tbuckley/cabot-search huggingface dataset:
Incidence of Down's Syndrome in Rhode Island
Authors: Gail Barsel-Bowers
Journal: JAMA (1982)

<h3>To the Editor.—</h3> Using data from metropolitan Atlanta, Adams et al (1981; 246:758) have reported a decrease in the crude incidence of Down's syndrome from 1.33/1,000 births in 1960 to approximately 0.99/1,000 births in 1978. According to the authors, the explanation for this decrease is a reduction in the proportion of births to women aged 35 years or older. They suggest that estimates of resources for future services should be based on these data. We have been able to ascertain all cytogenetically proved cases of Down's syndrome live births in Rhode Island during 1976 to 1980. Since Rhode Island has only two cytogenetic laboratories where blood specimens for chromosomal analysis are routinely sent and one child development center where most children with Down's syndrome are followed up, we are confident that the ascertainment of all live-born children with Down's syndrome is as complete as can be achieved anywhere. Our demographic
RelA and RelB Transcription Factors in Distinct Thymocyte Populations Control Lymphotoxin-Dependent Interleukin-17 Production in γδ T Cells
Authors: Iwona Powolny-Budnicka, Marc Riemann, Simone Tänzer, Roland M. Schmid, Thomas Hehlgans, Falk Weih
Journal: Immunity (2011)
Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML
Authors: Zhihong Zeng, Dos D. Sarbassov, Ismael J. Samudio, Karen W. L. Yee, Mark F. Munsell, C. Ellen Jackson, Francis J. Giles, David M. Sabatini, Michael Andreeff, Marina Konopleva
Journal: Blood (2006)
1002. Therapeutic Design Principles for Achieving Long-Term Suppression of HIV-1 with RNA Interference
Authors: Joshua N. Leonard, David V. Schaffer
Journal: Molecular Therapy (2005)

RNA interference (RNAi) is a robust and highly evolutionarily conserved mechanism for down-regulating gene expression through targeted mRNA cleavage. It has been shown that RNAi can effectively reduce the expression of human immunodeficiency virus 1 (HIV-1) genes in vitro, but since several nucleotides of non-homology between the siRNA and the viral RNA are sufficient to significantly undermine target degradation, the emergence of resistant strains is a major potential obstacle to long term suppression of this highly mutable virus. We seek to identify quantitative design strategies for using RNAi to suppress HIV-1 in a manner that minimizes the chance of viral escape. In the results presented here, we have focused on RNAi strategies that target the viral TAR loop - a very highly conserved non-coding sequence that participates in a positive feedback loop with the viral early transcription factor, Tat.
High-Altitude Pulmonary Edema and Patent Foramen Ovale
Authors: Peter J. Fagenholz, N. Stuart Harris
Journal: JAMA (2007)

To the Editor: In their case-control study, Dr Allemann and colleagues identified an association between patent foramen ovale (PFO) and susceptibility to high-altitude pulmonary edema (HAPE) in mountaineers. In HAPEsusceptible participants, they observed low arterial oxygen saturation that preceded the onset of clinical HAPE. Their study suggests that intracardiac right-to-left shunting through a PFO is partly responsible for this hypoxemia. We believe that subclinical pulmonary edema may also contribute to the early hypoxemia observed in this group and suggest a means of evaluating this in future studies. The ascent to Capanna Regina Margherita induces subclinical pulmonary edema, even in those persons not developing clinical HAPE. Allemann et al describe no attempt to determine the degree of pulmonary edema present when their participants’ oxygen saturations were measured. Persons who subsequently developed clinical HAPE may have already incurred significant, if subclinical, pulmonary edema when their oxygen saturations were measured. Correspondingly, a portion of the exaggerated hypoxemia noted in HAPE-susceptible individuals who did not progress to clinical HAPE may share a similar etiology. Chest radiography was only performed at the study’s conclusion to confirm or exclude the diagnosis of HAPE and is relatively insensitive for identifying the early pulmonary edema that precedes clinical HAPE. Given this, even if radiography had been used to assess for pulmonary edema at the time oxygen saturations were measured, it might not have proven useful. As an alternative, chest ultrasonography may be more helpful to quantify pulmonary edema. The comet-tail technique of chest ultrasonography has been correlated with radiographic and thermodilution measures of pulmonary edema. The technique does not require equipment beyond the transthoracic ultrasound equipment usually used for monitoring pulmonary artery pressures in HAPE research. It may help distinguish the relative contributions of edema and intracardiac shunting to the hypoxemia present before and during clinical HAPE.
Improved Helper Virus-Free Packaging System for HSV Amplicon Vectors Using an ICP27-Deleted, Oversized HSV-1 DNA in a Bacterial Artificial Chromosome
Authors: Yoshinaga Saeki, Cornel Fraefel, Tomotsugu Ichikawa, Xandra O Breakefield, E.Antonio Chiocca
Journal: Molecular Therapy (2001)

