tbuckley/cabot-search huggingface dataset:
Monocyte Adhesion to Decidual Endothelial Cells Is Increased in Pregnancies Complicated by Type 1 Diabetes but not by Gestational Diabetes
Authors: Anoula Galettis, Suzanne Campbell, Jonathan M. Morris, Christopher J. Jackson, Steven M. Twigg, Eileen D.M. Gallery
Journal: Diabetes Care (2004)

Type 1 diabetes complicates ∼1 of every 200 pregnancies and gestational diabetes a further 2–3% of pregnancies (1). Systemic atheromatous vascular disease can develop or accelerate during diabetic pregnancy. We and others (2) have observed similar vascular lesions in placental bed vessels (Fig. 1 A ) associated with impaired placental function and fetal growth.

Genesis of atheroma involves adherence of peripheral blood monocytes to endothelium (3–5). To determine whether a similar process underlies the placental bed vasculopathy of diabetes, we examined cell adhesion in an in vitro coculture system using decidual endothelial cells from normal pregnancies and monocytes from both normal and diabetic pregnancies.

This study was approved by the Human Research Ethics Committee of Royal North Shore Hospital. All subjects gave written informed consent.

Blood for monocyte isolation was collected from three groups of women, i.e., normal (control), type 1 diabetes (confirmed prepregnancy by a history of diabetic ketoacidosis and/or presence of anti-GAD antibodies), and gestational diabetes ( n = 6 in each group) groups, in the third trimester of pregnancy.

Endothelial cells were isolated from decidual biopsies collected from a separate group of nine healthy pregnant women at elective lower-segment caesarean section (6 …
Association of hospital admission and forced vital capacity endpoints with survival in patients with idiopathic pulmonary fibrosis: analysis of a pooled cohort from three clinical trials
Authors: Michael T Durheim, Harold R Collard, Rhonda S Roberts, Kevin K Brown, Kevin R Flaherty, Talmadge E King, Scott M Palmer, Ganesh Raghu, Laurie D Snyder, Kevin J Anstrom, Fernando J Martinez
Journal: The Lancet Respiratory Medicine (2015)
Characteristics of rat aortic baroreceptors with nonmedullated afferent nerve fibers.
Authors: P Thorén, W R Saum, A M Brown
Journal: Circulation Research (1977)

Nervous activity was recorded from nonmedullated afferent baroreceptor fibers in the left aortic nerve of normotensive rats. The aortic arch was perfused in vitro with oxygenated Krebs-Henseleit solution. Two different patterns of aortic C fiber discharge were found. One type (5 of 29 fibers) had a regular discharge at constant pressure whereas the other type had an irregular discharge. The differences between the two types were independent of the mean steady state rates of discharge. The average threshold pressure for the receptors with the regular discharge was 87 mm Hg (range, 65-125); it was 152 mm Hg (range, 85-260) for the irregularly discharging receptors. During a pressure step the receptors in either group normally showed an initial high frequency burst of activity and a sustained discharge which had a lower frequency. Furthermore, the peak discharge and the sustained discharge were lower on the average in the receptors with the irregular type of firing. We also found that addition of norepinephrine to the perfusate lowered threshold. Since unmyelinated axons are the predominant fiber type in the rat aortic nerve and since some receptors are activated at physiological pressures they may contribute to the tonic control of blood pressure. Their effects should be particularly important when the blood pressure is increased.
The HMGB1/RAGE axis triggers neutrophil-mediated injury amplification following necrosis
Authors: Peter Huebener, Jean-Philippe Pradere, Celine Hernandez, Geum-Youn Gwak, Jorge Matias Caviglia, Xueru Mu, John D. Loike, Rosalind E. Jenkins, Daniel J. Antoine, Robert F. Schwabe
Journal: Journal of Clinical Investigation (2019)

