tbuckley/cabot-search huggingface dataset:
Abstract 4646: Notch and DLL4 expression in bevacizumab-treated colon cancer patients.
Authors: Francesca Negri, Cecilia Bozzetti, Pellegrino Crafa, Costanza Lagrasta, Stefano Cavalli, Giuseppe Pedrazzi, Giorgio Gardini, Ione Tamagnini, Rosa Porzio, Luigi Cavanna, Carlo Paties, Ida Romano, Antonino Musolino, Gianluca Tomasello, Pier Giorgio Petronini, Andrea Ardizzoni
Journal: Cancer Research (2013)

Abstract Background: In order to investigate mechanisms of resistance to angiogenesis inhibitors, Notch and Delta-like 4 ligand (DLL4) expression was correlated with response and survival in a series of bevacizumab treated advanced colon cancer patients. DLL4-mediated Notch signalling has recently emerged as an attractive target for angiogenesis-based cancer therapies, given that DLL4 is an important component of Notch-mediated stem cell self-renewal and vascular development. DLL4-induced Notch signalling mediates tumour-resistance to anti-VEGF therapy by inducing the formation of large vessels and activating multiple pathways in preclinical models. Method: Notch and DLL4 expression was evaluated by immunohistochemistry (IHC) on 65 primary colon cancer patients enrolled within randomized clinical trials assessing first-line bevacizumab plus chemotherapy. Results: Notch positivity was localized to the cytoplasm of malignant epithelial cells. In all, 10/60 (17%) evaluable primary tumours had a high Notch expression. Five of the 10 cases (50%) with high Notch expression experienced progressive disease compared with 5/49 (10%) Notch negative cases (p=0.008). Median progression-free survival (PFS) was 2.8 months for Notch positive cases compared with 13.07 months for Notch negative cases (p=0.045). Membranous and/or cytoplasmic DLL4 immunoreactivity of tumour vessels was observed in 30/56 (54%) evaluable colon cancers. No correlation was found between DLL4 expression and clinical outcome. Conclusion: Clinical trials investigating the therapeutic efficacy of bevacizumab in colon cancer did not explore the impact of DLL4-Notch pathway on response and clinical outcome. Our results seem to suggest that high Notch expression might be involved in tumour resistance in colon cancer patients treated with bevacizumab. Citation Format: Francesca Negri, Cecilia Bozzetti, Pellegrino Crafa, Costanza Lagrasta, Stefano Cavalli, Giuseppe Pedrazzi, Giorgio Gardini, Ione Tamagnini, Rosa Porzio, Luigi Cavanna, Carlo Paties, Ida Romano, Antonino Musolino, Gianluca Tomasello, Pier Giorgio Petronini, Andrea Ardizzoni. Notch and DLL4 expression in bevacizumab-treated colon cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4646. doi:10.1158/1538-7445.AM2013-4646 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Surgery or Assisted Suicide?
Authors: Nathan Schnaper
Journal: Annals of Internal Medicine (1991)

Letters1 June 1991Surgery or Assisted Suicide?Nathan Schnaper, MDNathan Schnaper, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-114-11-995_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors: A bright, alert, elderly man with several different life-threatening illnesses sought counseling for what he hoped would be an approach to euthanasia. He had long since thoroughly informed himself about the "Hemlock Society." Several months of nondirective discussion sessions resulted in his postponing active intervention.A "new" symptom precipitated the possibility of major surgery, albeit with an awareness on all sides of the poor prognosis. Nonetheless, the patient pushed for the surgery, which resulted in his death. The patient achieved his wish by seducing his medical caregivers to unwittingly expedite his demise.This letter was of necessity... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: University of Maryland Cancer Center University of Maryland Hospital Baltimore, MD 21201 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1991Volume 114, Issue 11Page: 995-995KeywordsCaregiversElderlyEuthanasiaSuicideSurgery Issue Published: 1 June 1991 PDF DownloadLoading ...
Genetic Counseling in Classic Hemophilia A
Authors: John B. Graham
Journal: New England Journal of Medicine (1977)

The usual counseling situation with a hemophilic family is that a sister or cousin or niece of a hemophilic patient wishes to have a child. Knowledge of the suffering and expenses incurred by the affected relative has caused indecision and frustration. She wishes to know whether she is a carrier, and if she is a carrier, whether she can avoid having a hemophilic son. The latter problem is more easily dealt with than the former, at least scientifically, since the sex of an unborn child can be determined by amniocentesis and the birth of males simply avoided. But deciding whether . . .
Would a medium-nicotine, low-tar cigarette be less hazardous to health?
Authors: R Stepney
Journal: BMJ (1981)

