tbuckley/cabot-search huggingface dataset:
Germinal cell mutagenesis in specially designed maize genotypes.
Authors: M J Plewa, E D Wagner
Journal: Environmental Health Perspectives (1981)

We have used three inbreds of Zea mays in our in situ and laboratory studies in environmental mutagenesis. Inbred W22 plants homozygous for wx-C were used in a study to detect the possible mutagenic properties of 32 pesticides or combination of pesticides under modern agricultural conditions. The large numbers of pollen grains analyzed and the ease in detecting mutant pollen grains enabled us to treat the experimental plants with field recommended rates of pesticides. In a current study we are evaluating the possible mutagenicity of Chicago municipal sewage sludge. We are measuring the frequency of mutant pollen grains in inbred M14 at both the wx-C and wx-90 heteroalleles. These plants were exposed to various concentrations of municipal sewage sludge under field conditions. We have inbred Early-Early Synthetic for five generations and tested this inbred with known mutagens. Early-Early Synthetic is a rapidly maturing inbred growing from kernel to anthesis in approximately 4 weeks and attaining a height of approximately 50 cm. Plants of this inbred have been chronically treated with ethylmethanesulfonate (EMS) or maleic hydrazide (MH) under laboratory conditions and forward mutation at the wx locus was measured in the pollen grains. EMS and MH were mutagenic at concentrations of 1 microM and 10 nM, respectively. The concentrations of EMS and MH were calibrated in Early-Early Synthetic to a linear increase in the frequency of forward mutant pollen grains. The construction of a maize monitor for environmental mutagens is currently in progress. This assay will measure forward or reverse mutation at the wx locus in pollen grains, point mutation in somatic cells and will incorporate a cytogenetic endpoint in root-tip cells.
Occupational all_ergic contact urticaria to yucca (<i>Yucca aloifolia</i>), weeping fig (<i>Ficus benjamina</i>), and spathe flower (<i>Spathiphyllum wall_isii</i>)
Authors: L. Kanerva, T. Estlander, L. Petman, S. Mäkinen‐Kiljunen
Journal: Allergy (2001)

Background: Occupational contact urticaria (CU) from plants is often reported, but it is less often attributed to decorative houseplants. We present an atopic gardener and caretaker of plants who developed CU when occupationall_y exposed to weeping fig, spathe flower, and yucca. Methods: Sensitization was evaluated by skin prick tests (SPT) and analyses for IgE antibodies. Results: SPT were positive to all_ three plants, and IgE antibodies were found to weeping fig and spathe flower. SPT were also performed with several decorative houseplants in more than 600 patients. Positive SPT was found to weeping fig (12%), African milk tree (8.3%), yucca (5.8%), Chinese rose (4.7%), massangana (4.6%), bird's nest fern (3.2%), and spathe flower (3.2%). Conclusions: Our study indicates that SPT and tests for IgE antibody are useful in detecting occupational CU caused by houseplants.
Abstract 4654: Genomic and proteomic profiling of signaling pathways targeted by a multi-kinase inhibitor, sorafenib.
Authors: Mari Masuda, Kazufumi Honda, Tesshi Yamada
Journal: Cancer Research (2013)

Abstract Background: Deregulation of intracellular signaling by various genetic alterations is a hallmark of cancer. Therapeutics targeting such activated signaling pathways have achieved significant progress, but the precise pathway(s) targeted by sorafenib has remained unclear. Methods: Using high-density reverse-phase protein arrays, we profiled the phosphorylation status of 180 signaling molecules in the 120 pathways registered on the NCI-Nature curated database in 23 hepatocellular carcinoma (HCC) cell lines showing different sensitivities to sorafenib. We also sequenced the entire coding regions of 518 protein kinase genes in 20 overlapping HCC cell lines. Results: We identified 25 non-synomymous alterations in the 4 mTOR and MAPK pathway genes (RPS6KA1, RPS6KA6, RPS6KB2, and BRAF) in HCC cell lines 1 to 11. We also found that the levels of phosphorylated S6 ribosomal protein and c-Raf were associated with the sensitivity of the HCC cell lines to sorafenib. A mTOR inhibitor, AZD8055, exerted growth-inhibitory activity against sorafenib-resistant HCC cell lines. Discussion: Although a recent phase III clinical trial has demonstrated the effectiveness of sorafenib in patients with unresectable HCC, only a small proportion of the patients achieved the anticipated therapeutic benefits. The present results indicate cross-talk between the mTOR and MAPK signaling pathways in sorafenib-resistant HCC cell lines. Use of a combination of mTOR and MAPK inhibitors may improve the efficacy of molecular targeting therapy against HCC. Citation Format: Mari Masuda, Kazufumi Honda, Tesshi Yamada. Genomic and proteomic profiling of signaling pathways targeted by a multi-kinase inhibitor, sorafenib. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4654. doi:10.1158/1538-7445.AM2013-4654
Ban on tobacco advertising moves a step closer
Authors: Z. Kmietowicz
Journal: BMJ (2002)

