tbuckley/cabot-search huggingface dataset:
Endothelial Cell Interactions With Synthetic Peptides From the Carboxyl-Terminal Heparin-Binding Domains of Fibronectin
Authors: Joseph C. Huebsch, James B. McCarthy, Clement A. Diglio, Daniel L. Mooradian
Journal: Circulation Research (1995)

Abstract Fibronectin (FN) plays an important role in endothelial cell adhesion, spreading, and motility. Within FN, a number of functional domains have been identified, including the 33/66-kD carboxyl-terminal heparin-binding fragments, which support the adhesion of vascular endothelial cells. A number of synthetic peptides representing amino acid sequences within the 33/66-kD fragments have been shown to promote the adhesion, spreading, and migration of a variety of cell types. Our working hypothesis is that one or more of these sequences may also mediate vascular endothelial cell adhesion, spreading, and migration to the 33/66-kD fragments. In support of this hypothesis, we have demonstrated that endothelial cells from various sources adhered in a concentration-dependent manner to surfaces coated with FN, the 33/66-kD fragments, and synthetic peptides derived from the 33/66-kD fragments of FN. FN and the 33/66-kD fragments also promoted endothelial cell spreading and migration. Although each of the six synthetic peptides tested supported endothelial cell adhesion, only one of these peptides within the carboxyl-terminal heparin-binding domain (FN-C/H-V) promoted endothelial cell spreading and migration. Cell spreading on FN-C/H-V, as well as on FN and the 33/66-kD fragments, was associated with the formation of a well-developed actin cytoskeleton and the formation of focal contacts. FN-C/H-V (but not scrambled FN-C/H-V) inhibited cell spreading on FN and the 33/66-kD fragments in a concentration-dependent manner. FN-C/H-V had a modest effect on the adhesion of a clonal population of rat heart endothelial cells (RHE-1A) to the 33/66-kD fragments of FN and no effect on RHE-1A cell adhesion to FN. These findings suggest that peptide FN-C/H-V is unique among this group of peptides derived from the 33/66-kD heparin-binding fragments of FN in its ability to promote the adhesion, spreading, and migration of vascular endothelial cells and further suggest that the sequence defined by this peptide plays an important role in vascular endothelial cell interactions with the 33/66-kD fragments of FN.
Lung Natural Helper Cells Are a Critical Source of Th2 Cell-Type Cytokines in Protease Allergen-Induced Airway Inflammation
Authors: Timotheus Y.F. Halim, Ramona H. Krauß, Ann C. Sun, Fumio Takei
Journal: Immunity (2012)

SummaryOverproduction of cytokines by T helper 2 (Th2) cells in the lung is thought to be a cause of asthma. Here we report that innate lymphocytes termed lung natural helper (LNH) cells are a T cell-independent source of Th2 cell-type cytokines in protease allergen-treated lungs. LNH (Lin−Sca-1+c-kit+/loCD25+CD127+) cells, when stimulated by IL-33 plus IL-2, IL-7, or thymic stroma lymphopoietin (TSLP), produced large amounts of IL-5 and IL-13. Intranasal administration of protease allergen papain induced eosinophil infiltration and mucus hyperproduction in the lung of wild-type and Rag1−/− mice, but not in Rag2−/−Il2rg−/− mice that lack LNH cells. LNH cell depletion inhibited papain-induced airway inflammation in Rag1−/− mice whereas adoptive transfer of LNH cells enabled Rag2−/−Il2rg−/− mice to respond to papain. Treatment of lung explants with papain induced IL-33 and TSLP production by stroma cells and IL-5 and IL-13 production by LNH cells. Thus, LNH cells are critical for protease allergen-induced airway inflammation.Graphical abstractGraphical AbstractHighlights► Lung natural helper cells produce large amounts of Th2 cell-type cytokines ► Protease allergen stimulates lung natural helper cells ► Stroma-derived cytokines stimulate lung natural helper cells ► Th2 cell-type cytokines from lung natural helper cells induce T cell-independent asthma
The Neuropeptide Secretoneurin Acts as a Direct Angiogenic Cytokine In Vitro and In Vivo
Authors: Rudolf Kirchmair, Roland Gander, Margot Egger, Allison Hanley, Marcy Silver, Andreas Ritsch, Toshinori Murayama, Nicole Kaneider, Wolfgang Sturm, Marianne Kearny, Reiner Fischer-Colbrie, Brigitte Kircher, Hannes Gaenzer, Christian J. Wiedermann, Allan H. Ropper, Douglas W. Losordo, Josef R. Patsch, Peter Schratzberger
Journal: Circulation (2004)