Smoking behaviour and exposure to carbon monoxide, nicotine, and tar were studied in 19 middle-tar smokers. All smoked their own brands for three weeks and then switched to either a conventional low-nicotine, low-tar brand (control) or a medium-nicotine, low-tar cigarette for a further three weeks, the order then being reversed. The medium-nicotine, low-tar brand also had a low delivery of carbon monoxide. With the medium-nicotine, low-tar cigarette mouth-level delivery and intake of nicotine was similar to that with the smokers9 usual brands, and significantly greater than with the control low-tar cigarette. Intake of carbon monoxide from the medium-nicotine, low-tar cigarette was significantly less than with either own or control brands. With both low-tar brands mouth-level exposure to tar was reduced relative to smokers9 usual cigarettes. There was no evidence, however, that the reduction in tar exposure was greater with the medium-nicotine brand than with the control low-tar cigarette. Both low tar brands were "9oversmoked" relative to subjects9 usual middle-tar cigarettes. The medium-nicotine, low-tar cigarette was marginally more acceptable than the control brand, and the particular design used in the study resulted in a lower intake of carbon monoxide. In terms of reducing mouth-level exposure to tar, however, the medium-nicotine, low-tar cigarette had no advantage over the control low-tar product. In part this was because of the ratio of tar to nicotine delivery obtained by human smokers was not the same as that obtained by smoking machine.
FETAL ECHOCARDIOGRAPHY PREDICTS CLINICAL PRESENTATION AND OUTCOME IN TETRALOGY OF FALLOT WITH ABSENT PULMONARY VALVE: A MULTICENTER STUDY
Authors: Anjali Chelliah, Dorothy Bulas, Sheila Carroll, Brooke Davey, Allison Divanovic, Catherine Gillespie, Lisa Howley, Ann Kavanaugh-McHugh, John Kovalchin, Stephanie Levasseur, Christopher Lindblade, Anita Moon-Grady, Shaine Morris, Jay Pruetz, Michael Puchalski, Jack Rychik, Cyrus Samai, Theresa Tacy, Margaret Vernon, Jacqueline Weinberg, Jay Yeh, Mary Donofrio
Journal: Journal of the American College of Cardiology (2014)
Experience with Emergency Aortocoronary Bypass Grafts in the Presence of Acute Myocardial Infarction
Authors: WILBERT J. KEON, PIERRE BEDARD, KANAKAIAHNAVARA R. SHANKAR, YASH AKYUREKLI, ALFREDO NINO, FRANK BERKMAN
Journal: Circulation (1973)

In the past 18 months 15 patients have undergone emergency aortocoronary bypass grafts using saphenous vein in the presence of acute myocardial infarction. Eight patients were in a state of cardiogenic shock, and seven patients were having severe cardiac arrhythmias, persistent hypotension, or signs of extending infarction. There were three operative deaths, all of which occurred in the cardiogenic shock group of patients. One patient died three months after operation of a cerebrovascular accident. There are 11 surviving patients. One patient presently has angina, and one patient shows signs of left heart failure. The remaining patients are well at the present time. We feel that angiography and surgery early in the course of a complicated myocardial infarct should diminish the immediate risk of death from both pump failure and cardiac rupture. Controlled prospective studies are required to elucidate the timing and indications for operation.
Cancer of the Cervix: Diagnosis of Early Forms
Authors: Clifford P. Goplerud
Journal: JAMA (1961)

The book is well written, and the publication of the discussion at the end of each paper is of value. The material presented brings out different ideas and attitudes that are usually discussed in journals and texts in the United States. The biochemical approach to the diagnosis of cervical malignancy is discussed and certainly is a field that merits further investigation. The morphology of the cervix in reference to aging is of interest and may be a guide to easier diagnoses and to fewer false-positive tissue studies when the cytological examination has revealed suspicious abnormality. The book is of interest to pathologists, cytologists, and physicians who are engaged in the treatment of gynecological malignancy.
Therapeutic Options for Laryngeal Cancer
Authors: Everett E. Vokes, Kerstin M. Stenson
Journal: New England Journal of Medicine (2003)

Every year in the United States, approximately 9500 new cases of laryngeal cancer are diagnosed, and 3800 patients die of this tumor. Persistent hoarseness is a warning sign that can lead to the detection of the tumor at an early stage. Such small tumors (stage T1 or T2, N0, and M0, according to the tumor–node–metastasis staging system) are treatable with radiotherapy alone or with modern surgical techniques, both of which can eradicate the tumor as well as preserve vocal quality. More advanced laryngeal cancers (stage III or IV) extend beyond the vocal cords into supraglottic structures, the thyroid cartilage, or . . .
PROGNOSTIC IMPACT OF MANAGEMENT IN PATIENTS WITH RENAL INSUFFICIENCY AND ACUTE CORONARY SYNDROME: FAST-MI 2010
Authors: Nicolas F. Meneveau, Etienne Puymirat, Samir Allam, René-Gabriel Huguet, Francois Schiele, Jean Ferrieres, Tabassome Simon, Nicolas Danchin
Journal: Journal of the American College of Cardiology (2013)
RECURRENT HERPES OF THE BUTTOCK
Authors: H. G. ADAMSON
Journal: British Journal of Dermatology (1911)

Journal Article RECURRENT HERPES OF THE BUTTOCK Get access H. G. ADAMSON, M.D., F.R.C.P. H. G. ADAMSON, M.D., F.R.C.P. Physician for Diseases of the Skin, St. Bartholomew's Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 23, Issue 10, 1 October 1911, Pages 322–327, https://doi.org/10.1111/j.1365-2133.1911.tb16659.x Published: 01 October 1911
WHO launches plan to fight drug resistant tuberculosis
Authors: Peter Moszynski
Journal: BMJ (2007)

The World Health Organization and the Stop TB Partnership, a global alliance of health, research, and funding organisations, last week launched a $2.2bn (£1.1bn; €1.6bn) plan to contain drug resistant tuberculosis, which includes multidrug resistant tuberculosis (MDR-TB) and the recently identified extensively drug resistant strains of the disease (XDR-TB).

Extensively drug resistant tuberculosis raises the possibility that tuberculosis that is susceptible to drug treatment will be replaced by a form with “severely restricted treatment options.” 

WHO warns: “If this happens it would jeopardise the progress made in recent years to control TB globally and would also put at risk the plans to progress towards universal …
STIM1 controls T cell–mediated immune regulation and inflammation in chronic infection
Authors: Ludovic Desvignes, Carl Weidinger, Patrick Shaw, Martin Vaeth, Theo Ribierre, Menghan Liu, Tawania Fergus, Lina Kozhaya, Lauren McVoy, Derya Unutmaz, Joel D. Ernst, Stefan Feske
Journal: Journal of Clinical Investigation (2015)

Chronic infections induce a complex immune response that controls pathogen replication, but also causes pathology due to sustained inflammation. Ca2+ influx mediates T cell function and immunity to infection, and patients with inherited mutations in the gene encoding the Ca2+ channel ORAI1 or its activator stromal interaction molecule 1 (STIM1) are immunodeficient and prone to chronic infection by various pathogens, including Mycobacterium tuberculosis (Mtb). Here, we demonstrate that STIM1 is required for T cell–mediated immune regulation during chronic Mtb infection. Compared with WT animals, mice with T cell–specific Stim1 deletion died prematurely during the chronic phase of infection and had increased bacterial burdens and severe pulmonary inflammation, with increased myeloid and lymphoid cell infiltration. Although STIM1-deficient T cells exhibited markedly reduced IFN-γ production during the early phase of Mtb infection, bacterial growth was not immediately exacerbated. During the chronic phase, however, STIM1-deficient T cells displayed enhanced IFN-γ production in response to elevated levels of IL-12 and IL-18. The lack of STIM1 in T cells was associated with impaired activation-induced cell death upon repeated TCR engagement and pulmonary lymphocytosis and hyperinflammation in Mtb-infected mice. Chronically Mtb-infected, STIM1-deficient mice had reduced levels of inducible regulatory T cells (iTregs) due to a T cell–intrinsic requirement for STIM1 in iTreg differentiation and excessive production of IFN-γ and IL-12, which suppress iTreg differentiation and maintenance. Thus, STIM1 controls multiple aspects of T cell–mediated immune regulation to limit injurious inflammation during chronic infection.
Three trusts deliberately misreported data, says Audit Commission
Authors: S. Hargreaves
Journal: BMJ (2003)

An Audit Commission report published this week has found that most NHS trusts have serious flaws in how they collect and report data on waiting lists.

Errors in reporting waiting lists were found in 19 of the 41 trusts investigated; system errors that could increase risk of reporting errors were found in 15 trusts; and three trusts deliberately misreported information on their waiting lists. Only three of 41 trusts were given the all clear.

The report, part of a five year rolling programme of spot checks …
Pulmonary oedema of mountains.
Authors: A Pines
Journal: BMJ (1972)

and immunotherapy (an attempt to assist natural defence) will be inst,tuted without necessarily predicting the site and nature of the malignant growth.Further work in this laboratory has not induced us to relinquish our tentative con- clusion' that there may well be a common antigen appearing in all human malignant neoplasms.If this is indeed so we may be optimistic that an effective treatment of cancer (whatever its primary cause(s) may be) is a problem essentially soluble with methodology already developed.-Weare, etc.,
Control of the development of CD8αα+ intestinal intraepithelial lymphocytes by TGF-β
Authors: Joanne E Konkel, Takashi Maruyama, Andrea C Carpenter, Yumei Xiong, Brian F Zamarron, Bradford E Hall, Ashok B Kulkarni, Pin Zhang, Remy Bosselut, WanJun Chen
Journal: Nature Immunology (2011)
Abstract 4103: Hepatocellular carcinoma-specific isoforms of methylated DNA-binding protein 2 and their therapeutic and diagnostic potential
Authors: Ziv M. Machnes, Barbara Stefanska, Moshe Szyf
Journal: Cancer Research (2012)

Abstract Liver cancer is the fifth most common cancer in the world. It is particularly prevalent in developing countries in Asia and Africa. In the US alone, it is estimated that 26,190 adults will be diagnosed with primary liver cancer this year, and 19,590 people will die of the disease. Hepatocellular carcinoma has no efficient cure, has a 5-year survival rate of 14% and is highly metastatic. In the last couple of decades, it has been established that many types of cancer involve major changes in the DNA methylation machinery and in turn, widespread yet highly specific changes in cytosine methylation. DNA methylation is a chemical modification on the DNA associated with gene inactivation, and in contrast to genetic mutation, is dynamic and reversible, making it a preferable target for therapeutics. Methylated-DNA Binding Proteins (MBD) have been shown to play a critical role in the progression and metastasis of cancers in general and specifically in hepatocellular carcinoma. We have identified two isoforms of the MBD2 protein (hcMBD2) that have not been previously reported in any somatic cells: these isoforms are totally silenced in normal liver cells and active in hepatocellular carcinoma. Specific inhibition of these isoforms of MBD2 in hepatocellular carcinoma (HePG2 cell line) has a dramatic effect on cell growth and cellular transformation, but no effect in normal cells, where the isoforms are not expressed. Knockdown experiments show dramatic reduction in cell invasiveness, reduced cell growth rate and increased cell death in HepG2 cells, while primary liver hepatocytes remain largely unaffected. A survey of several types of cancers and their surrounding tissue of origin shows the expression of hcMBD2 in several other types of cancer, such as breast cancer. These results position hcMBD as a promising candidate for cancer diagnostics and therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4103. doi:1538-7445.AM2012-4103
THE ORIGIN OF CANCER
Authors: A. Haig
Journal: BMJ (1909)

I 144Tpossibly mbay be associated with slight dilatation.Such a sound may be, however, present -when there is no reason ,o suspect any dilatation of the heart, but apical and basic systolic murmurs, although very common in quite young children, always indicate, I believe, the presence of dilatation,!and are, it seems to me, the most reliable signs of such dilatation.-Iam, etc., September 25th.
Scientists Seek to Gain Adherents, Avert Technological Ignorance 'Disaster'
Authors: Marsha F. Goldsmith
Journal: JAMA (1989)

EVERY CHILD is a natural scientist, filled with curiosity and eager to experiment, agreed participants in "Strategies for Change," a science literacy planning symposium organized by the American Medical Association (AMA) and seven other scientific societies. The poser is, why do so few in the United States sustain into adulthood sufficient interest in how the world works to propel them into scientific careers? Have insensitive parents and inadequate teachers squelched untold numbers of budding mathematicians and researchers? Does intimate acquaintance with the culture of poverty preclude caring about biological cultures? Is the affluence seemingly promised by business and the law luring analytical minds away from chemistry and physics? Can the entertainment industry's portrayal of white-coated scientists as evil or "weird" or "nerds" be blamed for discouraging the "regular guys"? Not to mention the many prospective technologists who aren't guys at all—and how many women engineers do<i>you</i>know? These questions
Giant Duodenal Ulceration
Authors: Robert F. Rider
Journal: JAMA (1969)

Dr.Robert J. Cihak: This 86-year-old man was admitted to this hospital with a history of increasing dyspnea for two months. Recently he noted intermittent abdominal pain which radiated to the back. He did not have a history of vomiting, nor was he jaundiced. His hematocrit reading was 32; white blood cell count, 13,000/cu mm; and the guaiac test on the stool was positive. Examination of the upper gastrointestinal tract was performed at the time of admission. <h3>Discussion</h3> Dr. Laurence L. Robbins: Dr. Shea, would you discuss this case? Dr. Thomas E. Shea: The obvious abnormality is in the area of the duodenal bulb which contains a grossly irregular collection of barium sulfate (Figure). There is no mucosal pattern within it. Several possibilities come to mind. Giant duodenal ulcer should be considered, particularly if there is a past history of peptic ulcer disease. That entity demonstrates a very large, globular
Echocardiographic left ventricular dimensions in two groups of road race cyclists during a training season
Authors: L. Fananapazir, B. Ryan-Woolley, C. Ward, J. A. White
Journal: British Journal of Sports Medicine (1982)

significant difference (.01 level) between events when the lactate values were treated by ANOVA (Table 3).ANOVA revealed a no-difference effect (.01 level of significance) between event-resting lactate values.
Mental Health Needs of Employees in Business and Industry
Authors: Cavin P. Leeman
Journal: JAMA (1974)

<h3>To the Editor.—</h3> A recent article by Dr. Modlin (226:50, 1973) considered the problems of collaboration between psychiatrists and occupational physicians in meeting the mental health needs of employees in business and industry. The psychiatrists discussed were expected to have little familiarity with the work situations of their patients. Recently, another approach to the mental health needs of a business community has been developed. A psychiatrist directs a program in which a psychologist or social worker serves as counselor to employees of a business firm. The counselor is stationed full-time within the work setting, readily accessible to employees. The psychiatrist supplies clinical supervision. Both counselor and psychiatrist get to know the work environment very well, which helps them to understand the employees and their problems. A program of this kind has been in operation for several years and has demonstrated its effectiveness.<sup>1</sup>Additional publicity in the<i>Psychiatric Quarterly and</i>
[526] ROLE OF HIV COINFECTION IN MORTALITY RELATED TO HEPATITIS C AND HEPATITIS B IN FRANCE
Authors: T. Asselah, F. Pequignot, J.-R. Zarski, N. Ganne, P. Hillon, E. Delarocque-Astagneau, D. Antona, M. Bovet, M. Mechain, I.-C. Desenclos, P. Marcellin, E. Jougla
Journal: Journal of Hepatology (2007)
Augmented Cardiac Cardiotrophin-1 in Experimental Congestive Heart Failure
Authors: Michihisa Jougasaki, Issei Tachibana, Andreas Luchner, Hanna Leskinen, Margaret M. Redfield, John C. Burnett
Journal: Circulation (2000)

Background —Cardiotrophin-1 (CT-1) is a potent hypertrophic factor discovered by coupling expression cloning in a mouse embryonic stem cell–based model of cardiogenesis. Methods and Results —The present study was designed to investigate the potential activation of atrial and ventricular CT-1 expression in pacing-induced experimental congestive heart failure (CHF) and its relationship to left ventricular hypertrophy by the method of Northern blot analysis and immunohistochemistry. We used a canine model of pacing-induced experimental CHF based on hemodynamic and neurohumoral characteristics that closely mimic human dilated cardiomyopathy. Northern blot analysis demonstrated that CT-1 gene expression was present in normal atrium and ventricle and was increased in CHF hearts. There was a positive correlation between ventricular CT-1 mRNA and left ventricular mass index. Immunohistochemistry revealed positive immunostaining in the atrial and ventricular cardiomyocytes from both normal and CHF hearts. CT-1 immunoreactivity was more intense in the atrium and ventricle from CHF hearts than in normal hearts. Conclusions —The present study demonstrates that both atrium and ventricle synthesize CT-1 and that cardiac production of CT-1 is augmented in a canine model of experimental CHF. This study also demonstrates that ventricular CT-1 mRNA correlates with left ventricular hypertrophy, suggesting that CT-1 plays an important role in the structural remodeling that characterizes CHF.