tbuckley/cabot-search huggingface dataset:
Endotoxin-induced Chorioamnionitis Modulates Innate Immunity of Monocytes in Preterm Sheep
Authors: Boris W. Kramer, Machiko Ikegami, Timothy J. M. Moss, Ilias Nitsos, John P. Newnham, Alan H. Jobe
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The preterm fetus is immune naive and has immature innate immune function. Although the preterm fetus is frequently exposed to chorioamnionitis, the effects of exposure of the fetal lung to inflammation on innate immune responses are unknown. Using the fetal sheep model of chorioamnionitis, cord blood monocytes were isolated from preterm lambs 1 to 14 days after intra-amniotic endotoxin injection, cultured for approximately 16 hours, and challenged with endotoxin in vitro. Compared with monocytes from adult sheep, the preterm monocytes produced less H(2)O(2) and interleukin-6, and toll-like receptor 4 expression was decreased. Three days after intra-amniotic endotoxin exposure, preterm monocyte responses to in vitro endotoxin challenge demonstrated decreased H(2)O(2) and interleukin-6 production and decreased CD14 and major histocompatibility complex class II expression. Preterm monocyte responses 7 to 14 days after endotoxin tended to exceed those of adults and preterm control animals indicating augmented function. In contrast, a second intra-amniotic endotoxin injection 7 days after the initial endotoxin exposure suppressed monocyte function at 14 days. The fetal monocytes demonstrated patterns of responses consistent with endotoxin tolerance (immune paralysis) as well as maturation of function. Modulation of fetal innate immune responses by exposure to inflammation may alter subsequent immune adaptation after birth.
Selective chromosome analysis in couples with two or more miscarriages: case-control study
Authors: Maureen T M Franssen, Johanna C Korevaar, Nico J Leschot, Patrick M M Bossuyt, Alida C Knegt, Klasien B J Gerssen-Schoorl, Cokkie H Wouters, Kerstin B M Hansson, Ron Hochstenbach, Kamlesh Madan, Fulco van der Veen, Mariette Goddijn
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To identify additional factors, such as maternal age or factors related to previous reproductive outcome or family history, and the corresponding probability of carrying a chromosome abnormality in couples with two or more miscarriages. <b>Design</b> Nested case-control study. <b>Setting</b> Six centres for clinical genetics in the Netherlands. <b>Participants</b> Couples referred for chromosome analysis after two or more miscarriages in 1992-2000; 279 carrier couples were marked as cases, and 428 non-carrier couples served as controls. <b>Main outcome measures</b> Independent factors influencing the probability of carrier status and the corresponding probability of carrier status. <b>Results</b> Four factors influencing the probability of carrier status could be identified: maternal age at second miscarriage, a history of three or more miscarriages, a history of two or more miscarriages in a brother or sister of either partner, and a history of two or more miscarriages in the parents of either partner. The calculated probability of carrier status in couples referred for chromosome analysis after two or more miscarriages varied between 0.5% and 10.2%. <b>Conclusions</b> The probability of carrier status in couples with two or more miscarriages is modified by additional factors. Selective chromosome analysis would result in a more appropriate referral policy, could decrease the annual number of chromosome analyses, and could therefore lower the costs.
Establishment and Characterization of a Panel of Human Uveal Melanoma Xenografts Derived from Primary and/or Metastatic Tumors
Authors: Fariba Némati, Xavier Sastre-Garau, Cécile Laurent, Jérôme Couturier, Pascale Mariani, Laurence Desjardins, Sophie Piperno-Neumann, Olivier Lantz, Bernard Asselain, Corine Plancher, Delphine Robert, Isabelle Péguillet, Marie-Hélène Donnadieu, Ahmed Dahmani, Marie-Andrée Bessard, David Gentien, Cécile Reyes, Simon Saule, Emmanuel Barillot, Sergio Roman-Roman, Didier Decaudin
Journal: Clinical Cancer Research (2010)

