tbuckley/cabot-search huggingface dataset:
Control of the adaptive response of the heart to stress via the Notch1 receptor pathway
Authors: Adrien Croquelois, Andrea A. Domenighetti, Mohamed Nemir, Mario Lepore, Nathalie Rosenblatt-Velin, Freddy Radtke, Thierry Pedrazzini
Journal: The Journal of Experimental Medicine (2008)

In the damaged heart, cardiac adaptation relies primarily on cardiomyocyte hypertrophy. The recent discovery of cardiac stem cells in the postnatal heart, however, suggests that these cells could participate in the response to stress via their capacity to regenerate cardiac tissues. Using models of cardiac hypertrophy and failure, we demonstrate that components of the Notch pathway are up-regulated in the hypertrophic heart. The Notch pathway is an evolutionarily conserved cell-to-cell communication system, which is crucial in many developmental processes. Notch also plays key roles in the regenerative capacity of self-renewing organs. In the heart, Notch1 signaling takes place in cardiomyocytes and in mesenchymal cardiac precursors and is activated secondary to stimulated Jagged1 expression on the surface of cardiomyocytes. Using mice lacking Notch1 expression specifically in the heart, we show that the Notch1 pathway controls pathophysiological cardiac remodeling. In the absence of Notch1, cardiac hypertrophy is exacerbated, fibrosis develops, function is altered, and the mortality rate increases. Therefore, in cardiomyocytes, Notch controls maturation, limits the extent of the hypertrophic response, and may thereby contribute to cell survival. In cardiac precursors, Notch prevents cardiogenic differentiation, favors proliferation, and may facilitate the expansion of a transient amplifying cell compartment.
Diabetes in Ramadan
Authors: B. Qureshi
Journal: Journal of the Royal Society of Medicine (2002)

Islam is the second largest religion in Britain, after Christianity. In 2001, the number of Muslims in Britain was around 2.5 million. Devoted healthy Muslims commemorate the revelation of the Holy Quran by Allah to the Prophet Mohammed by fasting in the month of Ramadan every year. Ramadan lasts for 29 or 30 days, depending on the sighting of the moon. While continuing their daily occupation without time off, fasting Muslims abstain from food, liquids, tobacco, sexual activity and medication (oral, inhaler or injection) from sunrise to sunset. However, the sick, the pregnant and nursing mothers and children are exempt; moreover, if a fasting person becomes ill, he or she is allowed to end the fast in the day.

Ramadan directly influences the control of diabetes because of the month-long changes in meal times, types of foods, use of medication and daily lifestyle1,2. Doctors and nurses who encounter Muslim diabetic patients need to understand the practicalities. What does a controlled diabetic Muslim do in Ramadan that a health professional should know about?
Compliance with indoor tanning advertising regulations in France
Authors: M.F. De Maleissye, F. Fay-Chatelard, A. Beauchet, P. Saiag, E. Mahé
Journal: British Journal of Dermatology (2011)

Journal Article Compliance with indoor tanning advertising regulations in France Get access M.F. De Maleissye, M.F. De Maleissye Research Unit EA 4339 ‘Skin, Cancer and Environment’Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar F. Fay‐Chatelard, F. Fay‐Chatelard Research Unit EA 4339 ‘Skin, Cancer and Environment’ Search for other works by this author on: Oxford Academic Google Scholar A. Beauchet, A. Beauchet Research Unit EA 4339 ‘Skin, Cancer and Environment’Department of Public Health, Ambroise Paré University Hospital, University of Versailles‐Saint Quentin en Yvelines, Assistance Publique‐Hôpitaux de Paris, 92100 Boulogne‐Billancourt, France Search for other works by this author on: Oxford Academic Google Scholar P. Saiag, P. Saiag Research Unit EA 4339 ‘Skin, Cancer and Environment’Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar E. Mahé E. Mahé Research Unit EA 4339 ‘Skin, Cancer and Environment’Department of Dermatology Emmanuel Mahé. E‐mail: emmanuel.mahe@apr.aphp.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 4, 1 April 2011, Pages 880–882, https://doi.org/10.1111/j.1365-2133.2011.10159.x Published: 01 April 2011
Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies.
Authors: Michael D Mattie, Christopher C Benz, Jessica Bowers, Kelly Sensinger, Linda Wong, Gary K Scott, Vita Fedele, David Ginzinger, Robert Getts, Chris Haqq
Journal: Molecular Cancer (2006)

