tbuckley/cabot-search huggingface dataset:
Use of recombinant congenic and congenic strains of NOD mice to identify a new insulin-dependent diabetes resistance gene.
Authors: D V Serreze, M Prochazka, P C Reifsnyder, M M Bridgett, E H Leiter
Journal: The Journal of Experimental Medicine (1994)

Insulin-dependent diabetes mellitus (IDDM) in NOD/Lt mice represents a complex polygenic disease. NOR/Lt is a recombinant congenic strain (RCS) in which limited regions of the NOD/Lt genome have been replaced by genome from the C57BL/KsJ strain. NOR mice are insulitis resistant and diabetes free despite genetic identity with NOD at numerous chromosomal regions containing previously described insulin-dependent diabetes (Idd) genes, including the strongly diabetogenic H2g7 major histocompatibility complex (MHC) haplotype. The present study revealed BKs-derived genome on segments of chromosomes (Chr) 1, 2, 4, 5, 7, 11, 12, and 18, approximating 11.6% of the total NOR genome analyzed. (NOD x NOR)F2 segregation analysis was employed to identify chromosomal regions in NOR containing Idd resistance alleles. IDDM developed in 33% (10/30) of F1 females, and 29.3% (36/123) of F2 females aged to 1 yr. A previously unrecognized diabetes resistance locus (designated Idd13r) strongly protective in homozygous state was identified on NOR Chr 2 in linkage with the Il1 alpha structural gene. The existence of this locus was confirmed by construction of a NOD stock congenic for NOR-derived markers on Chr 2. Our analysis shows the utility of RCS and congenic stocks for the identification and isolation of non-MHC genes with strong antidiabetogenic functions.
Survival after heart surgery continues to improve after publication of mortality data
Authors: O. Mashta
Journal: BMJ (2009)

Outcomes for adult cardiac patients have improved substantially in the past five years, even though more elderly and high risk patients are now being treated. Mortality rates after coronary artery surgery have fallen by 21% and for isolated valves by a third, a study by the Society for Cardiothoracic Surgery of Great Britain and Ireland has found.

For their report, Demonstrating Quality: The Sixth National Adult Cardiac Surgical Database , the society studied more than 400 000 operations. They found that since national publication of mortality rates in cardiac surgery began in 2001 the quality of care for patients has improved.

Fewer than one in 100 elective surgery patients younger than 70 who …
Altered peptide ligands can control CD4 T lymphocyte differentiation in vivo.
Authors: C Pfeiffer, J Stein, S Southwood, H Ketelaar, A Sette, K Bottomly
Journal: The Journal of Experimental Medicine (1995)

Antigen priming of naive CD4 T cells can generate effector CD4 T cells that produce interleukin 4 (T helper [Th]2-like) or interferon-gamma (Th1-like). Using a system in which priming leads to responses dominated by one or the other of these cell types, we show that varying either the antigenic peptide or the major histocompatibility complex class II molecule can determine whether Th1-like or Th2-like responses are obtained. Our results show that peptide/major histocompatibility complex class II complexes that interact strongly with the T cell receptor favor generation of Th1-like cells, while those that bind weakly favor priming of Th2-like T cells. Thus, signals from the T cell receptor can influence the differentiation of CD4 T cells into specific types of effector cells.
Development of New Tuberculosis Vaccines: A Global Perspective on Regulatory Issues
Authors: Michael J Brennan, Uli Fruth, Julie Milstien, Rosemary Tiernan, Sergio de Andrade Nishioka, Liliana Chocarro
Journal: PLoS Medicine (2007)

