tbuckley/cabot-search huggingface dataset:
Abstract P4-06-17: Antitumor activity of the novel mithramycin analog EC8042 in triple negative breast cancer
Authors: A Pandiella, JC Montero, D Cuenca, F Re-Louhau, LE Nuñez, F Moris, A Ocana
Journal: Cancer Research (2012)

Abstract Background: Triple negative breast cancer (TNBC) represents around 15% of all breast tumors. Therapeutic strategies in TNBC are mainly based on classical chemotherapeutic agents, with limited success in the metastatic setting. Here we have explored the action of a novel mithramycin analog named EC-8042 in TNBC. Methods: we used a panel of cell lines representative of triple negative tumors including BT549, HBL100, HCC-1037, HS578T, MDA-MB213, HCC-1187, HCC-3153 and HCC-70. Proliferation studies with EC-8042 were measured by MTT assays. Propidium iodide (PI) staining followed by FACS was used for cell cycle analyses and AnnexinV-fluorescein for analysis of apoptosis. Proteins involved in cell cycle control and apoptosis were evaluated by western blot. Mitochondrial membrane potential was assessed by measuring the fluorescence of tetramethylrhodamineethylester (TMRE) dye. Results: The IC50 values obtained were in the nM range, indicating that the drug had a potent effect on these cell lines. Mechanistically, the drug caused accumulation of cells in the S phase of the cell cycle at doses of 100 and 500 nM in MDA-MB231. Biochemically, EC-8042 caused an increase in cyclin E, cyclin A, cyclin D3, cyclin B, and p27, and decreased cyclin D1 and Rb phosphorylation at serine 780. These data are consistent with an action of EC-8042 on the cell cycle. Moreover, the increase in wee1 and pY15-CDK1 are in line with an effect of the drug blocking cell cycle progression through the S phase. Annexin V staining indicated that treatment with 500 nM of EC8042 provoked apoptosis, which was also revealed by PARP processing. The treatment reduced the amounts of MCL1, BCLXL, and XIAP, but did not affect BCL2 levels. Conclusion: our results indicate that EC-8042 has a strong antitumoral action on TNBC cells, which is caused by increased apoptosis and a decrease in cell cycle progression, and opens the possibility for further development of this drug in TNBC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-06-17.
THE FORMATION AND PROPERTIES OF POLIOVIRUS-NEUTRALIZING ANTIBODY
Authors: Sven-Eric Svehag, Benjamin Mandel
Journal: The Journal of Experimental Medicine (1964)

Transient 19S antibody formation was induced in rabbits by single or repeated stimuli with a small dose of poliovirus. Available evidence indicated that cessation of 19S synthesis was due to lack of continuous antigenic stimulation and not to loss of cells participating in antibody formation. "Immunological memory" in 19S antibody formation was demonstrable only within 2 to 3 days following discontinuation of synthesis but not thereafter. Following stimulation with a high dose of polio-virus both 19S and 7S antibodies were formed. The kinetics of their formation differed in several respects: (a) 19S antibody preceded 7S antibody by 1(1/2) days; (b) 19S antibody rose to peak titers at a rapid exponential rate within 1 week, while 7S antibody increased at a slow decelerating rate for 3 weeks; (c) 19S antibody formation was short-lasting while 7S antibody synthesis endured. A renewed formation of both antibodies occurred following restimulation with a high antigen dose. The secondary 19S and 7S antibody responses were similar to the respective primary responses, and the preexistence of 7S antibody synthesis did not detectably alter the secondary 19S response. Both 19S and 7S antibodies were formed and the kinetics of their formation was similar (a) for infectious and non-infectious (UV-) poliovirus antigen; (b) for the serologically unrelated poliovirus and Coxsackie B-4 virus; (c) when poliovirus was administered by different routes; (d) when 1-day-old or adult rabbits were immunized; (e) in antibody responses to poliovirus in rabbit, guinea pig, and man. Whole body x-irradiation 20 hours prior to antigenic stimulus (high dose) resulted in delayed but markedly prolonged 19S antibody formation and inhibition of 7S antibody synthesis. Thus, the formation of 19S and 7S antibody differed in (a) antigen dose requirements for induction and maintained synthesis; (b) kinetics; (c) retention of memory; and (d) sensitivity to prior x-irradiation. These differences are best explained on the assumption that the two antibodies are produced by different cells.
Bile acids induce eosinophil degranulation by two different mechanisms
Authors: K Yamazaki
Journal: Hepatology (2001)

