tbuckley/cabot-search huggingface dataset:
Endothelial Cells Modify the Costimulatory Capacity of Transmigrating Leukocytes and Promote Cd28-Mediated Cd4+ T Cell Alloactivation
Authors: Mark D. Denton, Christopher S. Geehan, Steve I. Alexander, Mohamed H. Sayegh, David M. Briscoe
Journal: The Journal of Experimental Medicine (1999)

Activated vascular endothelial cells (ECs) express major histocompatibility complex (MHC) class II molecules in vitro and in vivo in acute and chronic allograft rejection. However, human ECs may be limited in their ability to effectively activate CD4(+) T cells, because they do not express members of the B7 family (CD80 and CD86) of costimulatory molecules. In this study, we show that ECs promote the full activation of CD4(+) T cells via trans-costimulatory interactions. By reverse transcriptase polymerase chain reaction, Western blot, and FACS((R)) analysis, we could not detect the expression of CD80 and CD86 on activated ECs and found minimal expression on purified CD4(+) T cells. In contrast, both CD80 and CD86 were expressed in allogeneic CD4(+) T cell-EC cocultures. Expression of CD86 peaked at early times between 12 and 24 h after coculture, whereas CD80 was not expressed until 72 h. Addition of anti-CD86 but not anti-CD80 monoclonal antibodies to cocultures inhibited IL-2 production and the proliferation of CD4(+) T cells to allogeneic donor human umbilical vein ECs (HUVECs), as well as to skin and lung microvascular ECs. Furthermore, we found that interferon gamma-activated ECs but not untreated ECs induced mRNA and cell surface expression of CD80 and CD86 on CD4(+) T cells, and these T cells were functional to provide a trans-costimulatory signal to autologous CD4(+) T cells. Blockade of MHC class II and lymphocyte function-associated antigen 3 but not other EC cell surface molecules on IFN-gamma-activated ECs inhibited the induction of CD86 on CD4(+) T cells. Transmigration of purified populations of monocytes across EC monolayers similarly resulted in the induction of functional CD86, but also induced the de novo expression of the cytokines interleukin (IL)-1alpha and IL-12. In addition, EC-modified monocytes supported enhanced proliferation of allogeneic and autologous CD4(+) T cells. Taken together, these data define the ability of the endothelium to modify CD4(+) T cells and monocytes for trans-costimulatory events. This unique function of the endothelium in alloimmune T cell activation has functional consequences for the direct and the indirect pathways of allorecognition.
Paradoxical vocal cord adduction in an adolescent with cystic fibrosis.
Authors: P Shiels, J P Hayes, M X FitzGerald
Journal: Thorax (1995)

Many patients with cystic fibrosis have symptoms of dyspnoea and wheeze which are responsive to treatment with bronchodilators. An adolescent woman with cystic fibrosis is described who presented with inspiratory stridor and in whom the classical features of paradoxical vocal cord adduction were found.
STUDIES ON THE BIOLOGY OF STREPTOCOCCUS
Authors: Franklin A. Stevens, A. R. Dochez
Journal: The Journal of Experimental Medicine (1924)

1. Strains of hemolytic streptococci from cases of scarlet fever occurring in New York, San Francisco, Chicago, Baltimore, and Copenhagen, Denmark, all interagglutinate with immune sera prepared with these strains. 2. Sera prepared with these strains do not agglutinate pyogenic streptococci or strains isolated from cases of septic sore throat. 3. The strains obtained from the throats of patients from an epidemic of scarlet fever and the strain from the milk responsible for this epidemic fall into the scarlatinal group according to these agglutination tests. 4. Absorption tests can be carried out with these strains and sera under proper conditions. 5. A group of hemolytic streptococci biologically distinct from streptococci from other sources than scarlet fever is constantly associated with scarlatina. They constitute a group of closely related streptococci which may be identified by agglutination tests.
Screening for neuroblastoma in the north of England.
Authors: L. Parker, A. W. Craft, G. Dale, S. Bell, M. Cole, A. C. McGill, J. A. Seviour, J. Smith
Journal: BMJ (1992)

