tbuckley/cabot-search huggingface dataset:
Epidemiologic and Sociologic Features of A Large Urban Outbreak of Shigellosis
Authors: Wiley H. Mosley, Beatrice Adams, Edwin D. Lyman
Journal: JAMA (1962)

An outbreak of 87 bacteriologically confirmed cases of shigellosis occurred from September 1961 through January 1962 in 41 households and one nursing home in Omaha, Neb. Forty-three of these cases occurred in children under 5 years of age. The clinical picture varied from a prostrating illness terminating fatally in a 2-year-old child to asymptomatic infections. The majority of the infected households were concentrated in a low socioeconomic, predominantly nonwhite area of the city, where epidemiological investigation demonstrated person to person transmission. Correlations with household congestion and dilapidation by census tract revealed the attack rate to be directly associated with poor environmental living conditions.
Methotrimeprazine
Authors: Louis Lasagna
Journal: JAMA (1961)

Methotrimeprazine was evaluated as an analgesic agent in patients suffering from postoperative or postpartum pain. By injection, the drug provided pain relief comparable to that achieved with similar doses of morphine. Orally administered methotrimeprazine, on the other hand, produced no more pain relief than a placebo at dosages which caused a significant incidence of untoward effects.
The QRS complex during transient myocardial ischemia: studies in patients with variant angina pectoris and in a canine preparation.
Authors: J E Barnhill, J P Wikswo, A K Dawson, S Gundersen, R M Robertson, D Robertson, R Virmani, R F Smith
Journal: Circulation (1985)

We made continuous electrocardiographic recordings on magnetic tape during 15 episodes of ischemia in five patients with variant angina to determine the characteristics of the QRS changes. Orthogonal leads were used and the electrocardiograms were analyzed visually and by digital computer. Changes were quantified by subtracting baseline electrocardiograms from those obtained during ischemia. Large changes in the QRS occurred during ischemia but the waveform quickly returned to baseline when the episode subsided. In all patients there was prolongation of the QRS duration and an increase in QRS voltage during the terminal 40 msec of the waveform in the lead(s) showing the most marked ST displacement. The increase in the terminal QRS could be represented by a vector directed toward the ischemic zone. In a given patient the amplitude of ST displacement varied between episodes, presumably because of variation in the intensity of ischemia, but the QRS changes were directionally similar in each episode. In two patients there was also a smaller change involving the initial 40 msec of the QRS that could be represented by a vector directed away from the ischemic zone. To determine the possible mechanism for the electrocardiographic changes, ischemic episodes of 120 to 150 sec were produced in seven dogs and electrocardiographic recording and analysis techniques similar to those used in patients were employed. Myocardial conduction velocity was measured in three directions in the ischemic zone and was correlated with simultaneous electrocardiographic recordings from the body surface. The electrocardiographic changes in the dog preparation were virtually identical to those in the patients and strongly correlated with a fall in myocardial conduction velocity. We conclude that the QRS changes during variant angina result from the altered excitation pattern produced by conduction delay in the ischemic zone. The probable cause for the increase in terminal QRS voltage is delayed (and uncancelled) activation of the ischemic zone.
Probabilistic equilibria for evolutionarily stable strategies
Authors: Roger A. McCain
Journal: Behavioral and Brain Sciences (2007)

This commentary suggests that an equilibrium framework may be retained, in an evolutionary model such as Gintis's and with more satisfactory results, if rationality is relaxed in a slightly different way than he proposes: that is, if decisions are assumed to be related to rewards probabilistically, rather than with certainty. This relaxed concept of rationality gives rise to probabilistic equilibria.
Myocardial Irritability Associated with Lithium Carbonate Therapy
Authors: Tim N. Tangedahl, Gerald T. Gau
Journal: New England Journal of Medicine (1972)

