tbuckley/cabot-search huggingface dataset:
Pesticides and breast cancer risk: a review of DDT, DDE, and dieldrin.
Authors: S M Snedeker
Journal: Environmental Health Perspectives (2001)

Established risk factors for breast cancer explain breast cancer risk only partially. Hence, there has been interest in evaluating what role environmental chemicals, especially those with evidence of being hormonally active agents, play in breast cancer risk. Organochlorine pesticides have received the most attention because of their persistence in the environment, ability to concentrate up the food chain, continued detection in the food supply and breast milk, and ability to be stored in the adipose tissue of animals and humans. Although several early descriptive studies and a cohort study identified a strong positive association with breast cancer risk and adipose or blood levels of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) and/or its metabolite dichlorodiphenyldichloroethylene (DDE), most of the more recent case--control and nested case--control studies have not supported this association. In this review I discuss these findings and explore how exposure to different forms of DDT with varying estrogenicities may have affected the results of these studies. I also address how other factors influence the interpretation of the studies on DDT, DDE, and breast cancer risk. These include the effect of analytic methods, dietary factors, menopausal status, use of different types of control populations, lactation history, estrogen receptor status, ethnic/racial subgroups, breast tumor characteristics, and polymorphisms. I also discuss the emerging research on whether serum levels of the persistent organochlorine insecticide dieldrin are related to breast cancer risk in Danish and American women. Further research needs are also identified.
Increased expression of basement membrane components in human endothelial cells cultured in high glucose.
Authors: E Cagliero, M Maiello, D Boeri, S Roy, M Lorenzi
Journal: Journal of Clinical Investigation (1988)

Although the degree of hyperglycemia is a powerful and independent risk factor for diabetic microvascular disease, it has not been established if and how high glucose per se can induce the typical lesions of microangiopathy. We have investigated in human vascular endothelial cells the expression of messenger RNA (mRNA) for collagen type IV and fibronectin, the two glycoproteins characteristically increased in diabetic basement membranes. In 12 confluent primary cultures exposed for 11 +/- 1 d (mean +/- SD) to 30 mM glucose and exhibiting cell number and thymidine incorporation similar to control cultures, the levels of collagen IV and fibronectin mRNA were, respectively, 238 +/- 140 and 221 +/- 231 percent of control (P less than 0.01). The effects of high glucose were selective (the levels of collagen I and c-myc mRNA remained unchanged), independent of the proliferative activity of the cultures and of the plating substratum, and maintained throughout multiple passages. However, several days of exposure to high glucose were required before their appearance. These observations establish that high glucose is a perturbation sufficient to mimic the effects of diabetes on the regulation of basement membrane components and propose that modifications in gene expression may pertain to the chain of events leading to diabetic angiopathy.
Help Stamp Out Mandatory Continuing Education!
Authors: Glidden Neil Libby
Journal: JAMA (1975)

Mandatory continuing education programs for health professionals, as they are now administered, are predictable failures. Such programs may destroy the will to learn. Objective studies indicate that current continuing education programs do not influence the methods of practice of the health professional. Current programs are primarily pedagogical, reflecting the philosophies and techniques of child-youth education. Present methods of program evaluation are sorely inadequate. Adults may be coerced into attendance, but learning and subsequent application of knowledge may not be forced. Future continuing education programs should be problem-centered. The adult practitioner must become actively involved in the planning and execution of these programs. (<i>JAMA</i>233:797-799, 1975)
THE GROWING IMPORTANCE OF CHEMICAL STUDIES IN MEDICAL EDUCATION AND IN MEDICAL RESEARCH.Read in the Section of the Practice of Medicine and Physiology at the the Forty-second Annual Meeting of the American Medical Association, at Washington, D.C., May 5,1891.
Authors: VICTOR C. VAUGHAN
Journal: JAMA (1891)

<i>Gentlemen of the Section</i>:—The object which I have in view in the selection of this subject is to call your attention to the present importance of chemical studies in the elucidation of medical problems. Chemical theories and discoveries have frequently in the past been of service to medicine, but they offer much greater promises for the future. With the past services you are familiar, and I desire to point out some of the most important problems which are now being investigated or which only await careful study. <i>The Chemistry of the Animal Cell</i>.—With the form and size of the various cells of the animal body, both in health and in disease, we are fairly acquainted, but we must remember that these ultimate entities of life have also a physiological and a chemical history. Their function, as well as their form, is deserving of study. Upon what do they feed? What
Mortality from coronary heart disease and stroke in relation to degree of glycaemia: the Whitehall study.
Authors: J H Fuller, M J Shipley, G Rose, R J Jarrett, H Keen
Journal: BMJ (1983)

