tbuckley/cabot-search huggingface dataset:
Uteroglobin: A Steroid-Inducible Immunomodulatory Protein That Founded the Secretoglobin Superfamily
Authors: Anil B. Mukherjee, Zhongjian Zhang, Beverly S. Chilton
Journal: Endocrine Reviews (2007)

Blastokinin or uteroglobin (UG) is a steroid-inducible, evolutionarily conserved, secreted protein that has been extensively studied from the standpoint of its structure and molecular biology. However, the physiological function(s) of UG still remains elusive. Isolated from the uterus of rabbits during early pregnancy, UG is the founding member of a growing superfamily of proteins called Secretoglobin (Scgb). Numerous studies demonstrated that UG is a multifunctional protein with antiinflammatory/ immunomodulatory properties. It inhibits soluble phospholipase A2 activity and binds and perhaps sequesters hydrophobic ligands such as progesterone, retinols, polychlorinated biphenyls, phospholipids, and prostaglandins. In addition to its antiinflammatory activities, UG manifests antichemotactic, antiallergic, antitumorigenic, and embryonic growth-stimulatory activities. The tissue-specific expression of the UG gene is regulated by several steroid hormones, although a nonsteroid hormone, prolactin, further augments its expression in the uterus. The mucosal epithelia of virtually all organs that communicate with the external environment express UG, and it is present in the blood, urine, and other body fluids. Although the physiological functions of this protein are still under investigation, a single nucleotide polymorphism in the UG gene appears to be associated with several inflammatory/autoimmune diseases. Investigations with UG-knockout mice revealed that the absence of this protein leads to phenotypes that suggest its critical homeostatic role(s) against oxidative damage, inflammation, autoimmunity, and cancer. Recent studies on UG-binding proteins (receptors) provide further insight into the multifunctional nature of this protein. Based on its antiinflammatory and antiallergic properties, UG is a potential drug target.
Use of Intensive Care Services during Terminal Hospitalizations in England and the United States
Authors: Hannah Wunsch, Walter T. Linde-Zwirble, David A. Harrison, Amber E. Barnato, Kathryn M. Rowan, Derek C. Angus
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Despite broad concern regarding the provision and cost of health care at the end of life, country-specific patterns of care have rarely been compared.Objectives: To assess the use of hospital and intensive care services during terminal hospitalizations in England and the United States, two populations with similar socioeconomic backgrounds and life expectancies.Methods: Retrospective cohort study over a 1-year period (2001) using national (England) Hospital Episode Statistics, and regional (seven U.S. states) administrative discharge data as well as English and U.S. census data. We measured hospitalization rates and death rates during hospitalization with and without intensive care.Measurements and Main Results: Age-adjusted acute hospitalization rates were 110.5 per 1,000 population in England versus 105.3 in the seven U.S. states, with the same mortality rate (0.9 per 1,000 population) in both countries. Of all deaths, 50.3% occurred in hospital in England and 36.6% in the United States, yet only 5.1% of all deaths in England involved intensive care, versus 17.2% in the United States, representing 10.1% of hospital deaths in England versus 47.1% in the United States. Greater intensive care use in the U.S. was most notable with older age; among decedents 85+ years, intensive care was used for 31.5% of medical deaths and 61.0% of surgical deaths in the United States versus 1.9 and 8.5% of deaths in England.Conclusions: Despite similar overall hospitalization rates in England and the United States, there were marked differences in terminal hospitalizations, with far greater use of intensive care services in the United States, especially among medical patients and the elderly population.
Formation of the eIF4F Translation–Initiation Complex Determines Sensitivity to Anticancer Drugs Targeting the EGFR and HER2 Receptors
Authors: Pierre Zindy, Yann Bergé, Ben Allal, Thomas Filleron, Sandra Pierredon, Anne Cammas, Samantha Beck, Loubna Mhamdi, Li Fan, Gilles Favre, Jean-Pierre Delord, Henri Roché, Florence Dalenc, Magali Lacroix-Triki, Stéphan Vagner
Journal: Cancer Research (2011)

