tbuckley/cabot-search huggingface dataset:
Effect of Breast Augmentation on the Accuracy of Mammography and Cancer Characteristics
Authors: Diana L. Miglioretti
Journal: JAMA (2004)

Breast augmentation is not associated with an increased risk of breast cancer; however, implants may interfere with the detection of breast cancer thereby delaying cancer diagnosis in women with augmentation.To determine whether mammography accuracy and tumor characteristics are different for women with and without augmentation.A prospective cohort of 137 women with augmentation and 685 women without augmentation diagnosed with breast cancer between January 1, 1995, and October 15, 2002, matched (1:5) by age, race/ethnicity, previous mammography screening, and mammography registry, and 10 533 women with augmentation and 974 915 women without augmentation and without breast cancer among 7 mammography registries in Denver, Colo; Lebanon, NH; Albuquerque, NM; Chapel Hill, NC; San Francisco, Calif; Seattle, Wash; and Burlington, Vt.Comparison between women with and without augmentation of mammography performance measures and cancer characteristics, including invasive carcinoma or ductal carcinoma in situ, tumor stage, nodal status, size, grade, and estrogen-receptor status.Among asymptomatic women, the sensitivity of screening mammography based on the final assessment was lower in women with breast augmentation vs women without (45.0% [95% confidence interval [CI], 29.3%-61.5%] vs 66.8% [95% CI, 60.4%-72.8%]; P =.008), and specificity was slightly higher in women with augmentation (97.7% [95% CI, 97.4%-98.0%] vs 96.7% [95% CI, 96.6%-96.7%]; P<.001). Among symptomatic women, both sensitivity and specificity were lower for women with augmentation compared with women without but these differences were not significant. Tumors were of similar stage, size, estrogen-receptor status, and nodal status but tended to be lower grade (P =.052) for women with breast augmentation vs without.Breast augmentation decreases the sensitivity of screening mammography among asymptomatic women but does not increase the false-positive rate. Despite the lower accuracy of mammography in women with augmentation, the prognostic characteristics of tumors are not influenced by augmentation.
Transforming Growth Factor-β Suppresses Nonmetastatic Colon Cancer through Smad4 and Adaptor Protein ELF at an Early Stage of Tumorigenesis
Authors: Yi Tang, Varalakshmi Katuri, Radhika Srinivasan, Franz Fogt, Robert Redman, Girish Anand, Anan Said, Thomas Fishbein, Michael Zasloff, E. Premkumar Reddy, Bibhuti Mishra, Lopa Mishra
Journal: Cancer Research (2005)

Although transforming growth factor-beta (TGF-beta) is both a suppressor and promoter of tumorigenesis, its contribution to early tumor suppression and staging remains largely unknown. In search of the mechanism of early tumor suppression, we identified the adaptor protein ELF, a beta-spectrin from stem/progenitor cells committed to foregut lineage. ELF activates and modulates Smad4 activation of TGF-beta to confer cell polarity, to maintain cell architecture, and to inhibit epithelial-to-mesenchymal transition. Analysis of development of colon cancer in (adult) elf+/-/Smad4+/-, elf+/-, Smad4+/-, and gut epithelial cells from elf-/- mutant mouse embryos pinpoints the defect to hyperplasia/adenoma transition. Further analysis of the role of ELF in human colorectal cancer confirms reduced expression of ELF in Dukes' B1 stage tissues (P < 0.05) and of Smad4 in advanced colon cancers (P < 0.05). This study indicates that by modulating Smad 4, ELF has a key role in TGF-beta signaling in the suppression of early colon cancer.
In defence of eponyms.
Authors: V Wright
Journal: BMJ (1991)

done a complete post-take ward round, and returned to pick them up as they finished a leisurely cup of coffee.The difference is that I know that if I forgo that ward round and later discover that something is amiss I will have to spend the whole evening there sorting it out, instead of doing whatever I had planned for what we consultants laughingly call "off duty."The candidates also need to see some of the professional satisfaction and the heartache that each day brings.I also suggest to them that, to make their decision to apply to medical school, they should spend one or two days with a hospital consultant, such as myself, perhaps a week with their general practitioner, and a fortnight on the "executive side" actually doing something with the sick, such as working in an old folks' home or a handicapped children's home.If, after all of this, they still feel comfortable with this environ- ment, are not revolted, and are not physically or mentally overtired then they have the potential to go into medicine, qualify, and find a fulfilling niche.
Oxidative stress influences cholesterol efflux in THP-1 macrophages: Role of ATP-binding cassette A1 and nuclear factors☆
Authors: V MARCIL, E DELVIN, A SANE, A TREMBLAY, E LEVY
Journal: Cardiovascular Research (2006)