Tobacco advertising could become illegal in the United Kingdom as early as this summer, after the government agreed to back legislation pushed through the House of Lords last week.

The proposed legislation will ban press, billboard, and internet advertising of tobacco products and end the promotion of smoking through free distribution of tobacco products, coupons, and mailshots. Also, new controls will restrict how tobacco products are promoted and displayed in shops, and sponsorship by tobacco companies of sporting and other events will be ended. Only formula one motor racing, which secured a …
Use of <i>in Vitro</i> HTS-Derived Concentration–Response Data as Biological Descriptors Improves the Accuracy of QSAR Models of <i>in Vivo</i> Toxicity
Authors: Alexander Sedykh, Hao Zhu, Hao Tang, Liying Zhang, Ann Richard, Ivan Rusyn, Alexander Tropsha
Journal: Environmental Health Perspectives (2010)

Quantitative high-throughput screening (qHTS) assays are increasingly being used to inform chemical hazard identification. Hundreds of chemicals have been tested in dozens of cell lines across extensive concentration ranges by the National Toxicology Program in collaboration with the National Institutes of Health Chemical Genomics Center.Our goal was to test a hypothesis that dose-response data points of the qHTS assays can serve as biological descriptors of assayed chemicals and, when combined with conventional chemical descriptors, improve the accuracy of quantitative structure-activity relationship (QSAR) models applied to prediction of in vivo toxicity end points.We obtained cell viability qHTS concentration-response data for 1,408 substances assayed in 13 cell lines from PubChem; for a subset of these compounds, rodent acute toxicity half-maximal lethal dose (LD50) data were also available. We used the k nearest neighbor classification and random forest QSAR methods to model LD50 data using chemical descriptors either alone (conventional models) or combined with biological descriptors derived from the concentration-response qHTS data (hybrid models). Critical to our approach was the use of a novel noise-filtering algorithm to treat qHTS data.Both the external classification accuracy and coverage (i.e., fraction of compounds in the external set that fall within the applicability domain) of the hybrid QSAR models were superior to conventional models.Concentration-response qHTS data may serve as informative biological descriptors of molecules that, when combined with conventional chemical descriptors, may considerably improve the accuracy and utility of computational approaches for predicting in vivo animal toxicity end points.
miR-122 regulates hepatic lipid metabolism and tumor suppression
Authors: Jessica Wen, Joshua R. Friedman
Journal: Journal of Clinical Investigation (2012)

In this issue of JCI, two independent groups describe the effects of germline and liver-specific deletion of Mir122a, the predominant liver miRNA. Their findings reveal a critical role for miR-122 in fat and cholesterol metabolism but suggest that other metabolic actions of the liver are independent of miR-122. Knockout mice also displayed hepatic inflammation, fibrosis, and a high incidence of hepatocellular carcinoma, suggesting that miR-122 has a tumor suppressor role in hepatocytes.
The Cost of Hospitalization for Firearm Injuries
Authors: Michael J. Martin
Journal: JAMA (1988)

