tbuckley/cabot-search huggingface dataset:
Endothelial Arginase II
Authors: Sungwoo Ryoo, Gaurav Gupta, Alexandre Benjo, Hyun Kyo Lim, Andre Camara, Gautam Sikka, Hyun Kyung Lim, Jayson Sohi, Lakshmi Santhanam, Kevin Soucy, Eric Tuday, Ezra Baraban, Monica Ilies, Gary Gerstenblith, Daniel Nyhan, Artin Shoukas, David W. Christianson, Nicholas J. Alp, Hunter C. Champion, David Huso, Dan E. Berkowitz
Journal: Circulation Research (2008)

Oxidized low-density lipoproteins increase arginase activity and reciprocally decrease endothelial NO in human aortic endothelial cells. Here, we demonstrate that vascular endothelial arginase activity is increased in atherogenic-prone apolipoprotein E–null (ApoE −/− ) and wild-type mice fed a high cholesterol diet. In ApoE −/− mice, selective arginase II inhibition or deletion of the arginase II gene (Arg II −/− mice) prevents high-cholesterol diet–dependent decreases in vascular NO production, decreases endothelial reactive oxygen species production, restores endothelial function, and prevents oxidized low-density lipoprotein–dependent increases in vascular stiffness. Furthermore, arginase inhibition significantly decreases plaque burden. These data indicate that arginase II plays a critical role in the pathophysiology of cholesterol-mediated endothelial dysfunction and represents a novel target for therapy in atherosclerosis.
P14 * LOCALISED RADIATION THERAPY FOR PINEAL PARENCHYMA TUMOUR WITH INTERMEDIATE DIFFERENTIATION: A SINGLE INSTITUTE EXPERIENCE
Authors: P. Das, D. S. Conkey, J. A. Harney
Journal: Neuro-Oncology (2014)

INTRODUCTION: Pineal Parenchyma tumour with intermediate differentiation (PPTID) is a rare disorder, first classified by World Health Organisation in 2000.There are very few published data available and optimal management is yet to be determined. Management has varied from surgery alone to craniospinal radiotherapy with or without chemotherapy. We present our experience of PPTID treated with radiotherapy alone. METHOD: We conducted a retrospective review of patients who were diagnosed with PPTID and treated with radiation therapy at our institute from 2011 onwards. RESULTS: Between January 2011 to January 2014, 4 patients of PPTID were treated at our institute. Median age is 44 (range 24 to 61). All patients had preoperative MRI scan of brain and spine. Imaging did not identify any cerebrospinal fluid (CSF) dissemination. None of the patients underwent a gross total resection, due to the tumour location and technical difficulties. All patients were treated with external beam radiation therapy to primary lesion with a dose of 54 Gee in 30 fractions after surgery. 2 patients had good partial response (near complete response) and the remaining 2 have recently completed their treatment. Patients with partial response remain relapse free after 15 and 9 months. So far there is no evidence of cerebral white matter abnormalities on MRI scan or neurocognitive disorders. CONCLUSION: Localised radiotherapy for PPTID patients without CSF dissemination may be a valid treatment option, although more mature data is required to assess overall and disease free survival and adverse effect.
Standardized Low–Molecular-Weight Heparin Bridging Regimen in Outpatients on Oral Anticoagulants Undergoing Invasive Procedure or Surgery
Authors: V. Pengo, U. Cucchini, G. Denas, N. Erba, G. Guazzaloca, L. La Rosa, V. De Micheli, S. Testa, R. Frontoni, D. Prisco, G. Nante, S. Iliceto
Journal: Circulation (2009)