In contrast to microbially triggered inflammation, mechanisms promoting sterile inflammation remain poorly understood. Damage-associated molecular patterns (DAMPs) are considered key inducers of sterile inflammation following cell death, but the relative contribution of specific DAMPs, including high–mobility group box 1 (HMGB1), is ill defined. Due to the postnatal lethality of Hmgb1-knockout mice, the role of HMGB1 in sterile inflammation and disease processes in vivo remains controversial. Here, using conditional ablation strategies, we have demonstrated that epithelial, but not bone marrow–derived, HMGB1 is required for sterile inflammation following injury. Epithelial HMGB1, through its receptor RAGE, triggered recruitment of neutrophils, but not macrophages, toward necrosis. In clinically relevant models of necrosis, HMGB1/RAGE-induced neutrophil recruitment mediated subsequent amplification of injury, depending on the presence of neutrophil elastase. Notably, hepatocyte-specific HMGB1 ablation resulted in 100% survival following lethal acetaminophen intoxication. In contrast to necrosis, HMGB1 ablation did not alter inflammation or mortality in response to TNF- or FAS-mediated apoptosis. In LPS-induced shock, in which HMGB1 was considered a key mediator, HMGB1 ablation did not ameliorate inflammation or lethality, despite efficient reduction of HMGB1 serum levels. Our study establishes HMGB1 as a bona fide and targetable DAMP that selectively triggers a neutrophil-mediated injury amplification loop in the setting of necrosis.
Increased live birth rates with GnRH agonist addition for luteal support in ICSI/IVF cycles: a systematic review and meta-analysis
Authors: D. Kyrou, E.M. Kolibianakis, H.M. Fatemi, T.B. Tarlatzi, P. Devroey, B.C. Tarlatzis
Journal: Human Reproduction Update (2011)

BACKGROUNDThe aim of this systematic review and meta-analysis was to evaluate whether the addition of GnRH agonist for luteal support in ICSI/IVF cycles enhances the probability of live birth.
Advances in Bone Biology: The Osteoclast*
Authors: G. DAVID ROODMAN
Journal: Endocrine Reviews (1996)

BONE is a dynamic tissue that constantly undergoes remodeling. Bone remodeling is a coupled process in which bone resorption is normally followed by new bone formation. During early life, bone formation exceeds bone resorption with a net increase in bone mass, while late in life, bone resorption exceeds bone formation with net loss of bone. During some pathological processes, such as in patients with advanced stages of multiple myeloma, bone remodeling is uncoupled, and bone resorption is not followed by new bone formation. The primary cell responsible for bone resorption is the multinucleated osteoclast. Although many questions still remain unanswered about the factors that regulate osteoclast formation and osteoclastic bone resorption, major advances have been made recently in our understanding of the cell biology and molecular biology of the osteoclast, as well as the role that the marrow microenvironment plays in regulating osteoclast formation and bone resorption.
The Physiology and Pharmacology of Spinal Opiates
Authors: T L Yaksh, R Noueihed
Journal: The Annual Review of Pharmacology and Toxicology (1985)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
Mangafodipir prevents liver injury induced by acetaminophen in the mouse
Authors: Sassia Bedda, Alexis Laurent, Filomena Conti, Chistiane Chéreau, Agnès Tran, Jeanne Tran-Van Nhieu, Patrick Jaffray, Olivier Soubrane, Claire Goulvestre, Yvon Calmus, Bernard Weill, Frédéric Batteux
Journal: Journal of Hepatology (2003)
Constitutive AP-1 Activity and EBV Infection Induce PD-L1 in Hodgkin Lymphomas and Posttransplant Lymphoproliferative Disorders: Implications for Targeted Therapy
Authors: Michael R. Green, Scott Rodig, Przemyslaw Juszczynski, Jing Ouyang, Papiya Sinha, Evan O'Donnell, Donna Neuberg, Margaret A. Shipp
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Programmed cell death ligand 1 (PD-L1) is a molecule expressed on antigen-presenting cells that engages the PD-1 receptor on T cells and inhibits T-cell receptor signaling. The PD-1 axis can be exploited by tumor cells to dampen host antitumor immune responses and foster tumor cell survival. PD-1 blockade has shown promise in multiple malignancies but should be directed toward patients in whom it will be most effective. In recent studies, we found that the chromosome 9p24.1 amplification increased the gene dosage of PD-L1 and its induction by JAK2 in a subset of patients with classical Hodgkin lymphoma (cHL). However, cHLs with normal 9p24.1 copy numbers also expressed detectable PD-L1, prompting analyses of additional PD-L1 regulatory mechanisms. Experimental Design: Herein, we utilized immunohistochemical, genomic, and functional analyses to define alternative mechanisms of PD-L1 activation in cHL and additional EBV+ lymphoproliferative disorders. Results: We identified an AP-1–responsive enhancer in the PD-L1 gene. In cHL Reed–Sternberg cells, which exhibit constitutive AP-1 activation, the PD-L1 enhancer binds AP-1 components and increases PD-L1 promoter activity. In addition, we defined Epstein–Barr virus (EBV) infection as an alternative mechanism for PD-L1 induction in cHLs with diploid 9p24.1. PD-L1 was also expressed by EBV-transformed lymphoblastoid cell lines as a result of latent membrane protein 1–mediated, JAK/STAT-dependent promoter and AP-1–associated enhancer activity. In addition, more than 70% of EBV+ posttransplant lymphoproliferative disorders expressed detectable PD-L1. Conclusions: AP-1 signaling and EBV infection represent alternative mechanisms of PD-L1 induction and extend the spectrum of tumors in which to consider PD-1 blockade. Clin Cancer Res; 18(6); 1611–8. ©2012 AACR.
Assessment of Left Ventricular Torsional Deformation by Doppler Tissue Imaging
Authors: Yuichi Notomi, Randolph M. Setser, Takahiro Shiota, Maureen G. Martin-Miklovic, Joan A. Weaver, Zoran B. Popović, Hirotsugu Yamada, Neil L. Greenberg, Richard D. White, James D. Thomas
Journal: Circulation (2005)

