tbuckley/cabot-search huggingface dataset:
Adverse effects of high dose aspirin on platelet adhesion to experimental autogenous vein grafts
Authors: A. H GERSHLICK, Y D. S. COURT, A. J MURDAY, C T. LEWIS, P. G MILLS
Journal: Cardiovascular Research (1985)

Prostacyclin (PGI2) production and platelet adhesion were studied in veins grafted into the arterial system of rabbits. Animal groups consisted of: no treatment; low dose aspirin (ASA) (0.5 mg . kg-1 X 24 h-1) plus dipyridamole (2 mg . kg-1 X 6 h-1); high dose ASA (40 mg . kg-1 X 24 h-1) plus dipyridamole (2 mg . kg-1 X 6 h-1); dipyridamole (2 mg . kg-1 X 6 h-1) alone. Results showed that vein grafts from animals treated with high dose ASA plus dipyridamole produced significantly less PGI2 than the other three groups (p less than 0.05 compared with the dipyridamole group; p less than 0.01 compared with the other two groups). In addition, there was significantly greater platelet deposition on the vein grafts from this high dose ASA group as compared to the low dose ASA group (p less than 0.05). By contrast, animals treated with dipyridamole alone had significantly less platelet deposition compared to both the control and high dose ASA groups (p less than 0.05). High dose ASA given to prevent thrombotic occlusion following coronary artery bypass grafting may, by reducing PGI2, result in enhanced platelet deposition. This in turn is likely to increase intimal hyperplasia as has been demonstrated previously with high dose ASA. Clinical studies, which have shown the early anti-thrombotic benefits of high dose ASA plus dipyridamole, have not measured graft intimal thickness. Since this process is an important cause of graft narrowing, ASA, in high dose, may adversely affect long-term graft survival.
Prevalence of barriers for physical activity in adults according to gender and socioeconomic status
Authors: Sebastião Sequeira, Cristina Cruz, Diogo Pinto, Luís Santos, Adilson Marques
Journal: British Journal of Sports Medicine (2011)

The aim of this study was to analyse the prevalence of barriers to physical activity (PA) among adults according to the gender and socioeconomic status (SES). A total of 2236 subjects (927 men, 1309 women) aged between 30 and 50 y (M = 42±5 y) participated in the study. The data was collected through a questionnaire. Qui-square tests were performed to analyse the differences between genders and SES on perceived barriers. Significance level was p &lt;0.05. Only 31% (32% male, 31% female) achieved the current PA recommendation. The most cited barriers were lack of time (55%), costs (20%), the desire to do other things (15%), the failure to consider themselves as athletes (15%) and lack of infrastructures near where they live. All other reasons were mentioned by less than 10% of the individuals tested. Among the most cited barriers, women reported costs more than men (12% male vs 25% female, p&lt;0.001). On the other hand, men reported more often the lack of infrastructures in the neighbourhood (14% male, 9% female, p&lt;0.001). In all of the most cited barriers there were significant differences between subjects with low and high SES. The barriers most associated with prevalence of inactivity among those with low SES were the failure to consider themselves as athletes (p&lt;0.001), the costs (p&lt;0.001), no time to practise (p=0.002) and the lack of infrastructures (p=0.002). The subjects with higher SES cited more often the desire to do other things. Women reported more often the barriers for PA in general, with big prevalence in the costs. Man, who practices informal PA more easily, reported more often the lack of infrastructures in the neighbourhood. Perceived barrier for PA were more prevalent in subjects with low SES. However, lack of time was a barrier most cited by men and women with high or low SES.
Targeting Notch1 signaling pathway positively affects the sensitivity of osteosarcoma to cisplatin by regulating the expression and/or activity of Caspase family
Authors: Lei Wang, Fangchun Jin, An Qin, Yongqiang Hao, Yufeng Dong, Shengfang Ge, Kerong Dai
Journal: Molecular Cancer (2014)

The introduction of cisplatin has improved the long-term survival rate in osteosarcoma patients. However, some patients are intrinsically resistant to cisplatin. This study reported that the activation of Notch1 is positively correlated with cisplatin sensitivity, evidenced by both clinical and in vitro data. In this study, a total 8 osteosarcoma specimens were enrolled and divided into two groups according to their cancer chemotherapeutic drugs sensitivity examination results. The relationship between Notch1 expression and cisplatin sensitivity of osteosarcoma patients was detected by immunohistochemistry and semi-quantitative analysis. Subsequently, two typical osteosarcoma cell lines, Saos-2 and MG63, were selected to study the changes of cisplatin sensitivity by up-regulating (NICD1 plasmid transfeciton) or decreasing (gamma-secretase complex inhibitor DAPT) the activation state of Notch1 signaling pathway. Our results showed a significant correlation between the expression of Notch1 and cisplatin sensitivity in patient specimens. In vitro, Saos-2 with higher expression of Notch1 had significantly better cisplatin sensitivity than MG63 whose Notch1 level was relatively lower. By targeting regulation in vitro, the cisplatin sensitivity of Saos-2 and MG63 had significantly increased after the activation of Notch1 signaling pathway, and vice versa. Further mechanism investigation revealed that activation/inhibition of Notch1 sensitized/desensitized cisplatin-induced apoptosis, which probably depended on the changes in the activity of Caspase family, including Caspase 3, Caspase 8 and Caspase 9 in these cells. Our data clearly demonstrated that Notch1 is critical for cisplatin sensitivity in osteosarcoma. It can be used as a molecular marker and regulator for cisplatin sensitivity in osteosarcoma patients.
Galectin-3 Inhibits Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis by Activating Akt in Human Bladder Carcinoma Cells
Authors: Natsuo Oka, Susumu Nakahara, Yukinori Takenaka, Tomoharu Fukumori, Victor Hogan, Hiro-omi Kanayama, Takashi Yanagawa, Avraham Raz
Journal: Cancer Research (2005)

Abstract The antiapoptotic molecule galectin-3 was previously shown to regulate CD95, a member of the tumor necrosis factor (TNF) family of proteins in the apoptotic signaling pathway. Here, we question the generality of the phenomenon by studying a different member of this family of proteins [e.g., TNF-related apoptosis-inducing ligand (TRAIL), which induces apoptosis in a wide variety of cancer cells]. Overexpression of galectin-3 in J82 human bladder carcinoma cells rendered them resistant to TRAIL-induced apoptosis, whereas phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY-294002) blocked the galectin-3 protecting effect. Because Akt is a major downstream PI3K target reported to play a role in TRAIL-induced apoptosis, we questioned the possible relationship between galectin-3 and Akt. Parental J82 and the control vector–transfected J82 cells (barely detectable galectin-3) exhibit low level of constitutively active Akt, resulting in sensitivity to TRAIL. On the other hand, J82 cells overexpressing galectin-3 cells expressed a high level of constitutively active Akt and were resistant to TRAIL. Moreover, the blockage of TRAIL-induced apoptosis in J82 cells seemed to be mediated by Akt through the inhibition of BID cleavage. These results suggest that galectin-3 involves Akt as a modulator molecule in protecting bladder carcinoma cells from TRAIL-induced apoptosis.
Prospective, Randomized Comparison of High-Dose Chemotherapy With Stem-Cell Support Versus Intermediate-Dose Chemotherapy After Surgery and Adjuvant Chemotherapy in Women With High-Risk Primary Breast Cancer: A Report of CALGB 9082, SWOG 9114, and NCIC MA-13
Authors: William P. Peters, Gary L. Rosner, James J. Vredenburgh, Elizabeth J. Shpall, Michael Crump, Paul G. Richardson, Michael W. Schuster, Lawrence B. Marks, Constance Cirrincione, Larry Norton, I.C. Henderson, Richard L. Schilsky, David D. Hurd
Journal: Journal of Clinical Oncology (2005)

The prognosis for women with primary breast cancer involving multiple axillary nodes remains poor. High-dose chemotherapy with stem-cell support produced promising results in initial clinical trials conducted at single institutions.Seven hundred eighty-five women aged 22 to 66 years with stage IIA, IIB, or IIIA breast cancer involving 10 or more axillary lymph nodes were randomized after surgery and standard adjuvant chemotherapy to either high-dose cyclophosphamide, cisplatin, and carmustine (HD-CPB) with stem-cell support or intermediate-dose cyclophosphamide, cisplatin, and carmustine (ID-CPB) with G-CSF support but without stem cells. Planned treatment for all patients included locoregional radiation therapy. Hormone-receptor-positive patients were to receive 5 years of tamoxifen. Event-free survival (EFS) was the primary end point.Median follow-up was 7.3 years. Event-free survival was not significantly different between the two treatment groups (P = .24). The probability of being free of an event at 5 years with HD-CPB was 61% (95% CI, 56% to 65%), and was 58% (95% CI, 53% to 63%) for ID-CPB. Thirty-three patients died of causes attributed to HD-CPB, compared with no therapy-related deaths among women treated with ID-CPB. Overall survival for the two arms was identical at 71% at 5 years (P = .75).HD-CPB with stem-cell support was not superior to ID-CPB for event-free or overall survival among all randomized women with high-risk primary breast cancer.
Medical Writings: A New Section for Annals
Authors: David R. Goldman
Journal: Annals of Internal Medicine (1997)

Editorials1 January 1997Medical Writings: A New Section for AnnalsDavid R. Goldman, MD, Deputy EditorDavid R. Goldman, MD, Deputy EditorSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-1-199701010-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The New Year is always a time of anticipation. Not entirely satisfied with everything we are and do, we formulate new resolutions and hope for better from ourselves and others in the future. And so it is with Annals. Since the last New Year, the journal has seen changes in both content and appearance, changes that we hope have made it better. But more change is afoot.With this issue, we retire our familiar Literature of Medicine section and inaugurate a new one entitled “Medical Writings.” In place of the few familiar book reviews and occasional longer essays, we anticipate ... Author, Article, and Disclosure InformationAffiliations: Corresponding Author: David R. Goldmann, MD, American College of Physicians, Independence Mall West, Sixth Street at Race, Philadelphia, PA 19106. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByReading and writing book reviews across the disciplinesBook reviewing in the BJET: a survey of BJET's referees' and writers' viewsImproving the Clarity of Journal Abstracts in PsychologyMedical Writings RevisitedDavid R. Goldmann, MDFrom Structured Abstracts to Structured Articles: A Modest ProposalNo Laughing Matter: Vaughn Meader, the Kennedy administration, and presidential impersonations on radio 1 January 1997Volume 126, Issue 1Page: 83KeywordsForecastingHealth services researchHistory of medicineMedical educationPatients Issue Published: 1 January 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Endometriosis: a high-risk population for major chronic diseases?
Authors: M. Kvaskoff, F. Mu, K. L. Terry, H. R. Harris, E. M. Poole, L. Farland, S. A. Missmer
Journal: Human Reproduction Update (2015)

Despite an estimated prevalence of 10% in women, the etiology of endometriosis remains poorly understood. Over recent decades, endometriosis has been associated with risk of several chronic diseases, such as cancer, autoimmune diseases, asthma/atopic diseases and cardiovascular diseases. A deeper understanding of these associations is needed as they may provide new leads into the causes or consequences of endometriosis. This review summarizes the available epidemiological findings on the associations between endometriosis and other chronic diseases and discusses hypotheses for underlying mechanisms, potential sources of bias and methodological complexities. We performed a comprehensive search of the PubMed/Medline and ISI Web of Knowledge databases for all studies reporting on the associations between endometriosis and other diseases published in English through to May 2014, using numerous search terms. We additionally examined the reference lists of all identified papers to capture any additional articles that were not identified through computer searches. We identified 21 studies on the associations between endometriosis and ovarian cancer, 14 for breast cancer, 8 for endometrial cancer, 4 for cervical cancer, 12 for cutaneous melanoma and 3 for non-Hodgkin's lymphoma, as well as 9 on the links between endometriosis and autoimmune diseases, 6 on the links with asthma and atopic diseases, and 4 on the links with cardiovascular diseases. Endometriosis patients were reported to be at higher risk of ovarian and breast cancers, cutaneous melanoma, asthma, and some autoimmune, cardiovascular and atopic diseases, and at decreased risk of cervical cancer. Increasing evidence suggests that endometriosis patients are at higher risk of several chronic diseases. Although the underlying mechanisms are not yet understood, the available data to date suggest that endometriosis is not harmless with respects to women's long-term health. If these relationships are confirmed, these findings may have important implications in screening practices and in the management and care of endometriosis patients.
The Genetics of Hair Cell Development and Regeneration
Authors: Andrew K. Groves, Kaidi D. Zhang, Donna M. Fekete
Journal: Annual Review of Neuroscience (2013)

