tbuckley/cabot-search huggingface dataset:
Folic Acid Improves Endothelial Function in Coronary Artery Disease via Mechanisms Largely Independent of Homocysteine Lowering
Authors: Sagar N. Doshi, Ian F.W. McDowell, Stuart J. Moat, Nicola Payne, Hilary J. Durrant, Malcolm J. Lewis, Jonathan Goodfellow
Journal: Circulation (2002)

Background — Homocysteine is a risk factor for coronary artery disease (CAD), although a causal relation remains to be proven. The importance of determining direct causality rests in the fact that plasma homocysteine can be safely and inexpensively reduced by 25% with folic acid. This reduction is maximally achieved by doses of 0.4 mg/d. High-dose folic acid (5 mg/d) improves endothelial function in CAD, although the mechanism is controversial. It has been proposed that improvement occurs through reduction in total (tHcy) or free (non–protein bound) homocysteine (fHcy). We investigated the effects of folic acid on endothelial function before a change in homocysteine in patients with CAD. Methods and Results — A randomized, placebo-controlled study of folic acid (5 mg/d) for 6 weeks was undertaken in 33 patients. Endothelial function, assessed by flow-mediated dilatation (FMD), was measured before, at 2 and 4 hours after the first dose of folic acid, and after 6 weeks of treatment. Plasma folate increased markedly by 1 hour (200 compared with 25.8 nmol/L; P &lt;0.001). FMD improved at 2 hours (83 compared with 47 μm; P &lt;0.001) and was largely complete by 4 hours (101 compared with 51 μm; P &lt;0.001). tHcy did not significantly differ acutely (4-hour tHcy, 9.56 compared with 9.79 μmol/L; P =NS). fHcy did not differ at 3 hours but was slightly reduced at 4 hours (1.55 compared with 1.78 μmol/L; P =0.02). FMD improvement did not correlate with reductions in either fHcy or tHcy at any time. Conclusions — These data suggest that folic acid improves endothelial function in CAD acutely by a mechanism largely independent of homocysteine.
Nitric oxide synthase 2 is required for conversion of pro-fibrogenic inflammatory CD133+ progenitors into F4/80+ macrophages in experimental autoimmune myocarditis
Authors: Przemyslaw Blyszczuk, Corrine Berthonneche, Silvia Behnke, Marcel Glönkler, Holger Moch, Thierry Pedrazzini, Thomas F. Lüscher, Urs Eriksson, Gabriela Kania
Journal: Cardiovascular Research (2012)

Experimental autoimmune myocarditis (EAM) model mirrors important mechanisms of inflammatory dilated cardiomyopathy (iDCM). In EAM, inflammatory CD133+ progenitors are a major cellular source of cardiac myofibroblasts in the post-inflammatory myocardium. We hypothesized that exogenous delivery of macrophage-colony-stimulating factor (M-CSF) can stimulate macrophage lineage differentiation of inflammatory progenitors and, therefore, prevent their naturally occurring myofibroblast fate in EAM. EAM was induced in wild-type (BALB/c) and nitric oxide synthase 2-deficient (Nos2−/−) mice and CD133+ progenitors were isolated from inflamed hearts. In vitro, M-CSF converted inflammatory CD133+ progenitors into nitric oxide-producing F4/80+ macrophages and prevented transforming growth factor-β-mediated myofibroblast differentiation. Importantly, only a subset of heart-infiltrating CD133+ progenitors expresses macrophage-specific antigen F4/80 in EAM. These CD133+/F4/80hi cells show impaired myofibrogenic potential compared with CD133+/F4/80− cells. M-CSF treatment of wild-type mice with EAM at the peak of disease markedly increased CD133+/F4/80hi cells in the myocardium, and CD133+ progenitors isolated from M-CSF-treated mice failed to differentiate into myofibroblasts. In contrast, M-CSF was not effective in converting CD133+ progenitors from inflamed hearts of Nos2−/− mice into macrophages, and M-CSF treatment did not result in increased CD133+/F4/80hi cell population in hearts of Nos2−/− mice. Accordingly, M-CSF prevented post-inflammatory fibrosis and left ventricular dysfunction in wild-type but not in Nos2−/− mice. Active and NOS2-dependent induction of macrophage lineage differentiation abrogates the myofibrogenic potential of heart-infiltrating CD133+ progenitors. Modulating the in vivo differentiation fate of specific progenitors might become a novel approach for the treatment of inflammatory heart diseases.
Aspects of the Rationale for the Women's Health Trial
Authors: R. L. Prentice, F. Kakar, S. Hursting, L. Sheppard, R. Klein, L. H. Kushi
Journal: JNCI Journal of the National Cancer Institute (1988)

