tbuckley/cabot-search huggingface dataset:
Differential Enhancement of Breast Cancer Cell Motility and Metastasis by Helical and Kinase Domain Mutations of Class IA Phosphoinositide 3-Kinase
Authors: Huan Pang, Rory Flinn, Antonia Patsialou, Jeffrey Wyckoff, Evanthia T. Roussos, Haiyan Wu, Maria Pozzuto, Sumanta Goswami, John S. Condeelis, Anne R. Bresnick, Jeffrey E. Segall, Jonathan M. Backer
Journal: Cancer Research (2009)

Class IA (p85/p110) phosphoinositide 3-kinases play a major role in regulating cell growth, survival, and motility. Activating mutations in the p110alpha isoform of the class IA catalytic subunit (PIK3CA) are commonly found in human cancers. These mutations lead to increased proliferation and transformation in cultured cells, but their effects on cell motility and tumor metastasis have not been evaluated. We used lentiviral-mediated gene transfer and knockdown to produce stable MDA-MB-231 cells in which the endogenous human p110alpha is replaced with either wild-type bovine p110alpha or the two most common activating p110alpha mutants, the helical domain mutant E545K and the kinase domain mutant H1047R. The phosphoinositide 3-kinase/Akt pathway was hyperactivated in cells expressing physiologic levels of helical or kinase domain mutants. Cells expressing either mutant showed increased motility in vitro, but only cells expressing the helical domain mutant showed increased directionality in a chemotaxis assay. In severe combined immunodeficient mice, xenograft tumors expressing either mutant showed increased rates of tumor growth compared with tumors expressing wild-type p110alpha. However, tumors expressing the p110alpha helical domain mutant showed a marked increase in both tumor cell intravasation into the blood and tumor cell extravasation into the lung after tail vein injection compared with tumors expressing wild-type p110alpha or the kinase domain mutant. Our observations suggest that, when compared with kinase domain mutations in a genetically identical background, expression of helical domain mutants of p110alpha produce a more severe metastatic phenotype.
Alcoholism—A Problem in Perspective
Authors: Robert G. Niven
Journal: JAMA (1984)

It is gratifying that the American Medical Association is dedicating this issue ofThe Journalto focus on the illness of alcoholism and related problems, since these affect millions of Americans. This is another in a long list of AMA contributions to our understanding of alcohol-related health problems and their solutions. In November 1956, the AMA House of Delegates issued a statement recognizing that alcoholism is an illness that comes within the scope of medical practice. The AMA has prepared several editions and revisions of its<i>Manual on Alcoholism</i>, first published in 1968, and has likewise facilitated the awareness and education of physicians concerning addictive disorders with its<i>Manual on Drug Abuse</i>. The Association has sponsored a series of conferences on the impaired physician to raise the consciousness of the clinical community to its own susceptibiliity and to stress the very important fact that alcoholism, drug abuse, and mental illness
Impotence Is Not Always Psychogenic-Reply
Authors: Richard F. Spark
Journal: JAMA (1980)

In Reply.—  The purpose of our article was to alert physicians to the frequency with which disorders of the hypothalamic-pituitary-gonadal axis occur in patients whose initial complaint is impotence.  Parenthetically, the word impotence, defined in Merriam-Webster's as  physical or psychological abnormal state of a male characterized by inability to copulate, is perfectly clear, understood by all, and preferable to the currently trendy bland euphemism erection problems.  Dr Kavich-Sharon's contention that we need more information to fully understand the biochemistry of sexual function and dysfunction is, of course, correct. We neither recommend nor condone the use of a therapeutic trial of testosterone therapy in impotent patients who have normal serum testosterone values. The treatment is reserved for those who, for one reason or another, are unable to produce adequate amounts of testosterone spontaneously.  The reference to our patients as last resort is unwarranted. We did have some concern that the
Long-term study of indomethacin and alclofenac in treatment of rheumatoid arthritis.
Authors: M Aylward, R J Parker, F Holly, J Maddock, D B Davies
Journal: BMJ (1975)