Herpes simplex virus type 1 (HSV-1) amplicons are prokaryotic plasmids containing one or more transcriptional units and two cis-acting HSV-1 sequences: a viral origin of DNA replication and a viral DNA cleavage/packaging signal. In the presence of HSV-1 "helper" functions, amplicons are replicated and packaged into HSV-1 virions. Despite recent improvements in packaging methods, stocks of amplicon vectors are still contaminated with replication-competent helper virus at a frequency of 10−4–10−6. To overcome this problem, we report that: (i) genetic modifications of HSV-1 genomes can be routinely achieved in Escherichia coli, either by homologous or site-specific recombination, (ii) a novel HSV-1 bacterial artificial chromosome (fHSVΔpacΔ27 0+), which has a deletion in the essential gene encoding ICP27 and an addition of ICP0 "stuffer" sequences to increase its size to 178 kb, supports the replication and packaging of cotransfected amplicon DNA without generating replication-competent helper virus (<1 helper virus per 108 TU amplicon vectors), and (iii) the resulting amplicon stocks have titers of up to 3–10 × 108 TU/ml after concentration. Elimination of replication-competent helper virus from HSV-1 amplicon vector stocks further improves safety in gene transfer applications.
P116Exposure of rats to continuous light impairs cardiac cell-to-cell coupling and decrease threshold to VF: however Omacor intake offers protection
Authors: T Benova, C Viczenczova, J Radosinska, B Bacova, J Zurmanova, V Knezl, M Zeman, B Obsitnik, N Tribulova
Journal: Cardiovascular Research (2014)

Background and Purpose: Melatonin in addition to regulation of circadian rhythm exhibits antihypertensive, free radicals scavenging and antiarrhythmic effects as we have shown recently. While melatonin deficiency and lower omega-3 index observed in pts suffering from CHD and hypertension as well as in SHR can contribute to disease progression and pro-arrhythmia. Continuous light suppresses melatonin production that is deleterious to the heart. We aimed to explore whether cardioprotective compound Omacor might be beneficial in these conditions. Design and Methods: Males, age-matched SHR and healthy Wistar rats were housed under standard 12h light/12h dark cycle or exposed to continuous light under 24h light/day for 6 weeks. Half of these rats received Omacor (omega-3 ethyl ester, 25g/kg diet). Left ventricular tissue was analyzed for mRNA of electrical coupling protein, connexin-43 (Cx43), proinflammatory NFkB and iNOS - by using real time PCR, while protein expression of Cx43 and PKCε by western blots. Inducible ventricular fibrillation (VF) was examined using isolated-perfused heart. Key Results: Comparing to the healthy rats plasma levels of melatonin and omega-3 index were lower in SHR. Continuous light caused mild elevation of BP in healthy rats and enhanced it in SHR and also decreased threshold to induce VF in both groups comparing to the rats under normal light cycle. Myocardial Cx43 mRNA level was not altered but Cx43 protein and its functional phosphorylated forms (which affect electrical coupling) were decreased in SHR due to continuous light and partially restored by Omacor. Treatment with Omacor increased threshold for VF and it was associated with attenuation of continuous light-induced increase of myocardial iNOS and proinflammatory NFkB gene expression that down-regulates Cx43. Conclusions: Findings indicate that continuous light itself impairs Cx43 channels-mediated cardiac cell-to-cell coupling that may increase propensity of SHR to malignant arrhythmias. These adverse effects can be, in part, eliminated by treatment with Omacor.
Antigen-specific B cells can acquire and present the rheumatoid arthritis candidate autoantigen aggrecan from a non-internalisable surface
Authors: M. Ciechomska, C. Wilson, A. Rowan, J. H. Robinson, A. M. Knight
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Recent experiments propose an essential role for B cells in the development of several autoimmune diseases either as autoantibody-producing cells or an antigen presenting cells (APC). However, the exact contribution of B cells in the early stages of rheumatoid arthritis (RA) remains unknown. One candidate autoantigen in RA is aggrecan, which, together with the disaccharide polymer hyaluron (HA), forms a major structural component of cartilage as part of an extracellular matrix (ECM). As B cells have been shown to be capable of acquiring antigens tethered to the surface of other cells, it is also possible that ECM tethered components may also be potential targets for joint-specific B cells. Therefore, we aimed to test the hypothesis that autoreactive B cells are important in the initiation of RA due to their unique ability to acquire integral joint autoantigens such as aggrecan leading to the activation of autoreactive T cells and subsequently disease progression. <h3>Materials and methods</h3> To monitor the acquisition of aggrecan we generated aggrecan-specific B cells. We have then addressed whether antigen-specific B cells are able to extract aggrecan tethered via HA to a non-internalisable surface measured by flow cytometry and T cell activation assays. <h3>Results</h3> We show, as expected, that aggrecan-specific B cells are able to present soluble aggrecan to CD4 T cells approximately 10<sup>3</sup>–10<sup>4</sup> times more efficiently than non-specific B cells. Based on kinetic analysis, we also demonstrate that aggrecan-specific B cells are able to acquire HA-tethered aggrecan from an immobilised surface within periods as short as 1 h. Furthermore, we show that aggrecan acquisition by specific B cells leads to efficient autoreactive T cell activation. Finally we have also extended this novel assay to mimic the synovial ECM, where aggrecan-specific B cells can extract aggrecan directly from nasal cartilage explants. <h3>Conclusion</h3> We demonstrate that antigen-specific B cells can acquire immobilised aggrecan leading to the stimulation of autoreactive CD4 T cells. These findings support the hypothesis that B cells may play an essential APC role in the early stage of joint pathogenesis. Therefore, a better understanding of these early processes could lead to define novel targets for therapy suitable in the early phase of RA.
Infectious Diseases in Obstetrics and Gynecology
Authors: John A. Morris
Journal: JAMA (1975)

