tbuckley/cabot-search huggingface dataset:
Blood levels after sublingual nitroglycerin.
Authors: P W Armstrong, J A Armstrong, G S Marks
Journal: Circulation (1979)

Pharmacokinetic analysis of nitroglycerin (GTN) has been hampered by the lack of a sensitive and specific method for measuring GTN in blood. Therefore, we examined the appearance of GTN in blood after administering 0.6 mg sublingually in 10 studies of normal volunteers. We used a gas-liquid chromatographic method with electron-capture detection and isosorbide dinitrate as the internal standard. GTN appeared in blood at 0.5 minutes, reached a peak of 2.3 +/- 0.36 ng/ml at 2 minutes, fell to 50% of peak value at 7.5 minutes and was barely detectable at 20 minutes. These blood levels paralleled the changes in heart rate and systolic blood pressure. These data show rapid appearance and disappearance of GTN from blood after sublingual administration, a large volume of distribution, and a rapid rate of total body clearance that precludes the liver from being the sole elimination site. This method for analysis of GTN and isosorbide dinitrate should be helpful in defining the role of chronic nitrate therapy.
Differences in hepatic processing of dietary and intravenously administered copper in rats
Authors: M Dijkstra, F Kuipers, G J van den Berg, R Havinga, R J Vonk
Journal: Hepatology (1997)

The biliary pathway represents the major excretory route for copper (Cu). It has been suggested that glutathione (GSH) plays a role in this process. However, biliary secretion of endogenous Cu is unaffected in canalicular multispecific organic anion transporter (cmoat)/multi-drug resistance protein (mrp2)-deficient GY/TR- rats, which is a mutant rat strain expressing defective canalicular adenosine triphosphate (ATP)-dependent GSH-conjugate transport and which is unable to secrete GSH into bile. Secretion of Cu after iv Cu load is markedly impaired in GY/TR- rats when compared with normal Wistar (NW) rats. Administration, iv, of 65, 325, or 2300 nmol/100 g body wt CuSO4 dose-dependently increased Cu secretion in normal Wistar (NW) rats. Secretion rates in GY/TR rats were much lower and plateaued with higher loads at a level of about 35 nmol/h/100 g body wt. Clearance of an intravenous (iv) bolus of 64Cu (250 nmol/100 g body wt) was faster in GY/TR- rats than in controls, but secretion of 64Cu into bile was clearly reduced in the mutants. Specific activity of biliary Cu was similar in both groups. To investigate the removal of excess dietary Cu via bile, GY/TR and NW rats received water supplemented with Cu (CuSO4 8 mmol/L) for up to 12 weeks (Cu-fed) or tap water (controls). Cu feeding resulted in an increase of biliary Cu secretion from approximately 6 to approximately 30 nmol/h/100 g body wt within two weeks, both in NW and GY/TR- rats; Cu secretion also did not further increase during the course of the experiment. Hepatic Cu content was similar in NW and GY/TR- rats and progressively increased during Cu feeding. Our data indicate that biliary secretion of diet-derived Cu proceeds exclusively via a saturable Cu transporting system, which is distinct from cmoat/mrp2 and which is independent of biliary GSH. This transport may be mediated by the recently identified Cu-ATPase. In contrast, excess hepatic Cu after iv Cu load depends on cmoat/mrp2 activity for rapid removal. It is concluded that iv administered and dietary (endogenous) Cu is, in part, processed differently by rat liver, which might be related to differences in Cu redox state.
Mixed messages over breast milk and brainy babies
Authors: Mary McCartney
Journal: BMJ (2007)