Uveal melanoma is the most common primary intraocular malignant tumor in adults and is defined by a poor natural outcome, as 50% of patients die from metastases. The aim of this study was to develop and characterize a panel of human uveal melanoma xenografts transplanted into immunodeficient mice.Ninety tumor specimens were grafted into severe combined immunodeficient mice, and 25 transplantable xenografts were then established (28%). Relationship between tumor graft and clinical, biological, and therapeutic features of the patients included were investigated. Characterization of 16 xenografts included histology, molecular analyses by immunohistochemistry, genetic alteration analysis (single-nucleotide polymorphism), and specific tumor antigen expression by quantitative reverse transcription-PCR. Pharmacologic characterization (chemosensitivity) was also done in four models using two drugs, temozolomide and fotemustine, currently used in the clinical management of uveal melanoma.Take rate of human uveal melanoma was 28% (25 of 90). Tumor take was independent of size, histologic parameters, or chromosome 3 monosomy but was significantly higher in metastatic tumors. Interestingly, in vivo tumor growth was prognostic for a lower metastasis-free survival in patients with primary tumors. A high concordance between the patients' tumors and their corresponding xenografts was found for all parameters tested (histology, genetic profile, and tumor antigen expression). Finally, the four xenografts studied displayed different response profiles to chemotherapeutic agents.Based on these results, this panel of 16 uveal melanoma xenografts represents a useful preclinical tool for both pharmacologic and biological assessments.
Why inflammatory phenotyping is necessary for successful drug evaluation in asthma and COPD
Authors: Peter G. Gibson
Journal: European Respiratory Journal (2013)

Identifying and treating the eosinophilic subtype of asthma has now achieved renewed importance for clinicians and scientists involved in clinical trials. This has happened following the near-demise of an anti-interleukin (IL)-5 monoclonal antibody (mepolizumab) as a candidate for asthma treatment [1] and its resurrection in trials based around using induced sputum eosinophils to identify a treatment responsive phenotype [2, 3]. The improvement in outcome was spectacular. An effect size close to zero was converted to a massive effect size of a 50% reduction in asthma exacerbations, simply by using assessment of clinical status and eosinophils to identify a treatment responsive phenotype. The spotlight is now firmly on clinical trial design in airway diseases and how to identify disease subtypes for testing new therapies. An article by Dasgupta et al . [4], in this issue of the European Respiratory Journal , addresses this issue by reporting a systematic review of the use of one biomarker, sputum eosinophils, in randomised controlled trials over the past 10 years, and assesses the implications for study design, analysis and sample size in particular.

For a long time, asthma pharmacotherapy has been based around β2-agonists and corticosteroids, which are regularly reformulated to tweak their clinical efficacy. The promise of new blockbuster treatments has remained both a hope and a necessity, but elusive. Basic scientists have elucidated …
Members of New FDA Board Tied to Industry
Authors: J. B. Finkelstein
Journal: JNCI Journal of the National Cancer Institute (2008)

The Food and Drug Administration’s most recent steps toward modernizing the drug approval process have renewed some old questions about the FDA’s relationship with the industries it regulates. Several public advocacy groups affi liated with physicians and researchers have voiced their concern over the appointment of certain members to a newly formed agency board. The groups have warned that some members may have confl icts of interest due to past or current roles as board members of pharmaceutical and biotechnology fi rms. In September, Congress passed the latest version of the Prescription Drug User Fee Act — the law that established an accelerated new-drug application process funded through industry-paid fees. It included a provision requiring the FDA to establish a private – public partnership that would facilitate the Critical Path Initiative, the agency’s ongoing effort to streamline and modernize the drug approval process. The partnership, called the Reagan – Udall Foundation, will be responsible for setting goals and priorities for the Critical Path Initiative, as well as awarding grants and contracts to meet those goals, among other things. The foundation’s board of directors, appointed by the FDA commissioner, will be largely responsible for establishing bylaws, selecting an executive director to oversee day-to-day operations, and reporting to Congress on foundation activities and operations. The federal statute stipulates that of the 14 members named to the board, four members should come from industry, three from academia, two from consumer or patient advocacy organizations, and one from the health provider community. The remaining four spots are open to anyone with relevant expertise. The FDA has already chosen the members and is organizing the Reagan – Udall Foundation. However, some advocacy groups are concerned that several nonindustry members have strong ties to pharmaceutical and biotechnology companies, including one who is currently under investigation by the Senate Finance Committee. Tadataka “Tachi” Yamada, M.D., currently heads the Bill and Melinda Gates Foundation’s global health program but until 2006 worked as head of research for the pharmaceutical company GlaxoSmithKline. Senate investigators have uncovered evidence suggesting that, during his tenure with the company, he may have been involved in an effort to intimidate a scientist who was raising questions about the heart risks associated with the com pany’s blockbuster diabetes drug rosiglitazone maleate (Avandia). In a news article published in Nature
Novel approaches for the identification of biomarkers of aggressive prostate cancer
Authors: Yunee Kim, Thomas Kislinger
Journal: Genome Medicine (2013)