OBJECTIVE--To determine the feasibility of establishing a system of screening for neuroblastoma. DESIGN--Prospective study of mass screening in four clearly defined geographical areas. SETTING--Four health districts of the Northern region of England. SUBJECTS--20,829 babies aged 6 months, 92% of target population. INTERVENTIONS--Collection of urine on filter paper for analysis of content of homovanillic and vanillylmandelic acid in relation to urinary creatinine concentrations. MAIN OUTCOME MEASURES--Derivation of reference range. Identification of babies with homovanillic or vanillylmandelic acid &gt; 3 SD above the mean (positive cases). Investigation of positive cases for evidence of neuroblastoma. RESULTS--The upper limit of normal (3 SD above the mean) for vanillylmandelic acid was 15 mumol/mmol creatinine and for homovanillic acid 24 mumol/mmol creatinine. Of the 20,829 babies screened, 2537 (12.2%) required a second sample to be taken because the first sample was inadequate. Of these, 527 (2.5%) provided a liquid urine specimen and 10 (0.04%) had positive results for neuroblastoma. Two of them had neuroblastoma (true positives) and eight did not (false positives). A further three children from the cohort were subsequently found to have neuroblastoma; they had raised homovanillic acid or vanillylmandelic acid values, or both, but screened negative at 6 months. CONCLUSIONS--Screening for neuroblastoma is possible in the health care system of the United Kingdom. Evaluation of the efficacy of screening in reducing the mortality from neuroblastoma requires a controlled trial.
Determinants of Pulmonary Vascular Volume
Authors: Attilio Maseri, Paolo Caldini, Peter Harward, Ramesh C. Joshi, Solbert Permutt, Kenneth L. Zierler
Journal: Circulation Research (1972)

This study attempted to evaluate the relative roles of vessel distensibility and vessel recruitment in the changes in pulmonary blood volume induced by changes in pulmonary intravascular pressure. Pulmonary blood volume was determined by a double-injection indicator-dilution technique in eight anesthetized open-chest dogs with a right and left ventricular bypass which allowed independent control of pulmonary artery and left atrial pressures. In three dogs, measurements were also taken during reverse perfusion (from the left atrium to the pulmonary artery). During forward perfusion, when left atrial pressure was increased from 7 to 26 cm H 2 O, and, by reducing flow from 3.4 to 1.2 liters'/min, pulmonary artery pressure was maintained at 30 cm H 2 O so that recruitment could be considered constant, pulmonary blood volume did not change but remained at about 260 ml. Pulmonary blood volume also did not change during reverse perfusion when pulmonary artery pressure was increased from 8 to 27 cm H 2 O at a constant left atrial pressure (inflow pressure). By contrast, when pulmonary artery pressure was raised by increasing flow, so that vessel recruitment could occur, pulmonary blood volume increased 12 ml for each 1-cm H 2 O increase in pulmonary artery pressure at a constant left atrial pressure of 5 cm H 2 O, and pulmonary blood volume increased 7 ml for each 1-cm H 2 O increase in pulmonary artery pressure at a constant left atrial pressure of 33 cm H 2 O. Therefore, in the range of pressures that we explored, the role of large-vessel distensibility in the changes in pulmonary blood volume observed when intravascular pressures were raised was small.
Right ventricular contractile reserve is markedly impaired and correlates with exercise capacity in pulmonary arterial hypertension: A dobutamine stress echocardiography study
Authors: Edmund Lau, Phillip Munoz, Tripura Sharma, Preeti Choudhary, David Celermajer
Journal: European Respiratory Journal (2014)

Background:  Right ventricular (RV) function is the main determinant of prognosis and exercise capacity in pulmonary arterial hypertension (PAH). We hypothesized that assessment of RV contractile reserve using dobutamine stress echocardiography would provide information additional to resting measurements.   Methods:  We used a low-dose dobutamine protocol (peak dose 20 mcg/kg/min) to assess RV contractile reserve in 16 PAH patients and 18 age-matched controls. Contractile reserve was assessed by the change (Δ = peak stress minus resting value) in two echocardiographic indices of RV longitudinal systolic function: (1) Δ tricuspid annular plane systolic excursion (ΔTAPSE) and (2) Δ tricuspid annular systolic velocity (ΔS9). A subgroup of 13 PAH patients underwent cardiopulmonary exercise testing to determine peak oxygen consumption (VO 2 ) .    Results:  At rest, TAPSE and S9 were reduced in PAH group compared with controls (1.7±0.4 vs. 2.4±0.3 cm and 10.1±3.0 vs. 12.5±1.2 cm/s, respectively, both p l0.001). Contractile reserve was markedly attenuated in PAH compared to controls (ΔTAPSE: 0.1±0.4 vs. 0.6±0.3 cm; and ΔS9: 5.0±3.3 vs. 11.2±3.6 cm/s, both p l0.001). In the subgroup of PAH patients with preserved RV systolic function at rest, contractile reserve remained depressed compared to controls. Peak VO 2  was significantly correlated with ΔS9 (r=0.87, p=0.0003) and Δ stroke volume (r=0.59, p=0.03).   Conclusions:  RV contractile reserve can be assessed using DSE and may reveal subclinical RV dysfunction not apparent at rest. A correlation with exercise capacity suggests potential clinical value beyond resting measurements.
Small-bowel ulcerations at wireless capsule endoscopy: go the whole way
Authors: F Wartel, V Maunoury, P Bulois, S Papadopoulos, B Filoche, J F Colombel
Journal: Gut (2007)

