tbuckley/cabot-search huggingface dataset:
How Health Care Reform Can Benefit Children and Adolescents
Authors: Judith S. Palfrey
Journal: New England Journal of Medicine (2009)

Medical and scientific advances have reduced the rates of acute childhood illnesses and childhood mortality and increased the positive outcomes of a wide variety of serious childhood illnesses; nevertheless, children's health in the United States currently falls short. Our infant mortality rate is higher than that of 29 other countries, and the United Nations Children's Fund (UNICEF) ranks the United States last among 21 developed countries in terms of children's health and safety.1 The children's health community is looking to health care reform to improve access, provide needed preventive and comprehensive benefits, and develop quality initiatives for all children and . . .
Autoantibodies to desmoplakin I and II in patients with erythema multiforme.
Authors: D Foedinger, G J Anhalt, B Boecskoer, A Elbe, K Wolff, K Rappersberger
Journal: The Journal of Experimental Medicine (1995)

Erythema multiforme (EM) represents a syndrome of chronic recurrent inflammatory skin disease. Depending on the severity and extent of skin and mucosal involvement, it is defined either as EM minor or EM major. In this study we demonstrate the presence of autoantibodies (aAbs) against desmoplakin I and II, two major proteins of the desmosomal plaque, in six of six patients with the severe variant of EM, EM major. Light microscopic studies of lesional skin and mucous membranes localized in vivo bound immunoglobulin G (IgG) in a dotted desmosomal pattern along the cytoplasmic membranes of keratinocytes. By immunoelectronmicroscopy, in vivo bound IgG was confined to the desmosomal plaques. These findings were confirmed by indirect immunolocalization studies that demonstrated the presence of IgG aAbs in the serum of patients during active disease. These aAbs did not only bind to desmosomal plaques of epithelial cells where they colocalized with defined murine monoclonal antibodies directed against desmoplakin I and II, but also labeled the intercalated discs of myocardial cells. Biochemical characterization of circulating IgG aAbs revealed desmoplakin I and II as actual target autoantigens. By passive transfer of serum into newborn mice, in vivo binding of serum aAbs to keratinocytes was shown. The findings presented in this study imply a humoral immune response in certain patients with EM major and indicate a potential pathogenetic role of aAbs against desmoplakin I and II in this disease.
A new member of the immunoglobulin superfamily that has a cytoplasmic region homologous to the leukocyte common antigen.
Authors: M Streuli, N X Krueger, L R Hall, S F Schlossman, H Saito
Journal: The Journal of Experimental Medicine (1988)

A human gene (LAR) that hybridizes to mouse leukocyte common antigen cDNA under relaxed hybridization conditions was isolated. The LAR gene is expressed in a broad range of cells, including T lymphocytes, kidney, and prostate cells. The structure of the protein encoded by the LAR gene was deduced by determining the nucleotide sequences of a 7.7-kb LAR cDNA. The putative LAR protein is composed of a 1,234 amino acid extracellular region, a 24 amino acid transmembrane segment, and a 623 amino acid cytoplasmic region. The cytoplasmic region contains two homologous domains that have extensive sequence similarity to the cytoplasmic region of the leukocyte common antigens. The NH2-terminal region of the extracellular segment of the LAR protein contains three tandem Ig-like domains and nine non-Ig-like domains. Among the known Ig-like proteins, the LAR protein has the highest degree of similarity to neural-cell adhesion molecule. The non-Ig-like domains of the LAR protein are also similar to the non-Ig-like domains of neural-cell adhesion molecule.
Genetic Disorders Affecting Proteins of Iron Metabolism: Clinical Implications
Authors: Sujit Sheth, Gary M. Brittenham
Journal: Annual Review of Medicine (2000)

