tbuckley/cabot-search huggingface dataset:
Increased endothelin levels in congestive heart failure: does it come from the lungs? Does it matter?
Authors: J DUPUIS
Journal: Cardiovascular Research (2004)

Endothelin-1 (ET) is a potent vasoconstrictor and promitogenic peptide produced ubiquitously by the vascular endothelium.It is formed by cleavage of the 39amino acid precursor big endothelin-1 (big ET) through the action of the endothelin converting enzymes (ECEs).Although it is generally accepted that ET is released constitutively in a preferentially paracrine fashion, a smaller, measurable fraction is released into the vascular lumen.Circulating ET levels are increased in various cardiovascular conditions, including congestive heart failure (CHF) [1-3], and are related to the subsequent event rate [4].At first glance, it could be straightforwardly concluded that higher circulating ET levels reflects activation of this system, with increased synthesis and subsequent overflow into plasma.The biology of the ET system, however, is more intricate due to the presence of endothelial ET B receptors that are capable of clearing circulating ET from plasma [5].Thus, the increase in circulating ET could result from increased production, reduced clearance, or a combination of both.Since the lungs display the highest ET and ECE content and are recognized as the major site for circulating ET clearance, they may occupy a central role in the modulation of plasma ET.The observation that ET levels correlate especially well with the severity of pulmonary hypertension associated with CHF lends support to this hypothesis.These observations therefore raise the possibility that increased plasma ET levels could reflect the severity of pulmonary vascular endothelial dysfunction associated with CHF.
32 Increased expression of renal neutral endopeptidase (EC 3.4.24.11) in rats with CCL4-induced ascitic cirrhosis: Acute effects of its pharmacological inhibition with IV. Candoxatrilat
Authors: G. Sansoe, M. Aragno, R. Mastrocola, F. Restivo, S. Silvano, G. Mengozzi, A. Smedile, F. Rosina, O. Danni, M. Rizzetto
Journal: Journal of Hepatology (2004)
Adriamycin cardiomyopathy in the rabbit: alterations in contractile proteins and myocyte function
Authors: S M. Jones, M. S Kirby, S. E Harding, V. Giorgio, R. B Wanless, L. D. Libera, P. A Poole-Wilson
Journal: Cardiovascular Research (1990)

Journal Article Adriamycin cardiomyopathy in the rabbit: alterations in contractile proteins and myocyte function Get access S Mary Jones, S Mary Jones Correspondence to: Dr Harding Search for other works by this author on: Oxford Academic PubMed Google Scholar Mark S Kirby, Mark S Kirby Search for other works by this author on: Oxford Academic PubMed Google Scholar Sian E Harding, Sian E Harding Search for other works by this author on: Oxford Academic PubMed Google Scholar Vescova Giorgio, Vescova Giorgio Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard B Wanless, Richard B Wanless Search for other works by this author on: Oxford Academic PubMed Google Scholar Luciano Dalla Libera, Luciano Dalla Libera Search for other works by this author on: Oxford Academic PubMed Google Scholar Philip A Poole-Wilson Philip A Poole-Wilson Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 24, Issue 10, October 1990, Pages 834–842, https://doi.org/10.1093/cvr/24.10.834 Published: 01 October 1990 Article history Received: 14 February 1990 Accepted: 16 May 1990 Published: 01 October 1990
Trial of Roxithromycin in Subjects with Asthma and Serological Evidence of Infection with<i>Chlamydia pneumoniae</i>
Authors: PETER N. BLACK, FRANCESCO BLASI, CHRISTINE R. JENKINS, RAFFAELE SCICCHITANO, GRAHAM D. MILLS, ABRAHAM R. RUBINFELD, RICHARD E. RUFFIN, PETER R. MULLINS, JOSETTE DANGAIN, BRUCE C. COOPER, DENISE BEM DAVID, LUIGI ALLEGRA
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