Indomethacin and alclofenac were compared for 13 months under double-blind conditions in 109 patients with active, classical, or definite rheumatoid arthritis at a relatively early stage of the disease. Both indomethacin and alclofenac were clearly effective: most patients either improved or remained as well controlled as on entry. Alclofenac proved the more effective drug, however, producing a significantly greater reduction in morning stiffness, articular index, and erythrocyte sedimentation rate, and only in the alclofenac-treated group did functional capacity improve and latex-agglutination titres diminish. Comprehensive laborabory tests showed no significant deviation from normal which could have been attributed to either drug.
While awaiting the next pandemic of influenza
Authors: R G Webster
Journal: BMJ (1994)

gramme is to enhance computerisation of the data analysis and to examine the feasibility of a European database.The experiences of New York and San Francisco show that the threats posed by infectious diseases can never be forgotten and that we abandon surveillance and control measures at our peril.At a time when finances in the public sector are under fierce scrutiny it is important not to make false economies.The treatment and control of tuberculosis remain among the most cost effective health strategies available today.
Medical Education in Saudi Arabia
Authors: GEORGE T. HARRELL
Journal: Annals of Internal Medicine (1976)

Abroad1 November 1976Medical Education in Saudi ArabiaGEORGE T. HARRELL, M.D., F.A.C.P.GEORGE T. HARRELL, M.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-85-5-677 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSaudi Arabia is rapidly changing as the wealth derived from its oil is used to develop a modern state. It is largely mountain plateau and desert with little rain except along coastal strips. Most of the country is plagued with dust storms. Oil is found largely on the east coast. Jeddah on the west coast is the traditional seaport and point of entry for the more than a million pilgrims each year on the 1-month hajj to Mecca. Though foreign embassies remain in Jeddah, the capital is Riyadh in the central region.Most of the country lacks adequate water supplies.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByParental responses to consanguinity and genetic disease in Saudi Arabia 1 November 1976Volume 85, Issue 5Page: 677-678KeywordsDustMedical educationOilsStorms Issue Published: 1 November 1976 PDF DownloadLoading ...
Polymyalgia rheumatica: an arthroscopic study of the shoulder joint.
Authors: W A Douglas, B A Martin, J H Morris
Journal: Annals of the Rheumatic Diseases (1983)

A careful selection of 19 patients fitting the classical description of polymyalgia rheumatica have been examined by arthroscopy and thoroughly screened and followed up to exclude rheumatoid arthritis and other disease processes. Synovitis of the shoulder joint has been observed through the arthroscope in 17 and synovitis of varying degrees noted histologically, 4 of whom were studied by immunofluorescence. Five patients had radioactive joint scans.
THE DANGERS OF THE DOMESTIC USE OF ILLUMINATING GAS AND THE MEANS OF AVOIDING THEM.
Authors: HENRY LEFFMANN
Journal: JAMA (1905)

The employment of illuminating gas manufactured from coal is about a century old. The original method, exclusively in vogue for many years, was by destructive distillation of soft coal. The operation is simple: The coal is heated strongly in a closed vessel, and the gases produced are cooled, purified and distributed. The impurities of the crude gas are numerous, but of only few types. Ammonium compounds and sulphur compounds are the most objectionable, and much attention has been given to devising methods for their removal, which in well-operated works is satisfactorily accomplished. The purified gas as conducted into the storage tanks consists principally of hydrogen and hydrocarbons, among the latter being methane, ethene and benzene. Some carbon monoxid is also present. Laboratory experiment and clinical experience have shown that gas made in this manner has not very high toxic qualities. The hydrocarbons and hydrogen are rather negative than positive. They
The "five-sites" rule and the evolution of red and green color vision in mammals
Authors: S. Yokoyama, F. B. Radlwimmer
Journal: Molecular Biology and Evolution (1998)

Amino acid changes S180A (S-->A at site 180), H197Y, Y277F, T285A, and A308S are known to shift the maximum wavelength of absorption (lambda max) of red and green visual pigments toward blue, essentially in an additive fashion. To test the generality of this "five-sites" rule, we have determined the partial amino acid sequences of red and green pigments from five mammalian orders (Artiodactyla, Carnivora, Lagomorpha, Perissodactyla, and Rodentia). The result suggests that cat (Felis catus), dog (Canis familiaris), and goat (Capra hircus) pigments all with AHYTA at the five critical sites have lambda max values of approximately 530 nm, whereas rat (Rattus norvegicus) pigment with AYYTS has a lambda max value of approximately 510 nm, which is accurately predicted by the five-sites rule. However, the observed lambda max values of the orthologous pigments of European rabbit (Oryctolagus cuniculus), white-tailed deer (Odocoileus virginianus), gray squirrel (Sciurus carolinensis), and guinea pig (Cavia procellus) are consistently more than 10 nm higher than the predicted values, suggesting the existence of additional molecular mechanisms for red and green color vision. The inferred amino acid sequences of ancestral organisms suggest that the extant mammalian red and green pigments appear to have evolved from a single ancestral green-red hybrid pigment by directed amino acid substitutions.
Intrinsic washout rates of thallium-201 in normal and ischemic myocardium after dipyridamole-induced vasodilation.
Authors: G A Beller, H H Holzgrefe, D D Watson
Journal: Circulation (1985)

Infusion of dipyridamole has been suggested as an alternative to exercise stress for myocardial perfusion imaging for detection of ischemia, but the mechanism and significance of thallium-201 (201Tl) redistribution after administration of dipyridamole are uncertain. If disparate intrinsic cellular efflux rates of 201Tl from normal and relatively underperfused myocardium in response to dipyridamole-induced vasodilation were observed, this could explain delayed 201Tl redistribution. We investigated eht effect of an intravenous infusion of 0.15 mg/kg dipyridamole on the intrinsic myocardial washout rate of 201Tl as measured with a gamma-detector probe after intracoronary injection (50 muCi) of the radionuclide in open-chested anesthetized dogs. In six normal dogs the t 1/2 for intrinsic 201Tl washout from the myocardium was 89 +/- 11 min (SE) at control conditions and became more rapid at 59 +/- 10 min (p = .0001) after dipyridamole. This corresponded to a significant increase in microsphere-determined epicardial (0.95 +/- 0.11 to 2.23 +/- 0.46 ml/min/g; p = .01) and endocardial (0.86 +/- 0.10 to 1.53 +/- 0.27; p = .029) flows. In 12 dogs with a critical coronary stenosis, the 201Tl intrinsic washout rate slowed from 70 +/- 5 to 104 +/- 6 min (p = .0001) after production of the stenosis and slowed even further to 169 +/- 21 min (p = .003) after dipyridamole.(ABSTRACT TRUNCATED AT 250 WORDS)
Investigating the Contribution of Common Genetic Variants to the Risk and Pathogenesis of ADHD
Authors: Evangelia Stergiakouli, Marian Hamshere, Peter Holmans, Kate Langley, Irina Zaharieva, Ziarah Hawi, Lindsey Kent, Michael Gill, Nigel Williams, Michael J. Owen, Michael O'Donovan, Anita Thapar
Journal: American Journal of Psychiatry (2011)

A major motivation for seeking disease-associated genetic variation is to identify novel risk processes. Although rare copy number variants (CNVs) appear to contribute to attention deficit hyperactivity disorder (ADHD), common risk variants (single-nucleotide polymorphisms [SNPs]) have not yet been detected using genome-wide association studies (GWAS). This raises the concern as to whether future larger-scale, adequately powered GWAS will be worthwhile. The authors undertook a GWAS of ADHD and examined whether associated SNPs, including those below conventional levels of significance, influenced the same biological pathways affected by CNVs.The authors analyzed genome-wide SNP frequencies in 727 children with ADHD and 5,081 comparison subjects. The gene sets that were enriched in a pathway analysis of the GWAS data (the top 5% of SNPs) were tested for an excess of genes spanned by large, rare CNVs in the children with ADHD.No SNP achieved genome-wide significance levels. As previously reported in a subsample of the present study, large, rare CNVs were significantly more common in case subjects than comparison subjects. Thirteen biological pathways enriched for SNP association significantly overlapped with those enriched for rare CNVs. These included cholesterol-related and CNS development pathways. At the level of individual genes, CHRNA7, which encodes a nicotinic receptor subunit previously implicated in neuropsychiatric disorders, was affected by six large duplications in case subjects (none in comparison subjects), and SNPs in the gene had a gene-wide p value of 0.0002 for association in the GWAS.Both common and rare genetic variants appear to be relevant to ADHD and index-shared biological pathways.
Comparing the Costs, Risks, and Benefits of Competing Strategies for the Primary Prevention of Venous Thromboembolism
Authors: Jerry Avorn, Wolfgang C. Winkelmayer
Journal: Circulation (2004)

Systematic cost-effectiveness analyses of regimens used for preventing venous thromboembolism (VTE) are becoming increasingly important for several reasons: the aging of the population, with an accompanying increase in admissions for orthopedic procedures or other surgery; expanded indications for thromboprophylaxis in nonsurgical patients; and the introduction of more expensive new agents that may increase safety and efficacy. At the same time, health care systems are under unprecedented pressure to contain the costs of care, particularly medications. Such economic analyses are made more difficult by the paucity of clinical trials comparing treatment regimens to one another rather than to placebo. Several methodological issues must be kept in mind when evaluating cost-effectiveness analyses of VTE prophylaxis. These include the perspective from which the analysis is performed (eg, the health care system as a whole versus a particular payer), limitations of trial data (eg, artificially short time horizons), and definition of outcomes (eg, flawed definition and grouping together of adverse effects or treatment failures). Quantifying costs across nations and health care systems is problematic as well. Another challenge is the extrapolation of efficacy data from highly monitored study patients to routine practice settings. Nevertheless, cost-effectiveness analyses of VTE treatments conducted in orthopedic surgery, trauma, general surgery, and acute medical settings can help define the relationships among expenditures, adverse outcomes, and patient benefit for particular therapeutic strategies in a variety of clinical situations.
Neglect of growth and development in the clinical monitoring of children and teenagers with inflammatory bowel disease: review of case records
Authors: S. Ghosh, H. E Drummond, A. Ferguson
Journal: BMJ (1998)

Failure of growth and retarded sexual development are serious and common problems in children and teenagers with inflammatory bowel disease, particularly Crohn's disease. Thus height, weight, sexual staging, and bone age should be closely monitored in such patients. In 1989 we reported serious underrecording of these variables of growth in a cohort of Scottish children with inflammatory bowel disease.1 We assessed the situation a decade later.

We studied 28 boys and 13 girls aged 16 years at first admission to hospital with ulcerative colitis (n=14) or Crohn's disease (n=27). These patients, identified from the Scottish hospitals database of inpatients statistics for 1984-88, were resident in four of the Scottish regions.

We reviewed the patients' case records and noted whether height, …
Bacterial flora of comedones
Authors: S. MADLI PUHVEL, DEBORAH A. AMIRIAN
Journal: British Journal of Dermatology (1979)

Open comedones from thirty-eight patients with acne vulgaris on the face or back were compared for microbial flora. A total of eighty-three comedones from the face and sixty-three from the upper back were individually processed for quantitative bacterial analysis. The greatest difference between the flora of comedones at these two sites was that 44.6% of comedones from the back (compared to 9.6% from the face) harboured no aerobic cocci. The decreased prevalence of staphylococci in the lesions from the back reflects the relative absence of these organisms in isolated follicles from normal uninvolved skin of the back. The geometric mean count of anaerobes in comedones from the back was in the same range as the count found in isolated follicles in normal uninvolved skin in a previous study. This work supports the concept that the bacterial flora of comedones is an extension of the follicular flora and may be unrelated to the event of comedogenesis.
Expression of Functional Angiotensin-Converting Enzyme and AT <sub>1</sub> Receptors in Cultured Human Cardiac Fibroblasts
Authors: Sassan Hafizi, John Wharton, Kevin Morgan, Sean P. Allen, Adrian H. Chester, John D. Catravas, Julia M. Polak, Magdi H. Yacoub
Journal: Circulation (1998)

Background —Angiotensin II (Ang II) has been implicated in the development of cardiac fibrosis. The aims of the present study were to examine expression and activity of ACE and of angiotensin receptors in human cardiac fibroblasts cultured from dilated cardiomyopathic and ischemic hearts. The effects of Ang II on fibroblasts were also investigated. Methods and Results —Human cardiac fibroblasts were cultured from ventricular and atrial myocardium and characterized immunohistochemically. Expression of ACE and the angiotensin AT 1 receptor was demonstrated in cardiac fibroblasts by reverse transcriptase–polymerase chain reaction and radioligand binding. Functional ACE activity, measured by radiolabeled substrate conversion assay, was detected in both ventricular (V max · K m −1 · mg −1 , 0.031±0.010; n=13) and atrial (0.034±0.012; n=6) fibroblasts. Fibroblast ACE activity was increased after 48 hours of treatment with basic fibroblast growth factor, dexamethasone, and phorbol ester. Ang II did not affect DNA synthesis but stimulated [ 3 H]proline incorporation in cardiac fibroblasts (20.0±4.0% increase above control by 10 μmol/L; P &lt;0.05, n=7), which was abolished by losartan 10 μmol/L but not PD123319 1 μmol/L. Ang II also stimulated a rise in intracellular calcium (basal, 56±1 nmol/L; Ang II, 355±24 nmol/L) via the AT 1 receptor, as shown by complete inhibition with losartan. Conclusions —We have demonstrated expression and activity of ACE and AT 1 receptor in cultured human cardiac fibroblasts. In addition, cardiac fibroblasts respond to Ang II with AT 1 receptor–mediated collagen synthesis. The presence of local ACE and AT 1 receptors in human fibroblasts suggests their involvement in the development of cardiac fibrosis.
Treatment of ductal carcinoma in situ
Authors: J. A. Smith
Journal: BMJ (2011)

New data refine the risk estimates associated with various treatments

As knowledge of the clinical and pathological subtypes of ductal carcinoma in situ (DCIS) grows, medical oncologists, surgical oncologists, and radiation oncologists have an increasingly complex task in diagnosing and treating this disease, and advising their patients on the best course of action.

DCIS accounts for about one in five of all new cases of breast cancer in the United States each year (~60 000), and about two thirds of these are oestrogen receptor positive tumours (National Institutes of Health. State-of-the-science conference: diagnosis and management of ductal carcinoma in situ (DCIS). September 22-24, 2009, Bethesda, MA, USA). DCIS has the potential to progress to invasive breast cancer and confers an increased risk of ipsilateral and contralateral invasive breast cancer. The incidence of DCIS rose from 1.87 per 100 000 women in 1973-5 to 32.5 per 100 000 women in 2005. Incident increases were greatest in tumours with no necrosis within the DCIS, and although the increase was seen across all ages, it was greater in women over 50 years of age.1 2 3 

The national surgical adjuvant breast and bowel project (NSABP) trials B-17 and B-24 have been of pivotal importance in assessing the association between local control, local and distant recurrence, new …
Health, Human Rights, and Humanitarian Assistance During War and Conflicts
Authors: Annette Flanagin
Journal: JAMA (1992)

Is war inevitable? Despite the end of the cold war and the current wave of democratization, 120 armed conflicts exist in the world today. Thirty of these conflicts are considered major, involving more than 1000 battle-related deaths.<sup>1</sup> Many people are unaware of the major armed conflicts in India, Myanmar, Chad, and Sri Lanka, as we can barely keep up with the even larger conflicts in Somalia, the former Yugoslavia, Liberia, and Mozambique. And many are unaware that the majority of victims are civilians, including children.<sup>2,3</sup>Political and military leaders in Somalia, the former Yugoslavia, and Liberia, unlike their counterparts in Lebanon and El Salvador, are not responding to the silent pleas of innocent children who suffer untold violence and die in unknown numbers. Why is such suffering allowed to continue?<sup>4</sup>Haven't we learned from history? The histories of Sumeria, Egypt, Assyria, Persia, and Greece are chronicles of
The mid-depth method and HIV-1: a practical approach for testing hypotheses of viral epidemic history
Authors: O. G. Pybus, E. C. Holmes, P. H. Harvey
Journal: Molecular Biology and Evolution (1999)

We introduce the mid-depth method, a practical approach for testing hypotheses of demographic history using genealogies reconstructed from sequence data. The relative positions of internal nodes within a genealogy contain information about past population dynamics. We explain how this information can be used to (1) test the null hypothesis of constant population size and (2) estimate the growth rate and current population size of an exponentially growing population. Simulation tests indicate that, as expected, estimates of exponential growth rates are sometimes biased. The mid-depth method is computationally rapid and does not require knowledge of the sample's mutation rate. However, it does assume that the reconstructed genealogy is correct and is therefore best suited to the analysis of variation-rich viral data sets. When applied to HIV-1 sequence data, the mid-depth method provides phylogenetic evidence of different exponential growth rates for subtypes A and B. We posit that this difference in growth rate reflects the different transmission routes and epidemiological histories of the two subtypes.