tbuckley/cabot-search huggingface dataset:
Effect of Angiotensin on the Renal Transport of Sodium in Essential Hypertension
Authors: Hermanvillarreal, Heribertoarcila, Jorgedíaz, Pedrosierra
Journal: Circulation (1967)

The renal function, including sodium excretion rates, were studied in 27 patients with early essential hypertension, before and during angiotensin infusions. The patients had a preparatory period of salt loading for four days taking a supplement of 7 g of NaCl. Determinations were made during two 30-minute periods before the angiotensin and for two 30-minute periods afterward. Arterial blood pressure was increased in all 27 patients and renal plasma flow decreased in 25. The glomerular filtration rate changes were not statistically significant, showing some increase in 15 and a decrease in 11 patients. When the group was divided into those in which there was a decrease in sodium excretion (11 patients), and those in which there was an increase in sodium excretion (16 patients), with angiotensin infusion, a correlation with the control blood pressure was evident. The patients in whom an increase occurred had a control mean blood pressure greater than 136 mm Hg, and those exhibiting a decrease of sodium exc...
Identification of Risk Factors in Hypertensive Patients
Authors: FrançoisGueyffier, Jean-PierreBoissel, StuartPocock, FlorentBoutitie, JohnCoope, JeffreyCutler, TordEkbom, RobertFagard, LawrenceFriedman, KarlaKerlikowske, MitchellPerry, RonaldPrineas, EleanorSchron
Journal: Circulation (1999)

Background—Predicting individual risk is needed to target preventive interventions toward people with the highest probability of benefit over a given time period. We assessed which prognostic factors should be used in predicting risk for hypertensive patients and in searching for treatment modifiers. Methods and Results—Data from 24 390 hypertensive participants who constituted the control groups from 8 controlled trials (1726 deaths over 5 years) were analyzed in multivariate survival models. Outcomes were coronary heart disease death, stroke death, and cardiovascular death. We explored systematically the heterogeneity of results between trials. Left ventricular hypertrophy was electrocardiographically confirmed to be a powerful risk factor and should be included in risk scoring. Height, glomerular filtration rate, and serum uric acid deserve further exploration. Body mass index and heart rate were not confirmed as independent cardiovascular risk factors in this population. The association between male s...
Abstract 4006: Serine protease PRSS8 suppresses colorectal carcinogenesis and metastasis
Authors: Yonghua Bao, Yongchen Guo, Yiqiong Yang, Xiaonan Wei, Xiangdong Zhu, Wei Zhang, Wancai Yang
Journal: Cancer Research (2018)

Abstract PRSS8 is a serine protease and has important physiological and pathophysiological functions, but its roles in cancer initiation and progression are unclear. In this study, a conditional knockout mouse model of Prss8 fl/fl,p-Villin-Cre+ mice were developed and thoroughly characterized at the ages of 3, 6 and 9 months. Intestinal epithelial cell proliferation, migration, and differentiation, were determined. The approaches of gain- and loss of expression of PRSS8 in human colon cancer cells were performed to evaluate anti-cancer and anti-metastasis in vitro and in nude mice by mouse subcutaneous injection, tail vein injection and intra-spleen transplantation. Gene profile and gene set enrichment analysis and mechanistic studies were conducted in vitro and in human colorectal cancer tissues. Results: Genetic deficiency of the Prss8 gene caused spontaneous formation of colitis and inflamed rectum at the early age, but caused intestinal tumors and lymph node metastasis at late age, which was linked to increased intestinal cell proliferation and migration, but decreased cell differentiation. Increased PRSS8 expression showed inhibition of cancer cell growth and metastasis in nude mice, and inhibited migration, invasion, colony formation and tumor sphere formation in vitro, but reduced expression of PRSS8 facilitated malignancies. Mechanistic studies revealed that PRSS8 targets Wnt/β-catenin, epithelial-mesenchymal-transition, and stem cell signaling pathways, which was supported by the results from the Cancer Genome Atlas, and were validated in human colorectal cancers. Conclusion: PRSS8 is a novel tumor suppressor that plays critical roles in the suppression of carcinogenesis and metastasis via targeting Wnt/β-catenin, EMT and stem cell signaling pathway. Citation Format: Yonghua Bao, Yongchen Guo, Yiqiong Yang, Xiaonan Wei, Xiangdong Zhu, Wei Zhang, Wancai Yang. Serine protease PRSS8 suppresses colorectal carcinogenesis and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4006.
Abstract 243: Bystander CPR May Not Improve Survival from Cardiac Arrest in Patients with Epilepsy
Authors: EricStecker, AudreyUy-Evanado, KyndaronReinier, CarmenTeodorescu, KarenGunson, JonathanJui, SumeetChugh
Journal: Circulation (2014)

