tbuckley/cabot-search huggingface dataset:
Monocytes can be induced by lipopolysaccharide-triggered T lymphocytes to express functional factor VII/VIIa protease activity.
Authors: B P Tsao, D S Fair, L K Curtiss, T S Edgington
Journal: The Journal of Experimental Medicine (1984)

In the present study we demonstrate that human monocytes can be induced by the model stimulus, lipopolysaccharide (LPS), to produce and assemble on their surface functional Factor VII/VIIa. This protease was not induced in relatively purified monocytes alone following exposure to LPS; but was induced in the presence of Leu-3a positive helper/inducer T cells. The Factor VII/VIIa protease activity represented 35-40% of the potential initiating activity for the extrinsic coagulation pathway and was demonstrated using functional coagulation assays, as well as in amidolytic assays for the activation of Factor X. This activity of cell-bound Factor VII/VIIa appeared to involve a tight adduct of calcium. The identity of the Factor X-activating protease as Factor VII/VIIa was confirmed by the capacity of antibody specific for Factor VII/VIIa to neutralize the cell-bound protease. Further propagation of the extrinsic pathway following generation of Factor Xa required addition of exogenous Factor Va. These results expand the repertoire of proteases that have been identified with appropriately triggered cells of the monocyte/macrophage series, and suggest that initiation and propagation of the extrinsic coagulation protease network on induced monocytes involves not only expression of the initiating cofactor molecule, tissue factor, but also production of Factor VII and its organization into the molecular assembly. Thus, in the absence of exogenous Factor VII/VIIa a directly proteolytic effector cell can be generated. Further molecular assembly of the extrinsic pathway on the monocyte surface sequentially expands the proteolytic capacity of this response. The synthesis and assembly of the extrinsic activation complex by the monocyte and its derived progeny, the macrophage, provides a mechanism by which coagulation is initiated under T cell instruction at sites of immunologic responses.
Evaluation of children with craniopharyngioma using carbon-11 methionine PET prior to proton therapy
Authors: Benjamin S. Laser, Thomas E. Merchant, Daniel J. Indelicato, Chia-Ho Hua, Barry L. Shulkin, Scott E. Snyder
Journal: Neuro-Oncology (2013)

Fluorine-18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) is limited in its evaluation of brain tumors due to the high basal activity of the cerebral cortex and white matter. Carbon-11 methionine (11C MET) has little uptake under normal conditions. We prospectively investigated the uptake of 18F FDG and 11C MET PET in patients with craniopharyngioma prior to proton therapy. Ten patients newly diagnosed with craniopharyngioma underwent PET imaging using 18F FDG and 11C MET. PET and MRI studies were registered to help identify tumor volume. Measurements of maximum standardized uptake value (SUVmax) were taken of the tumor and compared with noninvolved left frontal background white matter using a paired t-test. Uptake was graded using a 4-point scale. Median patient age was 9 years (range 5–19). Seven patients were diagnosed by pathology, 1 by cyst fluid aspiration, and 2 by neuroimaging. Median FDG SUVmax for tumor and background were 2.65 and 3.2, respectively. Median MET SUVmax for tumor and background were 2.2 and 1, respectively. There was a significant difference between MET tumor SUVmax and MET background SUVmax (P = .0001). The difference between FDG tumor SUVmax and FDG background SUVmax was not significant (P = .3672). 11C MET PET uptake is significantly greater within the tumor compared with noninvolved background white matter, making it more useful than FDG PET in identifying active tumor in patients with craniopharyngioma. Future work will focus on using 11C MET PET to discriminate between active and inactive tumor after irradiation.
Infection of the finger-nail by Pyrenochaeta unguis-hominis
Authors: MARY P. ENGLISH
Journal: British Journal of Dermatology (1980)

Infection of the finger-nail of an elderly woman by Pyrenochaeta unguis-hominis is reported. The small lesion was extending slowly into the healthy nail plate. The fungus has been isolated from diseased toe-nails on two previous occasions but its extra-human habitat is unknown.
Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury
Authors: Kiyoshi Mori, H. Thomas Lee, Dana Rapoport, Ian R. Drexler, Kirk Foster, Jun Yang, Kai M. Schmidt-Ott, Xia Chen, Jau Yi Li, Stacey Weiss, Jaya Mishra, Faisal H. Cheema, Glenn Markowitz, Takayoshi Suganami, Kazutomo Sawai, Masashi Mukoyama, Cheryl Kunis, Vivette D’Agati, Prasad Devarajan, Jonathan Barasch
Journal: Journal of Clinical Investigation (2005)

