tbuckley/cabot-search huggingface dataset:
Compensatory changes of the distal coronary vascular bed during progressive coronary constriction.
Authors: K L Gould, K Lipscomb, C Calvert
Journal: Circulation (1975)

The degree and effectiveness of compensatory changes in the distal coronary vascular bed during progressive proximal coronary stenosis have not been described. In this study, coronary vascular bed resistance and pressure gradient-flow relationships were determined for 157 different stenoses in nine opened-chest dogs by measuring coronary flow, aortic pressure, and coronary pressure distal to a coronary constrictor while flow was varied from resting to maximal values by the intracoronary injection of Hypaque-M, 75% (previously shown to cause transient, maximal vasodilatation comparable to ten second occlusion). This approach provided a means of hemodynamically characterizing coronary stenoses in a standary, experimental manner for quantitative analysis of different arteries at different flow rates as found in the intact coronary circulation. The results show that 1) pressure gradient-flow characteristics or hydraulic resistance of stenoses do not become abnormal enough to alter normal resting coronary flow nor to elicit compensatory changes for stenoses up to constriction of approximately 60% of the diameter, 2) compensatory vasodilatation of the distal coronary vascular bed maintains near normal resting flow for lesions between 60% and 85% diameter stenosis but adaptive vasodilatation fails to compensate for the high resistance of lesions greater than 85% diameter stenosis, and 3) there is vasodilator reserve still present when total coronary artery flow is reduced below normal by a stenosis. This vasodilator reserve probably exists in the epicardium since the endocardium is characteristically underperfused due to the low coronary pressure caused by stenosis and is therefore likely to be maximally vasodilated with no remaining vasodilator reserve.
Analysis of glycoprotein E-selectin ligands on human and mouse marrow cells enriched for hematopoietic stem/progenitor cells
Authors: Jasmeen S. Merzaban, Monica M. Burdick, S. Zeineb Gadhoum, Nilesh M. Dagia, Julia T. Chu, Robert C. Fuhlbrigge, Robert Sackstein
Journal: Blood (2011)
Drugs and the QT Interval — Caveat Doctor
Authors: Barbara A. Liu, David N. Juurlink
Journal: New England Journal of Medicine (2004)

All drugs have the potential to cause adverse effects. Occasionally, serious adverse effects are not identified in preclinical studies and become apparent only when a drug is in widespread clinical use — a particular problem with adverse events that are rare and result in few symptoms. One example of relevance to clinicians and regulatory agencies is drug-induced prolongation of the QT interval. During the past few years, many drugs have been removed from the market or required to include "black box" warnings on their labels because of the potential for QT-interval prolongation. The list of causative medications is daunting, and . . .
Abstract 2824: PENAO: A small molecule tumor metabolism inhibitor
Authors: Pierre J. Dilda, Stephanie Decollogne, Lakmini Weerakoon, Philip J. Hogg
Journal: Cancer Research (2011)

