tbuckley/cabot-search huggingface dataset:
Degradation of Human Exonuclease 1b upon DNA Synthesis Inhibition
Authors: Mahmoud El-Shemerly, Pavel Janscak, Daniel Hess, Josef Jiricny, Stefano Ferrari
Journal: Cancer Research (2005)

In response to DNA damage, signaling pathways are triggered that either block the cell division cycle at defined transitions (G1-S and G2-M) or slow down progression through the S phase. Nucleases play important roles in DNA synthesis, recombination, repair, and apoptosis. In this study, we have examined the regulation of human exonuclease 1 (hEXO1b). The endogenous hEXO1b protein was only detected upon enrichment by immunoprecipitation. We found that hEXO1b was constantly expressed throughout the cell cycle. However, treatment of cells with agents that cause arrest of DNA replication led to rapid degradation of hEXO1b. This effect was fully reversed upon removal of the block. Analysis of synchronized cells showed that degradation of hEXO1b during the S phase was strictly dependent on DNA synthesis inhibition. DNA damage caused by UV-C radiation, ionizing radiation, cisplatin, or the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine did not affect hEXO1b stability. We show that hEXO1b was phosphorylated in response to inhibition of DNA synthesis and that phosphorylation coincided with rapid protein degradation through ubiquitin-proteasome pathways. Our data support the evidence that control of exonuclease 1 activity may be critical for the maintenance of stalled replication forks.
Rebuttal from Authors re: Richard J. Sylvester. Bacillus Calmette-Guérin versus Mitomycin C for the Treatment of Intermediate-Risk Non–Muscle-Invasive Bladder Cancer: The Debate Continues. Eur Urol 2009;56:266–8
Authors: Riikka Järvinen, Eero Kaasinen, Anna Sankila, Erkki Rintala
Journal: European Urology (2009)
PHYSIOLOGIC CONSIDERATIONS IN THE TREATMENT OF OBSTRUCTIVE JAUNDICE
Authors: WALTMAN WALTERS
Journal: JAMA (1926)

The more common lesions of the biliary tract complicated by obstructive jaundice are stones in the common bile duct, empyema of the gallbladder with cholangeitis, stricture of the common duct, and tumors of the head of the pancreas, usually carcinomatous, rarely inflammatory. In this group, relief of the obstruction and removal or drainage of the infected gallbladder, when such is indicated, is followed by recovery unless the obstruction is the result of a carcinoma at the head of the pancreas. In the latter condition, although the patient eventually dies from the malignant disease, an anastomosis between the distended gallbladder and the intestine allows the distended biliary tract to empty; jaundice disappears and the itching, so often the only distressing symptom in this group of cases, is relieved. General functional impairment of the body and tissues in patients with obstructive jaundice is evidenced by the loss of weight and strength, the
Identification of a new point mutation in hypoxanthine phosphoribosyl transferase responsible for hyperuricemia in a female patient
Authors: Taku Inokuchi, Yuji Moriwaki, Sumio Takahashi, Zenta Tsutsumi, Tuneyoshi Ka, Asako Yamamoto, Jidong Cheng, Tomoko Hashimoto-Tamaoki, Toshikazu Hada, Tetsuya Yamamoto
Journal: Metabolism (2004)
Swine dust causes intense airways inflammation in healthy subjects.
Authors: K A Larsson, A G Eklund, L O Hansson, B M Isaksson, P O Malmberg
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Fourteen healthy, nonsmoking subjects were exposed to swine dust while weighing pigs for 3 to 5 h in a swine-confinement building. All but one participant was previously unexposed to swine dust. Bronchoalveolar lavage (BAL) was performed and blood samples were drawn before and after exposure. Total dust and endotoxins were measured by air sampling in filter cassettes carried in the breathing zone. The air concentration of endotoxins was 0.6 (range, 0.08 to 1.3) micrograms/m3, and of total dust was 13.5 (range, 5.6 to 24.0) mg/m3. The air concentrations of ammonia, carbon dioxide, and hydrogen sulfide were low. The exposure induced fever in three and malaise and drowsiness in six of the subjects. Compared with preexposure values, a 75-fold increase in neutrophilic granulocytes, a two- to threefold increase in mononuclear cells, and a significant increase in eosinophilic granulocytes were observed in the BAL fluid obtained 1 day (approximately 22 h) after exposure (p < 0.01 for all cell types). The fibronectin and albumin concentrations in the BAL fluid significantly increased (p < 0.01 for both). The number of leukocytes in peripheral blood was almost doubled 6 h after exposure and was still significantly elevated after 1 day. Blood concentrations of orosomucoid and C-reactive protein (CRP) were significantly increased 1 day after exposure. We conclude that exposure to swine dust in a swine-confinement building induces an intense inflammatory reaction in the airways as assessed by BAL. The airway cellular response is characterized by a dramatic increase in neutrophils. The components in the swine dust that cause the reaction are not clear.
RANDOMISED TRIAL OF ENDOSCOPIC VERSUS PERCUTANEOUS STENT INSERTION IN MALIGNANT OBSTRUCTIVE JAUNDICE
Authors: AntonyG. Speer, R. Christopher, G. Russell, AdrianR.W. Hatfield, KennethD. Macrae, PeterB. Cotton, RichardR. Mason, JosephW.C. Leung, Joan Houghton, ChristinaA. Lennon
Journal: The Lancet (1987)
More intensive care unit beds are needed
Authors: P. A Cupples, A. P Makin, S. S McKinnon, N. D Storey
Journal: BMJ (1997)

