tbuckley/cabot-search huggingface dataset:
Reduced Agonist-Induced Endothelium-Dependent Vasodilation in Uremia Is Attributable to an Impairment of Vascular Nitric Oxide
Authors: Jens Passauer, Frank Pistrosch, Eckhart Bu[Combining Diaeresis]ssemaker, Grit La[Combining Diaeresis]ssig, Kay Herbrig, Peter Gross
Journal: Journal of the American Society of Nephrology (2005)

Current concepts for the explanation of endothelial dysfunction and accelerated atherosclerosis in uremia propose a reduced vascular bioavailability of nitric oxide (NO). The aim of the present study was to test the contributions of NO and NO/prostacyclin (PGI(2))-independent mechanisms to both baseline vascular tone and agonist-induced endothelium-dependent vasodilation in patients on hemodialysis (HD). In 10 HD patients and eight matched healthy control subjects, forearm blood flow (FBF) was measured at rest and during intrabrachial infusions of norepinephrine (NE; endothelium-independent vasoconstrictor, 60, 120, and 240 pmol/min) and N-monomethyl-L-arginine (blocker of NO synthases, 16 micromol/min). After inhibition of cyclo-oxygenase by ibuprofen (1200 mg orally), endothelium-dependent and -independent vasodilation was assessed by infusion of acetylcholine (ACh; 1, 5, 10, 50, 100, and 300 nmol/min) and sodium-nitroprusside (2.5, 5, and 10 microg/min). NO/PGI(2)-independent vasodilation was tested by equal infusions of ACh during NO clamp. N-monomethyl-L-arginine reduced resting FBF to a comparable degree in both groups. Vascular responses to ACh were reduced in HD (P = 0.003 versus control by ANOVA), whereas those to sodium nitroprusside were mainly at control level. Infusion of ACh during NO clamp caused a similar increment of FBF in both groups. NO-mediated vasodilation as calculated by the difference between ACh-induced responses without and with NO clamp was substantially impaired in HD (P < 0.001) compared with control. In HD patients, baseline NO-mediated arteriolar tone is at control level. This study provides first evidence that endothelial dysfunction of uremic patients as shown by reduced agonist-induced endothelium-dependent vasodilation is attributable to reduced stimulation of NO, whereas the NO/PGI(2)-resistant portion of ACh-mediated vasodilation is unaffected.
Cost-Effective Early Childhood Development Programs from Preschool to Third Grade
Authors: Arthur J. Reynolds, Judy A. Temple
Journal: Annual Review of Clinical Psychology (2008)

Although findings on the positive effects of early childhood development programs have been widely disseminated, less attention has been given to program impacts across the entire period of early childhood. This review summarizes evidence on the effects and cost-effectiveness of programs and services from ages 3 to 9. The major focus is preschool programs for 3- and 4-year-olds, full-day kindergarten, school-age programs including reduced class sizes, and preschool-to-third-grade interventions. Participation in preschool programs was found to have relatively large and enduring effects on school achievement and child well-being. High-quality programs for children at risk produce strong economic returns ranging from about $4 per dollar invested to over $10 per dollar invested. Relative to half-day kindergarten, the positive effects of full-day kindergarten have been found to be relatively small and generally do not last for more than a year. Although no formal economic analyses have been conducted, the economic return per dollar invested would be expected to be close to zero. Among early-school-age programs, preschool plus school-age interventions (PK-3) for children at risk are linked to higher levels of school performance into adolescence. The Child-Parent Center PK-3 Program shows a return of $6 to $9 per dollar invested. Class-size reductions show evidence of positive effects, with economic returns of roughly $3 per dollar invested. The causal mechanisms of long-term effects are discussed. Key principles to promote intervention effectiveness are offered.
1194 SUSTAINED VIROLOGIC RESPONSE AND BOCEPREVIR RESISTANCE-ASSOCIATED VARIANTS OBSERVED IN PATIENTS INFECTED WITH HCV GENOTPYPE 1A/1B WHEN TREATED WITH BOCEPREVIR PLUS PEGINTERFERON ALFA-2B/RIBAVIRIN
Authors: C. Brass, R.J.O. Barnard, J.A. Howe, R.A. Ogert, R. Ralston, N. Boparai, M. Burroughs, V. Sniukiene, P. Mendez, J. Albrecht
Journal: Journal of Hepatology (2011)
Molecular response to imatinib in late chronic-phase chronic myeloid leukemia
Authors: Gianantonio Rosti, Giovanni Martinelli, Simona Bassi, Marilina Amabile, Elena Trabacchi, Barbara Giannini, Daniela Cilloni, Barbara Izzo, Antonio De Vivo, Nicoletta Testoni, Giovanna Rege Cambrin, Francesca Bonifazi, Simona Soverini, Simona Luatti, Enrico Gottardi, Daniele Alberti, Fabrizio Pane, Francesco Salvatore, Giuseppe Saglio, Michele Baccarani
Journal: Blood (2003)
Myocardin-Related Transcription Factor-A Controls Myofibroblast Activation and Fibrosis in Response to Myocardial Infarction
Authors: Eric M. Small, Jeffrey E. Thatcher, Lillian B. Sutherland, Hideyuki Kinoshita, Robert D. Gerard, James A. Richardson, J. Michael DiMaio, Hesham Sadek, Koichiro Kuwahara, Eric N. Olson
Journal: Circulation Research (2010)

