tbuckley/cabot-search huggingface dataset:
Sinclair Morris Evans
Authors: R. Evans
Journal: BMJ (2002)

Former general practitioner Baslow, Derbyshire (b Leicester 1908; q Cambridge/St Thomas's Hospital, London, 1933; MD (honorary)), d 13 July 2001.

After house jobs at St Thomas's and Addenbrooke's Hospital, Cambridge, Morris joined a rural practice in Baslow, Derbyshire, where he was to remain for the rest of his working life. The practice encompassed every level of society from aristocrats to hard pressed farmers and quarrymen. Morris was at ease with them all. He served on various local committees and was involved in teaching general practice to medical students. Predeceased by his wife, he leaves two children and two grandchildren.
<sup>111</sup>In-Labeled Nonspecific Immunoglobulin Scanning in the Detection of Focal Infection
Authors: Robert H. Rubin, Alan J. Fischman, Ronald J. Callahan, Ban-An Khaw, Francis Keech, Marsood Ahmad, Robert Wilkinson, H. William Strauss
Journal: New England Journal of Medicine (1989)

We performed radionuclide scanning after the intravenous injection of human IgG labeled with indium-111 in 128 patients with suspected focal sites of inflammation. Localization of 111In-labeled IgG correlated with clinical findings in 51 infected patients (21 with abdominal or pelvic infections, 11 with intravascular infections, 7 with pulmonary infections, and 12 with skeletal infections). Infecting organisms included gram-positive bacteria, gram-negative bacteria, Pneumocystis carinii, Mycoplasma pneumoniae, and Candida albicans. No focal localization of 111In-labeled IgG was observed in 63 patients without infection. There were five false negative results, and nine results were unusable. Serial scans were carried out in eight patients: continued localization correctly predicted relapse in six, and the absence of localization indicated resolution in two. To determine whether 111In-labeled IgG localization was specific for inflammation, we studied 16 patients with cancer. Focal localization occurred in 13 of these patients (5 with melanomas, 5 with gynecologic cancers, and 1 each with lymphoma, prostate cancer, and malignant fibrous histiocytoma). No localization was seen in patients with renal or colon cancer or metastatic medullary carcinoma of the thyroid. We conclude that 111In-labeled IgG imaging is effective for the detection of focal infection and that serial scans may be useful in assessing therapeutic efficacy. This technique may also be helpful in the evaluation of certain cancers. (N Engl J Med 1989; 321:935–40.)
The Predictive Power and Cost of Screening for Chlamydia
Authors: Mark Rice
Journal: JAMA (1988)

<h3>To the Editor.—</h3> In a recent article entitled "Cost-effectiveness of Screening Women at Moderate Risk for Genital Infections Caused by<i>Chlamydia trachomatis</i>,"<sup>1</sup>there appear to be two contradictory statements that are crucial to the conclusions made by the authors. At one point, the statement is made that "the absolute sensitivity of a single endocervical direct antigen test was assumed to be 53% (ie, a direct antigen test would detect a true infection 53% of the time), and the specificity, 96%." Later in the article, while discussing the strategy of performing this test on all patients and treating those with positive results, the authors state that, "if this strategy were implemented, only 53% of treated patients would actually be infected." And later in the same paragraph comes another confusing statement that is more in agreement with their first statement regarding the test's sensitivity: "only half of infected patients would be
Novel <i>MEK1</i> Mutation Identified by Mutational Analysis of Epidermal Growth Factor Receptor Signaling Pathway Genes in Lung Adenocarcinoma
Authors: Jenifer L. Marks, Yixuan Gong, Dhananjay Chitale, Ben Golas, Michael D. McLellan, Yumi Kasai, Li Ding, Elaine R. Mardis, Richard K. Wilson, David Solit, Ross Levine, Kathrin Michel, Roman K. Thomas, Valerie W. Rusch, Marc Ladanyi, William Pao
Journal: Cancer Research (2008)