Background— Left ventricular (LV) torsional deformation is a sensitive index for LV performance but difficult to measure. The present study tested the accuracy of a novel method that uses Doppler tissue imaging (DTI) for quantifying LV torsion in humans with tagged magnetic resonance imaging (MRI) as a reference. Methods and Results— Twenty patients underwent DTI and tagged MRI studies. Images of the LV were acquired at apical and basal short-axis levels to assess LV torsion. We calculated LV rotation by integrating the rotational velocity, determined from DTI velocities of the septal and lateral regions, and correcting for the LV radius over time. LV torsion was defined as the difference in LV rotation between the 2 levels. DTI rotational and torsional profiles throughout systole and diastole were compared with those by tagged MRI at isochronal points. Rotation and torsion by DTI were closely correlated with tagged MRI results during systole and early diastole (apical and basal rotation, r =0.87 and 0.90, respectively; for torsion, 0.84; P &lt;0.0001, by repeated-measures regression models). Maximal torsion showed even better correlation ( r =0.95, P &lt;0.0001). Conclusions— The present study has shown that DTI can quantify LV torsional deformation over time. This novel method may facilitate noninvasive quantification of LV torsion in clinical and research settings.
Quality of health information on the Internet in pediatric neuro-oncology
Authors: Darren R. Hargrave, Ursula A. Hargrave, Eric Bouffet
Journal: Neuro-Oncology (2006)