CARDIAC symptoms have not been conspicuous in cases of human lithium carbonate intoxication,1 and the effect of therapeutic doses of lithium on the human myocardium has been described as "benign."2 , 3 In a recent report concerning a patient, taking thioridazine and lithium carbonate, who manifested major ventricular arrhythmias and was found to be hypokalemic, the authors attributed her arrhythmia to thioridazine and concluded, "We know of no evidence which would link lithium to the production of ventricular arrhythmias."4 In the following case symptomatic premature ventricular contractions were associated with ingestion of lithium carbonate, which produced an intracellular potassium depletion.Case Report . . .
Abstract B6: Epigenetic regulation of Hedgehog pathway transcriptional output by BET bromodomain proteins
Authors: Yujie Tang, Simone Schubert, Jun Qi, Brian Nguyen, Sabran Masoud, Nujsaunusi Vue, Brianna Balansay, Furong Yu, Scott X. Atwood, Ramon J. Whitson, Anitha Ponnuswami, Spencer Chen, Sharareh Gholamin, Woo J. Pamelyn, Michelle Monje-Diesseroth, Sekyung Oh, Alex Lee, Jean Y. Tang, Rob Wechsler-Reya, Anthony E. Oro, James E. Bradner, Yoon-Jae Cho
Journal: Cancer Research (2014)

Abstract Aberrant activation of Hedgehog signaling drives oncogenesis in several types of cancer. As a result, there has been significant interest in developing therapeutic strategies targeting this pathway, most notably through inhibition of Smoothened. Though Smoothened inhibitors have shown efficacy in several cancer clinical trials, the initial enthusiasm for these inhibitors has been tempered by emergence of resistance and a priori resistance, often via mutation of Smoothened itself or through dysregulation of downstream components of the Hedgehog signaling axis. Here we reveal a strategy that overcomes these resistance mechanisms by targeting the far downstream transcriptional mediators of Hedgehog signaling through inhibition of the BET bromodomain protein, BRD4. We show that knockdown of BRD4 or treatment with the BET bromodomain inhibitor, JQ1, dramatically inhibits transcription of GLI1 and other Hedgehog target genes upon ligand-mediated or genetic activation of the Hedgehog pathway. We confirm the inhibitory effect of JQ1 occurs downstream of SMO and SUFU and verify by chromatin immunoprecipitation that Brd4 directly occupies the GLI1 and GLI2 promoters, with a substantial decrease in the engagement of these genomic sites upon treatment with JQ1. We observe a corresponding downregulation of genes associated with medulloblastoma-specific GLI1 binding sites upon exposure to JQ1, confirming the direct regulation of GLI1 by BET bromodomain proteins. Finally, using patient- and GEMM-derived cell lines of Hedgehog-driven cancer (basal cell carcinoma, medulloblastoma and ATRT), we show that JQ1 decreases Hh pathway output and proliferation, even in cell lines resistant to Smoothened inhibitors. These results expand the role of BET bromodomain inhibitors to targeting Hedgehog-driven cancers and highlight a strategy that overcomes the limitation of Hedgehog pathway inhibitors currently in clinical use. Citation Format: Yujie Tang, Simone Schubert, Jun Qi, Brian Nguyen, Sabran Masoud, Nujsaunusi Vue, Brianna Balansay, Furong Yu, Scott X. Atwood, Ramon J. Whitson, Anitha Ponnuswami, Spencer Chen, Sharareh Gholamin, Woo J. Pamelyn, Michelle Monje-Diesseroth, Sekyung Oh, Alex Lee, Jean Y. Tang, Rob Wechsler-Reya, Anthony E. Oro, James E. Bradner, Yoon-Jae Cho. Epigenetic regulation of Hedgehog pathway transcriptional output by BET bromodomain proteins. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr B6.
Approaching Death: Improving Care at the End of Life
Authors: Lisa Stepp
Journal: Annals of Internal Medicine (1998)

Medical Writings: Book Notes1 June 1998Approaching Death: Improving Care at the End of LifeLisa Stepp, MS, RNLisa Stepp, MS, RNDallas, TexasAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-11-199806010-00034 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Approaching Death: Improving Care at the End of Life; 437 pages. Washington, DC: National Academy Pr; 1997. $66.00. ISBN 0309063728. Order phone 800-624-6242.Field of medicine: Hospice and palliative care.Format: Hardcover book.Audience: Medical students, graduate students, and physicians seeking an understanding of the components of and quality standards for end-of-life care.Purpose: To strengthen popular and professional understanding of good care at the end of life.Content: This report presents the findings of an Institute of Medicine study evaluating end-of-life care in the United States. It argues that we can do much more to relieve suffering and increase ... Author, Article, and Disclosure InformationAffiliations: Dallas, Texas Previousarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAssessing the Acceptability and Feasibility of Leveraging Emergency Department Social Workers' Advanced Communication Skills to Assess Elderly Patients' Goals and Values 1 June 1998Volume 128, Issue 11Page: 964KeywordsEnd of life careGraduate medical educationPalliative careTouchTreatment guidelines ePublished: 15 August 2000 Issue Published: 1 June 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Same peculiar subset of HML1 + lymphocytes present within normal intestinal epithelium is associated with tumoral epithelium of gastrointestinal carcinomas.
Authors: A Jarry, N Cerf-Bensussan, N Brousse, D Guy-Grand, F Muzeau, F Potet
Journal: Gut (1988)