Abstract Tumors reorganize the metabolic steps used by normal tissues for glucose utilization and ATP production. Normal tissues rely heavily on oxidative phosphorylation for ATP, while tumor cells employ a route that includes a much greater dependency on glycolysis. This aberrant metabolism allows for tumor survival when oxygen is limiting while providing a mechanism to poison the extracellular environment with acid, which facilitates invasion and metastasis. In particular, tumors harness a crucial enzyme, hexokinase II (HKII), to entrap and channel glucose toward glycolysis. HKII is bound to mitochondria via interaction with the voltage dependent anion channel (VDAC). This affords HKII preferential access to the mitochondrial ATP via inner-membrane adenine nucleotide translocase (ANT) to rapidly phosphorylate and trap the incoming glucose, effectively initiating and regulating the glycolytic flux across the tumor cytosol. We have developed a novel covalent inhibitor of ANT called PENAO, (4-(N-(S-penicillaminylacetyl)amino)phenylarsonous acid) (1). This molecule blocks ANT delivery of ATP to VDAC-bound HKII, thus inhibiting tumor cell metabolism, and triggers the mitochondrial permeability transition pore, resulting in proliferation arrest and apoptotic cell death. PENAO rapidly enters the cell via an organic ion transporter and reacts with Cys160 and Cys257 on the matrix face of ANT, which leads to arrest of proliferation of the cell and then apoptosis. PENAO targets both proliferating endothelial and tumor cells. It is very well tolerated in mice and has potent anti-tumor activity in murine tumor models when administered either subcutaneously or intravenously. PENAO is the most potent anti-tumor compound of its type so far reported and will enter a Phase I/IIa clinical trial in adults with solid tumors refractory to standard therapy in 2011. 1. Dilda PJ, Decollogne S, Weerakoon L, et al. Optimization of the antitumor efficacy of a synthetic mitochondrial toxin by increasing the residence time in the cytosol. J Med Chem 2009;52(20):6209-16. 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 2824. doi:10.1158/1538-7445.AM2011-2824
B.C.G. Vaccination in the Newborn
Authors: W. Gaisford, M. Griffiths
Journal: BMJ (1951)

MEDICALJOHURNAL-~~~~~~~~~~~~~~~~~~~~~~~~~~~~MEIA ORA a refractory state.This failure of adequate response is not only seen with low dosage but may develop in spite of con- tinued high initial dosage, usually appearing after four to eight weeks of treatment.Attempts to explain these failures have so far been unsuccessful.The following possibilities have been excluded by special study: masked corticogenic hypothyroidism; diminished response of the peripheral target-organs; vita- min C deficiency; and decreased activity of the pituitary hormone preparations.Investigations into the possible development of neutralizing antibodies or a shift in the hormone production of the adrenals appear to be indicated.The administration of A.C.T.H. in cases of rheumatoid arthritis should still be regarded as worthy of investigation.
Re-thinking the functions of IgA<sup>+</sup>plasma cells
Authors: Jennifer L Gommerman, Olga L Rojas, Jörg H Fritz
Journal: Gut Microbes (2014)

The intestinal mucosa harbors the largest population of antibody (Ab)-secreting plasma cells (PC) in the human body, producing daily several grams of immunoglobulin A (IgA). IgA has many functions, serving as a first-line barrier that protects the mucosal epithelium from pathogens, toxins and food antigens (Ag), shaping the intestinal microbiota, and regulating host–commensal homeostasis. Signals induced by commensal colonization are central for regulating IgA induction, maintenance, positioning and function and the number of IgA+ PC is dramatically reduced in neonates and germ-free (GF) animals. Recent evidence demonstrates that the innate immune effector molecules tumor necrosis factor α (TNFα) and inducible nitric oxide synthase (iNOS) are required for IgA+ PC homeostasis during the steady state and infection. Moreover, new functions ascribed to PC independent of Ab secretion continue to emerge, suggesting that PC, including IgA+ PC, should be re-examined in the context of inflammation and infection. Here, we outline mechanisms of IgA+ PC generation and survival, reviewing their functions in health and disease.
CDC calls for urgent action to combat rise of drug resistant pathogens
Authors: Michael McCarthy
Journal: BMJ (2013)

The US Centers for Disease Control and Prevention (CDC) has called for aggressive and immediate action to halt the spread of drug resistant pathogens, in a new report.1

“We talk about a pre-antibiotic era and an antibiotic era; if we’re not careful we will soon be in a post-antibiotic era,” said the CDC’s director, Tom Frieden, in a teleconference with reporters on 16 September. “In fact, for some patients and some microbes we are already there.”

The report estimates that two million people become ill from antibiotic resistant infections in the United States each year, of whom 23 000 will die.

Frieden called this estimate “very conservative,” because it only includes hospital associated infections.

