tbuckley/cabot-search huggingface dataset:
Prominin-1/CD133<sup>+</sup> Lung Epithelial Progenitors Protect from Bleomycin-induced Pulmonary Fibrosis
Authors: Davide Germano, Przemyslaw Blyszczuk, Alan Valaperti, Gabriela Kania, Stephan Dirnhofer, Ulf Landmesser, Thomas F. Lüscher, Lukas Hunziker, Henryk Zulewski, Urs Eriksson
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

The mouse model of bleomycin-induced lung injury offers an approach to study idiopathic pulmonary fibrosis, a progressive interstitial lung disease with poor prognosis. Progenitor cell-based treatment strategies might combine antiinflammatory effects and the capacity for tissue repair.To expand progenitor cells with reparative and regenerative capacities and to evaluate their protective effects on pulmonary fibrosis in vivo.Prominin-1/CD133(+) epithelial progenitor cells (PEPs) were expanded from adult mouse lungs after digestion and culture of distal airways. Lung fibrosis was induced in C57Bl/6 mice by instillation of bleomycin. Two hours later, animals were transplanted with PEPs. Inflammation and fibrosis were assessed by immunohistochemistry, bronchoalveolar lavage fluid differentials, and real-time polymerase chain reaction.PEPs expanded from mouse lungs were of bone marrow origin, coexpressed stem and hematopoietic cell markers, and differentiated in vitro into alveolar type II surfactant protein-C(+) epithelial cells. In bleomycin-challenged mice, intratracheally injected PEPs engrafted into the lungs and differentiated into type II pneumocytes. Furthermore, PEPs suppressed proinflammatory and profibrotic gene expression, prevented the recruitment of inflammatory cells, and protected bleomycin-challenged mice from pulmonary fibrosis. Mechanistically, the protective effect depended on upregulation of inducible nitric oxide synthase in PEPs and nitric oxide-mediated suppression of alveolar macrophage proliferation. Accordingly, PEPs from iNOS(-/-) but not iNOS(+/+) mice failed to protect from bleomycin-induced lung injury.The combined antiinflammatory and regenerative capacity of bone marrow-derived pulmonary epithelial progenitors offers a promising approach for development of cell-based therapeutic strategies against pulmonary fibrosis.
Effect of sustained stretch on dispersion of ventricular fibrillation intervals in normal rabbit hearts
Authors: F Burton
Journal: Cardiovascular Research (1998)

Objective: To determine the effect of acute left ventricular dilatation on refractoriness in normal hearts. Methods: During sustained ventricular fibrillation (VF) in isolated perfused hearts, recording of local activation time yields VF intervals which provide an index of local refractoriness. Simultaneous measurement from multiple sites enables study of spatial aspects of changes in refractoriness. We studied the effects of stretch on the magnitude and dispersion of changes in VF interval in 10 isolated, Langendorff-perfused rabbit hearts using a flexible epicardial array containing 240 unipolar electrodes. The left ventricular pressure was increased from 0 to 40 mmHg by inflation of an intraventricular balloon during sustained VF. Results: The current threshold for VF induction fell from 64±11 mA to 43±11 mA (mean±SE, P<0.01) following ventricular dilatation. Mean VF interval at 0 mmHg was 79.8±1.3 ms and fell to 70.2±1.7 ms (P<0.01) at 40 mmHg. There was a corresponding increase in dispersion of VF interval (coefficient of variation) from 8.13±0.8 to 13.3±0.8 (P<0.01). There was regional heterogeneity in the areas of greatest reduction in VF interval, which varied between hearts. Following balloon inflation there was an increase in the number of activation waves. Conclusions: Acute ventricular dilatation produces spatially heterogeneous changes in refractoriness which would predispose to the maintenance of reentrant arrhythmias.
Uremia and Host Defenses
Authors: Nina E. Tolkoff-Rubin, Robert H. Rubin
Journal: New England Journal of Medicine (1990)