Elucidating how cancer cells respond to antagonists of HER receptor family members is critical to understanding mechanisms of therapeutic resistance that arise in patients. In large part, resistance to such agents appears to arise from deregulation of the phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR pathway. mTOR-dependent phosphorylation of the translation repressor 4E-BP1 leads to its dissociation from eIF4E, thereby causing an increase in the formation of the eIF4F complex, which also comprises eIF4G and eIF4A. In this study, we show that trastuzumab, cetuximab, and erlotinib all decrease the formation of the eIF4F complex in breast, colon, and head and neck cancer cells, respectively. Ectopic expression of eIF4E restores the trastuzumab-dependent defect in eIF4F formation, renders cells resistant to the trastuzumab-mediated decrease in cell proliferation, and rescues breast cancer xenografts from inhibition by trastuzumab. In breast tumor specimens, the level of eIF4E expression is associated with the therapeutic response to a trastuzumab-based regimen. Together, our findings suggest that formation of the eIF4F complex may be a critical determinant of the response to anticancer drugs that target HER2 and epidermal growth factor receptor.
Plant polycistronic precursors containing non-homologous microRNAs target transcripts encoding functionally related proteins
Authors: Francisco Merchan, Adnane Boualem, Martin Crespi, Florian Frugier
Journal: Genome biology (2009)

Abstract Background MicroRNAs (miRNAs) are endogenous single-stranded small RNAs that regulate the expression of specific mRNAs involved in diverse biological processes. In plants, miRNAs are generally encoded as a single species in independent transcriptional units, referred to as MIRNA genes, in contrast to animal miRNAs, which are frequently clustered. Results We performed a comparative genomic analysis in three model plants (rice, poplar and Arabidopsis ) and characterized miRNA clusters containing two to eight miRNA species. These clusters usually encode miRNAs of the same family and certain share a common evolutionary origin across monocot and dicot lineages. In addition, we identified miRNA clusters harboring miRNAs with unrelated sequences that are usually not evolutionarily conserved. Strikingly, non-homologous miRNAs from the same cluster were predicted to target transcripts encoding related proteins. At least four Arabidopsis non-homologous clusters were expressed as single transcriptional units. Overexpression of one of these polycistronic precursors, producing Ath-miR859 and Ath-miR774, led to the DCL1-dependent accumulation of both miRNAs and down-regulation of their different mRNA targets encoding F-box proteins. Conclusions In addition to polycistronic precursors carrying related miRNAs, plants also contain precursors allowing coordinated expression of non-homologous miRNAs to co-regulate functionally related target transcripts. This mechanism paves the way for using polycistronic MIRNA precursors as a new molecular tool for plant biologists to simultaneously control the expression of different genes.
Effect of Lutein and Zeaxanthin on Macular Pigment and Visual Function in Patients with Early Age-related Macular Degeneration
Authors: Le Ma, Shao-Fang Yan, Yang-Mu Huang, Xin-Rong Lu, Fang Qian, Hong-Lei Pang, Xian-Rong Xu, Zhi-Yong Zou, Peng-Cheng Dong, Xin Xiao, Xun Wang, Ting-Ting Sun, Hong-Liang Dou, Xiao-Ming Lin
Journal: Ophthalmology (2012)
An Emergency Department Thawed Plasma Protocol for Severely Injured Patients
Authors: Zayde A. Radwan, Yu Bai, Nena Matijevic, Deborah J. del Junco, James J. McCarthy, Charles E. Wade, John B. Holcomb, Bryan A. Cotton
Journal: JAMA Surgery (2013)

In an effort to expedite delivery of plasma for patients requiring massive transfusions, US medical centers began keeping thawed plasma (TP) in their blood banks (BBs), markedly reducing time to release of plasma; however, the time to transfusion was still excessively long.To expedite delivery and transfusion of TP through implementation of an emergency department (ED) protocol.Retrospective cohort study in an American College of Surgeons-verified level I trauma center.Using the Trauma Registry of the American College of Surgeons database, we evaluated all adult trauma patients admitted from June 1, 2009, through August 31, 2010, who arrived directly from the scene, were the institution's highest level trauma activation, and received at least 1 U of red blood cells and 1 U of plasma in the first 6 hours after admission. The protocol was initiated in February 2010 by giving 4 U of AB plasma to patients in the ED. Patients were then divided into 2 groups: those admitted 8 months before (TP-BB) and 8 months after implementing TP location change (TP-ED).Primary outcome was time to first unit of plasma. Secondary outcomes included 24-hour blood use and 24-hour and 30-day mortality.A total of 294 patients met the study criteria (130 in the TP-BB group and 164 in the TP-ED). Although the patient demographics were similar, TP-ED patients had greater anatomical injury (median Injury Severity Score, 18 vs 25; P = .02) and more physiologic disturbances (median weighted Revised Trauma Score, 6.81 vs 3.83; P = .008). The TP-ED patients had a shorter time to first plasma transfusion (89 vs 43 minutes, P < .001). The TP-ED protocol was associated with a reduction in 24-hour transfusion of RBCs (P = .04), plasma (P = .04), and platelets (P < .001). Logistic regression identified TP-ED as an independent predictor of decreased 30-day mortality (odds ratio, 0.43; 95% CI, 0.194-0.956; P = .04).We demonstrated that implementation of an ED-TP protocol expedites transfusion of plasma to severely injured patients. This approach is associated with a reduction in overall blood product use and a 60% decreased odds in 30-day mortality.
SKELETAL MUSCLE AS A PRIVILEGED SITE FOR ORTHOTOPIC SKIN ALLOGRAFTS
Authors: Clyde F. Barker, R. E. Billingham
Journal: The Journal of Experimental Medicine (1973)