▪ Abstract Remarkable progress is being made in understanding the molecular basis of disorders of human iron metabolism. Recent work has uncovered unanticipated relationships with the immune and nervous systems, intricate interconnections with copper metabolism, and striking homologies between yeast and human genes involved in the transport of transition metals. This review examines the clinical consequences of new insights into the pathophysiology of genetic abnormalities affecting iron metabolism. The proteins recently found to be involved in the absorption, transport, utilization, and storage of iron are briefly described, and the clinical manifestations of genetic disorders that affect these proteins are discussed. This chapter considers the most common inherited disorder in individuals of European ancestry (hereditary hemochromatosis), a widespread disease in sub-Saharan populations for which the genetic basis is still uncertain (African dietary iron overload), and several less frequent or rare disorders (juvenile hemochromatosis, atransferrinemia, aceruloplasminemia, hyperferritinemia with autosomal dominant congenital cataract, Friedreich’s ataxia, and X-linked sideroblastic anemia with ataxia).
Intentional versus unintentional contact as a mechanism of injury in youth ice hockey
Authors: Scott R Darling, Douglas E Schaubel, John G Baker, John J Leddy, Leslie J Bisson, Barry Willer
Journal: British Journal of Sports Medicine (2010)

Background Youth ice hockey injury rates and mechanisms have been described by various classification systems. Intentional versus unintentional contact was used to classify mechanisms of injuries. All injuries (n=247) in one youth hockey programme over a 5-year period were recorded and included in the analysis. Purpose To evaluate youth ice hockey injuries and compare programmes that allow body checking versus programmes that do not allow body checking. A primary goal was to determine whether programmes that allow body checking have increased injury rates from intentional body contact. Another goal was to describe the rates of injury across ages, levels of competitive play and during games versus practices. Methods Rates of injury were compared for three levels of competition (house, select and representative) for approximately 3000 boys aged 4–18 years over a 5-year period. This represents 13 292 player years. Data were collected prospectively in this cohort study. All injuries were reported prospectively by a designated team official and verified by a physician. The log injury rate (per 1000 player hours) was modelled via Poisson regression with log player hours used as an offset. Rate ratio was used to explain the covariate-adjusted injury rate for each of three groups (all injuries, intentional injuries, unintentional injuries). Results Unintentional contacts accounted for 66.0% of overall injuries (95% CI 60.0 to 72.0), compared with 34.0% from intentional contacts (p&lt;0.001;Z=5.25). Serious injuries (fractures, dislocations, concussions) resulted more often from unintentional collisions (p=0.04). Players in more competitive leagues that allow body checking had a greater incidence of total injuries than less competitive leagues. Conclusions Most injuries in the youth hockey programme studied were the result of unintentional contact, and were generally more severe. These findings were not expected given previously published research.
DiR-labeled Embryonic Stem Cells for Targeted Imaging of <i>in vivo</i> Gastric Cancer Cells
Authors: Jing Ruan, Hua Song, Chao Li, Chenchen Bao, Hualin Fu, Kan Wang, Jian Ni, Daxiang Cui
Journal: Theranostics (2012)

Embryonic stem (ES) cells have great potential in applications such as disease modeling, pharmacological screening and stem cell therapies.Up to date, there is no related report on the use of ES cells as tracking and contrast reagents of cancer cells in vivo.Herein we report that DiR-labeled murine ES cells can recognize and target gastric cancer cells in vivo.DiR-labeled murine ES (mES) cells (5×10 6 ) were intravenously injected into gastric tumor-bearing mice.The biodistribution of DiR-labeled mES cells was monitored by IVIS imaging within 24 h.Major organs were harvested and analyzed by immunofluorescence staining and Western blotting.Chemotaxis assay was employed to investigate the chemotaxis of ES cells tracking cancer cells.Fluorescent imaging results showed that DiR-labeled mES cells targeted gastric cancer tissue in vivo as early as 10 min post-injection, reaching a peak at 2h post-injection.Immunofluorescence staining and Western blotting results showed gastric cancer tissues specifically expressed SSEA-1.In vitro migration tests confirmed that mES cells actively moved to test sites with different concentration of CXCL12 in a dose-dependent manner.In conclusion, DiR-labeled mES cells may be used for gastric cancer targeted imaging in vivo, and have great potential in applications such as identifying and imaging of early gastric cancer in near future.
THE INFECTION OF CHIMPANZEES WITH ECHO VIRUSES
Authors: Heihachi Itoh, Joseph L. Melnick
Journal: The Journal of Experimental Medicine (1957)