IN the first edition of his Principles and Practice of Medicine, Sir William Osler stated that the clinical manifestations of uremia are caused by the retention of the excretory products. The nature of these poisonous ingredients is not yet known. It was formerly thought that the urea was the offending substance, and it has been found increased in the blood in uraemia.... It is more probable, however, that there are several toxic agents at work.1 Nearly a century later, Ruiz et al.2 have employed modern immunologic techniques to investigate one important aspect of the uremic syndrome — the effects . . .
Relation between left ventricular global and regional function and extent of myocardial ischemia in the canine heart
Authors: Makoto Akaishi, Ricky M. Schneider, Richard J. Mercier, Franco F. Naccarella, Jair B. Agarwal, Richard H. Helfant, William S. Weintraub
Journal: Journal of the American College of Cardiology (1985)
Congestive Heart Failure Treatment
Authors: Bernard A. Schwetz
Journal: JAMA (2001)

The FDA has approved nesiritide (Natrecor; Scios Inc, Sunnyvale, Calif) for initial intravenous treatment of patients with acutely decompensated congestive heart failure (ADCHF). The drug is a sterile, purified preparation containing the human B-type natriuretic peptide.
The Value of Capsule Endoscopy in Pediatric Patients with a Suspicion of Crohn’s Disease
Authors: F. Argüelles-Arias, A. Caunedo, J. Romero, A. Sánchez, M. Rodríguez-Téllez, F. Pellicer, F. Argüelles-Martín, J. Herrerías
Journal: Endoscopy (2004)

Background and Study Aims: The aim of this study was to assess the safety and usefulness of capsule endoscopy (CE) in pediatric patients with a suspicion of Crohn’s disease. Patients and Methods: CE was used in 12 patients (four girls, eight boys; age 12 - 16; weight range 43 - 87 kg). The indication was a clinical suspicion of Crohn’s disease not confirmed with traditional methods. Gastroscopy, colonoscopy, and small-bowel follow-through examinations were carried out in all of the patients, without any diagnostic findings. Ileoscopy was possible in 50 % of the patients, and the ileal mucosa and biopsies were normal in all cases.
Predicting Outcomes in Cervical Cancer: A Kinetic Model of Tumor Regression during Radiation Therapy
Authors: Zhibin Huang, Nina A. Mayr, William T.C. Yuh, Simon S. Lo, Joseph F. Montebello, John C. Grecula, Lanchun Lu, Kaile Li, Hualin Zhang, Nilendu Gupta, Jian Z. Wang
Journal: Cancer Research (2010)

Abstract Applications of mathematical modeling can improve outcome predictions of cancer therapy. Here we present a kinetic model incorporating effects of radiosensitivity, tumor repopulation, and dead-cell resolving on the analysis of tumor volume regression data of 80 cervical cancer patients (stages 1B2-IVA) who underwent radiation therapy. Regression rates and derived model parameters correlated significantly with clinical outcome (P &amp;lt; 0.001; median follow-up: 6.2 years). The 6-year local tumor control rate was 87% versus 54% using radiosensitivity (2-Gy surviving fraction S2 &amp;lt; 0.70 vs. S2 ≥ 0.70) as a predictor (P = 0.001) and 89% vs. 57% using dead-cell resolving time (T1/2 &amp;lt; 22 days versus T1/2 ≥ 22 days, P &amp;lt; 0.001). The 6-year disease-specific survival was 73% versus 41% with S2 &amp;lt; 0.70 versus S2 ≥ 0.70 (P = 0.025), and 87% vs. 52% with T1/2 &amp;lt; 22 days versus T1/2 ≥ 22 days (P = 0.002). Our approach illustrates the promise of volume-based tumor response modeling to improve early outcome predictions that can be used to enable personalized adaptive therapy. Cancer Res; 70(2); 463–70
1431 MINIMAL IMPACT OF SOFOSBUVIR+RIBAVIRIN ON HEALTH RELATED QUALITY OF LIFE (HRQL) COMPARED TO PEGYLATED INTERFERON + RIBAVIRIN FOR CHRONIC HEPATITIS C (CH-C): RESULTS FROM FISSION+POSITRON STUDIES
Authors: Z.M. Younossi, M. Stepanova, H.M. Mir, I.M. Jacobson, E. Gane, F. Nader, S. Hunt
Journal: Journal of Hepatology (2013)
Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls
Authors: J. A C Sterne, I. R White, J. B Carlin, M. Spratt, P. Royston, M. G Kenward, A. M Wood, J. R Carpenter
Journal: BMJ (2009)

