tbuckley/cabot-search huggingface dataset:
Diacylglycerol kinase ζ regulates microbial recognition and host resistance to <i>Toxoplasma gondii </i>
Authors: Cheng-Hu Liu, Fabiana S. Machado, Rishu Guo, Kim E. Nichols, A. Wesley Burks, Julio C. Aliberti, Xiao-Ping Zhong
Journal: The Journal of Experimental Medicine (2007)

Mammalian Toll-like receptors (TLRs) recognize microbial pathogen-associated molecular patterns and are critical for innate immunity against microbial infection. Diacylglycerol (DAG) kinases (DGKs) regulate the intracellular levels of two important second messengers involved in signaling from many surface receptors by converting DAG to phosphatidic acid (PA). We demonstrate that the ζ isoform of the DGK family (DGKζ) is expressed in macrophages (Mφ) and dendritic cells. DGKζ deficiency results in impaired interleukin (IL) 12 and tumor necrosis factor α production following TLR stimulation in vitro and in vivo, increased resistance to endotoxin shock, and enhanced susceptibility to Toxoplasma gondii infection. We further show that DGKζ negatively controls the phosphatidylinositol 3–kinase (PI3K)–Akt pathway and that inhibition of PI3K activity or treatment with PA can restore lipopolysaccharide-induced IL-12 production by DGKζ-deficient Mφ. Collectively, our data provide the first genetic evidence that an enzyme involved in DAG/PA metabolism plays an important role in innate immunity and indicate that DGKζ promotes TLR responses via a pathway involving inhibition of PI3K.
Bronchodilator Response and Airway Nitric Oxide Flux Correlate in a Pediatric Asthma Population
Authors: J.L. Puckett, S.P. Galant, R.W.E. Taylor, L.C. Cirson, J.L. Warren, O.L. Guijon, A.A. Aledia, S.C. George
Journal: Journal of Allergy and Clinical Immunology (2009)
Reduction of fatigue in Sjogren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study
Authors: S Dass, S J Bowman, E M Vital, K Ikeda, C T Pease, J Hamburger, A Richards, S Rauz, P Emery
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS. <h3>Methods:</h3> A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) &gt;50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with &gt;20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy. <h3>Results:</h3> There was significant improvement from baseline in fatigue VAS in the rituximab group (p&lt;0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group. <h3>Conclusions:</h3> This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.
Residual Disease Monitoring in Childhood Acute Myeloid Leukemia by Multiparameter Flow Cytometry: The MRD-AML-BFM Study Group
Authors: Claudia Langebrake, Ursula Creutzig, Michael Dworzak, Ondrej Hrusak, Ester Mejstrikova, Frank Griesinger, Martin Zimmermann, Dirk Reinhardt
Journal: Journal of Clinical Oncology (2006)

Monitoring of residual disease (RD) by flow cytometry in childhood acute myeloid leukemia (AML) may predict outcome. However, the optimal time points for investigation, the best antibody combinations, and most importantly, the clinical impact of RD analysis remain unclear.Five hundred forty-two specimens of 150 children enrolled in the AML-Berlin-Frankfurt-Muenster (BFM) 98 study were analyzed by four-color immunophenotyping at up to four predefined time points during treatment. For each of the 12 leukemia-associated immunophenotypes and time points, a threshold level based on a previous retrospective analysis of another cohort of children with AML and on control bone marrows was determined.Regarding all four time points, there is a statistically significant difference in the 3-year event-free survival (EFS) in those children presenting with immunologically detectable blasts at 3 or more time points. The levels at bone marrow puncture (BMP) 1 and BMP2 turned out to have the most significant predictive value for 3-year-EFS: 71% +/- 6% versus 48% +/- 9%, P(Log-Rank) = .029 and 70% +/- 6% versus 50% +/- 7%, P(Log-Rank) = .033), resulting in a more than two-fold risk of relapse. In a multivariate analysis, using a combined risk classification based on morphologically determined blasts at BMP1 and BMP2, French-American-British classification, and cytogenetics, the influence of immunologically determined RD was no longer statistically significant.RD monitoring before second induction has the same predictive value as examining levels at four different time points during intensive chemotherapy. Compared with commonly defined risk factors in the AML-BFM studies, flow cytometry does not provide additional information for outcome prediction, but may be helpful to evaluate the remission status at day 28.
The staphylococcal scalded skin syndrome in two elderly immunocompromised patients.
Authors: R O'Keefe, J H Dagg, R M MacKie
Journal: BMJ (1987)