Recent studies indicate that microRNAs (miRNAs) are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a novel combination of linear amplification and labeling of miRNA for highly sensitive expression microarray profiling requiring only picogram quantities of purified microRNA. Comparison of microarray and qRT-PCR measured miRNA levels from two different prostate cancer cell lines showed concordance between the two platforms (Pearson correlation R2 = 0.81); and extension of the amplification, labeling and microarray platform was successfully demonstrated using clinical core and excision biopsy samples from breast and prostate cancer patients. Unsupervised clustering analysis of the prostate biopsy microarrays separated advanced and metastatic prostate cancers from pooled normal prostatic samples and from a non-malignant precursor lesion. Unsupervised clustering of the breast cancer microarrays significantly distinguished ErbB2-positive/ER-negative, ErbB2-positive/ER-positive, and ErbB2-negative/ER-positive breast cancer phenotypes (Fisher exact test, p = 0.03); as well, supervised analysis of these microarray profiles identified distinct miRNA subsets distinguishing ErbB2-positive from ErbB2-negative and ER-positive from ER-negative breast cancers, independent of other clinically important parameters (patient age; tumor size, node status and proliferation index). In sum, these findings demonstrate that optimized high-throughput microRNA expression profiling offers novel biomarker identification from typically small clinical samples such as breast and prostate cancer biopsies.
<i>CISH</i>and Susceptibility to Infectious Diseases
Authors: Chiea C Khor, Fredrik O Vannberg, Stephen J Chapman, Haiyan Guo, Sunny H Wong, Andrew J Walley, Damjan Vukcevic, Anna Rautanen, Tara C Mills, Kwok-Chiu Chang, Kai-Man Kam, Amelia C Crampin, Bagrey Ngwira, Chi-Chiu Leung, Cheuk-Ming Tam, Chiu-Yeung Chan, Joseph J Y Sung, Wing-Wai Yew, Kai-Yee Toh, Stacey K H Tay, Dominic Kwiatkowski, Christian Lienhardt, Tran-Tinh Hien, Nicholas P Day, Nobert Peshu, Kevin Marsh, Kathryn Maitland, J Anthony Scott, Thomas N Williams, James A Berkley, Sian Floyd, Nelson L S Tang, Paul E M Fine, Denise L M Goh, Adrian V S Hill
Journal: New England Journal of Medicine (2010)

The interleukin-2–mediated immune response is critical for host defense against infectious pathogens. Cytokine-inducible SRC homology 2 (SH2) domain protein (CISH), a suppressor of cytokine signaling, controls interleukin-2 signaling.
Impaired delayed type cutaneous hypersensitivity in rheumatoid arthritis reversed by chrysotherapy.
Authors: M D Smith, A Smith, J O'Donnell, M J Ahern, P J Roberts-Thomson
Journal: Annals of the Rheumatic Diseases (1989)

A prospective 24 week study of 31 patients with active rheumatoid arthritis (18 women, 13 men) was undertaken to determine whether weekly intramuscular sodium aurothiomalate (gold) would influence delayed type cutaneous hypersensitivity (DTH) and other indices of cell mediated immunity. DTH to seven recall antigens was measured by Multitest on three occasions during the study. Twenty five patients completed the study. At entry 13 patients (12 female) were anergic, and no significant correlations were found between DTH and other clinical and immunological indices. Women showed a significantly greater depression of DTH than men. At week 24 only three of the patients were anergic with significant increase in mean DTH score being noted particularly to tuberculin, candida, and streptococcus. Improvement in DTH was observed in both gold responders and non-responders. In conclusion, patients with active rheumatoid arthritis show impairment of DTH, which is reversed by chrysotherapy. This effect is most apparent in women and appears to be relatively independent of the clinical response.
Swine Flu myocarditis presenting with life threatening ventricular tachycardia
Authors: Sethumadhavan Vijayan, Alexander Chase, James Barry
Journal: Journal of the Royal Society of Medicine (2012)

Acute myocarditis is a complication of influenza A H1N1 infection and signs of cardiac dysfunction in a patient diagnosed or suspected to have the infection should alert the clinician to myocarditis and its complications.
Glioblastoma and increased survival with longer chemotherapy duration.
Authors: Dory Abou-Jaoude, Joseph A Moore, Matthew B Moore, Philip Twumasi-Ankrah, Elizabeth Ablah, Dennis F. Moore, Dennis F Moore
Journal: Journal of Clinical Oncology (2013)

