tbuckley/cabot-search huggingface dataset:
An Unusual ECG Artifact— Results of a Faulty Recorder
Authors: Shashi K. Agarwal
Journal: JAMA (1979)

<h3>To the Editor.—</h3> Accurate interpretation of an ECG requires that it is free from distortion and artifact. However, with the increasing use of monitoring devices, ECG artifacts are on the increase and, in a recent survey, were found to be present in as many as 58% of all tracings.<sup>1</sup>Most of these were due to poor techniques and can be easily recognized by an experienced and attentive interpreter. Artifacts from malfunctioning equipment, although uncommon, are known to occur and may lead to serious diagnostic consequences.<sup>2</sup>I was recently confronted with an unusual ECG, which was subsequently found to be the result of an instrument-related defect. <h3>Report of a Case.—</h3> The patient was a 36-year-old man in whom shortness of breath and pleuritic retrosternal and right-sided chest pain developed. He was known to have a case of malignant pleural mesothelioma of the right side of the chest and had
Adventures In Medical Research: A Century of Discovery at Johns Hopkins
Authors: Gert H. Brieger
Journal: JAMA (1976)

The general history of the Johns Hopkins Medical School, pioneer in American higher education and seedbed of reform in medical education, has already been well-chronicled by Alan Chesney and recently completed through World War II by Thomas B. Turner. Does the Hopkins then deserve yet another book, a large one at that? The answer is an emphatic yes because Dr Harvey, for nearly 30 years Professor of Medicine of the Johns Hopkins Hospital, has, in this series of essays, begun to put together the history of clinical research. America's rise to preeminence in world medicine has been influenced in an astounding way by the medical school envisioned by Daniel C. Gilman and brought to fruition by Welch, Osler, Halsted, Kelly, Mall, Abel, and their many students who fanned out from Baltimore, spreading the gospel while providing new loci for productive work. In 26 chapters, all of which first appeared as
The doctor writer's handbook
Authors: Theodore Dalrymple
Journal: BMJ (2007)

Every so often a junior doctor would come to me and confess that he or she wanted to write. This was not in itself absurd: the number of doctor writers is, after all, legion. 

Junior doctors afflicted with literary ambition would ask my advice. I had only three pieces of advice to give: firstly, that they should continue in the hospital for a few more years, because human nature was concentrated and distilled there as if for the express purpose of training writers; secondly, that on no account should they consort with academics of the humanities departments of any university, for to do so was the primrose path to stylistic perdition; and finally, that they should read a great deal.

“Yes, but …
Abstract 2262: Elevated peroxiredoxin expression in breast cancer and its protective role in doxorubicin-resistance
Authors: Jillian Muhlbauer, Gregg Perlmutter, Caitlin McDonald, Harry Cintineo, Caterina Aiello, Shelley A. Phelan
Journal: Cancer Research (2014)

Abstract Peroxiredoxin (Prdx) proteins are thiol-specific antioxidants that protect cells from oxidative stress in various normal and disease states. There are six different Prdx proteins expressed in mammals, each possessing a characteristic tissue and subcellular distribution. Recent studies have revealed elevated Prdx levels in many cancers, suggesting a protective role for these proteins in cancer cell survival. In the present study we analyzed Prdx levels in several human breast tumor samples, and also investigated the function of Prdx proteins in the MCF-7 breast cancer cell line. Analysis of breast tumor and adjacent normal breast tissue from almost 20 patients showed elevated levels of most Prdx proteins in tumor tissue from the majority of patients. To address the role of Prdxs in breast cancer, we used transient siRNA transfections of MCF-7 cells and examined resulting cell viability in the absence and presence of doxorubicin treatment. Our data show that individual suppression of four of six of the Prdx proteins leads to increased cell death, as well as increased sensitivity to doxorubicin-induced toxicity. Finally, we show that clonal selection of doxorubicin-resistant MCF-7 cells by two-week culture in 0.1uM doxorubicin resulted in a marked elevation in the expression of several Prdx proteins. Similar studies are currently underway in the highly metastatic MDA cell line, and possible upstream regulators of Prdx overexpression in these lines are being investigated. Together, these data show a strong protective role for Peroxiredoxins in breast cancer cell survival, and suggest that Prdx overexpression in breast cancer may play a role in chemotherapy-resistance. Citation Format: Jillian Muhlbauer, Gregg Perlmutter, Caitlin McDonald, Harry Cintineo, Caterina Aiello, Shelley A. Phelan. Elevated peroxiredoxin expression in breast cancer and its protective role in doxorubicin-resistance. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2262. doi:10.1158/1538-7445.AM2014-2262
Immunoproteasome beta subunit 10 is increased in chronic antibody-mediated rejection
Authors: Joanna Ashton-Chess, Hoa Le Mai, Vojislav Jovanovic, Karine Renaudin, Yohann Foucher, Magali Giral, Anne Moreau, Emilie Dugast, Michael Mengel, Maud Racapé, Richard Danger, Claire Usal, Helga Smit, Marina Guillet, Wilfried Gwinner, Ludmilla Le Berre, Jacques Dantal, Jean-Paul Soulillou, Sophie Brouard
Journal: Kidney International (2010)
THE DESTRUCTION OF CHILDREN'S TEETH—CAUSE AND PREVENTION.
Authors: J. G. HENISTER
Journal: JAMA (1896)