Ce syndrome est generalement observe chez le nouveau-ne ou chez le jeune enfant. On ne connait que 18 cas chez l'adulte; presentation de 2 nouvelles observations chez des femmes de 67 et 81 ans, traitees par immunodepresseurs et hospitalisees dans le meme service. Les staphylocoques responsables sont du groupe II
Comparison of Allogeneic vs Autologous Bone Marrow–Derived Mesenchymal Stem Cells Delivered by Transendocardial Injection in Patients With Ischemic Cardiomyopathy
Authors: Joshua M. Hare, Joel E. Fishman, Gary Gerstenblith, Darcy L. DiFede Velazquez, Juan P. Zambrano, Viky Y. Suncion, Melissa Tracy, Eduard Ghersin, Peter V. Johnston, Jeffrey A. Brinker, Elayne Breton, Janice Davis-Sproul, John Byrnes, Richard George, Albert Lardo, Ivonne H. Schulman, Adam M. Mendizabal, Maureen H. Lowery, Didier Rouy, Peter Altman, Cheryl Wong Po Foo, Phillip Ruiz, Alexandra Amador, Jose Da Silva, Ian K. McNiece, Alan W. Heldman
Journal: JAMA (2012)

Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared.To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM.A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up.Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites.Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs). Efficacy assessments included 6-minute walk test, exercise peak VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index.Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%. The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46). At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10). Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO2 max. Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P < .001) and sphericity index but did not increase EF. Allogeneic MSCs reduced LV end-diastolic volumes. Low-dose concentration MSCs (20 million cells) produced greatest reductions in LV volumes and increased EF. Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions.In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions. In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling.clinicaltrials.gov Identifier: NCT01087996.
Aberrant Splicing of<i>Hugl-1</i>Is Associated with Hepatocellular Carcinoma Progression
Authors: Xuefeng Lu, Xiujing Feng, Xiaobo Man, Guang Yang, Liang Tang, Dan Du, Fan Zhang, Haixin Yuan, Qin Huang, Zhe Zhang, Yinkun Liu, Dennis Strand, Zhengjun Chen
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Lethal giant larvae functions as a cell polarity regulator and a tumor suppressor in Drosophila. Its evolutionary conservation implies a tumor suppressor role for its human homologue, Hugl-1. The aims of this study were to characterize Hugl-1 and to determine the clinical significance of Hugl-1 alterations in hepatocellular carcinoma (HCC). Experimental Design: Sequence alterations of Hugl-1 from 80 HCC specimens and 5 HCC cell lines were characterized by reverse transcription-PCR and sequence analysis. Western blot was used for determining Hugl-1 expression. The biological activities of Hugl-1 and its aberrant variants were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound healing assay, Boyden chamber assay, and tumorigenicity assay. Results: In 32.5% (26 of 80) of the specimens and 20.0% (one of five) of HCC cell lines, 23 unique aberrant Hugl-1 transcripts were identified, most of which resulted from skipping part of and/or entire exon or insertion of intron sequences. The majority of these aberrant Hugl-1 transcripts encoded truncated proteins lacking one or more conserved WD-40 repeat motifs. Two truncated Hugl-1 proteins were found exclusively in HCC tissues. Aberrant Hugl-1 transcripts (78.3%, 20 of 23) had a short “direct repeat” sequence flanking their deleted regions. The abnormal Hugl-1 was significantly correlated with poor differentiation and large tumor size of HCC. Overexpression of two representative HCC-derived aberrant Hugl-1 variants promoted HCC cell migration, invasion, and tumorigenicity in nude mice. Conclusions: We provide the first evidence that Hugl-1 mRNA is frequently mutated by aberrant splicing exclusively in HCC, which may be involved in HCC progression.
Endothelin A Receptor Blockade Causes Adverse Left Ventricular Remodeling but Improves Pulmonary Artery Pressure After Infarction in the Rat
Authors: Quang Trinh Nguyen, Peter Cernacek, Angelino Calderoni, Duncan J. Stewart, Pierre Picard, Pierre Sirois, Michel White, Jean L. Rouleau
Journal: Circulation (1998)