Abstract Genetic lesions affecting a number of kinases and other elements within the epidermal growth factor receptor (EGFR) signaling pathway have been implicated in the pathogenesis of human non–small-cell lung cancer (NSCLC). We performed mutational profiling of a large cohort of lung adenocarcinomas to uncover other potential somatic mutations in genes of this pathway that could contribute to lung tumorigenesis. We have identified in 2 of 207 primary lung tumors a somatic activating mutation in exon 2 of MEK1 (i.e., mitogen-activated protein kinase kinase 1 or MAP2K1) that substitutes asparagine for lysine at amino acid 57 (K57N) in the nonkinase portion of the kinase. Neither of these two tumors harbored known mutations in other genes encoding components of the EGFR signaling pathway (i.e., EGFR, HER2, KRAS, PIK3CA, and BRAF). Expression of mutant, but not wild-type, MEK1 leads to constitutive activity of extracellular signal–regulated kinase (ERK)-1/2 in human 293T cells and to growth factor–independent proliferation of murine Ba/F3 cells. A selective MEK inhibitor, AZD6244, inhibits mutant-induced ERK activity in 293T cells and growth of mutant-bearing Ba/F3 cells. We also screened 85 NSCLC cell lines for MEK1 exon 2 mutations; one line (NCI-H1437) harbors a Q56P substitution, a known transformation-competent allele of MEK1 originally identified in rat fibroblasts, and is sensitive to treatment with AZD6244. MEK1 mutants have not previously been reported in lung cancer and may provide a target for effective therapy in a small subset of patients with lung adenocarcinoma. [Cancer Res 2008;68(14):5524–8]
Structure and Function of a Middle-sized Accident Department
Authors: R. H. Hardy
Journal: BMJ (1974)

An account of the working of a middle-sized accident department is given, based on the study of nearly 33,000 attendance records. The work load, management, and staffing as it is actually organized is briefly described. The effectiveness of the service given is bedevilled by certain features of the N.H.S.-in particular, the deplorable conditions of employment of staff in casualty departments.
The Effect of Pregnancy on the Murmurs of Mitral and Aortic Regurgitation
Authors: FRANK I. MARCUS, GORDON A. EWY, ROBERT A. O'ROURKE, BERNARD WALSH, ALLAN C. BLEICH
Journal: Circulation (1970)

The effect of pregnancy on the intensity of murmurs of aortic and mitral regurgitation has not been reported previously. Twenty-five women with these murmurs, singly or in combination, were examined when pregnant as well as when not pregnant. During pregnancy the murmur of aortic regurgitation decreased in intensity or became inaudible in 10 patients, remained unchanged in four, and increased in one. The murmur of mitral regurgitation decreased in intensity or became inaudible in eight patients, became shorter in duration in two, was unchanged in three, and became louder in one. Three of the patients who did not show a decrease in intensity of the mitral or aortic regurgitation murmur and the patient whose murmurs increased during pregnancy had the appearance or persistence of systemic hypertension during pregnancy. Phenylephrine consistently increased the loudness of the murmurs, usually to the level present in the nonpregnant state. The diminished intensity of these murmurs may be related to the decrease in peripheral resistance known to occur during pregnancy. It is apparent that (1) aortic regurgitation or mitral regurgitation may be missed during pregnancy, since these murmurs may become inaudible, and (2) the severity of these cardiac lesions may be underestimated clinically because of a decrease in intensity of these murmurs during pregnancy. It is important to determine the existence of valvular heart disease, since endocarditis is a hazard during parturition, and prophylactic antibiotic therapy should be given to these patients.
The William C. Menninger Memorial Lecture: College Mental Health and Social Change.
Authors: Dana L. Farnsworth
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970The William C. Menninger Memorial Lecture: College Mental Health and Social Change.Dana L. Farnsworth, M.D.Dana L. Farnsworth, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-776_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe mental health of college students has been a concern of some colleges for more than half a century, but for most an awareness of college students' problems has been a recent acquisition. Today the questions raised are numerous. Are suicide rates showing a dramatic increase? Are college students adopting use of drugs—especially the amphetamines and hallucinogens—as a way of life? What motivates the destructive student radicals? Are they mentally ill, or is their apparent fanatic devotion to their cause a purely sociologic phenomenon? What are the main types and causes of morbidity among college students?Coincident with the growing... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cambridge, Mass. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 776-776KeywordsAmphetaminesDrugsMorbidityPsychiatry and mental healthSuicide Issue Published: 1 May 1970 PDF downloadLoading ...
Secretion of soluble chemotactic factors, including interleukin-6: A mechanism for the recruitment of cd8-positive t lymphocytes to human liver allografts during rejection
Authors: Mark Hathaway, David Burnett, Elwyn Elias, David H. Adams
Journal: Hepatology (1993)

