tbuckley/cabot-search huggingface dataset:
Abstract ES2-3: The Clonal and Mutational Composition of Triple Negative Breast Cancers
Authors: S Aparicio
Journal: Cancer Research (2012)

Abstract The notion that cancers are mosaics, composed of clones of cells has been fundamental to cancer biology for several decades. Clonal evolution may underpin clinical features of cancer, such as emergence of treatment resistance, the heterogeneous responses of metastatic disease within individual patients and divergence between primary and metastatic disease. Spatial and temporal variation in clonal composition poses significant challenges for diagnostic sampling and disease monitoring. We have recently developed next generation sequencing approaches to these questions and applied them to the understanding of mutational and clonal composition of primary triple negative breast cancers (TNBC). The notion that triple negative breast cancers form a distinct disease entity is already strongly challenged by expression analysis and small scale mutational analysis. Our results show that both the mutational composition and clonal structure of primary triple negative breast cancers is in fact a complete spectrum, exploding the notion of TNBC (currently defined), as a distinct disease. Clonal analysis suggests a means by which the genetic complexity might be reduced by following patient evolution over time and space. I will discuss the specific implications of the mutational and transcriptome landscapes of TNBC in relation to possible disease biologies. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES2-3.
Red Blood Cell Nitric Oxide as an Endocrine Vasoregulator
Authors: Borunendra Datta, Timothy Tufnell-Barrett, Robert A. Bleasdale, Christopher J.H. Jones, Ian Beeton, Vincent Paul, Michael Frenneaux, Philip James
Journal: Circulation (2004)

A respiratory cycle for nitric oxide (NO) would involve the formation of vasoactive metabolites between NO and hemoglobin during pulmonary oxygenation. We investigated the role of these metabolites in hypoxic tissue in vitro and in vivo in healthy subjects and patients with congestive heart failure (CHF).We investigated the capacity for red blood cells (RBCs) to dilate preconstricted aortic rings under various O2 tensions. RBCs induced cyclic guanylyl monophosphate-dependent vasorelaxation during hypoxia (35+/-4% at 1% O2, 4.7+/-1.6% at 95% O2; P<0.05). RBC-induced relaxations during hypoxia correlated with S-nitrosohemoglobin (SNO-Hb) (R2=0.88) but not iron nitrosylhemoglobin (HbFeNO) content. Relaxation responses for RBCs were compared with S-nitrosoglutathione across a range of O2 tensions. The fold increases in relaxation evoked by RBCs were significantly greater at 1% and 2% O2 compared with relaxations induced at 95% (P<0.05), consistent with an allosteric mechanism of hypoxic vasodilation. We also measured transpulmonary gradients of NO metabolites in healthy control subjects and in patients with CHF. In CHF patients but not control subjects, levels of SNO-Hb increase from 0.00293+/-0.00089 to 0.00585+/-0.00137 mol NO/mol hemoglobin tetramer (P=0.005), whereas HbFeNO decreases from 0.00361+/-0.00109 to 0.00081+/-0.00040 mol NO/mol hemoglobin tetramer (P=0.03) as hemoglobin is oxygenated in the pulmonary circulation. These metabolite gradients correlated with the hemoglobin O2 saturation gradient (P<0.05) and inversely with cardiac index (P<0.05) for both CHF patients and control subjects.We confirm that RBC-bound NO mediates hypoxic vasodilation in vitro. Transpulmonary gradients of hemoglobin-bound NO are evident in CHF patients and are inversely dependent on cardiac index. Hemoglobin may transport and release NO bioactivity to areas of tissue hypoxia or during increased peripheral oxygen extraction via an allosteric mechanism.
A mechanism-mediated model for carcinogenicity: model content and prediction of the outcome of rodent carcinogenicity bioassays currently being conducted on 25 organic chemicals.
Authors: R Purdy
Journal: Environmental Health Perspectives (1996)

