tbuckley/cabot-search huggingface dataset:
Abnormalities of sodium handling and of cardiovascular adaptations during high salt diet in patients with mild heart failure.
Authors: M Volpe, C Tritto, N DeLuca, S Rubattu, M A Rao, F Lamenza, A Mirante, I Enea, V Rendina, A F Mele
Journal: Circulation (1993)

BACKGROUND Sodium retention and hormonal activation are fundamental hallmarks in congestive heart failure. The present study was designed to assess the ability of patients with asymptomatic to mildly symptomatic heart failure and no signs or symptoms of congestion to excrete ingested sodium and to identify possible early abnormalities of hormonal and hemodynamic mechanisms related to sodium handling. METHODS AND RESULTS The effects of a high salt diet (250 mEq/day for 6 days) on hemodynamics, salt-regulating hormones, and renal excretory response were investigated in a balanced study in 12 untreated patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (NYHA class I-II, ejection fraction &lt; 50%) (HF) and in 12 normal subjects, who had been previously maintained a 100 mEq/day NaCl diet. In normal subjects, high salt diet was associated with significant increases of echocardiographically measured left ventricular end-diastolic volume, ejection fraction, and stroke volume (all P &lt; .001) and with a reduction of total peripheral resistance (P &lt; .001). In addition, plasma atrial natriuretic factor (ANF) levels increased (P &lt; .05), and plasma renin activity and aldosterone concentrations fell (both P &lt; .001) in normals in response to salt excess. In HF patients, both left ventricular end-diastolic and end-systolic volumes increased in response to high salt diet, whereas ejection fraction and stroke volume failed to increase, and total peripheral resistance did not change during high salt diet. In addition, plasma ANF levels did not rise in HF in response to salt loading, whereas plasma renin activity and aldosterone concentrations were as much suppressed as in normals. Although urinary sodium excretions were not significantly different in the two groups, there was a small but systematic reduction of daily sodium excretion in HF, which resulted in a significantly higher cumulative sodium balance in HF than in normals during the high salt diet period (P &lt; .001). CONCLUSIONS These results show a reduced ability to excrete a sodium load and early abnormalities of cardiac and hemodynamic adaptations to salt excess in patients with mild heart failure and no signs or symptoms of congestion.
Abstract 1167: The GNAS1 T393C polymorphism is a predictor of clinical outcome in esophageal cancer
Authors: Katharina E. Effenberger, Safije Musici, Emre F. Yekebas, Asad Kutup, Till Kamradt, Sormeh Mina, Viacheslav Kalinin, Burkhard Brandt, Klaus Pantel, Jakob R. Izbicki, Yogesh K. Vashist
Journal: Cancer Research (2010)

Abstract Background: There is a paucity of prognostic markers in esophageal cancer (EC). Genetic variations determined in the germline DNA of cancer patients may serve as important prognostic factors of clinical outcome since genomic DNA remains unbiased by instability occurring in tumor DNA and is easily accessible in the peripheral blood. G-protein α subunit (Gαs) polymorphism has been identified as a prognostic marker of tumor recurrence and survival in various tumor entities. We genotyped the single nucleotide T393C polymorphism in the GNAS1 gene encoding Gαs, and focused on three different genotypes, TT, TC, and CC. The aim of this study was to evaluate the potential prognostic value of the GNAS1 polymorphism in EC. Methods: Genomic DNA was extracted from peripheral blood leucocytes of 190 patients who underwent complete resection for esophageal cancer and did not receive any neoadjuvant or adjuvant therapy. The GNAS1 genotypes were correlated with clinicopathological parameters, tumor cell dissemination in bone marrow and clinical outcome. Results: The TT and TC genotypes correlated with advanced disease, predominantly characterized by the presence of lymph node metastases (p&amp;lt;0.001) and tumor cell dissemination (p=0.01). In line with this, significantly more TT and TC genotype patients displayed disseminated tumor cells in bone marrow compared to the CC genotype group (p=0.01). Accordingly, the disease recurrence rate was higher in TT and TC than in CC patients. Kaplan-Meier estimates for disease-free (DFS) and overall survival (OS) displayed better outcome in CC compared to TT and TC genotypes. Furthermore, in multivariate Cox proportional hazard analysis, GNAS1 polymorphism independently predicted disease progression with the CC group presenting the best outcome (OS: p=0.001, DFS p=0.002). Conclusion: The GNAS1 polymorphism was identified as a strong independent prognostic factor for DFS and OS in EC patients supporting a functional role of Gαs in this tumor entity. Preoperative determination of the GNAS1 polymorphism will allow allocation of patients into different risk profiles as well as stratification into individual therapy regimen. 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 1167.
"Collagen disease" due to carbamazepine (Tegretol).
Authors: J. R. Simpson
Journal: BMJ (1966)