Understanding the mechanisms involved in oxidative stress-induced foam cell formation is of fundamental importance for atherosclerosis. Our aim was to characterize the effects of oxidative stress on key receptors of macrophage cholesterol homeostasis, on the nuclear transcription factors PPAR and LXR regulating their expression, and on macrophage cholesterol handling.The incubation of macrophages derived from the human monocyte cell line THP-1 with iron (100 microm)/ascorbate (1000 microm) for a period of 4 h induced a strong peroxidation, as demonstrated by the elevation of malondialdehyde (220%, P < 0.001). The production of lipid peroxidation affected cholesterol efflux, which was probably due to decreased ABCAI gene and protein expression. On the other hand, cholesterol influx remained unchanged as did the mRNA and protein levels of SR-BI and CD36, important protein receptors that participate in cholesterol import. Experiments using RT-PCR showed that the ABCAI modulation was orchestrated by the nuclear receptors LXRalpha, LXRbeta, PPARalpha, and PPARgamma. Treatment with powerful antioxidants (Trolox and BHT) prevented the adverse effects of iron-ascorbate on cholesterol movement, conceivably supporting the role of oxidative stress.Our results show that oxidative stress can directly be induced in macrophages and concomitantly impairs the expression of receptors involved in cholesterol flux, which could influence foam cell formation and atherosclerosis development.
Lack of In Vivo Function of Osteopontin in Experimental Anti-GBM Nephritis
Authors: JOHN MICHAEL BONVINI, URSULA SCHATZMANN, BEATRICE BECK-SCHIMMER, LI KANG SUN, SUSAN R. RITTLING, DAVID T. DENHARDT, MICHEL LE HIR, RUDOLF P. WÜTHRICH
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Osteopontin (Opn) is a potent chemoattractant for mononuclear cells that is upregulated in various inflammatory states of the kidney. Opn is believed to contribute to mononuclear cell infiltration and renal injury. The importance of Opn was examined in vivo in rapidly progressive glomerulonephritis in Opn knockout mice. Glomerulonephritis was induced by intravenous injection of rabbit anti-mouse glomerular basement membrane antiserum in mice that had been presensitized to rabbit IgG. Immunologic responsiveness to rabbit IgG (assessed by cutaneous delayed-type hypersensitivity and antibody titers) showed no significant difference between wild-type and Opn -/- mice. Proteinuria was also similar in both groups. Glomerular crescent formation was not different in Opn +/+ and -/- groups (26 ± 6% versus 29 ± 7%). Tubulointerstitial infiltration was assessed qualitatively and showed no significant difference between the two genotypes. Formation of thrombi in the glomerular capillaries on a scale from 0 to 3 also showed no significant difference (1.3 ± 0.3 for Opn +/+ and 1.4 ± 0.3 for Opn -/- mice). Northern blot analysis of total kidney RNA showed a 5.1-fold increase of Opn expression in Opn +/+ mice compared with untreated controls and the absence of expression in Opn -/- mice, as expected. Regulated upon activation, normal T cell expressed and secreted (RANTES) and monocyte chemoattractant protein-1 mRNA levels were also markedly upregulated with no significant difference between the two strains, excluding compensatory overexpression of these two chemokines in Opn -/- mice. It is concluded that the known upregulation of Opn in murine anti-glomerular basement membrane nephritis does not significantly contribute to the glomerular and tubulointerstitial mononuclear cell infiltration in this model.
The Risk of Overall Mortality in Patients With Type 2 Diabetes Receiving Glipizide, Glyburide, or Glimepiride Monotherapy
Authors: Kevin M. Pantalone, Michael W. Kattan, Changhong Yu, Brian J. Wells, Susana Arrigain, Anil Jain, Ashish Atreja, Robert S. Zimmerman
Journal: Diabetes Care (2010)

