tbuckley/cabot-search huggingface dataset:
Abstract 5348: Detection of herpes simplex viruses in thyroid cancer
Authors: Vasyl V. Vasko, Kirk Jensen, Aneeta Patel, Andrew Bauer
Journal: Cancer Research (2010)

Abstract Introduction: There is limited information about the role of herpesviridae viruses in thyroid cancer. Materials and Methods: Thyroid tissues from 109 patients with benign (44) and malignant (65) lesions were analyzed for HSV1 and HSV2 DNA. Confirmatory studies included direct sequencing, analysis of viral gene expression and activation of viral-inducible signaling pathways. Expression of viral entry receptor Nectin-1 was examined in human samples and in cancer cell lines. In vitro experiments were performed to explore the molecular mechanisms underlying thyroid cancer cell susceptibility to HSV. Results: HSV was detected in 43/109 (39.4%) of examined samples. HSV positive tumors were characterized by interferon-beta expression, nuclear NFkB expression and Akt activation. Lymphocytes infiltration and oncocytic cellular features were common in HSV positive tumors. HSV1 was detected with same frequency in benign and malignant thyroid tumors. HSV2 was significantly associated with papillary thyroid cancer and presence of lymph nodes metastases. Nectin-1 expression was increased in thyroid tumors compared to normal thyroid tissue and further increased in papillary thyroid cancer. The level of Nectin-1 expression in cancer cell lines correlated with their susceptibility to HSV. Inhibition of PI3K/AKT or MAPK/ERK signaling did not affect the level of Nectin-1 expression but decreased thyroid cancer cell susceptibility to HSV. Thyroid cancer cell with epithelial-like morphology underwent epithelial to mesenchymal transition after chronic exposure to TNF. Induction of epithelial to mesenchymal transition was associated with increased thyroid cancer cell susceptibility to HSV. Conclusion. HSV was detected in human thyroid tumors and HSV2 was associated with metastatic thyroid cancers. In vivo and vitro data showed that during tumor progression thyroid cells acquire increased susceptibility to HSV due to 1) increased expression of viral entry mediator Nectin-1; 2) activation of mitogenic signaling and 3) induction of EMT in metastatic cancers. 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 5348.
Once-weekly trelagliptin versus daily alogliptin in Japanese patients with type 2 diabetes: a randomised, double-blind, phase 3, non-inferiority study
Authors: Nobuya Inagaki, Hitoshi Onouchi, Hideaki Maezawa, Shingo Kuroda, Kohei Kaku
Journal: The Lancet Diabetes & Endocrinology (2015)
Intensity-Modulated Radiotherapy After Extrapleural Pneumonectomy in the Combined-Modality Treatment of Malignant Pleural Mesothelioma
Authors: Alexander Chi, Zhongxing Liao, Nam P. Nguyen, Carol Howe, Daniel Gomez, Si Young Jang, Ritsuko Komaki
Journal: Journal of Thoracic Oncology (2011)
Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex
Authors: Jianghui Hou, Aparna Renigunta, Martin Konrad, Antonio S. Gomes, Eveline E. Schneeberger, David L. Paul, Siegfried Waldegger, Daniel A. Goodenough
Journal: Journal of Clinical Investigation (2008)

Tight junctions (TJs) play a key role in mediating paracellular ion reabsorption in the kidney. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an inherited disorder caused by mutations in the genes encoding the TJ proteins claudin-16 (CLDN16) and CLDN19; however, the mechanisms underlying the roles of these claudins in mediating paracellular ion reabsorption in the kidney are not understood. Here we showed that in pig kidney epithelial cells, CLDN19 functioned as a Cl– blocker, whereas CLDN16 functioned as a Na+ channel. Mutant forms of CLDN19 that are associated with FHHNC were unable to block Cl– permeation. Coexpression of CLDN16 and CLDN19 generated cation selectivity of the TJ in a synergistic manner, and CLDN16 and CLDN19 were observed to interact using several criteria. In addition, disruption of this interaction by introduction of FHHNC-causing mutant forms of either CLDN16 or CLDN19 abolished their synergistic effect. Our data show that CLDN16 interacts with CLDN19 and that their association confers a TJ with cation selectivity, suggesting a mechanism for the role of mutant forms of CLDN16 and CLDN19 in the development of FHHNC.
Abstract 1763: Frequency of homologous recombination repair defects across breast cancer subtypes.
Authors: Kirsten M. Timms, Victor Abkevich, Chris Neff, Brian Morris, Jennifer Potter, Thanh V. Tran, Jian Chen, Zaina Sangale, Eliso Tikishvili, Andrey Zharkikh, Michael Perry, Alexander Gutin, Jerry Lanchbury
Journal: Cancer Research (2013)