Eosinophil infiltration and activation occur in the vicinity of the bile ducts in immune cholangiopathies. When cholangiocytes are injured, bile acids may cross the damaged biliary epithelia and affect periductal immune cells. Although immunomodulatory actions of bile acids have been well explored, their effects on eosinophils have never been examined. In this study, we tested the hypothesis that bile acids directly activate eosinophils and induce their effector functions. We found that a hydrophobic bile acid, taurine-con- jugated chenodeoxycholic acid (TCDCA), induces eosinophil degranulation in vitro via 2 different mechanisms depending on its concentration. Degranulation induced by 100 to 500 μmol/L TCDCA was an active and regulated release because it was completely abolished by a tyrosine kinase inhibitor (genistein), by a microfilament inhibitor (cytochalasin B), and by incubation at 4°C. Furthermore, eosinophils stimulated with 10 to 250 μmol/L TCDCA vigorously produced superoxide and interleukin-8 (IL-8). In contrast, at higher concentrations (e.g., ≥ 1,000 μmol/L), TCDCA induced granule protein release without concomitant superoxide production and IL-8 production. Further genistein and cytochalasin B failed to inhibit eosinophil degranulation induced by 2,500 μmol/L TCDCA, suggesting that TCDCA at this concentration induced passive degranulation via cytolysis. The analyses of cell morphology and functional viability also supported the presence of 2 mechanisms for TCDCA-induced eosinophil degranulation. Taurine-conjugated ursodeoxycholic acid, a hydrophilic bile acid, similarly activated human eosinophils at relatively low concentrations, although the potency was always lower compared with that of TCDCA. In conclusion, we have shown that bile acids are capable of directly activating eosinophils.
Abstract P4-12-07: Diabetes Increases the Risk of Breast Cancer
Authors: PJ Hardefeldt, S Edirimanne, GD Eslick
Journal: Cancer Research (2012)

Abstract Background: The hyperinsulinaemia associated with type 2 diabetes and the known proliferative effects of insulin lead to the hypothesis that diabetes mellitus increases the risk of breast cancer. The aim of this meta-analysis was to collate and analyse all primary observational studies investigating the risk of breast cancer associated with diabetes. In addition, we aimed to complete sub group analyses by both type of diabetes and gender of study participants to further clarify the origin of any such association between the two. Method: Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross checking of reference lists. Databases were searched using subject headings, keyword searches and text word searches wherever possible using the search terms ‘diabetes’ AND ‘breast cancer’ OR ‘breast carcinoma’ OR ‘breast neoplasm’. Inclusion criteria required a confirmed diagnosis of both diabetes and breast cancer, reporting of an odds ratio or data to calculate an unadjusted odds ratio (and 95% confidence interval) and the use of an internal control group as the comparator. Collated data was assessed for heterogeneity and a pooled odds ratio calculated. Results: 34 studies were included in the meta-analysis with 31 studies investigating breast cancer in women and 5 studies investigating breast cancer in men. Overall, we found a significantly increased risk of breast cancer associated with diabetes in both women (OR 1.25, 95% CI 1.13–1.38) and men (OR 1.40, 95% CI 1.10–1.79). The pooled odds ratio was consistent across both case control studies (OR 1.25, 95% CI 1.06–1.46) and cohort studies (OR 1.26, 95% CI 1.09–1.45). Heterogeneity was significant (I2 = 73.40, p &amp;lt; 0.001) and publication bias was present (p = 0.03). The 31 studies investigating breast cancer in women were sub grouped by type of diabetes with the association strengthened by a diagnosis of type 2 diabetes (OR 1.32, 95% CI 1.09–1.61) but nullified with gestational diabetes (OR 1.06, 95% CI 0.79–1.40). There were insufficient studies to calculate a pooled odds ratio of the risk of breast cancer associated with type 1 diabetes. Conclusion: Diabetes increases the risk of breast cancer in both women and men. This association is strengthened in women with type 2 diabetes and supports the hypothesis that diabetes is an independent risk factor for breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-12-07.
ULTRASTRUCTURAL MORPHOLOGY AND HISTOCHEMISTRY (ACID PHOSPHATASE) OF THE CUTANEOUS INFILTRATION BY POLYVINYLPYRROLIDONE
Authors: J. THIVOLET, T. K. LEUNG, J. DUVERNE, J. LEUNG, H. VOLLE
Journal: British Journal of Dermatology (1970)

SUMMARY.– Two new cases of skin infiltration by polyvinylpyrrolidone are reported. One had 2 types of macroscopic lesion: erythematous plaques, often with yellow pseudo‐xanthoniatous papules in the centre, localized round the neckline and the front of the thorax, and small fibromata on the thighs and legs. The other patient had slightly indurated skin in the epigastric region. The ultrastructure of the histiocyte infiltration consisted of dense bodies and vacuoles with various structural variations. The authors stress the extremely generalized nature of this infiltration, affecting all the cell types of the skin, and the presence of intermediary forms linking the dense bodies to the vacuoles. Acid phosphatase activity is present in the dense bodies and certain intermediary vacuoles but absent from the large vacuoles. It is suggested that the dense bodies represent lysosomes with enzyme accumulation which then become loaded with polyvinylpyrrolidone, thus leading to the formation of large vacuoles with no enzyme activity. The well‐developed Golgi apparatus in the histiocytes plays a part in the synthesis of lysosomal enzymes.
A theme issue in 2011 on unpublished evidence
Authors: E. Loder
Journal: BMJ (2011)

The BMJ is calling for your articles

The BMJ has long championed efforts to ensure complete publication of clinical trial results. Studies published in the BMJ and elsewhere show that unpublished or selectively reported clinical research findings lead to distorted perceptions of treatment effects.1 2 The harm is compounded when the results of individual trials are combined in systematic reviews or meta-analyses. Doctors, patients, and policy makers rely on these evidence syntheses as authoritative summaries of knowledge about clinical questions. But when important evidence is unavailable the conclusions reached by these research summaries may be wrong.

Such evidence syntheses are widely considered to represent the highest form of evidence, but as we have asked in a previous editorial, “is this a tenable world view when so much evidence is missing?”3 The existing flawed clinical evidence base cannot simply be ignored because it forms the basis for future research. The current emphasis on comparative effectiveness research, in which new treatments are compared with established treatments rather than placebo, makes tackling the problem even more urgent. If the evidence base for established treatments is …
Gastro-oesophageal reflux and tachykinins in asthma and chronic cough
Authors: A. H Morice
Journal: Thorax (2007)

A possible new therapeutic option

There is no doubt that gastro-oesophageal reflux can cause a chronic cough. However, how frequently reflux is the underlying cause in patients presenting to the readers of Thorax is a matter of much debate. This confusion can be laid squarely at the door of the gastroenterologists who have taken one symptom of acidic reflux—heartburn—and made it the sine qua non for gastro-oesophageal reflux disease. This characterisation of gastro-oesophageal reflux disease as heartburn has led to the denial of the non-acid extra-oesophageal symptoms of reflux. In reality, however, reflux is almost universal in humans because our upright posture has disrupted the anatomy of the lower oesophageal sphincter. Measurement of electrical impedance within the gullet in fact shows that only a small number of reflux episodes are acidic (below pH 4)1 and, while it takes a lot …
Belt Tightening at the NIH
Authors: Alan Blum
Journal: JAMA (1980)

SHOULD cost containment, an increasingly prominent consideration in clinical medicine, be applied equally to biomedical research? Or ought publicly financed research be shielded in some way from economic constraints, not to mention political and social pressures? As an alarm is sounded<sup>1</sup>over proposed cutbacks in allocations to the National Institutes of Health (NIH), it is necessary for physicians and other members of the health care field to seek answers to these questions. Such scrutiny may affront many researchers who rightly see themselves as devoted workers and innocent bystanders (or victims) of political tugs-of-war. Indeed, scientists at the NIH and many "alumni" throughout the country have every reason to be proud of their investigations into the cause, detection, therapy, and prevention of disease. To call the NIH the foremost biomedical research center in the world is an understatement. Even the casual visitor to its campus shares the excitement and privilege of
People... Not Patients: A Source Book for Living With Inflammatory Bowel Disease
Authors: Stephen B. Hanauer
Journal: JAMA (1986)

<i>People... Not Patients</i>was produced by a consortium of lay and professional leaders to "give people with IBD [inflammatory bowel disease] the tools to become advocates in their own behalf [and] to help them understand the diseases, learn about their legal rights, and begin to fight back." The book accomplishes these worthwhile goals by briefly reviewing what we currently understand about inflammatory bowel disease and how it is diagnosed and by providing a primer on medications and side effects, skin care, and adjusting to an ostomy. The introductory chapters are succinct, practically pertinent to everyday life for patients, and written in easily understood terms. The most emotionally provocative concepts (eg, adjusting to an ostomy, total parenteral nutrition, dealing with friends) often are accompanied by personal comments from patients who offer guidelines that helped them to adapt to life and to turn adversity into opportunity. This optimistic attitude and approach is
DNA Vaccines Encoding Ii-PADRE Generates Potent PADRE-specific CD4+ T-Cell Immune Responses and Enhances Vaccine Potency
Authors: Chien-Fu Hung, Ya-Chea Tsai, Liangmei He, T-C Wu
Journal: Molecular Therapy (2007)

It is now clear that CD4+ T cells play a crucial role in the generation of CD8+ T effector and memory T-cell immune responses. In this study, we enhanced the CD4+ T-cell immune responses in mice by constructing a DNA vaccine encoding an invariant (Ii) chain in which the class II–associated Ii peptide (CLIP) region is replaced with a CD4+ T-helper epitope, PADRE (Ii-PADRE) (invariant Pan HLA-DR reactive epitope). C57BL/6 mice vaccinated with DNA encoding Ii-PADRE showed significantly greater PADRE-specific CD4+ T-cell immune responses than mice vaccinated with DNA encoding the Ii chain alone (Ii DNA). More important, administration of DNA encoding human papillomavirus (HPV) E6 or E7 antigen with DNA encoding Ii-PADRE led to significantly stronger E6- or E7-specific CD8+ T-cell immune responses and more potent protective and therapeutic anti-tumor effects against an E6/E7-expressing tumor model in mice than administration of E6 or E7 DNA with Ii DNA. Overall, our data indicate that administration of DNA vaccines with Ii-PADRE DNA represents an effective approach to enhancing the generation of CD4+ T cells and eliciting stronger antigen-specific CD8+ T-cell immune responses. Therefore, this strategy may be expected to have significant potential for clinical translation. It is now clear that CD4+ T cells play a crucial role in the generation of CD8+ T effector and memory T-cell immune responses. In this study, we enhanced the CD4+ T-cell immune responses in mice by constructing a DNA vaccine encoding an invariant (Ii) chain in which the class II–associated Ii peptide (CLIP) region is replaced with a CD4+ T-helper epitope, PADRE (Ii-PADRE) (invariant Pan HLA-DR reactive epitope). C57BL/6 mice vaccinated with DNA encoding Ii-PADRE showed significantly greater PADRE-specific CD4+ T-cell immune responses than mice vaccinated with DNA encoding the Ii chain alone (Ii DNA). More important, administration of DNA encoding human papillomavirus (HPV) E6 or E7 antigen with DNA encoding Ii-PADRE led to significantly stronger E6- or E7-specific CD8+ T-cell immune responses and more potent protective and therapeutic anti-tumor effects against an E6/E7-expressing tumor model in mice than administration of E6 or E7 DNA with Ii DNA. Overall, our data indicate that administration of DNA vaccines with Ii-PADRE DNA represents an effective approach to enhancing the generation of CD4+ T cells and eliciting stronger antigen-specific CD8+ T-cell immune responses. Therefore, this strategy may be expected to have significant potential for clinical translation.
Potassium-Induced Lesions of the Small Bowel
Authors: Arthur C. Allen, Scott J. Boley, Leon Schultz, Solomon Schwartz
Journal: JAMA (1965)

The etiologic role of potassium in the development of characteristically circumferential, stenosing ulcers of the small bowel has been previously inferred and is now established as fact. Precisely how the potassium effects ulcerogenesis is the subject of this communication. The conclusion that an orally administered agent ulcerates the intestine by a topical, escharotic action is the natural one but the morphological and physiological evidence does not substantiate it. In our judgment, the lesion is essentially a hemorrhagic infarct which, depending on its extent and fulminance, produces edema, hemorrhage, erosion, perforation, or cicatrizing stenosis. In the majority of instances, an antedating or perhaps, concomitant organic change in the appertaining vessels may contribute to the vascular insufficiency. In other instances, the vascular insufficiency in both humans and in the experimental animal appears to occur on a functional, probably venomotor, basis and is reflected in segmental hemorrhagic infarctions.
The long-term course of cyclosporine-associated chronic nephropathy
Authors: Bryan D. Myers, Richard Sibley, Lynne Newton, Stephen J. Tomlanovich, Christopher Boshkos, Edward Stinson, John A. Luetscher, Darlene J. Whitney, David Krasny, Norman S. Coplon, Mark G. Perlroth
Journal: Kidney International (1988)
Atherosclerotic Popliteal Aneurysm in a Man Thirty-five Years Old
Authors: RAY W. GIFFORD, THOMAS W. PARKIN, JOSEPH M. JANES
Journal: Circulation (1954)

This case of atherosclerotic aneurysm of the popliteal artery is of interest because the patient was a man 35 years old and because the condition was discovered only because palpation of the peripheral arteries was included as a part of routine examination. Only after the aneurysm had been found was a history of intermittent claudication elicited. The indications for the surgical treatment of popliteal aneurysms are discussed.
Model predicts who benefits from carotid endarterectomy
Authors: Z. Kmietowicz
Journal: BMJ (1999)

A risk modelling study has been developed to identify which patients stand to benefit most from carotid endarterectomy.

Evidence from large trials on the use of carotid surgery has previously shown that most patients who undergo carotid endarterectomy to reduce their risk of stroke have the operation unnecessarily. Although the procedure lowers the risk of stroke by 50%in …
Variable effect of angiotensin infusion on left ventricular function
Authors: R. A. O'ROURKE, B. PEGRAM, V. S. BISHOP
Journal: Cardiovascular Research (1972)

Journal Article Variable effect of angiotensin infusion on left ventricular function Get access ROBERT A. O'ROURKE, ROBERT A. O'ROURKE 2 From the Department of Medicine, University of Arizona, and Department of Pharmacology, University of Texas Medical School, San Antonio, Texas, U.S.A. 2 Dr. O'Rourke is recipient of Sinsheimer Grant-in-Aid for Cardiovascular Research. Supported in part by U.S. Public Health Service Research Grant HE 12415-01 from the National Heart Institute and the Texas Heart Association Center. Reprint requests to him at: Cardiovascular Division Department of Medicine, University Hospital of San Diego County, San Diego, California 92103, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar BARBARA PEGRAM, BARBARA PEGRAM From the Department of Medicine, University of Arizona, and Department of Pharmacology, University of Texas Medical School, San Antonio, Texas, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar VERNON S. BISHOP VERNON S. BISHOP From the Department of Medicine, University of Arizona, and Department of Pharmacology, University of Texas Medical School, San Antonio, Texas, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 6, Issue 3, May 1972, Pages 240–247, https://doi.org/10.1093/cvr/6.3.240 Published: 01 May 1972
Third-Trimester Maternal Glucose Levels From Diurnal Profiles in Nondiabetic Pregnancies
Authors: Elena Parretti, Federico Mecacci, Marta Papini, Riccardo Cioni, Lucia Carignani, Marcella Mignosa, Pasquale La Torre, Giorgio Mello
Journal: Diabetes Care (2001)

To assess the 24-h glucose levels in a group of nondiabetic, nonobese pregnant women and to verify the presence of correlations between maternal glucose levels and sonographic parameters of fetal growth.A total of 66 Caucasian nonobese pregnant women with normal glucose challenge tests (GCT) enrolled in the study; from this population, we selected 51 women who delivered term (from 37 to 42 weeks completed) live-born infants without evidence of congenital malformations. The women were requested to have three main meals and to perform daily glucose profiles fortnightly from 28-38 weeks without modifying their lifestyle or following any dietary restriction. All subjects were taught how to monitor their blood glucose by using a reflectance meter. Fetal biometry was evaluated by ultrasound scan according to standard methodology at 22, 28, 32, and 36 weeks of pregnancy.The overall daily mean glucose level during the third trimester was 74.7 +/- 5.2 mg/dl. Daily mean glucose values increased between 28 (71.9 +/- 5.7 mg/dl) and 38 (78.3 +/- 5.4 mg/dl) weeks of pregnancy. We found a significant positive correlation at 28 weeks between 1-h postprandial glucose values and fetal abdominal circumference (AC). At 32 weeks, we documented positive correlations between fetal AC and maternal blood glucose levels 1 h after breakfast, 1 and 2 h after lunch, and 1 and 2 h after dinner. At 36 weeks, there was a positive correlation between fetal AC and 1- and 2-h postprandial blood glucose levels. In addition, there was a negative correlation between head-abdominal circumference ratio and 1-h postprandial blood glucose values.This longitudinal study first provides a contribution toward the definition of normoglycemia in nondiabetic, nonobese pregnant women; moreover, it reveals significant correlations of postprandial blood glucose levels with the growth of insulin-sensitive fetal tissues and, in particular, between 1-h postprandial blood glucose values and fetal AC.