Today's obstetrician-gynecologist finds himself uncommonly concerned with chorioamnionitis, puerperal sepsis, postoperative febrile morbidity, the venereal diseases, "prophylactic" antibiotic therapy, anaerobic infections, and the like. There is, to my knowledge, no more current, readily available, or comprehensive reference work than this excellent text by Monif and 15 contributors. The text is divided into four sections; of these, section II ("Organisms") is concerned in the main with viral, bacterial, protozoal, fungal, and spirochetal infections. Every chapter is current, timely, informative, and useful to the clinician. This section comprises one half the text and is sufficiently strong to stand alone. In contrast, section I ("General Considerations") could easily have been omitted. Or it might have been replaced by a chapter, such as chapter 23 of section IV ("Problem Areas: Gynecological"), which is written by Bill Ledger and is entitled "Anaerobic Infection." Dr. Ledger addresses the problem immediately in this chapter, describing the huge
Idiopathic Bence Jones Proteinuria
Authors: Robert A. Kyle, Philip R. Greipp
Journal: New England Journal of Medicine (1982)

We studied seven patients with idiopathic Bence Jones proteinuria (excretion > 1.0 g per 24 hours) who did not have acquired Fanconi's syndrome or an intact monoclonal immunoglobulin in the serum. None had evidence of overt multiple myeloma, of its variants, of systemic amyloidosis, or of malignant lymphoproliferative diseases when the proteinuria was recognized. In three of the seven patients, symptomatic multiple myeloma (associated with systemic amyloidosis in one) developed 8.8 to 21.1 years later. A fourth patient has asymptomatic myeloma and has not been treated. A fifth patient had an evolving myeloma at nine years but died of an unrelated cause. The remaining two patients still have apparently benign Bence Jones proteinuria after 7.7 and 12 years. Plasma-cell labeling indexes were low in all cases tested. This experience shows that although idiopathic Bence Jones proteinuria may remain stable for years, multiple myeloma or amyloidosis often develops, and consequently these patients must be kept under observation indefinitely. (N Engl J Med. 1982; 306:564–7.)
Budesonide As Induction Treatment For Active Eosinophilic Esophagitis In Adolescents And Adults: A Randomized, Double-blind, Placebo-controlled Study
Authors: A. Straumann, L. Degen, S. Felder, C. Bussmann, S. Conus, C. Thalmann, H. Simon
Journal: Journal of Allergy and Clinical Immunology (2009)
Myocardial Notch Signaling Reprograms Cardiomyocytes to a Conduction-Like Phenotype
Authors: Stacey Rentschler, Alberta H. Yen, Jia Lu, Nataliya B. Petrenko, Min Min Lu, Lauren J. Manderfield, Vickas V. Patel, Glenn I. Fishman, Jonathan A. Epstein
Journal: Circulation (2012)