VaccineInitiative of the World Health Organization (WHO) Initiative for Vaccine Research convened a working meeting of regulators, investigators, and clinicians from developing and developed countries involved in tuberculosis (TB) vaccine regulation and research (see Text S1 for a list of participants).The purpose of the meeting was to specifi cally discuss the regulatory challenges for testing and introducing investigative TB vaccines into countries where the disease is endemic.A particular focus of this meeting was a discussion among representatives of regulatory authorities from the Developing Countries Vaccine Regulators Network (DCVRN) with those of the United Kingdom and the United States about the important challenges that each regulatory agency will need to address if effective new TB vaccines are to be registered in their countries.The DCVRN is a new WHO initiative establishing a network of vaccine regulators from nine countries: Brazil, China, Cuba, the Republic of South Korea, India, Indonesia, the Russian Federation, South Africa, and Thailand.It provides a forum for discussion, advancement of knowledge, and exposure to policies and procedures pertaining to evaluation of clinical trial proposals and clinical trial data.In this article we describe key vaccine and regulatory issues arising during the meeting.We propose innovative recommendations that may be used to make important decisions for proceeding into various stages of clinical trials and for the fi nal registration of new TB vaccines.We hope that this article will be particularly valuable to regulatory authorities of developing countries.
Clinical Evaluation of a New Oral Nonmercurial Diuretic
Authors: BENJAMIN WAINFELD, JACOB J. YARVIS, ARTHUR FANKHAUSER
Journal: Circulation (1957)

The oral administration of the organomercurial drugs in patients requiring prolonged management of congestive failure has been rather unsatisfactory because of occasional toxic signs and symptoms. With the development of the pyrimidinedione derivatives as diuretic agents and encouraging pharmacologic studies in animals, clinical trial is warranted. A group of 24 patients who had received injections of mercurial diuretics for at least 6 months prior to study were treated with this new diuretic. Results of this experience are described.
Reference Values for Continuous Glucose Monitoring in Chinese Subjects
Authors: Jian Zhou, Hong Li, Xingwu Ran, Wenying Yang, Qiang Li, Yongde Peng, Yanbing Li, Xin Gao, Xiaojun Luan, Weiqing Wang, Weiping Jia
Journal: Diabetes Care (2009)

OBJECTIVE The widespread clinical application of continuous glucose monitoring (CGM) is limited by the lack of generally accepted reference values. This multicenter study aims to establish preliminary normal reference values for CGM parameters in a sample of healthy Chinese subjects. RESEARCH DESIGN AND METHODS A total of 434 healthy individuals with normal glucose regulation completed a 3-day period of glucose monitoring using a CGM system. The 24-h mean blood glucose (24-h MBG) and the percentage of time that subjects' blood glucose levels were ≥140 mg/dl (PT140) and ≤70 mg/dl (PT70) within 24 h were analyzed. RESULTS There was excellent compliance of finger stick blood glucose values with CGM measurements for subjects. Among the 434 subjects, the daily blood glucose varied from 76.9 ± 11.3 to 144.2 ± 23.2 mg/dl. The 24-h MBG, PT140, and PT70 were 104 ± 10 mg/dl, 4.1 ± 5.8%, and 2.4 ± 5.3%, respectively. As for these parameters, no significant differences were found between men and women. The 95th percentile values were adopted as the upper limits of CGM parameters, which revealed 119 mg/dl (6.6 mmol/l) for 24-h MBG, 17.1% for PT140, and 11.7% for PT70. CONCLUSIONS We recommend a 24-h MBG value &amp;lt;119 mg/dl, PT140 &amp;lt;17% (4 h), and PT70 &amp;lt;12% (3 h) as normal ranges for the Chinese population.
The clinical relevance of BAALC and ERG expression levels in pediatric AML
Authors: M C H Hermkens, M M van den Heuvel-Eibrink, S T C J M Arentsen-Peters, A Baruchel, J Stary, D Reinhardt, M Zimmerman, V de Haas, R Pieters, C M Zwaan
Journal: Leukemia (2012)
The Next Challenge in Cancer Immunotherapy: Controlling T-Cell Traffic to the Tumor
Authors: Jean-Pierre Abastado
Journal: Cancer Research (2012)