Background —Endothelin A (ET A ) receptor antagonists have been shown to improve ventricular remodeling and survival in rats when started 10 days after infarction. Whether starting them earlier would have a more or less beneficial effect is uncertain. Methods and Results —Rats surviving an acute myocardial infarction (MI) for 24 hours (n=403) were assigned to saline or the ET A receptor antagonist LU 127043 or its active enantiomer LU 135252 for 4 weeks. Chronic LU treatment had no effect on survival, with 46% of LU rats and 47% of saline-treated rats with large MI surviving to the end of the study. LU treatment led to scar thinning, further left ventricular (LV) dilatation, an increase in LV end-diastolic pressure, and an increase in wet lung weight ( P &lt;0.05). Despite this detrimental effect on LV function, LU led to a significant decrease in RV systolic (50±2 to 44±2 mm Hg, P &lt;0.05 vs saline) and right atrial pressures. LU treatment also prevented the increase in pulmonary ET-1 found in saline-treated rats with large MI but did not modify the increase in cardiac ET-1 in hearts with large MI. Conclusions —The early use of the ET A receptor antagonists LU 127043 or its active enantiomer LU 135252 after infarction in the rat leads to impaired scar healing and LV dilatation and dysfunction. This is accompanied by a decrease in RV systolic and right atrial pressures and a decrease in pulmonary but not cardiac ET-1 levels. It would thus appear that the early use of ET A receptor antagonists after infarction may be detrimental.
Varicosities of Veins
Authors: L. Rogers
Journal: BMJ (1939)

This subject naturally falls into three parts: (1) vari- cosities of veins, (2) choice of treatment, and (3) end- results, and it would appear desirable to consider it under these three headings. Varicosities of VeinsI propose to confine my remarks to varices occurring elsewhere than in the anal canal, and, in order not to provoke too wide a discussion, to consider chiefly varicose veins in the lower limb ; but it is necessary to remember that they may be met with in the pampiniform plexus, in the lower oesophageal region, occasionally in the walls of the chest or abdomen, and in the scalp, and also that they are not very uncommon in both the cranial and spinal parts of the pia mater.The fact that varicosity may affect the veins of the pia mater indicates a developmental.origin, and the view, therefore, that varicose veins in the legs are the result of the upright posture anid occupational factors such 4s prolonged standing would appear to be incomplete unless the influence of a con- genital factor is assumed to be present also.It is probable
A Unifying Microenvironment Model in Follicular Lymphoma: Outcome Is Predicted by Programmed Death-1–Positive, Regulatory, Cytotoxic, and Helper T Cells and Macrophages
Authors: Björn Engelbrekt Wahlin, Mohit Aggarwal, Santiago Montes-Moreno, Luis Francisco Gonzalez, Giovanna Roncador, Lidia Sanchez-Verde, Birger Christensson, Birgitta Sander, Eva Kimby
Journal: Clinical Cancer Research (2010)