e13006 Background: The 5-year survival for patients (pts) with glioblastoma (GBM) is low at approximately 3%. Radiotherapy plus concomitant and adjuvant temozolomide (TMZ) remain the standard of care. The optimal duration of therapy with TMZ is unknown, though treatment periods of 6 months (mo), 12 mo and longer have been utilized. Whether or not there is a benefit with longer treatment duration is controversial. Methods: A retrospective chart review of all pts diagnosed with GBM who were treated at a regional referral center was conducted with data obtained from their electronic medical records. These pts were treated with TMZ for up to 2 years between January 1, 2002 and December 31, 2011. Survival was calculated as the time from initial surgical diagnosis until death. The Kaplan-Meier method with log-rank test was used to estimate the progression-free survival (PFS) as well as the overall survival (OS) distribution of pts after treatment. The results were compared to historical controls and data from previous clinical trials of pts treated up to 1 year. Results: Data from 56 pts were evaluated, the majority of whom had gross total resection and had external pathology review confirming the diagnosis of GBM. The OS probability was 55.4% (SE = 0.068) at 1 year, 26.9% (SE = 0.067) at 2 years and 20.1% (SE = 0.065) at 3 years. The median PFS time in this study group was 8 mo (95% CI = 4.0 – 9.0 mo). The probability of no progression at 2 years was 8.6% (SE = 0.05). Seven pts (12.5%) were treated with TMZ for 2 years. The probability of disease progression at 2 years among these pts was 33.3% with a median time-to-progression of 20 mo (95% CI = 5.0-28.0). These patients showed an increased survival probability at 3 years compared to pts who did not receive the 2 year treatment of TMZ (log-rank test Chi-square = 12.4, p = 0.0004). Conclusions: This analysis suggests that there may be an advantage for a longer duration of TMZ therapy in pts with GBM. In this review, treatment with TMZ for 2 years was associated with an increased survival benefit. While we consider the sample size to be too small for generalization, a prospective/multicenter study with a larger sample size might better evaluate the question of duration of TMZ therapy, particularly if both clinical and basic science data are paired.
An overview of rheumatological research in the European Union
Authors: G. S Mela, M. A Cimmino
Journal: Annals of the Rheumatic Diseases (1998)

To evaluate the distribution and scope of papers published by authors from the European Union (EU) in rheumatological journals and the impact of rheumatological research in the EU in comparison with that produced elsewhere.Papers published during the year 1995 in the 17 rheumatological journals screened by ISI were considered. The journal impact factor (IF) was noted. All key words, both those reported by the authors and those attributed by ISI, were identified and their frequency was calculated using a special purpose program.2331 papers were published in the rheumatological literature during 1995. Of them, 1316 (56.5%) came from the EU (29.4% from the UK, 17.4% from France, 11.5% from Germany, and 10.8% from Italy) and 544 (23.3%) from the USA. The mean IF of EU papers was approximately 2 in comparison with 3.5 for the USA and 2.4 for other countries. In 1995, 2680 key words attributed by the authors and 5651 attributed by ISI appeared in the rheumatological literature. Less than a quarter of them was cited more than twice. The leading key words were rheumatoid arthritis for diseases and methotrexate for drugs.Bibliometric findings are useful to follow research trends. These data show the relevance of EU rheumatological research and the high scientific production of small countries. Dispersion of key words should be avoided and journal editors should promote their standardisation.
Isolation and molecular phylogenetic analysis of actin-coding regions from Emiliania huxleyi, a Prymnesiophyte alga, by reverse transcriptase and PCR methods.
Authors: Debashish Bhattacharya, Shawn K. Stickel, Mitchell L. Sogin
Journal: Molecular Biology and Evolution (1993)

Reverse transcriptase and polymerase chain reaction methods were used to amplify and clone actin cDNAs from the chlorophylls a + C-containing unicellular alga, Emiliania huxleyi (Prymnesiophyta). Actins in E. huxleyi are defined by a gene family containing at least six distinct coding regions that were derived from relatively recent gene duplications. Five of the coding regions (types 1, 2, and 4-6) varied only among synonymous codons. A nonsynonomous change in a sixth coding region (type 3 actin) produced a serine-to-phenylalanine replacement. The G + C composition of third positions in E. huxleyi actin genes is 98%, which contrasts with the mean value of 50% G + C content for first and second positions. Distance-matrix and parsimony analyses of actin genes identified the prymnesiophytes as a photosynthetic lineage that is not already related to other eukaryotic algal groups.
CCAAT/Enhancer Binding Protein α Knock-in Mice Exhibit Early Liver Glycogen Storage and Reduced Susceptibility to Hepatocellular Carcinoma
Authors: Ee Hong Tan, Shing Chuan Hooi, Mirtha Laban, Esther Wong, Sathivel Ponniah, Aileen Wee, Nai-dy Wang
Journal: Cancer Research (2005)

Abstract The CCAAT/enhancer binding protein α (C/EBPα) is vital for establishing normal hepatic energy homeostasis and moderating hepatocellular growth. CEBPA loss-of-function mutations identified in acute myeloid leukemia patients support a tumor suppressor role for C/EBPα. Recent work showed reductions of C/EBPα levels in human hepatocellular carcinoma with the reductions correlating to tumor size and progression. We investigated the potential of reactivating c/ebpα expression during hepatic carcinogenesis to prevent tumor cell growth. We have developed a c/ebpα knock-in mouse in which a single-copy c/ebpα is regulated by one allele of the α-fetoprotein (AFP) gene promoter. The knock-in mice are physically indistinguishable from wild-type (WT) controls. However, knock-in animals were found to deposit fetal hepatic glycogen earlier than WT animals. Quantitative real-time PCR confirmed early c/ebpα expression and early glycogen synthase gene activation in knock-in fetuses. We then used diethylnitrosamine to induce hepatocellular carcinoma in our animals. Diethylnitrosamine produced half the number of hepatocellular nodules in knock-in mice as in WT mice. Immunohistochemistry showed reduced C/EBPα content in WT nodules whereas knock-in nodules stained strongly for C/EBPα. The p21 protein was examined because it mediates a C/EBPα growth arrest pathway. Nuclear p21 was absent in WT nodules whereas cytoplasmic p21 was abundant; knock-in nodules were positive for nuclear p21. Interestingly, only C/EBPα-positive nodules were positive for nuclear p21, suggesting that C/EBPα may be required to direct p21 to the cell nucleus to inhibit growth. Our data establish that controlled C/EBPα production can inhibit liver tumor growth in vivo.
Dietary Fat and Heart Failure: Moving From Lipotoxicity to Lipoprotection
Authors: William C. Stanley, Erinne R. Dabkowski, Rogerio F. Ribeiro, Kelly A. O'Connell
Journal: Circulation Research (2012)

There is growing evidence suggesting that dietary fat intake affects the development and progression of heart failure. Studies in rodents show that in the absence of obesity, replacing refined carbohydrate with fat can attenuate or prevent ventricular expansion and contractile dysfunction in response to hypertension, infarction, or genetic cardiomyopathy. Relatively low intake of n-3 polyunsaturated fatty acids from marine sources alters cardiac membrane phospholipid fatty acid composition, decreases the onset of new heart failure, and slows the progression of established heart failure. This effect is associated with decreased inflammation and improved resistance to mitochondrial permeability transition. High intake of saturated, monounsaturated, or n-6 polyunsaturated fatty acids has also shown beneficial effects in rodent studies. The underlying mechanisms are complex, and a more thorough understanding is needed of the effects on cardiac phospholipids, lipid metabolites, and metabolic flux in the normal and failing heart. In summary, manipulation of dietary fat intake shows promise in the prevention and treatment of heart failure. Clinical studies generally support high intake of n-3 polyunsaturated fatty acids from marine sources to prevent and treat heart failure. Additional clinical and animals studies are needed to determine the optimal diet in terms of saturated, monounsaturated, and n-6 polyunsaturated fatty acids intake for this vulnerable patient population.
Single Oral Challenge by Advanced Glycation End Products Acutely Impairs Endothelial Function in Diabetic and Nondiabetic Subjects
Authors: Jaime Uribarri, Alin Stirban, Denise Sander, Weijing Cai, Monica Negrean, Cristina E. Buenting, Theodore Koschinsky, Helen Vlassara
Journal: Diabetes Care (2007)

The current study was designed to test the acute effects of dietary advanced glycation end products (AGEs) on endothelial function of diabetic and nondiabetic subjects.Flow-mediated dilation (FMD) of the brachial artery and serum levels of AGEs, plasminogen activator inhibitor 1 (PAI-1), vascular cell adhesion molecule 1 (VCAM-1), and glucose were assessed before and after a single oral AGE challenge (approximately 1.8 x 10(6) AGE units) in 44 diabetic and 10 nondiabetic subjects.The diabetic patients had higher baseline levels of serum AGEs (P = 0.020), PAI-1 (NS), and VCAM-1 (P = 0.033) and lower baseline values of FMD compared with nondiabetic subjects (P = 0.032). Ninety minutes after a single oral AGE challenge, serum AGEs and PAI-1 levels increased and FMD decreased significantly in both healthy subjects (AGEs: 7.2 +/- 0.5 to 9.3 +/- 1 units/ml, P = 0.014; PAI-1: 5.4 +/- 0.4 to 6.8 +/- 0.4 ng/ml, P = 0.007; and FMD: 9.9 +/- 0.7 to 7.4 +/- 0.9%, P = 0.019) and diabetic subjects (AGEs: 10.5 +/- 0.7 to 14.2 +/- 1 units/ml, P = 0.020; PAI-1: 6.5 +/- 1 to 10 +/- 2 ng/ml, P = 0.030; and FMD: 5.4 +/- 0.4 to 4.0 +/- 0.3%, P = 0.032). Serum glucose and VCAM-1 levels remained unchanged.Significant increases in serum AGEs can occur together with altered clinical measures of endothelial function in diabetic and nondiabetic subjects after a single modest AGE-rich beverage. Thus, repeated or chronic exposure to high AGE diets could over time lead to and/or accelerate vascular disease.
Ornithine Decarboxylase Inhibition by α-Difluoromethylornithine Activates Opposing Signaling Pathways via Phosphorylation of Both Akt/Protein Kinase B and p27Kip1 in Neuroblastoma
Authors: Dana-Lynn T. Koomoa, Lisette P. Yco, Tamas Borsics, Christopher J. Wallick, André S. Bachmann
Journal: Cancer Research (2008)

Abstract Ornithine decarboxylase (ODC) is a key enzyme in mammalian polyamine biosynthesis that is up-regulated in various types of cancer. We previously showed that treating human neuroblastoma (NB) cells with the ODC inhibitor α-difluoromethylornithine (DFMO) depleted polyamine pools and induced G1 cell cycle arrest without causing apoptosis. However, the precise mechanism by which DFMO provokes these changes in NB cells remained unknown. Therefore, we further examined the effects of DFMO, alone and in combination with phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 or Akt/protein kinase B (PKB) inhibitor IV, on the regulation of cell survival and cell cycle–associated pathways in LAN-1 NB cells. In the present study, we found that the inhibition of ODC by DFMO promotes cell survival by inducing the phosphorylation of Akt/PKB at residue Ser473 and glycogen synthase kinase-3β at Ser9. Intriguingly, DFMO also induced the phosphorylation of p27Kip1 at residues Ser10 (nuclear export) and Thr198 (protein stabilization) but not Thr187 (proteasomal degradation). The combined results from this study provide evidence for a direct cross-talk between ODC-dependent metabolic processes and well-established cell signaling pathways that are activated during NB tumorigenesis. The data suggest that inhibition of ODC by DFMO induces two opposing pathways in NB: one promoting cell survival by activating Akt/PKB via the PI3K/Akt pathway and one inducing p27Kip1/retinoblastoma-coupled G1 cell cycle arrest via a mechanism that regulates the phosphorylation and stabilization of p27Kip1. This study presents new information that may explain the moderate efficacy of DFMO monotherapy in clinical trials and reveals potential new targets for DFMO-based combination therapies for NB treatment. [Cancer Res 2008;68(23):9825–31]
Pharmacotherapy for Nicotine Dependence
Authors: J. E. Henningfield, R. V. Fant, A. R. Buchhalter, M. L. Stitzer
Journal: CA A Cancer Journal for Clinicians (2005)

Approximately 50% of long-term cigarette smokers die prematurely from the adverse effects of smoking, including on cancer, cardiovascular disease, lung disease, or other illness. This risk can be substantially reduced by smoking cessation, with greater benefits occurring the earlier in the smoking career that cessation occurs. However, cessation provides benefits at any stage, including after the onset of smoking-related disease, by improving the prognosis and quality of life. Clinicians can have a significant impact on reducing tobacco use by their patients by following the US Public Health Service Clinical Practice Guidelines. Proven strategies include structured methods of advising cigarette smokers to quit and guidance to facilitate their efforts, as well as the use of various pharmacotherapies. Pharmacotherapies for tobacco dependence include nicotine replacement medications in the form of gum, transdermal patch, lozenge, sublingual tablet, nasal spray, and vapor inhaler formulations. The only nonnicotine medication that has been approved by the US Food and Drug Administration is bupropion. Combination therapies, long-term medication therapies, and harm reduction strategies may further improve outcome with approved medications. Further, new medications such as varenicline and rimonabant are likely to reach tobacco users who are refractory to current treatments. Increasing the treatment options, increasing availability, and reducing the perceived cost of these medications may have an additional public health impact.