Background— Secretoneurin is an abundant neuropeptide of the central, peripheral, and autonomic nervous systems, located in nerve fibers characterized by a close interaction with blood vessels and known to stimulate endothelial cell migration. Methods and Results— We hypothesized that secretoneurin might act as an angiogenic cytokine and tested for these effects in vivo using a mouse cornea neovascularization model and in vitro by assessing capillary tube formation in a matrigel assay. In vivo, secretoneurin-induced neovasculature is characterized by a distinct pattern of arterial and venous vessels of large diameter and length. Immunohistochemical staining for CD-31 revealed endothelial lining of the inner surface of these vessels, and recruitment of α-smooth muscle actin–positive perivascular cells suggests vessel maturation. In vitro, secretoneurin-induced capillary tube formation was dose dependent and specific, confirming that effects of secretoneurin occur directly on endothelial cells. Secretoneurin also stimulated proliferation and exerted antiapoptotic effects on endothelial cells and activated intracellular phosphatidylinositol 3′ kinase/Akt and mitogen-activated protein kinase pathways, as demonstrated by increased phosphorylation of Akt and extracellular signal–regulated kinase. Conclusions— These data show that secretoneurin represents a novel direct angiogenic cytokine and reiterate the coordinated relationship between nervous and vascular systems.
Physical activity and maintaining physical function in older adults
Authors: T M Manini, M Pahor
Journal: British Journal of Sports Medicine (2008)

Older Americans, the most rapidly growing age group, are the least physically active1 and generate the highest healthcare expenditures.2 For example, older persons who were functionally dependent accounted for 46% of the healthcare expenditures, but only made up 20% of the older adult population.3 Additionally, they spent $5000 more per year than people who remained independent. Physical activity (PA) may play an important role in maintaining health and physical function while reducing the healthcare burden.4 Recommendations for PA began in 1975 with the American College of Sports Medicine’s (ACSM) guidelines for exercise testing and prescription. While little space was devoted to PA in older adults, likely due to the limited amount of research, today a wealth of literature is available touting its benefits. Throughout the past two decades many obstacles to adopting PA, a safe and effective modality for improving physical capacity in older adults, have been overcome. Many questions still remain; the one which we attempt to address in this brief review is whether PA can maintain physical function in older adults.

Physical activity has a myriad of effects that stem from physiological adaptations that may transfer to improvements in clinical outcomes such as reducing the risk of falls.5 The purpose of this article is to briefly review the current literature regarding whether PA can help maintain physical function in older adults and offer some suggestions for clinicians wanting to improve physical function with PA. As illustrated in fig 1, individuals who begin a regular PA programme early in life and maintain this over the years will likely have high physical performance throughout the lifespan, although a decline in physical function is inevitable. Potentially more clinically relevant is whether a PA programme can set a person on a different trajectory over time (see …
Endometrial wave-like activity in the non-pregnant uterus
Authors: I van Gestel, M M IJland, H J Hoogland, J L H Evers
Journal: Human Reproduction Update (2003)

The non-pregnant uterus shows wave-like activity throughout the menstrual cycle. This uterine activity was first detected using intra-uterine pressure recordings. The use of ultrasound has made it possible to study the movements of the uterus in a non-invasive manner. Throughout the menstrual cycle, several wavelike activity patterns have been described; these patterns change throughout the menstrual cycle and are governed by steroid hormones. An adequate wave pattern seems to be related to successful reproduction in spontaneous cycles and assisted reproduction. Further insight into the phenomenon of endometrial wave-like activity might offer an opportunity to correct abnormal wave patterns and thereby improve pregnancy rates.
Association between severity of type A hepatitis and nucleotide variations in the 5` non-translated region of hepatitis A virus RNA: strains from fulminant hepatitis have fewer nucleotide substitutions
Authors: K Fujiwara, O Yokosuka, T Ehata, H Saisho, N Saotome, K Suzuki, K Okita, K Kiyosawa, M Omata
Journal: Gut (2002)