The microenvironment influences outcome in follicular lymphoma. Our hypothesis was that several immune cell subsets are important for disease outcome and their individual prognostic importance should be demonstrable in the same analysis and in competition with clinical factors.Seventy follicular lymphoma patients with extreme clinical outcome ("poor" and "good" cases) were selected in a population-based cohort of 197. None of the 37 good-outcome patients died from lymphoma, whereas all the 33 poor-outcome patients succumbed in <or=5 years. Furthermore, the good-outcome patients were followed for a long time and needed no or little treatment. A tissue microarray was constructed from diagnostic, pretreatment biopsies. Cellular subsets were quantified after immunostaining, using computerized image analysis, separating cells inside and outside the follicles (follicular and interfollicular compartments). Flow cytometry data from the same samples were also used.Independently of the Follicular Lymphoma International Prognostic Index, CD4(+) cells were associated with poor outcome and programmed death-1-positive and CD8(+) cells were associated with good outcome. The prognostic values of CD4(+) and programmed death-1-positive cells were accentuated when they were follicular and that of CD8(+) cells were accentuated when they were interfollicular. Follicular FOXP3(+) cells were associated with good outcome and interfollicular CD68(+) cells were associated with poor outcome. Additionally, high CD4/CD8 and CD4 follicular/interfollicular ratios correlated with poor outcome.There are many important immune cell subsets in the microenvironment of follicular lymphoma. Each of these is independently associated with outcome. This is the first study showing the effect of the balance of the entire microenvironment, not only of individual subsets.
Posterior cruciate ligament injuries in sports: treatment options
Authors: George Tsikouris
Journal: British Journal of Sports Medicine (2011)

Lecture 4 Diagnosis and management of posterior and cruciate ligament tears has advanced over the past two decades due to important understanding of the natural history of injury and basic science principles. Despite the current advances, our understanding of posterior cruciate ligament (PCL) injury and treatment continues to lag behind that of the anterior cruciate ligament (ACL). In addition, there is still controversy regarding indications for surgical intervention, use of one versus two reconstructive graft bundles, location of the femoral tunnels and the ideal degree of graft tensioning. The classic mechanism of injury to the PCL in sports due to a fall on a flexed knee with the foot in plantar flexion. A PCL injury can be partial or complete and it can be isolated or involve multiple ligaments. The grading system is normal: A, B and C. Grade A is defined as partial tear and grade B as a complete PCL tear. Grade C PCL injuries are frequently associated with additional injury to the posterolateral corner or the medial aspect of the knee. In general, acute isolated grade A and B PCL injuries can be treated non-operatively. In grade C injuries with associated ligament pathology, we recommend repairing or reconstructing all ligaments.
Normal values for maximal inspiratory and expiratory pressures of adolescents
Authors: Karla Mendonça, Diana Freitas, Ivanözia Silva, Raquel Mendes, Raössa Borja, Thalita Macêdo, Verônica Parreira, Ingrid Guerra Azevedo, Tania Campos
Journal: European Respiratory Journal (2013)

Introduction: The literature offers few studies with normal values for maximal respiratory pressures (MRP) of adolescents. Objectives: To provide normal values and lower limits of normal (LLN) for maximal inspiratory and expiratory pressures (MIP and MEP, respectively) of healthy adolescents. Methods: 182 adolescents with a mean age of 15±2 (age range from 12 to 18 years old) were assessed: 98 boys (BMI: 20±3.15 Kg/m2) and 84 girls (BMI: 19±4 Kg/m2). Spirometry was performed prior to the assessment of respiratory muscle strength. MIP and MEP were measured with a digital manometer with the adolescent in the seated position wearing a nose clip. Participants randomly selected the first MRP to be assessed. MIP was performed from residual volume and MEP from total lung capacity. A maximum of nine maneuvers were performed for each MRP. Data were expressed as mean and standard deviation. The LLN was calculated by subtracting a value two times greater than the standard deviation of measurements from mean MRP. Results: The normal values and the LLN for MIP and MEP are shown in table 1.

