tbuckley/cabot-search huggingface dataset:
Breast Cancer Risk Estimates for Relatives of White and African American Women With Breast Cancer in the Women's Contraceptive and Reproductive Experiences Study
Authors: Michael S. Simon, Jeannette F. Korczak, Cecilia L. Yee, Kathleen E. Malone, Giske Ursin, Leslie Bernstein, Jill A. McDonald, Dennis Deapen, Brian L. Strom, Michael F. Press, Polly A. Marchbanks, Ronald T. Burkman, Linda K. Weiss, Ann G. Schwartz
Journal: Journal of Clinical Oncology (2006)

Purpose Family history is a well-recognized risk factor for breast cancer. Familial aggregation and segregation analyses have estimated breast cancer risk based on family history primarily for white women; such information is limited for African American (AA) women. The purpose of this report is to update breast cancer risk estimates associated with a family history of breast cancer for white and AA women. Methods We used family cancer history from 2,676 white and 1,525 AA women with breast cancer (probands) in the population-based National Institute of Child Health and Human Development's Women's Contraceptive and Reproductive Experiences (CARE) Study to estimate age-specific breast cancer risks in their first degree adult female relatives. Cumulative hazard curves were calculated for relatives of all probands using Cox proportional hazards models, and were stratified by the proband's race and age at diagnosis and number of relatives affected. Results Breast cancer risks for white and AA women with a family history of the disease are similar through age 49 years, but diverge afterwards, with higher risks by age 79 in white women than in AA women (17.5% [SE, 0.9%] v 12.2% [SE, 1.1%]; P &lt; .001). These risks increase as the number of affected first degree relatives increases, reaching 25.2% (SE, 3.4%) and 16.9% (SE, 4.0%) in white and AA women with more than one affected relative, respectively (P = .3). Conclusion We found age-related racial differences in breast cancer risk in women with a family history of breast cancer and have updated risk estimates for white and AA women for clinical use.
Antitumor Vascular Strategy for Controlling Experimental Metastatic Spread of Human Small-Cell Lung Cancer Cells with ZD6474 in Natural Killer Cell–Depleted Severe Combined Immunodeficient Mice
Authors: Seiji Yano, Hiroaki Muguruma, Yuka Matsumori, Hisatsugu Goto, Emiko Nakataki, Nobutaka Edakuni, Hideki Tomimoto, Soji Kakiuchi, Akihiko Yamamoto, Hisanori Uehara, Anderson Ryan, Saburo Sone
Journal: Clinical Cancer Research (2005)

Abstract Background: Small-cell lung cancer is often characterized by rapid growth and metastatic spread. Because tumor growth and metastasis are angiogenesis dependent, there is great interest in therapeutic strategies that aim to inhibit tumor angiogenesis. Methods: The effect of ZD6474, an orally available inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor tyrosine kinases, was studied in experimental multiple-organ metastasis models with human small-cell lung cancer cell lines (SBC-3 or SBC-5) in natural killer cell–depleted severe combined immunodeficient mice. Results: Intravenously inoculated SBC-5 cells produced experimental metastases in the liver, lung, and bone whereas SBC-3 cells produced the metastases in the liver, systemic lymph nodes, and kidneys. Daily oral treatment with ZD6474 (50 mg/kg), started on day 14 (after the establishment of micrometastases), significantly reduced the frequency of large (&amp;gt;3 mm) metastatic colonies (in the liver and lymph nodes) and osteolytic bone lesions. ZD6474 treatment did not significantly reduce the frequency of small (&amp;lt;2-3 mm) metastatic lesions found in the lung (SBC-5) or kidney (SBC-3), consistent with an antiangiogenic mechanism of action. Immunohistochemical analysis of SBC-5 metastatic deposits in the liver showed that ZD6474 treatment inhibited VEGFR-2 activation and induced apoptosis of tumor-associated endothelial cells, resulting in decreasing tumor microvessel density. ZD6474 treatment was also associated with a decrease in tumor cell proliferation and an increase in tumor cell apoptosis. The antitumor effects of ZD6474 were considered likely to be due to inhibition of VEGFR-2 tyrosine kinase because gefitinib, a small-molecule inhibitor of epidermal growth factor receptor tyrosine kinase, was inactive in these models. Conclusions: These results suggest that ZD6474 may be of potential therapeutic value in inhibiting the growth of metastatic small-cell lung cancer in humans. Phase II trials with ZD6474 are currently ongoing in a range of solid tumors.
Conserved Enhancer in the Serum Response Factor Promoter Controls Expression During Early Coronary Vasculogenesis
Authors: Timothy J. Nelson, Stephen A. Duncan, Ravi P. Misra
Journal: Circulation Research (2004)