The ability to distinguish indolent from aggressive prostate tumors remains one of the greatest challenges in the management of this disease. Ongoing efforts to establish a panel of molecular signatures, comprising gene expression profiles, proteins, epigenetic patterns, or a combination of these alterations, are being propelled by rapid advancements in 'omics' technologies. The identification of such biomarkers in biological fluids is an especially attractive goal for clinical applications. Here, we summarize recent progress in the identification of candidate prognostic biomarkers of prostate cancer using biological fluid samples.
Drug treatment of adults with nausea and vomiting in primary care
Authors: J. S. Furyk, R. Meek, S. McKenzie
Journal: BMJ (2014)

A usually healthy 25 year old man presents to you as his general practitioner at 9 am. He has had fluctuating nausea with four vomits and one loose stool overnight, associated with colicky central abdominal pain. No blood was present in the vomit or stool, and he reports that his girlfriend was recently diagnosed as having “viral gastro.” He is afebrile, intermittently uncomfortable, but otherwise well, with mild epigastric tenderness but no guarding or rebound. Clinically, you believe viral gastroenteritis is the most likely cause of his symptoms, and you consider his request for treatment that will help to stop his vomiting so that he can get to his evening shift at a factory.

Nausea and vomiting are a common reason for patients to seek treatment in primary care, which we take here to include general practice and the emergency department. Identification and management of underlying problems are important, if these are apparent on clinical grounds. This article will focus on common causes in primary care such as gastroenteritis (usually viral), adverse drug reactions, pregnancy, vestibular disorders, and motion sickness. Other causes of nausea and vomiting such as postoperative, chemotherapy and radiotherapy associated, and specific conditions such as migraines are briefly discussed but are beyond the scope of this article.

Although still incompletely understood, nausea and vomiting are thought to follow activation of a medullary “vomiting centre,” by either afferent input from the gastrointestinal tract due to presence of local irritants or stimulation of the central chemoreceptor trigger zone by circulating emetogenic substances; however, other pathways exist. Dopamine and serotonin seem to be key transmitters both centrally and in the gastrointestinal tract.

Surveys of emergency physicians in Australia and the United States identified the most commonly prescribed agents as metoclopramide, prochlorperazine, promethazine, droperidol, and ondansetron.1 2 Anecdotally, cyclizine and …
Haemodynamic response to exercise after combined sympathetic and parasympathetic blockade of the heart
Authors: I. Nordenfelt
Journal: Cardiovascular Research (1971)

Journal Article Haemodynamic response to exercise after combined sympathetic and parasympathetic blockade of the heart Get access I. Nordenfelt I. Nordenfelt From the Department of Clinical Physiology, Lasarettet, Lund, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 5, Issue 2, April 1971, Pages 215–222, https://doi.org/10.1093/cvr/5.2.215 Published: 01 April 1971
Effect of mental stress and nitroglycerin on vascular compliance in human volunteers
Authors: U.J. Chaudhari, S.C. Umansky, M. Diem, M.E. Bradley, L.A. Acculto, G. Cuozzo, A. Madrid, R. Cody, N.M. Cosgrove, J.A. Barone, C.R. Lacy, J.B. Kostis
Journal: Journal of the American College of Cardiology (1998)
Transport of K <sup>42+</sup> , Na <sup>24+</sup> , and I <sup>131</sup> + by the Pulmonary Circulation
Authors: DAVID YUDILEVICH
Journal: Circulation Research (1961)

The transport of K 42+ , Na 24+ , and I 131+ by blood through the heart and lungs in the canine heart-lung preparation was studied. Simultaneous injection of each tracer was performed together with nondiffusible Risa as a reference label. The data show that in a single passage through the lung, a fraction of the injected radioactive electrolyte moves out from the blood and partially returns. This alters the shapes of the dilution curves and the results of cardiac output and central volume calculations. The implications of these findings in the suggested use of radioactive electrolytes for the application of the Stew art-Hamilton method in human and animal investigations is discussed. The possibility is suggested that in the Starling preparation, the difference in flows calculated from the extrapolated and complete dilution curves of a non-diffusible tracer may he related to the coronary flow.
Activation of vascular BK channels by docosahexaenoic acid is dependent on cytochrome P450 epoxygenase activity
Authors: R.-x. Wang, Q. Chai, T. Lu, H.-C. Lee
Journal: Cardiovascular Research (2010)