Balkrishnan for help in the statistical analysis of the data on liver- function tests.ADDENDUM.-Ihave realized since this paper was written that my assumption concerning the lower cost of sequential oral contraceptives may be incorrect.It is possible that the increased cost of packaging and ensuring that the right tablets are always packed may more than offset any saving in cost of materials.If this is the case, the most economical oral contraceptive for a national family planning programme may still be a low-dose combination tablet.
Phenotypic Profiling of Engineered Mouse Melanomas with Manipulated Histamine Production Identifies Histamine H2 Receptor and Rho-C as Histamine-Regulated Melanoma Progression Markers
Authors: Zoltán Pós, Géza Sáfrány, Kerstin Müller, Sára Tóth, András Falus, Hargita Hegyesi
Journal: Cancer Research (2005)

Abstract In the present study, the impact of acquired neoplastic l-histidine decarboxylase (HDC) expression, and its direct consequence, the release of histamine in the tumor environment, was assessed on melanoma tumor progression. B16-F10 mouse melanoma cells were manipulated via stable transfection, and nine novel transgenic variants were generated in triplicates, constitutively expressing the full-length sense mouse HDC mRNA, a mock control, and an antisense HDC RNA segment, respectively. Establishing both primary skin tumors and lung metastases in C57BL/6 mice, the nine variants with different histamine-releasing capacities were subjected to a comprehensive comparative progression profiling in vivo. Our analyses showed trends of markedly accelerated tumor growth (P &amp;lt; 0.001), and moderately increased metastatic colony-forming potential (P = 0.010) along with rising levels of local histamine production. Using RNase protection assay for screening of the melanoma progression profile, and Western blotting for subsequent result validation, we looked for molecular progression markers affected by melanoma histamine secretion. Investigation of 21 functionally clustered markers associated with tumor proliferation, angiogenesis, invasivity, metastasis formation, local or systemic immunomodulation, and histamine signaling revealed positive correlations between histamine production, tumor histamine H2 receptor and rho-C expression (P &amp;lt; 0.001, P = 0.002, respectively). These observations confirm the involvement of histamine in the molecular machinery of melanoma progression.
Cell Cycle Status of CD34+ Hemopoietic Stem Cells Determines Lentiviral Integration in Actively Transcribed and Development-related Genes
Authors: Eleni Papanikolaou, Anna Paruzynski, Ioannis Kasampalidis, Annette Deichmann, Evangelos Stamateris, Manfred Schmidt, Christof von Kalle, Nicholas P Anagnou
Journal: Molecular Therapy (2014)