<b>Background:</b> Type A hepatitis is still a considerable problem in both underdeveloped and developed countries. Why some patients progress to fulminant type A hepatitis and others do not is unclear. <b>Aims:</b> To determine if nucleotide differences in the genome of hepatitis A virus (HAV) are responsible for the range of clinical severities, we analysed the 5` non-translated region (5`NTR) of the HAV genome, which has an internal ribosomal entry site and is important for cap independent translation of the viral message. <b>Methods:</b> Serum samples from 84 Japanese patients with sporadic type A hepatitis from five distant regions of Japan, comprising 12 patients with fulminant hepatitis (FH), 13 with severe acute hepatitis (AHs), and 59 with acute hepatitis (AH), were examined for HAV RNA. The fragment between nucleotides 75 and 638 of the 5`NTR was amplified by reverse transcription-polymerase chain reaction, and the nucleotide sequence was determined by direct sequencing. <b>Results:</b> Comparison of sequences of the 5`NTR revealed relatively fewer nucleotide substitutions in FH and AHs patients compared with the considerable sequence variations found in strains of AH. This tendency was most prominent between nucleotides 200 and 500. Strains from FH and AHs cases had fewer nucleotide substitutions (p&lt;0.001) in this region. <b>Conclusions:</b> Nucleotide variations in the central portion of the 5`NTR of HAV may influence the severity of type A hepatitis.
Clinical burden of erosive hand osteoarthritis and its relationship to nodes
Authors: J. Bijsterbosch, I. Watt, I. Meulenbelt, F. R. Rosendaal, T. W. J. Huizinga, M. Kloppenburg
Journal: Annals of the Rheumatic Diseases (2010)

To describe the clinical burden of erosive osteoarthritis (EOA) of the hand in terms of pain, functioning and health-related quality of life (HRQL) and its relationship to nodal osteoarthritis (OA).Patients with EOA (n=42) and non-EOA (n=194) of the hand were compared. Pain was assessed with the Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Michigan Hand Outcome Questionnaire (MHQ) and pain intensity upon pressure. Functioning was evaluated with AUSCAN, MHQ, grip strength, pinch grip and hand mobility tests. HRQL was measured with the Short Form-36. Patient satisfaction with hand function and aesthetics were also evaluated. The presence of nodal OA as well as its extent (reflected by the number of nodes) was assessed. Mean differences between patient groups were estimated with linear mixed models. To determine whether differences were independent of the nodal character of the disease, adjustments were made for the number of nodes.Patients with EOA experienced more pain, more functional limitation, less satisfaction with hand function and aesthetics and worse hand mobility than patients with non-EOA. HRQL was similar for the two groups. Patients with EOA had more nodes. A higher number of nodes was associated with worse outcome. After correction for the number of nodes, only hand mobility and patient satisfaction remained different between the groups.Patients with EOA have a higher clinical burden than those with non-erosive disease. This higher burden is only partly attributed to the erosive disease itself, but mainly to the nodal character of the disease.
End-of-Life Practices in European Intensive Care Units
Authors: Charles L Sprung, Simon L Cohen, Peter Sjokvist, Mario Baras, Hans-Henrik Bulow, Seppo Hovilehto, Didier Ledoux, Anne Lippert, Paulo Maia, Dermot Phelan, Wolfgang Schobersberger, Elisabet Wennberg, Tom Woodcock
Journal: JAMA (2003)