An association has been reported between chronic infection with Chlamydia pneumoniae and the severity of asthma, and uncontrolled observations have suggested that treatment with antibiotics active against C. pneumoniae leads to an improvement in asthma control. We studied the effect of roxithromycin in subjects with asthma and immunoglobulin G (IgG) antibodies to C. pneumoniae ⩾ 1:64 and/or IgA antibodies ⩾ 1:16. A total of 232 subjects, from Australia, New Zealand, Italy, or Argentina, were randomized to 6 wk of treatment with roxithromycin 150 mg twice a day or placebo. At the end of 6 wk, the increase from baseline in evening peak expiratory flow (PEF) was 15 L/min with roxithromycin and 3 L/min with placebo (p = 0.02). With morning PEF, the increase was 14 L/min with roxithromycin and 8 L/min with placebo (NS). In the Australasian population, the increase in morning PEF was 18 L/min and 4 L/min, respectively (p = 0.04). At 3 mo and 6 mo after the end of treatment, differences between the two groups were smaller and not significant. Six weeks of treatment with roxithromycin led to improvements in asthma control but the benefit was not sustained. Further studies are necessary to determine whether the lack of sustained benefit is due to failure to eradicate C. pneumoniae. Keywords: asthma; Chlamydia pneumoniae; roxithromycin; randomized, controlled trial
The hepatitis B virus X protein promotes tumor cell invasion by inducing membrane-type matrix metalloproteinase-1 and cyclooxygenase-2 expression
Authors: Enrique Lara-Pezzi, Maria Victoria Gómez-Gaviro, Beatriz G. Gálvez, Emilia Mira, Miguel A. Iñiguez, Manuel Fresno, Carlos Martínez-A., Alicia G. Arroyo, Manuel López-Cabrera
Journal: Journal of Clinical Investigation (2002)

Hepatocellular carcinoma is strongly associated with chronic infection by the hepatitis B virus (HBV) and has poor prognosis due to intrahepatic metastasis. HBx is often the only HBV protein detected in hepatic tumor cells; however, its contribution to tumor invasion and metastasis has not been established so far. In this work, we show that HBx enhances tumor cell invasion, both in vivo and in vitro. The increased invasive capacity induced by HBx is mediated by an upregulation of membrane-type 1 matrix metalloproteinase (MT1-MMP) expression, which in turn activates matrix metalloproteinase-2. Induction of both MT1-MMP expression and cell invasion by HBx is dependent on cyclooxygenase-2 (COX-2) activity. In addition, HBx upregulates the expression of COX-2, which is mediated by the transcriptional activation of the COX-2 gene promoter in a nuclear factor of activated T cell–dependent (NF-AT–dependent) manner. These results demonstrate the ability of HBx to promote tumor cell invasion by a mechanism involving the upregulation of MT1-MMP and COX-2 and provide new insights into the mechanism of action of this viral protein and its involvement in tumor metastasis and recurrence of hepatocellular carcinoma.
Eicosapentaenoic acid and chemoprevention of FAP
Authors: P. M. Lynch
Journal: Gut (2010)

In this issue of Gut , West et al 1 report positive results of a chemoprevention trial in British subjects with familial adenonomatous polyposis (FAP) ( see page 918 ).

There is a long history of use of natural products in FAP and other adenoma prevention trials.2 4 In most cases the rationale seems predicated on notions of likely safety and acceptability, as well as hoped-for efficacy. Moreover, since FAP is an uncommon disease, the greater significance of any positive FAP trial seems to be in the potential for carrying over the experience gained from a relatively easy-to-conduct FAP trial to the testing of the same agent(s) in the much larger population of subjects with non-familial polyps. Put another way, if an agent such as fish oil can actually regress adenomas in FAP, then it may well hold promise in sporadic adenoma patients.

There are both opportunities and challenges in conducting chemoprevention trials in FAP. First, while FAP is a great human model for human ‘adenomagenesis’ and colorectal carcinogenesis, it must be borne in mind that regression of adenomas is not the same as prevention of adenomas. In FAP, sulindac was shown to regress existing adenomas but not to prevent initial ones.5 6 Thus, the stage of disease may matter.

Second, the limited sample sizes and duration of treatment in FAP trials may fail to demonstrate other problems. The experience with COX2 inhibitors7 8 is instrumental here. Because several trials showed …
Heat Stress: Effects Upon Coagulation.
Authors: Lewis H. Dennis
Journal: Annals of Internal Medicine (1969)