Serum response factor (SRF) is a transcription factor required for mesoderm formation in the developing mouse embryo that is important for myogenic differentiation, including notably, the differentiation of the proepicardial organ (PEO) into coronary vascular cells during early development. To identify regulatory sequences that control SRF expression during early mouse development, we used a novel transgenic approach to study the role of conserved noncoding DNA sequences (CNCS) in the SRF gene. Embryonic stem (ES) cells containing a targeted single-copy of putative SRF regulatory sequences were used to directly generate transgenic embryos by tetraploid aggregation. Because the ES cell-derived targeted embryos are genetically equivalent, except for the putative regulatory sequence of interest, differences in transgene expression can be attributed directly to these sequences. Using this approach, we identified an E-box/Ets containing 270-bp cis -acting module in the SRF promoter that mediates expression in the PEO. Reporter transgenes containing this module express in derivatives of the PEO that give rise to the coronary vasculature, but do not express in the PEO-derived epicardium. These results are the first reported in vivo analysis of SRF regulatory elements that control expression during early development. Using this reporter module and this approach, it should be possible to begin to elucidate molecular mechanisms involved in the differentiation of coronary vasculature progenitor cells, as well as identify additional SRF regulatory elements important during mammalian development.
Monitoring Sedation Status Over Time in ICU Patients
Authors: E. Wesley Ely, Brenda Truman, Ayumi Shintani, Jason W. W. Thomason, Arthur P. Wheeler, Sharon Gordon, Joseph Francis, Theodore Speroff, Shiva Gautam, Richard Margolin, Curtis N. Sessler, Robert S. Dittus, Gordon R. Bernard
Journal: JAMA (2003)

ContextGoal-directed delivery of sedative and analgesic medications is recommended as standard care in intensive care units (ICUs) because of the impact these medications have on ventilator weaning and ICU length of stay, but few of the available sedation scales have been appropriately tested for reliability and validity.ObjectiveTo test the reliability and validity of the Richmond Agitation-Sedation Scale (RASS).DesignProspective cohort study.SettingAdult medical and coronary ICUs of a university-based medical center.ParticipantsThirty-eight medical ICU patients enrolled for reliability testing (46% receiving mechanical ventilation) from July 21, 1999, to September 7, 1999, and an independent cohort of 275 patients receiving mechanical ventilation were enrolled for validity testing from February 1, 2000, to May 3, 2001.Main Outcome MeasuresInterrater reliability of the RASS, Glasgow Coma Scale (GCS), and Ramsay Scale (RS); validity of the RASS correlated with reference standard ratings, assessments of content of consciousness, GCS scores, doses of sedatives and analgesics, and bispectral electroencephalography.ResultsIn 290-paired observations by nurses, results of both the RASS and RS demonstrated excellent interrater reliability (weighted κ, 0.91 and 0.94, respectively), which were both superior to the GCS (weighted κ, 0.64; P&lt;.001 for both comparisons). Criterion validity was tested in 411-paired observations in the first 96 patients of the validation cohort, in whom the RASS showed significant differences between levels of consciousness (P&lt;.001 for all) and correctly identified fluctuations within patients over time (P&lt;.001). In addition, 5 methods were used to test the construct validity of the RASS, including correlation with an attention screening examination (r = 0.78, P&lt;.001), GCS scores (r = 0.91, P&lt;.001), quantity of different psychoactive medication dosages 8 hours prior to assessment (eg, lorazepam: r = − 0.31, P&lt;.001), successful extubation (P = .07), and bispectral electroencephalography (r = 0.63, P&lt;.001). Face validity was demonstrated via a survey of 26 critical care nurses, which the results showed that 92% agreed or strongly agreed with the RASS scoring scheme, and 81% agreed or strongly agreed that the instrument provided a consensus for goal-directed delivery of medications.ConclusionsThe RASS demonstrated excellent interrater reliability and criterion, construct, and face validity. This is the first sedation scale to be validated for its ability to detect changes in sedation status over consecutive days of ICU care, against constructs of level of consciousness and delirium, and correlated with the administered dose of sedative and analgesic medications.
Extracardiac control of embryonic cardiomyocyte proliferation and ventricular wall expansion
Authors: Hua Shen, Susana Cavallero, Kristine D. Estrada, Ionel Sandovici, S. Ram Kumar, Takako Makita, Ching-Ling Lien, Miguel Constancia, Henry M. Sucov
Journal: Cardiovascular Research (2015)