In the Whitehall study of 18 403 male civil servants aged 40-64 years the 10 year mortality rates from coronary heart disease and stroke showed a non-linear relation to two hour blood glucose values, with a significantly increased risk for glucose intolerant subjects with concentrations above the 95th centile point (5.4-11.0 mmol/l; 96-199 mg/100 ml) and for diabetics (blood glucose greater than or equal to 11.1 mmol/l; greater than or equal to 200 mg/100 ml). Multiple logistic analysis showed that between one half and three quarters of the relative risks for deaths from coronary heart disease and stroke were "unexplained" by between group differences in risk factors such as age, blood pressure, obesity, smoking, cholesterol concentration, and electrocardiographic abnormalities. Within the glucose intolerant and diabetic groups the risk factors most strongly related to subsequent death from coronary heart disease were age and blood pressure, with less consistent relations for smoking, cholesterol concentration, and obesity. This study confirms the importance of hypertension as a cardiovascular risk factor in groups with glucose intolerance and diabetes, and this may have important preventive implications.
Abstract A37: Anti-telomerase therapy provokes ALT and mitochondrial adaptive mechanism in cancer
Authors: Jian Hu, Sarah Hwang, Adam Boutin, Alan Wang, Lynda Chin, Marc Liesa, Orian Shiriha, Ronald DePinho
Journal: Clinical Cancer Research (2012)

Abstract Because telomerase is activated in 85–90% of all human cancers, inhibition of telomerase activity has been proposed as an anti-cancer strategy. However, telomere erosion resulting from telomerase inhibition can generate rampant genomic instability which may fuel adaptive mechanisms. Here, we determined the impact of telomerase activation and its subsequent extinction in T-cell lymphomas arising in Atm−/− mice engineered with an inducible telomerase reverse transcriptase-estrogen receptor (TERT-ER) knock-in allele. Endogenous telomerase reactivation in late generation TERTER/ER Atm−/− mice with telomere dysfunction enabled full malignant progression with accompanying alleviation of telomere checkpoint signaling and acquisition of copy number alterations targeting genes known to be important in human T-cell lymphomas/leukemia. Upon telomerase extinction, tumors eventually showed impaired growth due to reinstatement of telomere dysfunction-induced checkpoint signaling, yet subsequently resumed growth with accompanying alternative lengthening of telomeres (ALT) features. Transcriptomic analysis of ALT+ tumors showed altered transcriptional networks centering on mitochondrial biology and oxidative defense, and genomic analysis showed amplification of PGC-1β, a master regulator of mitochondrial biogenesis and oxidative defense. Relative to telomerase+ tumors, ALT+ tumors showed marked sensitivity to PGC-1β or SOD2 knockdown which compromised mitochondrial function and/or caused increased reactive oxygen species (ROS). Together, these studies provide in vivo genetic evidence that naturally arising tumors adapt to telomerase extinction by acquisition of both ALT and mitochondrial maintenance mechanisms, and show that targeting mitochondrial function and oxidative defense may enhance the effectiveness of anti-telomerase therapy in cancer.
Passing a nasogastric tube
Authors: P. Steele, S. Bennett, H. Duthie, M. Bullock
Journal: BMJ (1980)

A comparison of the combination of antacids and cimetidine with antacids alone (suggested by your leading article) has already been reported in the treatment of patients with established acute mucosal bleeding.8Haemostasis was achieved earlier with cimetidine but it is noteworthy that bleeding stopped within 48 hours in only 330N) of either treatment group.This fact-that established acute gastrointestinal haemorrhage may be difficult to control-and the disastrous results of surgical intervention in the few patients in whom medical treatment is unsuccessful contradict your final sanguine conclusion that "treatment may reasonably be reserved for those in whom bleeding occurs."It is true that prophylaxis should be reserved for high-risk patients-those with severe burns, head injuries or multiple injuries, and major operations, especially when these conditions are complicated by hypotension, jaundice, sepsis, renal failure, or severe respiratory insufficiency.Cimetidine infused slowly intravenously has fewer side effects than antacids, may be used even when the gut is not functioning, and is more convenient.For the most effective prophylaxis intragastric pH should be maintained above 4 and antacids may occasionally need to be added to cimetidine to achieve this.
Maternal blood test is more effective than standard screening for Down's syndrome, study shows
Authors: S. Mayor
Journal: BMJ (2015)