The hospital records for all patients (N = 131) admitted during 1984 to San Francisco General Hospital because of firearm injuries were studied to determine the hospital costs and sources of payment for these injuries. Because San Francisco General Hospital is the regional trauma center, the sample is population based, representing all firearm victims hospitalized in San Francisco during 1984. Only hospital costs (excluding professional fees) for the first hospitalization were studied. The total costs for the year were $905 809, an average cost per patient of $6915. Public sources paid 85.6% of this cost, while private sources paid only 14.4%. These findings have important implications for legislators considering bills to restrict the availability of firearms. These legislators must be aware that the issue is not simply one of individual rights, since taxpayers pay most of the costs (estimated to be more than $1 billion per year for the United States) associated with firearm injuries. (<i>JAMA</i>1988;260:3048-3050)
Abstract 5115: The role of Cdc42-interacting protein 4 (CIP4) in osteosarcoma tumorigenesis
Authors: Nadezhda V. Koshkina, Ge Yang, Eugenie S. Kleinerman
Journal: Cancer Research (2010)

Abstract Osteosarcoma (OS) remains a devastating disease and requires better understanding of its biology for the development of novel therapeutic approaches. Tumor growth and metastases formation require an ability of cells to have a flexible cytoskeletal organization. Cdc42-interacting protein 4 (CIP4) is one of the scaffolding cytoskeleton-regulatory protein, whose role in tumors remains unknown. In the current study we investigated the role of CIP4 in OS tumorigenesis. We transfected highly aggressive mouse OS cells, DLM8 with the plasmid that downregulated expression of CIP4 protein (DLM8/shCIP4). We found that the growth rate of DLM8/shCIP4 clones was reduced by 30% when compared with non-transfected DLM8 cells or DLM8 cells transfected with control plasmid (DLM8/sh). When DLM8/shCIP4 cells were injected into mice subcutaneously they formed tumors that grew significantly slower than DLM8 or DLM8/sh control cells (p&amp;lt;0.02). We also found that inhibition of CIP4 expression in DLM8 cells decreased their motility and invasion properties in vitro, indicating on its ability to impair metastases growth. Fluorescent immunostaining for actin in DLM8/shCIP4 cells revealed lower perinuclear actin stress filaments formation and lower actin bridge to the lipid bilayer of the lipid cell membrane when compared with wild-type DLM8 or DLM8/sh. We also observed that downregulation of CIP4 changed cell membrane morphology in DLM8 cells - they had less protrusions and smoother cell surface than control cells. All these findings indicate that CIP4 may also play a role in metastatic behavior of OS cells and needs further investigation. 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 5115.
41 Differences in treatment outcome to antiviral therapy based on genotype and viral load in hepatitis C genotypes 2 and 3 in the Win-R trial
Authors: R.S. Brown, I.M. Jacobson, N. Afdhal, B. Freilich, M.P. Pauley, F. Regenstein, S. Flamm, P. Kwo, L. Griffel, C.A. Brass
Journal: Journal of Hepatology (2006)
A genome–wide search for human non–insulin–dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2
Authors: C.L. Hanis, E. Boerwinkle, R. Chakraborty, D.L. Ellsworth, P. Concannon, B. Stirling, V.A. Morrison, B. Wapelhorst, R.S. Spielman, K.J. Gogolin-Ewens, J.M. Shephard, S.R. Williams, N. Risch, D. Hinds, N. Iwasaki, M. Ogata, Y. Omori, C. Petzold, H. Rietzsch, H.-E. Schröder, J. Schulze, N.J. Cox, S. Menzel, V.V. Boriraj, X. Chen, L.R. Lim, T. Lindner, L.E. Mereu, Y.-Q. Wang, K. Xiang, K. Yamagata, Y. Yang, G.I. Bell
Journal: Nature Genetics (1996)
Induction of interleukin 2 receptor beta chain expression by self-recognition in the thymus.
Authors: T Hanke, R Mitnacht, R Boyd, T Hünig
Journal: The Journal of Experimental Medicine (1994)