Bridging therapy with low-molecular-weight heparin is usually recommended in patients who must stop oral anticoagulants before surgical or invasive procedures. To date, there is no universally accepted bridging regimen tailored to the patient's thromboembolic risk. This prospective inception cohort management study was designed to assess the efficacy and safety of an individualized bridging protocol applied to outpatients.Oral anticoagulants were stopped 5 days before the procedure. Low-molecular-weight heparin was started 3 to 4 days before surgery and continued for 6 days after surgery at 70 anti-factor Xa U/kg twice daily in high-thromboembolic-risk patients and prophylactic once-daily doses in moderate- to low-risk patients. Oral anticoagulation was resumed the day after the procedure with a boost dose of 50% for 2 days and maintenance doses afterward. The patients were followed up for 30 days. Of the 1262 patients included in the study (only 15% had mechanical valves), 295 (23.4%) were high-thromboembolic-risk patients and 967 (76.6%) were moderate- to low-risk patients. In the intention-to-treat analysis, there were 5 thromboembolic events (0.4%; 95% confidence interval, 0.1 to 0.9), all in high-thromboembolic-risk patients. There were 15 major (1.2%; 95% confidence interval, 0.7 to 2.0) and 53 minor (4.2%; 95% confidence interval, 3.2 to 5.5) bleeding episodes. Major bleeding was associated with twice-daily low-molecular-weight heparin administration (high-risk patients) but not with the bleeding risk of the procedure.This management bridging protocol, tailored to patients' thromboembolic risk, appears to be feasible, effective, and safe for many patients, but safety in patients with mechanical prosthetic valves has not been conclusively established.
Isotopic and Enzymatic IgE Assays in Non‐Allergic Subjects
Authors: R. Stein, S. Evans, R. Milner, C. Rand, J. Dolovich
Journal: Allergy (1983)

In order to establish normal values in an adult population for serum IgE concentration, sera were obtained from 446 ambulatory Canadian Caucasian subjects with negative allergy histories. A standard isotopic procedure, the Phadebas paper radioimmunosorbent test (PRIST), was compared with the new enzymatic counterpart, the Phadezyme PRIST. By the isotopic method, serum IgE concentrations in women and men were comparable from one age group to another with no age‐related trend in the seven age groups examined (15–20, 21–30, 31–40, 41–50, 51–60, 61–70, above 70). The median and 95th percentile units (U)/ml respectively were 17.5 and 145 for 224 women and 25.5 and 275 for 222 men. Mean values ± 1 SD for women were 43 ± 102 and for men, 58 ± 137. Levels were significantly higher in men as a group. Sera with IgE concentrations above 100 U and a sampling of additional sera were tested for specific IgE antibodies to 13 common allergens by the radioallergosorbent test (RAST). After exclusion of RAST‐positive sera, the mean U/ml values ± 1 SD were 22 ± 29 for 204 women and 37 ± 54 for 196 men. Geometric mean U/ml values for these sera were 14.6 for women and 22.3 for men and the median and 95th percentile U/ml respectively for the women were 15 and 66, for the men, 24 and 135. These 95th percentile values are considered the upper limits of normal in this population. The RAST identification of antibodies to allergens to which sensitization was demonstrated provided a potential explanation for serum IgE concentrations above 100 U/ml in less than 30% of the sera in this population with negative allergy histories. The isotopic method and the counterpart enzymatic method (Phadezyme PRIST) were highly comparable; the correlation coefficient (r) for all the sera was + 0.93 ( P &lt; 0.001). IgE levels were significantly higher in male smokers than non‐smokers by both methods but these differences were not significant in women.
Genome re-annotation: a wiki solution?
Authors: Steven L Salzberg
Journal: Genome biology (2007)

The annotation of most genomes becomes outdated over time, owing in part to our ever-improving knowledge of genomes and in part to improvements in bioinformatics software. Unfortunately, annotation is rarely if ever updated and resources to support routine reannotation are scarce. Wiki software, which would allow many scientists to edit each genome's annotation, offers one possible solution.
Effects of cyclical etidronate combined with calcitriol versus cyclical etidronate alone on spine and femoral neck bone mineral density in postmenopausal osteoporotic women
Authors: T Masud, B Mulcahy, A V Thompson, S Donnelly, R W Keen, D V Doyle, T D Spector
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVES</h3> Few data are available on the effects of combination therapy for the treatment of osteoporosis. The aim of this study was to compare the effects of intermittent cyclical etidronate (E) therapy alone with a combination of cyclical etidronate and calcitriol (E+C) on spine and femoral neck bone mineral density (BMD) at one year. <h3>METHODS</h3> Postmenopausal women with at least one non-traumatic vertebral fracture or z score &lt; −1.5 were randomly allocated to an E group (each cycle = oral etidronate 400 mg daily for 14 days followed by calcium 500 mg daily for 76 days) or an E+C group (as for E plus oral calcitriol 0.5 μg daily). Lumbar spine and femoral neck BMDs were measured by dual energy <i>x</i> ray absorptiometry at baseline and at one year. The study design did not contain a placebo group. <h3>RESULTS</h3> The mean % increase in lumbar spine BMD was 5.2% (95%CI= 3.4 to 7.0) in the E+C group (n=24), which was significantly greater than the 2.7% (95%CI= 1.3 to 4.1) increase in the E group (n=23) (p&lt;0.05). The femoral neck BMD in the E+C group increased by 2.0% (95%CI= 0.8 to 3.2), which was significantly different from the E group where there was a −0.4% (95%CI=−2.4 to 1.6) change (p=0.046). <h3>CONCLUSIONS</h3> These data show that a combination of cyclical etidronate and calcitriol is better than cyclical etidronate alone in terms of changes in BMD at both spine and femoral neck sites. Although further data are needed on fracture efficacy, this study suggests that combination therapies have additive therapeutic potential that may exceed that expected from their theoretical mode of action.
Local Delivery of lnterleukin-12 Using T Cells Targeting VEGF Receptor-2 Eradicates Multiple Vascularized Tumors in Mice
Authors: Dhanalakshmi Chinnasamy, Zhiya Yu, Sid P. Kerkar, Ling Zhang, Richard A. Morgan, Nicholas P. Restifo, Steven A. Rosenberg
Journal: Clinical Cancer Research (2012)