OBJECTIVE Sulfonylureas have historically been analyzed as a medication class, which may be inappropriate given the differences in properties inherent to the individual sulfonylureas (hypoglycemic risk, sulfonylurea receptor selectivity, and effects on myocardial ischemic preconditioning). The purpose of this study was to assess the relationship of individual sulfonylureas and the risk of overall mortality in a large cohort of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record (EHR) system to identify 11,141 patients with type 2 diabetes (4,279 initiators of monotherapy with glyburide, 4,325 initiators of monotherapy with glipizide, and 2,537 initiators of monotherapy with glimepiride), ≥18 years of age with and without a history of coronary artery disease (CAD) and not on insulin or a noninsulin injectable at baseline. The patients were followed for mortality by documentation in the EHR and Social Security Death Index. Multivariable Cox models were used to compare cohorts. RESULTS No statistically significant difference in the risk of overall mortality was observed among these agents in the entire cohort, but we did find evidence of a trend toward an increased overall mortality risk with glyburide versus glimepiride (hazard ratio 1.36 [95% CI 0.96–1.91]) and glipizide versus glimepiride (1.39 [0.99–1.96]) in those with documented CAD. CONCLUSIONS Our results did not identify an increased mortality risk among the individual sulfonylureas but did suggest that glimepiride may be the preferred sulfonylurea in those with underlying CAD.
Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance
Authors: Andrew W Duncan, Frédérique M Rattis, Leah N DiMascio, Kendra L Congdon, Gregory Pazianos, Chen Zhao, Keejung Yoon, J Michael Cook, Karl Willert, Nicholas Gaiano, Tannishtha Reya
Journal: Nature Immunology (2005)
Fetal, Developmental, and Parental Influences on Childhood Systolic Blood Pressure in 600 Sib Pairs
Authors: David A. Leon, Ilona Koupil, Vera Mann, Torsten Tuvemo, Gunilla Lindmark, Rawya Mohsen, Liisa Byberg, Hans Lithell
Journal: Circulation (2005)

Little is known about the contribution of maternal and paternal factors to the inverse association between birth weight and later blood pressure in human offspring. A study of within- and between-family associations of birth weight with blood pressure, which collected data on both parents, would address this gap in our knowledge.The study examined families composed of mother, father, and 2 full sibs delivered between 38 and 41 weeks' gestation within 36 months of each other. A total of 1967 families meeting our inclusion criteria were contacted and 602 were examined (children 5 to 14 years old, 1998 to 2000). Birth weight and gestational age were available from obstetric records. Systolic blood pressure in childhood was inversely associated with birth weight within families (-2.3 mm Hg/kg, 95% CI -4.4 to -0.3) after adjustment for gestational age, sex, height, and weight at examination. The between-family effect (-1.5 mm Hg/kg, -3.1 to 0.0) was strengthened on adjustment for maternal and paternal height and weight, whereas adjustment for paternal and maternal systolic blood pressure at examination independently attenuated the effect.The existence of an inverse association of birth weight with systolic blood pressure within families (adjusted for height and weight at examination) demonstrates that factors that vary between pregnancies in the same woman (including fetal genotype) can influence the later blood pressure of offspring. We conclude that this apparent fetal programming effect on blood pressure will not be eliminated solely by interventions aimed at modifying growth and cumulative nutritional status from conception through childhood or other fixed characteristics of future mothers.
MiR-328 promotes glioma cell invasion via SFRP1-dependent Wnt-signaling activation
Authors: Sabit Delic, Nadine Lottmann, Anja Stelzl, Franziska Liesenberg, Marietta Wolter, Silke Götze, Marc Zapatka, Yuzuru Shiio, Michael C. Sabel, Jörg Felsberg, Guido Reifenberger, Markus J. Riemenschneider
Journal: Neuro-Oncology (2013)