Abstract One of the steps that limits the efficacy of T-cell–based immunotherapy of cancer is T-cell access to the tumor. We recently showed that several chemotherapeutic drugs induce intratumoral expression of chemokines that attract effector T cells. Moreover, in a cohort of patients with melanoma who had been treated with dacarbazine, one of the most frequently used chemotherapies for metastatic melanoma, tumor response to the treatment correlated with intratumoral expression of T-cell–attracting chemokines and with T-cell infiltration. These findings reveal the possibility of developing novel systemic strategies aimed at improving T-cell homing to tumors. Such strategies, used alone or in combination with adoptive T-cell therapies or therapeutic cancer vaccines, may prove to be more efficient in prolonging patient survival. Cancer Res; 72(9); 2159–61. ©2012 AACR.
Disabling Supraventricular Tachycardia of Wolff-Parkinson-White Syndrome (Type A) Controlled by Surgical A-V Block and a Demand Pacemaker after Epicardial Mapping Studies
Authors: MARSHALL C. DUNAWAY, SPENCER B. KING, CHARLES R. HATCHER, R. BRUCE LOGUE
Journal: Circulation (1972)

A patient with W-P-W syndrome (type A) and disabling supraventricular tachycardia was studied with epicardial mapping prior to surgical interruption of the circus pathway. Analysis of the delta vector and results of the epicardial mapping strongly suggested aberrant pathway located very posteriorly and crossing the atrioventricular sulcus in or adjacent to the interventricular septum. A circus movement responsible for the supraventricular tachycardia was felt to be a mechanism of antegrade A-V conduction and retrograde accessory bundle conduction. Attempts to interrupt the aberrant pathway primarily were unsuccessful, and surgical A-V block was performed. An epicardial demand pacemaker was inserted as a safety feature. Since the operation the patient has been free of supraventricular tachycardia. The postoperative electrocardiograms demonstrated antegrade accessory pathway conduction, but neither antegrade nor retrograde A-V conduction. Failure to interrupt the accessory pathway after incision of the entire right posterior A-V sulcus supported a location with, or to the left of, the atrioventricular septum for the pathway. This case, with the recent results of others, adds to the further understanding of accessory pathway location in W-P-W syndrome (type A).
Margaret McCartney: For Scotland, the real winner is democracy
Authors: M. McCartney
Journal: BMJ (2014)

A sleepless night. I was on the sleeper train—that little bit of Scotland that comes nightly to London—unable to stay away from my Twitter feed, my heart pounding. The votes are now in. Scotland is staying, the Union is unbroken, and even though I voted No (it’s complicated), I feel tearfully disappointed for the passionate Yes supporters, sitting in George Square in central Glasgow, gutted (as we say).

The real winner is democracy. The voter turnout was 85%, compared with just over 50% at the Scottish election in 2011. On buses, in queues, in shops, pubs, and coffee houses, the conversation has been all about the referendum. The past few days have been electric: tartan, saltires, posters in the windows of ordinary homes (“yes I said …
286. Biodistribution and Cearance Following Intraperitoneal Injection of Murine Interleukin-12 Plasmid Formulated with a Novel Polymeric Delivery System
Authors: Elaine Brunhoeber, Majed Matar, Khursheed Anwer, Jason G. Fewell
Journal: Molecular Therapy (2006)