The present study shows that the distribution of T lymphocytes in gastrointestinal carcinomas and their metastases mimic the distribution of T lymphocytes in normal intestine. The composition of the peritumoral reaction resembled that of normal lamina propria with a predominance of CD3 + CD4 + T cells. In contrast, lymphocytes located between carcinomatous cells showed phenotypical features similar to those of intraepithelial lymphocytes (IEL) in normal intestine; in particu(abstractlar they expressed the antigen defined by HML-1, a monoclonal antibody raised against normal human intestinal IEL which reveals 95% IEL but very few cells in lymphoid (abstractorgans and blood. As normal intestinal IEL, the majority of intratumoral lymphocytes had the CD3+ CD8+ phenotype. A panel of monoclonal antibodies and double immunostaining techniques permitted a better characterisation of minor subsets of IEL. Two subsets of HML1 + CD3 + CD4- CD8- and of HML1+ CD3- cells, representing 2% and 3% of normal intestinal IEL respectively, did not significantly increase in carcinomatous epithelium. In contrast, in carcinomatous epithelium, but not in normal intestinal epithelium, we observed the appearance of a few lymphocytes displaying the phenotype of activated T cells (CD25+) or of natural killer cells (NKHI+) or of suppressor cells (CD11+). Such cells may participate in antitumoral defence. Although a similar population of HML1+ lymphocytes is associated with normal and carcinomatous intestinal epithelium, some interactions between lymphocytes and epithelial cells may not be maintained in tumoral epithelium. It has previously been shown that HLA-DR expression by enterocytes is modulated by intraepithelial lymphocytes. In our study, no correlation could be shown between the degree of lymphocytic infiltration and the expression of HLA-DR antigens on carcinomatous cells.
Abstract 5479: Mcl-1 is differentially regulated in acute myeloid leukemia cells treated with all trans retinoic acid and arsenic trioxide
Authors: Rui Wang, Samuel Waxman, Yongkui Jing
Journal: Cancer Research (2011)

Abstract Both all trans retinoic acid (ATRA) and arsenic trioxide (ATO) induce complete remission in acute promyelocytic leukemia (APL) patients. Using the APL derived NB4 cell line containing the PML-RARα fusion protein it has been found that ATRA induced differentiation while ATO mainly induced apoptosis. Previously it has been reported that the antiapoptotic proteins Bcl-2 and Bfl-1/A1 were regulated during ATRA-induced differentiation process in APL cells. However, the regulation of Mcl-1, a major antiapoptotic protein required during myeloid granulocyte differentiation, has not been determined. Recently it has been shown that ERK phosphorylates Mcl-1 and regulates its stability. The regulation of Mcl-1 and p-ERK by ATRA and ATO were investigated in NB4 and its subclone R4 cells, HL-60 and its subclone HL-60/Res cells. Both NB4 and R4 cells contain PML-RARα while HL-60 and HL-60/Res cells contain RARα. However, the ATRA binding domain in PML-RARα and RARα is mutant in R4 and HL-60/Res cells, respectively. The levels of Mcl-1 were induced by ATRA in both NB4 and HL-60 cells, but not in R4 cells nor HL-60/Res cells. The induction of Mcl-1 in NB4 and HL-60 cells correlated with the induction of differentiation and the increased level of p-ERK. Unlike ATRA treatment, ATO treatment decreased the levels of Mcl-1 in both NB4 and R4 cells, but not in HL-60 nor in HL-60/Res cells, which correlated with the induction of apoptosis and down-regulation of p-ERK. Both NB4 and R4 cells contain PML-RARα which is degraded by ATO, suggesting that PML-RARα plays a role in ATO-mediated down-regulation of Mcl-1. To test the effect of PML-RARα on the regulation of Mcl-1 after ATO treatment, U937/PR9 cells with the inducible expression of PML-RARα were used. Expression of PML-RARα increased the levels of Mcl-1 and p-ERK. ATO treatment decreased the levels of both Mcl-1 and p-ERK. These data suggest that ATRA increases the level of Mcl-1 through activating ERK due to overcoming PML-RARα transcriptional repression and activating RARα while ATO decreases the level of Mcl-1 through inactivation of ERK due to inducing degradation of PML-RARα. The increased level of Mcl-1 after ATRA treatment protects against cell death and promotes differentiation while the decreased level of Mcl-1 after ATO-treatment sensitizes apoptosis induction. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5479. doi:10.1158/1538-7445.AM2011-5479
MEASUREMENT OF THE SENSITIVITY OF THE SMALLEST BLOOD VESSELS IN HUMAN SKIN: RESPONSES TO GRADED MECHANICAL STIMULATION IN NORMAL MEN 1
Authors: Joseph R. Di Palma, Samuel R. M. Reynolds, Frances I. Foster
Journal: Journal of Clinical Investigation (1941)