A 5.5-fold range in breast cancer incidence rates in 21 countries shows strong correlation with national estimates of per capita intake of dietary fat, but not with other caloric sources (proteins and carbohydrates). It Is argued that certain breast cancer and hormone factors may contribute little to the explanation of such international variations In incidence of this neoplasm. It Is further argued that experimental studies in animals support a specific role for dietary fat in the promotion of mammary tumors, but the effects of calories alone seem to be largely restricted to tumor initiation. Finally, data from international, migrant-population, and analytic epidemiologic investigations are used to motivate the basic relative risk assumption of study designs thus far proposed for the Women's Health Trial, and some continuing motivations for a dietary intervention (low-fat diet) trial are discussed.
A CONTRIBUTION TO THE STUDY OF MOUNTAIN FEVER.
Authors: R. HARVEY REED
Journal: JAMA (1901)

I find in the arid plateaus of the Rocky Mountains three types of fever that predominate during the summer and fall. These more prevalent forms of febrile disturbances are familiarly known as malaria, typhoid and mountain fever. It is true that malarial fever is found to exist throughout the entire year, but it is more prevalent during spring, summer and autumn. We are not yet prepared to say that mountain fever is or is not a modified type of typhoid or malarial fever. Whether or not it is a relative to these diseases, the writer is satisfied that it has enough distinctive features, peculiar to itself, to warrant it in being worthy of separate consideration. It is not the purpose of the writer in this contribution to attempt to defend the so-called "mountain fever" against those who may disclaim its existence. As a member of the medical profession, I feel
Telomere damage induced by the G-quadruplex ligand RHPS4 has an antitumor effect
Authors: Erica Salvati, Carlo Leonetti, Angela Rizzo, Marco Scarsella, Marcella Mottolese, Rossella Galati, Isabella Sperduti, Malcolm F.G. Stevens, Maurizio D’Incalci, Maria Blasco, Giovanna Chiorino, Serge Bauwens, Béatrice Horard, Eric Gilson, Antonella Stoppacciaro, Gabriella Zupi, Annamaria Biroccio
Journal: Journal of Clinical Investigation (2007)

Functional telomeres are required for the replicability of cancer cells. The G-rich strand of telomeric DNA can fold into a 4-stranded structure known as the G-quadruplex (G4), whose stabilization alters telomere function limiting cancer cell growth. Therefore, the G4 ligand RHPS4 may possess antitumor activity. Here, we show that RHPS4 triggers a rapid and potent DNA damage response at telomeres in human transformed fibroblasts and melanoma cells, characterized by the formation of several telomeric foci containing phosphorylated DNA damage response factors gamma-H2AX, RAD17, and 53BP1. This was dependent on DNA repair enzyme ATR, correlated with delocalization of the protective telomeric DNA-binding protein POT1, and was antagonized by overexpression of POT1 or TRF2. In mice, RHPS4 exerted its antitumor effect on xenografts of human tumor cells of different histotype by telomere injury and tumor cell apoptosis. Tumor inhibition was accompanied by a strong DNA damage response, and tumors overexpressing POT1 or TRF2 were resistant to RHPS4 treatment. These data provide evidence that RHPS4 is a telomere damage inducer and that telomere disruption selectively triggered in malignant cells results in a high therapeutic index in mice. They also define a functional link between telomere damage and antitumor activity and reveal the key role of telomere-protective factors TRF2 and POT1 in response to this anti-telomere strategy.
Aftermath of the Abortion Decisions: Action in the Legislatures and in the Courts
Authors: William J. Curran
Journal: New England Journal of Medicine (1973)

IT has become a cliché to say that the abortion decisions of the United States Supreme Court in 1973 left more questions unanswered than they answered. The basic holdings in the two cases were outlined in an earlier column.1 The American people were just about evenly, but very fiercely, divided about abortion, particularly abortion on demand, at the time of the decisions. Since the cases came down, the state legislatures have been very active in considering and in passing legislation.During the 1973 sessions, some 200 abortion bills were introduced in over 40 of the states. Twenty-eight states considered bills . . .
Codon Bias and Base Composition Are Poor Indicators of Horizontally Transferred Genes
Authors: Liisa B. Koski, Richard A. Morton, G. Brian Golding
Journal: Molecular Biology and Evolution (2001)