Intraperitoneal delivery of an interleukin-12 (IL-12) plasmid formulated with a novel polymeric delivery system (PPC) into nanocomplexes has shown efficacy in treating a variety of disseminated peritoneal malignancies in mice. Pre-clinical GLP studies were conducted to evaluate the biodistribution of plasmid following intraperitoneal administration of increasing doses of PPC formulated murine IL-12 plasmid into CD-1 mice. In the study a total of 54 male mice and 54 female mice were evaluated. Animals were divided equally into control group, low dose (10 mg; ∼1.5 mg/m2) and high dose (250 mg, ∼38 mg/m2) groups. The doses selected for this study were based upon preliminary toxicology studies and represent significant multiples of the starting dose currently being used in Phase I clinical testing. Specifically the low and high doses are approximately 2.5 and 60 times the starting dose in humans based on a 25 g mouse and a 70 kg human. Animal tissues were harvested at 3, 30 and 88 days after treatment and analyzed using a qPCR assay that was determined to be sensitive to ∼10 copies of plasmid/mg DNA and quantifiable at >100 copies/mg DNA. A total of 11 samples were collected from each animal and included; injection site, blood, gonads, liver, heart, kidneys, lung, mesenteric lymph nodes, spleen, left femur and brain. The results indicated that following IP dosing, plasmid was detectable in all examined tissues with the highest levels located in the organs of the peritoneal cavity and at the site of injection. Considerably lower plasmid levels were found in the blood, heart, femur (marrow) and brain. Distribution did not appear to be affected by dose with proportional levels found in all tissues at the different doses. An approximate 95% clearance occurred within 1 month with 99% clearance by three months in almost all tissues, however slightly higher levels still remained at the sight of injection at the end of the study. In summary these data indicate that plasmid formulated with PPC and injected IP will lead to both local and systemic uptake of plasmid. However, the plasmid is readily cleared from all tissues over time. Full-time employee of Expression Genetics, Inc.
Cardiopulmonary Resuscitation-Reply
Authors: Leon Chameides
Journal: JAMA (1993)

<h3>In Reply.</h3> —The phrase from the 1992 PALS guidelines, "This technique enables effective support of oxygenation...," is challenged as unreferenced and inaccurate. However, Drs Burke and Mellick have omitted the subsequent qualifying phrase, "although carbon dioxide elimination may be suboptimal." The statement is referenced at the beginning of the paragraph.<sup>1</sup>In a study of dogs weighing 21 to 30 kg, the PaO<sub>2</sub>was consistently maintained above 130 mm Hg during 30 minutes of manual ventilation via percutaneous needle cricothyrotomy.<sup>1</sup>The paucity of pediatric data is acknowledged in the guidelines: "Percutaneous needle cricothyrotomy has only been effective in small animals. [reference]. However, only anecdotal reports of this method of ventilation in children have been published so further evaluation is needed." The two clinical review articles cited by Burke and Mellick confirm that needle cricothyrotomy may not support oxygenation and ventilation in adults. As Yealy et al observed, "The
THE BLOOD-PRESSURE RAISING PRINCIPLE OF THE SUPRARENAL GLAND.
Authors: JOKICHI TAKAMINE
Journal: JAMA (1902)

which in turn is connected with a tube filled with half saturated sodium carbonate solution, to prevent the blood from clotting, leading to the manometer.The solutions-adrenalin or preparations from the supra- renal gland-for injection should be very carefully prepared, and of such a strength that they can be read- ily diluted in case the primary injection is found to produce too marked a rise in the blood pressure.The injections may be made either in the jugular vein or into the femoral vein, preferably the latter.As will be noticed from tracing (No. 5) an injection of the prepa- ration that is being assayed is preceded or followed by the injection of a known quantity of a standard prepa- ration.
Baby milk companies accused of breaching marketing code
Authors: J. Wise
Journal: BMJ (1997)