ContextWhile the adoption of practice guidelines is standardizing many aspects of patient care, ethical dilemmas are occurring because of forgoing life-sustaining therapies in intensive care and are dealt with in diverse ways between different countries and cultures.ObjectivesTo determine the frequency and types of actual end-of-life practices in European intensive care units (ICUs) and to analyze the similarities and differences.Design and SettingA prospective, observational study of European ICUs.ParticipantsConsecutive patients who died or had any limitation of therapy.InterventionProspectively defined end-of-life practices in 37 ICUs in 17 European countries were studied from January 1, 1999, to June 30, 2000.Main Outcome MeasuresComparison and analysis of the frequencies and patterns of end-of-life care by geographic regions and different patients and professionals.ResultsOf 31 417 patients admitted to ICUs, 4248 patients (13.5%) died or had a limitation of life-sustaining therapy. Of these, 3086 patients (72.6%) had limitations of treatments (10% of admissions). Substantial intercountry variability was found in the limitations and the manner of dying: unsuccessful cardiopulmonary resuscitation in 20% (range, 5%-48%), brain death in 8% (range, 0%-15%), withholding therapy in 38% (range, 16%-70%), withdrawing therapy in 33% (range, 5%-69%), and active shortening of the dying process in 2% (range, 0%-19%). Shortening of the dying process was reported in 7 countries. Doses of opioids and benzodiazepines reported for shortening of the dying process were in the same range as those used for symptom relief in previous studies. Limitation of therapy vs continuation of life-sustaining therapy was associated with patient age, acute and chronic diagnoses, number of days in ICU, region, and religion (P&lt;.001).ConclusionThe limiting of life-sustaining treatment in European ICUs is common and variable. Limitations were associated with patient age, diagnoses, ICU stay, and geographic and religious factors. Although shortening of the dying process is rare, clarity between withdrawing therapies and shortening of the dying process and between therapies intended to relieve pain and suffering and those intended to shorten the dying process may be lacking.
Reproducibility of computer based neuropsychological testing among Norwegian elite football players
Authors: T M Straume-Naesheim, T E Andersen, R Bahr
Journal: British Journal of Sports Medicine (2005)

Head injuries account for 4-22% of all football injuries. The rate of brain injuries is difficult to assess, due to the problem of defining and grading concussion. Thus computerised testing programs for cognitive function have been developed.To assess the reliability of a computerised neuropsychological test battery (CogSport) among Norwegian professional football players.Norwegian professional football league players (90.3% participation) performed two consecutive baseline Cogsport tests before the 2004 season. CogSport consists of seven different subtasks: simple reaction time (SRT), choice reaction time (ChRT), congruent reaction time (CgRT), monitoring (MON), one-back (OBK), matching (Match) and learning (Learn).There was a small but significant improvement from repeated testing for the reaction time measurements of all seven subtasks (SRT: 0.7%, ChRT: 0.4%, CgRT: 1.2%, MON: 1.3%, OBK: 2.7%, Match: 2.0%, Learn: 1.1%). The coefficient of variation (CV) ranged from 1.0% to 2.7%; corresponding intraclass correlation coefficients ranged from 0.45 (0.34 to 0.55) to 0.79 (0.74 to 0.84). The standard deviation data showed higher CVs, ranging from 3.7% (Learn) to 14.2% (SRT). Thus, the variance decreased with increasing complexity of the task. The accuracy data displayed uniformly high CV (10.4-12.2) and corresponding low intraclass correlation coefficient (0.14 (0.01 to 0.26) to 0.31 (0.19 to 0.42)).The reproducibility for the mean reaction time measures was excellent, but less good for measures of accuracy and consistency. Consecutive testing revealed a slight learning effect from test 1 to test 2, and double baseline testing is recommended to minimise this effect.
Impact of Five Prophylactic Filgrastim Schedules on Hematologic Toxicity in Early Breast Cancer Patients Treated With Epirubicin and Cyclophosphamide
Authors: Paola Papaldo, Massimo Lopez, Paolo Marolla, Enrico Cortesi, Mauro Antimi, Edmondo Terzoli, Patrizia Vici, Carlo Barone, Gianluigi Ferretti, Serena Di Cosimo, Paolo Carlini, Cecilia Nisticò, Francesca Conti, Luigi Di Lauro, Claudio Botti, Franco Di Filippo, Alessandra Fabi, Diana Giannarelli, Federico Calabresi
Journal: Journal of Clinical Oncology (2005)