A semi-privileged status for rat skin allografts may be achieved by placing them on extensive open beds formed by panniculus carnosus muscle which prevents contact of the transplant with host skin. Such allografts enjoy approximately a twofold increase in their life expectancy, even if transplanted across a strong histocompatibility barrier. Experiments are described which rule out stress or a "central" weakening of response, such as enhancement, as explanations of this phenomenon. Intact skin "islands" separated from surrounding host skin on all sides by a broad border of bared panniculus were also found to serve as privileged sites. Dye injected into these islands failed to reach the regional nodes until about the 15th day after their preparation. These studies indicate that a lymphatic deficit is responsible for the observed privileged status of the allografts.
Oxaliplatin combined with irinotecan and 5-fluorouracil/leucovorin (OCFL) in metastatic colorectal cancer: a phase I–II study
Authors: Y. Seium, R. Stupp, T. Ruhstaller, P. Gervaz, G. Mentha, M. Philippe, A. Allal, C. Trembleau, J. Bauer, R. Morant, A.D. Roth
Journal: Annals of Oncology (2005)
IMMUNOREACTIONS INVOLVING PLATELETS
Authors: N. Raphael Shulman
Journal: The Journal of Experimental Medicine (1958)

Regulated intravenous doses of quinidine were given to patients with the antibody of quinidine purpura to produce controlled thrombocytopenia without clinical sequelae. The degree of thrombocytopenia and the rate at which it developed were dependent on the relative plasma concentration of quinidine and antibody. By relating in vivo changes in platelet levels to concurrent in vitro tests for antibody activity and to quantitative relationships between reactants determined in Papers I and III of this series, it was concluded that the amount of antibody which attaches to platelets when thrombocytopenia develops is insufficient to cause complement fixation or platelet agglutination. Platelets do not appear to be destroyed directly by reaction with antibody in vivo. The minimal amount of antibody which does attach to platelets in vivo appears to increase their susceptibility to the usual mechanisms of sequestration. Megakaryocytes and blood vessels do not appear to be affected directly by the antibody which causes quinidine purpura, and hemorrhagic manifestations of the disease appear to be consequent to changes in platelets alone. A safe method of performing in vivo tests for the presence of an antibody of drug purpura is described. The implications of the present work in idiopathic thrombocytopenic purpura are discussed.
HLA-DRB genotyping of an Italian mummy from the 16th century with signs of rheumatoid arthritis
Authors: G Fontecchio, L Ventura, R Azzarone, M A Fioroni, G Fornaciari, F Papola
Journal: Annals of the Rheumatic Diseases (2006)

Some paleopathological studies suggest that rheumatoid arthritis originated in the New World (among ancient Native Americans in Tennessee and neighbouring areas, 5000–500 BC); only after the discovery of America was the origin of the disease attributed to the Old World.1 In 1996, under the floors of the San Francisco church (Arezzo, Italy), a female mummy was discovered. This 50–55-year-old woman, re-named the “Braids Lady”, died at the end of the 16th century. Several diagnostic examinations disclosed distinctive rheumatoid arthritis skeletal deformities due to rheumatoid arthritis in her body: large erosions of the metacarpophalangeal joints of the left hand; lateral deviation of all the fingers, with a typical “Z” deformation of the first …
Role of the prostaglandin in norepinephrine release during augmented renal sympathetic nerve activity in the dog.
Authors: J A Oliver, R R Sciacca, J Pinto, P J Cannon
Journal: Circulation Research (1981)