s1 May 1969Heat Stress: Effects Upon Coagulation.Lewis H. Dennis, M.D., M. Bernadette Garvey, F.R.C.P. (C), Jesse Hano, M.D., Marcel E. Conrad, M.D., F.A.C.P.Lewis H. Dennis, M.D.Search for more papers by this author, M. Bernadette Garvey, F.R.C.P. (C)Search for more papers by this author, Jesse Hano, M.D.Search for more papers by this author, Marcel E. Conrad, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1082_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptRecent work showed that heat stroke is a hypercoagulable state associated with classic findings of disseminated intravascular coagulation, including depression of labile clotting factors V and VIII, increased fibrinolytic activity, and the appearance of fibrinogen degradation products. To investigate this phenomenon coagulation studies were performed on heat-acclimatized and -unacclimatized individuals undergoing the standard exercise and combat proficiency test of the U. S. Army at Fort Sam Houston, Tex. Ambient temperatures during the period of investigation averaged 100 F. Studies were conducted immediately before and after exercise. These studies were first performed within 3 days after the subject arrived in a... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Lewis H. Dennis, M.D.; M. Bernadette Garvey, F.R.C.P. (C); Jesse Hano, M.D.; Marcel E. Conrad, M.D., F.A.C.P.Affiliations: Washington, D. C. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byRenal, Metabolic, and Circulatory Responses to Heat and Exercise Studies in Military Recruits During Summer Training, with Implications for Acute Renal FailureROBERT W. SCHRIER, JESSE HANO, HOWARD I. KELLER, RICHARD M. FINKEL, PAUL F. GILLILAND, WILLIAM J. CIRKSENA, PAUL E. TESCHAN 1 May 1969Volume 70, Issue 5Page: 1082-1083KeywordsDisseminated intravascular coagulationExerciseFibrinogenStandard exerciseStrokeTemperature ePublished: 1 December 2008 Issue Published: 1 May 1969 PDF downloadLoading ...
The Genomic Landscape of Breast Cancer as a Therapeutic Roadmap
Authors: Matthew J. Ellis, Charles M. Perou
Journal: Cancer Discovery (2013)

Abstract Summary: The application of high-throughput techniques to profile DNA, RNA, and protein in breast cancer samples from hundreds of patients has profoundly increased our knowledge of the disease. The etiologic events that drive breast cancer are finally coming into focus and should be used to set priorities for clinical trials. In this Prospective, we summarize some of the headline conclusions from 6 recent breast cancer “omics profiling” articles in Nature, with an emphasis on the implications for systemic therapy. Cancer Discov; 3(1); 27–34. ©2012 AACR.
The Role of Investigational Therapy in Management of Patients With Advanced Metastatic Malignancy
Authors: Emil J Freireich, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2008)

There is reason for patients and physicians to question the role of palliative chemotherapy in patients with advanced malignancy. In this unfortunate clinical situation, patients and physicians often turn to palliative care and hospice care in lieu of chemotherapy, which is clearly palliative and offers the prospect of limited effectiveness with unpleasant adverse effects. The important question to be asked is when is it too soon to abandon the prospects for a favorable outcome from investigational therapy. Many authors have concluded that investigational therapy offers such small promise of benefit that it is not worth considering. It is the purpose of this communication to emphasize the potential for investigational therapy; to illustrate it with a description of two real patient experiences; and to encourage physicians not to abandon therapeutic approaches for their patients too soon.
Accident and emergency department attendance by asthmatic children.
Authors: S M O'Halloran, D P Heaf
Journal: Thorax (1989)

Attendances at the accident and emergency department of a children's hospital for treatment of acute asthma were studied for one year to determine the characteristics of the children attending and their management. Eight hundred and twenty children, median age 5.5 years, made 1389 visits. Records were available from 1046 visits. Clinical information and assessment of the severity of the attack in the department was often inadequate. Peak flow records were available for 366 (35%). Attendances were most frequent in September and during the evening, but there was no significant day to day variation. Eight hundred and three children (78%) were self referred. Before attendance 962 (92%) had used a bronchodilator, including nebulised salbutamol (11%); 2% had taken prednisolone and 21% antibiotics. Five hundred and sixteen visits (49%) led to admission and 19% of those admitted required intravenous treatment. Probably some children who at present attend hospital for treatment of acute asthma could be managed at home, but this cannot be assumed without better understanding of the reasons for hospital attendance. More information is needed.
EZH2-Mediated Concordant Repression of Wnt Antagonists Promotes β-Catenin–Dependent Hepatocarcinogenesis
Authors: Alfred S.L. Cheng, Suki S. Lau, Yangchao Chen, Yutaka Kondo, May S. Li, Hai Feng, Arthur K. Ching, Kin F. Cheung, Hoi K. Wong, Joanna H. Tong, Hongchuan Jin, Kwong W. Choy, Jun Yu, Ka F. To, Nathalie Wong, Tim H.-M. Huang, Joseph J.Y. Sung
Journal: Cancer Research (2011)

