tbuckley/cabot-search huggingface dataset:
Transglutaminase 2 and Its Role in Pulmonary Fibrosis
Authors: Keith C. Olsen, Ramil E. Sapinoro, R. M. Kottmann, Ajit A. Kulkarni, Siiri E. Iismaa, Gail V. W. Johnson, Thomas H. Thatcher, Richard P. Phipps, Patricia J. Sime
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Idiopathic pulmonary fibrosis (IPF) is a deadly progressive disease with few treatment options. Transglutaminase 2 (TG2) is a multifunctional protein, but its function in pulmonary fibrosis is unknown.To determine the role of TG2 in pulmonary fibrosis.The fibrotic response to bleomycin was compared between wild-type and TG2 knockout mice. Transglutaminase and transglutaminase-catalyzed isopeptide bond expression was examined in formalin-fixed human lung biopsy sections by immunohistochemistry from patients with IPF. In addition, primary human lung fibroblasts were used to study TG2 function in vitro.TG2 knockout mice developed significantly reduced fibrosis compared with wild-type mice as determined by hydroxyproline content and histologic fibrosis score (P < 0.05). TG2 expression and activity are increased in lung biopsy sections in humans with IPF compared with normal control subjects. In vitro overexpression of TG2 led to increased fibronectin deposition, whereas transglutaminase knockdown led to defects in contraction and adhesion. The profibrotic cytokine transforming growth factor-β causes an increase in membrane-localized TG2, increasing its enzymatic activity.TG2 is involved in pulmonary fibrosis in a mouse model and in human disease and is important in normal fibroblast function. With continued research on TG2, it may offer a new therapeutic target.
THE EFFECT OF INJECTIONS OF HEMOLYTIC STREPTOCOCCI ON SUSCEPTIBLE AND INSUSCEPTIBLE ANIMALS
Authors: J. Gardner Hopkins, Julia T. Parker
Journal: The Journal of Experimental Medicine (1918)

1. Streptococci injected into the circulation of cats are quickly withdrawn and are found most numerously in the lung, less numerously in the liver and spleen, and in small numbers in the bone marrow, lymph nodes, muscle, and kidney. 2. The streptococci taken up by the lung are killed within 5 to 8 hours, although they remain visible in films for a number of days. In the liver they are killed less rapidly, and in the spleen a few may remain viable for a considerable period. 3. This bactericidal action may be demonstrated in pieces of excised lung but not in lung extracts, and is apparently dependent on the action of the living cell. 4. Streptococci injected into a susceptible animal, the rabbit, are also promptly removed from the circulation, but are distributed in different proportions, the liver and spleen absorbing almost as many as the lung, and the muscles also taking up an appreciable number. 5. As in the cat, the organisms taken up by the lung and liver of the living rabbit are promptly killed. Those which lodge in the muscles, however, multiply rapidly. 6. About the time that the streptococci have begun to develop in the muscles (4 to 8 hours after injection) the number in the blood stream begins to increase. 7. The increase in the blood stream is not due to exhaustion of the mechanism of their removal nor have these organisms acquired a resistance sufficient to maintain them in the blood stream of a normal animal. The septicemia, then, is probably the resuit of washing out of organisms from the infected tissues. 8. Attempts to immunize rabbits have been unsuccessful, but in certain treated animals the distribution of the organisms among the various organs approached that found in insusceptible animals; i.e., cats.
Newborn Hearing Screening vs Later Hearing Screening and Developmental Outcomes in Children With Permanent Childhood Hearing Impairment
Authors: Anna M. H. Korver, Saskia Konings, Friedo W. Dekker, Mieke Beers, Capi C. Wever, Johan H. M. Frijns, Anne M. Oudesluys-Murphy, for the DECIBEL Collaborative Study Group
Journal: JAMA (2010)