Abstract Introduction: Defects in homologous recombination (HR) repair have potential therapeutic relevance, and current clinical studies are focused on examining the efficacy of agents that exploit HR deficiency in triple negative breast cancer. A homologous recombination deficiency (HRD) score based on whole genome tumor LOH profiles has been developed that is highly correlated with defects in BRCA1/2, and other HR pathway genes, in ovarian cancer(1), and which predicts response to platinum-based neoadjuvant therapy in triple negative breast cancer(2). This study examines the frequency of BRCA1/2 defects and elevated HRD score across breast cancer subtypes as defined by IHC hormone receptor status. Methods: A targeted custom hybridization panel was developed targeting BRCA1, BRCA2, and 50,000 selected SNPs across the entire human genome. This panel, in combination with sequencing on the Illumina HiSeq, was used to analyze approximately 50 randomly ascertained tumors from each of 4 breast cancer subtypes (triple negative, ER+/Her2-, ER-/Her2+, ER+/Her2+) for BRCA1/2 somatic and germline mutations, and SNP allele frequencies. HRD scores were calculated using LOH profiles reconstructed from the SNP analysis. A BRCA1 promoter methylation assay was also performed on all samples. Results: BRCA1/2 somatic and germline mutations were detected in all breast cancer subtypes. BRCA1/2 mutations were observed most frequently in triple negative and ER+/Her2+ tumors. BRCA1 promoter methylation was confined almost exclusively to triple negative tumors. Association between elevated HRD score and BRCA defects was observed regardless of tumor type, and BRCA1/2 intact tumors with elevated HRD scores were observed in all breast cancer subtypes. Conclusions: Elevated HRD score is significantly associated with BRCA1/2 defects in breast cancer. BRCA1/2 defects and elevated HRD scores were observed in all subtypes of breast cancer, suggesting the presence of HR defects in genes other than BRCA1/2 are present in all breast cancer subtypes. HRD score could potentially be used to facilitate the expansion of platinum or PARP inhibitor therapy beyond triple negative breast cancer into other subtypes. Citation Format: Kirsten M. Timms, Victor Abkevich, Chris Neff, Brian Morris, Jennifer Potter, Thanh V. Tran, Jian Chen, Zaina Sangale, Eliso Tikishvili, Andrey Zharkikh, Michael Perry, Alexander Gutin, Jerry Lanchbury. Frequency of homologous recombination repair defects across breast cancer subtypes. [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 1763. doi:10.1158/1538-7445.AM2013-1763
Impact of the Human Immunodeficiency Virus Epidemic on Mortality in Women of Reproductive Age, United States
Authors: Susan Y. Chu
Journal: JAMA (1990)

To assess the effect of the human immunodeficiency virus (HIV) on mortality in US women 15 to 44 years of age and to identify associated causes of death, we examined final (1980 through 1987) and provisional (1988) national mortality statistics. Between 1985 and 1988, the death rate for HIV/acquired immunodeficiency syndrome (AIDS) quadrupled (0.6 per 100 000 to 2.5 per 100 000), and by 1987, HIV/AIDS had become one of the 10 leading causes of death. In 1988, the death rate for black women (10.3 per 100 000) was nine times the rate for white women (1.2 per 100 000). The majority of deaths in both black and white women occurred in women 25 to 34 years of age, for whom HIV-related deaths accounted for 11% and 3% of all deaths in 1988, respectively. Among 1157 death certificates that included any mention of HIV/AIDS in 1987, other leading diagnoses included drug abuse (27%), Pneumocystis carinii pneumonia (20%), other pneumonias (14%), septicemia (10%), other infections not in the AIDS surveillance definition (7%), nephritis (6%), liver diseases (4%), and anemias (4%). If current mortality trends continue, HIV/AIDS can be expected to become one of the five leading causes of death by 1991 in women of reproductive age. Because women infected with HIV are the major source of infection for infants, these trends in AIDS mortality in women forecast the impact of HIV on mortality in children as well. (<i>JAMA</i>. 1990;264:225-229)
Urea Therapy in Sickle-Cell Anemia
Authors: Robert B. Scott
Journal: New England Journal of Medicine (1971)