“We know that …
A low-protein diet restricts albumin synthesis in nephrotic rats.
Authors: G A Kaysen, H Jones, V Martin, F N Hutchison
Journal: Journal of Clinical Investigation (1989)

High-protein diets increase albumin synthesis in rats with Heymann nephritis but albuminuria increases also, causing serum albumin concentration to be suppressed further than in nephrotic animals eating a low-protein diet. Experiments were designed to determine whether dietary protein augmentation directly stimulates albumin synthesis, or whether instead increased albumin synthesis is triggered by the decrease in serum albumin concentration. Evidence is presented that dietary protein augmentation directly stimulates albumin synthesis, accompanied by a proportional increase in steady-state hepatic albumin mRNA concentration (AlbmRNA) and by an increase in AlbmRNA transcription. When the increased albuminuria resulting from dietary protein augmentation is blunted with enalapril, serum albumin concentration is shown to increase in nephrotic rats. Both albumin synthesis and AlbmRNA increase in these animals despite the greater serum albumin concentration. Albumin synthesis correlates inversely with both serum albumin and serum oncotic pressure in nephrotic rats fed 40% protein, but does not correlate with serum albumin concentration in nephrotic rats fed 8.5% protein (LP), even when serum albumin concentration is reduced. Albumin masses are preserved in LP primarily because of reduced albuminuria. Reduced serum oncotic pressure and dietary protein augmentation combine to stimulate albumin synthesis in nephrotic rats at the level of gene transcription.
Academic medicine: time for reinvention: Non-clinician scientists are the missing clinical links
Authors: S. J Hopkins
Journal: BMJ (2004)

Editor—An Academy of Medical Sciences report and recent articles have outlined a decline in capacity to undertake clinical research and identified the need to reconsider funding.1-3 This has occurred despite a reorganisation of NHS research and development that aimed to create an NHS culture valuing research. The highlighted changes in university appointments, which have encouraged clinical academics to engage in more basic research, have perhaps also been accompanied by neglect of the role of other NHS staff willing and critically able to support research activity.

Surprisingly, non-clinician scientists in medical research were not mentioned at all, although they were the focus of an earlier academy report.4 That report urged “an imaginative approach... to questions of funding long-term posts for contract research workers” and identified other problems experienced by non-clinically qualified research staff in a clinical environment. These included exclusion, now further apparent from the academy's most recent report.3 These researchers contribute significantly to the clinical research effort and deserve greater consideration in the current debate.

Pressures on both clinicians and non-clinician scientists to engage in more fundamental research have been accompanied by deterioration in the infrastructure necessary for effective clinical research. New clinical research facilities address this to a degree, but to a large extent they are not where the patients are and they lack the infrastructure that might be provided in well resourced and organised teaching hospitals, with access to a range of good laboratory and investigational resources.

Can we hope that corrective measures will avoid the attractions of fashion and bandwagons in favour of a more integrated approach that will engage all areas of activity and all parties?
THE VALUE OF VOLUME INDEX IN THE DIAGNOSIS OF PERNICIOUS ANEMIA
Authors: RUSSELL L. HADEN
Journal: JAMA (1924)

A color index greater than 1, when correctly determined, is usually regarded as the most constant and characteristic blood finding in pernicious anemia. The great variation in hemoglobin readings in different laboratories, however, makes the color index a very uncertain diagnostic measure. The plus index is dependent on a macrocytosis of the red cells. It is apparent that an accurate measure of the macrocytosis is a more basic procedure than the determinaion of the color index. The increase in size of the erythrocytes is usually determined by noting the diameter of the cells in a stained blood film. Such a measurement does not take into account the thickness of the cells, and thus does not indicate the true volume of the cells. The volume of the average cells is best indicated by the volume index. This term was introduced by Capps,<sup>1</sup>in 1904, to denote the volume of the
Combat Casualty Care Research
Authors: Mike Mitka
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Identification of Prostaglandin E2 Receptor Subtype 2 As a Receptor Activated by OxPAPC
Authors: Rongsong Li, Kevin P. Mouillesseaux, Dennis Montoya, Daniel Cruz, Navid Gharavi, Martin Dun, Lukasz Koroniak, Judith A. Berliner
Journal: Circulation Research (2006)