We investigated the feasibility of delivering the proinflammatory cytokine interleukin (IL)-12 into tumor using T cells genetically engineered to express a chimeric antigen receptor (CAR) against the VEGF receptor-2 (VEGFR-2).Two different strains of mice bearing five different established subcutaneous tumors were treated with syngeneic T cells cotransduced with an anti-VEGFR-2 CAR and a constitutively expressed single-chain murine IL-12 or an inducible IL-12 gene after host lymphodepletion. Tumor regression, survival of mice, and persistence of the transferred cells were evaluated.Adoptive transfer of syngeneic T cells cotransduced with an anti-VEGFR-2 CAR and a constitutively expressing single-chain IL-12 resulted in the regression of five different established tumors of different histologies without the need for IL-2 administration. T cells transduced with either anti-VEGFR-2 CAR or single-chain IL-12 alone did not alter the tumor growth indicating that both of them had to be expressed in the same cell to mediate tumor regression. Anti-VEGFR-2 CAR and IL-12-cotransduced T cells infiltrated the tumors, expanded, and persisted for prolonged periods. The antitumor effect did not require the presence of host T and B cells but was dependent on host IL-12R-expressing cells. The anti-VEGFR-2 CAR changed the immunosuppressive tumor environment by altering/reducing both the systemic and the intratumoral CD11b(+)Gr1(+) myeloid suppressor cell subsets that expressed VEGFR-2.These results suggest that targeted delivery of IL-12 into the tumor environment with T cells redirected against VEGFR-2 is a promising approach for treating patients with a variety of solid tumor types.
The Biological Outcome of CD40 Signaling Is Dependent on the Duration of CD40 Ligand Expression
Authors: Byung O. Lee, Laura Haynes, Sheri M. Eaton, Susan L. Swain, Troy D. Randall
Journal: The Journal of Experimental Medicine (2002)

CD40 ligand (CD154) expression on activated T cells can be separated into an early TCR-dependent phase, which occurs between 0 and 24 h after activation, and a later extended phase, which occurs after 24 h and is reciprocally regulated by the cytokines IL-4 and IL-12. IL-4 represses, whereas IL-12 sustains CD154 expression. Consistent with this, Th1, but not Th2, cells express CD154 for extended periods. Differences in the duration of CD154 expression have important biological consequences because sustained, but not transient, expression of CD154 on activated T cells can prevent B cell terminal differentiation. Thus, the differential ability of Th cells to sustain CD154 expression is an important part of their helper function and should influence the activities of other CD40-expressing cell types.
Cryptococcosis: an unusual cause of endobronchial obstruction
Authors: P Mahida, R Morar, A Goolam Mahomed, E Song, JP Tissandie, C Feldman
Journal: European Respiratory Journal (1996)