Since the first patient was treated with urea for sickle crisis over a year ago, controlled scientific data on its efficacy have been meager as compared to the information available from repetitive preliminary publications, oral presentations, news-media reports and even a book. No doubt, all this publicity has the salutary effect of focusing attention on the subject of sickle-cell anemia, the neglect of which has recently been pointed out.1 The questions for physicians to resolve still remain. Is urea treatment truly effective? Does its efficacy justify the hazards involved? Is it useful in all pain crises or in specific instances? . . .
Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations
Authors: Martin C. Müller, Jorge E. Cortes, Dong-Wook Kim, Brian J. Druker, Philipp Erben, Ricardo Pasquini, Susan Branford, Timothy P. Hughes, Jerald P. Radich, Lynn Ploughman, Jaydip Mukhopadhyay, Andreas Hochhaus
Journal: Blood (2009)
Expression of human bone-related proteins in the hematopoietic microenvironment.
Authors: M W Long, J L Williams, K G Mann
Journal: Journal of Clinical Investigation (1990)

Given the intimate relationship between bone and bone marrow, we hypothesized that the human bone marrow may function as a source (or reservoir) of bone-forming progenitor cells. We observed a population of cells within the bone marrow which produce bone-specific or bone-related proteins. The production of these proteins was developmentally regulated in human long-term bone marrow cell cultures; the bone protein-producing cells (BPPC) are observed under serum-free, short-term culture conditions, respond to bone-related and not hematopoietic growth factors, and are derived from a population of low-density, nonadherent, My10-negative (or low My10 density), marrow cells (My10 is an antigen found on most hematopoietic progenitor cells). Cultivation of marrow-derived BPPC in secondary, serum-containing cultures results in their differentiation into osteoblastlike cells. At this stage of development, BPPC produce an extracellular matrix which incorporates both bone-related proteins and radiolabeled calcium. Human bone marrow BPPC thus represent a newly described cell phenotype important to both bone and hematopoietic cell biology.
Streptozotocin-induced non-insulin-dependent diabetes protects the heart from infarction.
Authors: Y Liu, J D Thornton, M V Cohen, J M Downey, S W Schaffer
Journal: Circulation (1993)

BACKGROUND The vulnerability of the myocardium of a diabetic animal to an ischemic insult is controversial. To address this issue, streptozotocin-induced non-insulin-dependent diabetes (NIDD) was induced in rats, and the effects of regional myocardial ischemia were assessed by measuring infarct size. METHODS AND RESULTS Open-chest rats with NIDD and age-matched control rats underwent 30 or 45 minutes of regional ischemia and 2-hour reperfusion. Infarct size was measured by tetrazolium. Control rats had 32.0 +/- 3.3% infarction of the risk zone after a 30-minute coronary occlusion, whereas NIDD rats had significantly smaller infarcts (11.5 +/- 3.1% of the risk area, P &lt; .005). When ischemic time was extended to 45 minutes, infarct size in control animals averaged 57.9 +/- 6.2%, whereas only 37.3 +/- 5.6% of ischemic myocardium was infarcted in NIDD rats (P &lt; .05). In a subset NIDD group, rats experienced a period of ischemic preconditioning (three cycles of 5-minute ischemia/5-minute reperfusion) before 45-minute ischemia. Infarct size in these rats averaged only 6.9 +/- 3.0% (P &lt; .01 vs nonpreconditioned NIDD rats with 45-minute coronary occlusions). Collateral flow was measured in NIDD rat hearts with radioactive microspheres. Collateral flow was &lt; 1% of normal myocardial blood flow. CONCLUSIONS We conclude that NIDD protects the heart from infarction and that this protection is not related to the development of coronary collaterals. Furthermore, preconditioning can further protect the NIDD heart.
Features of the exercise test that reflect the activity of ischemic heart disease out of hospital.
Authors: S Campbell, J Barry, M B Rocco, E G Nabel, K Mead-Walters, G S Rebecca, A P Selwyn
Journal: Circulation (1986)