Oxidized 1-palmitoyl-2-arachidonoyl- sn -glycero-3-phosphorylcholine (OxPAPC), which has been shown to accumulate in atherosclerotic lesions and other sites of chronic inflammation, activates endothelial cells (EC) to bind monocytes by activation of endothelial β1 integrin and subsequent deposition of fibronectin on the apical surface. Our previous studies suggest this function of OxPAPC is mediated via a Gs protein–coupled receptor (GPCR). PEIPC (1-palmitoyl-2-epoxyisoprostane E2- sn -glycero-3-phosphorylcholine) is the most active lipid in OxPAPC that activates this pathway. We screened a number of candidate GPCRs for their interaction with OxPAPC and PEIPC, using a reporter gene assay; we identified prostaglandin E2 receptor EP2 and prostaglandin D2 receptor DP as responsive to OxPAPC. We focused on EP2, which is expressed in ECs, monocytes, and macrophages. OxPAPC component PEIPC, but not POVPC, activated EP2 with an EC 50 of 108.6 nmol/L. OxPAPC and PEIPC were also able to compete with PGE2 for binding to EP2 in a ligand-binding assay. The EP2 specific agonist butaprost was shown to mimic the effect of OxPAPC on the activation of β1 integrin and the stimulation of monocyte binding to endothelial cells. Butaprost also mimicked the effect of OxPAPC on the regulation of tumor necrosis factor-α and interleukin-10 in monocyte-derived cells. EP2 antagonist AH6809 blocked the activation of EP2 by OxPAPC in HEK293 cells and blocked the interleukin-10 response to PEIPC in monocytic THP-1 cells. These results suggest that EP2 functions as a receptor for OxPAPC and PEIPC, either as the phospholipid ester or the released fatty acid, in both endothelial cells and macrophages.
IMPORTANCE OF ALLERGY IN ETIOLOGY AND TREATMENT OF NASAL MUCOUS POLYPS
Authors: RICHARD A. KERN
Journal: JAMA (1934)

In a previous communication we<sup>1</sup>presented evidence which in our opinion justified the conclusion that allergy is a constant factor in the etiology of so-called mucous nasal polyps. At this time we present further clinical data which we feel confirm our original view. It may be well at the outset to define the type of lesion to which we refer. Nasal polyps, other than malignant forms, may be classified as (1) mucous polyps or edematous fibromas (a better term we feel is myxoid fibroma); (2) mixed polypoid hyperplasia, and (3) papillary hypertrophy or mulberry polyps. Mucous polyps or edematous fibromas (myxoid fibromas) may be single or multiple and are frequently pedunculated. They are smooth, pale and translucent, varying in color from translucent white or gray to bright yellow tinged with red. Older polyps may show marked discoloration. They possess a characteristic jelly-like softness and their consistency is such
The Ductus Arteriosus and Its Closure
Authors: Michael Tynan
Journal: New England Journal of Medicine (1993)

The lungs of the fetus do not have a role in gas exchange, since that function is served by the placenta. The fetal pulmonary vascular resistance is maintained at high levels to limit blood flow to the lungs, and the ductus arteriosus provides a conduit for blood entering the pulmonary artery to bypass the lungs and be directed into the descending aorta and the placenta.Unlike the aorta and the main pulmonary arteries, the ductus has a predominantly muscular media. Most of the muscle fibers are oriented circumferentially, particularly in the outer layers1. The muscle mass in the media . . .
Genetic Testing of Families With Hereditary Diseases
Authors: Alice Wexler
Journal: JAMA (1996)

