tbuckley/cabot-search huggingface dataset:
Democracy and DNA: American Dreams and Medical Progress
Authors: Selma Harrison Calmes
Journal: JAMA (1996)

<i>Democracy and</i>DNA arrived for review a week before a Joint Commission (JCAHO) visit. The usual last-minute flurry left little time to pay attention to a book, but the interesting title and an intriguing dust jacket design led me to open and browse through it that day. Soon I found myself reading a chapter on Elizabeth Blackwell, the country's first woman doctor. It was well-written and piqued my interest. Other names I ran across included Oliver Wendell Holmes, Frederick Law Olmstead, and Katherine Lee Bates. How did they all fit together? And, how is democracy related to DNA? I took the book home that night for more browsing. Finally, after the JCAHO visit, I got around to reading the book from beginning to end, and the early promise suggested by the title, the dust jacket, and the Blackwell chapter was met—and far exceeded. This is a most interesting book, which
Inflammation of solar keratoses following systemic 5-fluorouracil
Authors: V. BATAILLE, D. CUNNINGHAM, J. MANSI, P. MORTIMER
Journal: British Journal of Dermatology (1996)

Several cutaneous reactions have been reported following systemic 5‐fluorouracil (5‐FU) for the treatment of malignancies. We report three patients with marked inflammation of the solar keratoses following continuous infusion of 5‐FU for solid tumours. This side‐effect with 5‐FU. only previously reported in three other cases, was beneficial as most solar keratoses cleared following the inflammatory reaction. The reasons why 5‐FU should be selectively taken up by solar keratoses are discussed.
Abstract 1757: MEDI-573, an IGF-I/II neutralizing human antibody inhibits both IGF-1R and IR-A signaling pathways
Authors: Jin Gao, Jon W. Chesebrough, Leonard Incognito, Steven Coats, Klaus Bosslet, Bahija Jallal, Yong S. Chang
Journal: Cancer Research (2011)

Abstract Insulin-like growth factors (IGF), IGF-I and IGF-II, are small polypeptides involved in regulating cell proliferation, survival, differentiation and transformation. IGF activities are mediated through binding and activation of IGF-1R or insulin receptor isoform A (IR-A). Overexpression of IGF-II and IR-A has been reported in multiple types of cancer, and has also been proposed as a potential mechanism for cancer cells to develop resistance to IGF-1R targeting therapy. MEDI-573 is a dual targeting human antibody that neutralizes both IGF-I and IGF-II. We have shown previously that this antibody inhibits IGF-1R activation by IGF and demonstrated potent in vivo tumor growth inhibition activity in IGF driven xenograft models. Here we show that MEDI-573 inhibits IGF-II activated IR-A signal pathways without cross reactivity to insulin, and therefore has minimum impact on glucose metabolism, which is mediated mainly by insulin/IR interaction. MEDI-573 blocks the binding of IGF-II to, and inhibits the subsequent phosphorylation of IR-A and IRS-1. MEDI-573 inhibited IGF-II-induced in vitro growth of IR-A overexpressing cells with or without the presence of up to 10uIU of insulin in the medium. In addition, MEDI-573 inhibited IGF-II-induced proliferation of IR-A-overexpressing cells as effectively as it inhibited the IGF-1R-overexpressing cells. The anti-proliferative activity of MEDI-573 is not changed across heterogeneous mixed cell populations with various ratios of IR-A- versus IGF-1R-expressing cells. In contrast, an IGF-1R specific antibody was most active at inhibiting the proliferation of a pure IGF-1R expressing homogenous population, but lost activity when the heterogeneous cell population contained increasing percentages (25-50%) of IR-A-expressing cells. We also examined the relative abundance of IR-A versus IR-B (insulin receptor isoform B) mRNA in multiple cancer cell lines using a previously published quantitative RT-PCR method. The results show that IR-A is frequently the dominant isoform overexpressed in these cancer cells. Taken together, these results demonstrate that by neutralizing IGF-I and IGF-II ligands, MEDI-573 is a dual targeting antibody that offers an effective approach to selectively target both the IGF-1R and IR-A signaling pathways and potentially overcome IGF-1R targeting resistance. 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 1757. doi:10.1158/1538-7445.AM2011-1757
Who Teaches Physiological Chemistry?
Authors: Samuel P. Bessman
Journal: JAMA (1966)