To determine the role of the prostaglandins on renal norepinephrine release, the effect of inhibition of prostaglandin synthesis was examined in anesthetized dogs during reflex activation of the renal adrenergic nerves. Hypotension increased the renal vein plasma concentrations of norepinephrine from 380 +/- 59 to 608 +/- 106 pg/ml (mean +/- SEM; P less than 0.01) and of PGE2 from 55 +/- 7 to 81 +/- 41 pg/ml (P less than 0.05). Subsequent administration of indomethacin or meclofenamate lowered the renal venous concentration of PGE2 to 26 +/- 3 pg/ml (P less than 0.01), had no significant effect on the norepinephrine concentration (620 +/- 89 pg/ml). Administration of indomethacin or meclofenamate to dogs with sodium depletion lowered renal venin plasma concentration of PGE2 from 108 +/- 40 to 20 +/- 3 pg/ml (0.05 less than P less than 0.1) but had no effect on the renal venous norepinephrine concentration (475 +/- 50 vs. 397 +/- 46 pg/ml). In dogs fed a normal salt diet, inflation of a balloon placed in the thoracic inferior vena cava lowered cardiac output and increased the renal venous concentrations of norepinephrine from 212 +/- 60 to 496 +/- 112 pg/ml (P less than 0.01) and of PGE2 from 28 +/- 5 to 96 +/- 18 pg/ml (P less than 0.01). Subsequent administration of indomethacin lowered the renal venous concentration of PGE2 to 16 +/- 5 pg/ml (P less than 0.01), but had no significant effect on the concentration of norepinephrine (548 +/- 91 pg/ml). During the three experimental conditions examined, renal blood flow was lowered by inhibition of prostaglandin synthesis. These results in the dog suggest that the attenuating effect that prostaglandins exert on the renal vascular action of the adrenergic nerves is not due to inhibition of norepinephrine release.
Hepatic venoocclusive disease in autologous bone marrow transplantation of solid tumors and lymphomas.
Authors: L J Ayash, M Hunt, K Antman, L Nadler, C Wheeler, T Takvorian, A Elias, J H Antin, T Greenough, J P Eder
Journal: Journal of Clinical Oncology (1990)

Retrospective review of 291 solid tumor and lymphoma patients undergoing autologous bone marrow transplantation (BMT) was performed to determine the influence of pretransplant characteristics and preparative regimen to the development of hepatic venoocclusive disease (VOD). Twelve patients (4.1%) developed a clinical syndrome of right upper quadrant (RUQ) tenderness or hepatomegaly, jaundice, and ascites, with or without encephalopathy, within 40 days of marrow reinfusion. Evidence of metastatic liver disease was the only pretransplant characteristic predictive for VOD (P = .0002). Sex, age, histology, hepatitis B serology, and elevated liver function tests were not predictive. No individual preparative agent had a significant effect on the development of VOD. However, a single 2-hour infusion of carmustine (BCNU) (greater than or equal to 450 mg/m2) led to an increased incidence of VOD when compared with the same dose administered in a fractionated schedule (P = .0258) when given with two other chemotherapeutic agents. Seven of eight autopsy specimens confirmed the clinical diagnosis of VOD. The four patients in whom clinical VOD resolved had lower median peak bilirubins (7.3 v 15.9 mg/dL), lower median peak creatinines (2.1 v 4.1 mg/dL), and relatively quick engraftment of neutrophils (mean, 18.7 days). One of the four patients in whom VOD resolved had other grade 4 (life-threatening) toxicities in contrast to eight of eight who succumbed. In summary, VOD is an uncommon complication in autotransplantation of solid tumors and lymphomas. Our data suggest caution in selecting patients with known metastatic liver disease and consideration of a fractionated BCNU schedule especially in combination with other alkylating agents.
Estrogen and Progesterone Reduce Lipid Accumulation in Human Monocyte-Derived Macrophages
Authors: Jane A. McCrohon, Shirley Nakhla, Wendy Jessup, Keith K. Stanley, David S. Celermajer
Journal: Circulation (1999)