A hierarchical model consisting of quantitative structure-activity relationships based mainly on chemical reactivity was developed to predict the carcinogenicity of organic chemicals to rodents. The model is comprised of quantitative structure-activity relationships, QSARs based on hypothesized mechanisms of action, metabolism, and partitioning. Predictors included octanol/water partition coefficient, molecular size, atomic partial charge, bond angle strain, atomic acceptor delocalizibility, atomic radical superdelocalizibility, the lowest unoccupied molecular orbital (LUMO) energy of hypothesized intermediate nitrenium ion of primary aromatic amines, difference in charge of ionized and unionized carbon-chlorine bonds, substituent size and pattern on polynuclear aromatic hydrocarbons, the distance between lone electron pairs over a rigid structure, and the presence of functionalities such as nitroso and hydrazine. The model correctly classified 96% of the carcinogens in the training set of 306 chemicals, and 90% of the carcinogens in the test set of 301 chemicals. The test set by chance contained 84% of the positive thio-containing chemicals. A QSAR for these chemicals was developed. This posttest set modified model correctly predicted 94% of the carcinogens in the test set. This model was used to predict the carcinogenicity of the 25 organic chemicals the U.S. National Toxicology Program was testing at the writing of this article.
Cushing's syndrome and pituitary-adrenal suppression due to clobetasol propionate.
Authors: R C Staughton, P J August
Journal: BMJ (1975)

Widespread application of clobetasol propionate resulted in suppression of the hypothalamic pituitary axis in four patients. Three patients showed Cushigoid features and developed symptoms of adrenocortical insufficiency on withdrawal of clobetasol.
Health Status of 1458 Croatian Prisoners of War, 1991-1992
Authors: Josip Begovac
Journal: JAMA (1993)

<h3>To the Editor.</h3> —At the University Hospital of Infectious Diseases, Zagreb, Croatia, a team of professionals was formed to evaluate the health status of Croatian prisoners of war from the armed conflict in Croatia. We report herein the main clinical and laboratory findings in 1458 (1450 men) ex-prisoners examined in the period from November 1991 to September 1992. The mean age of former prisoners was 32.8 years (range, 7 to 72 years), six being younger than 15 years and 21 older than 60 years. The mean duration of confinement was 154 days (range, 12 to 474 days); 571 (39%) were imprisoned for up to 100 days and 12 (0.8%) for more than 300 days. Most of the examined survivors were captured in eastern Slavonia (979 [67%]) or Vukovar (535 [37%]). Seven hundred forty-eight (51%) belonged to the reserve Croatian National Guard and 189 (13%) were civilians. The period of captivity
Allergen sensitisation and impaired lung function in children
Authors: U Gupta
Journal: Thorax (2006)

▴ Illi S, von Mutius E, Lau S, et al. Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study. Lancet2006;368:763–70 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] This study investigated the role of allergic sensitisation early in life as a factor which may contribute to the progressive loss of pulmonary function in children with persistent asthma. 1314 children were followed from birth to age 13. IgE measurements and parental interviews about their child’s asthma … [1]: {openurl}?query=rft.jtitle%253DLancet%26rft.stitle%253DLancet%26rft.aulast%253DIlli%26rft.auinit1%253DS.%26rft.volume%253D368%26rft.issue%253D9537%26rft.spage%253D763%26rft.epage%253D770%26rft.atitle%253DPerennial%2Ballergen%2Bsensitisation%2Bearly%2Bin%2Blife%2Band%2Bchronic%2Basthma%2Bin%2Bchildren%253A%2Ba%2Bbirth%2Bcohort%2Bstudy.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252806%252969286-6%26rft_id%253Dinfo%253Apmid%252F16935687%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/S0140-6736(06)69286-6&link_type=DOI [3]: /lookup/external-ref?access_num=16935687&link_type=MED&atom=%2Fthoraxjnl%2F61%2F11%2F1008.atom [4]: /lookup/external-ref?access_num=000240240200028&link_type=ISI
"MILK SICK," OR WHITE SNAKEROOT POISONING
Authors: W. E. WALSH
Journal: JAMA (1926)

Eupatorium urticaelfolium, the white snakeroot, belongs to the aster family. It is sometimes called boneset, polewort or squaw weed. It grows from 1 to 4 feet high and is widely distributed in the Western states from Minnesota to Louisiana and eastward. Its habitat is rich, deep, shady woods, but it will grow on a hillside in the shade, and on well drained land in the open. The common thoroughwort belongs to the same family and grows in the same locality. The only way to eradicate snakeroot is to pull it out or cultivate the ground.  Dr. Dwight Marsh of the United States Department of Agriculture produced white snakeroot poisoning after the plants had been sterilized in autoclaves. Walter Sackett produced poisoning by extracts, and related experiments have been performed at the Purdue University and North Carolina agricultural stations. This work has determined that the trembles in cattle arise from their
Windblown Lead Carbonate as the Main Source of Lead in Blood of Children from a Seaside Community: An Example of Local Birds as “Canaries in the Mine”
Authors: Brian Gulson, Michael Korsch, Martin Matisons, Charles Douglas, Lindsay Gillam, Virginia McLaughlin
Journal: Environmental Health Perspectives (2008)

In late 2006, the seaside community in Esperance, Western Australia, was alerted to thousands of native bird species dying. The source of the lead was thought to derive from the handling of Pb carbonate concentrate from the Magellan mine through the port of Esperance, begun in July 2005. Concern was expressed for the impact of this process on the community.This study was designed to evaluate the source of Pb in blood of a random sample of the community using Pb isotope ratios.The cohort comprised 49 children (48 < 5 years of age) along with 18 adults (> 20 years of age) with a bias toward higher blood lead (PbB) values to facilitate source identification.Mean PbB level of the children was 7.5 microg/dL (range, 1.5-25.7 microg/dL; n = 49; geometric mean, 6.6 microg/dL), with four children whose PbB was > 12 microg/dL. The isotopic data for blood samples lay around two distinct arrays. The blood of all children analyzed for Pb isotopes contained a contribution of Pb from the Magellan mine, which for young children ranged from 27% up to 93% (mean, 64%; median, 71%). Subtraction of the ore component gave a mean background PbB of 2.3 mug/dL. Several children whose PbB was > 9 microg/dL and most of the older subjects have complex sources of Pb.The death of the birds acted as a sentinel event; otherwise, the exposure of the community, arising from such a toxic form of Pb, could have been tragic. Isotopic data and mineralogic and particle size analyses indicate that, apart from the recognized pathway of Pb exposure by hand-to-mouth activity in children, the inhalation pathway could have been a significant contributor to PbB for some of the very young children and in some parents.
Epidermolysis Bullosa Pruriginosa
Authors: Sivanie Vivehanantha, Richard A. Carr, John A. McGrath, Saleem M. Taibjee, Sharmila Madhogaria, Andrew Ilchyshyn
Journal: JAMA Dermatology (2013)

<h3>Importance</h3>Epidermolysis bullosa (EB) pruriginosa is a rare variant of dystrophic EB. It may manifest late in life and is characterized by intense pruritus, resulting in a phenotype resembling acquired inflammatory dermatoses. Dermatopathology textbooks include hereditary forms of EB among the "cell-poor" list of subepidermal blistering disorders.<h3>Observations</h3>We report a case of dominant dystrophic EB pruriginosa with late-onset cutaneous manifestations. A biopsy specimen showed subepidermal blistering with prominent inflammatory cells, including numerous eosinophils. Unfamiliarity with the distinctive clinicopathologic features of EB pruriginosa led to an initial erroneous histopathologic diagnosis of an acquired autoimmune blistering disorder. Direct immunofluorescence study results were negative for immune reactants. A strong clinical suspicion of hereditary EB pruriginosa led to mutation analysis of COL7A1, which confirmed a novel, heterozygous nonglycine missense mutation. Subsequently, 2 other family members who had nail dystrophy were also correctly diagnosed as having dominant dystrophic EB, highlighting the clinical spectrum of the disorder and the intrafamilial variability in disease presentation.<h3>Conclusions and Relevance</h3>The clinical features of EB pruriginosa are becoming more widely recognized, but dermatologists, dermatopathologists, and histopathologists should be aware that inflammatory infiltrates and late presentation are potential pitfalls in correctly diagnosing this subtype of hereditary EB.
Management of Tetanus
Authors: Benjamin H. Bonnlander
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Tetanus is relatively rare in America today. The rise of cases among addicts, however, and the increasing service of American physicians in underdeveloped regions in which immunization is rarely practiced demand greater familiarity and skill in the care of this disease. To the aspects of clinical management suggested by Henry Brown, MD (<b>204</b>:614, 1968), I would add some comments based on treating more than 100 neonatal and adult patients with tetanus in Haiti. Since both treatment and prognosis are directly related to severity, early objective classification of the degree of severity should always be made. Patel's five-grade system is simple to follow and in common use.<sup>1</sup>Mortality ranges from none in grade I to nearly 100% in grade V cases, and this system permits evaluation of the effectiveness of new drugs and treatments. Patients with tetanus pass through three distinct phases, the "build up" or
"Don't tell me on a Friday".
Authors: T Richards
Journal: BMJ (1986)

The author identifies himself as a homosexual with antibodies to human T cell lymphotropic virus III (HTLV-III). He describes his reactions to learning that he might develop acquired immunodeficiency syndrome (AIDS) and to the counseling sessions which helped him cope. While he does not advocate compulsory testing of homosexuals for antibody to HTLV-III, he recommends voluntary participation provided that counseling is immediately available for those who test positive.
Evidence for genetic restriction in the suppression of erythropoiesis by a unique subset of T lymphocytes in man.
Authors: J M Lipton, L M Nadler, G P Canellos, M Kudisch, C S Reiss, D G Nathan
Journal: Journal of Clinical Investigation (1983)

The suppression of erythropoiesis by lymphocytes from patients with a T cell lymphoproliferative syndrome and pure erythrocyte aplasia has been previously demonstrated. To study the nature of the suppressor cell and possible genetic restriction of this suppression, we investigated a patient with severe anemia, splenomegaly, lymphocytosis, and erythroid aplasia. A 3-mo course of low-dose daily oral cyclophosphamide achieved a complete remission for over 12 mo. The surface phenotype of his lymphocytes was analyzed by means of antibodies to lineage, differentiation, and activation-specific surface antigens. The cells expressed mature T cell antigens T3, T8, and T11, while lacking T1. Immature T cell, B cell, and the monocyte-specific antigen Mo2 were absent, while Mo1, a monocyte-associated antigen not normally expressed on T cells, was present. T10 and Ia expressed as activation antigens were also present. The cells, cryopreserved at diagnosis, were thawed and co-cultured in plasma clot with patient remission marrow samples at T cell/bone marrow ratios of 1:1 and 2:1. There was nearly 90% suppression of erythroid colony-forming unit expression and 60% suppression of erythroid burst-forming unit expression at 2:1 T cell to bone marrow ratios and somewhat less suppression at 1:1. Granulocyte/macrophage progenitor expression was unaffected. Erythroid progenitor differentiation in the marrows of two HLA identical siblings was similarly suppressed. The cells were co-cultured with the marrows of nine nonrelated donors to investigate the potential genetic restriction of this suppression. Colony suppression equal to that observed in the marrow of the patient and his siblings was found in studies of two partially HLA identical individuals. No suppression was detected in marrow co-cultures of two entirely HLA dissimilar individuals. These results show that suppression of erythropoiesis by a unique subset of T8, Mo1, Ia-positive lymphocytes isolated from a patient with lymphocytosis and erythrocyte aplasia is genetically restricted.
HLA-DM Is Localized to Conventional and Unconventional MHC Class II–Containing Endocytic Compartments
Authors: Philippe Pierre, Lisa K Denzin, Craig Hammond, James R Drake, Sebastian Amigorena, Peter Cresswell, Ira Mellman
Journal: Immunity (1996)

HLA-DM molecules remove invariant (Ii) chain peptides from newly synthesized MHC class II complexes. Their localization may thus delineate compartments, e.g., MIIC, specialized for loading peptides onto class II molecules. In murine A20 B cells, however, DM is not restricted to specialized endosomal class II-containing vesicles (CIIV). Although DM was found in CIIV, it was also found throughout the endocytic pathway, principally in lysosomes devoid of class II molecules. In human lymphoblasts, HLA-DM was found in structures indistinguishable from late endosomes or lysosomes, although in these cells the lysosomes contained MHC class II molecules. Thus, the distribution of HLA-DM does not necessarily identify specialized class II compartments. Many "MIIC" may represent conventional lysosomes that accumulate MHC class II and HLA-DM in a number of cell types.
FcγRI (CD64) Contributes Substantially to Severity of Arthritis, Hypersensitivity Responses, and Protection from Bacterial Infection
Authors: A Ioan-Facsinay, S.J de Kimpe, S.M.M Hellwig, P.L van Lent, F.M.A Hofhuis, H.H van Ojik, C Sedlik, S.A da Silveira, J Gerber, Y.F de Jong, R Roozendaal, L.A Aarden, W.B van den Berg, T Saito, D Mosser, S Amigorena, S Izui, G-J.B van Ommen, M van Vugt, J.G.J van de Winkel, J.S Verbeek
Journal: Immunity (2002)
Nurse delivered endoscopy
Authors: C. Norton, A. Grieve, M. Vance
Journal: BMJ (2009)

Is as clinically effective as that delivered by doctors, but may cost more

The multicentre randomised controlled trial by Williams and colleagues (doi:10.1136/bmj.b231) compares the clinical effectiveness of doctors and nurses undertaking upper and lower gastrointestinal endoscopy. The study by Richardson and colleagues (doi:10.1136/bmj.b270) assesses the cost effectiveness of this approach. The studies found no significant difference in clinical outcomes, although doctors seemed to be more cost effective.1 2

Nurse led services in the United Kingdom have been encouraged by government policy, a shortage of doctors, a willingness of nurses to adopt expanded roles, and a salaried NHS workforce where professionals are not in competition for income from patients. Evaluations of substituting doctors with nurses have consistently found little difference in performance. In primary care, no appreciable differences between doctors and nurses have been found in health outcomes for patients, process of care, or use and cost of resources, whereas nurse led care has resulted in higher patient satisfaction.3 These findings have been reported across a wide range of diseases. Nurse endoscopists are firmly established in the UK, with 350 nurses currently in practice.

Endoscopy is a diagnostic test so the results might …
Cardiac resynchronization therapy in patients with permanent atrial fibrillation. Is it mandatory to ablate the atrioventricular junction to obtain a good response?
Authors: José María Tolosana, Ana Martín Arnau, Antonio Hernández Madrid, Alfonso Macias, Ignacio Fernández Lozano, Joaquín Osca, Aurelio Quesada, Jorge Toquero, Roberto Matia Francés, Ignacio García Bolao, Antonio Berruezo, Marta Sitges, Mónica Gimenez Alcalá, Josep Brugada, Lluís Mont
Journal: European Journal of Heart Failure (2012)
Optimization of PCR-based minimal residual disease diagnostics for childhood acute lymphoblastic leukemia in a multi-center setting
Authors: V H J van der Velden, E R Panzer-Grümayer, G Cazzaniga, T Flohr, R Sutton, A Schrauder, G Basso, M Schrappe, J M Wijkhuijs, M Konrad, C R Bartram, G Masera, A Biondi, J J M van Dongen
Journal: Leukemia (2007)
Increased respiratory system resistance and bronchial smooth muscle hypertrophy in children with acute postoperative pulmonary hypertension.
Authors: M B Schindler, D J Bohn, A C Bryan, E Cutz, M Rabinovitch
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Following surgery for congenital heart disease, there is often an increased reactivity of the pulmonary vasculature to stimuli, resulting in rapid increases in pulmonary artery pressure and a clinical impression of stiff lungs. Lung mechanics were measured in 30 children, mean age 6.7 +/- 4.1 mo, who were ventilated and had pulmonary artery pressure monitoring following surgery for congenital heart disease. A group of 15 patients developed postoperative pulmonary hypertension. In these patients, respiratory system resistance was 43% higher (p = 0.001) and compliance 11% lower (p = 0.004) during acute pulmonary hypertension compared with baseline pulmonary artery pressure. No changes in resistance or compliance were seen in the 15 patients who did not develop pulmonary hypertension. The changes in lung mechanics interfered with mechanical ventilation, resulting in a 9.4% rise in PaCO2 during pulmonary hypertension. The bronchial smooth muscle was found to be increased by 68%, and the vascular smooth muscle was more than twice normal in lung biopsies from 9 pulmonary hypertension patients compared with 6 age-matched postmortem controls patients who had no cardiac or pulmonary disease. The bombesin-immunoreactive pulmonary neuroendocrine cells (PNEC) were also increased in the pulmonary hypertension patients. These findings suggest a coconstriction and cohypertrophy of bronchial and vascular smooth muscle during pulmonary hypertension. Mediators, such as bombesin, endothelin-1, and serotonin, are known to be produced by PNEC and may be involved in the observed vasoconstriction, increased respiratory system resistance, and smooth muscle hypertrophy.
Carbamazepine-Induced Dystonia
Authors: Daniel Jacome
Journal: JAMA (1979)

To the Editor.—  Chadwick et al1reviewed the topic of anticonvulsant-induced dyskinesia in 1976. They described limb chorea, orofacial dyskinesia, and dystonia occurring in association with phenytoin administration. They only found asterixis secondary to carbamazepine toxic reaction in one female patient who had a cerebellar syndrome. Carbamazepine, in addition to its anticonvulsant action, has been reported as helpful in treating paroxysmal kinesigenic choreoathetosis2and refractory inherited and acquired dystonia (Geller et al, 229:1755, 1974).  During the past year, I had the opportunity of observing four patients admitted to the Epilepsy Unit of the University of Minnesota because of intractable seizures. Three of the patients showed development of transient dystonia of the axial muscles, and one, of the hands, after carbamazepine was added as an anticonvulsant therapy in three of the patients and in the other, after the previous dose of carbamazepine was doubled.  In all of the patients