observations are happier, healthier, and brighter than those raised on formula milk," said the Daily Mail.But does it?What was not clear from most press reports was that some of the data-from the New Zealand Dunedin cohort-included in the Proceedings of the National Academy of Sciences study had already been examined, except with rather different results.The Dunedin cohort was included as part of a meta-analysis on the effect of breast feeding and intelligence-yes, the same study published in the BMJ in 2006, which found no effect.This study, which also included a prospective sibling pairs study, showed that crucially, once other factors including maternal intelligence had been adjusted for, there was no increased intelligence found in breast fed children.Multiple environmental influences affected child intelligence, explained the authors.The positive association of breast feeding with intelligence previously shown could be explained, not by the breast feeding itself, but by multiple confounding factors, mainly maternal intelligence, but also including maternal education, and the child's social environment.The abstract for the new Proceedings of the National Academy of Sciences study did not mention the previous meta-analysis.Instead it started with the assumption that "Breast fed children attain higher IQ scores than children not fed breast milk" without making it clear that this was (and is) unproven.Newspaper reports tended towards reporting the paper as certain evidence that breast feeding produced cleverer kids.Was this fair?While the authors did adjust for maternal intelligence, they did not show how much of the breast feeding effect this explained.Nor did they adjust their results for
Assessment of Pancreatic Cancer Care in the United States Based on Formally Developed Quality Indicators
Authors: Karl Y. Bilimoria, David J. Bentrem, Keith D. Lillemoe, Mark S. Talamonti, Clifford Y. Ko
Journal: JNCI Journal of the National Cancer Institute (2009)

Pancreatic cancer outcomes vary considerably among hospitals. Assessing pancreatic cancer care by using quality indicators could help reduce this variability. However, valid quality indicators are not currently available for pancreatic cancer management, and a composite assessment of the quality of pancreatic cancer care in the United States has not been done. Potential quality indicators were identified from the literature, consensus guidelines, and interviews with experts. A panel of 20 pancreatic cancer experts ranked potential quality indicators for validity based on the RAND/UCLA Appropriateness Methodology. The rankings were rated as valid (high or moderate validity) or not valid. Adherence with valid indicators at both the patient and the hospital levels and a composite measure of adherence at the hospital level were assessed using data from the National Cancer Data Base (2004–2005) for 49 065 patients treated at 1134 hospitals. Summary statistics were calculated for each individual candidate quality indicator to assess the median ranking and distribution. Of the 50 potential quality indicators identified, 43 were rated as valid (29 as high and 14 as moderate validity). Of the 43 valid indicators, 11 (25.6%) assessed structural factors, 19 (44.2%) assessed clinical processes of care, four (9.3%) assessed treatment appropriateness, four (9.3%) assessed efficiency, and five (11.6%) assessed outcomes. Patient-level adherence with individual indicators ranged from 49.6% to 97.2%, whereas hospital-level adherence with individual indicators ranged from 6.8% to 99.9%. Of the 10 component indicators (contributing 1 point each) that were used to develop the composite score, most hospitals were adherent with fewer than half of the indicators (median score = 4; interquartile range = 3–5). Based on the quality indicators developed in this study, there is considerable variability in the quality of pancreatic cancer care in the United States. Hospitals can use these indicators to evaluate the pancreatic cancer care they provide and to identify potential quality improvement opportunities.
A novel Notch ligand, Dll4, induces T-cell leukemia/lymphoma when overexpressed in mice by retroviral-mediated gene transfer
Authors: Xiao-Qiang Yan, Ulla Sarmiento, Yu Sun, Guo Huang, Jane Guo, Todd Juan, Gwyneth Van, Mei-Ying Qi, Sheila Scully, Giorgio Senaldi, Frederick A. Fletcher
Journal: Blood (2001)
Maternal Hypercholesterolemia Enhances Atherogenesis in Normocholesterolemic Rabbits, Which Is Inhibited by Antioxidant or Lipid-Lowering Intervention During Pregnancy
Authors: Claudio Napoli, Joseph L. Witztum, Federico Calara, Filomena de Nigris, Wulf Palinski
Journal: Circulation Research (2000)