Most studies have some missing data. Jonathan Sterne and colleagues describe the appropriate use and reporting of the multiple imputation approach to dealing with them
Abstract DDT01-04: SGN-CD19A: A novel Anti-CD19 antibody drug conjugate
Authors: Tina M. Albertson, Lali Sandalic, Baiteng Zhao, Ana Kostic, Che-Leung Law
Journal: Cancer Research (2014)

Abstract CD19, a member of the immunoglobulin superfamily, is a B-cell specific marker that is found on B cells as early as the pro-B cell stage. CD19 is maintained upon malignant transformation and is expressed in the majority of patients with B-lineage acute lymphocytic leukemia (ALL) and non-Hodgkin lymphoma (NHL). SGN CD19A is a novel antibody-drug conjugate (ADC) composed of a humanized anti-CD19 monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin F (MMAF) via a maleimidocaproyl (mc) linker. Upon binding to CD19, SGN-CD19A internalizes and releases cys-mcMMAF, which binds to tubulin and induces G2/M arrest and apoptosis in the targeted cells. In mice bearing B-lineage ALL and lymphoma xenografts, SGN-CD19A induced dose-dependent tumor growth delay and extended survival. Two first-in-human, phase 1, dose-escalation studies are ongoing to investigate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SGN CD19A; one trial in adult and pediatric patients with relapsed or refractory (R/R) B cell ALL or highly aggressive B-cell lymphoma (CT.gov NCT01786096) and the second trial in adult patients with R/R B-cell NHL (CT.gov NCT01786135). Both trials employ a modified continual reassessment method (CRM) to estimate the dose-toxicity relationship and to estimate the maximum tolerated dose. Exploratory analyses include correlation of target (CD19) expression, target saturation, and apoptotic cellular markers with clinical response and clearance of leukemic blasts; dose and PK of SGN-CD19A will also be correlated with target saturation and intracellular levels of cys-mcMMAF. Early PK analyses indicate that plasma SGN-CD19A ADC generally increases with higher doses. Rapid clearance of ADC was observed at low doses in patients with leukemia, suggesting target-mediated drug disposition. Dose escalation of SGN-CD19A is ongoing in both clinical trials. In preliminary safety analyses, SGN-CD19A was generally tolerable at doses examined to date. Encouraging antitumor activity has been observed, with multiple patients achieving complete remissions in both trials. Citation Format: Tina M. Albertson, Lali Sandalic, Baiteng Zhao, Ana Kostic, Che-Leung Law. SGN-CD19A: A novel Anti-CD19 antibody drug conjugate. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr DDT01-04. doi:10.1158/1538-7445.AM2014-DDT01-04
ME-01 * GLIOMA CELL ADHESION AND INVASION REGULATED BY PROINFLAMMATORY CYTOKINE IN A NOVEL SURFACE/MATRIX CULTURE SYSTEM
Authors: M. Barish, N. Baghdadchi, A. Dickan, N. Khosh, V. Mahadev, S. Forman, C. Brown
Journal: Neuro-Oncology (2014)