A consortium of 27 religious and health organizations has released a report entitled "Cracking the Code," which criticizes the bottle-feeding marketing techniques used by Nestle, Gerber, Mead Johnson, Wyeth, and Nutricia. Research for the report was carried out in Thailand, Bangladesh, South Africa, and Poland using a random sample of 800 mothers and 120 health workers in each country. In all 4 sites, women had received information that violated the World Health Organization's 1981 international code of marketing breast milk substitutes. Violations included promoting artificial feeding without recognizing breast feeding as the best source of infant nutrition. The investigation also found that women and health workers in all 4 sites received free samples of artificial milk. The report includes detailed examples of manufacturer representatives making unrequested visits to give product information to mothers, providing incentives to health workers to promote products, and promoting products outside of health care facilities. While the International Association of Infant Food Manufacturers condemned the study as biased, the Nestle company promised to review the allegations contained in the report and to deal with any breaches in the code. The Interagency Group on Breastfeeding Monitoring, which prepared the report, was created in 1994 to provide data to groups supporting a boycott of Nestle for code violations.
Results of T4 Surgical Cases in the Japanese Lung Cancer Registry Study: Should Mediastinal Fat Tissue Invasion Really be Included in the T4 Category?
Authors: Shun-ichi Watanabe, Hisao Asamura, Etsuo Miyaoka, Meinoshin Okumura, Ichiro Yoshino, Yoshitaka Fujii, Yoichi Nakanishi, Kenji Eguchi, Masaki Mori, Noriyoshi Sawabata, Kohei Yokoi
Journal: Journal of Thoracic Oncology (2013)
P256 Aclidinium bromide: a Phase IIb, dose-finding study
Authors: D. Singh, H. Magnussen, A. Kirsten, S. Mindt-Pruefert, C. Caracta, D. Jarreta, E. Garcia Gil
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Aclidinium bromide, a second-generation, long-acting muscarinic antagonist with low systemic activity, is in clinical development for the twice daily maintenance treatment of chronic obstructive pulmonary disease (COPD). This Phase IIb study investigated the dose-response bronchodilation of aclidinium twice daily vs placebo and an active control (formoterol 12 μg twice daily) in patients with moderate to severe COPD. <h3>Methods</h3> In this double-blind, double-dummy, cross-over study, 79 patients received 7-day treatments of aclidinium 100 μg, 200 μg and 400 μg, formoterol 12 μg and placebo twice daily over five treatment periods separated by a 7-day washout. The primary endpoint was change from baseline in normalised forced expiratory volume in 1 second (FEV<sub>1</sub>) area under the curve (AUC)<sub>0–12</sub> at Day 7. Other efficacy assessments included change from baseline at Day 7 in normalised FEV<sub>1</sub> AUC<sub>0–24</sub> and morning pre-dose (trough) and peak FEV<sub>1</sub>. Adverse events (AEs) were reported throughout the study. <h3>Results</h3> Aclidinium provided dose-dependent bronchodilation compared with placebo as assessed by change from baseline in normalised FEV<sub>1</sub> AUC<sub>0–12</sub> and FEV<sub>1</sub> AUC<sub>0–24</sub> at Day 7 (Abstract P256 table 1). The bronchodilation provided by aclidinium 400 μg during the first 12 h was comparable to the active control, formoterol 12 μg. Aclidinium improved morning pre-dose trough FEV<sub>1</sub> and peak FEV<sub>1</sub> after 7 days compared with placebo; the 400 μg dose was most comparable to formoterol 12 μg. Aclidinium was well tolerated; the safety profile of all doses was comparable to that of placebo. <h3>Conclusion</h3> A dose-dependent bronchodilation was observed with aclidinium twice daily. The bronchodilation provided by the highest dose of aclidinium (400 μg) twice daily was comparable to formoterol 12 μg twice daily. The safety profile of aclidinium was similar to placebo, with no dose-dependent AEs observed.
238. Stem Cell Gene Delivery to Immunocompetent Mice Using a Non-Myeloablative Regimen Results in Long-Term Transgene Expression and Stable Mixed Chimerism
Authors: Brian W. Bigger, Simon N. Waddington, Mamta Buch, Megha Nivsarkar, Nicholas Jones, Suzanne M. Watt, Kathryn Wood, Michael Themis
Journal: Molecular Therapy (2005)