In 35 patients receiving first liver transplants we assessed the chemotactic responsiveness of peripheral blood lymphocytes to bile, the subset composition of the responding population and the ability of peripheral blood lymphocytes to produce chemotactic factors. In 13 patients in whom acute rejection developed, lymphocyte chemotaxis in vitro was significantly greater in bile sampled 1 or 2 days after transplantation and before episodes of acute rejection than in bile sampled when rejection was clinically apparent or after steroid therapy during stable graft function. The chemotactic factors present showed preferential activity for CD8-positive T cells. Bile sampled during the same posttransplant periods from 11 patients who did not exhibit rejection showed significantly less chemotactic activity. In vitro cultured peripheral blood lymphocytes from patients in whom rejection developed produced lymphocyte chemotactic factors that induced a similar pattern of chemotactic responsiveness with preferential activity for CD8-positive T cells. Separate culture of purified CD4-positive and CD8-positive T cells obtained from patients in whom rejection developed showed that CD4-positive cells produced the factor(s). Analysis of the subset responses of normal peripheral blood lymphocytes to a variety of chemotactic cytokines showed interleukin-6 to have specificity similar to that observed with chemotactic bile, mixed peripheral blood lymphocyte culture supernatants and supernatants of CD4-positive T cells. Chemotactic activity was reduced by 45% to 90% in five chemotactic bile samples and three peripheral blood lymphocyte culture supernatants by treatment with affinity purified interleukin-6 monoclonal antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
Reduced activation of epidermal phosphorylase in the lesions of psoriasis
Authors: P. D. MIER, J.M.A. JOSE, VAN HURK
Journal: British Journal of Dermatology (1974)

The percentage activation of the enzyme phosphorylase in extracts prepared from the epidermis of psoriatic lesions was found to be significantly lower than normal. This observation lends strong support to the concept of a reduced level of cyclic AMP in the lesion of this disease.
Managing conjunctivitis in general practice: Recommendations depend on health system
Authors: M. R Nelson
Journal: BMJ (2006)

I just wanted to be a doctorWe need to be more than "just" doctors Editor-Hunt articulates the feelings of many doctors on discovering that the effective practice of modern medicine requires a range of skills beyond the provision of direct clinical care. 1 Her slightly delayed entry into medicine may explain why this issue is troubling her now, rather than later in her career: certainly these are sentiments I hear more commonly from consultant colleagues than juniors.However, to imagine that good medical practice is confined to the delivery of care to one patient at a time is to overlook the role of doctors in organising healthcare systems and delivery in the wider context.It is disappointing that Hunt's appraiser chose to frame the process in terms of her trust's participation in the clinical negligence scheme, since most junior doctors value well conducted appraisals.Nevertheless, cheaper insurance premiums for hospitals mean more money to spend on health care, and also indicate that organisations that carry out effective appraisal make fewer clinical errors: presumably these are both outcomes that Hunt would approve of.Furthermore, research and audit without the active participation of doctors will soon become clinically irrelevant or ineffective.We have a wider responsibility for patient care that is served by informed participation in these and many other activities, such as teaching and continuous quality improvement (which also seem to get irritatingly in the way of a narrowly focused approach to patient care).However, all is not lost.Hunt appears well placed to fall into the "Modernising Medical Careers" vacuum that currently threatens to swallow those junior doctors who are too old for a foundation programme yet too young to have secured a specialist registrar post.If this does indeed curtail all opportunities for career progression she may end up as "just" a doctor after all.
Naming versus referring in the selection of words
Authors: Peter C. Gordon
Journal: Behavioral and Brain Sciences (1999)

The theory of lexical selection presented by Levelt, Roelofs &amp; Meyer addresses the mechanisms of semantic activation that lead to the selection of isolated words. The theory does not appear to extend naturally to the referential use of words (particularly pronouns) in coherent discourse. A more complete theory of lexical selection has to consider the semantics of discourse as well as lexical semantics.
Treatment may not be simple
Authors: D. K. Murray
Journal: BMJ (2010)