Gene therapy utilizing lentiviral-vectors (LVs) is postulated as a dynamic therapeutic alternative for monogenic diseases. However, retroviral gene transfer may cause insertional mutagenesis. Although, such risks had been originally estimated as extremely low, several reports of leukemias or clonal dominance, have led to a re-evaluation of the mechanisms operating in insertional mutagenesis. Therefore, unraveling the mechanism of retroviral integration is mandatory toward safer gene therapy applications. In the present study, we undertook an experimental approach which enabled direct correlation of the cell cycle stage of the target cell with the integration profile of LVs. CD34+ cells arrested at different stages of cell cycle, were transduced with a GFP-LV. LAM-PCR was employed for integration site detection, followed by microarray analysis to correlate transcribed genes with integration sites. The results indicate that ~10% of integration events occurred in actively transcribed genes and that the cell cycle stage of target cells affects integration pattern. Specifically, use of thymine promoted a safer profile, since it significantly reduced integration within cell cycle-related genes, while we observed increased possibility for integration into genes related to development, and decreased possibility for integration within cell cycle and cancer-related genes, when transduction occurs during mitosis. Gene therapy utilizing lentiviral-vectors (LVs) is postulated as a dynamic therapeutic alternative for monogenic diseases. However, retroviral gene transfer may cause insertional mutagenesis. Although, such risks had been originally estimated as extremely low, several reports of leukemias or clonal dominance, have led to a re-evaluation of the mechanisms operating in insertional mutagenesis. Therefore, unraveling the mechanism of retroviral integration is mandatory toward safer gene therapy applications. In the present study, we undertook an experimental approach which enabled direct correlation of the cell cycle stage of the target cell with the integration profile of LVs. CD34+ cells arrested at different stages of cell cycle, were transduced with a GFP-LV. LAM-PCR was employed for integration site detection, followed by microarray analysis to correlate transcribed genes with integration sites. The results indicate that ~10% of integration events occurred in actively transcribed genes and that the cell cycle stage of target cells affects integration pattern. Specifically, use of thymine promoted a safer profile, since it significantly reduced integration within cell cycle-related genes, while we observed increased possibility for integration into genes related to development, and decreased possibility for integration within cell cycle and cancer-related genes, when transduction occurs during mitosis.
Abstract IA05: Targeting the oxidative stress pathway in rhabdomyosarcoma
Authors: Michael A. Dyer
Journal: Cancer Research (2014)

Abstract Rhabdomyosarcoma is a soft-tissue sarcoma with molecular and cellular features of developing skeletal muscle. Histologically, there are two major subtypes of rhabdomyosarcoma, embryonal and alveolar, which have distinct clinical, molecular, and genetic features. Patients with resected localized disease are highly curable, but patients with recurrent, metastatic or large unresectable tumors have a poor clinical outcome. In this study, we performed whole-genome sequencing, exome sequencing, RNA-sequencing and DNA methylation profiling of embryonal and alveolar rhabdomyosarcomas. The embryonal tumors had more structural and copy number variations than did alveolar tumors and those lesions result from the accumulation of chromosomal lesions over time. Mutations in the RAS/NF1 pathway were significantly associated with intermediate- and high-risk embryonal rhabdomyosarcoma. In contrast, alveolar rhabdomyosarcoma had fewer genetic lesions overall and there were no known cancer consensus genes that were recurrently mutated other than the PAX3/7-FOXO1translocation that is a hallmark of alveolar rhabdomyosarcoma. DNA methylation profiling and RNA-seq analysis showed that embryonal and alveolar rhabdomyosarcomas are distinct and the alveolar tumors more closely resemble normal myoblasts and myotubes. To identify novel therapeutics for embryonal rhabdomyosarcomas, we developed and characterized 6 orthotopic xenografts of tumors in our discovery cohort. High throughput screening of primary cultures derived from those xenografts identified oxidative stress as a pathway of therapeutic relevance for embryonal rhabdomyosarcoma. Citation Format: Michael A. Dyer. Targeting the oxidative stress pathway in rhabdomyosarcoma. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr IA05.
Aneurysm of the Membranous Septum with Interventricular Septal Defect Producing Right Ventricular Outflow Obstruction
Authors: SUNIL K. DAS, EDWARD J. JAHNKE, WELDON J. WALKER
Journal: Circulation (1964)