Brain tumors are complex integrated tissues containing microglia and tumor associated macrophages in addition to glioma cells and vascular elements. These monocyte-lineage cells make important contributions to the tumor microenvironment. Activated M1-polarized microglia secrete a number of proinflammatory cytokines including tumor necrosis factor (TNF). We have previously reported that TNF increases surfaced expression of the adhesion molecule VCAM-1 [Mahadev et al. (2014) PLoSOne 9:e95123; PMID:24787244], and expression profiling indicates an increase in markers of mesenchymal phenotype. We have extended these observations to examine glioma cell adhesion and invasion in a novel 2.5D culture system. In brain, one route of brain tumor dissemination from an already-formed mass is along blood vessels in their associated extracellular matrix (ECM). We have recapitulated this arrangement by initiating tumor cell cultures by placing 10 µl drops of 500-10,000 patient-derived brain tumor cells in stem cell medium supplemented with 3% Matrigel in the centers of 12-mm diameter glass coverslips, allowing them to adhere, and then flooding the well with 1 ml of the same culture solution. Addition of TNF (2.5-20 ng/ml) increased surface expression of VCAM-1 and CD44, and enhanced formation of fascicles resembling chain migration of neural progenitor, and of subsidiary tumor islands. These processes are reminiscent of tumor cell invasion in vivo. These studies will be extended to include activated monocyte-lineage cells and other cell types in vitro, and subsequently into in vivo xenograft models.
Escitalopram for the Prevention of Peginterferon-α2a–Associated Depression in Hepatitis C Virus–Infected Patients Without Previous Psychiatric Disease
Authors: Martin Schaefer, Rahul Sarkar, Viola Knop, Susanne Effenberger, Astrid Friebe, Loni Heinze, Ulrich Spengler, Thomas Schlaepfer, Jens Reimer, Peter Buggisch, Johann Ockenga, Ralph Link, Michael Rentrop, Hans Weidenbach, Gwendolyn Fromm, Klaus Lieb, Thomas F. Baumert, Andreas Heinz, Thomas Discher, Konrad Neumann, Stefan Zeuzem, Thomas Berg
Journal: Annals of Internal Medicine (2012)

Background: Depression is a major complication during treatment of chronic hepatitis C virus (HCV) infection with interferon-α (IFN-α). It is unclear whether antidepressants can prevent IFN-induced depression in patients without psychiatric risk factors. Objective: To examine whether preemptive antidepressant treatment with escitalopram can decrease the incidence or severity of depression associated with pegylated IFN-α in HCV-infected patients without a history of psychiatric disorders. Design: Randomized, multicenter, double-blind, prospective, placebo-controlled, parallel-group trial. (ClinicalTrials.gov registration number: NCT00136318) Setting: 10 university and 11 academic hospitals in Germany. Patients: 181 HCV-infected patients with no history of psychiatric disorders enrolled between August 2004 and December 2008. Intervention: Escitalopram, 10 mg/d (n = 90), or placebo (n = 91) administered 2 weeks before and for 24 to 48 weeks during antiviral therapy. Measurements: The primary end point was the incidence of depression, defined as a Montgomery–Asberg Depression Rating Scale (MADRS) score of 13 or higher. Secondary end points were time to depression, incidence of major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, quality of life, sustained virologic response, tolerability, and safety. Results: 32% (95% CI, 21% to 43%) of the patients in the escitalopram group developed a MADRS score of 13 or higher compared with 59% (CI, 48% to 69%) in the placebo group (absolute difference, 27 percentage points [CI, 12 to 42 percentage points]; P < 0.001). Major depression was diagnosed in 8% of the patients in the escitalopram group and 19% in the placebo group (absolute risk difference, 11 percentage points [CI, 5 to 15 percentage points]; P = 0.031). Tolerability and safety parameters did not differ between the groups. In the escitalopram group, 56% (CI, 46% to 66%) of patients achieved a sustained virologic response compared with 46% (CI, 37% to 57%) in the placebo group (P = 0.21). Limitations: Results might not be generalizable to patients with previous psychiatric disease. Some patients withdrew or developed temporary elevated MADRS scores after randomization but before the study medication was started. Conclusion: Prophylactic antidepressant treatment with escitalopram was effective in reducing the incidence and severity of IFN-associated depression in HCV-infected patients without previous psychiatric disease. Primary Funding Source: Roche Pharma and Lundbeck.
Pirfenidone inhibits the induction of iNOS stimulated by interleukin-1β at a step of NF-κB DNA binding in hepatocytes
Authors: Hideki Nakanishi, Masaki Kaibori, Shigeru Teshima, Hideyuki Yoshida, A-Hon Kwon, Yasuo Kamiyama, Mikio Nishizawa, Seiji Ito, Tadayoshi Okumura
Journal: Journal of Hepatology (2004)
In pursuit of the “holy grail”: recombinant allergens and peptides as catalysts for the allergen‐specific immunotherapy
Authors: S. Mohapatra, Y. Cao, H. Ni, D. Salo
Journal: Allergy (1995)