<h3>Abstract</h3> Parental provisioning of offspring with physiological products occurs in many animals. Within amphibians, maternal provisioning has evolved multiple times, including in South American dendrobatid and Malagasy mantellid poison frogs. In some of these species, mothers feed unfertilized eggs to their developing tadpoles for several months until tadpoles complete metamorphosis. We conducted field studies in Ecuador and Madagascar to ask whether convergence at the behavioral level provides similar benefits to offspring and whether nursing behavior relies on shared neural mechanisms across frogs and vertebrates more broadly. At an ecological level, we found that nursing allows poison frog mothers to provide chemical defenses to their tadpoles in both species. At the level of brain regions, nursing behavior was associated with increased neural activity in the lateral septum and preoptic area in both species, demonstrating recruitment of shared brain regions in the convergent evolution of maternal care within frogs and across vertebrates. In contrast at a molecular level, only mantellids showed increased oxytocin neuron activity akin to that in nursing mammals. Taken together, our findings demonstrate that convergently evolved maternal provisioning behavior provides similar benefits to offspring and relies on similar brain regions. However, the molecular mechanisms underlying the convergence in nursing behavior may be different, suggesting evolutionary versatility in the mechanisms promoting maternal behavior.
YMDD motif in hepatitis B virus DNA polymerase influences on replication and lamivudine resistance: A study byin vitrofull-length viral DNA transfection
Authors: Suzane Kioko Ono-Nita, Naoya Kato, Yasushi Shiratori, Tsutomu Masaki, Keng-Hsin Lan, Flair José Carrilho, Masao Omata
Journal: Hepatology (1999)

Recently, lamivudine used to treat patients with hepatitis B virus (HBV) infection was revealed to have potent antiviral activity. However, HBV resistance to lamivudine has been reported and shown to have amino acid substitutions in the methionine residue of the conserved tyrosine (Y), methionine (M), aspartate (D), aspartate (D) motif of RNA–dependent DNA polymerase. To explore the consequences of substitutions in this motif (YMDD), we made 7 variants by substituting the methionine of the YMDD motif with isoleucine (I), valine (V), alanine (A), leucine (L), lysine (K), arginine (R), and threonine (T). Replication ability of these variants was evaluated by transfection into human hepatoma cells. Sensitivity to lamivudine was tested for replication–competent variants. Four variants with hydrophobic substitutions (I, V, A, and L) remained replication–competent, whereas 3 others with hydrophilic substitutions (K, R, and T) exhibited impaired replication. Of the 4 replication–competent variants, 2 (I and V) were resistant, and 2 (A and L) were sensitive to lamivudine. Because the polymerase and the surface gene overlap, the introduction of these mutations affected the secretion of hepatitis B surface antigen (HBsAg), namely 4 variants (I, V, L, and R) secreted HBsAg, whereas 3 variants (A, K, and T) did not. Our study elucidated that only one amino acid substitution in the YMDD motif was sufficient to cause lamivudine resistance in vitro . As a result of replication competence and lamivudine sensitivity, only viruses having YIDD or YVDD sequences may appear during treatment with lamivudine. This in vitro system could be used to study HBV mutations, replication competence, and their susceptibility to antivirals.
Abstract 2270: ATM is hyperactivated in triple-negative breast cancer tissues
Authors: Xiaojing Guo, Ting Lei, Mianen Sun, Chunying Yang, Li Fu, Bo Xu
Journal: Cancer Research (2011)