Newborn hearing screening programs have been implemented in many countries because it was thought that the earlier permanent childhood hearing impairment is detected, the less developmentally disadvantaged children would become. To date, however, no strong evidence exists for universal introduction of newborn hearing screening.To study the effect of newborn hearing screening vs distraction hearing screening, conducted at 9 months of age, on development, spoken communication, and quality of life.Between 2002 and 2006, all 65 regions in The Netherlands replaced distraction hearing screening with newborn hearing screening. Consequently, the type of hearing screening offered was based on availability at the place and date of birth and was independent of developmental prognoses of individual children. All children born in The Netherlands between 2003 and 2005 were included. At the age of 3 to 5 years, all children with permanent childhood hearing impairment were identified. Evaluation ended December 2009.Performance (education and spoken and signed communication), development (general and language), and quality of life.During the study period, 335,560 children were born in a newborn hearing screening region and 234,826 children in a distraction hearing screening region. At follow-up, 263 children in newborn hearing screening regions (0.78 per 1000 children) and 171 children in distraction hearing screening regions (0.73 per 1000 children) had been diagnosed with permanent childhood hearing impairment. Three hundred one children (69.4%) participated in analysis of general performance measures. There was no difference between groups in the primary mode of communication or type of education. Analysis of extensive developmental outcomes included 80 children born in newborn hearing screening regions and 70 in distraction hearing screening regions. Multivariate analysis of variance showed that overall, children in newborn hearing screening regions had higher developmental outcome scores compared with children in distraction hearing screening regions (Wilks λ = 0.79; F(12) = 2.705; P = .003). For social development, the mean between-group difference in quotient points was 8.8 (95% CI, 0.8 to 16.7) and for gross motor development, 9.1 (95% CI, 1.1 to 17.1). For quality of life, the mean between-group difference was 5.3 (95% CI, 1.7 to 8.9), also in favor of children in newborn hearing screening regions.Compared with distraction hearing screening, a newborn hearing screening program was associated with better developmental outcomes at age 3 to 5 years among children with permanent childhood hearing impairment.
Consultations for asthma: will greater patient involvement deliver better health?
Authors: C J Griffiths
Journal: Thorax (2005)

Self-management of asthma is a complicated activity, perhaps more demanding for asthma than for any other chronic illness. People with asthma are faced with an illness whose causes and fluctuations are poorly understood (witness the pages of this journal), to be controlled with an often mysterious collection of inhalers. Our increasingly high expectations of patients’ abilities to self-care are fuelled by trials in selected populations1 and politicians with visions of reduced healthcare costs.2,3 The realities of asthma self-management are often scepticism and low uptake.4 The consultation remains the most important opportunity for helping patients to develop the ability to manage their asthma. Rightly, the consultation continues to be subject to a range of critical perspectives.

Social scientists offer a number of deficiencies that hinder success in promoting self-care: the infrequency with which doctors seek and patients air fears about medication and side effects, lack of opportunity for patient involvement in treatment decisions, lack of recognition of the coexistence of lay and popular remedies. We stand accused of an enthusiasm for authoritarian, positivist, illness centred medicine.5,6–10 Ethicists show how …
Analysis of Maryland Cancer Patient Participation in National Cancer Institute–Supported Cancer Treatment Clinical Trials
Authors: Claudia R. Baquet, Gary L. Ellison, Shiraz I. Mishra
Journal: Journal of Clinical Oncology (2008)

We examined the relationship of sociodemographic factors, urban/rural residence, and county-level socioeconomic factors on accrual of Maryland patients with cancer to National Cancer Institute (NCI) -sponsored cancer treatment clinical trials.
Frequencies of T Cells Expressing Interleukin-4 and Interleukin-5 in Atopic Asthmatic Children
Authors: NORBERT KRUG, THOMAS JUNG, UTE NAPP, KATHRIN WAGNER, GERHARD SCHULTZE-WERNINGHAUS, CHRISTOPH HEUSSER, CHRISTIAN H. L. RIEGER, UWE SCHAUER, HELMUT FABEL
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