Horizontal gene transfer is now recognized as an important mechanism of evolution. Several methods to detect horizontally transferred genes have been suggested. These methods are based on either nucleotide composition or the failure to find a similar gene in closely related species. Genes that evolve vertically between closely related species can be divided into those that retain homologous chromosomal positions (positional orthologs) and those that do not. By comparing open reading frames in the Escherichia coli and Salmonella typhi genomes, we identified 2,728 positional orthologs since these species split 100 MYA. A group of 1,144 novel E. coli genes were unusually diverged from their S. typhi counterparts. These novel genes included those that had been horizontally transferred into E. coli, as well as members of gene pairs that had been rearranged or deleted. Positional orthologs were used to investigate compositional methods of identifying horizontally transferred genes. A large number of E. coli genes with normal nucleotide composition have no apparent ortholog in S. typhi, and many genes of atypical composition do, in fact, have positional orthologs. A phylogenetic approach was employed to confirm selected examples of horizontal transmission among the novel groups of genes. Our analysis of 80 E. coli genes determined that a number of genes previously classified as horizontally transferred based on base composition and codon bias were native, and genes previously classified as native appeared to be horizontally transferred. Hence, atypical nucleotide composition alone is not a reliable indicator of horizontal transmission.
The Metabolic Basis of Inherited Disease
Authors: John H. Talbott
Journal: JAMA (1961)

It is a slack day in the editorial office if less than a dozen books are received for review. In most cases, they can be readily classified, using a 1, 2, 3 grading system. In the first category (selected) are the books that I reserve for review or to excerpt the essentials for an editorial. An example is the discussion of "The Health of the Presidents," (p. 324) in this issue. Books in the second category (excellent) either are reviewed by a member of the staff or are sent to a consultant on the book review panel, composed of more than 400 physicians or medical scientists in this country. Not every book in the "excellent" category is reviewed. Sometimes limitation of space or procrastination by the reviewer is responsible. A portion of the books consigned to the third category are reprint editions or revisions and, though usually excellent, are listed
When It Comes to Advice, Congress Offers Some of Most-Heeded Suggestions to NIH
Authors: Charles Marwick
Journal: JAMA (1988)

THE NATIONAL Institutes of Health (NIH) currently spends more than $22 million getting advice from some 3000 scientists about how to use its annual $6.7-billion budget. But it is Congress that often makes the decisions. Three recent events underscore the point. Despite the fact that four years ago the Institute of Medicine urged a moratorium on the formation of new institutes at the NIH, Congress is currently in the final stages of approving a deafness institute. Two senators were instrumental in the National Heart, Lung, and Blood Institute's reversing its decision to stop the development of a fully implantable artificial heart. A new political action committee has been formed to back the election of legislators who favor breast cancer research. The idea, of course, is to convince the National Cancer Institute to focus more attention on the disease. There is nothing new in these events. There has long been tension
Dermatological problems in British troops during the Gulf War
Authors: N.C. Hepburn
Journal: British Journal of Dermatology (1992)

Journal Article Dermatological problems in British troops during the Gulf War Get access N.C. Hepburn N.C. Hepburn University Department of Dermatology, The Royal Infirmary Edinburgh, Edinburgh EH3 9YW, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 126, Issue 2, 1 February 1992, Pages 200–201, https://doi.org/10.1111/j.1365-2133.1992.tb07822.x Published: 01 February 1992
Hazard of peritoneal dialysis: contaminated fluid.
Authors: W. K. Stewart, D. C. Anderson, M. I. Wilson
Journal: BMJ (1967)

Ascorbic Acid and Colds-Walker et al.MEDIBRLJISHURNA that administering very large doses of vitamin to well-nourished people does not have the same effect.It is sometimes said that the colds produced at this unit are not comparable to those which occur in people who are exposed to natural infection and who may develop hypothetical secondary bacterial infections.We, on the other hand, are impressed with the fact that the colds observed here experi- mentally are very similar clinically to those, caused by the same viruses, which are observed in clinical practice (Tyrrell, 1965), and we should be surprised if ascorbic acid had any prophylactic or therapeutic value for well-nourished subjects who caught colds at home or at work. SummaryPreliminary experiments showed no evidence that ascorbic acid protected cultures against several respiratory viruses or white mice against influenza.In further experiments 91 volunteers were given either 3 g. of ascorbic acid daily or placebo tablets.Three days after the treatment began they received intranasal drops containing an M rhinovirus, an H rhinovirus, a " new " rhinovirus which grows only in organ cultures, influenza virus type B, or a "new" virus related to avian bronchitis.The number, duration, and severity of the resulting colds were the same in the treated and control groups.There was no evidence that colds produced by any single virus were favourably affected.
Defining Sepsis-Reply
Authors: Edward Abraham
Journal: JAMA (1994)