The destruction of children's teeth is to me, as it must be to all of you, a source of the greatest regret, and ordinary methods have failed to overcome the difficulty. It would be useless for me to attempt to go into details as to the cause of this condition, as it must be perfectly apparent to all, who stop to consider a moment. I think the first and greatest cause is neglect and ignorance as to the proper time and means of caring for the teeth. I tell you, gentlemen, it is astonishing to see the ignorance of some parents in regard to the teeth of their children. They will come into your office with a child and point to a six-year molar with the crown nearly destroyed, and say: "Doctor I wish you would extract this little snag." You will answer, "That is a permanent tooth and should
LONGITUDINAL FRACTURE OF THE LOWER END OF THE RADIUS TOWARD THE ULNAR SURFACE
Authors: James C. Wilhoit
Journal: JAMA (1913)

Longitudinal fractures of the lower end of the radius are exceedingly rare. Cotton<sup>1</sup>of only three specimens. Parrish Parrish<sup>2</sup>bly have ll<sup>3</sup>only roentgenographic illustration of the lesion. So far as fcan learn, this case is the only longitudinal fracture of the radius that split toward the ulnthat split toward the ulnar surface. J. H..G.,er aged 38, May 3, 1913, was boxing hats; his antagonist caught him by the fingers of his right band handerking to fr.ee himfreeelt something in his wrist snap. wonsulted me the day of the injury and on injury and on roent genosccpyacture was located. <h3>Gentleness in Surgery.</h3> \Theoperators that duce little constitutional disturbance, little shock, by thelittle shock, by the performancetion which at the hands of another causes very serious collserious collapse, o differences patient, in the anesthetist, in the method, s,in anything else bute surgeon himselb. There are surgeons who operate on the
Can the Intensive Care Unit Be Harmful?
Authors: Donald H. Spodick
Journal: JAMA (1983)

<h3>To the Editor.—</h3> Dr Knaus' editorial (1983;249:1059) covering uncertainties about the impact of intensive care units (ICUs) hits the target squarely—"not a single scientific study claiming that, by itself, intensive care unit support cures any disease." He reasonably suggests an approach by "rigorous selective study of acutely ill patients, through the prospective identification of important physiological indicators." Beyond this, however, not a single scientific study has investigated whether ICU support actually harms some patients, since it is clear that invasive instrumentation per se has this potential.<sup>1</sup> In essence, Dr Knaus appropriately considers the ICU itself to be a form of treatment. I think his objectives, shared by all of us—essentially determination of risk-benefit ratios—can best be approached by the most scientific and ethical method of getting an answer about any kind of treatment: a prospective randomized, controlled therapeutic trial.<sup>2</sup>One method for doing this would be to have
Abstract 471: Acute activation of beta2-adrenergic receptor inhibits in vitro renal carcinoma cell migration through betaArrestin2-mediated regulation of p115RhoGEF
Authors: Xiaojie Ma, Yu Zhao, Yehia Daaka, Zhongzhen Nie
Journal: Cancer Research (2012)