The oral and parenteral infections of chimpanzees receiving echo Types 6 and 4 viruses successively are described. The two infections, spaced 2(1/2) months apart, and given by the same route in each animal, failed to induce overt disease. The inapparent infections were demonstrated by virus excretion in the throat and the stools and the development of neutralizing antibodies. Complement-fixing antibodies also appeared after Type 6 infection, but fell more rapidly than the neutralizing antibodies. After oral infection, echo-6 virus was found for equal periods in both the throat and feces, but echo-4 persisted in the throat for much longer periods than in the lower bowel. Almost no virus carriage occurred after parenteral inoculation. No true viremia was exhibited in any of the animals. One of the chimpanzees had neutralizing antibodies against Type 6 virus in its pre-inoculation serum. It responded extraordinarily to the Type 6 exposure, developing antibody levels of 1:50,000 to echo-6, of 1:1024 against the echo-6' variant, and of 1:64 against the echo 6'' variant. Although Type 4 antibodies developed after the exposure, they proved difficult to measure by ordinary methods. However, they could be satisfactorily assayed by the plaque reduction method. Three other chimpanzees fed echo-2, echo-3, and an untypable echo virus, respectively, yielded results confirming those established with Types 4 and 6.
Tumor-Associated Macrophages in SHH Subgroup of Medulloblastomas
Authors: Ashley S. Margol, Nathan J. Robison, Janahan Gnanachandran, Long T. Hung, Rebekah J. Kennedy, Marzieh Vali, Girish Dhall, Jonathan L. Finlay, Anat Erdreich-Epstein, Mark D. Krieger, Rachid Drissi, Maryam Fouladi, Floyd H. Gilles, Alexander R. Judkins, Richard Sposto, Shahab Asgharzadeh
Journal: Clinical Cancer Research (2014)

Medulloblastoma in children can be categorized into at least four molecular subgroups, offering the potential for targeted therapeutic approaches to reduce treatment-related morbidities. Little is known about the role of tumor microenvironment in medulloblastoma or its contribution to these molecular subgroups. Tumor microenvironment has been shown to be an important source for therapeutic targets in both adult and pediatric neoplasms. In this study, we investigated the hypothesis that expression of genes related to tumor-associated macrophages (TAM) correlates with the medulloblastoma molecular subgroups and contributes to a diagnostic signature.
Is clinical presentation different between men and women with COPD
Authors: Olatz Llaguno, Igor Murga, David Bravo, Julia García, Jose Luis Lobo, Agustina Rivas, Patricia Sobradillo
Journal: European Respiratory Journal (2014)

Background 

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality throughout the world, traditionally associated with men. However, recent epidemiological studies have shown significant increase in the prevalence of COPD among women. The aim of our study was to recognize gender differences in clinical characteristics of COPD patients in the area of Vitoria.

Methods 

We included patients with COPD diagnosis controlled in an outpatient clinic of Universitary Hospital of Araba-Txagorritxu, from March to November 2013. Clinical, functional and radiological data were obtained and classified according to GOLD recommendations. Patients were grouped according to Spanish guideliness. Variables were expressed as percentage, mean and standard deviation. Student t-test and Chi-square were used for the comparisons between groups. P-value < 0.05 was considered statistically significant.

Results 

A total of 84 patients were included in the study, 21 women and 63 men. Main characteristics and differences are shown in table 1.

![Figure][1] 



Conclusions: 

− Prevalence of COPD among women in our cohort is 25%.

− When compared with men, women were younger and showed a trend to be diagnosed earlier.

− No differences were found according to dyspnea, CAT and airflow limitation.

− Women show emphysema phenotype more frequently than men.

 [1]: pending:yes
The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress.
Authors: Y Ikeda, M Handa, K Kawano, T Kamata, M Murata, Y Araki, H Anbo, Y Kawai, K Watanabe, I Itagaki
Journal: Journal of Clinical Investigation (1991)

Exposure of platelets to shear stress leads to aggregation in the absence of exogenous agonists. We have now found that different adhesive proteins and platelet membrane glycoproteins are involved in aggregation depending on the shear stress conditions and the concentration of divalent cations in the medium. When blood is collected with trisodium citrate as anticoagulant, which causes a decrease in the levels of external ionized calcium ([Ca2+]o), platelet aggregation can be induced under low shear force (12 dyn/cm2) and is mediated by fibrinogen binding to the glycoprotein IIb-IIIa complex. Aggregates formed under these conditions are not stable, and when shear force is increased to 68 dyn/cm2, disaggregation results. By contrast, platelets from blood collected with hirudin as anticoagulant, wherein [Ca2+]o is within normal plasma levels, do not undergo low shear-induced aggregation; however, after exposure to a shear force above 80 dyn/cm2, aggregation is observed but only when von Willebrand factor is present and can interact with both its platelet binding sites, glycoprotein Ib-IX and glycoprotein IIb-IIIa. Fibrinogen is not involved in high shear-induced aggregation which, in fact, occurs normally in patients with severe afibrinogenemia. Thus, von Willebrand factor in the absence of exogenous agonists can mediate platelet aggregation in experimental conditions that may mimic the hemorheological situation of partially occluded arteries. This pathway of platelet aggregation involving only one adhesive ligand and two membrane adhesion receptors may play a relevant role in thrombogenesis.
Vagally induced block and delayed conduction as a mechanism for circus movement tachycardia in frog atria.
Authors: L V Rosenshtraukh, A V Zaitsev, V G Fast, A M Pertsov, V I Krinsky
Journal: Circulation Research (1989)

Episodes of tachycardia induced by strong vagal stimulation in spontaneously beating isolated atria of frog (Rana temporaria) were studied with multielectrode mapping technique. These episodes were inducible in 19 of 39 preparations. The arrhythmia started several seconds after cessation of vagal stimulation strong enough to cause sinus arrest, without electrical stimulation of the myocardium. The arrhythmia consisted of two to 20 beats (6 +/- 4, mean +/- SD, n = 42) with a cycle length of 100-500 msec. Recording from 32 sites with spatial resolution of 1-2 mm showed that the arrhythmia was due to intra-atrial circus movement. The estimated perimeter of the reentrant circuit ranged from 6 to 20 mm. In circuits of the minimal size, the average conduction velocity along the circuit was as low as 2-3 cm/sec. Paroxysms of the tachycardia were always preceded by vagally induced nonuniform depression of conduction, with some areas of atria being completely blocked. As the vagal influence decreased, the blocked areas recovered in an inhomogeneous manner, their unblocking being significantly (p less than 0.05) delayed after inhibition of tissue cholinesterase by proserine. The reentrant tachycardia was initiated when a sinus impulse arrived during certain phase of the unblocking. Unlike the well-known mechanism of reentrant excitation, which is based on inhomogeneous refractoriness and critically timed extrabeat(s), the circus movement in our model depended on vagally induced conduction block and could be launched by a single sinus impulse.
Spectral analysis of heart rate and blood pressure variability in primary Sjogren's syndrome
Authors: P J Barendregt
Journal: Annals of the Rheumatic Diseases (2002)

Autonomic dysfunction has been described in primary Sjögren's syndrome (SS).To investigate the circulatory autonomic regulation in patients with primary SS by power spectral analysis of heart rate and blood pressure variability.Forty three (42 female) patients with primary SS, mean age 52 years (range 23-80), with a mean disease duration of eight years (range 1-30) and 30 (15 female) healthy controls, mean age 43 years (range 21-68) were studied. In each patient blood pressure, heart rate, and respiration were measured continuously during supine rest and orthostatic challenge (60 degrees head-up tilt). Power spectral analysis was performed to determine possible differences in short term sympathetic and parasympathetic autonomic regulation between patients and controls. Furthermore, spectral parameters were studied in relation to illness severity and disease duration of the patients with primary SS.After controlling for differences in age, heart rate variability of the mid-frequency band and the variation coefficient of systolic blood pressure were significantly lower in patients with primary SS than in controls during supine rest. During 60 degrees tilt patients with primary SS showed a significantly higher mean heart rate, mean systolic blood pressure, and variation coefficient of diastolic blood pressure, and a significantly lower baroreflex index than controls. After controlling for age, no differences were found either in heart rate variability, blood pressure results, and baroreflex sensitivity during supine rest and tilt between the subgroups divided according to disease duration, Schirmer test results, or between the subgroups with different fatigue scores. No differences were found in spectral data between the groups with and without positive antinuclear antibody serology.For the group no differences in sympathetic and parasympathetic cardiac control were seen between patients with primary SS and controls, as assessed by spectral techniques, although some cardiovascular differences were found, particularly during orthostatic challenge.
Interventions to improve symptoms and quality of life of patients with fibrotic interstitial lung disease: a systematic review of the literature
Authors: Sabrina Bajwah, Joy R Ross, Janet L Peacock, Irene J Higginson, Athol U Wells, Amit Suresh Patel, Jonathan Koffman, Julia Riley
Journal: Thorax (2012)

<h3>Background</h3> Patients with fibrotic interstitial lung disease have symptom control and quality of life (QoL) needs. This review aims to evaluate the evidence for the use of interventions in improving dyspnoea, other symptoms and QoL. <h3>Methods</h3> Eleven databases, relevant websites and key journals were hand-searched. Studies were assessed and data extracted independently by two researchers using standardised proformas. Meta-analyses were performed where possible with 95% CI. <h3>Results</h3> 34 papers with 19 interventions in 3635 patients were included. Meta-analyses showed no significant effect of interferon γ-1b or sildenafil on 6-minute walking distance (6MWD) or dyspnoea. Pulmonary rehabilitation and pirfenidone had a positive effect on 6MWD (mean difference (95% CI) 27.4 (4.1 to 50.7)) and 24.0 (4.3 to 43.7), respectively), and pulmonary rehabilitation had a mixed effect on dyspnoea. Both pulmonary rehabilitation and sildenafil showed a trend towards significance in improving QoL. There was weak evidence for the improvement of 6MWD using oxygen; dyspnoea using prednisolone, diamorphine, D-pencillamine and colchicine; cough using interferon α and thalidomide; anxiety using diamorphine; fatigue using pulmonary rehabilitation; and QoL using thalidomide and doxycycline. A wide range of outcome scales was used and there were no studies with economic evaluation. <h3>Conclusions</h3> There is strong evidence for the use of pulmonary rehabilitation and pirfenidone to improve 6MWD and moderate evidence for the use of sildenafil and pulmonary rehabilitation to improve QoL. Future recommendations for research would include careful consideration of the dichotomy of radical and palliative treatments when deciding on how symptom and QoL outcome measures are used and data presented.
Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial
Authors: Frits van Rhee, Raymond S Wong, Nikhil Munshi, Jean-Francois Rossi, Xiao-Yan Ke, Alexander Fosså, David Simpson, Marcelo Capra, Ting Liu, Ruey Kuen Hsieh, Yeow Tee Goh, Jun Zhu, Seok-Goo Cho, Hanyun Ren, James Cavet, Rajesh Bandekar, Margaret Rothman, Thomas A Puchalski, Manjula Reddy, Helgi van de Velde, Jessica Vermeulen, Corey Casper
Journal: The Lancet Oncology (2014)
Impact of a Higher Radiation Dose on Local Control and Survival in Breast-Conserving Therapy of Early Breast Cancer: 10-Year Results of the Randomized Boost Versus No Boost EORTC 22881-10882 Trial
Authors: Harry Bartelink, Jean-Claude Horiot, Philip M. Poortmans, Henk Struikmans, Walter Van den Bogaert, Alain Fourquet, Jos J. Jager, Willem J. Hoogenraad, S. Bing Oei, Carla C. Wárlám-Rodenhuis, Marianne Pierart, Laurence Collette
Journal: Journal of Clinical Oncology (2007)

Purpose To investigate the long-term impact of a boost radiation dose of 16 Gy on local control, fibrosis, and overall survival for patients with stage I and II breast cancer who underwent breast-conserving therapy. Patients and Methods A total of 5,318 patients with microscopically complete excision followed by whole-breast irradiation of 50 Gy were randomly assigned to receive either a boost dose of 16 Gy (2,661 patients) or no boost dose (2,657 patients), with a median follow-up of 10.8 years. Results The median age was 55 years. Local recurrence was reported as the first treatment failure in 278 patients with no boost versus 165 patients with boost; at 10 years, the cumulative incidence of local recurrence was 10.2% versus 6.2% for the no boost and the boost group, respectively (P &lt; .0001). The hazard ratio of local recurrence was 0.59 (0.46 to 0.76) in favor of the boost, with no statistically significant interaction per age group. The absolute risk reduction at 10 years per age group was the largest in patients ≤ 40 years of age: 23.9% to 13.5% (P = .0014). As a result, the number of salvage mastectomies has been reduced by 41%. Severe fibrosis was statistically significantly increased (P &lt; .0001) in the boost group, with a 10-year rate of 4.4% versus 1.6% in the no boost group (P &lt; .0001). Survival at 10 years was 82% in both arms. Conclusion After a median follow-up period of 10.8 years, a boost dose of 16 Gy led to improved local control in all age groups, but no difference in survival.