This presentation reviews recent progress in knowledge of (i) molecular biology and immunology of allergens and (ii) the methods for the modulation of allergen-specific immune response, with special emphasis on our grass pollen allergens, particularly Pao p IX AL, used as a model. The last few years have seen tremendous progress in molecular characterization of allergens, leading to synthesis of a number of recombinant allergens. Furthermore, studies of the structure-activity relationship of allergens have led to the delineation of the epitopes of these allergens and of widespread cross-reactivities among diverse allergens. In view of the requirement for extensive pre-clinical studies, the application of the recombinant allergens and epitopes in the clinical realm has just begun. Studies in murine systems suggest that these allergens and/or their epitopic peptides downregulate allergen-specific immune responses de novo. The potential and drawbacks of the recombinant allergens and peptides for improving the existing immunotherapeutic approaches and for developing new approaches to specific immunotherapy are discussed.
Work for young people and care of elderly people are problems as world's population hits seven billion
Authors: N. Hawkes
Journal: BMJ (2011)

The world’s population will exceed seven billion for the first time in the next few days, just 12 years after it passed the six billion mark. The milestone, expected to be reached on 31 October, is “a challenge, an opportunity, and a call for action,” said Babatunde Osotimehin, executive director of the United Nations Population Fund

In a new report the fund says that greater investment is needed in young people aged 10 to 24 years, who make up 1.8 billion of the world’s seven billion. It also calls for greater equality between the sexes, empowering women and girls to make …
Evaluation of relationship between myocardial contractile state and left ventricular function in patients with aortic regurgitation.
Authors: W F Shen, G S Roubin, C Y Choong, B F Hutton, P J Harris, P J Fletcher, D T Kelly
Journal: Circulation (1985)

We studied the relationship between myocardial contractile state and left ventricular functional response to exercise in 14 asymptomatic patients with isolated moderate-to-severe aortic regurgitation and six control subjects. The slope of the systolic blood pressure-left ventricular end-systolic volume (pressure-volume) relationship determined by radionuclide ventriculography during angiotensin infusion was used as an indirect measure of myocardial contractility and was compared with left ventricular ejection fraction at rest and during both isometric handgrip and dynamic bicycle exercise. The slope of the pressure-volume relationship was significantly lower in patients with aortic regurgitation than in the control subjects (1.75 +/- 0.57 vs 2.78 +/- 0.42, p less than 0.01). The slope correlated exponentially with resting ejection fraction and was linearly related to changes in left ventricular ejection fraction during both handgrip and bicycle exercise. In patients with aortic regurgitation, resting ejection fraction may overestimate myocardial function. The slope of the pressure-volume relationship measured during afterload stress and left ventricular ejection fraction response to exercise intervention more reliably reflect the degree of left ventricular dysfunction.
Doctors to be advised on organ removal at necropsy
Authors: J. Warden
Journal: BMJ (1999)

The Royal College of Pathologists in London is considering drawing up good practice guidelines for retaining organs after postmortem examinations.