To better understand the relationship between the transient myocardial ischemia seen during an exercise test and ischemic activity out of hospital, 39 patients with well-documented coronary artery disease underwent standard treadmill exercise testing (Bruce protocol) and 24 to 48 hr of continuous ambulatory electrocardiographic monitoring during normal daily activities. A total of 245 episodes of transient ischemia were recorded in 21 of 32 patients with positive exercise electrocardiograms (group I), whereas seven patients with negative test results (group II) had no episodes of transient ischemia, during monitoring out of hospital (p less than .01). Certain measures in the exercise test were related to the severity of ischemia out of hospital: there were more episodes and a greater total duration of transient ischemia per 24 hr of ambulatory monitoring in patients who developed ischemic electrocardiographic changes before 6 min of exercise (p less than or equal to .021) or at a heart rate of less than 150 beats/min (p = .005) and in those in whom these ST segment changes persisted for more than 5 min after exercise (p less than or equal to .016). In contrast, there was no relationship between transient ischemia out of hospital and the commonly quoted exercise variables: chest pain, total exercise duration, and the maximum levels of heart rate, systolic blood pressure, and double product. Thus, patients with coronary artery disease and negative exercise electrocardiograms are most unlikely to experience active ischemia during normal daily life.(ABSTRACT TRUNCATED AT 250 WORDS)
Severe bronchoconstriction after inhalation of budesonide.
Authors: D V McGivern, J T MacFarlane
Journal: BMJ (1984)

<h3>Background</h3> Osteitis condensans ilii (OCI) is regarded as a non-inflammatory disorder, which is considered to be induced by mechanical stress (e.g., by pregnancy and delivery). The diagnosis is normally based on wide spread sclerosis of the sacroiliac joint without erosions or ankyloses on imaging. More recently, paraarticular bone marrow oedema has been described on MRI, which can occur early but also intermittently later in the course of the disease. The clinical characteristics of OCI patienst have not been well described. To date, there are no published systematic data on the characteristics of OCI as compared to axial spondyloarthritis (axSpA). <h3>Objectives</h3> The objective of this matched case-control study was to investigate demographic, clinical, and lab characteristics of OCI as compared to axSpA. <h3>Methods</h3> Using medical database search we have identified n=103 patients aged ≥18 years who were diagnosed with OCI upon presentation with chronic back pain in the Early Spondyloarthritis Clinic of the rheumatology department in the Charité University Hospital between January 2010 and May 2015. These patients were contacted in order to obtain an informed consent and to complete a survey on the disease-related history. n=60 OCI patients who provided an informed consent and completed the survey were included in the final analysis. These patients were matched with a 1:2 ratio according to the back pain duration to patients with definite axSpA diagnosed in the same setting in order to compare demographic, clinical and lab characteristics. <h3>Results</h3> The main characteristics of the two groups are presented in the table. Most importantly, all but 2 patients with OCI were females and had a significantly lower prevalence of inflammatory back pain, lower level of CRP stressing a rather non-inflammatory nature of this condition. All patients were referred because of possible axial SpA, therefore SpA features, although being lower than in axSpA patients (table 1), were higher than can normally expected in OCI patients. This is probably the reason why a statistical significance in comparison to axSpA was observed for uveitis only. There was no difference in age of back pain onset (but age &lt;45 years was a referral parameter). Signs of sacroiliitis at physical examination were only slightly more frequent in axSpA; there were no differences in spinal mobility. The level of symptoms (BASDAI) and the perceived level of functional disability (BASFI) were comparable between groups. 83% of female patients with OCI reported a history of at least one pregnancy with a mean number of pregnancies of 3 (median=3, range 1–8). <h3>Conclusions</h3> OCI manifesting with chronic back pain starting prior to 45 years of age represents an important differential diagnosis for axSpA. A constellation of a female sex (with a history of pregnancies), negative HLA-B27 and negative CRP seems to be of differential diagnostic value as compared to axSpA. <h3>Disclosure of Interest</h3> None declared
Tests of Glycemia in Diabetes Mellitus
Authors: Daniel E. Singer
Journal: Annals of Internal Medicine (1989)