Sensory hair cells are exquisitely sensitive vertebrate mechanoreceptors that mediate the senses of hearing and balance. Understanding the factors that regulate the development of these cells is important, not only to increase our understanding of ear development and its functional physiology but also to shed light on how these cells may be replaced therapeutically. In this review, we describe the signals and molecular mechanisms that initiate hair cell development in vertebrates, with particular emphasis on the transcription factor Atoh1, which is both necessary and sufficient for hair cell development. We then discuss recent findings on how microRNAs may modulate the formation and maturation of hair cells. Last, we review recent work on how hair cells are regenerated in many vertebrate groups and the factors that conspire to prevent this regeneration in mammals.
Anti-inflammatory cytokine release by alveolar macrophages in pulmonary sarcoidosis.
Authors: G Zissel, J Homolka, J Schlaak, M Schlaak, J Müller-Quernheim
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Sarcoidosis is a systemic, granulomatous disorder with a high rate of spontaneous remission indicating the presence of antiinflammatory mechanisms. Antiinflammatory mediators such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) should be able to induce spontaneous remission of sarcoidosis. By measuring the release of both mediators in culture supernatants of bronchoalveolar lavage (BAL) cells, we investigated their relevance in the spontaneous remission of sarcoidosis. No spontaneous IL-10 release was observed by BAL cells of sarcoid patients. In supernatants of BAL cells of seven patients found retrospectively to be free of any interstitial lung disease, we found 612 +/- 261.2 pg/ml (mean +/- SEM) TGF-beta. TGF-beta release was recorded in 20 of 39 patients with active disease. Patients with active disease without TGF-beta release in BAL cell culture either required therapy (n = 21; 677 +/- 159 pg/ml) or showed evidence of persisting disease (n = 6; 762 +/- 419 pg/ml). Patients with active disease without indications for therapy and with significantly increased TGF-beta release (n = 12; 1,422 +/- 215 pg/ml; p < 0.004 in all comparisons) had a spontaneous remission within 6 mo. Increased TGF-beta release (1,560 +/- 353 pg/ml) was observed in five of five patients receiving therapy. We conclude that TGF-beta is a regulator of the inflammatory process in sarcoidosis.
Streptococcus group A pneumonia in an intravenous drug misuser (IVDM)
Authors: PH McWhinney, D Nathwani
Journal: European Respiratory Journal (1991)

Streptococcus pyogenes appears to have become an uncommon cause of pneumonia. In view of the recent increase in S. pyogenes infections this situation is likely to change. An intravenous drug user presented with acute onset of fever and chills. At presentation pleuritic chest pain was a prominent symptom, and later he developed pulmonary abscesses and an empyema. The patient had a good response to benzyl penicillin, and his pulmonary lesions resolved completely. Although his clinical picture was characteristic of S. pyogenes pneumonia, it could easily be mistaken for Staphylococcus aureus septicaemia.
Sumoylated PPARα mediates sex-specific gene repression and protects the liver from estrogen-induced toxicity in mice
Authors: Nicolas Leuenberger, Sylvain Pradervand, Walter Wahli
Journal: Journal of Clinical Investigation (2009)

As most metabolic studies are conducted in male animals, understanding the sex specificity of the underlying molecular pathways has been broadly neglected; for example, whether PPARs elicit sex-dependent responses has not been determined. Here we show that in mice, PPARalpha has broad female-dependent repressive actions on hepatic genes involved in steroid metabolism and immunity. In male mice, this effect was reproduced by the administration of a synthetic PPARalpha ligand. Using the steroid oxysterol 7alpha-hydroxylase cytochrome P4507b1 (Cyp7b1) gene as a model, we elucidated the molecular mechanism of this sex-specific PPARalpha-dependent repression. Initial sumoylation of the ligand-binding domain of PPARalpha triggered the interaction of PPARalpha with GA-binding protein alpha (GABPalpha) bound to the target Cyp7b1 promoter. Histone deacetylase and DNA and histone methylases were then recruited, and the adjacent Sp1-binding site and histones were methylated. These events resulted in loss of Sp1-stimulated expression and thus downregulation of Cyp7b1. Physiologically, this repression conferred on female mice protection against estrogen-induced intrahepatic cholestasis, the most common hepatic disease during pregnancy, suggesting a therapeutic target for prevention of this disease.
Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells
Authors: Kuibeom Ko, Sayuri Yamazaki, Kyoko Nakamura, Tomohisa Nishioka, Keiji Hirota, Tomoyuki Yamaguchi, Jun Shimizu, Takashi Nomura, Tsutomu Chiba, Shimon Sakaguchi
Journal: The Journal of Experimental Medicine (2012)