We report the case of a 43 year old male patient, with normal immune function, who presented with right middle and lower lobe collapse. At bronchoscopy, a white lobulated lesion was seen, completely obstructing the origin of bronchus intermedius. Bronchial washings and biopsy of the lesion demonstrated cryptococcal organisms. The patient responded clinically and radiologically to amphotericin B and flucytosine; however, repeat bronchoscopy revealed only partial resolution of the endobronchial lesion.
Leptin neutralization interferes with pathogenic T cell autoreactivity in autoimmune encephalomyelitis
Authors: V. De Rosa
Journal: Journal of Clinical Investigation (2006)

Recent evidence has indicated that leptin, an adipocyte-secreted hormone belonging to the helical cytokine family, significantly influences immune and autoimmune responses. We investigate here the mechanisms by which in vivo abrogation of leptin effects protects SJL/J mice from proteolipid protein peptide PLP(139-151)-induced EAE, an animal model of MS. Blockade of leptin with anti-leptin Abs or with a soluble mouse leptin receptor chimera (ObR:Fc), either before or after onset of EAE, improved clinical score, slowed disease progression, reduced disease relapses, inhibited PLP(139-151)-specific T cell proliferation, and switched cytokine secretion toward a Th2/regulatory profile. This was also confirmed by induction of forkhead box p3 (Foxp3) expression in CD4 T cells in leptin-neutralized mice. Importantly, anti-leptin treatment induced a failure to downmodulate the cyclin-dependent kinase inhibitor p27 (p27) in autoreactive CD4 T cells. These effects were associated with increased tyrosine phosphorylation of both ERK1/2 and STAT6. Taken together, our data provide what we believe is a new molecular basis for leptin antagonism in EAE and envision novel strategies of leptin-based molecular targeting in the disease.
Asbestos induced pericardial effusion and constrictive pericarditis.
Authors: D Davies, M I Andrews, J S Jones
Journal: Thorax (1991)

The number of disorders attributable to asbestos exposure has increased gradually over the years. The latest to be recorded is pericardial effusion and constrictive pericarditis, and three cases are reported here. A man with bilateral pleural thickening and plaques developed acute pericarditis and an effusion and was treated by pericardiectomy. Two men died from constrictive pericarditis associated with bilateral pleural effusions and diffusion pleural thickening. The pericardium showed nonspecific fibrous thickening. All had been occupationally exposed to asbestos. In the fatal cases the lungs contained amphibole fibres, in keeping with a modest degree of occupational exposure. Asbestos produces progressive fibrosis of the pericardium that is similar to diffuse pleural thickening and may be fatal. Both conditions may develop after relatively short or light exposure.
Regulatory conservation of protein coding and microRNA genes in vertebrates: lessons from the opossum genome
Authors: Shaun Mahony, David L Corcoran, Eleanor Feingold, Panayiotis V Benos
Journal: Genome biology (2007)

Abstract Background Being the first noneutherian mammal sequenced, Monodelphis domestica (opossum) offers great potential for enhancing our understanding of the evolutionary processes that take place in mammals. This study focuses on the evolutionary relationships between conservation of noncoding sequences, cis -regulatory elements, and biologic functions of regulated genes in opossum and eight vertebrate species. Results Analysis of 145 intergenic microRNA and all protein coding genes revealed that the upstream sequences of the former are up to twice as conserved as the latter among mammals, except in the first 500 base pairs, where the conservation is similar. Comparison of promoter conservation in 513 protein coding genes and related transcription factor binding sites (TFBSs) showed that 41% of the known human TFBSs are located in the 6.7% of promoter regions that are conserved between human and opossum. Some core biologic processes exhibited significantly fewer conserved TFBSs in human-opossum comparisons, suggesting greater functional divergence. A new measure of efficiency in multigenome phylogenetic footprinting (base regulatory potential rate [BRPR]) shows that including human-opossum conservation increases specificity in finding human TFBSs. Conclusion Opossum facilitates better estimation of promoter conservation and TFBS turnover among mammals. The fact that substantial TFBS numbers are located in a small proportion of the human-opossum conserved sequences emphasizes the importance of marsupial genomes for phylogenetic footprinting-based motif discovery strategies. The BRPR measure is expected to help select genome combinations for optimal performance of these algorithms. Finally, although the etiology of the microRNA upstream increased conservation remains unknown, it is expected to have strong implications for our understanding of regulation of their expression.
T Cell Receptor Engagement Leads to Phosphorylation of Clathrin Heavy Chain during Receptor Internalization
Authors: Victoria L. Crotzer, Allan S. Mabardy, Arthur Weiss, Frances M. Brodsky
Journal: The Journal of Experimental Medicine (2004)