Myocardial infarction (MI) results in loss of cardiac myocytes in the ischemic zone of the heart, followed by fibrosis and scar formation, which diminish cardiac contractility and impede angiogenesis and repair. Myofibroblasts, a specialized cell type that switches from a fibroblast-like state to a contractile, smooth muscle-like state, are believed to be primarily responsible for fibrosis of the injured heart and other tissues, although the transcriptional mediators of fibrosis and myofibroblast activation remain poorly defined. Myocardin-related transcription factors (MRTFs) are serum response factor (SRF) cofactors that promote a smooth muscle phenotype and are emerging as components of stress-responsive signaling.We aimed to examine the effect of MRTF-A on cardiac remodeling and fibrosis.Here, we show that MRTF-A controls the expression of a fibrotic gene program that includes genes involved in extracellular matrix production and smooth muscle cell differentiation in the heart. In MRTF-A-null mice, fibrosis and scar formation following MI or angiotensin II treatment are dramatically diminished compared with wild-type littermates. This protective effect of MRTF-A deletion is associated with a reduction in expression of fibrosis-associated genes, including collagen 1a2, a direct transcriptional target of SRF/MRTF-A.We conclude that MRTF-A regulates myofibroblast activation and fibrosis in response to the renin-angiotensin system and post-MI remodeling.
Levels of soluble ICAM‐1 in atopic dermatitis A new marker for monitoring the clinical activity?
Authors: B. Wüthrich, H. Joller‐Jemelka, M.K. Kägi
Journal: Allergy (1995)

Levels of soluble intercellular adhesion molecule-1 (sICAM-1) were measured in sera from patients with an acute exacerbation of their atopic dermatitis (AD) (n = 16) on admission to and discharge from our department of dermatology. At admission, the sICAM-1 levels in sera from patients with AD were slightly higher than those of the blood donors (n = 100) and dropped at discharge significantly (P = 0.014) after improvement of the skin conditions. Therefore, sICAM-1 may be, together with soluble interleukin-2 receptor (sIL-2), eosinophilic cationic protein (ECP), and CD14, another marker for monitoring AD.
Eccentric cycling exercise: A novel form of rehabilitation for patients with severe COPD?
Authors: Riany De Sousa Sena, MacMillan Nora, Baril Jacinthe, Richard Ruddy, Perrault Helen, Taivassalo Tanja, Bourbeau Jean
Journal: European Respiratory Journal (2013)

During eccentric muscle contractions, greater levels of force are generated with lower metabolic cost, which can be an attractive alternate rehabilitation for severe COPD. The aim of this study is to estimate the extent to which eccentric compared to concentric training produces greater increases in isometric muscle force and fat free mass in patients with severe COPD. For this, a pilot randomized control trial was conducted in which 20 patients with COPD were randomly assigned to either high intensity concentric (CON, n=10) or eccentric (ECC, n=10) cycling training. Patients exercised 3 times per week, during 30 minutes and for the period of 10 weeks. Musle biopsy was conducted in a subgroup of 12 patients (CON, n=06, ECC, n=06). Study participants were older subjects (age: 65 (5) years old) with severe COPD (FEV%pred: 40 (9) %predicted) and with significant muscle weakness (quadriceps force:103(10)NM). Significant increases in isometric quadriceps force were found in the ECC group (+18Nm, 17% increase from baseline; p  0.05). Fat-free mass index (kg/m2) increased post-training (17.4±1.7kg/m2 to 17.6±1.7kg/m2) in the ECC group and decreased (18.5±2.7kg/m2 to 18.2±2.8kg/m2) in the CON group (p
Impaired Function of Endothelial Pressure-Activated Cation Channel in Salt-Sensitive Genetic Hypertension
Authors: RALF KO[Combining Diaeresis]HLER, REINHOLD KREUTZ, ALEXANDER GRUNDIG, LARS ROTHERMUND, CHANA YAGIL, YORAM YAGIL, AXEL R. PRIES, JOACHIM HOYER
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Mechanosensitive ion channels have been suggested to act as endothelial mechanosensors for hemodynamic forces. The present study tested the hypothesis that the pressure-activated cation channel (PAC), a novel type of endothelial mechanosensitive ion channel, is involved in salt sensitivity in the Sabra rat model of hypertension. Groups of Sabra salt-sensitive (SBH/y) and salt-resistant (SBN/y) rats were loaded with deoxycorticosterone-acetate (DOCA)-salt for 8 wk or were fed a regular diet. Single channel function of PAC in SBH/y and SBN/y rats was investigated in intact endothelium of mesenteric artery using the patch-clamp technique. After DOCA-salt treatment, the SBH/y rats showed a full hypertensive response, whereas SBN/y rats were normotensive. Rats of both strains that received a regular diet were normotensive. In endothelium of both Sabra rats, Ca 2+ permeable PAC that was activated by positive pipette pressures was identified. Apparent PAC density (percentage of patches with PAC activity) was reduced in hypertensive SBH/y rats that were loaded with DOCA-salt compared with salt-loaded normotensive SBN/y rats (6 ± 2% versus 24 ± 8%, respectively; P &lt; 0.05). In normotensive SBH/y and SBN/y rats that received a regular diet, PAC density was not altered. Mechanosensitivity and unitary conductance of endothelial PAC were similar in both strains under a regular diet as well as salt loading with DOCA-salt. In conclusion, the decreased density of PAC in mesenteric endothelium from hypertensive SBH/y rats indicates an impaired ion channel regulation. The defective PAC function presumably leads to an impaired mechanosensitive Ca 2+ entry and might contribute to endothelial dysfunction and high BP in this type of salt-sensitive genetic hypertension.
Acute systemic lupus erythematosus with fatal pneumonitis and disseminated intravascular coagulation.
Authors: M Chellingsworth, D G Scott
Journal: Annals of the Rheumatic Diseases (1985)

We reported the case of a 40-year-old female with acute onset of systemic lupus erythematosus, followed rapidly by the development of fatal pneumonitis and disseminated intravascular coagulation. The likely relationship between these events and the therapeutic options are discussed.
Effect of low-frequency KRAS mutations on the response to anti-EGFR therapy in metastatic colorectal cancer
Authors: D. Tougeron, T. Lecomte, J.C. Pagès, C. Villalva, C. Collin, A. Ferru, J.M. Tourani, C. Silvain, P. Levillain, L. Karayan-Tapon
Journal: Annals of Oncology (2013)
Immature Immunosuppressive CD14+HLA-DR−/low Cells in Melanoma Patients Are Stat3hi and Overexpress CD80, CD83, and DC-Sign
Authors: Isabel Poschke, Dimitrios Mougiakakos, Johan Hansson, Giuseppe V. Masucci, Rolf Kiessling
Journal: Cancer Research (2010)

Myeloid-derived suppressor cells (MDSC) have emerged as key immune modulators in various tumor models and human malignancies, but their characteristics in humans remain to be unequivocally defined. In this study, we have examined circulating CD14(+)HLA-DR(-/low) MDSC in 34 advanced malignant melanoma (MM) patients. Their frequency is significantly increased and associated with disease activity. Contrary to the common notion that MDSC are a heterogeneous population of exclusively immature cells, we find the coexpression of markers associated with mature phenotype. We show for the first time the overexpression of CD80, CD83, and DC-Sign in human MDSC. Further, increased levels of signal transducer and activator of transcription 3 (Stat3), an important regulator in MDSC development and function, were noted in MM-MDSC. Stat3 was altered toward an active, phosphorylated state in the HLA-DR(-) population of CD14(+) cells and was more reactive to activating stimuli in patients. Importantly, inhibition of Stat3 abolished their suppressive activity almost completely. The described MM-MDSC use arginase in conjunction with other yet undefined mechanisms to suppress CD4(+) and CD8(+) T cells. Several observations suggest a redox imbalance in MDSC and indicate an important role of Stat3-dependent oxidative stress in MDSC-mediated T-cell suppression. These results emphasize the diversity of MDSC in human cancer and provide potential targets for therapeutic interventions.
Limiting dilution analysis of cytotoxic T lymphocytes to human immunodeficiency virus gag antigens in infected persons: in vitro quantitation of effector cell populations with p17 and p24 specificities.
Authors: R A Koup, C A Pikora, K Luzuriaga, D B Brettler, E S Day, G P Mazzara, J L Sullivan
Journal: The Journal of Experimental Medicine (1991)