The strategies that control formation of the ventricular wall during heart development are not well understood. In previous studies, we documented IGF2 as a major mitogenic signal that controls ventricular cardiomyocyte proliferation and chamber wall expansion. Our objective in this study was to define the tissue source of IGF2 in heart development and the upstream pathways that control its expression. Using a number of mouse genetic tools, we confirm that the critical source of IGF2 is the epicardium. We find that epicardial Igf2 expression is controlled in a biphasic manner, first induced by erythropoietin and then regulated by oxygen and glucose with onset of placental function. Both processes are independently controlled by retinoic acid signalling. Our results demonstrate that ventricular wall cardiomyocyte proliferation is subdivided into distinct regulatory phases. Each involves instructive cues that originate outside the heart and thereby act on the epicardium in an endocrine manner, a mode of regulation that is mostly unknown in embryogenesis.
Chloroplast Genome Rearrangements and the Evolution of Giant Lobelias from Herbaceous Ancestors
Authors: EB Knox, SR Downie, JD Palmer
Journal: Molecular Biology and Evolution (1993)

Phylogenetic relationships among 16 species of Lobelia and single representatives of Monopsis and Sclerotheca (Lobeliaceae) were assessed by mapping restriction sites and major structural rearrangements (deletions and inversions) in the large single-copy region of the chloroplast genome. Eleven inversions and five different gene arrangements were found. A deletion involving 0RF5 12 is associated with many of the inversions, and all inversion endpoints are located in intergenic spacer regions. Analysis of 132 phylogenetically informative restriction sites produced three equally parsimonious trees of 2 19 steps, with a consistency index of 0.60. The restriction-site and inversion data yield congruent trees, indicating that the giant lobelias from around the world are derived from diploid herbaceous ancestors. The giant lobelias consist of a Chilean hexaploid group and a pantropical tetraploid group. The woody genus Sclerotheca is clearly derived from a giant Lobelia ancestor, while the herbaceous Monopsis is probably derived from herbaceous lobelias. The giant lobelias from eastern Africa are weakly supported as monophyletic with the inclusion of the Brazilian L. organensis. Relationships among the Pacific and Asian giant lobelias are not fully resolved and await more detailed study.
6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial
Authors: Xavier Pivot, Gilles Romieu, Marc Debled, Jean-Yves Pierga, Pierre Kerbrat, Thomas Bachelot, Alain Lortholary, Marc Espié, Pierre Fumoleau, Daniel Serin, Jean-Philippe Jacquin, Christelle Jouannaud, Maria Rios, Sophie Abadie-Lacourtoisie, Nicole Tubiana-Mathieu, Laurent Cany, Stéphanie Catala, David Khayat, Iris Pauporté, Andrew Kramar
Journal: The Lancet Oncology (2013)
Redistribution of Cardiac Output during Hemorrhage in the Unanesthetized Monkey
Authors: RALPH P. FORSYTH, BARRY I. HOFFBRAND, KENNETH L. MELMON
Journal: Circulation Research (1970)

Regional flow measurements were made, using the Rudolph and Heymann microsphere technique, before and after 10, 30, and 50% of the previously measured blood volume was withdrawn from five unanesthetized rhesus monkeys restrained in horizontally tilted primate chairs. Measurements at similar time intervals were also made in seven control monkeys. Systemic arterial and central venous pressures, cardiac output, stroke volume, and hematocrit decreased progressively at each level of bleeding. Heart rate (until severe hemorrhage), respiratory rate, and blood levels of α-glucosidase rose; bradykinin levels in arterial blood were unchanged. The fraction of cardiac output was found to be progressively increased to brain, heart, adrenal gland, and hepatic artery vascular bed at the expense of skin, spleen, and pancreas. The hepatic artery vascular bed was the only one that showed significant vasodilatation at either 30 or 50% hemorrhage. During acute endotoxin shock in monkeys, we have previously found a similar fall in systemic arterial pressure due to a decrease in total peripheral resistance and a different pattern of regional blood flow changes. The lack of bradykinin production, the integrity of cardioregulatory mechanisms, and the fall of hematocrit levels found during hemorrhage may help account for some of the hemodynamic differences between these two types of shock.
Transport of plasma free fatty acids and triglycerides in man: a theoretical analysis
Authors: David M. Shames, Arthur Frank, Daniel Steinberg, Mones Berman
Journal: Journal of Clinical Investigation (1970)