To evaluate the comparative efficacy of varying intensity schedules of recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) support in preventing febrile neutropenia in early breast cancer patients treated with relatively high-dose epirubicin plus cyclophosphamide (EC).From October 1991 to April 1994, 506 stage I and II breast cancer patients were randomly assigned to receive, in a factorial 2 x 2 design, epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 intravenously on day 1 every 21 days for 4 cycles +/- lonidamine +/- G-CSF. The following five consecutive G-CSF schedules were tested every 100 randomly assigned patients: (1) 480 microg/d subcutaneously days 8 to 14; (2) 480 microg/d days 8, 10, 12, and 14; (3) 300 microg/d days 8 to 14; (4) 300 microg/d days 8, 10, 12, and 14; and (5) 300 microg/d days 8 and 12.All of the G-CSF schedules covered the neutrophil nadir time. Schedule 5 was equivalent to the daily schedules (schedules 1 and 3) and to the alternate day schedules (schedules 2 and 4) with respect to incidence of grade 3 and 4 neutropenia (P = .79 and P = .89, respectively), rate of fever episodes (P = .84 and P = .77, respectively), incidence of neutropenic fever (P = .74 and P = .56, respectively), need of antibiotics (P = .77 and P = .88, respectively), and percentage of delayed cycles (P = .43 and P = .42, respectively). G-CSF had no significant impact on the delivered dose-intensity compared with the non-G-CSF arms.In the adjuvant setting, the frequency of prophylactic G-CSF administration during EC could be curtailed to only two administrations (days 8 and 12) without altering outcome. This nonrandomized trial design provides support for evaluating alternative, less intense G-CSF schedules for women with early breast cancer.
Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease
Authors: Susanne Schnittger, Claudia Schoch, Martin Dugas, Wolfgang Kern, Peter Staib, Christian Wuchter, Helmut Löffler, Cristina Maria Sauerland, Hubert Serve, Thomas Büchner, Torsten Haferlach, Wolfgang Hiddemann
Journal: Blood (2002)
Epidermodysplasia verruciformis associated with neurofibromatosis type 1: coincidental association or model for understanding the underlying mechanism of the disease?
Authors: E. Alpsoy, M.A. CiftCioGlu, I. Keser, E-M. De Villiers, C.C. Zouboulis
Journal: British Journal of Dermatology (2002)

Summary We describe a 25‐year‐old man with epidermodysplasia verruciformis (EV) associated with neurofibromatosis type 1 (NF1). The lesions, persisting for more than 15 years, consisted of widespread planar warts on the backs of the hands and wrists, and reddish‐brown macules on the trunk, neck and face. During the last 5 years, our patient developed several epithelial tumours, namely solar keratoses, plaques of Bowen's disease and squamous cell carcinomas (SCCs). He also presented with NF1 lesions with neurofibromas, café‐au‐lait macules, axillary freckling and Lisch nodules. He had left tibial bowing. Polymerase chain reaction analysis of the skin lesions demonstrated the presence of human papillomavirus (HPV) 15 in a flat wart, HPV 20 in a plaque of Bowen's disease, and HPV 15 and HPV 20 in an SCC lesion. Both EV and NF1 show an inherited predisposition to malignancy but the molecular mechanism underlying tumour development is not fully understood. The appearance of both diseases in our patient may be a coincidental association but may also contribute to the identification of loci for susceptibility to NF1 and EV on chromosome 17.
Diagnosis and management of gastrointestinal complications in adult cancer patients: evidence-based guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)
Authors: M.J.G.T. Vehreschild, J.J. Vehreschild, K. Hübel, M. Hentrich, M. Schmidt-Hieber, M. Christopeit, G. Maschmeyer, E. Schalk, O.A. Cornely, S. Neumann
Journal: Annals of Oncology (2013)
Sudden cardiac death -- 1978.
Authors: B Lown
Journal: Circulation (1979)

With the development of coronary care units in the 1960s, attitudes toward sudden cardiac death (SCD) began to change as physicians learned that cardiac arrest was reversible.The problem of SCD has two aspects an acute, precipitating factor and a chronic predisposition to electrical instability of the myocardium.Resolution of the problem requires identification and protection of the potential victim.Ven- tricular premature complexes (VPCs) have been related to the development of serious arrhythmias and early death, but the mere presence of VPCs does not discriminate risk of subsequent fatality.VPCs should be graded according to frequency, persistence, multiformity, repetitive pattern and degree of prematurity.Provocation of repetitive extrasystoles by R-on-T pacing may indicate the presence of a reduced threshold for ventricular fibrillation (VF).Prophylactic antiarrhythmic therapy may help protect patients resuscitated from VF against recurrent cardiac arrest.Neuropharmacologic factors perhaps affecting central nervous system sympathetic activity can alter cardiac vulnerability and may protect against VF.Findings in dogs indicate that psychologic stress can reduce the cardiac threshold for VF.If psychologic factors predispose to ventricular arrhythmias by increasing the level of sympathetic tone, lessening neural sympathetic activity should reduce the incidence of SCD.