The Internet is now the single largest source of health information and is used by many patients and their families who are affected by childhood brain tumors. To assess the quality of pediatric neuro-oncology information on the Internet, we used search engines to look for information on five common tumor types (brain stem glioma, craniopharyngioma, ependymoma, low-grade glioma, and medulloblastoma). The Web sites were evaluated for content quality by using the validated DISCERN rating instrument. Breadth of content and its accuracy were also scored by a checklist tool. Readability statistics were computed on the highest-rated sites. Of 114 evaluated Web sites, the sources were as follows: institutional, 46%; commercial, 35%; charitable, 15%; support group, 2%; and alternative medicine, 2%. Good interobserver correlation was found for both ratings instruments. The DISCERN tool rated Web sites as excellent (4%), good (7%), fair (29%), poor (39%), or very poor (21%). Only 5% of the Web sites provided one or more inaccurate pieces of information. Web sites were found deficient in topics covering etiology, late effects, prognosis, and treatment choices. Few sites offered information in languages other than English, and readability statistics showed an average required reading level of U.S. grade 12+ (the suggested level being grades 6-8 for an adult audience). The Internet is increasingly being used as a source of oncology information for patients and their families. Health care professionals should be actively involved in developing high-quality information for use in the next generation of Web sites.
Obstructive Uropathy in Mice and Humans
Authors: Sekiko Taneda, Kelly L. Hudkins, Stavros Topouzis, Debra G. Gilbertson, Vuddhidej Ophascharoensuk, Luan Truong, Richard J. Johnson, Charles E. Alpers
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Tubulointerstitial fibrosis is a major characteristic of progressive renal diseases. Platelet-derived growth factor (PDGF) is a family of growth regulatory molecules consisting of PDGF-A and -B, along with the newly discovered PDGF-C and -D. They signal through cell membrane receptors, PDGF receptor α (PDGF-Rα) and receptor β (PDGF-Rβ). Involvement of PDGF-B and PDGF-Rβ in the initiation and progression of renal fibrosis has been well documented. The authors studied the localization of PDGF ligands and receptors by immunohistochemistry, with emphasis on the role of PDGF-D in murine renal fibrosis induced by unilateral ureteral obstruction (UUO). In mice with UUO, <i>de novo</i> expression of PDGF-D was detected in interstitial cells at day 4, which increased to maximal expression at day 14. Increased expression of PDGF-B by interstitial cells and in some tubules was observed after day 4. The diseased mice did not show augmentation of PDGF-A or PDGF-C proteins in the areas of fibrosis. PDGF-Rα and -Rβ protein expression was increased in interstitial cells after day 4 and reached maximal expression at day 14. Human renal nephrectomies (<i>n</i> = 10) of chronic obstructive nephropathy demonstrated similar <i>de novo</i> expression of PDGF-D in interstitial cells, correlating with expression of PDGF-Rβ and PDGF-B, as it did in the murine model. These observations suggest that PDGF-D plays an important role in the pathogenesis of tubulointerstitial injury through binding of PDGF-Rβ in both human obstructive nephropathy and the corresponding murine model of UUO. E-mail: calp@u.washington.edu
Through Thick and Thin Collagen Fibrils, Stress, and Aortic Rupture
Authors: Janet T. Powell, Toste Länne
Journal: Circulation (2007)

his century has seen a leap forward in both treatment and understanding of the molecular and pathogenetic mechanisms underlying aortic dissection.The advantages of endovascular stenting are becoming obvious, and results from the Investigation of Stent Grafts in Patients With Type B Aortic Dissection (INSTEAD) trial are pending. 1Molecular and pathogenetic advances include genetic defects mapped to several chromosomes in familial thoracic aortic dissection, including splice and missense mutations in the TGFBR2 gene on chromosome 3 associated with a Marfanoid syndrome. 2Indeed, evidence is increasing that dysregulated transforming growth factor-␤ signaling is an underlying mechanism in aneurysm formation.The small leucine-rich proteoglycans, including biglycan, bind transforming growth factor-␤ and regulate collagen fibrillogenesis in vitro. 3The current article by Heegaard and colleagues, 4 as well as the recent work of Takaluoma et al, 5 uses mouse models to further our understanding of the weaknesses in collagen fibrils that can provoke the aortic dissection characteristic of Ehlers-Danlos syndrome.
TG4010 immunotherapy plus chemotherapy as first-line treatment of advanced non small cell lung cancer (NSCLC): Phase IIb results of the TIME trial
Authors: John Nemunaitis, Zsolt Papai, Hervé Léna, Gyorgy Losonczy, Frederic Forget, Christos Chouaid, Alexandra Szczesna, Radj Gervais, Christian H Ottensmeier, Joseph Beck, Andrzej Kazarnowicz, Virginie Westeel, Didier Debieuvre, Anne Madroszyk, Enriqueta Felip, Jean Limacher, Elisabeth Quoix
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts TG4010 is an immunotherapy using an attenuated and modified poxvirus (MVA) coding for MUC1 and interleukin-2 to induce a cellular immune response against MUC1 expressing tumors. Previous Phase 2 trials have demonstrated the efficacy and safety of TG4010 in combination with
Comparison of pixantrone-based regimen (CPOP-R) with doxorubicin-based therapy (CHOP-R) for treatment of diffuse large B-cell lymphoma
Authors: R. Herbrecht, P. Cernohous, A. Engert, S. Le Gouill, D. Macdonald, C. Machida, H. Myint, A. Saleh, J. Singer, M. Wilhelm, R. van der Jagt
Journal: Annals of Oncology (2013)
Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion
Authors: Menno C. van Zelm, Tomasz Szczepański, Mirjam van der Burg, Jacques J.M. van Dongen
Journal: The Journal of Experimental Medicine (2007)