Notch signaling has previously been shown to play an essential role in regulating cell fate decisions and differentiation during cardiogenesis in many systems including Drosophila, Xenopus, and mammals. We hypothesized that Notch may also be involved in directing the progressive lineage restriction of cardiomyocytes into specialized conduction cells.In hearts where Notch signaling is activated within the myocardium from early development onward, Notch promotes a conduction-like phenotype based on ectopic expression of conduction system-specific genes and cell autonomous changes in electrophysiology. With the use of an in vitro assay to activate Notch in newborn cardiomyocytes, we observed global changes in the transcriptome, and in action potential characteristics, consistent with reprogramming to a conduction-like phenotype.Notch can instruct the differentiation of chamber cardiac progenitors into specialized conduction-like cells. Plasticity remains in late-stage cardiomyocytes, which has potential implications for engineering of specialized cardiovascular tissues.
Clinical profile of homozygous JAK2 617V&gt;F mutation in patients with polycythemia vera or essential thrombocythemia
Authors: Alessandro M. Vannucchi, Elisabetta Antonioli, Paola Guglielmelli, Alessandro Rambaldi, Giovanni Barosi, Roberto Marchioli, Rosa Maria Marfisi, Guido Finazzi, Vittoria Guerini, Fabrizio Fabris, Maria Luigia Randi, Valerio De Stefano, Sabrina Caberlon, Agostino Tafuri, Marco Ruggeri, Giorgina Specchia, Vincenzo Liso, Edoardo Rossi, Enrico Pogliani, Luigi Gugliotta, Alberto Bosi, Tiziano Barbui
Journal: Blood (2007)
A comparison of global questions versus health status questionnaires as measures of the severity and impact of asthma
Authors: E.a. Barley, P.w. Jones
Journal: European Respiratory Journal (1999)

This study compared estimates of the severity and impact of asthma recorded using global questions of the type used in diary cards with health status measurements obtained using comprehensive questionnaires. Seventy-four outpatients with asthma, aged 17-76 yrs (mean 48 yrs) participated. Mean+/-SD forced expiratory volume in one second (FEV1) was 72+/-26% predicted. Patients recorded morning and evening peak expiratory flow rate (PEFR) and scaled their responses to the questions: "How has your asthma been today?" (asthma severity) and "How much effect has your asthma had on your life today?" (asthma impact) for 2 weeks. They then completed Juniper9s Asthma Quality of Life Questionnaire (AQLQ) and the St George9s Respiratory Questionnaire (SGRQ). Diary card scores for asthma impact were less severe than for asthma severity (p&lt;0.0001). Both correlated with AQLQ and SGRQ total scores (r&gt;0.7; p&lt;0.0001). Some patients responded 9none9 for asthma severity (n=10) or asthma impact (n=13) on all 14 days of recording. For these patients, FEV1 was &lt;80% predicted, morning PEFR was &lt;90% predicted and their AQLQ and SGRQ scores indicated significant health impairment. Diary card scores for asthma severity and impact were correlated with health status, but these global questions were insensitive in mild disease. Responses to these questions were influenced by their wording, so the number of symptom-free days calculated from diary cards will depend on the questions used. Standardization is required before symptom-free days can be used as a reliable measure of treatment efficacy.
Maternal drug abuse and human term placental xenobiotic and steroid metabolizing enzymes in vitro.
Authors: P Paakki, H Stockmann, M Kantola, P Wagner, U Lauper, R Huch, E Elovaara, P Kirkinen, M Pasanen
Journal: Environmental Health Perspectives (2000)