Diffusely infiltrative growth of human astrocytic gliomas is one of the major obstacles to successful tumor therapy. Thorough insights into the molecules and pathways signaling glioma cell invasion thus appear of major relevance for the development of targeted and individualized therapies. By miRNA expression profiling of microdissected human tumor biopsy specimens we identified miR-328 as one of the main miRNAs upregulated in invading glioma cells in vivo and further investigated its role in glioma pathogenesis. We employed miRNA mimics and inhibitors to functionally characterize miR-328, 3′ untranslated region luciferase assays, and T-cell factor/lymphoid enhancer factor reporter assays to pinpoint miR-328 targets and signaling pathways, and analyzed miR-328 expression in a large panel of gliomas. First, we corroborated the invasion-promoting role of miR-328 in A172 and TP365MG glioma cells. Secreted Frizzled-related protein 1 (SFRP1), an inhibitor of Wnt signaling, was then pinpointed as a direct miR-328 target. SFRP1 expression is of prognostic relevance in gliomas with reduced expression, being associated with significantly lower overall patient survival in both the Repository of Molecular Brain Neoplasia Data (REMBRANDT) and The Cancer Genome Atlas. Of note, miR-328 regulated both SFRP1 protein expression levels and Wnt signaling pathway activity. Finally, in human glioma tissues miR-328 appeared to account for the downregulation of SFRP1 preferentially in lower-grade astrocytic gliomas and was inversely related to SFRP1 promoter hypermethylation. Taken together, we report on a novel molecular miR-328–dependent mechanism that via SFRP1 inhibition and Wnt activation contributes to the infiltrative glioma phenotype at already early stages of glioma progression, with unfavorable prognostic implications for the final outcome of the disease.
Peanut Oral Immunotherapy (OIT) Induces a Transient Increase in CD4+CD25+FoxP3+ Tregs and a Sustained Decrease of Th2-type Cytokines
Authors: M. Kulis, P. Varshney, A. Scurlock, B. Vickery, T. Perry, S. Jones, A.W. Burks
Journal: Journal of Allergy and Clinical Immunology (2011)
Accelerated Drug Approval: FDA May Get Tougher; Companies Cite Hurdles
Authors: M. Goozner
Journal: JNCI Journal of the National Cancer Institute (2011)

T he U.S. Food and Drug Administration’s Oncology Drugs Advisory Committee (ODAC), at its February meeting, urged the agency to raise its standards for granting experimental cancer drugs accelerated approval on the basis of surrogate markers. ODAC also called on drug developers to conduct more tests more rapidly to determine whether drugs given accelerated approval actually extend life. The 16-member committee concluded that single-arm trials, which were used to justify more than half the accelerated approvals since the program’s inception in 1992, should be accepted only for rare cancers or when the evidence of effi cacy from a single-arm trial was overwhelmingly positive (this happened with imatinib[Gleevec] for Philadelphia chromosome – positive chronic myeloid leukemia). The committee also reached a consensus — no votes took place at the meeting — that the FDA should require at least two controlled trials as fi nal proof of effi cacy and recommended that those trials should be under way when accelerated approval is granted. “There will be exceptions to that for rare diseases and perhaps some other niche areas where there is a very high positive signal in the accelerated approval trial,” said Wyndham Wilson, M.D., Ph.D., chief of the lymphoma therapeutics section of the National Cancer Institute’s Center for Cancer Research, who chaired the committee. “There may be some overriding reason for not doing two [trials], but two ought to be the standard.”
Survival After Coronary Revascularization, With and Without Mitral Valve Surgery, in Patients With Ischemic Mitral Regurgitation
Authors: Benjamin H. Trichon, Donald D. Glower, Linda K. Shaw, Christopher H. Cabell, Kevin J. Anstrom, G. Michael Felker, Christopher M. O’Connor
Journal: Circulation (2003)