<h3>To the Editor.</h3> —For those of us concerned with predictive testing for Huntington disease (<i>HD</i>gene), it is gratifying to know that our experience has relevance for other diseases. However, the study of<i>BRCA1</i>testing by Dr Lerman and colleagues<sup>1</sup>considerably overstates the conclusions of a major 1992 Canadian study of<i>HD</i>gene testing by Wiggins et al.<sup>2</sup>According to Lerman et al, "the prospective study found that testing had long-term psychological benefits—both for carriers and for noncarriers of<i>HD</i>gene mutations." Actually, the study by Wiggins et al<sup>2</sup>is far more tentative in its conclusions, emphasizing the potential for benefits rather than benefits achieved, and acknowledging important qualifications. It concludes that predictive testing for the<i>HD</i>gene "may maintain or even improve the psychological well-being of many people at risk." The study also notes that predictive testing "appears to have improved" the psychological wellbeing "of many participants in the program."
The Medical Outcomes Study-Reply
Authors: Sheldon Greenfield
Journal: JAMA (1996)

<h3>In Reply.</h3> —Dr Testa and Dr Matz agree with our statement that in some cases the numbers of patients were small and precision was limited. However, our general conclusions are based on aggregated numbers of hypertensive and diabetic patients and aggregated measures. If clinicians in some system or specialty ignored or wrongly treated hypertension or NIDDM, notable deterioration would be expected.<sup>1</sup>We found little evidence of either poor outcomes or lack of care. The clinical index goes a long way toward eliminating the numbers problem. Hidden behind the small samples of patients is a much larger sample of nearly uncorrelated clinical measurements that we aggregated into a clinical index. An index can find small differences that appear in many measurements but not medium-sized differences on a single measurement such as HbA<sub>1c</sub>. Basing power on each individual measure would be needlessly expensive. Contrary to Testa's implication, we did control
Conserved hepatitis C virus sequences are highly immunogenic for CD4+ T cells: Implications for vaccine development
Authors: Vincenzo Lamonaca, Gabriele Missale, Simona Urbani, Massimo Pilli, Carolina Boni, Cristina Mori, Alessandro Sette, Marco Massari, Scott Southwood, Roberto Bertoni, Antonietta Valli, Franco Fiaccadori, Carlo Ferrari
Journal: Hepatology (1999)

The HLA class II-restricted T-cell response to hepatitis C virus (HCV) antigens is believed to influence the final outcome of hepatitis C, because it is vigorous in patients who recover from acute hepatitis C, but it is weak in those who develop a chronic infection. For this reason, exogenous stimulation of T-cell responses in chronic HCV infection may represent a strategy to cure patients with chronic hepatitis C by approximating the vigor of their T-cell reactivity to that of patients who succeed in recovering from hepatitis. It may also be a preventive approach to avoid spread of the virus by facilitating the development of a vigorous protective response at the very early stages of infection. T-cell-based vaccines composed of immunodominant, promiscuous, and conserved T-cell epitopes may represent a powerful tool to achieve optimal stimulation of the T-cell reactivity. To identify HLA class II-restricted T-cell epitopes useful for this purpose, 22 subjects with acute HCV infection were studied and followed for an average time of 29 months. Eight of them recovered from hepatitis, and 14 developed a chronic infection. Overlapping 20-mer peptides covering the entire core and NS4 antigens and a panel of peptides representing highly conserved regions of core, NS3, NS4, and NS5 were used. By direct peripheral blood T-cell stimulation and by fine-specificity analysis of HCV-specific T-cell lines and clones, highly immunogenic T-cell epitopes were identified within core, NS3, and NS4. All these epitopes are immunodominant and highly conserved among the known HCV isolates. Moreover, they are promiscuous, because they can be presented to T cells by different HLA class II molecules. Immunodominance, sequence conservation, and promiscuity make these epitopes ideal components of preventive or therapeutic T-cell-based vaccines against HCV.