The development of the medical school department of biochemistry may soon transform it to an institute only remotely related to the activities of the school. This process has been caused by two factors. The first is the Flexner Report and the second is the extensive growth of the discipline itself. When the Flexner Report established the need for the incorporation of scientific principles into the teaching of medicine, departments of physiological chemistry began to appear in medical schools. The growing new departments became havens for increasing numbers of biochemists who had found little opportunity to develop independently in other areas of the universities. They soon expanded their studies beyond the immediate problems of animal and human biochemistry into the field of fermentation, then enzymology, then into bacterial metabolism and the chemistry of genetics. This was a natural result of the generality of biochemistry, but clinical departments began to question the
An outbreak of scabies in a residential home
Authors: D.A. BURNS
Journal: British Journal of Dermatology (1987)

Journal Article An outbreak of scabies in a residential home Get access D.A. BURNS D.A. BURNS Leicester Royal Infirmary, Infirmary Square, Leicester LEI 5WW, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue 3, 1 September 1987, Pages 359–361, https://doi.org/10.1111/j.1365-2133.1987.tb04143.x Published: 01 September 1987
Education, Occupation, and Alzheimer's Disease-Reply
Authors: Yaakov Stern
Journal: JAMA (1994)

In Reply.  —We thank Dr Devitt and Dr Cohen for their comments. We agree that education and occupation serve as a marker for lower socioeconomic status. Thus, poverty-related conditions including malnutrition, lifestyle, health care, and environmental factors including exposure to pollutants could impact on the developing or mature brain to produce a reduction in reserve against AD. Still, there are suggestions in our data that this is not the entire explanation for the increased risk of incident dementia in individuals with less educational and occupational attainment.  None of our subjects were demented at the initial visit, which eliminates many of the potential disparities that might be introduced by gross neurological insult. Even when the subject cohort was restricted to those who performed relatively well on our examinations (by eliminating those with borderline dementia), the education/occupation effects remained, again arguing against the idea that one group was simply more impaired than
The refresher course
Authors: Isabeau Walker
Journal: BMJ (2007)

The setting is the Mengo hospital for plastic and reconstructive surgery in Kampala, the meeting the Ugandan Society of Anaesthesia's annual refresher course. I am working with Andrew Hodges, who has established the charity Interface Uganda and moved to Kampala with his wife and family to set up a plastic surgical training programme. Sarah Hodges is an anaesthetist and is coordinating the refresher meeting. There are a handful of speakers from Britain for the two courses, held back to back, which are attended by nearly all of the anaesthetists and anaesthetic officers in the country. That's a total of 280 of the 330 anaesthetic officers, 11 consultant anaesthetists, and three trainee anaesthetists currently in Uganda. The population of Uganda is 24 million. The Royal College of Anaesthetists has 13 000 anaesthetists on its books in the United Kingdom.

We …
Podophyllum Resin Poisoning With Complete Recovery
Authors: Marcello Balucani, Darryl D. Zellers
Journal: JAMA (1964)

A REVIEW of the literature of podophyllum resin poisoning revealed only four cases, of which three were fatal and the fourth involved neurological sequelae. It appears worthwhile to report our case because of the complete recovery of our patient. <h3>Report of a Case</h3> A 19-year-old white female was admitted to the hospital on Jan 18, 1964, with complaints of urinary frequency and burning at the micturition. Her last normal menses was on June 24, 1963. Her history was not contributory. Physical examination revealed a well-developed, well-nourished woman in no acute distress. Eyes, nose, throat, and chest wall were normal. The breasts were enlarged, with dark pigmentation of the areolae. The lungs were clear to auscultation and percussion. The heart examination did not reveal any murmur or enlargement. The blood pressure was 120/60 mm Hg; the pulse rate was 82 beats per minute, rhythmic and regular. The abdomen was enlarged as
Nuclear Anatomy of Diversionary Central Nervous System Shunts in Children
Authors: JOHN R. STY, BERNARD J. D??SOUZA, DAVID DANIELS
Journal: Clinical Nuclear Medicine (1978)

A simple method of demonstrating shunt morphology with 99m technetium diethylene triamine penta-acetic acid (99m Tc-DTPA) is described. The anatomic abnormalities are illustrated. Demonstration of the site of obstruction is useful in selecting the neurosurgical approach. The procedure is minimally invasive, accurate, and simple to interpret.
Impact of age and comorbidities on the criteria for remission and response in rheumatoid arthritis
Authors: E Krishnan
Journal: Annals of the Rheumatic Diseases (2005)

To determine to what extent health status impairment in rheumatoid arthritis (RA) measured by self report of pain, global assessment, and functional disability is attributable to age and other comorbid conditions as opposed to the disease itself.Pain, global assessment, and Health Assessment Questionnaire Disability Index (HAQ-DI) were measured in a random sample of 1530 adults in the Central Finland District, Finland. Median regressions were used for multivariable analyses.The mean age was 55.4 years and 72% were women. A large majority of the population reported some pain (76%) and less than perfect general health (83%). The overall mean values of pain, HAQ-DI, and general health were 20 mm, 0.25 units, and 21 mm, respectively. The most common self reported musculoskeletal comorbidities were osteoarthritis (24%) and chronic back pain (25%). Age and number of comorbidities were the only statistically significant correlates of pain and general health in multivariable analyses.Self reported disability, pain, and poor health were widely prevalent in the general population and are related to age and comorbid conditions. This needs to be taken into account when interpreting remission and response rates using current criteria and for future development of definitions for these end points in RA and other rheumatic diseases.
DIATHERMY IN TREATMENT OF GENERAL PARESIS
Authors: Hugh A. McKay, Kenneth G. Gray, William C. Winans
Journal: American Journal of Psychiatry (1932)

A series of 32 patients treated by diathermy in conjunction with chemotherapy is presented. The clinical outcome of 28 completed cases is described. The clinical course and post mortem findings of a case which died during treatment are outlined. Evidence that certain patients are susceptible to the elevation of temperature induced by diathermy is offered.
Land of the free
Authors: T. Greenhalgh
Journal: BMJ (2004)

At the age of 19, I got a job lifeguarding at a kids' summer camp in America. I let slip to a colleague that I didn't have a work permit. Next day, I got a ride in a yellow car with the siren screaming just like in Starsky and Hutch , while handcuffed to a hunky cop. I got six hours of questioning and my mugshot and fingerprints taken by the FBI. And I got deported.

Six months ago, I …
Paired Immunoglobulin-like Receptor (PIR)-A Is Involved in Activating Mast Cells through Its Association with Fc Receptor γ Chain
Authors: Akito Maeda, Mari Kurosaki, Tomohiro Kurosaki
Journal: The Journal of Experimental Medicine (1998)

Paired immunoglobulin-like receptor (PIR)-A and PIR-B possess similar ectodomains with six immunoglobulin-like loops, but have distinct transmembrane and cytoplasmic domains. PIR-B bears immunoreceptor tyrosine-based inhibitory motif (ITIM) sequences in its cytoplasmic domain that recruit Src homology (SH)2 domain–containing tyrosine phosphatases SHP-1 and SHP-2, leading to inhibition of B and mast cell activation. In contrast, the PIR-A protein has a charged Arg residue in its transmembrane region and a short cytoplasmic domain that lacks ITIM sequences. Here we show that Fc receptor γ chain, containing an immunoreceptor tyrosine-based activation motif (ITAM), associates with PIR-A. Cross-linking of this PIR-A complex results in mast cell activation such as calcium mobilization in an ITAM-dependent manner. Thus, our data provide evidence for the existence of two opposite signaling pathways upon PIR aggregation. PIR-A induces the stimulatory signal by using ITAM in the associated γ chain, whereas PIR-B mediates the inhibitory signal through its ITIMs.
Clinical course and prognosis of 91 patients with cirrhosis and type 1 hepatorenal syndrome (HRS) treated with terlipressin: a retrospective multicenter study
Authors: R. Moreau, C. Duhamel, T. Poynard, J.P. Cervoni, P. Ichai, A. Abergel, C. Halimi, M. Pauwels, J.F. Cadranel
Journal: Journal of Hepatology (2001)
Cholesterol and Mortality
Authors: James W. Hainer
Journal: JAMA (1987)

<h3>To the Editor.—</h3> I am interested in the fall in cholesterol level over time and its positive association with overall and cardiovascular mortality as reported by Anderson et al.<sup>1</sup>As I understand it, individual least squares regression lines were computed for each individual having at least five cholesterol measurements. Positive and negative slopes as binary variables relative to no change were entered into a model that included age and sex. Baseline cholesterol values of individuals with positive as opposed to those with negative slopes were not reported. I am concerned that individuals with negative slopes would have higher baseline cholesterol values due to the phenomenon of regression to the mean. The positive association with mortality would then be attributable to the higher baseline cholesterol values rather than the fall in cholesterol level.<sup>2,3</sup> Why the converse finding—ie, an inverse relationship between an increase in cholesterol level and mortality—is not
Inhibition of prostaglandin synthesis after metabolism of menadione by cultured porcine endothelial cells.
Authors: A Barchowsky, K Tabrizi, R S Kent, A R Whorton
Journal: Journal of Clinical Investigation (1989)

We have examined the effects of menadione on porcine aortic endothelial cell prostaglandin synthesis. Addition of 1-20 microM menadione caused a dose- and time-dependent inhibition of stimulated prostaglandin synthesis with an IC50 of 5 microM at 15 min. Concentrations greater than 100 microM menadione were necessary to increase 51Cr release from prelabeled cells. Recovery of enzyme inactivated by menadione required a 6-h incubation in 1% serum. In a microsomal preparation, menadione was shown to have no direct effect on conversion of arachidonic acid to prostaglandins. In intact cells menadione caused only a 40% inhibition of the conversion of PGH2 to prostacyclin. Enzymes involved in the incorporation and the release of arachidonic acid were not affected by menadione (20 microM, 15 min). Menadione undergoes oxidation/reduction reactions in intact cells leading to partial reduction of oxygen-forming, reactive oxygen species. In our cells menadione was found to increase KCN-resistant oxygen consumption. Further, an increased accumulation of H2O2 was observed with a time course consistent with menadione-induced inhibition of prostaglandin synthesis. We conclude that menadione at sublethal doses caused inhibition of prostaglandin synthesis. The mechanism involves inactivation of PGH2 synthase by a reactive species resulting from metabolism of menadione by endothelial cells.
Differential expression of PD-1 and Tim-3 marks activation versus exhaustion status of T cells in the tumor microenvironment
Authors: Jing Li, Robert L Ferris
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are two immune checkpoint receptors (ICR) highly co-expressed on tumor infiltrating T lymphocytes (TIL). PD-1 has been shown to inhibit T cell activation and type 1 T cell responses, while Tim-3 has been
Immune system boosters set for FDA go-ahead
Authors: C. Marwick
Journal: JAMA (1991)

GENETICALLY engineered immune system modulators are entering the mainstream of medical practice. An advisory committee to the Food and Drug Administration (FDA) has recommended that the commissioner license two of these agents.  One is granulocyte macrophage colony-stimulating factor (GM-CSF) and the other is granulocyte colony-stimulating factor (G-CSF) ( JAMA . 1990; 264:1233). Both are immune system boosters.  Their main role is the mitigation of infections in cancer patients. The agents increase the neutrophils that are killed by the chemotherapy these patients receive as treatment for their disease.  Marrow, Lymphoma, Leukemia  The first agent has been shown to be effective in stimulating engraftment of bone marrow transplants and in reducing infections in patients with non-Hodgkin's lymphoma and acute lymphoblastic leukemia. The GM-CSF is classified as an orphan drug and is currently available to patients under the treatment investigational new drug system.  Of the approximately 40 000 cases of non-Hodgkin's lymphoma that occur annually,
Newer Concepts in Hypertrophic Obstructive Cardiomyopathy II
Authors: Pravin M. Shah
Journal: JAMA (1979)

THE SYMPTOMS, when present, are generally those of left ventricular outflow obstruction, namely, dyspnea, syncope, angina, and palpitations. It is not uncommon to see a patient for evaluation of a murmur detected during a routine examination. <h3>Clinical Features</h3><h3>Dyspnea.—</h3> Effort dyspnea and paroxysmal nocturnal dyspnea constitute the most common symptoms and represent evidence of pulmonary congestion. Because elevations in pulmonary venous and left atrial pressures occur in the face of a hyperdynamic, hypercontractile left ventricle, these must necessarily be attributed to reduced compliance of the ventricle. In some patients, especially those with volume overload, frank pulmonary edema may be noted. <h3>Syncope and Dizziness.—</h3> Frank syncope and dizziness short of loss of consciousness (presyncope) are common. These are generally effort related although not predictably so. The frequency of the episodes is highly variable. The exact mechanism is obscure; however, it is probably related to reflex vasodilation and hypotension induced by stretching
Why the Brugada syndrome is not yet a disease: Syndromes, diseases, and genetic causality
Authors: R CORONEL, G BERECKI, T OPTHOF
Journal: Cardiovascular Research (2006)