View this table:

Normal values and lower limits of normal for maximal respiratory pressures according to sex





Conclusion: The reference values and the LLN provided by this study for MRP may serve as an important parameter to the evaluation of respiratory muscle strength of adolescents.
Enhancement of platelet function by superoxide anion.
Authors: R I Handin, R Karabin, G J Boxer
Journal: Journal of Clinical Investigation (1977)

During the aerobic conversion of xanthine to uric acid by xanthine oxidase, superoxide anion and hydrogen peroxide are produced along with the hydroxyl radical. Our studies demonstrate that washed human platelets incubated with xanthine and xanthine oxidase aggregated and released [14C]serotonin. Aggregation and release were dependent on the duration of exposure to xanthine oxidase as well as the concentration of enzyme. Both reactions were inhibited by the superoxide scavenger enzyme superoxide dismutase but not by catalase, or the free radical scavenger mannitol, suggesting that they were induced by superoxide anion. Superoxide-dependent release was inhibited by prior incubation of platelets with 1 mM EDTA, 1 micronM prostaglandin E1, or 1 mM dibutyryl cyclic AMP, but was unaffected by 1 mM acetylsalicylic acid or 1 micronM indomethacin. After prolonged incubation with xanthine and xanthine oxidase there was also efflux of up to 15% of intraplatelet 51Cr, a cytosol marker. This leakage was prevented by the addition of catalase to the media but not by superoxide dismutase. Incubation with xanthine and xanthine oxidase did not produce malonyldialdehyde, the three-carbon fatty acid fragment produced during prostaglandin endoperoxide synthesis and lipid peroxidation. Prior exposure of platelets to low fluxes of superoxide anion lowered the threshold for release by subsequent addition of thrombin, suggesting a synergistic effect. We conclude that superoxide-dependent aggregation and release may be a physiologically important method to modulate hemostatic reactions particularly in areas of inflammation or vessel injury which could have high local concentrations of superoxide anion.
Endoscopic clipping versus injection and thermo-coagulation in the treatment of non-variceal upper gastrointestinal bleeding: a meta-analysis
Authors: J. J Y Sung, K. K F Tsoi, L. H Lai, J. C Y Wu, J. Y W Lau
Journal: Gut (2007)

Hemoclips, injection therapy and thermocoagulation (heater probe or electrocoagulation) are the most commonly used types of endoscopic hemostasis for the control of non-variceal gastrointestinal bleeding.To compare the efficacy of hemoclips versus injection or thermocoagulation in endoscopic hemostasis by pooling data from the literature.Publications in the English literature (MEDLINE, EMBASE and Cochrane Library) as well as abstracts in major international conferences were searched using the keywords "hemoclips" and "bleeding", and 15 trials fulfilling the search criteria were found. Outcome measures included: initial hemostasis (after endoscopic intervention); recurrent bleeding; definitive hemostasis (no recurrent bleeding until the end of follow-up); the requirement for surgical intervention; and all-cause mortality. The heterogeneity of trials was examined and the effects were pooled by meta-analysis.Of 1156 patients recruited in the 15 studies, 390 were randomly assigned to receive clips alone, 242 received clips combined with injection, 359 received injection alone, and 165 received thermocoagulation with or without injection. Definitive hemostasis was higher with hemoclips (86.5%) than injection (75.4%; RR 1.14, 95% CI 1.00-1.30), or endoscopic clips with injection (88.5%) compared with injections alone (78.1%; RR 1.13, 95% CI 1.03-1.23), leading to a reduced requirement for surgery but no difference in mortality. Compared with thermocoagulation, there was no improvement in definitive hemostasis with clips (81.5% versus 81.2%; RR 1.00, 95% CI 0.77-1.31). These estimates were robust in sensitivity analyses. There was also no difference between clips and thermocoagulation in rebleeding, the need for surgery and mortality. The reported locations of failed hemoclip applications included posterior wall of duodenal bulb, posterior wall of gastric body and lesser curve of the stomach.Successful application of hemoclips is superior to injection alone but comparable to thermocoagulation in producing definitive hemostasis. There was no difference in all-cause mortality irrespective of the modalities of endoscopic treatment.