Abstract —Maternal hypercholesterolemia during pregnancy is associated with a marked increase in aortic fatty streak formation in human fetuses and faster progression of atherosclerosis during normocholesterolemic childhood. However, the mechanisms responsible are unknown, and the contribution of genetic differences is difficult to assess in humans. The goal of this study was to determine whether maternal hypercholesterolemia per se may cause enhanced fatty streak formation in offspring and whether interventions during pregnancy can reduce it. During pregnancy, 1 group of New Zealand White rabbits was fed control chow and 8 groups were fed hypercholesterolemic diets Chol 1 (yielding plasma cholesterol of 153 mg/dL) or Chol 2 (yielding 359 mg/dL) without or with cholestyramine, vitamin E, or both. Offspring (n=15 to 25 per group) were killed at birth. Maternal hypercholesterolemia enhanced mean lesion size in the aorta of their offspring at birth from 44±18×10 3 μm 2 per section in controls to 85±26×10 3 in Chol 1 and 156±49×10 3 in Chol 2 groups ( P &lt;0.0001 for both). Cholestyramine or vitamin E treatment of mothers significantly reduced atherosclerosis at birth by up to 39% compared with controls on the same diet. Oxidized fatty acids and malondialdehyde in aortic atherosclerotic lesions and plasma were similarly affected by diets and treatment as atherosclerosis. Our results establish the causal role of hypercholesterolemia and peroxidation in fetal atherogenesis and demonstrate that both lipid-lowering and antioxidant interventions during pregnancy can reduce it. If it can be established that interventions in mothers also affect progression of lesions after birth, this may indicate a novel approach for the prevention of atherosclerosis.
Cyclic AMP Suppression Is Sufficient to Induce Gliomagenesis in a Mouse Model of Neurofibromatosis-1
Authors: Nicole M. Warrington, Scott M. Gianino, Erin Jackson, Patricia Goldhoff, Joel R. Garbow, David Piwnica-Worms, David H. Gutmann, Joshua B. Rubin
Journal: Cancer Research (2010)

Current models of oncogenesis incorporate the contributions of chronic inflammation and aging to the patterns of tumor formation. These oncogenic pathways, involving leukocytes and fibroblasts, are not readily applicable to brain tumors (glioma), and other mechanisms must account for microenvironmental influences on central nervous system tumorigenesis. Previous studies from our laboratories have used neurofibromatosis-1 (NF1) genetically engineered mouse (GEM) models to understand the spatial restriction of glioma formation to the optic pathway of young children. Based on our initial findings, we hypothesize that brain region-specific differences in cAMP levels account for the pattern of NF1 gliomagenesis. To provide evidence that low levels of cAMP promote glioma formation in NF1, we generated foci of decreased cAMP in brain regions where gliomas rarely form in children with NF1. Focal cAMP reduction was achieved by forced expression of phosphodiesterase 4A1 (PDE4A1) in the cortex of Nf1 GEM strains. Ectopic PDE4A1 expression produced hypercellular lesions with features of human NF1-associated glioma. Conversely, pharmacologic elevation of cAMP with the PDE4 inhibitor rolipram dramatically inhibited optic glioma growth and tumor size in Nf1 GEM in vivo. Together, these results indicate that low levels of cAMP in a susceptible Nf1 mouse strain are sufficient to promote gliomagenesis, and justify the implementation of cAMP-based stroma-targeted therapies for glioma.
TNF-alpha Down-Regulates Filaggrin and Loricrin Through c-Jun N-Terminal Kinase: Role for TNF Antagonists to Improve Skin Barrier
Authors: B.E. Kim, M.D. Howell, E. Guttman, P. Gilleaudeau, I. Cardinale, M. Boguniewicz, J.G. Krueger, D.Y. Leung
Journal: Journal of Allergy and Clinical Immunology (2011)
Identification of a common mutation in Finnish patients with nonketotic hyperglycinemia.
Authors: S Kure, M Takayanagi, K Narisawa, K Tada, J Leisti
Journal: Journal of Clinical Investigation (1992)

Nonketotic hyperglycinemia (NKH) is an autosomal recessive metabolic disorder caused by the defects in the glycine cleavage system (GCS; EC 2.1.2.10), a multienzyme system that consists of four individual components. NKH is a rare disorder in many countries, but with a very high incidence in northern Finland. To understand the genetic background of this high incidence, we examined the GCS in a typical case of NKH at the molecular level. The activity of P protein, a component of the GCS, was not detected in the lymphoblasts of the patient, while P protein mRNA of a normal size and level was present in the cells. Structural analysis of P protein mRNA from the patient revealed a single nucleotide substitution from G to T in the protein coding region, which resulted in an amino acid alteration from Ser564 to Ile564. No P protein activity was detected when the mutant P protein with this amino acid substitution was expressed in COS 7 cells. The patient was homozygous for this mutation. Furthermore, this mutation was present in 70% (14 of 20) of P protein gene alleles in Finnish patients with NKH, whereas it was not found in 20 alleles of non-Finnish patients. The results suggest that this mutation is responsible for the high incidence of NKH in Finland.
Non-canonical fibroblast growth factor signalling in angiogenesis
Authors: M. Murakami, A. Elfenbein, M. Simons
Journal: Cardiovascular Research (2007)