Stem cell gene delivery offers a potential cure for blood related disorders such as haemophilia B and degenerative diseases. We have shown permanent phenotypic correction of a murine model of haemophilia B for over a year by lentiviral delivery of the human factor IX gene to haematopoietic stem cells using a myeloablative conditioning regimen. In addition we were able to show full haematopoietic chimerism and robust tolerance, even after challenge with factor IX.
Poke Root Herbal Tea Poisoning
Authors: Peter R. Smith
Journal: JAMA (1979)

<h3>To the Editor.—</h3> All parts of poke (<i>Phytolacca americana</i>, synonym<i>P decandra</i>) are toxic, except aboveground parts growing early in the spring. The active components are triterpene saponins, eg, phytolaccigenin, and a proteinaceous mitogen, PWM. Ingestion of the saponins elicits gastroenteritis, while ingestion and absorption through skin abrasions of PWM may result in plasmacytosis, mitotic changes in peripheral blood cells, and other hematologic abnormalities.<sup>1</sup> Poisonings were widespread in eastern North America during the 19th century from overdoses of poke root tinctures then used as an antirheumatic and from eating berries or roots in error for parsnip, Jerusalem artichoke, or horseradish. Recoveries were common, but fatalities occurred.<sup>2,3</sup> Increasing numbers of persons are purchasing plant materials as foods from an expanding health food industry. Unfortunately, the public is unaware of the dangers of certain of these products, including poke that until recently had not been generally available for sale (240:109,
Cardiac Arrest Following Fluorescein Angiography
Authors: Philip Lempert
Journal: JAMA (1980)

To the Editor.—  The report of a Cardiac Arrest Following Fluorescein Angiography by Eugene E. Cunningham, MD, and Venkataraman Balu, MD (242:2431, 1979), suggests a relationship between the intravenous fluorescein and the cardiac complication.  It is well known that phenylephrine hydrochloride 10%, a frequently used concentration in eye drops for pupillary dilation, can precipitate cardiac arrhythmias and increases in blood pressure. Unfortunately, the article does not include a statement of the drops that were instilled before the angiogram. If phenylephrine or some other sympathomimetic drug were used, it would seem that these drugs would more likely be related to the cardiac arrest.
Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity
Authors: Hiroyuki Mori, Reiko Hanada, Toshikatsu Hanada, Daisuke Aki, Ryuichi Mashima, Hitomi Nishinakamura, Takehiro Torisu, Kenneth R Chien, Hideo Yasukawa, Akihiko Yoshimura
Journal: Nature Medicine (2004)
Grand Larceny at the Cellular Level
Authors: Samuel Vaisrub
Journal: JAMA (1980)

Our awareness of vascular thievery dates back to 1961 when Reivich et al<sup>1</sup>described the "subclavian steal." In this syndrome blood is siphoned from the opposite vertebral-basilar system to a vertebral artery deprived of its blood supply by a proximal subclavian artery obstruction. The ensuing reversal of blood flow causes symptoms of cerebral ischemia in the areas supplied by the unobstructed vessel. Similar hemodynamic mischief has since been recognized in other situations wherein blood is shunted either by siphoning or by other mechanisms responsible for circulatory redistribution.<sup>2</sup> Theft of blood is theft of oxygen. The latter, however, may occur without the former. Fox and his associates<sup>1</sup>describe a syndrome of oxygen theft by the large numbers of immature leukocytes in leukemic patients. Having observed a degree of arterial hypoxemia disproportionate to the lung involvement in several such patients, these investigators studied arterial Po<sub>2</sub>in multiple blood specimens
Crisis in the maternity services
Authors: J. E O'Hara
Journal: BMJ (1988)

relieving the symptoms of the postmenopausal syndrome.Meanwhile, perhaps it would be wise to maintain circulating concentrations of oestradiol above 150 pmol/l, since this has been shown to relieve the postmenopausal syndrome and arrest bone loss,2 but below 440 pmol/l.Such an approach may enable the maximum clinical benefit to be obtained from replacement treatment with the minimum of risk.