The presence of cytotoxic T lymphocytes (CTL) to the gag antigens of human immunodeficiency virus (HIV) has been described in infected populations. We found that the majority of this immune response as measured in bulk CTL assays of unstimulated peripheral blood mononuclear cells (PBMC) is directed against the p24 component of the p55 gag precursor protein. Using limiting dilution analysis of this effector cell population we confirm that the majority of activated gag-specific CTL circulating in the PBMC of infected hemophilic patients are directed at p24 determinants and are present at frequencies of 1/36,000 to 1/86,000 lymphocytes. By performing in vitro stimulation after limiting dilution, the precursor population of gag-specific CTL are characterized and quantitated. HIV gag-specific CTL precursors are identified at frequencies of 1/1700 to 1/17,000 lymphocytes and are made up of cells with both p17 and p24 specificities. No HIV gag-specific CTL precursor cells are identified in the PBMC of HIV-uninfected individuals. These studies demonstrate that CTL directed at both p17 and p24 determinants make up the cellular immune repertoire in HIV-infected individuals but that only the p24-specific CTL are routinely found in an activated state in the circulation.
Reperfusion injury after myocardial infarction
Authors: B P. Morgan
Journal: BMJ (1995)

differing natural courses,' and their inclusion could require intolerable variations in manage- ment.The hospice environment may seem more dis- tressing for patients with diseases other than cancer; moreover, if such patients were treated in hospices, patients with cancer might have greater difficulties with body image and in accepting the inconsistency of more active management being given for non-malignant diseases.5Hospices are deliberately not generally equipped to deliver such management so that overmedicalisation of terminal care is avoided.Presently hospices see only about half of patients with cancer, which leaves little scope for the needs of a wider population (estimated at 150% extra bed days required for patients with diseases other than cancer6).Hospice-style input for non-malignant diseases remains equally important but requires appro- priate provision in addition to traditional hospices.Adequate community services could also meet much of this need.Hospices offer quality rather than quantity and should not be seen as an easy and cheaper option for providing care for patients with terminal disease as if they were a homogeneous group.
Inhaled nedocromil sodium as additional treatment to high dose inhaled corticosteroids in the management of bronchial asthma
Authors: UG Svendsen, H Jorgensen
Journal: European Respiratory Journal (1991)

Thirty five asthmatic patients were included in a randomized, double-blind, placebo-controlled, parallel group study of inhaled nedocromil sodium (4 x 4 mg daily) as an additional treatment to high dose (greater than or equal to 1,000 micrograms) inhaled corticosteroids in the management of bronchial asthma. Following a four week baseline, patients received nedocromil sodium (17) or placebo treatment (18) for eight weeks. Five patients (four in the group subsequently randomized to nedocromil sodium) used short course oral corticosteroid therapy during the baseline and four placebo treated patients used oral steroid therapy during treatment. Fifteen patients (11 nedocromil sodium) reported unusual symptoms. Two nedocromil sodium treated patients were withdrawn owing to treatment taste and vomiting. Statistically significant treatment differences in favour of nedocromil sodium were seen for daytime symptoms (p = 0.03) and morning peak expiratory flow (PEF) (p = 0.012) during weeks 5-8, and for clinician opinion (p = 0.02). Patient opinion (p = 0.053) and evening PEF (p = 0.08) failed to reach statistical significance. Eight out of fifteen and three out of seventeen patients considered nedocromil sodium and placebo, respectively, to be very or moderately effective. The results indicate that the addition of nedocromil sodium (4 mg four times daily) to moderate to severe asthmatics not fully controlled on a regimen of greater than or equal to 1,000 micrograms inhaled corticosteroids and inhaled bronchodilators can produce improvements in symptoms and pulmonary function.
Management of lower urinary tract symptoms in men: summary of NICE guidance
Authors: C. Jones, J. Hill, C. Chapple
Journal: BMJ (2010)