Abstract Triple-negative breast cancer (TNBC) represents a phenotype defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) expression. TNBCs are extremely aggressive and lack effective therapeutic targets. The DNA damage response is an active mechanism which prevents genetic instability and tumorigenesis. We have recently found the existence of active DNA damage responses in late stage breast cancer tissues. Here we report a critical role of the Ataxia-Telangiectasia-Mutated (ATM) kinase, a key transducer of DNA damage signals, in TNBC metastasis. By analyzing ATM activity in 169 cases of TNBC using immunohistochemistry, we found that ATM activity is enhanced in TNBCs, compared to 210 cases of non-TNBCs (P=0.003). Among the TNBC cases, 62.1% have lymph node metastasis, and ATM is hyperactive in these cases. As epithelial-mesenchymal transition (EMT) is associated with increased aggressiveness and metastatic potential, we also assessed the occurrence of EMT in these tissues. Interestingly, our results showed that tumors with higher ATM activity displayed increased expression levels of Snail, an early EMT marker (P=0.001). We also observed a strong correlation of ATM activity with up-regulation of another EMT marker, vimentin (P=0.015), and with reduction of characteristic epithelial markers, E-cadherin and cytokeratin (P=0.002 and P=0.036, respectively). Among the TNBC cases, the expression levels of activated ATM and Snail were significantly correlated with lymph node metastasis (P=0.008 and P=0.01, respectively). In our laboratory, we have extensively studied the molecular link between ATM and Snail, demonstrating that an active ATM-Snail pathway is essential for breast cancer metastasis. Taken together, our clinical data indicate that deficiency of ER, PR and HER2 may lead to hyperactive ATM and Snail, which contribute to high invasiveness and metastasis of TNBCs. 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 2270. doi:10.1158/1538-7445.AM2011-2270
Inoculability of Cancer—A Question of Priority
Authors: Joseph Leidy
Journal: JAMA (1913)

To  Editor:  —An interesting editorial note (The Limatations of Specificity in  Transmission of Disease,The Journal, March 1, p. 675), on  inoculability of cancer in different species of animals, gives  impression that those observations and experiments are only recent in time. In  good name of American science, I refer you to  Proceedings of  Academy of Natural Science, Philadelphia, May and June, 1851, in which  late Joseph Leidy repeats  results of his experiments on  inoculability of cancer. The experiments were conducted at  Academy of Science, and from  results obtained by introducing portions of (human) cancerous tissue into frogs, Leidy observed after a full description and demonstration before  academy, that the experiments not only proved  independent vitality of tissues, which was generally admitted, but rendered it exceedingly probable that cancer was inoculable, for as, in  experiments
Actual causes of death in the United States
Authors: S. A. Glantz
Journal: JAMA (1994)

To the Editor.  —Drs McGinnis and Foege 1 recently published an article pointing out that the most prominent cause of death is tobacco (419 000 deaths) compared with other behaviors, such as illicit use of drugs (20 000 deaths), which command much greater public attention. Their article only tells half the story, however. As the Figure demonstrates, the federal government devotes resources to these problems in inverse proportion to the real public health impacts, despite the fact that there are proven public health interventions that can control many of these diseases, particularly tobacco. For example, in California voters increased the tobacco tax by 25 cents per pack of cigarettes and devoted 5 cents to an aggressive media and community-based tobacco control campaign. Despite the fact that the legislature and governor have never fully funded these programs, 2 the rate of decline in tobacco consumption in California tripled. 3 At a
Parotid fluid cortisol and cortisone
Authors: Fred H. Katz, Ira L. Shannon
Journal: Journal of Clinical Investigation (1969)

Parotid fluid corticosteroids, substantially comprised of cortisol and cortisone, were previously demonstrated to rise to far greater levels 4 hr after administration of ACTH than they did in the third trimester of pregnancy, although the plasma total corticosteroid concentrations were similar in these two states. It was therefore suggested that only nonproteinbound corticosteroid gains access to parotid fluid. In the present study parotid fluid cortisol and cortisone and plasma dialyzable cortisol concentrations have been measured in normal men before and 2 hr after 40 U ACTH, and, in another group, before and after 10 days of diethystilbestrol (5 mg daily). Total plasma cortisol rose from a mean of 6.3 to 17.9 mug/100 ml after ACTH and from 14.6 to 39.4 mg/100 ml after the estrogen. However parotid fluid cortisol plus cortisone rose from 0.8 to 2.6 mug/100 ml after ACTH and to only 2.2 after estrogen. This rise resembled that of the plasma dialyzable cortisol (control 0.4, ACTH 1.8, estrogen 1.2 mug/100 ml) rather than the increase in total plasma cortisol which was over twice as high after estrogen as after ACTH. Thus parotid fluid corticosteroids seem to be a good measure of nonprotein-bound corticosteroid, the cortisol available to the cell. The total amount of cortisol plus cortisone excreted is approximately constant, independent of parotid fluid flow rate. Cortisone exceeds cortisol in parotid fluid in the basal state, but after ACTH the situation is reversed.