n-3 Polyunsaturated fatty acids (PUFAs) are known to protect the cardiovascular system and improve blood pressure control. These important dietary constituents are converted into bioactive metabolites, but their role in regulation of the cardiovascular system is unclear. In particular, the functions of the cytochrome P450 (CYP) metabolites of n-3 PUFAs remain virtually unexplored. In this study, we examined the effects of docosahexaenoic acid (DHA) on the regulation of large-conductance calcium-activated potassium (BK) channel activities in coronary arterial smooth muscle cells. Using whole-cell patch-clamp techniques, we found that DHA is a potent activator of BK currents in rat coronary arterial smooth muscle cells with an EC50 of 0.23 ± 0.03 µM. This effect was abolished by pre-incubation with the CYP epoxygenase inhibitor, SKF525A (10 µM). The effects of DHA on the BK channels were reproduced by 16,17-epoxydocosapentaenoic acid (16,17-EpDPE) with an EC50 of 19.7 ± 2.8 nM. The physiological role of the CYP metabolites of DHA was confirmed by measuring DHA-mediated vasodilatation in isolated rat coronary arteries. DHA dilated pressurized isolated coronary arteries in a dose-dependent manner, and the DHA effects were abolished after pre-treatment with SKF525A (10 µM) or with iberiotoxin (100 nM). In addition, 16,17-EpDPE directly produced coronary vasodilatation that was iberiotoxin sensitive. These results suggest that DHA-mediated vasodilatation is mediated through CYP epoxygenase metabolites by activation of vascular BK channels.
PIKing the Right Patient
Authors: Alexa B. Turke, Jeffrey A. Engelman
Journal: Clinical Cancer Research (2010)

Abstract HER2 amplification and PIK3CA mutation were validated as biomarkers for sensitivity to the single-agent phosphoinositide 3-kinase (PI3K) inhibitor, GDC-0941, in breast cancer models. A novel expression profile was developed to identify other breast cancers sensitive to PI3K inhibitors. These expression studies highlighted feedback networks connecting TORC1, PI3K, and mitogen-activated protein kinase (MAPK) pathways, and underscored the potential for combination therapies. Clin Cancer Res; 16(14); 3523–5. ©2010 AACR.
Platelet Granule Secretion Continuously Prevents Intratumor Hemorrhage
Authors: Benoit Ho-Tin-Noé, Tobias Goerge, Stephen M. Cifuni, Daniel Duerschmied, Denisa D. Wagner
Journal: Cancer Research (2008)

Abstract Cancer is associated with a prothrombogenic state capable of platelet activation. Platelets, on the other hand, can support angiogenesis, a process involved in the progression of tumor growth and metastasis. However, it is unclear whether platelet/tumor interactions substantially contribute to tumor physiology. We investigated whether platelets stabilize tumor vessels and studied the underlying mechanisms. We induced severe acute thrombocytopenia in mice bearing s.c. Lewis lung carcinoma or B16F10 melanoma. Intravital microscopy revealed that platelet depletion led to a rapid destabilization of tumor vessels with intratumor hemorrhage starting as soon as 30 min after induction of thrombocytopenia. Using an inhibitor of glycoprotein Ibα (GPIbα) and genetically engineered mice with platelet adhesion defects, we investigated the role of platelet adhesion receptors in stabilizing tumor vessels. We found that a single defect in either GPIbα, von Willebrand factor, P-selectin, or platelet integrin activation did not lead to intratumor hemorrhage. We then compared the ability of transfused resting and degranulated platelets to prevent intratumor hemorrhage. Whereas resting platelets prevented thrombocytopenia-induced tumor bleeding, circulating degranulated platelets did not. This suggests that the prevention of intratumor hemorrhage by platelets relies on the secretion of the content of platelet granules. Supporting this hypothesis, we further found that thrombocytopenia dramatically impairs the balance between propermeability and antipermeability factors in tumor-bearing animals, in particular depleting blood of angiopoietin-1 and serotonin. Our results show a crucial contribution of platelets to tumor homeostasis through continuous prevention of severe intratumor hemorrhage and consequent cell death. The study also suggests platelet function as a reasonable target for specific destabilization of tumor vessels. [Cancer Res 2008;68(16):6851–8]
PREVENTION OF GRAM-NEGATIVE SHOCK AND DEATH IN SURGICAL PATIENTS BY ANTIBODY TO ENDOTOXIN CORE GLYCOLIPID
Authors: Jean-Daniel Baumgartner, J.Allen Mccutchan, Guy Van Melle, Markus Vogt, Ruedi Luethy, MichelP. Glauser, ElizabethJ. Ziegler, MelvilleR. Klauber, Erika Muehlen, Rene Chiolero, Stefanos Geroulanos
Journal: The Lancet (1985)
Hydatid cyst of the liver with intrathoracic rupture.
Authors: D S Xanthakis, E Katsaras, M Efthimiadis, G Papadakis, G Varouchakis, C Aligizakis
Journal: Thorax (1981)