Background —Males have an earlier onset and greater prevalence of clinical atherosclerosis than age-matched females, which is consistent with an atheroprotective effect of the female sex steroids, estrogen and progesterone. We therefore examined the effects of estrogen and progesterone on human foam cell formation, a key early event in atherogenesis. Methods and Results —Monocytes from healthy female and male donors were obtained from white cell concentrates and allowed to differentiate into macrophages over 10 days. These human monocyte-derived macrophages (MDMs) were exposed to either control (0.1% vol/vol ethanol) or estrogen or progesterone treatment on days 3 through 10. Lipid loading was achieved on days 8 through 10 by incubation with acetylated LDL. Lipid from the MDMs was then extracted for analysis of cholesteryl ester (CE) content. 17β-Estradiol at both physiological (2 nmol/L) and supraphysiological (20 and 200 nmol/L) concentrations produced a significant reduction in macrophage CE content (88±3%, 88±2%, and 85±4%, respectively; P &lt;0.02 compared with control). Physiological and supraphysiological levels of progesterone (2, 10, and 200 nmol/L) produced an even more dramatic reduction in CE content (74±9%, 56±10%, and 65±8%, respectively; P &lt;0.002 compared with control). This effect could be abrogated by coincubation with the progesterone receptor antagonist RU486. Neither estrogen nor progesterone produced a reduction in lipid loading in male-donor–derived MDMs. Detailed lipid trafficking studies demonstrated that both estrogen and progesterone altered macrophage uptake and/or processing of modified LDL. Conclusions —Physiological levels of estrogen and progesterone are associated with a female-sex–specific reduction in human macrophage lipid loading, which is consistent with an atheroprotective effect.
Risk of injury on artificial turf and natural grass in young female football players
Authors: Kathrin Steffen, Thor Einar Andersen, Roald Bahr
Journal: British Journal of Sports Medicine (2007)

Background: Artificial turf is becoming increasingly popular, although the risk of injury on newer generations of turf is unknown. Aim: To investigate the risk of injury on artificial turf compared with natural grass among young female football players. Study design: Prospective cohort study. Methods: 2020 players from 109 teams (mean (SD) 15.4 (0.8) years) participated in the study during the 2005 football season. Time-loss injuries and exposure data on different types of turf were recorded over an eight-month period. Results: 421 (21%) players sustained 526 injuries, leading to an injury incidence of 3.7/1000 playing hours (95% CI 3.4 to 4.0). The incidence of acute injuries on artificial turf and grass did not differ significantly with respect to match injuries (rate ratio (RR) 1.0, 95% CI 0.8 to 1.3; p = 0.72) or training injuries (RR 1.0, 95% CI 0.6 to 1.5, p = 0.93). In matches, the incidence of serious injuries was significantly higher on artificial turf (RR 2.0, 95% CI 1.3 to 3.2; p = 0.03). Ankle sprain was the most common type of injury (34% of all acute injuries), and there was a trend towards more ankle sprains on artificial turf than on grass (RR 1.5, 95% CI 1.0 to 2.2; p = 0.06). Conclusion: In the present study among young female football players, the overall risk of acute injuries was similar between artificial turf and natural grass.
The Costs of Visits to Emergency Departments
Authors: Robert M. Williams
Journal: New England Journal of Medicine (1996)

Many visits to emergency departments are for minor medical problems, and these visits are criticized as being expensive and economically inefficient. This study examines the marginal costs (the extra costs for an additional visit) of emergency department visits.Monthly data on the costs of hospital and physicians' services from 1991 through 1993 were obtained from a sample of six community hospitals in Michigan. The data were analyzed with ordinary least-squares regression techniques to determine the ratio of marginal to average costs. Average and marginal costs were then determined for 24,010 visits during 12 randomly selected weeks in 1993. A visit by an individual patient was the unit analysis, and visits were classified as nonurgent, semiurgent, or urgent according to explicit criteria. Costs and charges were determined for all visits and were classified according to the degree of urgency.For all emergency department visits, the average charge was $383, the average cost was $209, and the marginal cost was $88 (42 percent of the average cost). Thirty-two percent of the visits were classified as nonurgent, 26 percent as semiurgent, and 42 percent as urgent. For nonurgent visits, the average charge was $124, the average cost was $62, and the marginal cost was only $24. For semiurgent visits, the average charge was $312, the average cost was $159, and the marginal cost was $67. For urgent visits, the average charge was $621, the average cost was $351, and the marginal cost was $148.The true costs of nonurgent care in the emergency department are relatively low. The potential savings from a diversion of nonurgent visits to private physicians' offices may therefore be much less than is widely believed.