Introduction: Sudden cardiac arrest (SCA) is the major cause of death among patients with epilepsy and occurs in the absence of a terminal seizure in approximately two-thirds. We aimed to evaluate the effectiveness of conventional cardiac arrest resuscitation factors (Utstein elements) in predicting survival among patients with epilepsy. Methods: This analysis was conducted as part of a large, ongoing, population-based study of SCA in the Northwest US (the Oregon Sudden Unexpected Death Study, community pop. approx. 1 million). Data were obtained from multiple sources (first responders, medical practitioners and medical examiner) between 2002 and 2011 for adult patients with attempted resuscitation. Those with non-cardiac causes of arrest (e.g. severe COPD or metastatic cancer) were excluded. Those with a history of infantile febrile seizures or alcoholic withdrawal seizures were considered non-epileptic. The impact of Utstein resuscitation factors on survival to hospital discharge among patients with epi...
Baseline Values but Not Treatment-Induced Changes in Carotid Intima-Media Thickness Predict Incident Cardiovascular Events in Treated Hypertensive Patients
Authors: AlbertoZanchetti, MichaelHennig, ReginaHollweck, GeneBond, RongTang, CesareCuspidi, GianfrancoParati, RitaFacchetti, GiuseppeMancia
Journal: Circulation (2009)

Background— Baseline carotid intima-media thickness (IMT) and plaques are considered predictors of cardiovascular events, but whether they maintain predictive value in treated hypertensive patients and whether time-related (or treatment-induced) IMT changes are additional predictors are unknown. Methods and Results— Analyses were performed of the data from the European Lacidipine Study on Atherosclerosis (ELSA), a large, randomized, intervention trial in which 2334 hypertensive patients from 7 European countries were followed up under effective antihypertensive treatment for 3.75 years. Kaplan–Meier curves indicated progressively lower survival free of any type of outcome except stroke, with increasing baseline IMT quartiles or increasing IMT values, even after adjustment for major baseline risk factors. Incidence of any outcome except stroke also was related to baseline number of carotid plaques. However, when both baseline and on-treatment IMT values were entered in Cox proportional-hazards models, diff...
Limitation of Excessive Extracellular Matrix Turnover May Contribute to Survival Benefit of Spironolactone Therapy in Patients With Congestive Heart Failure
Authors: FaiezZannad, FrançoisAlla, BrigitteDousset, AlfonsoPerez, BertramPitt
Journal: Circulation (2000)

Background—In congestive heart failure (CHF), extracellular matrix turnover is a major determinant of cardiac remodeling. It has been suggested that spironolactone may decrease cardiac fibrosis. We investigated the interactions between serum markers of cardiac fibrosis and the effect of spironolactone on outcome in patients with CHF. Methods and Results—A sample of 261 patients from the Randomized Aldactone Evaluation Study (RALES) were randomized to placebo or spironolactone (12.5 to 50 mg daily). Serum procollagen type I carboxy-terminal peptide, procollagen type I amino-terminal peptide, and procollagen type III amino-terminal peptide (PIIINP) were assessed at baseline and at 6 months. Baseline PIIINP >3.85 μg/L was associated with an increased risk of death (relative risk [RR] 2.36, 95% CI 1.34 to 4.18) and of death+hospitalization (RR 1.83, 95% CI 1.18 to 2.83). At 6 months, markers decreased in the spironolactone group but remained unchanged in the placebo group. The spironolactone effect on outcome...
HPV vaccine safety: Cochrane launches urgent investigation into review after criticisms
Authors: Nigel Hawkes
Journal: BMJ (2018)

A Cochrane review that gave the all-clear to vaccines designed to prevent cervical cancer did not include all the relevant trials and ignored possible sources of bias, a new analysis has found.1

The review was published in May 2017 and based its conclusions on 26 studies involving 73 428 women.2 But it could have included as many as 46 trials involving more than 120 000 women, say researchers Lars Jorgensen and Peter Gotzsche from the Nordic Cochrane Centre in Copenhagen, and Tom Jefferson of the Centre for Evidence Based Medicine in Oxford.

Cochrane reviews are meant to be the last word in evidence based medicine, winnowing out the most authoritative trials to reach conclusions on the efficacy and safety of treatments. This one provided reassuring conclusions about vaccines against human papillomavirus (HPV), the …
Abstract 158: GSKJ4, a selective jumonji histone H3 lysine27 demethylase inhibitor, targets ovarian cancer stem cells
Authors: Hirotsugu Sakaki
Journal: Cancer Research (2018)

Abstract Background/Aim: Global increase in the trimethylation of histone H3 at lysine 27 (H3K27me3) has been associated with the differentiation of normal stem cells and cancer cells, however, the role of H3K27me3 in the control of cancer stem cells (CSCs) remains poorly understood. We investigated the impact of increased H3K27me3 on ovarian CSCs using GSKJ4, a selective jumonji H3K27 demethylase inhibitor. Materials and Methods: The effect of GSKJ4 on the viability as well as on the self-renewal and tumor-initiating capacity of CSCs derived from A2780 and TOV21G human ovarian cancer cell line, was examined. Results: GSKJ4 induced cell death in A2780 CSC and TOV21G CSC at a concentration non-toxic to normal human fibroblasts. Furthermore, GSKJ4 induced differentiation and inhibited sphere formation as well as stem cell marker expression of A2780 CSC and TOV21G CSC that survived GSKJ4 treatment. Conclusion: Using ovarian CSCs as a model, we have demonstrated for the first time that GSKJ4 can target CSCs, suggesting a critical role for H3K27 methylation in their maintenance and survival. Our findings thus provide an initial clue to explore the role of GSKJ4 as a potent CSC-targeting agent for ovarian cancer and other types of human cancer. Citation Format: Hirotsugu Sakaki. GSKJ4, a selective jumonji histone H3 lysine27 demethylase inhibitor, targets ovarian cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 158.
Abstract 12149: Associations of Intima-Media Thickness of Different Segments of Carotid Arteries and Prevalent Cardio-Metabolic Diseases in Middle-age Adults and Elders in Taiwan
Authors: Li-Yu Wang, Hsin-Lung Chan, Po-Ching Chi, Chung-Lieh Hung, Chun-Chieh Liu, Tzu-Wei Wu, Shih-Wei Wang, Yih-Jer Wu, Shwun-De Wang, Hung-I Yeh
Journal: Circulation (2015)

Background and Aim: Carotid intima-media thickness (IMT) is a well-studied phenotype of atherosclerosis in developed countries, however, there was only a few studies in developing countries. The aim of the study was to explore the relationships between carotid IMTs and prevalent cardio-metabolic diseases in Chinese. Methods: 1579 residents aged 40-74 years from three communities in northern Taiwan were recruited in 2010-2012. The far-wall intima-media thickness (IMTs) of the right and left common carotid arteries (CCAs), internal carotid arteries (ICA), and carotid bifurcation (BIF) were measured by B mode ultrasound. All participants were assessed for cardio-metabolic profiles and 10-year general cardiovascular risks by the Framingham Risk Score. Results: Correlation analyses showed that there were significant linear trends with age and estimated 10-year general cardiovascular risks for all segmental carotid IMTs. The linear trends were the strongest for CCA IMTs, followed by BIF IMTs, and the least for ICA IMTs, and stronger for the average IMTs of the right and left carotid arteries than one-sided IMTs alone. Male sex, central obesity, high BMI, high LDL-/HLD-C ratio, high blood pressure, and high blood sugar were significantly correlated with thicker carotid IMTs. Subjects affected with hypertension, diabetes mellitus (DM), metabolic syndrome, and cardiovascular diseases (CVDs) had significantly thicker carotid IMTs. After adjustment for traditional cardio-metabolic risk factors, subjects who had mean or maximum CCA or mean BIF IMTs &gt;= the 3rd quartiles had significantly higher likelihoods of having prevalent CVDs. The adjusted ORs were 2.13 (95% CI: 1.30-3.49), 1.73 (95% CI: 1.06-2.82), and 1.59 (95% CI: 1.01-2.51), respectively. The adjusted ORs were not significant for subjects who had elevated mean or maximum ICA or maximum BIF IMTs. Conclusions: Carotid IMTs were significantly correlated with most traditional cardio-metabolic risk factors. Among different segmental carotid IMTs, CCA IMTs demonstrated stronger associations with prevalent CVDs and DM. Carotid IMTs may be used as an intermediate marker of advanced vascular diseases in Chinese.
Similarities Between Clinical Toxemia of Pregnancy and Experimental Hypertension
Authors: Louistobian
Journal: Circulation (1964)

Many of the features of human toxemia of pregnancy can also be found in certain types of experimental hypertension. The similarity is especially close with regard to desoxycorti-costerone hypertension in rats. A working hypothesis concerning toxemia is presented which involves the rate of synthesis of placental steroids, their rate of degradation, and the degree of antihypertensive capacity.
Explaining the Increase in Coronary Heart Disease Mortality in Beijing Between 1984 and 1999
Authors: JuliaCritchley, JingLiu, DongZhao, WangWei, SimonCapewell
Journal: Circulation (2004)

Background— Coronary heart disease (CHD) mortality is rising in many developing countries. We examined how much of the increase in CHD mortality in Beijing, China, between 1984 and 1999 could be attributed to changes in major cardiovascular risk factors and assessed the impact of medical and surgical treatments. Methods and Results— A validated, cell-based mortality model synthesized data on (1) patient numbers, (2) uptake of specific medical and surgical treatments, (3) treatment effectiveness, and (4) population trends in major cardiovascular risk factors (smoking, total cholesterol, blood pressure, obesity, and diabetes). Main data sources were the WHO MONICA and Sino-MONICA studies, the Chinese Multi-provincial Cohort Study, routine hospital statistics, and published meta-analyses. Age-adjusted CHD mortality rates increased by ≈50% in men and 27% in women (1608 more deaths in 1999 than expected by application of 1984 rates). Most of this increase (≈77%, or 1397 additional deaths) was attributable to s...
Correlation of Altmetric Attention Score With Article Citations in Cardiovascular Research
Authors: Amr F. Barakat, Nayef Nimri, Mohamed Shokr, Dhruv Mahtta, Hend Mansoor, Mohammad K. Mojadidi, Ahmed N. Mahmoud, Mourad Senussi, Ahmad Masri, Islam Y. Elgendy
Journal: Journal of the American College of Cardiology (2018)
Abstract 2821: Tousled like Kinase 1 binds to and regulates the protein kinase Nek1: Its implication in prostate cancer
Authors: Vibha Singh, Praveen K. Jaiswal, Hari K. Koul, Xiuping Yu, Arrigo Benedetti
Journal: Cancer Research (2018)