Taking a blood sample from women at 10 to 14 weeks of pregnancy and analysing cell-free fetal DNA for an extra chromosome is more effective than standard non-invasive screening tests in diagnosing Down’s syndrome, a large multi-centre study has found.

The prospective study, reported in the New England Journal of Medicine ,1 followed up pregnancy outcomes in nearly 16 000 women. The cell-free fetal DNA blood test correctly identified all 38 fetuses with Down’s syndrome, confirmed by examination of the newborn or by genetic analysis. This type of …
Abstract 3731: Beta2-Integrin Activation on T-cell Subsets is an Independent Prognostic Factor in Patients with Unstable Angina Pectoris
Authors: Mathias H Konstandin, Hülya Acksoy, Guido H Wabnitz, Christian Erbel, Evangelos Giannitsis, Yvonne Samstag, Hugo A Katus, Thomas J Dengler
Journal: Circulation (2008)

Cardiac troponins provide excellent risk stratification in unstable angina (UA), but no reliable markers are available in troponin-negative patients. Beta2-integrin mediated T cell recruitment plays a pivotal role in coronary atherosclerotic plaque rupture. The present study investigates beta2-integrin activation on T cell subsets as a risk marker in UA. Functional activation (affinity/avidity) of beta2-integrins on T cells was measured using a flow cytometry-based whole blood assay in 87 patients with UA. Beta2-integrin activation was significantly higher in patients with severe coronary artery disease (sC) and myocardial infarction (MI) compared to patients with no/minimal coronary atherosclerosis (no/mC), irrespective of troponin status. Adjusted for cardiovascular risk factors, medication, left ventricular function, MI at enrollment and high sensitivity C-reactive protein (hsCRP), beta2-integrin activation was independently associated with incidence of revascularization, hospitalization and all major cardiovascular events during 9 months of follow-up after index investigation. The highest prognostic value of beta2-integrin activation was seen in troponin-and hsCRP-negative patients. Quantitative assessment of T cell beta2-integrin activation allows to identify high risk patients with UA and sC without established MI; furthermore, it is associated with incidence of future cardiovascular events independent of conventional risk factors (troponin, hsCRP).
Chewing‐Gum Preservative Induced Toxidermic Vasculitis
Authors: D. A. Moneret‐Vautrin, G. Faure, M. C. Bene
Journal: Allergy (1986)

This paper reports the case of a young female patient who presented with a cutaneous urticarial disseminated eruption. Drug‐induced side effects were eliminated, and the only recent dietary change was the regular use of chewing‐gums containing chlorophylla (E140), menthol and BHT (butylhydroxytoluene). Immunohistological analysis of a cutaneous lesion revealed signs of vasculitis. Within 1 week after stopping chewing gum, the eruption subsided. Oral provocation tests at 4‐day intervals confirmed the responsibility of BHT by the reinduction of the cutaneous signs after a few hours.
Senile Dementia of the Binswanger Type
Authors: Gustavo C. Román
Journal: JAMA (1987)

Computed tomography and magnetic resonance imaging in the elderly have demonstrated the common occurrence of deep white-matter lesions in the aging brain. These radiologic lesions (leukoaraiosis) may represent an early marker of dementia. At autopsy, an ischemic periventricular leukoencephalopathy (Binswanger's disease) has been found in most cases. The clinical spectrum of Binswanger's disease appears to range from asymptomatic radiologic lesions to dementia with focal deficits, frontal signs, pseudobulbar palsy, gait difficulties, and urinary incontinence. The name senile dementia of the Binswanger type (SDBT) is proposed for this poorly recognized, vascular form of subcortical dementia. The SDBT probably results from cortical disconnection most likely caused by hypoperfusion. In contrast, multi-infarct dementia is correlated with multiple large and small strokes that cause a loss of over 50 to 100 mL of brain volume. The periventricular white matter is a watershed area irrigated by long, penetrating medullary arteries. Risk factors for SDBT are small-artery diseases, such as hypertension and amyloid angiopathy, impaired autoregulation of cerebral blood flow in the elderly, and periventricular hypoperfusion due to cardiac failure, arrhythmias, and hypotension. The SDBT may be a potentially preventable and treatable form of dementia.
MESENTERIC VASCULAR OCCLUSION WITH RECOVERY
Authors: Nathan Ralph
Journal: JAMA (1934)

