: implications for early intervention strategies
Authors: Pratap Neelakantan, Gareth Gerrard, Claire Lucas, Dragana Milojkovic, Philippa May, Lihui Wang, Christos Paliompeis, Marco Bua, Alistair Reid, Katayoun Rezvani, Stephen O'Brien, Richard Clark, John Goldman, David Marin
Journal: Blood (2013)
Cardiac services to expand in Ireland
Authors: D. Payne
Journal: BMJ (1998)

The Irish government has announced a radical overhaul and expansion of heart and lung surgery services. The scheme, to cost in excess of £Ir40m (£48m), will increase the capacity for cardiac surgery by more than 50%–which will give the country one of the highest cardiac operations ratios per capita in the world (about 1000 per million of population).

The announcement was made just days before details of a study of cardiac waiting lists at two major Dublin hospitals showed that not only had …
389 Soluble α-subunit (S-α)—A humoral form of the high affinity IgE receptor—Is present in serum and nasal lavages of allergic individuals
Authors: L POULSEN, H JACOBI, J KOCHAN, C REIMERT, P SKOV, N MYGIND, T BJERKE
Journal: Journal of Allergy and Clinical Immunology (1996)
Altered naive and memory CD4+ T-cell homeostasis and immunosenescence characterize younger patients with myelodysplastic syndrome
Authors: J X Zou, D E Rollison, D Boulware, D-T Chen, E M Sloand, L V Pfannes, J J Goronzy, F Bai, J S Painter, S Wei, D Cosgrove, A F List, P K Epling-Burnette
Journal: Leukemia (2009)
Identification of somatic JAK1 mutations in patients with acute myeloid leukemia
Authors: Zhifu Xiang, Yu Zhao, Vesselin Mitaksov, Daved H. Fremont, Yumi Kasai, AnnaLynn Molitoris, Rhonda E. Ries, Tracie L. Miner, Michael D. McLellan, John F. DiPersio, Daniel C. Link, Jacqueline E. Payton, Timothy A. Graubert, Mark Watson, William Shannon, Sharon E. Heath, Rakesh Nagarajan, Elaine R. Mardis, Richard K. Wilson, Timothy J. Ley, Michael H. Tomasson
Journal: Blood (2007)
DISEASES OF THE ANTRUM.
Authors: WILLIAM CARR
Journal: JAMA (1889)

In the preparation of this paper, it was not deemed necessary to describe the anatomy of the maxillary sinus or to mention all its pathological conditions, as the principal end in view was to present in a practical manner a few observations on that form of antral disease that is of especial interest to us as oral surgeons, namely, suppuration. Different authors vary in opinion regarding the causes leading to suppuration. The throat specialist and the dentist view this disease from the standpoint with which each is most familiar, and it is difficult to form an accurate estimate of the specific causes that produce the greatest number of cases. Zuckerkandl, in his treatise on "The Normal and Pathological Anatomy of the Air Passages," claims that a majority of the cases of suppuration of the maxillary sinus directly result from "the extension of the inflammatory process of the nasal mucous membrane,