The physiological responses of the smallest blood vessels in human skin to mechanical and chemical stimuli have been the subject of numer- ous studies and several important monographs (1, 2, 3, and others).The qualitative aspects of the white and red reactions of the triple response have been well-defined and their localization to the smallest vessels has been established.Despite the extent of, and widespread interest in this subject, no attempt has been made until now to put these on a simple quantitative basis.Such experiments should enable an observer to measure the sensi- tivity of the skin capillaries in a subject from day to day, and to compare such data among a group of individuals.The present report offers one of two such methods which we have developed.The procedure usually employed experimentally to elicit the several components of the triple re- sponse are mechanical pressure and local infiltration (by pricking or iontophoresis) of vasodilator or vasoconstrictor drugs.The chemical methods have been used in a quasi-quantitative manner (4, 5, 6) but these tests depend upon a number of fac- tors which may only indirectly involve the sensi- tivity of the capillaries.Plethysmographic studies and measurements of skin temperature likewise fail to reflect the irritability of the smallest vessels (7, 8).The response of these vessels to graded mechanical stimulation offers, on the contrary, a direct approach to this problem.The technic de- scribed below depends upon this principle.Its ap- plication rests upon control of two qualities of a stimulus, namely, intensity and duration.Thus, if a true measure of the excitability of the vessels were obtained, a typical strength-duration curve like that found in determining the threshold of
Protective ischaemia in patients: preconditioning and postconditioning
Authors: A. Granfeldt, D. J. Lefer, J. Vinten-Johansen
Journal: Cardiovascular Research (2009)

Infarct size can be limited by reducing the determinants of infarct size or increasing collateral blood flow by treatment initiated before the ischaemic event.Reperfusion is the definitive treatment for permanently reducing infarct size and restoring some degree of contractile function to the affected myocardium.Innate survival mechanisms in the heart can be stimulated by short, non-lethal periods of ischaemia and reperfusion, applied either before or after the ischaemic event.Preconditioning, a series of transient intervals of ischaemia and reperfusion applied before the lethal 'index' ischaemic event, sets in motion molecular and cellular mechanisms that increase cardiomyocyte survival to a degree that had not hitherto been seen before.The cardioprotective ischaemic-reperfusion protocol applied at onset of reperfusion, termed 'postconditioning' (Postcon), is also associated with significant cardioprotection that can be applied at the point of reperfusion treatment in the catheterization laboratory or operating room.Both preconditioning and Postcon have been successfully applied to the clinical setting and have been found to reduce infarct size and other attributes of post-ischaemic injury.This review will summarize the physiological preclinical data on preconditioning and Postcon that are relevant to their translation to clinical therapeutics and treatment.
Do the Eyes Have It?
Authors: Samuel Vaisrub
Journal: JAMA (1979)

Even though Beethoven was still able to compose music after he became deaf, it can hardly be denied that deafness to a musician is as calamitous as blindness to a painter. For a physician in search of diagnostic leads to heart disease, both loss of hearing and loss of sight are crippling handicaps. But which of the two evils is the greater? Pointless as the question may sound (or look), it is not entirely a product of idle curiosity. The answer may shed light on some important changes in our approaches to cardiac diagnosis that have taken place during the past few decades. Earlier in the century, cardiologists might have viewed deafness as the greater handicap. So much depended on auscultatory findings. How else could one diagnose valvular and congenital heart diseases or detect pulmonary hypertension? New technology, however, with its graphic and cinematographic representations, radically altered the relative importance
Uptake of transferrin‐bound and nontransferrin‐bound iron by reticulocytes from the belgrade laboratory rat: Comparison with wistar rat transferrin and reticulocytes
Authors: Elizabeth A. Farcich, Evan H. Morgan
Journal: American Journal of Hematology (1992)