Whereas fibroblast growth factors (FGFs) classically transmit their signals via high-affinity tyrosine kinase receptors (FGFR1-4), recent evidence strongly implicates non-tyrosine kinase receptors (NTKR) or cell-surface FGFR-interacting proteins as important players in FGF signalling. Although NTKR have lower affinity for FGFs in comparison with cognate tyrosine kinase receptors, because of their high abundance they can effectively bind FGFs and produce unique biological effects independent of FGFRs. A prime example of such NTKR is the syndecan family of plasma membrane proteoglycans and, in particular, syndecan-4, which transmits FGF signalling via a protein kinase Calpha pathway. Another NTKR, alpha(v)beta(3) integrin, functions as an FGF signalling modulator by binding both FGF2 and FGFR1. Yet another NTKR, neural cell adhesion molecule (NCAM), can serve as an FGFR ligand and assemble an FGFR signalling complex in the absence of FGFs. Furthermore, N-cadherin, which has been reported to associate with FGFR, appears to activate FGFR in both ligand (FGF)-dependent and ligand-independent manners. Finally, gangliosides are implicated as a co-receptor system of FGFs. The biological consequence of non-canonical FGF signalling tends to be less discernable compared to the canonical FGFR activation because of the overlap between these two pathways; nevertheless, non-canonical signalling is important and sometimes essential for cellular functions. Given the diversity of FGF activities through embryonic development to adult physiology, the existence of the non-canonical signalling system may account for the different cellular response to the FGF input in different biological contexts. In this review, we will discuss recent findings related to non-canonical FGF signalling with emphasis on the endothelial biology and angiogenesis.
Banff schema for grading liver allograft rejection: An international consensus document
Authors: Anthony J. Demetris, Kenneth P. Batts, Amar P. Dhillon, Linda Ferrell, John Fung, Stephen A. Geller, John Hart, Pekka Hayry, Walter J. Hofmann, Stephan Hubscher, Josef Kemnitz, George Koukoulis, Randall G. Lee, Klaus J. Lewin, Jurgen Ludwig, Rod S. Markin, Lidija M. Petrovic, James M. Phillips, Bernard Portmann, Jorge Rakela, Parmjeet Randhawa, Finn P. Reinholt, Michel ReynÈS, Marie Robert, Hans Schlitt, Kim Solez, Dale Snover, Eero Taskinen, Swan N. Thung, Weldon G. Tillery, Russell H. Wiesner, Derek D.G. Wight, James W. Williams, Hirohiko Yamabe
Journal: Hepatology (1997)

A panel of recognized experts in liver transplantation pathology, hepatology, and surgery was convened for the purpose of developing a consensus document for the grading of acute liver allograft rejection that is scientifically correct, simple, and reproducible and clinically useful. Over a period of 6 months pertinent issues were discussed via electronic communication media and a consensus conference was held in Banff, Canada in the summer of 1995. Based on previously published data and the combined experience of the group, the panel agreed on a common nomenclature and a set of histopathological criteria for the grading of acute liver allograft rejection, and a preferred method of reporting. Adoption of this internationally accepted, common grading system by scientific journals will minimize the problems associated with the use of multiple different local systems. Modifications of this working document to incorporate chronic rejection are expected in the future.
THE PREVENTION OF POSTERIOR BOWING IN COMPOUND FRACTURE OF THE FEMUR
Authors: C. B. Alexander
Journal: BMJ (1919)