Lower urinary tract symptoms (LUTS) in men are related to problems with storage and voiding of urine and can occur after micturition. The many causes of LUTS include abnormalities or abnormal function of the bladder, prostate, urethra, or sphincters. The prevalence of LUTS increases as men get older, with about 30% of men aged 65 years and older having troublesome symptoms,1 which may require treatment. This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on LUTS.2 NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the guideline development group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. Lower urinary tract symptoms have been categorised according to the three stages of the bladder cycle3: storage (when filling of the bladder occurs), voiding (when the bladder actively expels its contents), and post micturition (immediately after voiding, while returning to the storage stage) (box). #### Categories of lower urinary tract symptoms3 ##### Storage (also symptoms of overactive bladder) ##### Voiding ##### Post-micturition ### Initial assessment At initial assessment (in any setting and by a healthcare professional without specific training in managing LUTS in men) take the following actions.
Early detection of liver steatosis by magnetic resonance imaging in rats infused with glucose and Intralipid solutions and correlation to insulin levels
Authors: Gaspard d'Assignies, Ghislaine Fontés, Claude Kauffmann, Martin Latour, Louis Gaboury, Yvan Boulanger, Bernard E. Van Beers, Gilles Soulez, Vincent Poitout, An Tang
Journal: Metabolism (2013)
Detection of human tumor cells by amplicon fusion site polymerase chain reaction (AFS-PCR)
Authors: Axel Weber, Sylvia Taube, Sven Starke, Eckhard Bergmann, Nina Merete Christiansen, Holger Christiansen
Journal: Journal of Clinical Investigation (2011)

Reliable diagnostic strategies for individuals with cancer demand practical methods for highly sensitive and specific detection of tumor cells. Amplification of genomic regions that include putative oncogenes is common in tumor cells of various types. Genomic array platforms offer the opportunity to identify and precisely map amplified genomic regions (ampGRs). The stable existence of these tumor cell–specific genomic aberrations during and after therapy, in theory, make ampGRs optimal targets for cancer diagnostics. In this study, we mapped ampGRs around the proto-oncogene MYCN of human neuroblastomas using a high-resolution tiling array (HR-TA). Based on the HR-TA data, we were able to precisely describe the telomeric and centromeric borders of the ampGRs and deduce virtual fusion sites of the joined ampGRs (amplicon fusion sites [AFSs]). These AFSs served as blueprints for the subsequent design of AFS bridging PCR assays (AFS-PCRs). Strikingly, these assays were absolutely tumor cell specific and capable of detecting 1 tumor cell in 1 × 106 to 8 × 106 control cells. We successfully proved the in vivo practicability of AFS-PCR by detecting and quantifying the specific AFS DNA of human MYCN-amplified neuroblastomas in the patients’ corresponding peripheral blood and bone marrow samples. Thus, we believe AFS-PCR could become a powerful and nevertheless feasible personalized diagnostic tool applicable to a large number of cancer patients, including children with MYCN-amplified neuroblastomas.
Contamination of rhinovirus stocks with poliovirus type 1
Authors: T Wilkinson
Journal: Thorax (2003)

▴ Davies M, Bruce C, Bewley K, et al . Poliovirus type 1 in working stocks of typed human rhinoviruses. Lancet2003;361:1187–8 [OpenUrl][1][CrossRef][2][PubMed][3] ▴ Savolainen C, Hovi T. Caveat: poliovirus may be hiding under other labels. Lancet2003;361:1145–6 [OpenUrl][4][CrossRef][5][PubMed][6] One of the major successes of public health vaccination programmes has been the eradication of circulating poliovirus from the majority of countries in the world. Reintroduction of wild type poliovirus may occur following spread from sources of virus stored in virological and other laboratories for … [1]: {openurl}?query=rft.jtitle%253DLancet%26rft.stitle%253DLancet%26rft.aulast%253DDavies%26rft.auinit1%253DM.%26rft.volume%253D361%26rft.issue%253D9364%26rft.spage%253D1187%26rft.epage%253D1188%26rft.atitle%253DPoliovirus%2Btype%2B1%2Bin%2Bworking%2Bstocks%2Bof%2Btyped%2Bhuman%2Brhinoviruses.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252803%252912919-4%26rft_id%253Dinfo%253Apmid%252F12686044%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/S0140-6736(03)12919-4&link_type=DOI [3]: /lookup/external-ref?access_num=12686044&link_type=MED&atom=%2Fthoraxjnl%2F58%2F7%2F579.atom [4]: {openurl}?query=rft.jtitle%253DLancet%26rft.stitle%253DLancet%26rft.aulast%253DSavolainen%26rft.auinit1%253DC.%26rft.volume%253D361%26rft.issue%253D9364%26rft.spage%253D1145%26rft.epage%253D1146%26rft.atitle%253DCaveat%253A%2Bpoliovirus%2Bmay%2Bbe%2Bhiding%2Bunder%2Bother%2Blabels.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252803%252912965-0%26rft_id%253Dinfo%253Apmid%252F12686032%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [5]: /lookup/external-ref?access_num=10.1016/S0140-6736(03)12965-0&link_type=DOI [6]: /lookup/external-ref?access_num=12686032&link_type=MED&atom=%2Fthoraxjnl%2F58%2F7%2F579.atom