<h3>To the Editor:—</h3> The article by J. R. Green and C. H. Allen on mesenteric vascular occlusion with recovery (The Journal, July 7) is concise, frank and instructive. The case report seems to me, however, after a close study, to be one of volvulus of the small intestine secondary possibly to adhesions from the previous appendectomy. The two conditions give the same pathologic end result—gangrene from occluded blood supply— but as their etiology is so vastly different, as is also their prognosis, I thought it would be no mere quibbling to call this to your attention. The authors themselves mention the importance of looking for an etiologic factor in a vascular mesenteric thrombosis, but in their pathologic description they have pointed out none. Furthermore, the age of the patient, 24, would make a primary mesenteric thrombosis extremely rare, whereas it is entirely compatible with the usual age incidence of volvulus.
Doctors Have Feelings Too
Authors: Stephen T. Sinatra
Journal: Annals of Internal Medicine (1994)

Letters15 August 1994Doctors Have Feelings TooStephen T. Sinatra, MDStephen T. Sinatra, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-4-199408150-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I was deeply touched by Dr. Kasman's essay processing the events of her shift. Her essay brought back so many unpleasant memories for me. In the past, I was able to bury the psychic pain that I had experienced on numerous occasions. When events like these happen, a physician's loneliness and despair are absolutely heartbreaking; for many, they cause retraction and denial that eventually cut them off from their true feelings. I appreciate her courage in stepping forward. Her article has helped me and probably others as well. She spoke directly to my heart. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 August 1994Volume 121, Issue 4Page: 309KeywordsEmotionsHeartMemory ePublished: 15 August 2000 Issue Published: 15 August 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
868. Effective Purification of Adeno-Associated Virus Vectors by Disposable Ion Exchange Membranes
Authors: Takashi Okada, Mutsuko Nonaka-Sarukawa, Takayuki Ito, Takashi Matsushita, Hiroaki Mizukami, Akihiro Kume, Keiya Ozawa
Journal: Molecular Therapy (2005)

Background: In vivo gene transduction with the adeno-associated virus (AAV)-based vectors require cumbersome procedures for the production of the vector stocks. Downstream purification steps with chromatography following intermediate purification through CsCl density centrifugation would meet end-product specifications for the clinical utility. However, resin-based packed-bed chromatography suffers from a number of limitations, such as pressure drop, slow pore diffusion, and large bed volume. Here we have adapted disposable strong anion- and cation-exchange membranes with a bed volume of 0.18 ml to purify recombinant viruses. In combination with our cell transduction protocol to use a large culture vessel with an active gassing, we now have at hand a simple and efficient system to produce AAV-based vector stocks in a high titer.
The association between aneurysm of the abdominal aorta and peptic ulceration
Authors: A. W. Jones, R. S. Kirk, K. Bloor
Journal: Gut (1970)

In a survey of 7,044 necropsies there were 99 cases of aneurysm of the abdominal aorta and 523 cases of peptic ulceration. The incidence of peptic ulceration in the general necropsy population was 7·2% whilst in cases with aneurysm it was 22·6%. There was a significant increase in duodenal ulceration in males with abdominal aortic aneurysms. The possible causes for this increased incidence are discussed.
7. Transduction of Quiescent Human Cells Using an SIVsmmPBj-Derived Lentiviral Vector
Authors: Matthias Schweizer, Nina Wolfrum, Michael Muehlebach, Julia Kaiser, Silke Schuele, Klaus Cichutek
Journal: Molecular Therapy (2005)