The contribution of proliferation to B lymphocyte homeostasis and antigen responses is largely unknown. We quantified the replication history of mouse and human B lymphocyte subsets by calculating the ratio between genomic coding joints and signal joints on kappa-deleting recombination excision circles (KREC) of the IGK-deleting rearrangement. This approach was validated with in vitro proliferation studies. We demonstrate that naive mature B lymphocytes, but not transitional B lymphocytes, undergo in vivo homeostatic proliferation in the absence of somatic mutations in the periphery. T cell–dependent B cell proliferation was substantially higher and showed higher frequencies of somatic hypermutation than T cell–independent responses, fitting with the robustness and high affinity of T cell–dependent antibody responses. More extensive proliferation and somatic hypermutation in antigen-experienced B lymphocytes from human adults compared to children indicated consecutive responses upon additional antigen exposures. Our combined observations unravel the contribution of proliferation to both B lymphocyte homeostasis and antigen-induced B cell expansion. We propose an important role for both processes in humoral immunity. These new insights will support the understanding of peripheral B cell regeneration after hematopoietic stem cell transplantation or B cell–directed antibody therapy, and the identification of defects in homeostatic or antigen-induced B cell proliferation in patients with common variable immunodeficiency or another antibody deficiency.
End-of-Life Care Preferences of Pediatric Patients With Cancer
Authors: Pamela S. Hinds, Donna Drew, Linda L. Oakes, Maryam Fouladi, Sheri L. Spunt, Christopher Church, Wayne L. Furman
Journal: Journal of Clinical Oncology (2005)

The viewpoint of the terminally ill child at the time of an end-of-life decision has not been formally investigated. We identified the preferences of children and adolescents with advanced cancer about their end-of-life care and the factors that influenced their decisions.Pediatric patients 10 or more years of age were interviewed within 7 days of participating in one of the following three end-of-life decisions: enrollment onto a phase I trial (n = 7), adoption of a do not resuscitate order (n = 5), or initiation of terminal care (n = 8). The patient, a parent, and the primary pediatric oncologist were interviewed separately by using open-ended interview questions.Twenty patients, aged 10 to 20 years (mean, 17 years and 4 months), with a refractory solid tumor (n = 12), brain tumor (n = 4), or leukemia (n = 4) participated. Eighteen patients (90%) accurately recalled all of their treatment options and identified their own death as a consequence of their decision. The factors that were most frequently identified included the following: for patients, caring about others (n = 19 patients); for parents, the child's preferences (n = 18 parents); and for physicians, the patient's prognosis and comorbid conditions (n = 14 physicians).These children and adolescents with advanced cancer realized that they were involved in an end-of-life decision, understood the consequences of their decision, and were capable of participating in a complex decision process involving risks to themselves and others. The decision factors most frequently reported by patients were relationship based; this finding is contrary to existing developmental theories.
Human Tissue Act: implications for sports science
Authors: James H K Hull, Paula Ansley, Les Ansley
Journal: British Journal of Sports Medicine (2008)

In September 2006, an Act with significant implications for sports science research conducted in the UK came into force. The Human Tissue (HT) Act replaced the previous version of 1961 and affects all scientific practice that involves human tissue sampling and storage.1 The HT Act was conceived in response to shortcomings revealed in a series of public inquiries into UK hospital practice over the past 25 years;2 3 in particular, to address the use of human tissue and organs without appropriate patient consent. Consequently, its purpose is to provide a new legal framework for the acquisition, analysis and storage of human tissue in England, Wales and Northern Ireland. In order to implement this Act, a special authority (the Human Tissue Authority; HTA) was also established. Since inception, the Act has had significant implications for both clinical and research practice in the UK.4 5 Indeed, although the Act primarily concerns pathological specimens, it affects all practice that involves human tissue sampling. This is particularly true in sports science, where collection, storage and analysis of human samples are fundamental to many studies. #### Categories of "relevant" human samples in the HT Act ##### I. Specifically identified relevant material This includes material such as bodily organs and tissues, consisting largely or entirely of cells, and clearly identifiable and regarded as such. The category includes internal organs and tissues, skin and bone; and specifically the following: