tbuckley/cabot-search huggingface dataset:
Hypertrophic cardiomyopathy characterised by -adrenoceptor density, relative amount of -adrenoceptor subtypes and adenylate cyclase activity
Authors: S. GOLF, E. MYHRE, M. ABDELNOOR, D. ANDERSEN, V. HANSSON
Journal: Cardiovascular Research (1985)

The total quantity of beta-adrenoceptors and the relative amount of beta 1 and beta 2 receptor subtypes were determined in heart biopsies of 10 patients with various heart diseases and 5 patients suffering from hypertrophic cardiomyopathy (HOCM). In membrane particle preparations from the same patients we also examined the activity of the adenylate cyclase (AC), and its response to isoprenaline, terbutaline, histamine and sodium fluoride (NaF). The high affinity ligand [125I] (1)-cyanopindolol (CYP) was used in the binding assays, and the highly beta 2-selective antagonist ICI 118 551 for the determination of beta-adrenoceptor subtypes. No differences were found in total beta-adrenoceptor density between patients with HOCM and "controls" (27.6 +/- 14.2 vs 26.5 +/- 10.7 fmol . mg-1 protein). The relative amounts of beta 1 and beta 2 receptor subtypes were similar, patients with HOCM had 82.1 +/- 4.9% of beta 1 and 14.4 +/- 3.9% of the beta 2 receptor subtype, compared with 76.3 +/- 11.5% of beta 1 and 20.7 +/- 11.0% of the beta 2 subtype in the "control" patients. Both absolute activity of AC (pmol . mg-1 protein . min) as well as the relative responses to the various stimulators were not significantly different between the two groups. Thus, this study does not support the hypothesis that HOCM is a disorder with altered beta-adrenoceptor number or adenylate cyclase response to adrenergic agonists. Furthermore, HOCM is not associated with altered response of the AC system to histamine or NaF.
Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura
Authors: V Blanchette, M Adams, E Wang, J McMillan, P Imbach, M Andrew, R Milner, K Ali, D Barnard, M Bernstein, D Esseltine, K.W Chan, B deVeber, S Israels, N Kobrinsky, B Luke
Journal: The Lancet (1994)
Glycemic Variability Is Associated With Reduced Cardiac Autonomic Modulation in Women With Type 2 Diabetes
Authors: Jesper Fleischer, Simon Lebech Cichosz, Pernille Hoeyem, Esben Laugesen, Per Loegstrup Poulsen, Jens Sandahl Christiansen, Lise Tarnow, Troels Krarup Hansen
Journal: Diabetes Care (2015)

OBJECTIVE To investigate the sex differences in cardiac autonomic modulation in patients with newly diagnosed type 2 diabetes and to determine whether cardiac autonomic modulation is associated with glycemic variability. RESEARCH DESIGN AND METHODS We investigated a cohort consisting of 48 men and 39 women with non-insulin-treated type 2 diabetes and a known duration of diabetes &amp;lt;5 years. All patients were equipped with a continuous glucose monitoring sensor for 3 days, and the mean amplitude of glycemic excursions (MAGE) was calculated to obtain individual glycemic variability. Cardiac autonomic modulation was quantified by analysis of heart rate variability (HRV) in time and frequency domains and during cardiovascular reflex tests (response to standing [RS], deep breathing [expiration–inspiration], and Valsalva maneuver). RESULTS Sex differences in age- and heart rate–adjusted HRV measures were observed in both active and passive tests. Low frequency (LF; P = 0.036), LF/high frequency (HF; P &amp;lt; 0.001), and RS (P = 0.006) were higher in men, whereas expiration–inspiration (P &amp;lt; 0.001), but not HF, was higher in women. In women, reduced cardiac autonomic modulation as assessed by the standard deviation of normal-to-normal intervals (P = 0.001), the root mean square of successive differences (P = 0.018), LF (P &amp;lt; 0.001), HF (P = 0.005), total power (P = 0.008), RS ratio (P = 0.027), and expiration-to-inspiration ratio (P = 0.006) was significantly associated with increased glycemic variability as assessed by MAGE. This was not the case in men. The association in women persisted in a multivariate regression analysis controlling for weight, mean heart rate, blood pressure (systolic), and triglycerides. CONCLUSIONS In patients with newly diagnosed and well-controlled type 2 diabetes, increased glycemic variability was associated with reduced cardiac autonomic modulation in women but not in men.
The Declaration of Helsinki and Clinical Trials: A Focus on Placebo-Controlled Trials in Schizophrenia
Authors: William T Carpenter, Paul S Appelbaum, Robert J Levine
Journal: American Journal of Psychiatry (2003)

The authors' goal was to consider ethical approaches to placebo-controlled clinical trials in the light of the evolving Declaration of Helsinki, with special attention to applications to research on schizophrenia.They review the Helsinki position on placebos, including the 2002 Clarification, exploring the potential negative effects of banning placebos in studies involving conditions for which at least partially effective treatments exist. The Clarification is examined as an approach to this issue that, in contrast to earlier formulations, better acknowledges the complexity of clinical research and the need for protocol-specific determinations. Placebo controls in schizophrenia studies are used to illustrate issues relevant to all clinical research on therapeutic interventions.The Helsinki Clarification provides a basis for operationalizing criteria for review of placebo use in clinical trials. Six criteria are proposed for judging the ethical acceptability of placebo controls, including the likelihood that the intervention being tested will have clinically significant advantages over existing treatments, the presence of compelling reasons for placebo use, subject selection that minimizes the possibility of serious adverse consequences, and a risk-versus-benefit analysis that favors the advantages from placebo use over the risks to subjects.The Helsinki Clarification constitutes an important advance in international approaches to placebo use, requiring protocol-by-protocol judgments on complex issues of clinical research ethics. When operationalized, it provides review boards with a useful methodology for reaching determinations on the appropriateness of placebo controls in particular studies.
Syntheses and Photodynamic Activity of Pegylated Cationic Zn(II)-Phthalocyanines in HEp2 Cells
Authors: Benson G. Ongarora, Xiaoke Hu, Susan D. Verberne-Sutton, Jayne C. Garno, M. Graça H. Vicente
Journal: Theranostics (2012)

Di-cationic Zn(II)-phthalocyanines (ZnPcs) are promising photosensitizers for the photodynamic therapy (PDT) of cancers and for photoinactivation of viruses and bacteria. Pegylation of photosensitizers in general enhances their water-solubility and tumor cell accumulation. A series of pegylated di-cationic ZnPcs were synthesized from conjugation of a low molecular weight PEG group to a pre-formed Pc macrocycle, or by mixed condensation involving a pegylated phthalonitrile. All pegylated ZnPcs were highly soluble in polar organic solvents but were insoluble in water; they have intense Q absorptions centered at 680 nm and fluorescence quantum yields of ca. 0.2 in DMF. The non-pegylated di-cationic ZnPc 6a formed large aggregates, which were visualized by atomic force microscopy. The cytotoxicity, cellular uptake and subcellular distribution of all cationic ZnPcs were investigated in human carcinoma HEp2 cells. The most phototoxic compounds were found to be the α-substituted Pcs. Among these, Pcs 4a and 16a were the most effective (IC(50) ca. 10 μM at 1.5 J/cm(2)), in part due to the presence of a PEG group and the two positive charges in close proximity (separated by an ethylene group) in these macrocycles. The β-substituted ZcPcs 6b and 4b accumulated the most within HEp2 cells but had low photocytoxicity (IC(50) > 100 μM at 1.5 J/cm(2)), possibly as a result of their lower electron density of the ring and more extended conformations compared with the α-substituted Pcs. The results show that the charge distribution about the Pc macrocycle and the intracellular localization of the cationic ZnPcs mainly determine their photodynamic activity.
The Absence of Interleukin 9 Does Not Affect the Development of Allergen-induced Pulmonary Inflammation nor Airway Hyperreactivity
Authors: Sarah J. McMillan, Benjamin Bishop, Michael J. Townsend, Andrew N. McKenzie, Clare M. Lloyd
Journal: The Journal of Experimental Medicine (2002)

Interleukin (IL)-9 is a pleiotropic cytokine secreted by T helper (Th)2 cells and has been proposed as a candidate gene for asthma and allergy. We have used mice genetically deficient in IL-9 to determine the role of this cytokine in the pathophysiologic features of the allergic pulmonary response–airway hyperreactivity (AHR) and eosinophilia. We have demonstrated that IL-9 is not required for the development of a robust Th2 response to allergen in sensitized mice. IL-9 knockout mice developed a similar degree of eosinophilic inflammation and AHR to their wild-type littermates. Goblet cell hyperplasia and immunoglobulin (Ig) E production were also unaffected by the lack of IL-9. Moreover, levels of bronchoalveolar lavage (BAL) IL-4, IL-5, and IL-13 were comparable between wild-type and knockout mice. These findings indicate that IL-9 is not obligatory for the development of eosinophilia and AHR, and imply that other Th2 cytokines can act in a compensatory fashion.
It's Not Just the Patient
Authors: Charlie M Wray
Journal: Annals of Internal Medicine (2013)

On Being a Doctor19 March 2013It's Not Just the PatientCharlie M. Wray, DOCharlie M. Wray, DOFrom Loma Linda University, Loma Linda, California.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-158-6-201303190-00014 Audio Reading - “It's Not Just the Patient” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "It's Not Just the Patient," by C.M. Wray. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail It was around 11 a.m. on a Saturday morning. We had a lighter patient load than usual and had just finished rounds. My senior resident paged me and told me about a new admission: “53-year-old male with history of hep C and possible alcohol withdrawals. Go see patient and page me when you're done.” At a county hospital in a highly underserved area, this sort of admission was not unusual. I headed down to the emergency department to knock out what I thought would be something very straightforward. I could be done in 45 minutes and would be able to ... Author, Article, and Disclosure InformationAffiliations: From Loma Linda University, Loma Linda, California.Corresponding Author: Charlie M. Wray, DO, Loma Linda University, Department of Medicine, 11234 Anderson Street, Loma Linda, CA 92354; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “It's Not Just the Patient” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "It's Not Just the Patient," by C.M. Wray. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 19 March 2013Volume 158, Issue 6Page: 497KeywordsAlcoholsElderlyGamesHepatitisMemoryRunningUltrasound imagingWalking ePublished: 19 March 2013 Issue Published: 19 March 2013 Copyright & PermissionsCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Characteristics and Clinical Impacts of the Immune Environments in Colorectal and Renal Cell Carcinoma Lung Metastases: Influence of Tumor Origin
Authors: Romain Remark, Marco Alifano, Isabelle Cremer, Audrey Lupo, Marie-Caroline Dieu-Nosjean, Marc Riquet, Lucile Crozet, Hanane Ouakrim, Jeremy Goc, Aurélie Cazes, Jean-François Fléjou, Laure Gibault, Virginie Verkarre, Jean-François Régnard, Olivier-Nicolas Pagès, Stéphane Oudard, Bernhard Mlecnik, Catherine Sautès-Fridman, Wolf-Herman Fridman, Diane Damotte
Journal: Clinical Cancer Research (2013)

If immune cells are involved in tumor surveillance and have a prognostic impact in most primary tumors, little is known about their significance in metastases. Because patients' survival is heterogeneous, even at metastatic stages, we hypothesized that immune cells may be involved in the control of metastases. We therefore characterized the tumor immune microenvironment and its prognostic value in colorectal and renal cell carcinoma (RCC) metastases, and compared it to primary tumors.We analyzed by immunohistochemistry (n = 192) and qPCR (n = 32) the immune environments of colorectal carcinoma and RCC lung metastases.Metastases from colorectal carcinoma and RCC have different immune infiltrates. Higher densities of DC-LAMP(+) mature dendritic cells (P < 0.0001) and lower densities of NKp46(+) NK cells (P < 0.0001) were observed in colorectal carcinoma as compared to RCC metastases, whereas densities of T cells were similar. High densities of CD8(+) and DC-LAMP(+) cells correlated with longer overall survival (OS) in colorectal carcinoma (P = 0.008) and shorter OS in RCC (P < 0.0001). High NK-cell densities were associated with improved survival in RCC (P = 0.002) but not in colorectal carcinoma. Densities of immune cells correlated significantly from primary to relapsing metastases for the same patient. A TH1 orientation was found in colorectal carcinoma metastases, whereas a heterogeneous immune gene expression was found in RCC metastases.Our results show a major prognostic value of the immune pattern (CD8(+)/DC-LAMP(+) cell densities) in colorectal carcinoma and RCC, reproducible from primary to metastatic tumors, although with opposite clinical impacts, and highlight the role of the tumor cell in shaping its immune environment.
Cholinergic atrial fibrillation: IK,ACh gradients determine unequal left/right atrial frequencies and rotor dynamics
Authors: F Sarmast
Journal: Cardiovascular Research (2003)