Three different multicompartmental models of free fatty acid (FFA) and very low density lipoprotein triglyceride fatty acid (VLDL-TGFA) transport in man are formulated from plasma FFA and VLDL-TGFA tracee and tracer data collected over a 24 hr interval after the injection of palmitate-(14)C. All modeling and data fitting were performed on a digital computer using the SAAM program. Structural differences in the three models relate to the position of the slowly turning over compartment required to generate the late portion of the plasma VLDL-TGFA tracer data. The positions of this slow compartment are along the hepatic pathway from FFA to VLDL-TGFA (model A) or in the distribution system of VLDL-TGFA (model B) or in the distribution system of FFA (model C). Although all three models are equally consistent with our experimental data and are supported by observations of others, each reveals inconsistency with some data obtained from the literature. Consequently, a combination model of FFA-TGFA transport, incorporating properties of models A, B, and C would be more consistent with all available data. Experiments that would help to determine the quantitative significance of each of the slow compartments in the combination model are suggested. Several other models suggesting recycling of plasma VLDL-TGFA through the plasma FFA pool, kinetic heterogencity of the plasma VLDL-TGFA pool, and contamination of plasma VLDL-TGFA radioactivity with low density lipoprotein (LDL) TGFA radioactivity were tested. The first model does not explain the late portion of the plasma VLDL-TGFA tracer data. The second and third models, while consistent with our tracee and tracer data, have steady-state implications with respect to the extent of kinetic heterogeneity and size of the LDL-TGFA contaminant that make them unlikely. Assumptions underlying other investigator's models of FFA and TGFA transport in man are reviewed within the logical framework of our models. Quantitative differences among the various models are shown by evaluating all of the models with respect to a common set of plasma FFA and VLDL-TGFA data.
Discontinuity and variability in relational complexity: Cognitive and brain development
Authors: Donna Coch, Kurt W. Fischer
Journal: Behavioral and Brain Sciences (1998)

Relational complexity theory has important virtues, but the present model omits key aspects and evidence. In contrast, skill theory specifies (1) a detailed series of developmental changes in relational complexity from birth to age 30, (2) processes of interaction of content and structure that produce variability in complexity, (3) the role of cortical development, and (4) empirical criteria for complexity levels, including developmental discontinuities. Many findings support these specifications.
Notch1 Signaling Promotes Primary Melanoma Progression by Activating Mitogen-Activated Protein Kinase/Phosphatidylinositol 3-Kinase-Akt Pathways and Up-regulating N-Cadherin Expression
Authors: Zhao-Jun Liu, Min Xiao, Klara Balint, Keiran S.M. Smalley, Patricia Brafford, Ruihua Qiu, Chelsea C. Pinnix, Xueli Li, Meenhard Herlyn
Journal: Cancer Research (2006)

Abstract Cellular signaling mediated by Notch receptors results in coordinated regulation of cell growth, survival, and differentiation. Aberrant Notch activation has been linked to a variety of human neoplasms. Here, we show that Notch1 signaling drives the vertical growth phase (VGP) of primary melanoma toward a more aggressive phenotype. Constitutive activation of Notch1 by ectopic expression of the Notch1 intracellular domain enables VGP primary melanoma cell lines to proliferate in a serum-independent and growth factor–independent manner in vitro and to grow more aggressively with metastatic activity in vivo. Notch1 activation also enhances tumor cell survival when cultured as three-dimensional spheroids. Such effects of Notch signaling are mediated by activation of the mitogen-activated protein kinase (MAPK) and Akt pathways. Both pathways are activated in melanoma cells following Notch1 pathway activation. Inhibition of either the MAPK or the phosphatidylinositol 3-kinase (PI3K)-Akt pathway reverses the Notch1 signaling-induced tumor cell growth. Moreover, the growth-promoting effect of Notch1 depends on mastermind-like 1. We further showed that Notch1 activation increases tumor cell adhesion and up-regulates N-cadherin expression. Our data show regulation of MAPK/PI3K-Akt pathway activities and expression of N-cadherin by the Notch pathway and provide a mechanistic basis for Notch signaling in the promotion of primary melanoma progression. (Cancer Res 2006; 66(8): 4182-90)
Sirolimus (Rapamycin) Monotherapy Prevents Graft Vascular Disease in Nonhuman Primate Recipients of Orthotopic Aortic Allografts
Authors: Camille Dambrin, Jochen Klupp, Tudor Bîrsan, Jorge Luna, Takeshi Suzuki, Tuan Lam, Peter Stähr, Bernard Hausen, Uwe Christians, Peter Fitzgerald, Gerald Berry, Randall Morris
Journal: Circulation (2003)