T-cell-derived cytokines have been implicated in the pathogenesis of asthma and it has been suggested that Th2-type cytokines (interleukin-4 [IL-4], interleukin-5 [IL-5]) are pivotal in the allergic inflammation. However, there are little data on human cytokine production by individual T cells at the protein level, in particular in asthmatic children. In this study we analyzed the cytokine production at the single cell level in peripheral blood from mild atopic asthmatic (AA) children and adults and age-matched atopic nonasthmatic (AN) and nonatopic nonasthmatic (NN) control subjects (n = 9 in each group) using the technique of intracellular cytokine detection by flow cytometry. Comparing asthmatic children with atopic and nonatopic control subjects, an increased percentage of IL-5-producing T cells (AA: median 4.9% [range 1.1 to 8.9%]; AN: 0.3% [0.2 to 0.9%], p = 0.003; NN: 0.4% [0.1 to 3.8%], p = 0.001) was detectable, with a positive correlation to the number of peripheral eosinophils and to bronchial hyperresponsiveness. The frequency of IL-4-producing T cells was increased in both atopic groups compared with nonatopic controls (AA: 1.2% [0.2 to 2.6%], p = 0.011; AN: 0.8% [0.4 to 3.7%], p = 0.007; NN: 0.4% [0.2 to 0.9%]) with a positive correlation to total IgE concentration. In adults there were no differences in IL-5- or IL-4-producing T cells between all three groups. A substantial proportion of T cells coproducing IL-4 and IL-5 was not detectable in children and adults. These findings indicate that in asthmatic children the frequencies of Th2-type-producing T cells are increased and that expression of IL-4 and IL-5 is regulated independently.
Physician-assessed and patient-reported outcome measures in chemotherapy-induced sensory peripheral neurotoxicity: two sides of the same coin
Authors: P. Alberti, E. Rossi, D.R. Cornblath, I.S.J. Merkies, T.J. Postma, B. Frigeni, J. Bruna, R. Velasco, A.A. Argyriou, H.P. Kalofonos, D. Psimaras, D. Ricard, A. Pace, E. Galiè, C. Briani, C. Dalla Torre, C.G. Faber, R.I. Lalisang, W. Boogerd, D. Brandsma, S. Koeppen, J. Hense, D. Storey, S. Kerrigan, A. Schenone, S. Fabbri, M.G. Valsecchi, G. Cavaletti, G. Cavaletti, D.R. Cornblath, I.S.J. Merkies, T.J. Postma, M.G Valsecchi, S. Galimberti, E. Rossi, G. Cavaletti, B. Frigeni, F. Lanzani, L. Mattavelli, M.L. Piatti, P. Alberti, D. Binda, P. Bidoli, M. Cazzaniga, D. Cortinovis, J. Bruna, R. Velasco, A.A. Argyriou, H.P. Kalofonos, D. Psimaras, D. Ricard, A. Pace, E. Galiè, C. Briani, M. Lucchetta, M. Campagnolo, C. Dalla Torre, I.S.J. Merkies, C.G. Faber, I.S.J. Merkies, E.K. Vanhoutte, M. Bakkers, B. Brouwer, R.I. Lalisang, W. Boogerd, D. Brandsma, S. Koeppen, J. Hense, R. Grant, D. Storey, S. Kerrigan, A. Schenone, L. Reni, B. Piras, S. Fabbri, L. Padua, G. Granata, M. Leandri, I. Ghignotti, R. Plasmati, F. Pastorelli, T.J. Postma, J.J. Heimans, M. Eurelings, R.J. Meijer, W. Grisold, E. Lindeck Pozza, A. Mazzeo, A. Toscano, C. Tomasello, G. Altavilla, M. Penas Prado, C. Dominguez Gonzalez, S.G. Dorsey, J.M. Brell
Journal: Annals of Oncology (2013)
On the unproductiveness of language and linguistics
Authors: David M. W. Powers
Journal: Behavioral and Brain Sciences (2006)

van der Velde &amp; de Kamps (dvV&amp;dK) present a response to Jackendoff's four challenges in terms of a computational model. This commentary supports the position that neural assemblies mediated by recurrence and delay indeed have sufficient theoretical power to deal with all four challenges. However, we question the specifics of the model proposed, in terms of both neurophysiological plausibility and computational complexity.
RELATIONSHIP BETWEEN THE EXTENT OF LIPID-RICH PLAQUE ASSESSED BY NEAR-INFRARED SPECTROSCOPY AND CLINICAL PRESENTATION: A COLOR REGISTRY ANALYSIS
Authors: Fuyu Qiu, Akiko Maehara, Annapoorna Kini, David Rizik, Emmanouil Brilakis, Kendrick Shunk, Jonathan Tobis, Kosaku Goto, Tomotaka Dohi, Ke Xu, Gregg Stone, Gary Mintz, James Muller, Giora Weisz
Journal: Journal of the American College of Cardiology (2014)
Randomized Phase III Trial Comparing Weekly Docetaxel Plus Cisplatin Versus Docetaxel Monotherapy Every 3 Weeks in Elderly Patients With Advanced Non–Small-Cell Lung Cancer: The Intergroup Trial JCOG0803/WJOG4307L
Authors: Tetsuya Abe, Koji Takeda, Yuichiro Ohe, Shinzoh Kudoh, Yukito Ichinose, Hiroaki Okamoto, Nobuyuki Yamamoto, Hiroshige Yoshioka, Koichi Minato, Toshiyuki Sawa, Yasuo Iwamoto, Hideo Saka, Junki Mizusawa, Taro Shibata, Shinichiro Nakamura, Masahiko Ando, Akira Yokoyama, Kazuhiko Nakagawa, Nagahiro Saijo, Tomohide Tamura
Journal: Journal of Clinical Oncology (2015)

Purpose This phase III trial aimed to confirm the superiority of weekly docetaxel and cisplatin over docetaxel monotherapy in elderly patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Chemotherapy-naïve patients with stage III, stage IV, or recurrent NSCLC age ≥ 70 years with a performance status of 0 or 1 who were considered unsuitable for bolus cisplatin administration were randomly assigned to receive docetaxel 60 mg/m 2 on day 1, every 3 weeks, or docetaxel 20 mg/m 2 plus cisplatin 25 mg/m 2 on days 1, 8, and 15, every 4 weeks. The primary end point was overall survival (OS). Results In the first interim analysis, OS of the doublet arm was inferior to that of the monotherapy arm (hazard ratio [HR], 1.56; 95% CI, 0.98 to 2.49), and the predictive probability that the doublet arm would be statistically superior to the monotherapy arm on final analysis was 0.996%, which led to early study termination. In total, 276 patients with a median age of 76 years (range, 70 to 87 years) were enrolled. At the updated analysis, the median survival time was 14.8 months for the monotherapy arm and 13.3 months for the doublet arm (HR, 1.18; 95% CI, 0.83 to 1.69). The rates of grade ≥ 3 neutropenia and febrile neutropenia were higher in the monotherapy arm, and those of anorexia and hyponatremia were higher in the doublet arm. Conclusion This study failed to demonstrate any survival advantage of weekly docetaxel plus cisplatin over docetaxel monotherapy as first-line chemotherapy for advanced NSCLC in elderly patients.
IL-13 stimulates vascular endothelial cell growth factor and protects against hyperoxic acute lung injury
Authors: Jonathan Corne, Geoffrey Chupp, Chun Guen Lee, Robert J. Homer, Zhou Zhu, Qingsheng Chen, Bing Ma, Yuefen Du, Francoise Roux, John McArdle, Aaron B. Waxman, Jack A. Elias
Journal: Journal of Clinical Investigation (2000)

Hyperoxia is an important cause of acute lung injury. To determine whether IL-13 is protective in hyperoxia, we compared the survival in 100% O2 of transgenic mice that overexpress IL-13 in the lung and of nontransgenic littermate controls. IL-13 enhanced survival in 100% O2. One hundred percent of nontransgenic mice died in 4–5 days, whereas 100% of IL-13–overexpressing mice lived for more than 7 days, and many lived 10–14 days. IL-13 also stimulated VEGF accumulation in mice breathing room air, and it interacted with 100% 2 to increase VEGF accumulation further. The 164–amino acid isoform was the major VEGF moiety in bronchoalveolar lavage from transgenic mice in room air, whereas the 120– and 188–amino acid isoforms accumulated in these mice during hyperoxia. In addition, antibody neutralization of VEGF decreased the survival of IL-13–overexpressing mice in 100% 2. These studies demonstrate that IL-13 has protective effects in hyperoxic acute lung injury. They also demonstrate that IL-13, alone and in combination with 100% 2, stimulates pulmonary VEGF accumulation, that this stimulation is isoform-specific, and that the protective effects of IL-13 are mediated, in part, by VEGF.
Clinical Questions Raised by Clinicians at the Point of Care
Authors: Guilherme Del Fiol, T. Elizabeth Workman, Paul N. Gorman
Journal: JAMA Internal Medicine (2014)

In making decisions about patient care, clinicians raise questions and are unable to pursue or find answers to most of them. Unanswered questions may lead to suboptimal patient care decisions.To systematically review studies that examined the questions clinicians raise in the context of patient care decision making.MEDLINE (from 1966), CINAHL (from 1982), and Scopus (from 1947), all through May 26, 2011. STUDY SELECTION Studies that examined questions raised and observed by clinicians (physicians, medical residents, physician assistants, nurse practitioners, nurses, dentists, and care managers) in the context of patient care were independently screened and abstracted by 2 investigators. Of 21,710 citations, 72 met the selection criteria.Question frequency was estimated by pooling data from studies with similar methods.Frequency of questions raised, pursued, and answered and questions by type according to a taxonomy of clinical questions. Thematic analysis of barriers to information seeking and the effects of information seeking on decision making. RESULTS In 11 studies, 7012 questions were elicited through short interviews with clinicians after each patient visit. The mean frequency of questions raised was 0.57 (95% CI, 0.38-0.77) per patient seen, and clinicians pursued 51% (36%-66%) of questions and found answers to 78% (67%-88%) of those they pursued. Overall, 34% of questions concerned drug treatment, and 24% concerned potential causes of a symptom, physical finding, or diagnostic test finding. Clinicians' lack of time and doubt that a useful answer exists were the main barriers to information seeking.Clinicians frequently raise questions about patient care in their practice. Although they are effective at finding answers to questions they pursue, roughly half of the questions are never pursued. This picture has been fairly stable over time despite the broad availability of online evidence resources that can answer these questions. Technology-based solutions should enable clinicians to track their questions and provide just-in-time access to high-quality evidence in the context of patient care decision making. Opportunities for improvement include the recent adoption of electronic health record systems and maintenance of certification requirements.
The Development of Murine Plasmacytoid Dendritic Cell Precursors Is Differentially Regulated by FLT3-ligand and Granulocyte/Macrophage Colony-Stimulating Factor
Authors: Michel Gilliet, Andre Boonstra, Carine Paturel, Svetlana Antonenko, Xiu-Ling Xu, Giorgio Trinchieri, Anne O'Garra, Yong-Jun Liu
Journal: The Journal of Experimental Medicine (2002)

Plasmacytoid predendritic cells or type 1 interferon (IFN)-producing cells (IPCs) have recently been identified in mice. Although culture systems giving rise to different murine dendritic cell subsets have been established, the developmental regulation of murine plasmacytoid IPCs and the culture conditions leading to their generation remain unknown. Here we show that large numbers of over 40% pure CD11c+CD11b−B220+Gr-1+ IPCs can be generated from mouse bone marrow cultures with FLT3-ligand. By contrast GM-CSF or TNF-α, which promote the generation of CD11c+CD11b+B220− myeloid DCs, block completely the development of IPCs. IPCs generated display similar features to human IPCs, such as the plasmacytoid morphology, the ability to produce large amounts of IFN-α in responses to herpes simplex virus, and the capacity to respond to ligands for Toll-like receptor 9 (TLR-9; CpG ODN 1668), but not to ligands for TLR-4 (lipopolysaccharide [LPS]). Unlike human IPCs which produce little IL-12p70, mouse IPCs produce IL-12p70 in response to CpG ODN 1668 and herpes simplex virus. This study demonstrates that the development of murine CD11c+CD11b−B220+Gr-1+ IPCs and CD11c+CD11b+B220− myeloid DCs is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor. Human IPCs and mouse IPCs display different ability to produce IL-12p70. Large numbers of mouse IPCs can now be obtained from total bone marrow culture.
Striate palmoplantar keratoderma arising from desmoplakin and desmoglein 1 mutations is associated with contrasting perturbations of desmosomes and the keratin filament network
Authors: H. Wan, P.J.C. Dopping-Hepenstal, M.J. Gratian, M.G. Stone, G. Zhu, P.E. Purkis, A.P. South, F. Keane, D.K.B. Armstrong, R.S. Buxton, J.A. McGrath, R.A.J. Eady
Journal: British Journal of Dermatology (2004)

Background Several hereditary human diseases are now known to be caused by distinct mutations in genes encoding various desmosome components. Although the effects of some of these mutant genes have been analysed by targeted disruption experiments in mouse models, little is known about the cell and tissue changes in affected human patients. Objectives To investigate the effects of heterozygous nonsense mutations in desmoplakin (Dp) and desmoglein (Dsg) 1 which cause the autosomal dominant disorder striate palmoplantar keratoderma (SPPK), focusing on changes in desmosome structure and composition and the associated keratin intermediate filament (KIF) network in palm skin, and in cultured keratinocytes generated from the same site. Methods We analysed palm and nonpalm skin sections from four SPPK patients with Dp mutations and one patient with a Dsg1 mutation with respect to tissue and subcellular morphologies, and correlated the in vivo and in vitro findings. Results Using electron microscopy, we found abnormalities of desmosomes and cell–cell adhesion in the suprabasal layers in the epidermis from patients with both Dsg1‐ and Dp‐associated SPPK. These changes were more advanced in skin from patients with Dp mutations. Both Dp and Dsg1 mutations were accompanied by significantly reduced numbers of desmosomes in the suprabasal layers, while decreased desmosome size was evident only in Dsg1‐associated SPPK. Confocal microscopy analysis showed marked differences in the expression of keratins and of desmosome components, both between the two types of SPPK, and between SPPK and normal skin. The expression of keratins K5, K14 and K10 was reduced in Dsg1‐associated SPPK skin, whereas perinuclear aggregation of keratin filaments was more evident in Dp‐associated SPPK. In both types of SPPK upregulation of K16 was pronounced and involucrin labelling was abnormal. Conclusions Mutations in Dp and Dsg1 genes causing SPPK may be associated with perturbations in epidermal differentiation accompanied by a marked disruption of several components of the epidermal scaffold including desmosomes and the KIF network.
EFFECTS OF OXYGEN BREATHING ON THE HEART RATE, BLOOD PRESSURE, AND CARDIAC INDEX OF NORMAL MEN—RESTING, WITH REACTIVE HYPEREMIA, AND AFTER ATROPINE*
Authors: Walter J. Daly, Stuart Bondurant
Journal: Journal of Clinical Investigation (1962)

known quantity of dye + 0.05 mg.All injections were made during the end-expiratory phase of respiration.A Harvard withdrawal pump was used to draw blood through a Waters XP-100A densitometer from the brachial arterial needle at a rate of 19.4 ml per minute.