Abstract Metastatic renal cell carcinoma (RCC) is fatal with no current effective treatment. Molecular mechanisms underlying progression to metastatic RCC are not fully understood, and gene array studies have revealed increased expression of beta2-adrenergic receptors (beta2AR) and betaArrestin2 genes in RCC. We examined the regulation of RCC migration and invasion, two critical steps in the progression to the metastatic disease, following beta2AR activation using scratch assays and Boyden chamber assays in cultured RCC cell lines Caki-1, SN12C and RCC7. Acute treatment with the selective beta2AR agonist formoterol inhibited migration of the three cell lines by 40% to 70% with an IC50 of 2.5 nM or less. We further examined contribution of G protein and betaArrestin signaling. Using the betaAR-inverse agonist carvedilol that is biased for[[Unsupported Character - &amp;#61472;]]betaArrestin signaling, combined with transient knockdown of Gs or betaArrestin2 by siRNA, or mouse embryonic fibroblasts from betaArrestin1 or betaArrestin2 knockout mice, we identified betaArrestin2 as a mediator of beta2AR-induced inhibition of cell migration. betaArrestin2 forms a complex with p115RhoGEF (guanine nucleotide exchange factor) that was previously shown to be regulated by Gq and G12/13. Activation of beta2AR promoted the translocation of p115RhoGEF to the plasma membrane, with consequent activation of RhoA which enhances formation of focal adhesions that restrain the cell migration. These results suggest that betaArrestin2 exerts cell compartment-specific effects on the cell migration. In the absence of acute beta2AR activation, betaArrestin2 sequesters p115RhoGEF in the cytosol, leading to relatively lower RhoA activity at the cell periphery and higher cell migration rate. Upon acute beta2AR activation, betaArrestin2 translocates to the plasma membrane with concomitant enrichment of p115RhoGEF at the plasma membrane, resulting in the activation of RhoA and decreased cell motility. Our results imply that betaArrestin2 and its effectors impact RCC metastasis and suggest its utility as a drug target to limit progression of the disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 471. doi:1538-7445.AM2012-471
Epigenetic inactivation of the CIP/KIP cell-cycle control pathway in acute leukemias
Authors: C.S. Chim, A.S.Y. Wong, Y.L. Kwong
Journal: American Journal of Hematology (2005)

Dysregulation of the cell cycle is important in oncogenesis. We analyzed the potential inactivation of the CIP/KIP family of the cyclin E/CDK/RB pathway by gene promoter hypermethylation in leukemias. The methylation-specific polymerase chain reaction (MSP) with primers for methylated (M-MSP) and unmethylated (U-MSP) alleles of the p21, p27, and p57 genes was used to study five leukemic cell lines, 50 acute myeloid leukemia (AML) samples, and 25 acute lymphoblastic leukemia (ALL) samples. p21 was hemizygously methylated in Raji and Jurkat but remained unmethylated in U937, HL60, and NB4. p27 was hemizygously methylated in Raji but unmethylated in the other cell lines. p57 was completely methylated in Raji and NB4, hemizygously methylated in U937, and unmethylated in HL60 and Jurkat. At diagnosis, p21 methylation was not detected in any case of AML or ALL. p27 methylation occurred in 2 (4%) AML patients and in 1 (4%) ALL patient. p57 methylation occurred in 1 (2%) AML patient and in 1 (4%) ALL patient. Therefore, methylation inactivation of the INK4/CDK/RB pathway in leukemia is infrequent. A review of the literature showed a marked variation in the frequencies of methylation of these genes, which might be attributable to difference in methodologies used to detect gene methylation.
Nonmyeloablative allogeneic stem cell transplantation in elderly patients with hematological malignancies: Results from the GITMO (Gruppo Italiano Trapianto Midollo Osseo) multicenter prospective clinical trial
Authors: Michele Falda, Alessandro Busca, Ileana Baldi, Nicola Mordini, Benedetto Bruno, Bernardino Allione, Alessandro Rambaldi, Enrico Morello, Franco Narni, Stella Santarone, Franco Locatelli, Andrea Bacigalupo
Journal: American Journal of Hematology (2007)