Neutrophil gelatinase–associated lipocalin (Ngal), also known as siderocalin, forms a complex with iron-binding siderophores (Ngal:siderophore:Fe). This complex converts renal progenitors into epithelial tubules. In this study, we tested the hypothesis that Ngal:siderophore:Fe protects adult kidney epithelial cells or accelerates their recovery from damage. Using a mouse model of severe renal failure, ischemia-reperfusion injury, we show that a single dose of Ngal (10 μg), introduced during the initial phase of the disease, dramatically protects the kidney and mitigates azotemia. Ngal activity depends on delivery of the protein and its siderophore to the proximal tubule. Iron must also be delivered, since blockade of the siderophore with gallium inhibits the rescue from ischemia. The Ngal:siderophore:Fe complex upregulates heme oxygenase-1, a protective enzyme, preserves proximal tubule N-cadherin, and inhibits cell death. Because mouse urine contains an Ngal-dependent siderophore-like activity, endogenous Ngal might also play a protective role. Indeed, Ngal is highly accumulated in the human kidney cortical tubules and in the blood and urine after nephrotoxic and ischemic injury. We reveal what we believe to be a novel pathway of iron traffic that is activated in human and mouse renal diseases, and it provides a unique method for their treatment.
The role of codon selection in regulation of translation efficiency deduced from synthetic libraries
Authors: Sivan Navon, Yitzhak Pilpel
Journal: Genome biology (2011)

Abstract Background Translation efficiency is affected by a diversity of parameters, including secondary structure of the transcript and its codon usage. Here we examine the effects of codon usage on translation efficiency by re-analysis of previously constructed synthetic expression libraries in Escherichia coli . Results We define the region in a gene that takes the longest time to translate as the bottleneck. We found that localization of the bottleneck at the beginning of a transcript promoted a high level of expression, especially if the computed dwell time of the ribosome within this region was sufficiently long. The location and translation time of the bottleneck were not correlated with the cost of expression, approximated by the fitness of the host cell, yet utilization of specific codons was. Particularly, enhanced usage of the codons UCA and CAU was correlated with increased cost of production, potentially due to sequestration of their corresponding rare tRNAs. Conclusions The distribution of codons along the genes appears to affect translation efficiency, consistent with analysis of natural genes. This study demonstrates how synthetic biology complements bioinformatics by providing a set-up for well controlled experiments in biology.
Understanding and Treating Insomnia
Authors: Richard R. Bootzin, Dana R. Epstein
Journal: Annual Review of Clinical Psychology (2011)

Sleep disturbance is intricately entwined with our sense of well-being, health, emotion regulation, performance and productivity, memory and cognitive functioning, and social interaction. A longitudinal perspective underscores the conclusion that persistent sleep disturbance, insomnia, at any time during the life span from infancy to old age has a lasting impact. We examine how insomnia develops, the evidence for competing explanations for understanding insomnia, and the evidence about psychological and behavioral treatments that are used to reduce insomnia and change daytime consequences. There are new directions to expand access to treatment for those who have insomnia, and thus a critical analysis of pathways for dissemination is becoming increasingly important.
Oral Cavity Carcinoma: Current Management, Controversies, and Future Directions
Authors: Steven B. Chinn, Jeffrey N. Myers
Journal: Journal of Clinical Oncology (2015)

Oral cavity carcinoma (OCC) remains a major cause of morbidity and mortality in patients with head and neck cancer. Although the incidence has decreased over the last decade, outcomes remain stagnant with only a 5% improvement in overall survival in the last 20 years. Although surgical resection remains the primary treatment modality, several areas of controversy exist with regard to work-up, management of the primary and neck tumors, and adjuvant therapy. As surgical techniques evolve, so has the delivery of radiotherapy and systemic treatment, which have helped to improve the outcomes for patients with advanced disease. Recently, the addition of cetuximab has shown promise as a way to improve outcomes while minimizing toxicity, and this remains an active area of study in the adjuvant setting. Advances in microvascular free-flap reconstruction have extended the limits of resection and enabled enhanced restoration of function and cosmesis. While these advances have led to limited survival benefit, evaluation of alternative modalities has gained interest on the basis of success in other head and neck subsites. Organ preservation with definitive chemoradiotherapy, though proven in the larynx and pharynx, remains controversial in OCC. Likewise, although the association of human papillomavirus is well established in oropharyngeal carcinoma, it has not been proven in the pathogenesis or survival of OCC. Future study of the molecular biology and pathogenesis of OCC should offer additional insight into screening, treatment selection, and novel therapeutic approaches.
Inhaled Granulocyte/Macrophage Colony–Stimulating Factor as Treatment of Pneumonia-associated Acute Respiratory Distress Syndrome
Authors: Susanne Herold, Katrin Hoegner, István Vadász, Tobias Gessler, Jochen Wilhelm, Konstantin Mayer, Rory E. Morty, Hans-Dieter Walmrath, Werner Seeger, Juergen Lohmeyer
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
CHANGES IN RESPONSE OF VASTUS LATERALIS AND BICEPS FEMORIS AFTER A PHYSICAL ACTIVITY PROGRAM IN SUBJECTS DIAGNOSED WITH ALZHEIMER'S DISEASE
Authors: David Rodríguez-Ruiz, Sarmiento Sarmiento, Darío Rodríguez-Matoso, Yessenia Henríquez del Pino, Lorena Álvarez-Piñera, Manuel García-Manso Juan
Journal: British Journal of Sports Medicine (2013)