1-2% of adult mouse thymocytes express the T cell receptor alpha/beta (TCR-alpha/beta) together with the interleukin (IL) 2R beta (p70), but not the alpha (p 55) chain. We show that the previously described alpha/beta-TCR +CD4-8- and the partially overlapping Ly6C+ thymocytes are contained within this subset. Most IL-2R beta+ alpha/beta-TCR+ cells have a mature and activated (heat stable antigen [HSA]-, thymic shared antigen 1 [TSA-1]-, CD44high, CD69+) phenotype. Overrepresentation of V beta 8.2 in both CD4-8- and CD4 and/or CD8+ IL-2R beta+ thymocytes suggests that IL-2R beta expression is induced by a TCR-mediated activation event. In mice transgenic for an H-2Kb-specific TCR, IL-2R beta+ cells were abundant under conditions of mainstream negative selection, i.e., in the presence of Kb, but absent under conditions of mainstream positive selection or in a nonselecting environment. Together, these results show that in addition to clonal deletion, self-recognition by immature thymocytes leads to phenotypic maturation of a small subset of thymocytes expressing IL-2R beta. IL-2-deficient mice contain normal numbers of IL-2R beta+ alpha/beta-TCR+ thymocytes, indicating that like mainstream T cell development, this minor pathway of positive selection does not depend on IL-2. However, in the absence of IL-2, the CD4/CD8 subset composition of IL-2R beta+ thymocytes is skewed towards CD4-8+, mostly at the expense of CD4-8-. A possible relevance of this finding for the development of the immune pathology of IL-2-deficient mice is discussed.
High Hopes—and Many Morals-Reply
Authors: Abigail Zuger
Journal: JAMA (1990)

<h3>In Reply. —</h3> I am grateful to Dr Kitchens and Dr Prager for, between them, illustrating so well the point I wanted Jerry Silver's story to make. It is a story with many possible morals. To some readers, the best interests of both Jerry and his physician will, in the final analysis, have been well served by New York State's do not resuscitate laws. To others, Jerry and his physician will stand as just two more casualties of the legislated ethical vogues of 20th-century medicine. Neither reading of this story is necessarily right or wrong. In this arena all of us, physicians no less than patients, have our own prejudices and preferences, our own definitions of a "good" life and a "good" death, our own personal calculus of pain, indignity, and hope. Thus, legislation that seeks to define all these intangibles for us may not, ultimately, serve each one of
Fiber types and myosin types in human atrial and ventricular myocardium. An anatomical description.
Authors: P Bouvagnet, J Leger, F Pons, C Dechesne, J J Leger
Journal: Circulation Research (1984)

Hybridomas were prepared from mice immunized with myosin from the enlarged left ventricle of a 53-year-old female with an obstructive cardiomyopathy. The specificity of 15 monoclonal antibodies to myosin heavy chains was assessed by the reactivity of muscle extracts and of chymotryptic myosin fragments of different sizes with these antibodies, as determined by the immune replicate technique; some of the monoclonal antibodies cross-reacted only with the ventricular V3-type myosin from hypothyroid rats, whereas the other antibodies cross-reacted both with the latter and with the ventricular V1-type myosins from normal young rats. Immunological heterogeneity of the fibers from human atrial muscles and from human ventricular muscles was detected by some of the antimyosin antibodies by means of indirect immunofluorescence. Histochemical fiber heterogeneity was also detected by adenosine triphosphatase staining of the same tissues. Because of the close correspondence observed between the immunological and histochemical responses of atrial fibers, it has been postulated that at least two distinct types of myosin exist in the human atrium, each myosin form being histochemically related to either alpha- or beta-like ventricular myosin heavy chains. In contrast, there was no direct correspondence between the two experimental approaches in human ventricles, and it is postulated that at least three distinct types of myosin exist within the human ventricles, one V1-type myosin, presumably corresponding to the very rare fibers with an alkaline-stable adenosine triphosphatase activity, and two other V3-type myosins corresponding to immunologically different fibers, each having an alkaline-labile adenosine triphosphatase activity. Monoclonal antibodies that can distinguish among the different myosin variants were further used to provide the basis for an anatomical description of fiber types and myosin types within the human atrial and ventricular myocardium in the whole hearts of two young boys who died sudden violent deaths. Small zones of myosin variation were seen to be scattered, but probably not randomly distributed, within large areas of myocardium in which the cellular distribution of myosin was constant; the large areas had one myosin distribution specific for each cardiac cavity. No clear-cut conclusions can yet be made concerning the physiological role of the regional variations observed in the distribution of the different molecular forms of myosin.
Megakaryocytic blast crisis as first presentation of chronic myeloid leukemia
Authors: L. Campiotti, A.M. Grandi, M.G. Biotti, C. Ultori, F. Solbiati, R. Codari, A. Venco
Journal: American Journal of Hematology (2006)