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the Polycomb-repressive complex 2 (PRC2) that represses gene transcription through histone H3 lysine 27 trimethylation (H3K27me3). Although EZH2 is abundantly present in various cancers, the molecular consequences leading to oncogenesis remain unclear. Here, we show that EZH2 concordantly silences the Wnt pathway antagonists operating at several subcellular compartments, which in turn activate Wnt/β-catenin signaling in hepatocellular carcinomas (HCC). Chromatin immunoprecipitation promoter array and gene expression analyses in HCCs revealed EZH2 occupancy and reduced expression of Wnt antagonists, including the growth-suppressive AXIN2, NKD1, PPP2R2B, PRICKLE1, and SFRP5. Knockdown of EZH2 reduced the promoter occupancy of PRC2, histone deacetylase 1 (HDAC1), and H3K27me3, whereas the activating histone marks were increased, leading to the transcriptional upregulation of the Wnt antagonists. Combinatorial EZH2 and HDAC inhibition dramatically reduced the levels of nuclear β-catenin, T-cell factor-dependent transcriptional activity, and downstream pro-proliferative targets CCND1 and EGFR. Functional analysis revealed that downregulation of EZH2 reduced HCC cell growth, partially through the inhibition of β-catenin signaling. Conversely, ectopic overexpression of EZH2 in immortalized hepatocytes activated Wnt/β-catenin signaling to promote cellular proliferation. In human HCCs, concomitant overexpression of EZH2 and β-catenin was observed in one-third (61/179) of cases and significantly correlated with tumor progression. Our data indicate that EZH2-mediated epigenetic silencing contributes to constitutive activation of Wnt/β-catenin signaling and consequential proliferation of HCC cells, thus representing a novel therapeutic target for this highly malignant tumor.
Role of Asymmetric Dimethylarginine in Vascular Injury in Transgenic Mice Overexpressing Dimethylarginie Dimethylaminohydrolase 2
Authors: Kazuhiro Hasegawa, Shu Wakino, Satoru Tatematsu, Kyoko Yoshioka, Koichiro Homma, Naoki Sugano, Masumi Kimoto, Koichi Hayashi, Hiroshi Itoh
Journal: Circulation Research (2007)

Dimethylarginie dimethylaminohydrolase (DDAH) degrades asymmetric dimethylarginine (ADMA), an endogenous nitric oxide (NO) synthase inhibitor, and comprises 2 isoforms, DDAH1 and DDAH2. To investigate the in vivo role of DDAH2, we generated transgenic mice overexpressing DDAH2. The transgenic mice manifested reductions in plasma ADMA and elevations in cardiac NO levels but no changes in systemic blood pressure (SBP), compared with the wild-type mice. When infused into wild-type mice for 4 weeks, ADMA elevated SBP and caused marked medial thickening and perivascular fibrosis in coronary microvessels, which were accompanied by ACE protein upregulation and cardiac oxidative stress. The treatment with amlodipine reduced SBP but failed to ameliorate the ADMA-induced histological changes. In contrast, these changes were abolished in transgenic mice, with a reduction in plasma ADMA. In coronary artery endothelial cells, ADMA activated p38 MAP kinase and the ADMA-induced ACE upregulation was suppressed by p38 MAP kinase inhibition by SB203580. In wild-type mice, long-term treatment with angiotensin II increased plasma ADMA and cardiac oxidative stress and caused similar vascular injury. In transgenic mice, these changes were attenuated. The present study suggests that DDAH2/ADMA regulates cardiac NO levels but has modest effect on SBP in normal conditions. Under the circumstances where plasma ADMA are elevated, including angiotensin II-activated conditions, ADMA serves to contribute to the development of vascular injury and increased cardiac oxidative stress, and the overexpression of DDAH2 attenuates these abnormalities. Collectively, the DDAH2/ADMA pathway can be a novel therapeutic target for vasculopathy in the ADMA or angiotensin II-induced pathophysiological conditions.
Medium-chain and long-chain acyl CoA dehydrogenase deficiency: Clinical, pathologic and ultrastructural differentiation from Reye's syndrome
Authors: William R. Treem, Camillus A. Witzleben, David A. Piccoli, Charles A. Stanley, Daniel E. Hale, Paul M. Coates, John B. Watkins
Journal: Hepatology (1986)