Editor—Peter G M Wallace and Paul G Lawler highlight the need for regional intensive care unit transfer teams.1 As members of a regional transfer team based at the Western Infirmary in Glasgow we write to confirm the value of such teams and the need for more beds in intensive care units. The Western Infirmary's transfer team, which was established in 1975, has transferred 3595 critically ill patients, with only one death in transit. We provide a transfer service to over 32 hospitals …
The priority of the individual in cultural inheritance
Authors: Taylor Davis, Eric Margolis
Journal: Behavioral and Brain Sciences (2014)

Abstract Smaldino's proposed extension of the theory of cultural evolution embraces emergent group-level traits. We argue, instead, that group-level traits reduce to the traits of individuals, particularly when it comes to the question of how group-level traits are inherited or transmitted, and that this metaphysical fact is integral to the theory of cultural evolution.
Decreased Coronary Flow Reserve in Hypertrophic Cardiomyopathy Is Related to Remodeling of the Coronary Microcirculation
Authors: R. Krams, M. J. M. Kofflard, D. J. Duncker, C. Von Birgelen, S. Carlier, M. Kliffen, F. J. ten Cate, P. W. Serruys
Journal: Circulation (1998)

Ischemia occurs frequently in hypertrophic cardiomyopathy (HCM) without evidence of epicardial stenosis. This study evaluates the hypothesis that the occurrence of ischemia in HCM is related to remodeling of the coronary microcirculation.End-diastolic septal wall thickness was significantly increased in patients with HCM (25.8+/-2.9 mm) in comparison with cardiac transplant recipients (control subjects: 11.4+/-3.0 mm; P<0.05). Although the diameter of the left anterior descending coronary artery was similar in both groups (3.0+/-0.8 versus 3.0+/-0.5 mm, P=NS), the coronary resistance reserve (CRR=CRRbasal/CRRhyperemic), corrected for extravascular compression (end-diastolic left ventricular pressure), was reduced to 1.5+/-0.6 in HCM (P<.05; control, 2.6+/-0.8). Arteriolar lumen (AL) divided by wall area was lower in HCM (21+/-5% versus 30+/-4%; P<.05), and capillary density tended to decrease (from 1824+/-424 to 1445+/-513 per mm2, P=.11) in HCM. CRR was linearly related to normalized AL according to the formula CRR=O.1 AL-0.45 (r=.57; P<.05). Further analysis revealed that CRR, AL, and capillary density were all linearly related to the degree of hypertrophy.Decrements in CRR were related to changes of the coronary microcirculation. Both the decrease in CRR and these changes in the coronary microcirculation were related to the degree of hypertrophy. All these factors might contribute to the well-known occurrence of ischemia in this patient group.
Persisting CD28<sup>null</sup>T cells, but not regulatory T cells, in muscle tissue of myositis patients after immunosuppressive therapy
Authors: Ingela Loell, Jayesh Pandya, Sukanya Raghvan, Mei Zong, Vivianne Malmström, Ingrid E Lundberg
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Introduction</h3> Polymyositis (PM) and dermatomyositis (DM) are characterised by infiltration of macrophages and T cells in skeletal muscle tissue. Immunosuppressive treatment has limited effects on the number of infiltrating cells providing a basis for persistent immune reaction targeting muscle fibers. Regulatory T cells are key players in the maintenance of peripheral tolerance by controlling T cell reactivity to self-antigen. CD28<sup>null</sup> T cells are a highly enriched subset of proinflammatory T cells in patients with autoimmune diseases and are suggested to be resistant to apoptosis. Our aim was to establish whether the persisting T cells in myositis tissue belong to the regulatory T cell subset or to the apoptosis resistant, proinflammatory CD28<sup>null</sup> T cell subset. <h3>Method</h3> Muscle tissue biopsies were obtained from 14 patients with PM/DM before and after 8 (4–16) month of treatment with glucocorticoids and additional immuno-suppressive drugs. Immunohistochemistry for CD3, FOXP3 and CD28<sup>null</sup> surrogate marker CD244 was performed on muscle tissue. For clinical evaluation serum creatine kinase (s-CK) and functional index (FI) of myositis was used. <h3>Results</h3> Patients significantly improved in Functional Index following treatment (p=0.002) but only one patient regained 100% muscle function. Serum CK-levels went back to normal in all patients after treatment (p=0.004). The CD28<sup>null</sup> T cell frequencies were increased or unaffected for majority of the patients, 11 out of 14, which was statistically significant (p&lt;0.05). The proportion of T<sub>regs</sub> did not differ before and after treatment at group level, but for the majority of the patients the frequency was lower or unaffected (10 out of 14). <h3>Conclusions</h3> Despite normalised CK-levels, patients only show partial functional improvement and many displayed persistent T cells in muscle tissue post-treatment. The relative number of regulatory T cells was unchanged or decreased, while the CD28<sup>null</sup> T cell proportion was mainly increased post-treatment suggesting that high doses of glucocorticoid treatment might impair the regulation of autoreactive/pathogenic T cells including the CD28<sup>null</sup> T cell populations in affected muscle.
Physician s Guide to Wills, Trusts, and Estates
Authors: Bernard D. Hirsh
Journal: JAMA (1962)

Almost every physician intends to make a will before he dies. Yet, it is a common occurrence for physicians to die without a will. Perhaps this neglect is due to inertia or an aversion to deal with matters which contemplates one's own demise. Ironically, this procrastination is shared with members of the legal profession. Lawyers who have spent a lifetime drawing wills for their clients often die without having drawn their own will. This guide can help you to minimize the taxes that may be due at your death and to understand the important aspects of a will so that you can plan more wisely for your family's future security.
Atlas of Infant Surgery
Authors: John G. Raffensperger
Journal: JAMA (1968)

<h3>Pediatric Plastic Surgery: Trauma</h3> , vol 1, by Francis X. Paletta, 245 pp, 419 illus, $27.50, St. Louis: C. V. Mosby Co., 1967. These two new books by St. Louis surgeons are fine additions to the pediatric surgical literature. They complement one another and should be side by side on the surgeon's bookshelf. Dr. Lewis'<i>Atlas of Infant Surgery</i>beautifully describes and illustrates the common congenital and neoplastic lesions encountered in practice. He succinctly outlines the special requirements for successful surgical care of infants. Each chapter is introduced with a graphic discussion of the embryology and diagnosis of a particular lesion. Alternative surgical solutions are mentioned, but the author limits the illustrations of operations to techniques he has found successful. The chapter on imperforate anus is particularly up to date, for I believe this is the first text in this country to illustrate the sacroabdominoperineal approach and the importance of puborectal
Treatment of Diabetic Cystopathy
Authors: C. FRIMODT-MØLLER
Journal: Annals of Internal Medicine (1980)

Neurogenic bladder disorders in diabetic patients may result in insufficient bladder emptying because of loss of reflex detrusor contraction. In those who are asymptomatic or have only moderate signs of diabetic cystopathy, treatment choices are scheduled voiding by the triple-voiding technique, cholinergic treatment either daily or twice weekly, and transurethral surgery of the bladder neck. In patients with total urine retention, an indwelling catheter will decrease the overstretched detrusor muscle. Cholinergic treatment with initially high parenteral doses of bethanecol may help to diminish residual urine. Transurethral surgery is often mandatory in such cases. Decensus of the bladder in females often requires surgery. Deficient bladder sensation is irreversible in diabetics, and follow-up of treatment should be lifelong.
Effects of Rofecoxib or Naproxen vs Placebo on Alzheimer Disease Progression
Authors: Paul S. Aisen, Kimberly A. Schafer, Michael Grundman, Eric Pfeiffer, Mary Sano, Kenneth L. Davis, Martin R. Farlow, Shelia Jin, Ronald G. Thomas, Leon J. Thal
Journal: JAMA (2003)

Context Laboratory evidence that inflammatory mechanisms contribute to neuronal injury in Alzheimer disease (AD), along with epidemiological evidence, suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) may favorably influence the course of the disease. Objective To determine whether treatment with a selective cyclooxygenase (COX) -2 inhibitor (rofecoxib) or a traditional nonselective NSAID (naproxen) slows cognitive decline in patients with mild-to-moderate AD. Design Multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to study medications. Setting Forty ambulatory treatment centers affiliated with the Alzheimer's Disease Cooperative Study consortium. Participants Participants with mild-to-moderate AD (Mini-Mental State Examination score of 13-26) were recruited from December 1999 to November 2000 using clinic populations, referrals from community physicians, and local advertising. Stable use of cholinesterase inhibitors, estrogen, low-dose aspirin, and vitamin E was allowed. Participants with inflammatory diseases that might respond to the study medications were excluded. Of 474 participants screened, 351 were enrolled. Interventions Once-daily rofecoxib, 25 mg, or twice-daily naproxen sodium, 220 mg, or placebo. Main Outcome Measures The primary outcome measure was the 1-year change in the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) subscale score. Secondary outcome measures included the Clinical Dementia Rating scale sum-of-boxes, the Neuropsychiatric Inventory, the Quality of Life-AD, and the time to attainment of significant end points (4-point decline from baseline ADAS-Cog score, 1-step worsening on the global Clinical Dementia Rating scale, 15-point decline on the ADCS activities of daily living inventory, institutionalization, or death). Results The 1-year mean (SD) change in ADAS-Cog scores in participants treated with naproxen (5.8 [8.0]) or rofecoxib (7.6 [7.7]) was not significantly different from the change in participants treated with placebo (5.7 [8.2]). Results of secondary analyses showed no consistent benefit of either treatment. Fatigue, dizziness, and hypertension were more commonly reported in the active drug groups, and more serious adverse events were found in the active treatment group than in the placebo group. Conclusion The results of this study indicate that rofecoxib or low-dose naproxen does not slow cognitive decline in patients with mild-to-moderate AD.
Maximal Blood Lactate Level Acts as a Major Discriminant Variable in Exercise Testing for Coronary Artery Disease Detection in Men
Authors: Jean-Claude Barthélémy, Frédéric Roche, Jean-Michel Gaspoz, André Geyssant, Pascal Minini, Anestis Antoniadis, Éric Page, Jean-Éric Wolf, Claude Wilner, Karl Isaaz, Chantale Cavallaro, Jean-René Lacour
Journal: Circulation (1996)

The interpretation of exercise stress testing for coronary artery disease detection is affected by the many differences in chosen variables and mathematical methods. We conducted a prospective trial to evaluate a global muscle fatigue parameter--the blood lactate level achieved at maximal exercise--as a method of distinguishing between diseased and nondiseased coronary status.We evaluated 236 consecutive male patients without previous myocardial infarction who had been referred for the diagnosis of coronary artery disease. None of the patients had cardiomyopathy, severe cardiac heart failure, or valvular heart disease. Blood lactate concentration at maximal exercise was measured as well as other classic variables. Correlations between variables and coronary status as assessed by coronary arteriography were described using receiver operating characteristic (ROC) curves and logistic regression analysis. The first four most powerful variables (lactate level, maximal power output, exercise duration, and percentage of maximal predicted heart rate), which are directly representative of the global functional capacity, showed values of 0.777, 0.775, 0.760, and 0.740, respectively, by ROC curve analysis. Mean +/- SD blood lactate level at peak exercise reached 7.68 +/- 2.70 mmol/L in the 153 diseased and 10.56 +/- 2.75 mmol/L in the 83 nondiseased patients (P < .0001). After adjustment for other variables, blood lactate level remained a significant predictor of coronary artery disease by logistic regression analysis (adjusted odds ratio, 1.2; confidence interval, 1.04 to 1.4).Global muscle fatigue as assessed by lactate levels in the blood at maximal exercise appears to be a powerful distinguisher of diseased and nondiseased coronary status.
Human RORγt+CD34+ Cells Are Lineage-Specified Progenitors of Group 3 RORγt+ Innate Lymphoid Cells
Authors: Elisa Montaldo, Luiz Gustavo Teixeira-Alves, Timor Glatzer, Pawel Durek, Ulrik Stervbo, Wiebke Hamann, Marina Babic, Daniela Paclik, Katharina Stölzel, Jörn Gröne, Laura Lozza, Kerstin Juelke, Nadine Matzmohr, Fabrizio Loiacono, Francesca Petronelli, Nicholas David Huntington, Lorenzo Moretta, Maria Cristina Mingari, Chiara Romagnani
Journal: Immunity (2014)
Fluorescent Treponemal Antibody-Absorption (FTA-ABS) Test for Syphilis
Authors: Wilbur E. Deacon
Journal: JAMA (1966)

The development of the fluorescent treponemal antibody-absorption (FTA-ABS) test<sup>1</sup>has been the result of continued attempts to improve the original FTA procedures,<sup>2,3</sup>in terms of sensitivity and specificity. Test improvement was made possible by the discovery that nonpathogenic treponemes such as<i>Treponema microdentium</i>and the Reiter treponeme share antigens in common with<i>T pallidum</i>, and the corresponding common antibodies are of frequent occurrence in serums from normal individuals. It was found, however, that such antibodies could be removed from test serums by intact Reiter treponeme absorption and that in serums so treated and subsequently examined there was an increased specificity and sensitivity of test results.<sup>4</sup>Later, the use of sonic-disrupted Reiter treponemes in place of intact organisms for absorption was described, the resulting procedure being identified as the FTA-ABS test.<sup>1</sup>At present, a stable water-soluble extract from Reiter treponemes is employed instead of sonicate. This change
High-Level Sensitization to Foods is Associated with Asthma ER Visits and Current Asthma in the U.S.: Results from NHANES 2005-2006
Authors: R. Jaramillo, M. Massing, S.H. Sicherer, R.A. Wood, S.A. Bock, A.W. Burks, D.C. Zeldin, A.H. Liu
Journal: Journal of Allergy and Clinical Immunology (2009)
Government pays 61% of healthcare costs in US
Authors: B. Roehr
Journal: BMJ (2008)

We combine household-level data on the choice to purchase flood insurance with experiment-based risk preference data and subjective risk perception data. The sample covers a wide geographic area (the entire U.S. Gulf Coast and Florida’s Atlantic Coast) and includes individuals exposed to varying levels of risk. This work represents one of very few analyses to do so. Results indicate that our experiment-based measure of risk aversion over the loss domain positively and significantly correlates with the decision to purchase a flood policy, as do perceived expectations of hurricane damage, eligibility for disaster assistance, and credibility of insurance providers. <i>(JEL D81, R22)</i>
Abstract 4006: Soluble ALK4 extracellular domain antagonizes oncogenic Cripto signaling and inhibits tumor growth
Authors: Benjamin T. Spike, Jonathan A. Kelber, Evan C. Booker, Richard L. Klemke, Geoffrey M. Wahl, Wylie W. Vale, Peter C. Gray
Journal: Cancer Research (2010)

Abstract Cripto is a small GPI-anchored glycoprotein that plays key roles during normal development and in tumorigenesis. Cripto is expressed at aberrantly high levels in human tumors and blocking its oncogenic effects on activin/Nodal/TGF-beta, Erk/MAPK and PI3K/Akt pathways represents a promising therapeutic strategy. Cripto functions as a Nodal co-receptor and binds directly to the extracellular domain (ECD) of the activin/Nodal type I receptor ALK4. We have shown that a kinase-deleted ALK4 mutant deficient in activin binding (ALK4-L75A) retains Cripto binding and can block Cripto effects on activin and Nodal signaling. We hypothesized that soluble ALK4-L75A ECD proteins would similarly bind Cripto and disrupt oncogenic Cripto function. To test this, we generated two soluble constructs incorporating the ALK4-L75A ECD, one with a C-terminal His tag (sALK4-L75A-His) and the other consisting of an ALK4-L75A ECD-Fc fusion with an N-terminal FLAG tag (sALK4-L75A-Fc). We expressed the sALK4-L75A-His and sALK4-L75A-Fc proteins in 293T cells and then purified them from conditioned media using Ni-NTA agarose and Protein-A agarose, respectively. The sALK4-L75A-Fc protein dose-dependently inhibited 125I-Cripto binding to 293T cells transfected with full length ALK4. In addition, sALK4-L75A-Fc blocked 125I-Cripto binding to untransfected human mammary epithelial MCF10A cells. In accordance with these binding data, sALK4-L75A-His inhibited Cripto-dependent Nodal signaling in 293T cells and sALK4-L75A-Fc inhibited Nodal-induced Smad2 phosphorylation in human NCCIT cells. sALK4-L75A-His also blocked Cripto-induced PI3K signaling while sALK4-L75A-Fc inhibited Cripto-induced MCF10A cell proliferation. Importantly, we have shown that sALK4-L75A-Fc can also inhibit the growth of tumor xenografts derived from NCCIT cells at doses where no toxicity was observed. Thus, we provide the first evidence that soluble forms of ALK4 inhibit oncogenic Cripto signaling. The efficacy of a soluble ALK4 receptor as an antitumor agent points to the utility of Cripto antagonists in the treatment of human cancer. 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 4006.
RELATIONSHIP BETWEEN SYSTOLIC BLOOD PRESSURE AT ADMISSION AND INDEX OF MICROCIRCULATORY RESISTANCE LEVEL AFTER PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Yuma Kurouzmi, Noritoshi Ito, Yasuji Doi, Daisuke Tonomura, Tomoaki Natsukawa, Noriaki Yamada, Ken-ichiro Okada, Hirotaka Sawano, Yasuyuki Hayashi, Tatsuro Kai, Toru Hayashi
Journal: Journal of the American College of Cardiology (2011)