A 22-year-old woman was referred to our hospital for abdominal pain, diarrhoea and weight loss. The patient had no history of surgery or illness. On physical examination, the abdomen was soft and no mass …
Selective inhibitors of nuclear export (SINE)– a novel class of anti-cancer agents
Authors: Kaushal Parikh, Shundong Cang, Arunabh Sekhri, Delong Liu
Journal: Journal of Hematology & Oncology (2014)

Dysregulation of the nucleo-cytoplasmic transport of proteins plays an important role in carcinogenesis. The nuclear export of proteins depends on the activity of transport proteins, exportins. Exportins belong to the karyopherin β superfamily. Exportin-1 (XPO1), also known as chromosomal region maintenance 1 (CRM1), mediates transport of around 220 proteins. In this review, we summarized the development of a new class of antitumor drugs, collectively known as selective inhibitors of nuclear export (SINE). KPT-330 (selinexor) as an oral agent is showing activities in early clinical trials in both solid tumors and hematological malignancies.
Progressive Multifocal Leukoencephalopathy in a Patient Treated with Natalizumab
Authors: Annette Langer-Gould, Scott W. Atlas, Ari J. Green, Andrew W. Bollen, Daniel Pelletier
Journal: New England Journal of Medicine (2005)

We describe the clinical course of a patient with multiple sclerosis in whom progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the central nervous system, developed during treatment with interferon beta-1a and a selective adhesion-molecule blocker, natalizumab. The first PML lesion apparent on magnetic resonance imaging was indistinguishable from a multiple sclerosis lesion. Despite treatment with corticosteroids, cidofovir, and intravenous immune globulin, PML progressed rapidly, rendering the patient quadriparetic, globally aphasic, and minimally responsive. Three months after natalizumab therapy was discontinued, changes consistent with an immune-reconstitution inflammatory syndrome developed. The patient was treated with systemic cytarabine, and two months later, his condition had improved.
Randomized, Double-Blind Study Comparing Saruplase With Streptokinase Therapy in Acute Myocardial Infarction: The COMPASS Equivalence Trial fn1fn1This study was supported by Grünenthal GmbH, the manufacturer of saruplase.
Authors: Ulrich Tebbe, Rolf Michels, Jennifer Adgey, Jean Boland, Avi Caspi, Bernard Charbonnier, Jürgen Windeler, Hannes Barth, Robert Groves, Gwyn R. Hopkins, William Fennell, Amadeo Betriu, Mikhail Ruda, Johannes Mlczoch
Journal: Journal of the American College of Cardiology (1998)
Risk stratification of HBV infection in Asia-Pacific region
Authors: Jia-Horng Kao
Journal: Clinical and Molecular Hepatology (2014)