The clinical and pathologic findings in 12 patients with medium-chain acyl CoA dehydrogenase deficiency and three patients with long-chain acyl CoA dehydrogenase deficiency are summarized. Although these inborn errors of intramitochondrial beta-oxidation of fatty acids present with similar findings to Reye's syndrome, there are clinical, laboratory and hepatic histologic differences. Younger age at presentation, history of unexplained sibling death, a previous episode of lethargy, hypoglycemia or acidosis precipitated by fasting stress and only mildly elevated serum transaminases with normal or only mildly prolonged prothrombin time may all suggest an acyl CoA dehydrogenase deficiency. Long-chain acyl CoA dehydrogenase deficiency is differentiated from medium-chain acyl CoA dehydrogenase deficiency by younger age at presentation, more profound cardiorespiratory depression, evidence of cardiomyopathy, and sequelae of muscle weakness, hypotonia and developmental delay. Definitive diagnosis is made by assay of medium-chain or long-chain enzyme activity in cultured skin fibroblasts or in leukocytes. Hepatic light microscopic alterations are essentially limited to steatosis, which may be either macro- or microvesicular. The cases with microvesicular steatosis can be differentiated morphologically from Reye's syndrome by electron microscopy, showing the absence of the mitochondrial changes characteristic of Reye's. Four of seven cases of acyl CoA dehydrogenase deficiency showed some variations from normal in the appearance of the hepatocyte mitochondria. The relationship of these variations to the basic metabolic defect(s) remains to be determined.
Radiogenomics: Using Genetics to Identify Cancer Patients at Risk for Development of Adverse Effects Following Radiotherapy
Authors: Sarah L. Kerns, Harry Ostrer, Barry S. Rosenstein
Journal: Cancer Discovery (2014)

Abstract Normal-tissue adverse effects following radiotherapy are common and significantly affect quality of life. These effects cannot be accounted for by dosimetric, treatment, or demographic factors alone, and evidence suggests that common genetic variants are associated with radiotherapy adverse effects. The field of radiogenomics has evolved to identify such genetic risk factors. Radiogenomics has two goals: (i) to develop an assay to predict which patients with cancer are most likely to develop radiation injuries resulting from radiotherapy, and (ii) to obtain information about the molecular pathways responsible for radiation-induced normal-tissue toxicities. This review summarizes the history of the field and current research. Significance: A single-nucleotide polymorphism–based predictive assay could be used, along with clinical and treatment factors, to estimate the risk that a patient with cancer will develop adverse effects from radiotherapy. Such an assay could be used to personalize therapy and improve quality of life for patients with cancer. Cancer Discov; 4(2); 155–65. ©2014 AACR.
Hypnotic Visual Illusion Alters Color Processing in the Brain
Authors: Stephen M. Kosslyn, William L. Thompson, Maria F. Costantini-Ferrando, Nathaniel M. Alpert, David Spiegel
Journal: American Journal of Psychiatry (2000)

This study was designed to determine whether hypnosis can modulate color perception. Such evidence would provide insight into the nature of hypnosis and its underlying mechanisms.Eight highly hypnotizable subjects were asked to see a color pattern in color, a similar gray-scale pattern in color, the color pattern as gray scale, and the gray-scale pattern as gray scale during positron emission tomography scanning by means of [(15)O]CO(2). The classic color area in the fusiform or lingual region of the brain was first identified by analyzing the results when subjects were asked to perceive color as color versus when they were asked to perceive gray scale as gray scale.When subjects were hypnotized, color areas of the left and right hemispheres were activated when they were asked to perceive color, whether they were actually shown the color or the gray-scale stimulus. These brain regions had decreased activation when subjects were told to see gray scale, whether they were actually shown the color or gray-scale stimuli. These results were obtained only during hypnosis in the left hemisphere, whereas blood flow changes reflected instructions to perceive color versus gray scale in the right hemisphere, whether or not subjects had been hypnotized.Among highly hypnotizable subjects, observed changes in subjective experience achieved during hypnosis were reflected by changes in brain function similar to those that occur in perception. These findings support the claim that hypnosis is a psychological state with distinct neural correlates and is not just the result of adopting a role.
Omalizumab pretreatment prevents allergic reactions due to rush immunotherapy (RIT)
Authors: T.B. Casale, J.N. Kline, W.W. Busse, Z.K. Ballas, M. Mokhtarani, V. Seyfert-Margolis, K. Bateman, M.H. Moss, R.G. Townley
Journal: Journal of Allergy and Clinical Immunology (2005)
Ipilimumab treatment enhances CD4+ T cell activation while decreasing Treg and MDSC frequency in advanced melanoma patients
Authors: Yago Pico de Coaña, Isabel Poschke, Yuya Yoshimoto, Sara Karlberg, Maria Nyström, Maria Wolodarski, Johan Hansson, Giuseppe Masucci, Rolf Kiessling
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Ipilimumab is a fully human antibody that blocks CTLA-4 and has proven to extend overall survival in patients with unresectable stage III or stage IV melanoma. There is a need for well-documented pharmacodynamic markers together with potential predictive biomarkers that may allow