The second known case of aneurysm of the membranous interventricular septum simulating infundibular pulmonic stenosis associated with an interventricular septal defect is described. Hemodynamic studies before and after successful surgical correction of both lesions are presented. The current literature on the subject is briefly reviewed.
Chronic Beryllium Disease and Sensitization at a Beryllium Processing Facility
Authors: Kenneth Rosenman, Vicki Hertzberg, Carol Rice, Mary Jo Reilly, Judith Aronchick, John E. Parker, Jackie Regovich, Milton Rossman
Journal: Environmental Health Perspectives (2005)

We conducted a medical screening for beryllium disease of 577 former workers from a beryllium processing facility. The screening included a medical and work history questionnaire, a chest radiograph, and blood lymphocyte proliferation testing for beryllium. A task exposure and a job exposure matrix were constructed to examine the association between exposure to beryllium and the development of beryllium disease. More than 90% of the cohort completed the questionnaire, and 74% completed the blood and radiograph component of the screening. Forty-four (7.6%) individuals had definite or probable chronic beryllium disease (CBD), and another 40 (7.0%) were sensitized to beryllium. The prevalence of CBD and sensitization in our cohort was greater than the prevalence reported in studies of other beryllium-exposed cohorts. Various exposure measures evaluated included duration; first decade worked; last decade worked; cumulative, mean, and highest job; and highest task exposure to beryllium (to both soluble and nonsoluble forms). Soluble cumulative and mean exposure levels were lower in individuals with CBD. Sensitized individuals had shorter duration of exposure, began work later, last worked longer ago, and had lower cumulative and peak exposures and lower nonsoluble cumulative and mean exposures. A possible explanation for the exposure-response findings of our study may be an interaction between genetic predisposition and a decreased permanence of soluble beryllium in the body. Both CBD and sensitization occurred in former workers whose mean daily working lifetime average exposures were lower than the current allowable Occupational Safety and Health Administration workplace air level of 2 microg/m3 and the Department of Energy guideline of 0.2 microg/m3.
Clinical Outcomes and Biomarker Profiles of Elderly Pretreated NSCLC Patients from the BATTLE Trial
Authors: Anne S. Tsao, Suyu Liu, J. Jack Lee, Christine Alden, George Blumenschein, Roy Herbst, Suzanne E. Davis, Edward Kim, Scott Lippman, David Stewart, Xi Ming Tang, Ignacio Wistuba, Waun Ki Hong
Journal: Journal of Thoracic Oncology (2012)
Abstract 1145: Molecular markers of neoadjuvant chemotherapy and combined chemoradiotherapy response in patients with oropharynx squamous cell carcinoma
Authors: Marcia Hatakeyama, Luciana A. Reis-Rosa, Fábio A. Marchi, Graziela Spilborghs, André L. Carvalho, Ulisses R. Nicolau, Luiz P. Kowalski, Silvia R. Rogatto
Journal: Cancer Research (2012)