EFEBr., RVNTO O OWNr version, aniid the lodgemilenit of the lhalf-breechi of thie fetus wibtin the placentl girdle (Fig. 3).At 7.15 p.m., two houn after version, the stiIlborn female child came througl the placenta.The fetus and placenta together weighed 6 lb. 13 oz.
Dysregulation of elastin expression by fibroblasts in pulmonary emphysema: role of cellular retinoic acid binding protein 2
Authors: L Plantier, C Rochette-Egly, D Goven, A Boutten, M Bonay, G Leseche, M Fournier, B Crestani, J Boczkowski
Journal: Thorax (2008)

<h3>Background:</h3> All-trans retinoic acid (ATRA) stimulates elastin synthesis by lung fibroblasts and induces alveolar regeneration in animal models of pulmonary emphysema. However, ATRA treatment has had disappointing results in human emphysema. It was hypothesised that a defect in the ATRA signalling pathway contributes to the defect of alveolar repair in the human emphysematous lung. <h3>Methods:</h3> Fibroblasts were cultured from the lung of 10 control subjects and eight patients with emphysema. Elastin and retinoic acid receptor (RAR)-β mRNAs were measured in those cells in the presence of incremental concentrations of ATRA. RARs, retinoic X receptors (RXRs) and cellular retinoic acid binding protein (CRABP) 1 and 2 mRNAs were measured as well as CRABP2 protein content. The effect of CRABP2 silencing on elastin and RAR-β expression in response to ATRA was measured in MRC5 lung fibroblasts. <h3>Results:</h3> ATRA at 10<sup>−9</sup> M and 10<sup>−8</sup> M increased median elastin mRNA expression by 182% and 126% in control but not in emphysema fibroblasts. RAR-β mRNA expression was induced by ATRA in control as well as emphysema fibroblasts. RARs, RXRs and CRABP1 mRNAs were similarly expressed in control and emphysema fibroblasts while CRABP2 mRNA and protein were lower in emphysema fibroblasts. CRABP2 silencing abrogated the induction of elastin but not RAR-β expression by ATRA in MRC5 fibroblasts. <h3>Conclusion:</h3> Pulmonary emphysema fibroblasts fail to express elastin under ATRA stimulation. CRABP2, which is necessary for elastin induction by ATRA in MRC-5 cells, is expressed at low levels in emphysema fibroblasts. This alteration in the retinoic acid signalling pathway in lung fibroblasts may contribute to the defect of alveolar repair in human pulmonary emphysema. These results are the first demonstration of the involvement of CRABP2 in elastin expression.
Progress in Cancer Screening Over a Decade: Results of Cancer Screening From the 1987, 1992, and 1998 National Health Interview Surveys
Authors: N Breen, D K Wagener, M L Brown, W W Davis, R Ballard-Barbash
Journal: JNCI Journal of the National Cancer Institute (2001)

Screening to detect cancer early, an increasingly important cancer control activity, cannot be effective unless it is widely used.Use of Pap smears, mammography, fecal occult blood tests (FOBTs), sigmoidoscopy, and digital rectal examination (DRE) was evaluated in the 1987, 1992, and 1998 National Health Interview Surveys. Levels and trends in screening use were examined by sex, age, and racial/ethnic group. The effects of income, educational level, and health care coverage were examined within age groups. Logistic regression analyses of 1998 data were used to develop a parsimonious, policy-relevant model.Use of all screening modalities increased over the period examined; for mammography and DRE, the increase was more rapid in the first half of the decade; for the Pap test and sigmoidoscopy, the increase was more rapid in the second half of the decade. Levels of colorectal cancer screening (both sigmoidoscopy and FOBTs) in 1998 were less than the level that prevailed a decade earlier for mammography. Patterns of change for all screening modalities differed between age, sex, and racial/ethnic groups, but prevalence of use during the study, within recommended time intervals, was consistently lower among groups with lower income and less education. Logistic regression analyses indicated that insurance coverage and, to a greater extent, usual source of care had strong independent associations with screening usage when age, sex, racial/ethnic group, and educational level were taken into account.While cancer screening is generally increasing in the United States, usage is relatively low for colorectal cancer screening and among groups that lack health insurance or a usual source of care.