In Reply.  —As noted by Drs Knaus, Harrell, and Wagner, the APACHE III system uses a broad range of physiological variables and other risk factors that are relevant for predicting outcome in critically ill patients. With modification, the APACHE III system has been adapted for septic patients, and in population studies it can serve to stratify risk of mortality in this clinical setting. 1 However, the APACHE III system does not include levels of mediators, such as cytokines or endotoxin, that have been shown to be elevated in sepsis and to correlate with outcome in severely ill septic patients. 2,3 The fact that the clinical syndrome of sepsis does not have any unique single biochemical marker implies that new therapies may need to be directed to subgroups of patients with altered production or release of specific mediators. Unfortunately, the APACHE III system will not allow identification of these subgroups defined
A selective EP4 PGE2 receptor agonist alleviates disease in a new mouse model of X-linked nephrogenic diabetes insipidus
Authors: Jian Hua Li, Chung-Lin Chou, Bo Li, Oksana Gavrilova, Christoph Eisner, Jürgen Schnermann, Stasia A. Anderson, Chu-Xia Deng, Mark A. Knepper, Jürgen Wess
Journal: Journal of Clinical Investigation (2009)

X-linked nephrogenic diabetes insipidus (XNDI) is a severe kidney disease caused by inactivating mutations in the V2 vasopressin receptor (V2R) gene that result in the loss of renal urine-concentrating ability. At present,no specific pharmacological therapy has been developed for XNDI, primarily due to the lack of suitable animal models. To develop what we believe to be the first viable animal model of XNDI, we generated mice in which the V2R gene could be conditionally deleted during adulthood by administration of 4-OH-tamoxifen.Radioligand-binding studies confirmed the lack of V2R-binding sites in kidneys following 4-OH-tamoxifen treatment, and further analysis indicated that upon V2R deletion, adult mice displayed all characteristic symptoms of XNDI, including polyuria, polydipsia, and resistance to the antidiuretic actions of vasopressin. Gene expression analysis suggested that activation of renal EP4 PGE2 receptors might compensate for the lack of renal V2R activity in XNDI mice. Strikingly, both acute and chronic treatment of the mutant mice with a selective EP4 receptor agonist greatly reduced all major manifestations of XNDI, including changes in renal morphology.These physiological improvements were most likely due to a direct action on EP4 receptors expressed on collecting duct cells. These findings illustrate the usefulness of the newly generated V2R mutant mice for elucidating and testing new strategies for the potential treatment of humans with XNDI.
Endocarditis Due to<i>Streptococcus mitis</i>with High-Level Resistance to Penicillin and Cefotaxime
Authors: John R. Lonks, Brian P. Dickinson, Valgerdur Runarsdottir
Journal: New England Journal of Medicine (1999)

To the Editor: Levitz reported (June 10 issue)1 on the successful use of intravenous vancomycin for treatment of a patient who had endocarditis caused by a penicillin-resistant strain of Streptococcus mitis. We treated a 48-year-old man with native-valve endocarditis due to penicillin- and cefotaxime-resistant S. mitis. He had a history of human immunodeficiency virus infection, injection-drug use, severe aortic insufficiency, and moderate mitral regurgitation. In the previous year, the patient had undergone several dental procedures. For prophylaxis against endocarditis, he received 3 g of amoxicillin one hour before each dental procedure and 1.5 g six hours after each procedure. His . . .
Chromosome 10, Frequently Lost in Human Melanoma, Encodes Multiple Tumor-Suppressive Functions
Authors: Lawrence N. Kwong, Lynda Chin
Journal: Cancer Research (2014)