Objetive The aim of this study was to evaluate the effects of a physical activity (PA) program and subsequent detraining on the contractile capacity of the Vastus Lateralis (VL) and Biceps Femoris (BF) in patients diagnosed with Alzheimer's Disease (AD). Methods A total of 37 subjects were divided in: the intervention group (IG) consisted of 19 subjects (75.58 years ±6.18) and the control group (CG) for 18 subjects (79.92 years ±7.03). The PA intervention program was 4 month length, 60 training sessions and 5 days/week. The Tensiomyography (TMG) was used to assess the maximum radial displacement of the muscle belly (Dm) and the normalized response velocity (Vrn) in VL and BF of both legs. The assessment was performed before intervention (Pre), at the end of four months of intervention (Post) and two months after finishing the intervention (Post 2). Results Vrn for VL in IG increased in both legs after the intervention program (p≤0.05) while later decreased in the post2 (p≤0.05). Although we observe an increase of Vrn in CG (p≤0.05) it was not significantly higher than baseline levels (pre). The BF shows the same trend than VL for Vrn in IG, whereas in CG there is a tendency to maintain values. Dm for VL shows a decrease in post and an increased in post 2 assessment in IG. Dm values for left BF show significant differences in IG whereas in CG there is a tendency to maintain values. Dm for VL in IG decrease in both legs in post assessment (p≤0.05), and increases in post2 (p≤0.05). However, Dm showed only significant increases in right VL post assessment compared to baseline. Conclusions A PA program adapted to elderly diagnosed with AD, produces changes in morphology and muscle responses. Further, it enhances balance and motor skills, which results in a reduction in the risk of falls, improves the quality of life, and return to baseline values.
Cancer Incidence in Israeli Jewish Survivors of World War II
Authors: L. Keinan-Boker, N. Vin-Raviv, I. Liphshitz, S. Linn, M. Barchana
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundIsraeli Jews of European origin have high incidence rates of all cancers, and many of them were exposed to severe famine and stress during World War II. We assessed cancer incidence in Israeli Jewish survivors of World War II.
NMNAT1 mutations cause Leber congenital amaurosis
Authors: Marni J Falk, Qi Zhang, Eiko Nakamaru-Ogiso, Chitra Kannabiran, Zoe Fonseca-Kelly, Christina Chakarova, Isabelle Audo, Donna S Mackay, Christina Zeitz, Arundhati Dev Borman, Magdalena Staniszewska, Rachna Shukla, Lakshmi Palavalli, Saddek Mohand-Said, Naushin H Waseem, Subhadra Jalali, Juan C Perin, Emily Place, Julian Ostrovsky, Rui Xiao, Shomi S Bhattacharya, Mark Consugar, Andrew R Webster, José-Alain Sahel, Anthony T Moore, Eliot L Berson, Qin Liu, Xiaowu Gai, Eric A Pierce
Journal: Nature Genetics (2012)
NOSOCOMIAL OUTBREAK OF CAMPYLOBACTER JEJUNI MENINGITIS IN NEWBORN INFANTS
Authors: Herman Goossens, Louis Kremp, Richard Boury, Linda Vlaes, Chantal Van Den Borre, Geneviève Henocque, Jean Rocque, Georges Alanio, Wim Hemelhof, Michel Macart, JeanPaul Butzler
Journal: The Lancet (1986)
Cancer Immunotherapy Using<i>In vitro</i>Genetically Modified Targeted Dendritic Cells
Authors: Huafeng Wei, Hao Wang, Bing Lu, Bohua Li, Sheng Hou, Weizhu Qian, Kexing Fan, Jianxin Dai, Jian Zhao, Yajun Guo
Journal: Cancer Research (2008)