Purpose: To assess t gluysician-based and self blood glucose monitoring, and assays of glycated hemoglobin in diagnosing and treating diabetes mellitus. Data Identification: Relevant literature in English from 1957 through early 1988 was identified via textbooks, original research articles, and review and policy papers, supplemented by a computer-based search of the National Library of Medicine MEDLINE database. Study Selection: Articles were selected because of prominence, based on frequent citation or policy authoritativeness, and relevance to the epidemiologic and clinical constructs of this paper. Results: We analyze the epidemiologic studies underlying the higher diagnostic glycemic thresholds for diabetes proposed by the National Diabetes Data Group and we suggest a diagnostic strategy in which glycated hemoglobin may substitute for glucose tolerance testing. Our section on treatment stresses matching the intensiveness of hypoglycemic therapy with the intensiveness of monitoring; emphasizing the role of self blood glucose monitoring. Our findings and recommendations are summarized in the figures and tables. Conclusions: Major advances in the diagnosis and management of diabetes have been made in the past 10 years. In particular, an array of epidemiologic studies have provided a logical basis for diagnostic standards, and two new means of assessing glycemia—glycated hemoglobin and self-monitoring of blood glucose—have become widely available. These tests allow more convenient approaches to diagnosis, and provide a fuller description of glycemia, permitting more informed and intensive therapy.
ABC of poisoning. Laboratory investigations in acute poisoning.
Authors: G Volans, B Widdop
Journal: BMJ (1984)

ACUTE POISONINGThere are no simple rules for the routine investigations that must be performed in each case of suspected poisoning.Common sense and 9 ~~~~._ ' ... . ..a .., .......economics dictate that investigation should be adapted to the individual case.Routine sample collection for possible toxicological analysis is, however, essential in all cases and should include not only blood, urine, and gastric contents but also samples ofthe suspected poison or items thought to be contaminated with the poison.In most cases, it will be possible .A.~~~~~~~~~~~eventually to discard the samples without analysis after the patient has recovered.In some, however, the samples will be vital to establish the diagnosis, determine treatment, and occasionally, for medicolegal purposes.In selected cases the samples may also be used to investigate the toxicity or non-toxicity of the poison for the benefit of future patients.All too often, sample collection is overlooked or samples inadvertently disposed ofwith the result that the case can never be fully evaluated.The admitting doctor should see that this does not happen.'World Health Organisation Consultative Group.The relationship between persisting spinal paralysis and poliomyelitis vaccine-results of a ten-year enquiry.
In vivo silencing of Reptin blocks the progression of human hepatocellular carcinoma in xenografts and is associated with replicative senescence
Authors: Ludovic Ménard, Danièle Taras, Aude Grigoletto, Valérie Haurie, Alexandra Nicou, Nathalie Dugot-Senant, Pierre Costet, Benoît Rousseau, Jean Rosenbaum
Journal: Journal of Hepatology (2010)
Exhibition pays tribute to St George's heritage
Authors: W. Moore
Journal: BMJ (2009)

Intercellular transfer of cell surface proteins by trogocytosis is common and could affect T cell responses. Yet, the role of trogocytosis in T cell function is still elusive, and it is unknown whether a molecule, once captured by T cells, harbors the same biological properties as in donor APC. In this study, we showed that FcγR as well as the associated FcRγ subunit could be detected at high levels on murine and human T cells after their intercellular transfer from FcγR-expressing APC. Capture of FcγR occurred during coculture of T cells with FcγR-expressing APC upon Ab- or Ag-mediated T cell stimulation. Once captured by T cells, FcγR were expressed in a conformation compatible with physiological function and conferred upon T cells the ability to bind immune complexes and to provision B cells with this source of Ag. However, we were unable to detect downstream signal or signaling-dependent function following the stimulation of FcγR captured by T cells, and biochemical studies suggested the improper integration of FcγR in the recipient T cell membrane. Thus, our study demonstrates that T cells capture FcγR that can efficiently exert ligand-binding activity, which, per se, could have functional consequences in T cell-B cell cooperation.
Pharmacology and Therapeutics: A Textbook for Students and Practitioners of Medicine and Its Allied Professions
Authors: Joseph R. Bertino
Journal: JAMA (1971)

Among the available textbooks of pharmacology and therapeutics, this seventh edition of Grollman and Grollman's<i>Pharmacy and Therapeutics</i>occupies an intermediate position in its treatment of the subject. The book is neither a succinct, "essentials" textbook, nor is it a "Goodman and Gilman." It probably will have most appeal to the average student attempting to learn enough pharmacology to earn him his MD degree. The book is well written, and since the book has two authors only, there is a consistency of style that the reader can expect from chapter to chapter. But, probably for the same reason, there is an inconsistency of the quality of each chapter. The reader who is not interested in scholarly referencing of statements or findings will find this book to his liking. However, since much of the science of pharmacology is not "hard facts," and controversial views exist in many areas, the lack of