Abstract The treatment currently considered standard for advanced oropharyngeal tumors involves concomitant chemo- and radiotherapy or surgery followed by adjuvant chemo- and radiotherapy. However, only 30 to 50% of patients with locally advanced disease survive more than three years, even with the advances in surgical techniques and the recognized benefits of therapy combined with radio- and chemotherapy. Treatment with induction TPF (docetaxel plus cisplatin and fluorouracil) chemotherapy followed by chemoradiotherapy was associated with a trend toward improved survival (Posner et al., 2007. N Engl J Med. 357:1705). The aim of this study was to investigate biological markers as potential predictors of response to chemotherapy and/or radiotherapy according to HPV infection in oropharyngeal carcinomas (OC). Thirty-two OC were evaluated by array CGH (4x180k, Agilent). A total of 35% of cases were HPV positives; HPV16 subtype was the most frequently detected (8/37), followed by subtype 18 (2/37). In general, HPV- cases showed a large number of copy number alterations (117 CNAs) in comparison with HPV+ samples. Losses on 7q22.1 and 14q12 were found exclusively in HPV+ tumors (p=0.044). Comparative analysis of genomic alterations among the patients which received combined chemoradiotherapy (22 cases) was done aiming to identify molecular markers that could predict the complete response (CR), partial response (PR) to treatment or progressive disease (PD). Tumors with CR showed a lower number of genomic alterations (90 CNAs versus 110 per cases in PR and PD). Losses at 1p21.3-p21.1 and gains on 10p13-p12.33 and 10p12.31-p12.1(p≤0.017) were exclusively found in patients with PD and PR. Overall survival (OS) analysis between HPV- and HPV+ cases demonstrated no significant differences (p&amp;gt;0.05). HPV- tumors showed more complexity and genomic instability than HPV+ tumors. Genomic losses or gains at different loci have been reported in HPV- compared to few or no alterations in HPV+ cases. In this study, it was detected specific chromosomal imbalances associated with therapy response and consequently, putative candidates to be validated in a large series of cases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1145. doi:1538-7445.AM2012-1145
Clinical Decision Support Systems and Antibiotic Prescribing
Authors: Johannes C. van der Wouden, Marijke M. Kuyvenhoven
Journal: JAMA (2006)

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Public health implications of environmental exposures.
Authors: C T De Rosa, H R Pohl, M Williams, A A Ademoyero, C H Chou, D E Jones
Journal: Environmental Health Perspectives (1998)

The Agency for Toxic Substances and Disease Registry (ATSDR) is a public health agency with responsibility for assessing the public health implications associated with uncontrolled releases of hazardous substances into the environment. The biological effects of low-level exposures are a primary concern in these assessments. One of the tools used by the agency for this purpose is the risk assessment paradigm originally outlined and described by the National Academy of Science in 1983. Because of its design and inherent concepts, risk assessment has been variously employed by a number of environmental and public health agencies and programs as a means to organize information, as a decision support tool, and as a working hypothesis for biologically based inference and extrapolation. Risk assessment has also been the subject of significant critical review. The ATSDR recognizes the utility of both the qualitative and quantitative conclusions provided by traditional risk assessment, but the agency uses such estimates only in the broader context of professional judgment, internal and external peer review, and extensive public review and comment. This multifaceted approach is consistent with the Council on Environmental Quality's description and use of risk analysis as an organizing construct based on sound biomedical and other scientific judgment in concert with risk assessment to define plausible exposure ranges of concern rather than a single numerical estimate that may convey an artificial sense of precision. In this approach biomedical opinion, host factors, mechanistic interpretation, molecular epidemiology, and actual exposure conditions are all critically important in evaluating the significance of environmental exposure to hazardous substances. As such, the ATSDR risk analysis approach is a multidimensional endeavor encompassing not only the components of risk assessment but also the principles of biomedical judgment, risk management, and risk communication. Within this framework of risk analysis, the ATSDR may rely on one or more of a number of interrelated principles and approaches to screen, organize information, set priorities, make decisions, and define future research needs and directions.
Chronic Renal Failure — A Vasculopathic State
Authors: Robert G. Luke
Journal: New England Journal of Medicine (1998)

Chronic renal insufficiency (defined by a serum creatinine concentration of 1.5 to 3.0 mg per deciliter [133 to 265 μmol per liter]), chronic renal failure (serum creatinine concentration, >3.0 mg per deciliter), and end-stage renal disease should be regarded as parts of a continuum. Of the 300,000 patients who are currently receiving renal-replacement therapy in the United States,1 220,000 receive dialysis therapy and the remainder depend on a successful kidney graft. The current annual increase in the number of patients receiving renal-replacement therapy is 6 to 7 percent; by extrapolation,2 at least 600,000 patients will be receiving such therapy by . . .