In the last 10 years we have operated on 33 cases of hydatid cyst of the liver with intrathoracic rupture. Twenty-one out of 33 cases ruptured into bronchi, in seven the rupture affected the pleural cavity, and in six simultaneous rupture into the bronchus and pleural cavity occurred. Laboratory tests were not carried out in all cases. The Casoni intradermal test was carried out in 23 cases and was positive in 18. A liver scan was performed in 10 and was positive in all. Conservative operations were carried out in 22 patients. In these the hepatic cavity was evacuated and separately drained. This was followed by suturing the diaphragmatic rupture and also closing the bronchial opening if present. Lung resections were performed in 11 out of 33 cases. In eight lobectomy was carried out and in three segmental resections. Resection was necessary when suppuration and bronchiectatic changes affected the lung. Ruptured cyst into the pleural cavity requires emergency thoracotomy after the anaphylactic shock is over. Removal of the parasite, re-expansion of the lung, and drainage of the pleural and hepatic cavities is necessary. Immediate and late complications occurred in 13 patients. In two postoperative haemorrhage occurred and in two postoperative empyema developed. Recurrent haemoptysis was seen in five, persistent bile fistula in one, and dissemination of hydatid cyst in three. In the remaining 20 cases there was no complication. Operative mortality was nil.
Innate immune response to respiratory syncytial virus and human rhinovirus in infants: Similarities and differences its effect on disease severity
Authors: Patricia Diaz, Aldo Gaggero, Guillermo Zepeda, Ricardo Pinto, Mabel Rivas, Maria Lina Boza, Maria Rosa Bono, Paola Uasapud
Journal: European Respiratory Journal (2014)

Respiratory syncytial virus (RSV) and Human rhinovirus (HRV) may cause lower tract respiratory infection. The contribution of the host response to disease severity is unclear. We studied the innate immune response of RSV infected patients of different severity compared to patients co-infected with HRV and HRV infected patients with a control group.

We studied in the nasopharyngeal aspirate (NPA) and in the plasma the following cytokines: IL-12, TNF-α, IL-10, IL-6, IL-1β, IL-8. A score previously described (Pediatrics 2012; 130:e840-11) was used to define severity. RSV load and HRV were determined by a qPCR technique. Cytokines were quantified by flow cytometry. Results were expressed as medians and analysis was performed by non-parametric test ANOVA Kruskal-Wallis. Study was approval by the ethics committee.

We identified 86 RSV infected infants, 38 had a severe disease, 28 a mild disease, 20 co-infected with HRV, 26 HRV infected and 33 controls. The severity was similar in RSV patients either with or without co-infection with HRV. Patients only infected with HRV had a mild disease. IL-6 obtained from NPA and plasma from mild RSV patients was significantly (p<0.05) increased compared to mild HRV. IL-12 obtained from plasma was increased (p<0.05) in HRV infected patients compared to mild RSV infected infants. All inflammatory cytokines were increased in plasma and NPA from HRV infected patients compared to healthy controls

Both viruses, RSV and HRV induce an innate inflammatory response. Il-12 and IL-6 have a different expression according to the type of virus and the severity of the desease.

Supported by a grant from Fondecyt 1120411.
Management of hepatocellular carcinoma in Asia: consensus statement from the Asian Oncology Summit 2009
Authors: Donald Poon, Benjamin O Anderson, Li-Tzong Chen, Koichi Tanaka, Wan Yee Lau, Eric Van Cutsem, Harjit Singh, Wan Cheng Chow, London Lucien Ooi, Pierce Chow, Maung Win Khin, Wen Hsin Koo
Journal: The Lancet Oncology (2009)