tbuckley/cabot-search huggingface dataset:
Abstract 4451: Long-term resistance to PI3K/mTOR inhibition requires increased expression of c-myc and YAP.
Authors: Taru E. Muranen, Jonathan Coloff, Laura Selfors, Amy Bui, Gordon B. Mills, Joan S. Brugge
Journal: Cancer Research (2013)

Abstract We have shown that extracellular matrix (ECM) contact contributes to PI3K/mTOR inhibitor resistance, where drug treatment leads to cytostasis but not cell death in ECM-attached cells. These cells do undergo proliferation arrest and this may reflect the situation in vivo, where PI3K/mTOR inhibitor treatment initially leads to growth arrest of the tumor cells. However this is often followed by re-initiation of proliferation, leading to relapse. In this study we have investigated the underlying molecular mechanisms that mediate long-term resistance to PI3K/mTOR inhibitors by selecting for cancer cells that proliferate after chronic inhibitor exposure in 3D cell cultures. To assess the mechanism of resistance, we performed reverse phase protein and RNA-seq arrays to identify signaling pathways that were altered in proliferating drug resistant cells. The protein arrays revealed up-regulated levels of c-myc and the Hippo pathway effector, YAP, in the resistant cells, and introduction of exogenous c-myc and YAP into drug sensitive cells rendered them resistant. While expression of c-myc alone induced partial resistance, YAP was also required, as knock-down of endogenous YAP resulted in loss of resistance. These data suggest that c-myc alone is not sufficient for generating resistance to PI3K/mTOR inhibitors, but an additional driver is required. Since the Hippo pathway is another major growth-promoting pathway (in addition to mTOR), it is conceivable that YAP compensates for the loss of mTOR signaling, contributing to resistance. Our current efforts are aimed at elucidating the mechanism by which YAP and c-myc mediate drug resistance to PI3K/mTOR inhibitors. Preliminary data suggests that c-myc-dependent glutamine metabolism contributes to drug resistance, as inhibition of glutaminase prevents resistance. Citation Format: Taru E. Muranen, Jonathan Coloff, Laura Selfors, Amy Bui, Gordon B. Mills, Joan S. Brugge. Long-term resistance to PI3K/mTOR inhibition requires increased expression of c-myc and YAP. [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 4451. doi:10.1158/1538-7445.AM2013-4451
737–2 Heart Fatty Acid-binding Protein can Provide a Higher Level of Accuracy than Myoglobin for the Early Detection of Acute Myocardial Infarction
Authors: Junnichi Ishii, Masanori Nomura, Toshikazu Ando, Mamoru Kimura, Hiroshi Kurokawa, Takeshi Kondo, Yoshihiko Watanabe, Hitoshi Hishida
Journal: Journal of the American College of Cardiology (1995)
Ampicillin and mononucleosis.
Authors: I J Nazareth
Journal: BMJ (1971)

The atd angle for the right hand is 102' and for the left hand 88', the sum of right and left being 190'.This value is very high, coming above the mean of 162' for Down's syndrome,7 yet not so high as the mean of 216' in Patau's syndrome.8Finger prints show an unusually complex pattern of six whorls, three ulnar loops, and one double loop (see Table ).
Abstract P4-13-06: Association of Age, Obesity and Incident Breast Cancer Phenotypes
Authors: R Scheri, S Power, J Marks, V Seewaldt, K Marcom, S Hwang
Journal: Cancer Research (2012)