Delayed treatment with sirolimus (SRL) halts progression of graft vascular disease (GVD) in nonhuman primate (NHP) aortic allograft recipients. In this study, we investigated whether SRL monotherapy prevents the development of GVD.Pairs of 3-cm infrarenal aortic segments were exchanged between mixed lymphocyte reaction-mismatched, blood group-compatible NHPs (n=12). Six NHPs were untreated controls, and 6 were treated orally with SRL starting on the day of transplantation. Follow-up was 105 days. SRL doses were adjusted individually by assessing SRL blood concentrations, immune function, and clinical status. The severity of GVD was determined every 3 weeks by intravascular ultrasound, which quantified intimal area (IA) and intimal volume (IV) for the middle 1-cm graft segments. The mean+/-SEM SRL plasma levels were 14.5+/-9 ng/mL. In grafts from treated NHPs, IA and IV values on days 63, 84, and 105 were significantly lower than for controls (P<0.05 to P<0.001). On day 105, in the grafts from SRL-treated NHPs compared with grafts from controls, values (mean+/-SEM) were IA, 2.9+/-0.9 versus 5.5+/-0.7 mm2, P<0.001 and IV, 29.6+/-4.6 versus 55.2+/-2.8 mm3, P<0.001; IA and IV values for grafts from SRL-treated NHPs did not increase significantly between days 21 and 105.We show that SRL monotherapy prevented GVD in NHP aortic allograft recipients, suggesting the value of SRL for controlling GVD in clinical transplantation.
The prevalence of tobacco smoking and respiratory symptoms among students of medical university
Authors: Tatiana Bilichenko, Maryana Tubekova, Inna Yakhutlova, Alexander Lipanovskiy
Journal: European Respiratory Journal (2011)

The aim  of the research was to study the smoking habits and respiratory symptoms (RS) in young patients.   Materials and methods:  The study involved students of fourth year and fifth year at the age of 20 to 38 years old: 62 boys and 169 girls (response rate was 72,0%). To assess smoking the standard WHO questionnaire was used, and RS were studied on the basis of GA2LEN questionnaire. The analysis was conducted using Statistica 7 version.   Results:  82,6% of males and 71,0% of females among the students have tried smoking once mostly aged 10-15 years. 38,7% of boys and 33,1% of girls regularly smoked for 12 months or more and during the month before the survey 32,3% and 26,0% of students respectively. Intensity of smoking among boys was 11,8±6,1 and among the girls 7,0±4,4 cigarettes per day. Wheezing in the chest during the last 12 months was marked by 22,6% of boys and 22,5% of girls. 14,5% of boys and 25,4% of girls woke up from coughing. Coughing up phlegm on most days for 3 months each year was indicated by 11,3% of boys and 13,6% of girls. Wheezing in the chest in smokers compared with never smokers were 2,2 times more frequently (31,7% and 17,4% respectively, OR = 2,20 95% CI 1,12-4,32; P    Conclusion:  The results showed a high prevalence of smoking among both boys and girls. Despite the brief period of smoking and its adverse effect is manifested by increased frequency of RS. These findings point to the need to strengthen prevention of smoking among young people and medical students.
Cardiovascular and hypokalaemic effects of inhaled salbutamol, fenoterol, and isoprenaline.
Authors: K Larsson, P Hjemdahl
Journal: Thorax (1989)

Long acting sulphonamide type drugs may be associated with alveolitis more commonly than is currently realised.Minor degrees of dyspnoea may not be picked up by doctors unaware of the association.Routine three monthly spirometry and possibly chest radiography may be indicated for people taking these drugs.Two particular aspects of our patient's history are the previous dapsone reaction, suggest- ing generalised hypersensitivity to sulphur drugs, and the onset of lung disease despite her taking corticosteroids.