A syndrome is a collection of symptoms and clinical signs that often occur in concert and suggest a common cause. Contrary to a disease, the cause–effect relations and pathophysiological mechanisms of syndromes are unknown or at least incompletely understood. The unveiling of pathophysiological mechanisms underlying a syndrome is one of the most rewarding accomplishments of biomedical research. Definitions of a syndrome are often disputed (see, for example, the definition of heart failure [1]), and its identifying signs may change.

In some syndromes an association exists with a genetic mutation that is present in only a minority of patients. This apparent discrepancy can indicate that 1) standard genetic screening methods fail to detect mutations; 2) other (genetic) factors are required; 3) the genetic mutation establishes a modulating factor that is not causative but occurs in a higher frequency in the syndrome population. We will expand on these issues below.

Failure to detect a mutation can result from methodological limitations. Koopmann et al. described a duplication of a large part of the DNA sequence in the gene encoding the pore-forming channel subunit for the rapidly activating delayed rectifier K+ current [2]. The mutation was present in a family with long QT syndrome (LQTS) [2]. Aberrancies of this type are not detected by conventional mutation screening techniques. Other causes for detection failure are the size of the gene, which practically prohibits mutation screening (e.g. RyR2 in arrhythmogenic right ventricular cardiomyopathy/dysplasia) [3], or incomplete knowledge of intronic and/or promoter regions.

Second, the inferential presence of other (genetic) factors …
Evolutionary Relationships Among “Jakobid” Flagellates as Indicated by Alpha- and Beta-Tubulin Phylogenies
Authors: Virginia P. Edgcomb, Andrew J. Roger, Alastair G. B. Simpson, David T. Kysela, Mitchell L. Sogin
Journal: Molecular Biology and Evolution (2001)

Jakobids are free-living, heterotrophic flagellates that might represent early-diverging mitochondrial protists. They share ultrastructural similarities with eukaryotes that occupy basal positions in molecular phylogenies, and their mitochondrial genome architecture is eubacterial-like, suggesting a close affinity with the ancestral alpha-proteobacterial symbiont that gave rise to mitochondria and hydrogenosomes. To elucidate relationships among jakobids and other early-diverging eukaryotic lineages, we characterized alpha- and beta-tubulin genes from four jakobids: Jakoba libera, Jakoba incarcerata, Reclinomonas americana (the "core jakobids"), and Malawimonas jakobiformis. These are the first reports of nuclear genes from these organisms. Phylogenies based on alpha-, beta-, and combined alpha- plus beta-tubulin protein data sets do not support the monophyly of the jakobids. While beta-tubulin and combined alpha- plus beta-tubulin phylogenies showed a sister group relationship between J. libera and R. americana, the two other jakobids, M. jakobiformis and J. incarcerata, had unclear affinities. In all three analyses, J. libera, R. americana, and M. jakobiformis emerged from within a well-supported large "plant-protist" clade that included plants, green algae, cryptophytes, stramenopiles, alveolates, Euglenozoa, Heterolobosea, and several other protist groups, but not animals, fungi, microsporidia, parabasalids, or diplomonads. A preferred branching order within the plant-protist clade was not identified, but there was a tendency for the J. libera-R. americana lineage to group with a clade made up of the heteroloboseid amoeboflagellates and euglenozoan protists. Jakoba incarcerata branched within the plant-protist clade in the beta- and the combined alpha- plus beta-tubulin phylogenies. In alpha- tubulin trees, J. incarcerata occupied an unresolved position, weakly grouping with the animal/fungal/microsporidian group or with amitochondriate parabasalid and diplomonad lineages, depending on the phylogenetic method employed. Tubulin gene phylogenies were in general agreement with mitochondrial gene phylogenies and ultrastructural data in indicating that the "jakobids" may be polyphyletic. Relationships with the putatively deep-branching amitochondriate diplomonads remain uncertain.