The most appropriate treatment for patients with ischemic mitral regurgitation (IMR) is often debated. We compared the survival rates of patients with IMR undergoing different treatment strategies, namely: medical therapy, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and CABG + mitral valve (MV) surgery.Patients undergoing catheterization between 1986 and 2001 were included. IMR was defined as: >or=grade 2+ mitral regurgitation (MR) and significant coronary artery disease (CAD) without primary mitral valve disease. Patients undergoing catheterization for the evaluation of congenital or other valvular heart disease were excluded. Multivariable Cox proportional hazards modeling was utilized to assess the independent relation between treatment and survival. Propensity score methods were used to correct for the nonrandom assignment of treatment. Of the 2,757 patients who met study criteria: 1,305 were treated medically, 537 underwent PCI, 687 underwent CABG, and 228 underwent CABG + MV surgery. The median duration of follow-up was 3.2 (0.9, 7.1) years. Patients undergoing CABG + MV surgery had more severe MR and more severe heart failure than those treated by other modalities. After adjusting for differences in baseline characteristics, patients undergoing PCI, CABG, and CABG + MV surgery had a 31% (hazards ratio [HR]=0.69; P=0.0001), 42% (HR=0.58; P=0.0001), and 42% (HR=0.58; P=0.0001) reduction in the risk of death, respectively, compared with those undergoing medical therapy. The performance of mitral valve surgery with CABG was not associated with improved survival versus CABG alone (P=0.258).Among patients with IMR, treatment with PCI, CABG, or CABG + MV surgery is associated with improved survival compared with medical therapy.
A Noninvasive Imaging Modality for Cardiac Arrhythmias
Authors: John E. Burnes, Bruno Taccardi, Yoram Rudy
Journal: Circulation (2000)

Background —The last decade witnessed an explosion of information regarding the genetic, molecular, and mechanistic basis of heart disease. Translating this information into clinical practice requires the development of novel functional imaging modalities for diagnosis, localization, and guided intervention. A noninvasive modality for imaging cardiac arrhythmias is not yet available. Present electrocardiographic methods cannot precisely localize a ventricular tachycardia (VT) or its key reentrant circuit components. Recently, we developed a noninvasive electrocardiographic imaging modality (ECGI) that can reconstruct epicardial electrophysiological information from body surface potentials. Here, we extend its application to image reentrant arrhythmias. Methods and Results —Epicardial potentials were recorded during VT with a 490 electrode sock during an open chest procedure in 2 dogs with 4-day-old myocardial infarctions. Body surface potentials were generated from these epicardial potentials in a human torso model. Realistic geometry errors and measurement noise were added to the torso data, which were then used to noninvasively reconstruct epicardial isochrones, electrograms, and potentials with excellent accuracy. ECGI reconstructed the reentry pathway and its key components, including (1) the central common pathway, (2) the VT exit site, (3) lines of block, and (4) regions of slow and fast conduction. This allowed for detailed characterization of the reentrant circuit morphology. Conclusions —ECGI can noninvasively image arrhythmic activation on the epicardium during VT to identify and localize key components of the arrhythmogenic pathway that can be effective targets for antiarrhythmic intervention.
Screening for Breast Cancer
Authors: David M. Eddy
Journal: Annals of Internal Medicine (1989)

There is very good evidence that screening for breast cancer reduces mortality in women older than 50 years and suggestive but inconsistent evidence that screening is effective in reducing long-term mortality in women younger than 50 years. The probability that an average-risk woman will be diagnosed with breast cancer in the coming 10 years is about 130 in 10,000 for a 40-year-old woman, 230 in 10,000 for a 55-year-old woman, and 280 in 10,000 for a 65-year-old woman. The chance of dying from breast cancer diagnosed in the coming 10 years is about 90 in 10,000, 123 in 10,000, and 120 in 10,000 for women age 40, 55, and 65, respectively. Mathematical models based on data from controlled trials of screening programs indicate that screening annually for 10 years with breast physical examination will decrease the probability of death from breast cancer by about 25 in 10,000 for women in the three age groups and increase life expectancy by about 20 days. Adding annual mammography will decrease the probability of death from breast cancer an additional 25 in 10,000 and increase life expectancy an additional 20 days. The actual reductions in mortality observed in controlled trials are slightly lower. If women are screened annually for 10 years with breast physical examination and mammography, the chance for a false-positive result over the 10-year period is approximately 2500 in 10,000. On the population level, if 25% of women age 40 to 75 are screened annually with both examinations, deaths from breast cancer would be decreased by about 4000 in the year 2000. Net annual costs would be approximately $1.3 billion. Recommending a screening strategy requires weighing the benefits against the risks and costs.