T cell stimulation via glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) can evoke effective tumor immunity. A single administration of agonistic anti-GITR monoclonal antibody (mAb) to tumor-bearing mice intravenously or directly into tumors provoked potent tumor-specific immunity and eradicated established tumors without eliciting overt autoimmune disease. A large number of CD4+ and CD8+ T cells, including interferon (IFN)-gamma-secreting cells, infiltrated regressing tumors. Tumor-specific IFN-gamma-secreting CD4+ and CD8+ T cells also increased in the spleen. The treatment led to tumor rejection in IFN-gamma-intact mice but not IFN-gamma-deficient mice. Furthermore, coadministration of anti-GITR and anti-CTLA-4 mAbs had a synergistic effect, leading to eradication of more advanced tumors. In contrast, coadministration of anti-CD25 and anti-GITR mAbs was less effective than anti-GITR treatment alone, because anti-CD25 depleted both CD25+-activated effector T cells and CD25+CD4+ naturally occurring regulatory T (T reg) cells. Importantly, CD4+ T cells expressing the T reg-specific transcription factor Foxp3 predominantly infiltrated growing tumors in control mice, indicating that tumor-infiltrating natural Foxp3+CD25+CD4+ T reg cells may hamper the development of effective tumor immunity. Taken together, T cell stimulation through GITR attenuates T reg-mediated suppression or enhances tumor-killing by CD4+ and CD8+ effector T cells, including those secreting IFN-gamma, or both. Agonistic anti-GITR mAb is therefore instrumental in treating advanced cancers.
Adult midgut expressed sequence tags from the tsetse fly Glossina morsitans morsitansand expression analysis of putative immune response genes
Authors: M J Lehane, S Aksoy, W Gibson, A Kerhornou, M Berriman, J Hamilton, M B Soares, M F Bonaldo, S Lehane, N Hall
Journal: Genome biology (2003)

Tsetse flies transmit African trypanosomiasis leading to half a million cases annually. Trypanosomiasis in animals (nagana) remains a massive brake on African agricultural development. While trypanosome biology is widely studied, knowledge of tsetse flies is very limited, particularly at the molecular level. This is a serious impediment to investigations of tsetse-trypanosome interactions. We have undertaken an expressed sequence tag (EST) project on the adult tsetse midgut, the major organ system for establishment and early development of trypanosomes. A total of 21,427 ESTs were produced from the midgut of adult Glossina morsitans morsitans and grouped into 8,876 clusters or singletons potentially representing unique genes. Putative functions were ascribed to 4,035 of these by homology. Of these, a remarkable 3,884 had their most significant matches in the Drosophila protein database. We selected 68 genes with putative immune-related functions, macroarrayed them and determined their expression profiles following bacterial or trypanosome challenge. In both infections many genes are downregulated, suggesting a malaise response in the midgut. Trypanosome and bacterial challenge result in upregulation of different genes, suggesting that different recognition pathways are involved in the two responses. The most notable block of genes upregulated in response to trypanosome challenge are a series of Toll and Imd genes and a series of genes involved in oxidative stress responses. The project increases the number of known Glossina genes by two orders of magnitude. Identification of putative immunity genes and their preliminary characterization provides a resource for the experimental dissection of tsetse-trypanosome interactions.
Hemodynamic Improvement of Pulmonary Arterial Hypertension After Bariatric Surgery: Potential Role for Metabolic Regulation
Authors: Meredith E. Pugh, John H. Newman, D. Brandon Williams, Evan Brittain, Ivan M. Robbins, Anna R. Hemnes
Journal: Diabetes Care (2013)

Insulin resistance, metabolic syndrome, and adipokine dysregulation are now implicated in hypertensive pulmonary vascular disease (1–3). Even in nonobese humans with idiopathic pulmonary arterial hypertension (IPAH), the prevalence of insulin resistance is nearly 50% (1,2), suggesting a link between glucose dysregulation and IPAH. Additionally, IPAH develops spontaneously in animal models of obesity and adipokine alterations (4). The underlying mechanisms by which metabolic mediators exacerbate or cause pulmonary vascular disease are unknown. We tested the hypothesis that improvements in metabolic hormones are associated with amelioration of pulmonary hemodynamics in a 48-year-old morbidly obese female IPAH patient who underwent bariatric surgery. Despite no change in IPAH therapy, she had dramatic hemodynamic improvement coupled with reduced insulin resistance, plasma lipids, and cholesterol levels.

The IPAH patient was New York Heart Association functional class III and desired bariatric surgery. After counseling about elevated …