Abstract This study aimed to evaluate the efficacy of a nonmyeloablative conditioning consisting of fludarabine and TBI in patients aged ≥60 years.A total of 32 patients (median age 62 years; range 60–70) with hematological malignancies were treated with fludarabine (30 mg/m 2 × 3–5 days) and 200 cCy TBI followed by allogeneic hematopoietic stem cell transplantation (HSCT) from a matched‐sibling donor. GVHD prophylaxis consisted of cyclosporine and mycophenolate. Neutrophil recovery occurred in all patients at a median time of 16 days (range 9–34). Six patients did not become granulocytopenic. On day +30, 10 patients had &gt;95% donor chimerism and 19 patients had mixed chimerism. The cumulative probabilities of Grade II–IV acute GVHD and chronic GVHD were 48 and 83%, respectively. Transplant‐related mortality at 100 days and 1 year was 6 and 10%, respectively. The probabilities of 2‐year overall (OS) and progression‐free survival (PFS) were 39 and 35%, respectively. The estimated 2‐year probability of OS and PFS for patients in early disease stages were 77 and 64%, respectively, which were significantly higher than the survival and PFS estimates of 0% obtained in patients with advanced disease stages at the time of transplant. Our analysis would suggest that for patients older than 60, this regimen is well tolerated and associated with a low incidence of transplant‐related mortality. The leukemic burden at time of transplant has proven to be the most important risk factor for the outcome. Am. J. Hematol. 82:863–866, 2007. © 2007 Wiley‐Liss, Inc.
Changing what we do
Authors: Douglas Kamerow
Journal: BMJ (2007)

It is not every day that readers come upon an article that leads them to change the way they do things. Research cautions us that reading papers rarely leads to changes in behavior. Undeterred by such warnings, we offer several candidates for your consideration in this issue.

Stroke is the leading cause of long-term disability in the United States. About four million Americans are living with the effects of a stroke. Millions of family members are caring for these patients at home, comprising a huge …
Association of IL1RL1, IL18R1, and IL18RAP gene cluster polymorphisms with asthma and atopy
Authors: Naomi E. Reijmerink, Dirkje S. Postma, Marcel Bruinenberg, Ilja M. Nolte, Deborah A. Meyers, Eugene R. Bleecker, Gerard H. Koppelman
Journal: Journal of Allergy and Clinical Immunology (2008)
Potential molecular mechanisms of oxidant-induced carcinogenesis.
Authors: J H Jackson
Journal: Environmental Health Perspectives (1994)

Chronic exposure to oxidants is associated with an increased incidence of malignancy; however, the mechanism(s) by which oxidants contribute to carcinogenesis is unknown. Since oncogene activation plays an important role in carcinogenesis, we hypothesized that hydroxyl radical-induced DNA damage might contribute to carcinogenesis by causing oncogene activation. The studies reported herein demonstrate that hydroxyl radical-induced DNA damage can activate the K-ras 4B and C-Raf-l oncogenes by causing point mutations and deletions, respectively. In addition, our results indicate that a) hydroxyl radical-induced DNA damage causes selective base substitutions; b) the four DNA bases have different susceptibilities to hydroxyl radical-induced mutations; and c) hydroxyl radical-induced mutations are not randomly distributed among oncogene codons. Our studies suggest that oncogene activation could be one potential mechanism by which oxidants contribute to carcinogenesis.
A7.4 Association of Galectin Single Nucleotide Polymorphisms with Autoimmune Diseases
Authors: Z Pál, P Antal, SK Srivastava, J Gál, S André, E Gordeeva, G Nagy, H Kaltner, NV Bovin, MJ Molnár, A Falus, HJ Gabius, EI Buzás
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Galectins are potent immune regulators. Surprisingly, genetic association of galectin genes with autoimmune diseases have not yet been studied. A polymorphism in the coding region of the galectin-8 gene (Rs2737713; F19Y) and a novel galectin-1 and interleukin 2 receptor β haplotype were investigated for association with rheumatoid arthritis and myasthenia gravis. <h3>Materials and Methods</h3> A case-control analysis and a related quantitative trait-association study were performed to investigate the association of the galectin 8 gene polymorphism in patients (myasthenia gravis 149, rheumatoid arthritis 214 and 134 as primary and repetitive cohorts, respectively) and 365 ethnically matched (Caucasian) healthy controls. Distribution was also investigated in patients grouped according to their antibody status and age at disease onset. Comparative testing for lectin activity was carried out in ELISA/ELLA-based binding tests with both wild-type and F19Y mutant galectin-8 from peripheral blood mononuclear cell lysates of healthy individuals with different genotypes as well as with recombinant wild-type and F19Y mutant galectin-8 proteins. Furthermore, we evaluated the association of regulatory region polymorphisms of the LGALS1 (Rs4820293, Rs4820294) and IL2Rβ (Rs743777, Rs228941) genes in 146 Caucasian myasthenia gravis patients compared to 291 ethnically matched controls. <h3>Results</h3> We found a strong association of the F19Y galectin 8 gene polymorphism with rheumatoid arthritis, and a mild one with myasthenia gravis. Moreover, the polymorphism also correlated with age at disease onset in the case of rheumatoid arthritis. The F19Y substitution did not appear to affect carbohydrate binding in solid-phase assays markedly. Also, a significant difference was found in the distribution of the Rs4820293/Rs743777 polymorphism haplotypes (p &lt; 0.01) in patients with myasthenia gravis and controls but not in rheumatoid arthritis. The Rs4820293 polymorphism of LGALS1, previously not described to be associated with any disease, did not affect LGALS1 expression in peripheral mononuclear cells and skeletal muscle. <h3>Conclusions</h3> This is the first study of an association between a galectin-based polymorphisms leading to a mutant protein and autoimmune diseases, with evidence for antagonistic pleiotropy.
The Application of Chemical Studies of Human Chorionic Gonadotropin to Visualize Its Three-Dimensional Structure*
Authors: JOYCE W. LUSTBADER, DAVID L. YARMUSH, STEVEN BIRKEN, DAVID PUETT, ROBERT E. CANFIELD
Journal: Endocrine Reviews (1993)