Objective: We tested the hypothesis that left atrial (LA) myocytes are more sensitive to acetylcholine (ACh) than right atrial (RA) myocytes, which results in a greater dose-dependent increase in LA than RA rotor frequency, increased LA-to-RA frequency gradient and increased incidence of wavelet formation during atrial fibrillation (AF). Methods and results: AF was induced in seven Langendorff-perfused sheep hearts in the presence of ACh (0.1–4.0 μM) and studied using optical mapping and bipolar recordings. Dominant frequencies (DFs) were determined in optical and electrical signals and phase movies were used to identify rotors and quantify their dynamics. DFs in both atria increased monotonically with ACh concentration until saturation, but the LA frequency predominated at all concentrations. Rotors were also seen more often in the LA, and although their life span decreased, their frequency and number of rotations increased. Patch-clamp studies demonstrated that ACh-activated potassium current ( IK,ACh ) density was greater in LA than RA sheep myocytes. Additionally, ribonuclease protection assay demonstrated that Kir3.4 and Kir3.1 mRNAs were more abundant in LA than in RA. Conclusions: A greater abundance of Kir3. x channels and higher IK,ACh density in LA than RA myocytes result in greater ACh-induced speeding-up of rotors in the LA than in the RA, which explains the ACh dose-dependent changes in overall AF frequency and wavelet formation.
Characteristics of Patients With Chronic Unexplained Nausea and Vomiting and Normal Gastric Emptying
Authors: Pankaj J. Pasricha, Ryan Colvin, Katherine Yates, William L. Hasler, Thomas L. Abell, Aynur Ünalp–Arida, Linda Nguyen, Gianrico Farrugia, Kenneth L. Koch, Henry P. Parkman, William J. Snape, Linda Lee, James Tonascia, Frank Hamilton
Journal: Clinical Gastroenterology and Hepatology (2011)
MicroRNA-24 Antagonism Prevents Renal Ischemia Reperfusion Injury
Authors: Johan M. Lorenzen, Tamas Kaucsar, Celina Schauerte, Roland Schmitt, Song Rong, Anika Hübner, Kristian Scherf, Jan Fiedler, Filippo Martino, Regalla Kumarswamy, Malte Kölling, Inga Sörensen, Hebke Hinz, Joerg Heineke, Eva van Rooij, Hermann Haller, Thomas Thum
Journal: Journal of the American Society of Nephrology (2014)

Ischemia-reperfusion (I/R) injury of the kidney is a major cause of AKI. MicroRNAs (miRs) are powerful regulators of various diseases. We investigated the role of apoptosis-associated miR-24 in renal I/R injury. miR-24 was upregulated in the kidney after I/R injury of mice and in patients after kidney transplantation. Cell-sorting experiments revealed a specific miR-24 enrichment in renal endothelial and tubular epithelial cells after I/R induction. In vitro, anoxia/hypoxia induced an enrichment of miR-24 in endothelial and tubular epithelial cells. Transient overexpression of miR-24 alone induced apoptosis and altered functional parameters in these cells, whereas silencing of miR-24 ameliorated apoptotic responses and rescued functional parameters in hypoxic conditions. miR-24 effects were mediated through regulation of H2A histone family, member X, and heme oxygenase 1, which were experimentally validated as direct miR-24 targets through luciferase reporter assays. In vitro, adenoviral overexpression of miR-24 targets lacking miR-24 binding sites along with miR-24 precursors rescued various functional parameters in endothelial and tubular epithelial cells. In vivo, silencing of miR-24 in mice before I/R injury resulted in a significant improvement in survival and kidney function, a reduction of apoptosis, improved histologic tubular epithelial injury, and less infiltration of inflammatory cells. miR-24 also regulated heme oxygenase 1 and H2A histone family, member X, in vivo. Overall, these results indicate miR-24 promotes renal ischemic injury by stimulating apoptosis in endothelial and tubular epithelial cell. Therefore, miR-24 inhibition may be a promising future therapeutic option in the treatment of patients with ischemic AKI.
Reperfusion-Activated Akt Kinase Prevents Apoptosis in Transgenic Mouse Hearts Overexpressing Insulin-Like Growth Factor-1
Authors: Kazuhito Yamashita, Jan Kajstura, Daryl J. Discher, Bernard J. Wasserlauf, Nanette H. Bishopric, Piero Anversa, Keith A. Webster
Journal: Circulation Research (2001)