We evaluated the impact of maternal drug abuse at term on human placental cytochrome P450 (CYP)-mediated (Phase I) xenobiotic and steroid-metabolizing activities [aromatase, 7-ethoxyresorufin O-deethylase (EROD), 7-ethoxycoumarin O-deethylase (ECOD), pyrene 1-hydroxylase (P1OH), and testosterone hydroxylase], and androstenedione-forming isomerase, NADPH quinone oxidoreductase (Phase II), UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST) activities in vitro. Overall, the formation of androstenedione, P1OH, and testosterone hydroxylase was statistically significant between control and drug-abusing subjects; we observed no significant differences in any other of the phase I and II activities. In placentas from drug-abusing mothers, we found significant correlations between ECOD and P1OH activities (p < 0. 001), but not between ECOD and aromatase or P1OH and EROD activities; we also found significant correlations between blood cotinine and UGT activities (p < 0.01). In contrast, in controls (mothers who did not abuse drugs but did smoke cigarettes), the P1OH activity correlated with ECOD, EROD (p < 0.001), and testosterone hydroxylase (p < 0.001) activities. Our results (wider variation in ECOD activity among tissue from drug-abusing mothers and the significant correlation between P1OH and ECOD activities, but not with aromatase or EROD activities) indicate that maternal drug abuse results in an additive effect in enhancing placental xenobiotic metabolizing enzymes when the mother also smokes cigarettes; this may be due to enhancing a "silent" CYP form, or a new placental CYP form may be activated. The change in the steroid metabolism profile in vitro suggests that maternal drug abuse may alter normal hormonal homeostasis during pregnancy.
Responsibilities of individual doctors
Authors: N. Dickson
Journal: BMJ (2010)

Chris Isles’ disturbing account (doi:10.1136/bmj.c1412) highlights both the continuing shortage of doctors in some parts of the country and the apparent failure of some agencies and doctors to provide reliable information about their skills and competence.

Of course, the onus is on employers to ensure that the doctors they employ are fit to carry out the role expected of them. However, that does not take away the responsibility of individual doctors to ensure that what they say about themselves is accurate in every particular.

The experience from this hospital raises serious questions about the role of locum agencies. These are …
The ABO and Lewis Blood-Group System
Authors: Donald M. Marcus
Journal: New England Journal of Medicine (1969)

DESPITE the recognized importance of the ABO and Lewis antigens in blood typing and transfusion, few physicians appreciate the extraordinary complexity of this system and its association with human disease. These antigens are found in secretions throughout the body and on the surface of epithelial and endothelial cells. Current interest in kidney transplantation has directed attention to their presence in the renal vascular endothelium. ABO incompatibility between mother and fetus may produce infertility or hemolytic disease of the newborn, and persons of certain blood groups have an increased susceptibility to peptic ulcer or gastric cancer. The purpose of this review . . .
Neuropeptide activity in venous effluent from the hyperaemic upper limb following short-term arterial occlusion
Authors: K.J. MiscH, M.W. GREAVES
Journal: British Journal of Dermatology (1983)

Journal Article Neuropeptide activity in venous effluent from the hyperaemic upper limb following short‐term arterial occlusion Get access K.J. MiscH, K.J. MiscH Institute of Dermatology, Homerton Grove, London E9 6BX Search for other works by this author on: Oxford Academic Google Scholar M.W. GREAVES M.W. GREAVES Institute of Dermatology, Homerton Grove, London E9 6BX Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 109, Issue 3, 1 September 1983, Pages 367–369, https://doi.org/10.1111/j.1365-2133.1983.tb03557.x Published: 01 September 1983
HLA typing in idiopathic hemochromatosis: Distinction between homozygotes and heterozygotes with biochemical expression
Authors: Mark L. Bassett, June W. Halliday, Lawrie W. Powell
Journal: Hepatology (1981)

In a study of 20 families with idiopathic hemochromatosis, relatives of probands were classified as either homozygous, heterozygous, or normal according to their HLA phenotype. An abnormality in the serum iron concentration, total iron-binding capacity, or serum ferritin concentration was present in all homozygotes and in 25% of heterozygotes. In heterozygotes, the mean total iron-binding capacity was significantly decreased, and the mean hepatic iron concentration was significantly increased compared to normals. However, in contrast to homozygotes, clinical evidence of iron overload was not observed in heterozygotes, and there was no biochemical or histological evidence of liver disease resulting from excessive iron stores. Progressive iron overload did not develop in 44 heterozygotes who were studied for up to 16 yr.
332 PEROXIDIZED FATTY ACIDS MAY INDUCE A PRO-INFLAMMATORY RESPONSE IN THE LIVER AND MAY TRIGGER THE OUTBREAK OF NON-ALCOHOLIC STEATOHEPATITIS (NASH)
Authors: T. Boehm, S. Sagmeister, H. Berger, A. Daryabeigi, E. Haslinger, M. Murkovic, N. Rohr-Udilova, K. Stolze, W. Huber, B. Grasl-Kraupp
Journal: Journal of Hepatology (2010)