Abstract The mechanism underlying the impaired uptake of iron from transferrin by reticulocytes from the Belgrade laboratory rat was investigated using 125 I‐ and 59 Fe‐labeled transferrin isolated from homozygous Belgrade rats and from Wistar rats, nontransferrin‐bound Fe(II) in an isotonic sucrose solution, and reticulocytes from Belgrade and Wistar rats. The Belgrade rat transferrin had the same molecular weight and net charge as Wistar rat transferrin, donated iron equally well to both types of reticulocytes, and competed equally for transferrin binding sites on the cells. Hence, the defect in iron uptake by Belgrade rat reticulocytes could not be attributed to an abnormality of the transferrin molecule. The rate of uptake of Fe(II) from sucrose into the cytosolic and stromal fractions of Belgrade rat reticulocytes was only about 35% as great as that by Wistar rat reticulocytes. With both types of cells, the uptake process was saturable, suggesting the presence of a carriermediated process. It was therefore concluded that the defect in iron uptake by Belgrade rat erythroid cells is probably the consequence of a deficiency in a membrane carrier for iron.
Points: Maternal age, illegitimacy, and postneonatal mortality
Authors: I F Greatorex
Journal: BMJ (1988)

American Society of Anaesthesiologists' (ASA) grade system (ASA I, healthy patient; ASA II, mild systemic disease; ASA III, severe, non- incapacitating systemic disease; ASA IV, severe, incapacitating systemic disease which is a constant threat to life; and ASA V, moribund patient, not expected to live for 24 hours with or without surgery) abnormal values were found in 1-5% of patients in grade I, 17% in grade II, 35% in grade III, and 48% in grades IV and V.' In addition, most abnormal values in patients in grade II were minor and not clinically important.Therefore patients in grades I and II do not need routine estimations of urea and electrolyte concentrations whereas those in grades III, IV, and V do, as the results are much more likely to be abnormal.I therefore suggest that this grading system, which could be easily learnt by junior medical staff, would be more appropriate than age as an indicator of the need for biochemical screening preoperatively.
Durable, Safe, Multi-gene Lentiviral Vector Expression in Feline Trabecular Meshwork
Authors: Pranay D Khare, Nils Loewen, Wulin Teo, Román A Barraza, Dyana T Saenz, Douglas H Johnson, Eric M Poeschla
Journal: Molecular Therapy (2007)

Multiple disease-specific considerations have led to interest in the potential of gene therapy to permanently correct elevated intraocular pressure (IOP), the main causal risk factor for primary open angle glaucoma (POAG). Since IOP elevation results from abnormal resistance to aqueous humor outflow from the eye through the trabecular meshwork (TM), a means to genetically modify this specialized outflow organ permanently and safely is a prioritized goal. Here we tested different lentiviral vector designs and doses for long-term transgene expression in a large animal model, and investigated whether exogenously introduced myocilin proteins influenced IOP. The anterior chambers of 18 domestic cats (36 eyes) were injected with dual-gene feline immunodeficiency virus (FIV) vectors. Substantial, well-tolerated green fluorescent protein (GFP) expression was achieved in TM and monitored non-invasively in vivo for 1.2-2.3 years, using both 5' cap-translation and internal ribosome entry site (IRES)-translation. In all 36 eyes, post-mortem examination revealed substantial TM transgene expression (which often greatly exceeded that observable non-invasively during life). However, co-expression with enhanced GFP of myocilin or a juvenile glaucoma-associated mutant myocilin did not elevate IOP. These results demonstrate a safe, long-term single and dual gene expression in TM and establish an experimental system for testing candidate therapeutic transgenes for POAG.
Endogenous CCL2 (monocyte chemotactic protein-1) modulates human immunodeficiency virus type-1 replication and affects cytoskeleton organization in human monocyte–derived macrophages
Authors: Laura Fantuzzi, Francesca Spadaro, Giuliana Vallanti, Irene Canini, Carlo Ramoni, Elisa Vicenzi, Filippo Belardelli, Guido Poli, Sandra Gessani
Journal: Blood (2003)