Abstract -Hearts of wild-type and insulin-like growth factor-1 overexpressing (Igf-1(+/-)) transgenic mice were subjected to Langendorff perfusions and progressive periods of ischemia followed by reperfusion. Apoptosis was measured by DNA nucleosomal cleavage and a hairpin probe labeling assay to detect single-base overhang. Transgenic hearts subjected to 20 minutes of ischemia and 4 hours of reperfusion (I/R) sustained a rate of apoptosis of 1.8+/-0.3% compared with 4.6+/-1.1% for wild-type controls (n=4; P<0.03). Phosphorylation of the protein kinase Akt/protein kinase B was elevated 6.2-fold in transgenic hearts at baseline and increased another 4.4-fold within 10 minutes of reperfusion, remaining elevated for up to 2 hours. I/R activated Akt in wild-type hearts but to a lesser extent (1.6+/-0.3-fold). Pretreatment of transgenic hearts with wortmannin immediately before and during ischemia eliminated reperfusion-mediated activation of Akt and neutralized the resistance to apoptosis. The stress-activated kinase p38 was also activated during ischemia and reperfusion in both wild-type and transgenic hearts. Perfusion with the p38 inhibitor SB203580 (10 micromol/L) blocked both p38 activation and phosphorylation of Akt and differentially modulated apoptosis in wild-type and transgenic hearts. Pretreatment with SB203580 reduced apoptosis in wild-type hearts but increased apoptosis in transgenic hearts. These results demonstrate that Akt phosphorylation during I/R is modulated by IGF-1 and prevents apoptosis in hearts that overexpress the IGF-1 transgene.
Inhaled corticosteroids and Churg-Strauss syndrome: a report of five cases
Authors: C. Le Gall, S. Pham, S. Vignes, G. Garcia, H. Nunes, D. Fichet, G Simonneau, P Duroux, M. Humbert
Journal: European Respiratory Journal (2000)

Churg-Strauss syndrome is an eosinophil-associated, small vessel granulomatous vasculitis, characterized by late onset asthma, upper airways disease, eosinophilia, and clinical manifestations of systemic vasculitis. Several cases of Churg-Strauss syndrome have been recognized in patients treated with cysteinyl leukotriene-receptor antagonists and weaned off systemic corticosteroids. These cases have led to a general warning on the possible development of Churg-Strauss syndrome after taking cysteinyl leukotriene-receptor antagonists. The authors report five cases of Churg-Strauss syndrome in severe steroid dependent asthmatics in whom inhaled corticosteroids allowed systemic corticosteroid withdrawal. It is concluded that physicians should monitor patients carefully when severe asthma is controlled with any substance allowing withdrawal from (or even avoidance) of systemic corticosteroids. Case-control studies should identify more precisely the risk factors of Churg-Strauss syndrome.
S11 The South East Essex (SEE) model of integrated COPD care and QUIP (Quality Innovation and Productivity) improvements
Authors: A. G. Davison, E. Paddison, C. Hanna, S. Taylor
Journal: Thorax (2010)

The coalition Government has announced there should be £20 billion saving over the next financial cycle in the health budget, and the QUIP (Quality, Innovation and Productivity) agenda is at the heart of this. The SEE model is an ongoing project of integrating COPD care across primary and secondary providers. A robust local network is at the centre of the project which includes increased Consultant community care (real and virtual), education of staff at the University of Essex, Hospital at Home, improved communication, increased community rehabilitation, community spirometry, improved pathways, self-management plans, oxygen alert cards, dedicated oxygen service and involvement of Breathe Easy. We have reviewed our data to see if productivity has improved in line with the QUIP agenda. <h3>Results</h3> (See Abstract S11 Table 1) Oxygen provision has been reviewed in a three-step process starting with the highest tariffs and extending to all patients on oxygen resulting in £250 000 saving per year. <h3>Conclusion</h3> Integrated services for COPD can bring care closer to home produce reduced admissions, reduced NP/FU ratios and saving on oxygen. Integrated services have achieved savings of at least £650 000 per annum and this is line with the QUIP agenda.