tbuckley/cabot-search huggingface dataset:
Chronic Hypoxia–Induced Angiogenesis Normalizes Blood Pressure in Spontaneously Hypertensive Rats
Authors: José Vilar, Ludovic Waeckel, Philippe Bonnin, Clément Cochain, Céline Loinard, Micheline Duriez, Jean-Sébastien Silvestre, Bernard I. Lévy
Journal: Circulation Research (2008)

We hypothesized that activation of angiogenesis by chronic hypoxia may affect vascular resistance and, subsequently, blood pressure levels in spontaneously hypertensive rats (SHRs). Five-week-old prehypertensive SHRs and age-matched normotensive Wistar–Kyoto (WKY) rats (n=8 per group) were maintained under normobaric normoxic or hypoxic (10% O 2 ) conditions for 8 weeks. Three weeks later, the systolic blood pressure was lower by 26% in hypoxic SHRs compared to normoxic SHRs ( P &lt;0.05) and remained at the normoxic WKY level. Total peripheral vascular resistance, calculated as the mean arterial pressure/cardiac output (assessed by ultrasound imaging and Doppler), was 30% lower in hypoxic than in normoxic SHRs ( P &lt;0.001) and returned to WKY levels. Interestingly, chronic hypoxia also significantly reduced systolic blood pressure in adult 12-week-old SHRs with established hypertension; blood pressure was normalized (versus normoxic WKY rats) after 4 weeks of hypoxia. Changes in hemodynamic parameters were associated with activation of proangiogenic pathways. Protein levels of vascular endothelial growth factor (VEGF)-A in the skeletal muscles were increased by 2.2-fold in hypoxic compared to normoxic SHRs ( P &lt;0.001). At the end of the hypoxic period, capillary density in the quadriceps muscle was 1.2-fold higher in hypoxic than in normoxic SHRs ( P &lt;0.001). Myocardial capillary density and VEGF-A protein contents were also 1.2- and 2.1-fold higher in hypoxic compared to normoxic SHRs ( P &lt;0.001 and P &lt;0.05, respectively). Moreover, treatment with neutralizing VEGF-A antibody abrogated the hypoxia-induced angiogenesis and subsequently worsened arterial hypertension. Therefore, our results suggest that chronic normobaric hypoxia (1) activates VEGF-A–induced angiogenesis and thereafter (2) prevents the occurrence of hypertension in young prehypertensive SHRs and (3) normalizes blood pressure in adult SHRs with established hypertension.
Overexpression of G1-S Cyclins and Cyclin-Dependent Kinases during Multistage Human Pancreatic Duct Cell Carcinogenesis
Authors: Maamoun M. Al-Aynati, Nikolina Radulovich, James Ho, Ming-Sound Tsao
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Molecular analysis of pancreatic intraepithelial neoplasia lesions and ductal adenocarcinoma suggested a multistage paradigm for pancreatic duct cell carcinogenesis. This study investigated the molecular basis for the neoplastic duct cells in this pancreatic intraepithelial neoplasia–carcinoma sequence to acquire progressive enhancement of their proliferative potential. Experimental Design: Using tissue microarray blocks containing 15 to 40 pancreatic intraepithelial neoplasia lesions and ductal adenocarcinoma of pancreas, we studied by immunohistochemistry the expression profiles of cyclins and cyclin dependent kinases (CDKs) that regulate the G1-S cell cycle checkpoints. The role of cyclins D3 and D1 in three pancreatic cancer cell lines was investigated using specific short interfering RNA technique. Results: Cyclin D3 overexpression was noted the earliest in pancreatic intraepithelial neoplasia-1A and was prevalent in 90% to 100% of high-grade pancreatic intraepithelial neoplasias and ductal cancer. Cyclin A overexpression was also noted early and reached 50% to 100% of high-grade pancreatic intraepithelial neoplasias and cancer, but the percentage of abnormal duct cells showing overexpression of cyclin A was significantly lower than cyclin D3. Cyclin E overexpression occurred in 20% to 25% of high-grade pancreatic intraepithelial neoplasias and in 75% of ductal carcinoma. Cyclin D1 demonstrated the lowest frequency of overexpression that occurred late. CDK2 and CDK4 overexpression was also noted in early pancreatic intraepithelial neoplasias and progressively increased to reach 60% to 75% in carcinoma. The down-regulation of cyclin D3 mRNA and protein levels using specific short interfering RNA resulted in growth inhibition of pancreatic cancer cell lines. Conclusion: The results provide additional insight into the mechanism of G1-S cell cycle checkpoints deregulation during stepwise pancreatic duct cell carcinogenesis, and suggest a p16-independent role for cyclin D3 in deregulating the G1 cell cycle checkpoints during early stages of pancreatic duct cell carcinogenesis.
Sympathoinhibitory mechanism of moxonidine: role of the inducible nitric oxide synthase in the rostral ventrolateral medulla
Authors: J. Peng, Y.-K. Wang, L.-G. Wang, W.-J. Yuan, D.-F. Su, X. Ni, X.-M. Deng, W.-Z. Wang
Journal: Cardiovascular Research (2009)