ALTHOUGH the primary structures (amino acid sequences) of each human and many mammalian gonadotropins were determined decades ago, their three-dimensional structures remain unknown. Since the demonstration by Anfinsen (1) that the information for generating the structure of a protein exists within the amino acid sequence alone, protein chemists have tried to decipher that information but have not yet succeeded. Although some successful methods have been devised to predict secondary structural elements from knowledge of the primary structure, little success has been achieved in generating a complete threedimensional model solely from the amino acid sequence. It is pertinent to inquire whether there is an intermediate solution to this important problem. Suppose, for example, that one has a large body of chemical and immunochemical information which permits the selection and modification of structural motifs that are based on models of likely loop structures in the protein and are consistent with the body of known information. Can such a very rough model be refined by computer algorithms into potentially real structures which can then be tested by experiments? Essentially, the question is whether one can use the computer to process biological and chemical information to generate a testable model of a protein structure. Such a model would be of great use to endocrinologists studying the glycoprotein hormones and would help in the design of structure-function studies, immunochemical measuring systems, and recombinant constructs. Essentially, such a three-dimensional image may prompt investigators to develop new hypotheses and experiments that may not have been apparent without such a visual aid. This is the purpose of presenting such a model in this review.
Oral Activity Cycles in Mild Chronic Schizophrenia
Authors: STANLEY FRIEDMAN
Journal: American Journal of Psychiatry (1968)

There has been speculation that the REM cycle functions as a cyclic waxing and waning of instinctual drive activity. Some studies have been made of spontaneous diurnal oral activity cycles of energy discharge which are hypothetical counterparts to the rhythmic energy discharges occurring during REM cycles. The present study hypothesized that mild chronic schizophrenic patients, under conditions of relaxed semi-isolation, would show spontaneous, cyclic oral activity. The oral activities of seven patients were recorded and scored in consecutive 20-minute periods; the scores yielded cyclic data that supported the author's hypothesis.
VIP-, substance P- and met-enkephalin-immunoreactive innervation of the human gastroduodenal mucosa and Brunner's glands.
Authors: G L Ferri, P Botti, G Biliotti, L Rebecchi, S R Bloom, L Tonelli, G Labo, J M Polak
Journal: Gut (1984)

VIP-, substance P- and met-enkephalin-containing innervation of the human gastroduodenal mucosa and Brunner9s glands was studied by immunocytochemistry on whole mount tissue preparations. A dense VIP-containing nerve supply was found around fundic and pyloric glands, while the few and scattered substance P-immunoreactive fibres tended to run across the full thickness of the gastric mucosa. In the duodenum, both VIP and substance P were present in a striking nerve network in the villi as well as in the muscularis mucosae and around blood vessels. Both peptides were also immunostained in nerve bundles and neuronal perikarya between the lobules of Brunner9s glands, while only very few fibres reached the proximity of acinar cells. Met-enkephalin-immunoreactivity was detected in a small number of nerve fibres, virtually confined to the basal parts of the mucosa and to the duodenal submucous plexus.