tbuckley/cabot-search huggingface dataset:
P1-09-07: Contribution of TP53 p.R337H Mutation to Breast Cancer Incidence in Brazil.
Authors: J Giacomazzi, CA Toledo de Bueno Osorio, P Koehler-Santos, MS Graudenz, G Marthel-Planche, MIW Achatz, FA Soares, JR Goldim, M Caleffi, P Hainaut, SA Camey, P Ashton-Prolla
Journal: Cancer Research (2011)

Abstract Background: The exact contribution of TP53 germline mutations, associated with Li Fraumeni Syndrome — LFS, to the overall burden of cancer is still only partially known. Studies in Southern and Southeastern Brazil have shown that a particular mutant, TP53 p.R337H, has incomplete penetrance and may be present in a significant number of subjects (estimated frequency at the populational level of 1:300 individuals). In an exploratory approach, the aim of this study is to assess the prevalence of the TP53 p.R337H mutation in women with breast cancer diagnosed before 46 and after 55 years of age, unselected for family history of cancer and resident in Southern and Southeastern Brazil. Methods: Formalin-fixed paraffin-embedded (FFPE) non-tumoral tissue of 521 women diagnosed with breast cancer between 2000 and 2010 in two pathology laboratories were obtained retrospectively and consecutively, and analyzed after anonimization. Genomic DNA was isolated with the QIAamp DNA Tissue Kit and genotyping performed by allelic discrimination using a TaqMan assay. Confirmation of all mutation-positive and a sample of mutation-negative cases was done by TP53 exon 10 sequencing. Results: Analysis of the first 299 cases identified the TP53 p.R337H mutation in the germline of 15 (5,0%) cases: 13/142 (9,2%) before 46 years and 2/157 (1,3%) diagnosed after 55 years. The p53 expression pattern assessed by immunohistochemistry in the breast tumors was not different between p.R337H mutation carriers and non-carriers. Conclusion: Preliminary analysis in a sample of women with breast cancer in Southern Brazil indicates that the germline TP53 p.R337H founder mutation is present in a high proportion of cases, especially those diagnosed at a young age. Germline TP53 mutations are considered rare, occurring in about 1:5000 individuals of the general population. The occurrence of this founder mutation at such a high frequency in a particular geographic region has important implications for disease management and cancer risk counseling for these patients and families. This mutation likely contributes to a significant proportion of the health burden associated with breast cancer in Southern Brazil. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-09-07.
Abstract 3415: Diverse roles for Snail transcription factor in epithelial-mesenchymal transition (EMT) and neuroendocrine differentiation (NED) in human prostate cancer
Authors: Danielle McKeithen, Tisheeka Graham, Colm Morrissey, Xiaotun Zhang, Leland W K Chung, Valerie Odero-Marah
Journal: Cancer Research (2011)

Abstract Snail transcription factor induces epithelial-mesenchymal transition (EMT) via decreased cell adhesion-associated molecules like E-cadherin, and increased mesenchymal markers like vimentin. We previously established Snail-mediated EMT model utilizing androgen-dependent LNCaP cells. These cells express increased vimentin protein and relocalization of E-cadherin from the cell membrane to the cytosol. Interestingly, Snail transfection in LNCaP cells resulted in cells acquiring a neuroendocrine-like morphology with long neurite-like processes. We tested for expression of neuroendocrine markers neuron specific enolase (NSE) and chromogranin A (CgA) by Western blot analysis, and performed proliferation assays to test for paracrine cell proliferation. LNCaP cells transfected with Snail displayed increase in the neuroendocrine markers, NSE and CgA as well as translocation of androgen receptor to the nucleus. We found that LNCaP C-33 cells that have been previously published as a Neuroendocrine Differentiation (NED) model exhibited increased expression levels of Snail protein as compared to LNCaP parental cells. Functionally, conditioned medium from the LNCaP-Snail transfected cells increased proliferation of parental LNCaP and PC-3 cells. In addition, NED in LNCaP-C33 cells or that induced in parental LNCaP cells by serum starvation could be inhibited by knockdown of Snail with siRNA. Knockdown of NSE and CgA with siRNA abrogated Snail induced paracrine cell proliferation in parental LNCaP and PC3 cells. Immunohistochemical staining of prostate cancer patient tissue revealed increased expression of Snail with prostate cancer progression and bone metastasis. Higher Snail staining was observed in primary prostate cancer tissue containing a neuroendocrine component (identified by CgA staining) as compared to primary cancer with no neuroendocrine differentiation. However, in metastatic tissue, Snail was highly expressed in both neuroendocrine and non-neuroendocrine cancer tissue. Overall our data provide evidence that Snail transcription factor may promote tumor aggressiveness in the prostate cancer cells through multiple processes; induction of EMT may be required to promote migration, while NED may promote tumor proliferation by a paracrine mechanism. Therefore, therapeutic targeting of Snail may prove beneficial in not only abrogating EMT but also NED. 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 3415. doi:10.1158/1538-7445.AM2011-3415
Evaluation of ketanserin in the prevention of restenosis after percutaneous transluminal coronary angioplasty. A multicenter randomized double-blind placebo-controlled trial.
Authors: P W Serruys, W Klein, J P Tijssen, W Rutsch, G R Heyndrickx, H Emanuelsson, S G Ball, O Decoster, E Schroeder, H Liberman
Journal: Circulation (1993)

BACKGROUND Ketanserin is a serotonin S2-receptor antagonist that inhibits the platelet activation and vasoconstriction induced by serotonin and also inhibits the mitogenic effect of serotonin on vascular smooth muscle cells. METHODS AND RESULTS We conducted a randomized, double blind, placebo-controlled trial to assess the effect of ketanserin in restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received either ketanserin (loading dose, 40 mg 1 hour before PTCA; maintenance dose, 40 mg bid for 6 months) or matched placebo. In addition, all patients received aspirin for 6 months. Coronary angiograms before PTCA, after PTCA, and at 6 months were quantitatively analyzed. Six hundred fifty-eight patients were entered into the intention-to-treat analysis. The primary clinical end point of the study was the occurrence between PTCA and 6 months of any one of the following: cardiac death, myocardial infarction, the need for repeat angioplasty, or bypass surgery. It also included the need for revascularization actuated by findings at 6-month follow-up angiography. The primary clinical end point was reached by 92 (28%) patients in the ketanserin group and 104 (32%) in the placebo group (RR, 0.89; 95% CI, 0.70, 1.13; P = .38). Quantitative angiography after PTCA and at follow-up was available in 592 patients (ketanserin, 287; control, 305). The mean difference in minimal lumen diameter between post-PTCA and follow-up angiogram (primary angiographic end point) was 0.27 +/- 0.49 mm in the ketanserin group and 0.24 +/- 0.52 mm in the control group (difference, 0.03 mm; 95% CI, -0.05, 0.11; P = .50). CONCLUSIONS Ketanserin at the dose administered in this trial failed to reduce the loss in minimal lumen diameter during follow-up after PTCA and did not significantly improve the clinical outcome.
American Physicians in Other Nations
Authors: Robert J. Snowe
Journal: JAMA (1979)

<h3>To the Editor.—</h3> Lest the medical profession (and other health workers) be seduced into a tranquil venture of international service, I would like to bring some reality to the correspondence of Charles Failmezger, MD, "On Volunteer Physicians in the Developing Nations" (241:132, 1979). He encourages short-term rotations (which in his case become even more abbreviated, with an average of less than two months spent in each country) while at the same time advising extensive prior preparations that he does not seem to include in his length of duty. I have been working for nearly 18 months in the same urban region of northeast Brazil, and even with on-site language training and experiences concerning local customs, I am just now at the periphery of understanding the people and environs here. The language problems should not be minimized. Whereas one may learn common expressions that help basic survival, involvement at a university
Reduction of <i>Staphylococcus aureus</i> in atopic skin lesions with acid electrolytic water ‐ a new therapeutic strategy for atopic dermatitis
Authors: M. Sasai‐Takedatsu, T. Kojima, A. Yamamoto, K. Hattori, S. Yoshijima, S. Taniuchi, S. Namura, H. Akamatsu, T. Horio, Y. Kobayashi
Journal: Allergy (1997)

The subjects studied were 22 pediatric patients newly diagnosed with atopic dermatitis (AD); 11 were treated with acid electrolytic water (AEW), which has a strong bactericidal activity (AEW group), and the other 11 with tap water (placebo group). AEW or tap water, 1 ml/cm 2 (body surface area), was sprayed on their skin lesions with a spray gun each twice a day for a week. There were no significant differences between the two groups in regard to sex, age, serum IgE, peripheral eosinophil counts, grading scores of AD, and duration of AD. The study was designed as a randomized, placebo‐controlled, double‐blind clinical trial. Colony counts of Staphylococcus aureus on skin lesions in the AEW group, both 3 min after spraying ( P &lt; 0.05) and after 1 week of skin treatment ( P &lt; 0.01), were significantly decreased as compared with colony counts before treatment, while there was no significant difference in the placebo group before and after treatment. Grading scores of AD also decreased in the AEW group ( P &lt;0.01), but not in the placebo group. Both the subjects' guardians' evaluation and a referee physician's evaluation of treatment effect were significantly higher in the AEW group than in the placebo group ( P &lt; 0.01). AEW may be potentially effective in preventing a staphylococcal chronic inflammation in AD because of its strong bactericidal activity.
Medicines and elderly people: a general practice survey.
Authors: R Law, C Chalmers
Journal: BMJ (1976)

All 151 patients of 75 years and over in one practice were visited at home to survey their health and how they managed their medicines. Altogehter 87% were on regular treatment, 34% taking three or four different drugs each day. Most were responsible for their own drugs and managed them well, but many left their drugs in exposed places and were uncertain about how to dispose of unwanted medicines. Overall they were prescribed about three times the number of drugs prescribed for the general population, and women took twice as many drugs regularly as men. Although many drugs were obtained directly from a pharmacist, his advice was rarely sought. Most were labelled, but more explicit instructions about indications for taking the drug would have been helpful, and information about hoarded drugs would have been enhanced by dispensing and expiry dates. Treatment was facilitated when patients brought their drugs to the consultation and careful records were made of repeat prescriptions. As so many patients take three or more different types of drugs each day a container in which a day's supply could be laid out would be useful.
Signaling Pathways and c-<i>fos</i>Transcriptional Response — Links to Inherited Diseases
Authors: Paolo Sassone-Corsi
Journal: New England Journal of Medicine (1995)

Intracellular signal-transduction pathways have central roles in processes such as growth, development, cellular differentiation, and neurotransmission. Alterations in the levels of various substances involved in signal-transduction pathways have profound effects on cellular functions, and many inherited diseases are caused by mutations that affect key components of signaling pathways.1 There are two major signal-transduction pathways, one using cyclic AMP (cAMP) and the other diacylglycerol. Each pathway is characterized by its specific protein kinase, protein kinase A and protein kinase C, respectively. The fine modulation of gene expression is achieved by the complex interactions between membrane receptors and the cytoplasmic constituents of . . .
Transatlantic divide in publication of content relevant to developing countries
Authors: Asad J Raja, Peter A Singer
Journal: BMJ (2004)

argue that democracy may be the best protection against the harmful effects of globalisation.This view is supported by, for example, the tobacco industry's exploitation of the situation in countries with widespread corruption and a lack of functioning democratic systems, 11 contrasted with the industry's growing record of failure when faced by democratic governments.So does the experience of the former Soviet bloc support the hypothesis that democracy is good for health?Although there have been winners and losers among populations everywhere, regardless of the progress towards democracy that their governments have made, 12 it seems that democracy is good for health.
Uncomplicated Myocardial Infarction
Authors: Nanette K. Wenger, Herman K. Hellerstein, Henry Blackburn, Samuel J. Castranova
Journal: JAMA (1973)

A questionnaire on management of uncomplicated acute myocardial infarction patients was mailed to 1,200 general practitioners, 1,200 internists, and 1,200 cardiologists. The 69% who responded managed approximately 70,000 patients with acute myocardial infarction in 1970. General practitioners saw three-fifths of these patients. Of acute myocardial infarction patients, 45% were considered to have uncomplicated infarction. Most responses were similar for general practitioners, internists, and cardiologists, who routinely hospitalized 95% of uncomplicated acute myocardial infarction patients for a 21-day hospital stay. Of physicians, 97% restricted smoking, 77% restricted calories, and 71% used anticoagulants. Of patients under age 65, 87% returned to work two to four months after uncomplicated myocardial infarction.
MS patients are in sustained remission after stem cell transplantation, small study finds
Authors: S. Mayor
Journal: BMJ (2014)

Most patients with relapsing remitting multiple sclerosis (MS) who are taking part in a small study of high dose immunosuppressive therapy followed by transplantation of their own haematopoietic stem cells have experienced sustained remission for three years, a study has found.

The ongoing study includes 25 MS patients who had experienced relapses with loss of neurologic function while on disease modifying therapies during the 18 months before recruitment. They …
The Lilly Lecture: Alveolar Ventilation.
Authors: W. Melville Arnott
Journal: Annals of Internal Medicine (1968)

s1 May 1968The Lilly Lecture: Alveolar Ventilation.W. Melville Arnott, T.D., M.D., F.R.C.P., F.R.C.P.(Edin.), F.R.C.P.(C), F.C.W. Melville Arnott, T.D., M.D., F.R.C.P., F.R.C.P.(Edin.), F.R.C.P.(C), F.C.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1139_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAdequate pulmonary ventilation requires that each alveolus should receive at each inspiration sufficient air to maintain an oxygen tension above, and a carbon dioxide tension below, that of pulmonary capillary blood. Evidence was presented that the design of the air passages in respect to dimensions, ratios of diameters of parent to daughter branches, and angles of branching approximate closely the theoretical optimum for mass movement of gas down to the level of terminal bronchioles (0.6 mm in diameter). Distal to this point the geometry of the passages supports the hypothesis that gas movement is by molecular diffusion.The single-breath nitrogen... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Path, Birmingham, PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1139-1139KeywordsAlveoliBloodBronchiolesCapillariesCarbon dioxideOxygen Issue Published: 1 May 1968 PDF DownloadLoading ...
Transduction characteristics of adeno-associated virus vectors expressing cap serotypes 7, 8, 9, and Rh10 in the mouse brain
Authors: Cassia N. Cearley, John H. Wolfe
Journal: Molecular Therapy (2006)

Recombinant adeno-associated viral (AAV) vectors can transduce cells of the CNS, resulting in long-term expression. AAV vector transduction varies depending on the serotype used and the region of the brain injected. AAV serotypes 7, 8, 9, and Rh10 have recently become available, but the transduction capabilities of these serotypes within the CNS have not been determined. We show that AAV 7, 8, 9, and Rh10 vectors expressing cDNA for a lysosomal enzyme transduce neurons, but not astrocytes or oligodendrocytes, in the cortex, striatum, hippocampus, and thalamus. Although all of the vectors contained the same genome, there were markedly different transduction patterns that could be due only to the differences in capsid proteins. The AAV 9 vector was found to undergo vector genome transport to distal neuronal cell bodies via known axonal pathways. This facilitated the distribution of enzyme, resulting in correction of lysosomal storage lesions in regions of a diseased brain that would not be corrected if the genome were not transported.
A History of Genetics
Authors: James E. Bowman
Journal: JAMA (1966)

There are few men today who have a claim equal to Sturtevant's for writing a history of genetics. The author has contributed extensively to the field since his undergraduate days at Columbia. His first paper, "The Linear Arrangement of Sex-Linked Factors in Drosophila, as Shown by Their Mode of Association" (<i>J Exper Zool</i><b>14</b>:43-59, 1913), was formulated one night (to the neglect of his homework). This investigation produced the first chromosome map, in the order and approximate spacing that these genes still appear on standard maps. This history has life in almost every page, for Sturtevant personally knew, and knows, most of the men active in 20th century genetics, This story begins with Hippocrates, reviews the events leading to Mendel's epochal paper, and develops the ideas and analyzes the men in genetics until about 1950. The author states that the history of science is primarily a history of ideas
Give-Away Medical Journals
Authors: Arthur F. Greenwald
Journal: JAMA (1971)

To the Editor.—  Having long urged our profession to police itself, I wish you would editorialize for reform among the give-away  journals, or else publish this letter. The plethora of free periodicals which inundate the physician are of questionable value. Most of the articles repeat what has already been published in standard textbooks or ethical journals such as yours. The special ills that I see in these journals, along with my proposals for reform, are as follows:   Diversion of scarce  talent from practice, teaching, or research. Even if the articles are written by a medical journalist, the physicians consulted are giving up valuable time for a fee or honorarium. If the physicians are really transmitting valuable experience to their colleagues in the great sharing tradition of our profession, let them donate their honorarium to the  college or hospital of their choice.  Increased advertising expense of
Elevated Skeletal Muscle Creatine Kinase MB Isoenzyme Levels in Marathon Runners
Authors: Arthur J. Siegel
Journal: JAMA (1983)

Mean serum creatine kinase MB isoenzyme (CK-MB) activity in 108 trained marathon runners after competition was 98 ±66 (SD) units/L measured by a quantitative electrophoretic technique (normal, &lt;5 units/L), or 7.9% of total CK activity. These levels in asymptomatic runners were comparable with peak serum values reported in patients during acute myocardial infarction. Elevated serum levels of CK-MB in runners can arise from skeletal muscle through exertional rhabdomyolysis, from silent injury to myocardium, or from a combined tissue source. To investigate this directly, we analyzed skeletal muscle obtained by needle biopsy for CK isoenzymes from 25 trained male marathon runners and ten sedentary male subjects. The MB isoenzyme accounted for 8.9% ± 1.3% (SD) of total CK activity per gram of total protein in the skeletal muscle of runners and 3.3% ± 0.7% (SD) in control tissue, which was significant. Total CK activity was not statistically different between the two groups. Similar relative concentrations of CK-MB in skeletal muscle (8.9%) and serum after competition (7.9%) strongly suggest that elevated serum CK-MB activity in asymptomatic runners arises from a noncardiac or skeletal muscle source. (<i>JAMA</i>1983;250:2835-2837)
Restricting Interactions With Industry to Promote Evidence-Based Prescribing
Authors: Joseph S. Ross
Journal: JAMA Internal Medicine (2014)

Over the past 15 years, interactions between physicians and the pharmaceutical and medical device industries have receivedevergreater scrutiny.While thebenefits of researchcollaboration have always been recognized, there are growingconcerns that financial relationships are threatening the integrity of research, professional education, patient care, and the public’s trust inmedicine. The Association of American Medical Colleges and the Institute of Medicine released statements calling for strengthening the policies governing these interactions, particularly amongacademicmedical centers andprofessional societies, and requiring transparencyand disclosure of financial relationships. In 2007, the American Medical Student Association, in collaboration with the Pew Charitable Trusts, released its “PharmFree Scorecard” that gradedmedical schools on thepresence or absence of a policy regulating interactionsbetween their students and faculty and the pharmaceutical and medical device industries. Since that time, medical school policies have become increasingly common and more restrictive. However, little evidence supported their widespread adoption until recently, when 2 studies determined that medical students and postgraduate trainees from medical schools with less restrictive policies were more likely to prescribe high-cost, low-value branded formulat ions of psychoact ive medications.1,2 The findings reported by Austad et al3 provide some measure of explanation, despite being derived from hypothetical case scenarios, noting that students and trainees who reported more extensive interactions with pharmaceutical sales representatives were less likely to recommend evidence-based medicines and were more likely to favor use of branded, as opposed to generic, medication formulations. Medical school and postgraduate training are times of rapid, intensive clinical learning, when professional identities are formed, and the “habits” of clinical practice are begun.There isnoeducational reasonfor industry to interactwith students and residentsduring these formativeperiods, andexposure to marketing promotion and sales representatives should be limited. Thus,medical schools and teaching hospitals shouldcontinue to takesteps towardadoptingpolicies that restrict interactions with industry. It is becoming increasingly clear that restricting these interactions during medical school andpostgraduate training leads tohigher-quality,more evidence-based prescribing amongphysicians,which is good for the profession, for patient care, and for the public’s trust in medicine.