Hepatitis B virus (HBV) infection is the major etiology of chronic liver disease worldwide and thus a global health problem, especially in Asia-Pacific region. The long-term outcomes of Asian HBV carriers vary widely; however, a significant proportion of them will finally develop end-stage liver disease. Over the past decade, several host and HBV factors predictive of clinical outcomes in Asian HBV carriers have been identified. The community-based REVEAL-HBV study illustrated the strong association between HBV-DNA level at study entry and risk of HCC over time, and male gender, older age, high serum alanine aminotransferase (ALT) level, positive HBeAg, higher HBV-DNA level, HBV genotype C infection and core promoter mutation are independently associated with a higher hepatocellular carcinoma (HCC) risk. Another hospital-based ERADICATE-B cohort further validated the HCC risk started to increase when HBV-DNA level was higher than 2,000 IU/mL. Of particular note, in patients with low viral load (HBV-DNA level <2,000 IU/mL), HBsAg level ≥1,000 IU/mL was a new independent risk factor for HCC. With the results from REVEAL-HBV study, a risk calculator for predicting HCC in adult non-cirrhotic patients has been developed and validated by independent international cohorts (REACH-B). With the combination of HBV-DNA, HBsAg, and ALT levels, ERADICATE-B study proposed an algorithm to predict disease progression and categorize risk levels of HCC as well as corresponding management in Asian HBV carriers. The introduction of transient elastography may further enhance the predictive power. In conclusion, HBsAg level can complement HBV-DNA level for the risk stratification of disease progression in Asian adult patients with chronic HBV infection. Keywords: Hepatitis B virus (HBV); Hepatocellular carcinoma; HBV-DNA; HBsAg; Risk stratification
Reduced Incidence and Severity of Antigen-induced Autoimmune Diseases in Mice Lacking Interferon Regulatory Factor-1
Authors: Yoshifumi Tada, Alexandra Ho, Toshifumi Matsuyama, Tak W. Mak
Journal: The Journal of Experimental Medicine (1997)

Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates interferon-induced genes and type I interferons. Recently, studies of IRF-1-deficient mice have revealed that IRF-1 regulates the induction of molecules that play important roles in inflammation, such as inducible nitric oxide synthase (iNOS) and interleukin-1β-converting enzyme (ICE). To study the role of IRF-1 in autoimmunity, we investigated type II collagen-induced arthritis (CIA), and experimental allergic encephalomyelitis (EAE), in mice lacking IRF-1. The incidence and severity of CIA were significantly decreased in IRF-1−/− mice compared with IRF-1+/− mice, as was the production of interferon (IFN)-γ in lymph node cells. Both IRF-1+/− and IRF-1−/− mice exhibited mild and transient disease after adoptive transfer of a type II collagen (CII)-specific T cell line together with sera from arthritic mice, but the IRF-1−/− mice were less severely affected than the IRF-1+/− mice. In addition, the incidence of EAE in IRF-1−/− mice was decreased as compared with IRF-1+/− mice. Reverse transcription polymerase chain reaction showed that IRF-1 mRNA was constitutively expressed in the spinal cords of IRF-1+/− mice, and was upregulated in mice with clinical EAE. Expression of iNOS was also detected in inflamed spinal cords. These results suggest that IRF-1 plays a key role in promoting inflammation and autoimmunity in CIA and EAE animal models.
Abstract A32: A specific antibody for Histone H3 Lys27Met mutation for the characterization of pediatric glioblastomas
Authors: Anita Lozsa, Robin T. Clark, Peter W. Lewis, Matthew S. Koletsky, Oren J. Becher, John Rosenfeld, Sturges Michael, David C. Allis, Trinette Chuang, Wayne Speckmann, Alejandra Solache
Journal: Cancer Research (2014)

Abstract Pediatric gliomas such as glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG) are aggressive brain tumors for which there is no effective therapy. The reason for the poor therapeutic outcome for children diagnosed with glioblastomas might be due to the therapeutic approach, which is not significantly different from the treatment of adult gliomas. Recent studies have shown that the gene expression profile of pediatric gliomas is distinct from histologically similar tumors in adults. These findings strongly suggest that the underlying mechanisms of tumor progression are different in these gliomas. Whole-genome sequencing of these pediatric tumors has revealed mutations in genes of H3F3A and HIST1H3B encoding histone H3.3 or H3.1, respectively. The mutations resulted in a substitution of lysine (K) to methionine (M) at position 27 of the protein (H3K27M). The lysine 27 residue of histone H3 is a posttranslational modification site, methylated by the polycomb repressive complex 2 (PRC2). A mutation like H3K27M might play a significant role in tumorigenesis and tumor progression since histones and their posttranslational modifications are key epigenetic regulators. In collaboration with the laboratory of David Allis, we raised antibodies against the K27M mutation of histone H3. Using this antibody, Lewis et al. corroborated the presence of H3 K27M protein in DIPG samples containing the mutant allele. Furthermore, they provided evidence that this mutation can alter the molecular processes in the nucleus through a gain-of-function mechanism in glioblastoma. Here we show that this Anti-Histone H3, K27M mutant antibody (Cat. No.: ABE419), together with other modified histone antibodies, are useful tools for the characterization and classification of different type of brain tumors and can be used in several applications including immunoblotting and chromatin immunoprecipitation (ChIP). Citation Format: Anita Lozsa, Robin T. Clark, Peter W. Lewis, Matthew S. Koletsky, Oren J. Becher, John Rosenfeld, Sturges Michael, David C. Allis, Trinette Chuang, Wayne Speckmann, Alejandra Solache. A specific antibody for Histone H3 Lys27Met mutation for the characterization of pediatric glioblastomas. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr A32.
Lymphomas complicating Sjogren's syndrome and hepatitis C virus infection may share a common pathogenesis: chronic stimulation of rheumatoid factor B cells
Authors: X Mariette
Journal: Annals of the Rheumatic Diseases (2001)