Abstract Introduction: Prostate Cancer (PCa) is one of the most common urological malignancies in men in the United States. Tousled Like kinases (TLKs) are involved in numerous cellular functions, including the DNA Damage Response (DDR). Through a novel proteomic approach, we have identified that NIMA kinase NEK1 strongly interacts and co-localizes with TLKs and has a role in the DDR, upstream of ATR and Chk1. In the present study we have tested Thioridazine (THD), an anti-psychotic drug and inhibitor of TLKs in inhibiting the activity of NEK1 in prostate cancer cell lines and LNCaP cell derived xenografts in NOD/SCID mice and the subsequent role of ATR-Chk1 axis following DNA damage. Material &amp; Methods: We have used a prostate cancer cell line viz. LNCaP, C4-2, C4-2b, 22Rv1, DU145 and PC3 and normal prostate cell line RWPE-1. Clonogenic activity was measured by colony formation assay. Immunoblotting was done for TLKs, NEK1, p-ATR and p-Chk1 protein in PCa cell line and tumor xenografts tissues. LNCaP xenografts in NOD/SCID mice were used in present study. We have used THD (alone) or in combination with the anti-androgen drug bicalutamide in PCa cell lines as well as in xenografts mice model. Results: Treatment with THD suppresses the outgrowth of androgen-independent (AI) colonies of LNCaP cells cultured with bicalutamide. Moreover, THD significantly inhibited the colony formation efficiency of several PCa cells in vitro (even of androgen independent lines). Intra-Peritoneal (I.P.) administration of THD or Bicalutamide long-term was not very effective in inhibiting tumor growth. In contrast, combination therapy of THD and Bicalutamide remarkably inhibited the tumor growth in LNCaP xenografts model. Further p-ATR and p-Chk1 axis was inhibited by treatment with THD and in combination with bicalutamide as evident by immunoblotting of residual tumors. In cells, following DNA damage, addition of the TLK inhibitor THD impaired ATR and Chk1 activation, indicating the existence of a TLK1&amp;gt;NEK1&amp;gt;ATR&amp;gt;Chk1 pathway. Conclusions: Our data indicated that THD repressed growth of PCa cells in vitro and in vivo, and for Androgen-dependent (LNCaP) cells, in combination with bicalutamide it was very effective at preventing outgrowth of AI cells and hence as a targeted ADT adjuvant therapy. Moreover, THD impaired DDR. Collectively, these results strongly suggest that THD might be a novel anti-tumor agent for use in prostate cancer. Citation Format: Vibha Singh, Praveen K. Jaiswal, Hari K. Koul, Xiuping Yu, Arrigo Benedetti. Tousled like Kinase 1 binds to and regulates the protein kinase Nek1: Its implication in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2821.
Survival signal REG3α prevents crypt apoptosis to control acute gastrointestinal graft-versus-host disease
Authors: Dongchang Zhao, Yeung-Hyen Kim, Seihwan Jeong, Joel K. Greenson, Mohammed S. Chaudhry, Matthias Hoepting, Erik R. Anderson, Marcel R.M. van den Brink, Jonathan U. Peled, Antonio L.C. Gomes, Ann E. Slingerland, Michael J. Donovan, Andrew C. Harris, John E. Levine, Umut Ozbek, Lora V. Hooper, Thaddeus S. Stappenbeck, Aaron Ver Heul, Ta-Chiang Liu, Pavan Reddy, James L.M. Ferrara
Journal: Journal of Clinical Investigation (2018)

Graft-versus-host disease (GVHD) in the gastrointestinal (GI) tract remains the major cause of morbidity and nonrelapse mortality after BM transplantation (BMT). The Paneth cell protein regenerating islet-derived 3α (REG3α) is a biomarker specific for GI GVHD. REG3α serum levels rose in the systematic circulation as GVHD progressively destroyed Paneth cells and reduced GI epithelial barrier function. Paradoxically, GVHD suppressed intestinal REG3γ (the mouse homolog of human REG3α), and the absence of REG3γ in BMT recipients intensified GVHD but did not change the composition of the microbiome. IL-22 administration restored REG3γ production and prevented apoptosis of both intestinal stem cells (ISCs) and Paneth cells, but this protection was completely abrogated in Reg3g-/- mice. In vitro, addition of REG3α reduced the apoptosis of colonic cell lines. Strategies that increase intestinal REG3α/γ to promote crypt regeneration may offer a novel, nonimmunosuppressive approach for GVHD and perhaps for other diseases involving the ISC niche, such as inflammatory bowel disease.
Abstract 3052: Identification and characterization of DPPA2 as a potential cancer stem cell marker in hepatocellular carcinoma
Authors: Dandan Yu, Qian Yan, Yu Zhang, Ling Guo, Chuanyue Wu, Xin-yuan Guan
Journal: Cancer Research (2018)

Abstract Cancer stem cells (CSC) are a small subpopulation of tumor cells that share many properties with embryonic stem cells, including the ability to differentiate and self-renew. The study of stemness-associated genes might give us a hint on the tumorigenesis and tumor progression. By comparing the expression profiles of human embryonic stem cells (ESC), endoderm, liver progenitors, premature hepatocytes as well as two pairs of non-tumor and tumor tissues of hepatocellular carcinoma (HCC), we found that the gene Developmental Pluripotency Associated 2 (DPPA2) was highly expressed in the stage of ESC, and decreased dramatically along with development, suggesting its role as a stemness associated gene. Analysis of HCC clinical samples showed that elevated expression of DPPA2 was significantly associated with differentiation, TNM stage, the number of tumor nodules and thrombus, as well as poorer prognosis. Functional studies demonstrated that DPPA2 - overexpressed cells displayed enhanced stemness feature, increasing the ability of self-renewal, tumorigenicity and chemo-resistance. We also found that overexpression of DPPA2 could increase the expression of some cancer stem cell markers. RNA-sequencing results suggested that Wnt signaling was abnormally activated after DPPA2 overexpression. Our findings point to a new potential cancer stem cell marker which may provide an attractive therapeutic target for HCC patients. Citation Format: Dandan Yu, Qian Yan, Yu Zhang, Ling Guo, Chuanyue Wu, Xin-yuan Guan. Identification and characterization of DPPA2 as a potential cancer stem cell marker in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3052.
Improvement of Endothelial Function by Chronic Angiotensin-Converting Enzyme Inhibition in Heart Failure
Authors: RémiVarin, PaulMulder, FabienneTamion, VincentRichard, Jean-PaulHenry, FrançoiseLallemand, GuyLerebours, ChristianThuillez
Journal: Circulation (2000)

Background—Chronic heart failure (CHF) impairs the endothelium-dependent, flow-mediated dilation (FMD) of small arteries. However, whether chronic angiotensin-converting enzyme (ACE) inhibition affects the impairment of FMD in CHF is unknown. We investigated the effects of long-term ACE inhibition on the FMD of peripheral arteries in rats with CHF and the mechanism(s) involved. Methods and Results—FMD was assessed in isolated, perfused gracilis muscle arteries from sham-operated, and untreated or ACE inhibitor-treated (perindopril 2 mg · kg−1 · day−1 for 10 weeks) rats with CHF (coronary artery ligation). The role of nitric oxide (NO), prostaglandins, and free radicals was assessed by pretreating the vessels with the NO synthase inhibitor NW-nitro-l-arginine, the cyclooxygenase inhibitor diclofenac, or the free radical scavenger N-2-mercaptopropionyl-glycine (MPG). Endothelial NO synthase mRNA expression was determined by reverse transcriptase polymerase chain reaction. In animals with hemodynamic and ech...