Although lentiviral vectors enable gene transfer into non-proliferating cells, particular quiescent human cells remain resistant to lentiviral transduction. Actually, several potential target cells of human gene therapy, particularly cells in the G0-state of the cell cycle such as freshly isolated primary monocytes, cannot be transduced using conventional HIV- or SIV-derived vectors.
Homologous recombination of wild-type JAK2, a novel early step in the development of myeloproliferative neoplasm
Authors: Mathias Vilaine, Damla Olcaydu, Ashot Harutyunyan, Jonathan Bergeman, Mourad Tiab, Jean-François Ramée, Jian-Min Chen, Robert Kralovics, Sylvie Hermouet
Journal: Blood (2011)
Salazopyrin EN in rheumatoid arthritis
Authors: R. A Asherson, M. Ridley
Journal: Annals of the Rheumatic Diseases (1987)

Salazopyrin EN in rheumatoid arthritisA meeting on the effects of Salazopyrin EN in rheumatoid arthritis was held at St Thomas's Hos- pital on 11 December 1986.Dr I Bjarnason (Northwick Park Hospital) pre- sented evidence to suggest that non-steroidal anti- inflammatory drugs (NSAIDs) increase intestinal permeability through a mechanism of reduced mucosal prostaglandin production.Salazopyrin
Presentation of benzo(a)pyrene to microsomal enzymes by asbestos fibers in the Salmonella/mammalian microsome mutagenicity test.
Authors: K Szyba, A Lange
Journal: Environmental Health Perspectives (1983)

The potential effect of asbestos fibers on mutagenicity of benzo(a)pyrene was investigated by using the Ames test. Asbestos fibers without a coating of benzo(a)pyrene or benzo(a)pyrene when not dissolved in DMSO lacked any mutagenic effect in the Salmonella/mammalian microsome mutagenicity test. However, when benzo(a)pyrene was adsorbed onto asbestos, significant numbers of mutated bacteria were observed. This shows that asbestos fibers can serve a carrier role presenting benzo(a)pyrene to the enzymatic microsomal system, thus enhancing mutagenicity of this compound.
Unusual case of mercury poisoning.
Authors: H. R. Johnson, O. Koumides
Journal: BMJ (1967)

Mycoplasmsa hominis in Abortion-Jones SMICiAL JOURNALa foetal tissue response.The organism may also be capable of infecting a living foctus, and there is evidence of this in Case 2. Infection with M. horninis probably more commonly extends only as far as the maternal genital tract, contributing to pyrexia associated with delivery.Of seven patients who aborted and who had M. hominis in the vagina, three developed a rise in antibody titre (Table II).These patients had a pyrexial illness, and presumably an infection of the genital tract due at least in part to M. hominis.The appearance of growth-inhibiting antibody, which does not persist for long in the circulation, is consistent with recent infection (Jones and Sequeira, 1966).It is of interest to note that when mycoplasmas are introduced into the bovine uterus, endometritis and endosalpingitis are produced (Hartman et al., 1964).Mycoplasmas, as oppor- tunists, may be able to produce similar infections in humans when conditions in the genital tract are favourable. SummaryThe isolation of Mycoplasma hominis from aborted foetuses, accompanied by significant levels of maternal antibody, is described.Rises in antibody titre to M. hominis were also detected in some patients who had this organism in the vagina at the time of abortion.These findings suggest that infection of the genital tract occurs in association with abortion, and sometimes this infection may involve the foetus.The possibility that such infection may sometimes cause abortion is discussed.I am indebted to Dr. James Davson for the histological reports, and to Dr.
Reiter Disease in Siblings
Authors: Stephen G. Gelfand
Journal: JAMA (1977)

<h3>To the Editor.—</h3> With the high incidence of HLA-B27 positivity, which has recently been recognized in Reiter disease,<sup>1</sup>it is unusual that the disease is not more prevalent in close family members. There have been very few reports of Reiter disease in more than one member of a family.<sup>2,3</sup>I wish to report two brothers with classic Reiter disease who were also found to be positive for the HLA-B27 histocompatibility antigen. <h3>Report of Cases.—Case 1.—</h3> In a 19-year-old white man, urethritis, conjunctivitis, acute arthritis of the right ankle and the left knee, balanitis circinata, and painless shallow ulcerations of the mucous membranes of the mouth developed. Cultures of urethral and synovial fluid were negative. The sedimentation rate was 46 mm/hr and rheumatoid arthritis latex test was nonreactive. X-ray films of the knees, ankles, lumbosacral spine, and sacroiliac joints were normal. The patient failed to respond to