The central antihypertensive drug moxonidine lowers blood pressure (BP) through stimulating an imidazoline receptor within the rostral ventrolateral medulla (RVLM). Nitric oxide (NO) generated by the inducible NO synthase (iNOS) in the RVLM has been suggested to be involved in tonic sympathetic inhibition. The aim of this study was to determine the role of NO generated by iNOS in mediating moxonidine-induced cardiovascular inhibition in rats.In anaesthetized rats, the cardiovascular response to local or systemic injection of moxonidine was observed after treatment with the selective iNOS inhibitor S-methylisothiourea (SMT) in the brain. Using immunohistochemical staining and western blot techniques, the protein expression of iNOS in the RVLM was measured in the moxonidine-infused rats. Intracerebroventricular (ICV) injection of SMT (1-100 nmol) dose-dependently attenuated the moxonidine (20 nmol, ICV)-induced decrease in BP and heart rate. Prior injection of SMT (20 and 200 pmol) into the RVLM also dose-dependently prevented the decrease in BP and renal sympathetic nerve activity evoked by RVLM microinjection of moxonidine (5 nmol) or intravenous injection of moxonidine (50 microg/kg). We further found that expression of iNOS protein following chronic ICV infusion of moxonidine (20 nmol, 2 weeks) is selectively upregulated in the RVLM but not in the nucleus tractus solitarius.The present data suggest that an NO mechanism generated by iNOS in the RVLM plays an important role in mediating the sympathetic inhibition of the centrally acting drug moxonidine.
Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study
Authors: Silvia de Sanjose, Wim GV Quint, Laia Alemany, Daan T Geraets, Jo Ellen Klaustermeier, Belen Lloveras, Sara Tous, Ana Felix, Luis Eduardo Bravo, Hai-Rim Shin, Carlos S Vallejos, Patricia Alonso de Ruiz, Marcus Aurelho Lima, Nuria Guimera, Omar Clavero, Maria Alejo, Antonio Llombart-Bosch, Chou Cheng-Yang, Silvio Alejandro Tatti, Elena Kasamatsu, Ermina Iljazovic, Michael Odida, Rodrigo Prado, Muhieddine Seoud, Magdalena Grce, Alp Usubutun, Asha Jain, Gustavo Adolfo Hernandez Suarez, Luis Estuardo Lombardi, Aekunbiola Banjo, Clara Menéndez, Efrén Javier Domingo, Julio Velasco, Ashrafun Nessa, Saibua C Bunnag Chichareon, You Lin Qiao, Enrique Lerma, Suzanne M Garland, Toshiyuki Sasagawa, Annabelle Ferrera, Doudja Hammouda, Luciano Mariani, Adela Pelayo, Ivo Steiner, Esther Oliva, Chris JLM Meijer, Waleed Fahad Al-Jassar, Eugenia Cruz, Thomas C Wright, Ana Puras, Cecilia Ladines Llave, Maria Tzardi, Theodoros Agorastos, Victoria Garcia-Barriola, Christine Clavel, Jaume Ordi, Miguel Andújar, Xavier Castellsagué, Gloria I Sánchez, Andrzej Marcin Nowakowski, Jacob Bornstein, Nubia Muñoz, F Xavier Bosch
Journal: The Lancet Oncology (2010)
Conversion and degradation of [125I] labelled angiotensin I in isolated perfused porcine coronary and carotid arteries
Authors: A. J. Danser, S. Chowdury, L. M de Lannoy, W. J van der Giessen, P. R Saxena, M. A. Schalekamp
Journal: Cardiovascular Research (1995)

Journal Article Conversion and degradation of [125I] labelled angiotensin I in isolated perfused porcine coronary and carotid arteries Get access AH Jan Danser, AH Jan Danser * aDepartment of Pharmacology Cardiovasculair Onderzoeksinstituut Erasmus University Rotterdam (COEUR), Erasmus University Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands *Correspondence to Dr Danser. Search for other works by this author on: Oxford Academic PubMed Google Scholar Suchandana Chowdury, Suchandana Chowdury aDepartment of Pharmacology Cardiovasculair Onderzoeksinstituut Erasmus University Rotterdam (COEUR), Erasmus University Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Larissa M de Lannoy, Larissa M de Lannoy aDepartment of Pharmacology Cardiovasculair Onderzoeksinstituut Erasmus University Rotterdam (COEUR), Erasmus University Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Willem J van der Giessen, Willem J van der Giessen bDepartment of Cardiology Cardiovasculair Onderzoeksinstituut Erasmus University Rotterdam (COEUR), Erasmus University Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Pramod R Saxena, Pramod R Saxena aDepartment of Pharmacology Cardiovasculair Onderzoeksinstituut Erasmus University Rotterdam (COEUR), Erasmus University Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Maarten ADH Schalekamp Maarten ADH Schalekamp cDepartment of Internal Medicine Cardiovasculair Onderzoeksinstituut Erasmus University Rotterdam (COEUR), Erasmus University Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 29, Issue 6, June 1995, Pages 789–795, https://doi.org/10.1016/S0008-6363(96)88614-7 Published: 01 June 1995 Article history Received: 27 September 1994 Accepted: 19 January 1995 Published: 01 June 1995
Co-Benefits of Climate Mitigation and Health Protection in Energy Systems: Scoping Methods
Authors: Kirk R. Smith, Evan Haigler
Journal: Annual Review of Public Health (2008)

Interventions in the energy sector offer significant opportunities for reducing both greenhouse and other health-damaging pollution, resulting in what are called “co-benefits.” The health community plays a critical role in evaluating such interventions to optimize progress of both sorts because both affect health. In detail, analyses require sophisticated modeling and specific local information. As a starting point, however, we offer here a set of scoping methods for obtaining a quick assessment of these co-benefits for interventions in the energy sector, the arena with the highest potential for significant co-benefits. Thus we combine relevant methods developed separately in recent years for cost-effectiveness assessments in the climate change, health, and development communities. We offer sample calculations, which illustrate the apparent high degree of co-benefit effectiveness for targeted interventions in the household energy sector in developing countries.
Interleukin-18/Interleukin-18 Binding Protein Signaling Modulates Ischemia-Induced Neovascularization in Mice Hindlimb
Authors: Ziad Mallat, Jean-Sébastien Silvestre, Sophie Le Ricousse-Roussanne, Laurence Lecomte-Raclet, Anne Corbaz, Michel Clergue, Micheline Duriez, Véronique Barateau, Shizuo Akira, Alain Tedgui, Gérard Tobelem, Yolande Chvatchko, Bernard I. Lévy
Journal: Circulation Research (2002)

Identification of factors that may stimulate ischemia-induced neovascularization without increasing atherosclerotic plaque progression is of major therapeutic importance. We hypothesized that interleukin-18 binding protein (IL-18BP), a major antiinflammatory protein with plaque-stabilizing activities, may affect the neovascularization in mice ischemic hindlimb. Ischemia was produced by artery femoral occlusion in mice that were subjected to in vivo intramuscular electrotransfer of either an empty plasmid or a murine IL-18BP plasmid. Angiographic score, capillary density (CD31 staining), and laser Doppler perfusion data at day 28 showed significant improvement in ischemic/nonischemic leg ratio by respectively 1.6-, 1.4-, and 1.5-fold in IL-18BP-treated mice compared with controls (P<0.01). This was associated with a significant 2-fold increase in both vascular endothelial growth factor (VEGF) and phospho-Akt protein content in the ischemic hindlimb of IL-18BP-treated mice (P<0.05). Similar results were obtained in IL-18-deficient mice. Because bone marrow-derived endothelial progenitor cells (BM-EPCs) are involved in postnatal vasculogenesis, EPCs were isolated and cultivated from bone marrow mononuclear cells. IL-18BP treatment led to a significant 1.8-fold increase in the percentage of BM-EPCs characterized as cells positive for both AcLDL-Dil and von Willebrand factor (P<0.001). In conclusion, IL-18BP stimulates ischemia-induced neovascularization in association with an activation of VEGF/Akt signaling and an increase in BM-EPCs mobilization and differentiation. Our findings strongly suggest a major antiangiogenic role of endogenous IL-18 in postischemic injury.
Exploring gender differences in the working lives of UK hospital consultants
Authors: Laura Jefferson, Karen Bloor, Karen Spilsbury
Journal: Journal of the Royal Society of Medicine (2015)

Internationally, increasing numbers of women are practising medicine. Gender differences in doctors' working hours, specialty choices and communication styles are well documented, but studies often neglect contextual factors such as the role of socialised gender expectations on behaviours in the workplace and the medical profession. These may be important as recent studies have reported gender differences in doctors' activity rates that cannot be explained by specialty or contracted hours, suggesting other sources of variation. This study sought to explore the working lives of hospital doctors and how their work is negotiated according to gender and context.Gender differences in the day-to-day work of hospital specialists (consultants) in the NHS were investigated using a qualitative approach, including observation and interview methods. Data were analysed inductively using qualitative observation and interview methods.Two NHS hospital trusts in England.Data were collected from 13 participants working in a variety of specialties and in a range of clinical and non-clinical settings.Various behaviours, attitudes and experiences were explored, such as doctor-patient communication, interactions with colleagues and workload.Influences at both individual and situational levels, appear to affect differentially the work of male and female doctors. Female consultants described awareness of the impact of behaviours on relationships with colleagues, and their interactions appeared to be more carefully performed. Nurses and other colleagues tend to demonstrate less cooperation with female consultants. Gender differences also exist in patient communication, feelings of work-family conflict and barriers to career progression.These variations in hospital consultants' work may have implications for both the quantity and quality of care provided by male and female consultants. This is timely and of importance to the medical workforce as the gender composition approaches parity.
Prime minister gives backing to more transparent drug trial data
Authors: A. O'Dowd
Journal: BMJ (2012)

David Cameron has added his support to efforts to ensure much greater availability of data from drug companies’ trials.

However, a leading expert has criticised Cameron for not making more of a commitment on forcing companies to publish all their clinical data.

The issue of drug companies not submitting all trial data was raised in the House of Commons on 5 December by Richard Bacon, the Conservative MP for South Norfolk.

The BMJ ’s open data campaign (bmj.com/tamiflu) is aimed at securing appropriate and necessary independent scrutiny of data from clinical trials after the failure of the drug company Roche to fulfil its promise made in 2009 to release …
Surgical repair of traumatic medial disruption of the elbow in competitive athletes.
Authors: G Inoue, Y Kuwahata
Journal: British Journal of Sports Medicine (1995)

Five active athletes with acute medial elbow rupture were treated with muscle-ligamentous repair and a spiked washer. All patients regained full strength as well as stability of the elbow, and resumed previous sporting activities within 3 months of surgery. Early surgical repair of the ligament and flexor mass should be considered for active athletes who exhibit gross instability of the elbow on a valgus stress test without anaesthesia.
Mediation of Electronegative Low-Density Lipoprotein Signaling by LOX-1
Authors: Jonathan Lu, Jun-Hai Yang, Alan R. Burns, Hsin-Hung Chen, Daming Tang, Jeffrey P. Walterscheid, Shinichi Suzuki, Chao-Yuh Yang, Tatsuya Sawamura, Chu-Huang Chen
Journal: Circulation Research (2009)

The lectin-like oxidized LDL receptor LOX-1 mediates endothelial cell (EC) uptake of experimentally prepared copper-oxidized LDL (oxLDL). To confirm the atherogenic role of this receptor cloned against copper-oxLDL, we examined whether it mediates EC uptake of L5, an electronegative LDL abundant in dyslipidemic but not normolipidemic human plasma. Hypercholesterolemic (LDL-cholesterol, &gt;160 mg/dL) human LDL was fractionated into L1–L5, increasingly electronegative, by ion-exchange chromatography. In cultured bovine aortic ECs (BAECs), L5 upregulated LOX-1 and induced apoptosis. Transfection of BAECs with LOX-1–specific small interfering RNAs (siLOX-1) minimized baseline LOX-1 production and restrained L5-induced LOX-1 upregulation. Internalization of labeled L1–L5 was monitored in BAECs and human umbilical venous ECs by fluorescence microscopy. LOX-1 knockdown with siLOX-1 impeded the endocytosis of L5 but not L1–L4. In contrast, blocking LDL receptor with RAP (LDL receptor–associated protein) stopped the internalization of L1–L4 but not L5. Although chemically different, L5 and oxLDL competed for EC entry through LOX-1. Via LOX-1, L5 signaling hampered Akt phosphorylation and suppressed EC expression of fibroblast growth factor-2 and Bcl-2. L5 also selectively inhibited Bcl-xL expression and endothelial nitric oxide synthase phosphorylation but increased synthesis of Bax, Bad, and tumor necrosis factor-α. Blocking Akt phosphorylation with wortmannin increased LOX-1 expression, suggesting a modulatory role of Akt in LOX-1 synthesis; L5 upregulated LOX-1 by dephosphorylating Akt. Because endothelial nitric oxide synthase and Bcl-2 activities are Akt-dependent, L5 impairs Akt-mediated growth and survival signals in vascular ECs by way of LOX-1. Thus, the L5/LOX-1 complex may play a critical role in atherogenesis and illuminate important targets for disease intervention.
Long-Term, Randomized Clinical Trial of Two Diets in the Metabolic Syndrome and Type 2 Diabetes
Authors: Lynne W. Scott, Ashok Balasubramanyam, Kay T. Kimball, Amy K. Aherns, C. Michael Fordis, Christie M. Ballantyne
Journal: Diabetes Care (2003)

The best dietary balance of fatty acids, protein, and carbohydrate in patients with both glucose and lipid metabolism disorders remains unclear (1). Substitution of carbohydrates for saturated fatty acids frequently leads to increased triglyceride and decreased HDL cholesterol (2), adverse effects not seen with increased dietary monounsaturated fatty acids (MUFAs) (3). Moderate hyperglycemia can contribute to increased turnover of protein, suggesting increased need for protein in type 2 diabetes (4).

Between January 2000 and February 2001, we randomized 35 patients with the metabolic syndrome or type 2 diabetes to the contemporary American Heart Association (AHA) diet (15% of calories from protein, 30% fat, and 15% MUFAs) or a diet higher in protein, total fat, and MUFAs …
Identification and Clinical Significance of Circulating Endothelial Progenitor Cells in Human Non–Small Cell Lung Cancer
Authors: Balazs Dome, Jozsef Timar, Judit Dobos, Livia Meszaros, Erzsebet Raso, Sandor Paku, Istvan Kenessey, Gyula Ostoros, Melinda Magyar, Andrea Ladanyi, Krisztina Bogos, Jozsef Tovari
Journal: Cancer Research (2006)

Abstract Until recently, it was generally accepted that vascularization of tumors arises exclusively from endothelial sprouting. Whether circulating bone marrow–derived endothelial progenitor cells (EPC) participate in the progression of non–small cell lung cancer (NSCLC) has not yet been evaluated. EPCs labeled with CD34, CD133, and vascular endothelial growth factor receptor-2 (VEGFR2) antibodies were counted by flow cytometry in the peripheral blood of 53 NSCLC patients. Furthermore, by means of a quantitative reverse transcription-PCR approach, we measured VEGFR2, CD133, CD34, and VE-cadherin mRNA in the peripheral blood samples of the same patient population. EPCs in tumor samples were identified by confocal microscopy using CD31, CD34, CD133, and VEGFR2 antibodies. Although immunofluorescent labeling of microvessels made clear that incorporation of EPCs is a rare phenomenon in NSCLC tissue (9 of 22 cases), circulating EPC levels before therapeutic intervention were increased in NSCLC patients (P &amp;lt; 0.002, versus healthy controls), and high pretreatment circulating EPC numbers correlated with poor overall survival (P &amp;lt; 0.001). Furthermore, in the subgroup of responders to treatment, the posttreatment EPC numbers in the peripheral blood were significantly lower compared with nonresponding patients. Interestingly, pretreatment mRNA levels of CD133, VE-cadherin, and CD34 were not significantly increased in NSCLC patients, whereas VEGFR2 expression was increased by 80-fold. Moreover, posttreatment VEGFR2 mRNA level in the peripheral blood was significantly higher in the subgroup of nonresponding patients when compared with posttreatment level of patients responding to antitumor therapy. Circulating levels of bone marrow–derived EPCs are significantly increased in NSCLC patients and correlate with clinical behavior. (Cancer Res 2006; 66(14): 7341-7)
Disruption of Fnip1 Reveals a Metabolic Checkpoint Controlling B Lymphocyte Development
Authors: Heon Park, Karen Staehling, Mark Tsang, Mark W. Appleby, Mary E. Brunkow, Daciana Margineantu, David M. Hockenbery, Tania Habib, H. Denny Liggitt, George Carlson, Brian M. Iritani
Journal: Immunity (2012)