T cell receptor (TCR) internalization by clathrin-coated vesicles after encounter with antigen has been implicated in the regulation of T cell responses. We demonstrate that TCR internalization after receptor engagement and TCR signaling involves inducible phosphorylation of clathrin heavy chain (CHC) in both CD4+ and CD8+ human T cells. Studies with mutant Jurkat T cells implicate the Src family kinase Lck as the responsible enzyme and its activity in this process is influenced by the functional integrity of the downstream signaling molecule ZAP-70. CHC phosphorylation positively correlates with ligand-induced TCR internalization in both CD4+ and CD8+ T cells, and CHC phosphorylation as a result of basal Lck activity is also implicated in constitutive TCR endocytosis by CD4+ T cells. Remarkably, irreversible CHC phosphorylation in the presence of pervanadate reduced both constitutive and ligand-induced TCR internalization in CD4+ T cells, and immunofluorescence studies revealed that this inhibition affected the early stages of TCR endocytosis from the plasma membrane. Thus, we propose that CHC phosphorylation and dephosphorylation are involved in TCR internalization and that this is a regulatory mechanism linking TCR signaling to endocytosis.
The Risk of a Persistent Glucose Metabolism Impairment After Gestational Diabetes Mellitus Is Increased in Patients With Polycystic Ovary Syndrome
Authors: Stefano Palomba, Angela Falbo, Tiziana Russo, Laura Rivoli, Marcello Orio, Andrea Gregorio Cosco, Raffaella Vero, Carmelo Capula, Achille Tolino, Fulvio Zullo, Annamaria Colao, Francesco Orio
Journal: Diabetes Care (2012)

To test the hypothesis that the risk of persistent glucose impairment after gestational diabetes mellitus (GDM) is increased in patients with polycystic ovary syndrome (PCOS).
The Leukemias: A Half-Century of Discovery
Authors: Emil J. Freireich, Peter H. Wiernik, David P. Steensma
Journal: Journal of Clinical Oncology (2014)

Studies of the leukemias in the laboratory and in the clinic have generated many new concepts and therapies that will undoubtedly continue to be rapidly applied to the other forms of systemic cancer, particularly the concept of narrowly targeted personalized therapy that has proven so effective in CML. It seems likely that other subtypes of leukemia will eventually approach the success achieved with APL, CML, and pediatric ALL.
Electrotonic Modulation of Cardiac Impulse Conduction by Myofibroblasts
Authors: Michele Miragoli, Giedrius Gaudesius, Stephan Rohr
Journal: Circulation Research (2006)

Structural remodeling of the myocardium associated with mechanical overload or cardiac infarction is accompanied by the appearance of myofibroblasts. These fibroblast-like cells express α-smooth muscle actin (αSMA) and have been shown to express connexins in tissues other than heart. The present study examined whether myofibroblasts of cardiac origin establish heterocellular gap junctional coupling with cardiomyocytes and whether ensuing electrotonic interactions affect impulse propagation. For this purpose, impulse conduction characteristics (conduction velocity [θ] and maximal upstroke velocity [dV/dt max ]) were assessed optically in cultured strands of cardiomyocytes, which were coated with fibroblasts of cardiac origin. Immunocytochemistry showed that cultured fibroblasts underwent a phenotype switch to αSMA-positive myofibroblasts that expressed connexin 43 and 45 both among themselves and at contact sites with cardiomyocytes. Myofibroblasts affected θ and dV/dt max in a cell density-dependent manner; a gradual increase of myofibroblast-to-cardiomyocyte ratios up to 7:100 caused an increase of both θ and dV/dt max , which was followed by a progressive decline at higher ratios. On full coverage of the strands with myofibroblasts (ratio &gt;20:100), θ fell &lt;200 mm/s. This biphasic dependence of θ and dV/dt max on myofibroblast density is reminiscent of “supernormal conduction” and is explained by a myofibroblast density-dependent gradual depolarization of the cardiomyocyte strands from −78 mV to −50 mV as measured using microelectrode recordings. These findings suggest that myofibroblasts, apart from their role in structural remodeling, might contribute to arrhythmogenesis by direct electrotonic modulation of conduction and that prevention of their appearance might represent an antiarrhythmic therapeutic target.