Abstract We describe an extremely rare case of megakaryocytic blast crisis as first presentation of chronic myeloid leukemia. The patient had a very high platelet count and developed an ischemic stroke with seizures. She was treated with hydroxyurea, platelet apheresis, ARA‐C, and idarubicin in order to obtain a prompt reduction of thrombocytosis and then with imatinib 600 mg/die PO. The therapy induced a complete hematological remission with a resolution of neurological signs within 4 weeks. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.
ANOMALIES IN OPHTHALMIC PRACTICE.
Authors: A. C. CORR
Journal: JAMA (1895)

In presenting this paper I am not proposing to present anything new, but merely to bring in a few topics that, to say the least, are out of the ordinary way in ophthalmic practice, and therefore are entitled to be designated as anomalies. <h3>Case 1.</h3> —<i>Congenital Interstitial Opaque Infiltration of the Cornea, not Syphilitic nor Cicatricial</i>. Dec. 1, 1893, was presented for treatment Anne H., a two months old, healthy, well-developed child. No appearance of disease, past or present, except that both cornea were nearly entirely opaque. At once I asked the mother when the baby had sore eyes, to which she replied: "Its eyes have not been sore." "When did you notice this condition of its eyes?" She replied: " When it was ten days old." " Has there been any yellow or gummy discharge from the child's eyes?" She replied: " There has not." "Had you any leucorrhea or whites
Infliximab in refractory spondyloarthropathies: a multicentre 38 week open study
Authors: E Collantes-Estevez
Journal: Annals of the Rheumatic Diseases (2003)

Some patients (20–30%) with spondyloarthropathies (SpA) have a persistent and disabling disease,1 for which a limited number of alternative therapeutic approaches exist.2 The successful results from randomised, double blind, placebo controlled trials in ankylosing spondylitis (AS) and SpA which have been published 3–5 suggest that treatment with infliximab is highly effective. However, in most of these studies, criteria for the selection of patients are based on active disease, but not on refractory disease (failure of response to previous drugs, including non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying antirheumatic drugs). Therefore, we aimed at assessing the effectiveness and safety of infliximab in patients with active and refractory SpA.

The study was an open label, multicentre, 38 week prospective study in 40 patients with active and refractory SpA: 34 patients had AS, 3 had arthritis with related inflammatory bowel disease, and 3 undifferentiated SpA. Infliximab (5 mg/kg) was given at weeks 0, …
At the Roots of Christian Bioethics: Critical Essays on the Thought of H. Tristram Engelhardt, Jr.
Authors: Jeffrey P. Bishop
Journal: JAMA (2010)

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Therapy for Systemic Lupus Erythematosus
Authors: Michael D. Lockshin
Journal: New England Journal of Medicine (1991)

THE history of clinical trials of therapy for systemic lupus erythematosus contains many tales of enthusiastically endorsed treatments that have proved with time to have limited value. Definitive controlled trials, common in evaluating the treatment of less heterogeneous diseases, are particularly elusive in the literature on the disease.In 1991, the accepted treatment for systemic lupus erythematosus is largely empirical, selected on the basis of specific symptoms. Serologic abnormalities and minor cytopenias unaccompanied by symptoms need no treatment. Rash and (according to some authorities) mild systemic symptoms are usually treated with antimalarial drugs. This latter practice is the basis of . . .
Starch acetate microparticles for drug delivery into retinal pigment epithelium—in vitro study
Authors: Laura Tuovinen, Eija Ruhanen, Tarja Kinnarinen, Seppo Rönkkö, Jukka Pelkonen, Arto Urtti, Soili Peltonen, Kristiina Järvinen
Journal: Journal of Controlled Release (2004)