The college's move is timely in view of public concern about the removal of hearts from about 180 children who died after surgery at Bristol Royal Infirmary, some as a result of operations that led to three doctors being found guilty of serious professional misconduct (20 February, p 486).

The Department of Health said last …
A New Procedure for the Removal of Gastric Polyps and Foreign Bodies
Authors: P. Mainguet
Journal: Endoscopy (1976)

A simple procedure for the removal of multiple gastric polyps and foreign bodies is described. Before endoscopy, the introduction of a catheter bearing a nylon bag at its proximal end in the stomach is necessary. The method is safe and efficient, only 1.4% of the polyps were lost in a series of 69 polypectomies.
AGE AND GENDER-RELATED SYMPTOMS RECURRENCE AFTER AV NODE RE-ENTRANT TACHYCARDIA
Authors: Beatrice Brembilla-Perrot, Jean Marc Sellal, Arnaud Olivier, Julie Vincent, Sarah Dorlet, Vladimir Manenti, Etienne Aliot, Christian de Chillou, Daniel Beurrier, Anne Moulin-Zinsch
Journal: Journal of the American College of Cardiology (2014)
p73, miR106b, miR34a, and Itch in chronic lymphocytic leukemia
Authors: Pia Rivetti di Val Cervo, Paola Tucci, Aneela Majid, Maria Anna Lena, Massimiliano Agostini, Sergio Bernardini, Eleonora Candi, Gerry Cohen, Pierluigi Nicotera, Martin J. S. Dyer, Gerry Melino
Journal: Blood (2009)
Patient-Physician Communication: Respect for Culture, Religion, and Autonomy
Authors: Louis A. Kazal
Journal: JAMA (1996)

<h3>To the Editor.</h3> —My colleagues and I read the article by Drs Carrese and Rhodes<sup>1</sup>with great interest. We practice rural medicine as employees of the Navajo Nation Health Foundation, a nonprofit, private Navajo organization located on the Navajo reservation in Ganado, Ariz. Nearly all of our patients are Navajo, and thus we encounter the Navajo concept of<i>hózhó</i>on a daily basis. The authors' findings are consistent with our experience. Over time, we have discovered that discussing potentially negative issues such as adverse effects of medications, complications from procedures, advance directives, and death is best done using the third person plural.<sup>2</sup>For example, instead of "you might develop a stomach ulcer using too much ibuprofen," the physicians say, "when people take too much ibuprofen, they might develop a stomach ulcer." The third person plural approach has been well received by our patients. In general, Navajo patients quickly
1032 COMPARATIVE STUDY BETWEEN DRUG-ELUTING BEAD (DC BEAD®) LOADED WITH DOXORUBICIN (DEBDOX) AND CONVENTIONAL TRANSARTERIAL CHEMOEMBOLIZATION IN THE TREATMENT OF HEPATOCELLULAR CARCINOMA
Authors: M.J. Song, D.S. Song, S.H. Yoo, H.Y. Kim, C.-H. Park, U.I. Chang, H.J. Chun, S.H. Bae, J.Y. Choi, J.M. Yang, S.K. Yoon
Journal: Journal of Hepatology (2012)
Health surveillance of preschool children: four years' experience.
Authors: A F Colver
Journal: BMJ (1990)

To monitor the implementation of a programme of health surveillance for preschool children and measure its effect on child health.Regular reporting to primary care teams of their own performance, and determining the overall effect of the programme on children in the district.All practices in Northumberland health district.All children of preschool age in Northumberland (3600 births each year).Proportion of eligible children immunised and screened for abnormalities. Age at diagnosis of congenital deafness, cerebral palsy, and special educational needs.Over 90% of eligible children were covered by the health surveillance scheme. Child health improved over the four years after the scheme was implemented. Uptake of immunisation against measles rose from 68% to 93% of eligible children, and the average age at which congenital deafness was diagnosed fell to 9 months.Maintaining the effectiveness of a surveillance programme and reporting this back to primary health care teams are processes which themselves improve health.