Although many DNA aberrations in melanoma have been well characterized, including focal amplification and deletions of oncogenes and tumor suppressors, broad regions of chromosomal gain and loss are less well understood. One possibility is that these broad events are a consequence of collateral damage from targeting single loci. Another possibility is that the loss of large regions permits the simultaneous repression of multiple tumor suppressors by broadly decreasing the resident gene dosage and expression. Here, we test this hypothesis in a targeted fashion using RNA interference to suppress multiple candidate residents in broad regions of loss. We find that loss of chromosome regions 6q, 10, and 11q21-ter is correlated with broadly decreased expression of most resident genes and that multiple resident genes impacted by broad regional loss of chromosome 10 are tumor suppressors capable of affecting tumor growth and/or invasion. We also provide additional functional support for Ablim1 as a novel tumor suppressor. Our results support the hypothesis that multiple cancer genes are targeted by regional chromosome copy number aberrations.
Radical Prostatectomy by the Retropubic, Perineal and Laparoscopic Approach: 12 Years of Experience in One Center
Authors: Laurent Salomon, Olivier Levrel, Alexandre de la Taille, Aristotelis G Anastasiadis, Fabien Saint, Safawat Zaki, Dimitrios Vordos, Antony Cicco, L.Eric Olsson, Andras Hoznek, Dominique Chopin, Clement-Claude Abbou
Journal: European Urology (2002)
Apparently Free Medical Care
Authors: John Lister
Journal: New England Journal of Medicine (1964)

IT is remarkable what one learns about human nature and public opinion from taxicab drivers, as I discovered when I was recently in America and had occasion to take a cab to make a hospital call. As soon as I asked the driver to take me to the hospital, he asked if I were a doctor and immediately passed me a letter from an insurance company. "Do you know about these insurance doctors?" he asked. Without waiting for an answer he explained that his son had been knocked down by a motorcar when he was only five. His whole body . . .
The Deep Subcutaneous Administration of Concentrated Heparin
Authors: Donald V. Baker, Richard Warren, John S. Belko
Journal: New England Journal of Medicine (1951)

HEPARIN and Dicumarol are at present widely used in the prevention and treatment of thromboembolic diseases. The former has maintained its place, despite its expense, because of its predictability, rapidity of anticoagulant effect and lack of side reactions. Since heparin is excreted or neutralized by the body in a few hours, it must be given continuously or intermittently over relatively short periods of time. Only the parenteral route has been found effective. The standard method has been the constant intravenous drip of 200 to 300 mg. in 1.5 liters of intravenous solution daily, as reported by Murray.1 , 2 Intermittent intravenous heparin, . . .
Control of Tachycardia By Procainamide
Authors: Albert H. Douglas
Journal: JAMA (1969)

<h3>To the Editor:—</h3> The article, "Large Doses of Procainamide for Paroxysmal Ventricular Tachycardia," which appeared inThe Journal(<b>209</b>:1221, 1929), described four cases of recurrent ventricular tachycardia controlled by procainamide in doses up to 10.5 gm daily. Long-term follow-up of these patients is not given, and the authors state that the dosage can usually be decreased after several weeks of therapy. About four years ago, I reported a similar observation.<sup>1</sup>A patient with coronary heart disease and recurrent ventricular tachycardia required 10.5 gm of procainamide daily to prevent recurrence. This dose was continued for three years, and was subsequently reduced to 8.0 gm daily. Any further reduction precipitated recurrent arrhythmia. Up to the present time, this patient has taken the large doses of the drug for seven years, without evidence of lupus erythematosus or other toxic condition.
Dasatinib-associated major molecular responses in patients with chronic myeloid leukemia in chronic phase following imatinib failure: response dynamics and predictive value
Authors: A Hochhaus, M C Müller, J Radich, S Branford, H M Kantarjian, B Hanfstein, P Rousselot, D-W Kim, J H Lipton, E Bleickardt, A Lambert, T P Hughes
Journal: Leukemia (2009)
Section Work at the Meetings of the American Medical Association.
Authors: E. W. Holmes
Journal: JAMA (1897)

Philadelphia, Pa., June 21, 1897. <h3>To the Editor:</h3> —Your discussion of "<i>The Ideals of the Profession</i>" is a most moderate and timely one. It is,<i>unfortunately</i>, based upon the idea that the members of our profession invariably improve, as they grow older, showing by the end of the tenth year a well rounded perfection in science, arts and ethics. If this were so, the suggestion to keep the younger men back till they had been in practice ten years, would be most valuable.<i>Unfortunately</i>, in some of us at least, time emphasizes our faults as well as our virtues, and there are no more blatant advertisers, none more ready to rush into print, in either the medical or the lay press, none more eager to be the first to report "something new" based mayhap upon a single case, than some of the so-called leaders of the profession who have been