Abstract Background: Obesity has been shown to be associated with increased risk of breast cancer in postmenopausal women. However, it is unclear whether this risk is isolated to a specific phenotype. We hypothesized that the increased levels of insulin, IGF-1 and estrogens associated with obesity preferentially drive an increased proportion of the luminal A phenotype of breast cancer. Methods: Between 2008 and 2011, 1001 women were diagnosed with invasive breast cancer at Duke University Medical Center and had weight and height recorded at the time of diagnosis. Tumor phenotypes were based on hormone receptor (HR: ER− and/or PR-positive) and Her2 testing with subtypes defined as follows: Luminal A: HR(+), Her2(−); Luminal B: HR(+), Her2(−); Her2: HR(−), Her2(+); triple negative: HR(−), Her2(−). Results: Median age of the cohort was 55.7 years; median BMI was 27.7. As expected, increasing BMI was associated with older age, with BMI almost evenly distributed between three groups: ≤ 25, 25–30, and &amp;gt;30. In the overall group, proportion of luminal B, Her2, and triple negative subtypes did not differ by BMI; however the proportion of patients with luminal A cancer increased from 65% for the lowest BMI group to 70% for the highest BMI group. Analysis stratified by age ≤ 40, 40 to 59, and ≥60 years showed a lower proportion of the triple-negative (19% vs. 6% vs. 4%, p &amp;lt; 0.001) and higher proportion of the luminal A (11% vs. 23% vs. 32%; p &amp;lt; 0.001) phenotype with older age group. This finding was limited to women with higher BMI only. Conclusions: Although there were no trends observed between BMI and incident phenotype in the overall cohort, age stratified analysis revealed striking correlations. High BMI was associated with triple negative phenotype in the youngest age group and luminal A phenotype in older age groups. These results suggest that obesity likely exerts different effects on tumor progression based on patient age and/or menopausal status. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-06.
Screening for Coronary Artery Disease
Authors: GEORGE A. DIAMOND
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 October 1987Screening for Coronary Artery DiseaseGEORGE A. DIAMOND, M.D.GEORGE A. DIAMOND, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-107-4-594_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Detrano and Froelicher (1) recently proposed using epidemiologic follow-up as a referent standard for defining the sensitivity and specificity of screening tests for coronary artery disease. Despite the appeal of this approach, it has an important fundamental limitation.Assume that a hypothetical test is used to define two prognostic subsets: a high-risk group of 200 patients with positive test responses, 20 of whom die during the next year (a 10% annual mortality), and a low-risk group of 800 patients with negative test responses, only 8 of whom die during the next year (a 1% annual mortality). At...Reference1. DETRANOFROELICHER RV. A logical approach to screening for coronary artery disease. Ann Intern Med. 1987;106:846-52. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cedars-Sinai Medical Center Los Angeles, CA 90048 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByInternational application of a new probability algorithm for the diagnosis of coronary artery disease 1 October 1987Volume 107, Issue 4Page: 594-595KeywordsEpidemiologyMortalityPatientsSpecificityStable coronary artery disease Issue Published: 1 October 1987 PDF DownloadLoading ...
Letter: Contraceptive practice and unplanned pregnancy in students.
Authors: L King
Journal: BMJ (1975)

The conclusion from a study of Australian university students that the proportion of university women experiencing sexual intercourse and the proportion of sexually active university women using contraceptives were greater than that found in Britain and America is challenged from the British experience. In Cambridge, England, the proportion of sexually experience undergraduate and secretarial female students was 57%, compared with 62% in the Australian study. When analyzed by age, the Australian study indicated that 15% of the women had engaged in sexual congress by the age of 16, and 95% had done so by the age of 19. These figures approximated those for non-university students in Britain. However, 89% of the British undergraduates and 72% of non-university students had used a reliable method of contraception on every occasion of sexual intercourse, compared with 49% in the Australian study. Also, 74% of the British undergraduates used oral contraceptives (OC), while only 30% used OCs in the Australian study. Nonetheless, only 60% of the experienced British women and 35% of the men felt that contraceptive advice was adequately available. Apprehension that OCs are regarded as the only reliable method of contraception available is expressed in light of circumstances in which OCs may not be suitable or available.
Delayed Enhancement and T2-Weighted Cardiovascular Magnetic Resonance Imaging Differentiate Acute From Chronic Myocardial Infarction
Authors: Hassan Abdel-Aty, Anja Zagrosek, Jeanette Schulz-Menger, Andrew J. Taylor, Daniel Messroghli, Andreas Kumar, Michael Gross, Rainer Dietz, Matthias G. Friedrich
Journal: Circulation (2004)

Delayed enhancement (DE) cardiovascular magnetic resonance (CMR) detects acute and chronic myocardial infarction (MI) by visualizing contrast media accumulation in infarcted segments. T2-weighted CMR depicts infarct-related myocardial edema as a marker of acute but not chronic myocardial injury. We investigated the clinical utility of an approach combining both techniques to differentiate acute from chronic MI.Seventy-three MI patients were studied in 2 groups. Group A consisted of 15 acute MI patients who were studied twice, on day 1 and 3 months after MI. In group B, 58 patients with acute or chronic MI underwent 1 CMR scan. T2-weighted and DE images of matched slices were acquired on a 1.5-T system. In group A, quantitative segmental and region of interest-based analyses were performed to observe signal changes between the acute and chronic phases. In group B, T2-weighted and DE images were examined visually by 2 blinded observers for the presence or absence of hyperintense areas in corresponding segments. For infarct localization, coronary angiography and/or ECG changes served as the reference standard. In group A, the contrast-to-noise ratio on T2-weighted images dropped in the infarcted segments from 2.7+/-1.1 on day 1 to 0.1+/-1.2 after 3 months (P<0.0001). There was no significant change in contrast-to-noise ratio in DE images (1.9+/-1.5 versus 1.3+/-1.0; P=NS). The qualitative assessment of T2-weighted and DE images in group B yielded a specificity of 96% to differentiate acute from chronic lesions.An imaging approach combining DE and T2-weighted CMR accurately differentiates acute from chronic MI.
No Effect of Bromocriptine in Acromegaly
Authors: Jörgen Lindholm, John Riishede, Sanne Vestergaard, Lotte Hummer, Ole Faber, Claus Hagen
Journal: New England Journal of Medicine (1981)