The occurrence of B cell non-Hodgkin's lymphoma is a complication of Sjögren's syndrome (SS) and, at least in some countries, of chronic hepatitis C virus (HCV) infection. Lymphomas occurring in both diseases share a number of characteristics: predominance of low grade, marginal zone histological type, frequency of mucosal localisation, possible transformation into a large B cell lymphoma, association with asymptomatic low level cryoglobulinaemia, absence of virus within lymphoma cells, but localisation of lymphomas in organs where the chronic viral infection is active in patients with HCV and where the autoimmune disease is active in patients with SS.It is proposed that in both diseases the first event of lymphomagenesis is the chronic stimulation at the site of the disease of polyclonal B cells secreting rheumatoid factor (RF). Then, that these RF B cells may become monoclonal and disseminate in other organs. The monoclonal secreted RF complexed with polyclonal IgG may cryoprecipitate. The following step would be a chromosomal abnormality (for example, trisomy 3 or bcl-2 translocation) which would confer to these cells a low grade B cell lymphoma comportment. A last event (for example, a mutation of p53) might transform this low grade B cell lymphoma into a high grade, large B cell lymphoma. The non-random utilisation of VH and VL by SS associated lymphoma B cells and the recent demonstration that these lymphoma B cells may display RF activity support the hypothesis that these lymphomas grow through an autoantigen driven process.The best preventive treatment of lymphoproliferations occurring in SS probably consists in decreasing the hyperactivation of autoreactive B cells when it is present, allowing the use of immunosuppressive drugs such as methotrexate or even tumour necrosis factor alpha antagonists, which in theory could favour other types of lymphoproliferation.
Regulation of phosphatidylinositol 3–kinase by polyisoprenyl phosphates in neutrophil-mediated tissue injury
Authors: Caroline Bonnans, Koichi Fukunaga, Raquel Keledjian, Nicos A. Petasis, Bruce D. Levy
Journal: The Journal of Experimental Medicine (2006)

Neutrophils play a central role in host defense, inflammation, and tissue injury. Recent findings indicate a novel role for polyisoprenyl phosphates (PIPPs) as natural down-regulatory signals in neutrophils. The relationship between PIPPs and neutrophil early activating signals, such as phosphoinositides, has not been previously determined. Here, we establish presqualene diphosphate (PSDP) as an endogenous PIPP regulator of phosphatidylinositol 3–kinase (PI3K). In human neutrophils, leukotriene B4 (LTB4) triggered rapid decreases in PSDP and reciprocal increases in PI3K activity. In addition, PSDP was identified by gas chromatography/mass spectrometry in p110γ–PI3K immunoprecipitates obtained 30 s after LTB4, indicating a physical interaction between PSDP and PI3K in activated neutrophils. Moreover, PSDP (0.4–800 pmol) directly inhibited recombinant human p110γ-PI3K activity. During an experimental model of lung injury and inflammation, a reciprocal relationship was also present in vivo for lung PSDP and PI3K activity. To investigate its therapeutic potential, we developed a new PSDP structural mimetic that blocked human neutrophil activation and mouse lung PI3K activity and inflammation. Together, our findings indicate that PSDP is an endogenous PI3K inhibitor, and suggest that in inflammatory diseases characterized by excessive neutrophil activation, PIPPs can serve as structural templates in a novel antineutrophil therapeutic strategy to limit tissue injury.
A calcium-induced signaling cascade leading to osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells
Authors: Ana M.C. Barradas, Hugo A.M. Fernandes, Nathalie Groen, Yoke Chin Chai, Jan Schrooten, Jeroen van de Peppel, Johannes P.T.M. van Leeuwen, Clemens A. van Blitterswijk, Jan de Boer
Journal: Biomaterials (2012)