Although bromocriptine, a dopamine receptor agonist, is now widely used in the treatment of acromegaly, there have been no controlled trials of its biochemical or clinical effects on this disorder. We assessed its effects in a double-blind, crossover study. Eighteen patients with acromegaly were given bromocriptine and placebo alternately for three months per medication. Their responses to oral glucose-tolerance tests during the two regimens did not differ significantly. The number of patients noting amelioration of clinical symptoms during treatment with bromocriptine was almost identical to the number with clinical improvement during placebo. We conclude that it remains doubtful whether bromocriptine has a beneficial effect in acromegaly.
Antonovsky’s Sense of Coherence: Trait or State?
Authors: Ulrich Schnyder, Stefan Büchi, Tom Sensky, Richard Klaghofer
Journal: Psychotherapy and Psychosomatics (2000)

&lt;i&gt;Background:&lt;/i&gt; The aim of this study was first to analyze the stability of Antonovsky’s Sense of Coherence (SOC) as a measure of a person’s world view over time; secondly, to investigate its relationship with depression and anxiety. &lt;i&gt;Methods:&lt;/i&gt; Data from two longitudinal studies were used: a study of severely injured accident victims (n = 96), and a study of patients suffering from rheumatoid arthritis (RA, n = 60). The 13 items short version of the SOC scale and measures of depression and anxiety (Symptom Checklist, Hospital Anxiety and Depression Scale) were administered repeatedly over 6–12 months in both studies. &lt;i&gt;Results:&lt;/i&gt; In the sample of accident victims, a significant decrease in the SOC mean score was observed during the first half year after the accident. During the same time period, symptoms of anxiety and depression decreased significantly. In the second half year after the accident, SOC as well as measures of psychopathology remained stable. RA patients showed high stability of SOC and measures of anxiety and depression over time. In both samples, between-time correlations of SOC scores were high (r ≥ 0.70, p &lt; 0.01), indicating a high test-retest stability of SOC. Furthermore, in both samples, significant negative correlations of a moderate to high degree (r = –0.28 to –0.73, p &lt; 0.01) were found between SOC and measures of anxiety and depression. &lt;i&gt;Conclusions:&lt;/i&gt; SOC can be seen as a relatively stable (trait) measure. However, traumatic events such as life-threatening accidents may change a person’s world view and thus their SOC, even if psychiatric symptoms abate. This suggests that SOC is not merely a proxy measure of psychopathology, but rather a partially independent, general measure of a person’s world view.
Rubella Vaccination-Reply
Authors: Stephen C. Schoenbaum
Journal: JAMA (1976)

<h3>In Reply.—</h3> Dr Nitzkin has cited a paper by Sinclair et al in which the sample of patients on whom premarital rubella titers were performed was said to represent "predominantly lower socioeconomic groups"; 46.5% of Cubans, 7.3% of blacks, and 22.7% of others were susceptible. Of Cubans living in the United States prior to the 1964 epidemic, 40% were susceptible. In that study, no attempt was made to indicate that this difference in susceptibility among ethnic groups within the lower socioeconomic class was related to contact with children in and around the home environment. Also, no mention was made of differences in seroconversion during the childbearing years. Our data indicate that primiparas, whether young or old, have a greater risk of having a baby with rubella syndrome. While ethnic and urbanrural differences in rubella susceptibility have been documented in the past, we do not believe that they are relevant to
Expanding the Donor Pool
Authors: Emilio Ramos, Sola Aoun, William E. Harmon
Journal: Journal of the American Society of Nephrology (2002)

The short-term success rate of cadaveric renal transplants has improved dramatically during the past decade. In 1990, one-year graft survival rates were about 70%; by 2000, they were greater than 90% (United States Renal Data System, 2001). Unfortunately, as transplantation has become more
The Relief of Resistant Edema by Utilization of a Sump Phenomenon
Authors: FERDINAND R. SCHEMM, AUGUSTO A. CAMARA
Journal: Circulation (1955)

Fourteen massively edematous patients with either cardiac disease or nephritis, who had hydrothorax and/or ascites, have proved resistant to the usual diuretic measures, but have been relieved of edema by repeated aspirations of fluid from either the pleural or peritoneal spaces. In the intervals between aspirations the fluid of the interstitial space appeared to seep readily into the sump from which fluid had just been removed. The repeated aspirations did not result in hyponatremia nor hypoproteinemia in these cases. As a means of by-passing "`reluctant" kidneys the utilization of the sump phenomenon has proved simple, safe and effective in some very obstinate cases.
Monitoring in chronic disease: a rational approach
Authors: Paul Glasziou, Les Irwig, David Mant
Journal: BMJ (2005)

ConclusionsClinical guidelines provide a useful reference for practising clinicians.However, they are often long, not easily approachable, and therefore underused.The sample case summaries presented here and the treatment flow chart in figure 1 provide a basis for the practical implementation of current guidelines and more recent clinical trial evidence.
DIFFERENTIATION OF T CELLS INDUCED BY PREPARATIONS FROM THYMUS AND BY NONTHYMIC AGENTS
Authors: M. P. Scheid, M. K. Hoffmann, K. Komuro, U. Hämmerling, J. Abbott, E. A. Boyse, G. H. Cohen, J. A. Hooper, R. S. Schulof, A. L. Goldstein
Journal: The Journal of Experimental Medicine (1973)

Summary of Experiments Showing Generation of T Cells from Precursor Cells under the Influence of Thymic and Nonthymlc Agents Material tested for inducer activity Criterion of T cell induction Source Mouse thymus Mouse spleen Description* Expression of TL or Thy-1 antigen Fr. 2 (KK) Fr. 2 (KK) Medium II: in I: in vitro~ nu/nu mice§ Induced cells % 20 <10 20,40 Mouse thymus Calf thymus Calf thymus Calf thymus Calf thymus Calf spleen Calf muscle Rat thymus Chicken thymus Human thymus Fr. 3 Fr. 2 Ft. 3 5 6 Ft. 3 Fr. 3 Ft. 2 Fr. 2 Ft. 3 20-23 <10 <10 m Calf thymus¶ (AG) 40-45 (KK) 20-25 (AG) 40-45 (AG) 25-30 (AG) 18-22 (AG) 40-45 (AG) 40-45 (KK) 20-25 (KK) 25-30 (AG) 25-30 20 25 20-25 15-19 < 10, < l0 25 10 30 <10 Appearance of helper effect in vitroll cAMP DB-cAMP Poly A:U Endotoxin BSA, Medium Ft. 2 (KK) + Aminophylline Fr. 2 (KK) + Insulin Fr. 2 (KK) + Medium PFC/culture 5th exp. 24 ~10 Because of space limitations, details of materials and methods can be indicated for the most part only by key references to where full descriptions can be found. * Fr = fraction. (KK) = fraction prepared by Dr. K. Komuro according to Goldstein
Nine in 10 primary care trusts are rationing access to four procedures
Authors: N. Hawkes
Journal: BMJ (2012)

Nine out of 10 primary care trusts now have policies in place to limit access for patients to at least one of four procedures deemed “non-urgent” or of “limited/low clinical value”—joint replacement, cataract surgery, tonsillectomy, and bariatric surgery.

Freedom of information requests by GP Magazine to all 151 trusts in England elicited 101 responses.1 Only eight of those responding said that they had no thresholds or limits on referrals: Airedale, Birmingham East and North, Bradford, Devon, Heart of Birmingham, Isle of Wight, Oldham, and Solihull. The rest had at least one limit in place, and 27 limited all four procedures.

Tonsillectomies were hardest hit, with 89% of trusts having limits in place. Two thirds limited cataract surgery …
Association of primary sclerosing cholangitis with HLA-B8.
Authors: R W Chapman, Z Varghese, R Gaul, G Patel, N Kokinon, S Sherlock
Journal: Gut (1983)

The frequency of HLA antigens was studied in 25 patients with primary sclerosing cholangitis and compared with a control group of 562 kidney donors. Fourteen patients also had ulcerative colitis. A significant increase in the frequency of HLA-B8 (60%) was found in the primary sclerosing cholangitis patients compared with controls (25%) (p less than 0.001). HLA-B8 was found in eight patients with ulcerative colitis. The frequency of HLA-B12 was significantly decreased (8%) compared with controls (30%) (p less than 0.02). Piecemeal necrosis was observed on liver histology in 66% of HLA-B8 positive and 50% of HLA-B8 negative patients. Low titres of serum autoantibodies were frequently found in the primary sclerosing cholangitis group but did not correspond to the presence of HLA-B8. Raised serum concentrations of IgM and IgG were not related to HLA-B8. This study has shown that in patients with primary sclerosing cholangitis there exists a disease susceptibility gene closely associated with the B locus of the major histocompatibility complex which may be modified by other factors such as ulcerative colitis. Patients with ulcerative colitis and HLA-B8 may be particularly liable to develop primary sclerosing cholangitis.
Differences in Both Total and Specific Ig E Against Mites, Cockroach and Ascaris Lumbricoides Among Colombian Asthmatic Children in a Poor Communities within the Colombian Caribbean Coast
Authors: Eduardo Alberto Egea, Daryluz Mendoza, Jorge Acosta, Gloria Egea, Fernado De lacruz, Gloria Tulia Garavito De Egea
Journal: Journal of Allergy and Clinical Immunology (2015)
Myeloprotective effect of short‐course high‐dose methylprednisolone treatment before consolidation therapy in children with acute myeloblastic leukemia
Authors: Selin Aytaç Elmas, Mualla Çetin, Murat Tuncer, Gönül Hiçsönmez
Journal: American Journal of Hematology (2005)

Abstract In our previous studies, short‐course high‐dose methylprednisolone (HDMP) has been shown to shorten the chemotherapy‐induced neutropenic period by stimulating the CD34 + hematopoietic progenitor cells in children with acute leukemia. In this study, we investigate the role of short‐course HDMP on induction of a myeloprotective effect when administered before consolidation therapy consisting of high‐dose cytosine arabinoside and daunorubicin. Thirty‐four consecutive newly diagnosed children with acute myeloblastic leukemia (AML) who received 64 courses of consolidation regimen were entered into the study. The patients received HDMP (group A) at a daily dose of 30 mg/kg methylprednisolone starting 4 days before the initiation of consolidation therapy. The control group did not receive HDMP (group B). There were no differences in the white blood cell (WBC) and absolute neutrophil counts (ANC) between group A (at day –4) and group B (at day 0) at the beginning of the study (medians: 3 × 10 9 /L vs. 3.2 × 10 9 /L and 1.5 × 10 9 /L vs. 1.7 × 10 9 /L, respectively). The WBC count increased significantly from 3 × 10 9 /L to 6.4 × 10 9 /L, and ANC increased from 1.5 × 10 9 /L to 3.9 × 10 9 /L after 4 days of HDMP treatment in group A ( P &lt; 0.01). Following high‐dose chemotherapy, the median values of WBC and ANC also remained higher than the control values during the 16 days of the follow‐up period. The neutropenic period was significantly shorter in the HDMP group than in the control group (9 ± 5.2 days vs. 22 ± 4.7 days) ( P &lt; 0.05). The duration of hospitalization and the interval between two chemotherapy cycles were significantly decreased in group A when compared group B (9 ± 2.7 vs. 14 ± 2.7 days; 22 ± 4.7 vs. 26 ± 4.2 days, respectively) ( P &lt; 0.05). Moreover, following consolidation therapy, the number of patients with ANC values below 0.5 × 10 9 /L was lower in group A when compared the group B. In conclusion, the administration of short‐course (4 days) HDMP before high‐dose chemotherapy has been found to be beneficial for reducing the duration and severity of neutropenia. Further studies with short‐course HDMP are required to evaluate its myeloprotective effects in patients with other malignancies. Am. J. Hematol. 80:1–5, 2005. © 2005 Wiley‐Liss, Inc.
Underdiagnosis and undertreatment of cardiovascular risk factors in patients with moderate to severe psoriasis
Authors: Alexa B. Kimball, Philippe Szapary, Ulrich Mrowietz, Kristian Reich, Richard G. Langley, Yin You, Ming-Chun Hsu, Newman Yeilding, Daniel J. Rader, Nehal N. Mehta
Journal: Journal of the American Academy of Dermatology (2011)
Soluble receptors for tumor necrosis factor are markers for clinical course but not for major metabolic changes in human immunodeficiency virus infection
Authors: Mieke H. Godfried, Johannes A. Romijn, Tom van der Poll, Gerrit J. Weverling, Eleonora P.M. Corssmit, Erik Endert, Jan K. Eeftinck Schattenkerk, Hans P. Sauerwein
Journal: Metabolism (1995)
GATA-3 regulates the self-renewal of long-term hematopoietic stem cells
Authors: Catherine Frelin, Robert Herrington, Salima Janmohamed, Mary Barbara, Gary Tran, Christopher J Paige, Patricia Benveniste, Juan-Carlos Zuñiga-Pflücker, Abdallah Souabni, Meinrad Busslinger, Norman N Iscove
Journal: Nature Immunology (2013)