Abstract Modest clinical outcomes of dendritic cell (DC) vaccine trials call for novel strategies. In this study, we have created a chimeric CD40 molecule that incorporates a single chain Fv (scFv) molecule specific for human ErbB2 antigen and fusing to the membrane spanning and cytosolic domains of murine CD40. After adenoviral transfer to bone marrow–derived DC, this chimeric receptor (CR) induced nuclear factor-κB (NF-κB)–dependent DC activation and effector function when cultured with immobilized ErbB2 protein or ErbB2-positive tumor cells in vitro. In vivo migration assays showed that ∼40% injected CR-modified DC (scFv-CD40-DC) effectively migrated to ErbB2-positive tumors, where they were activated after ErbB2 antigen stimulation, and sequentially homed into the draining lymph nodes. In murine ErbB2-positive D2F2/E2 breast tumor (BALB/c) and EL4/E2 thymoma (C57BL/6) models, i.v. injection of 1 × 106 scFv-CD40-DC significantly inhibited tumor growth and cured established tumors. Importantly, the cured mice treated by injection of scFv-CD40-DC were effective in preventing both ErbB2-positive and parental ErbB2-negative tumor rechallenge. Analysis of the underlying mechanism revealed that i.v. infusion of scFv-CD40-DC elicited tumor-specific CTL responses, and the transfer of CTLs from scFv-CD40-DC–treated mice protected naive mice against a subsequent tumor challenge. These results support the concept that genetic modification of DC with tumor-associated antigen-specific CD40 chimeric receptor might be a useful strategy for treatment of human cancers. [Cancer Res 2008;68(10):3854–62]
Effect of Bortezomib on Human Neuroblastoma Cell Growth, Apoptosis, and Angiogenesis
Authors: Chiara Brignole, Danilo Marimpietri, Fabio Pastorino, Beatrice Nico, Daniela Di Paolo, Michela Cioni, Federica Piccardi, Michele Cilli, Annalisa Pezzolo, Maria Valeria Corrias, Vito Pistoia, Domenico Ribatti, Gabriella Pagnan, Mirco Ponzoni
Journal: JNCI Journal of the National Cancer Institute (2006)

Bortezomib is a selective and reversible inhibitor of the 26S proteasome that shows potent antitumor activity in vitro and in vivo against several human cancers of adulthood. No data are available on bortezomib activity against human pediatric neuroblastoma.Ten neuroblastoma cell lines and suspensions of primary neuroblastoma cells from three patients were tested for sensitivity to bortezomib. Colony formation, cell proliferation, cell cycle progression, and apoptosis were evaluated by a clonogenic assay and by measuring 3H-thymidine incorporation, bromodeoxyuridine uptake, DNA fragmentation, and phosphatidylserine exposure and propidium iodide staining, respectively. Angiogenesis was assessed by the chick embryo chorioallantoic membrane (CAM) assay. Two mouse xenograft models that mimic the growth and spread of neuroblastoma in humans were used to examine in vivo sensitivity of neuroblastoma to bortezomib. All statistical tests were two-sided.Bortezomib inhibited proliferation and colony formation of neuroblastoma cell lines in a time- and dose-dependent manner. The mean bortezomib concentration that caused 50% inhibition of growth was 6.1 nM (95% confidence interval [CI] = 0.9 to 11.3 nM) at 72 hours. Bortezomib-treated neuroblastoma cells were arrested at G2/M and underwent apoptosis (mean percentage of apoptotic cells in four neuroblastoma cell lines treated with 20 nM bortezomib for 24 hours ranged from 20% to 35%, and caspases were activated by two- to fivefold with respect to untreated cells). Similar results were obtained for primary neuroblastoma cells exposed to bortezomib. Bortezomib inhibited angiogenesis in CAMs stimulated by conditioned medium from neuroblastoma cell lines, by neuroblastoma xenografts, and by primary neuroblastoma biopsy specimens (microvessel area: 2.9 x 10(-2) mm2, 95% CI = 1.8 x 10(-2) to 3.8 x 10(-2) mm2 in CAMs treated with biopsy specimens alone and 1.3 x 10(-2) mm2, 95% CI = 1 x 10(-2) to 1.5 x 10(-2) mm2 in CAMs treated with biopsy specimens plus bortezomib, P = .024). In both mouse models, mice treated with bortezomib lived statistically significantly longer than control mice (mean survival time in the pseudometastatic model: 74.2 versus 50.3 days, P<.001; mean survival time in the orthotopic model: 72.3 versus 50.6 days, P<.001).Bortezomib is an effective inhibitor of neuroblastoma cell growth and angiogenesis. These findings provide the rationale for further clinical investigation of bortezomib in pediatric neuroblastoma.
Dexamethasone in Adults with Bacterial Meningitis
Authors: Kathryn N Suh
Journal: New England Journal of Medicine (2003)

De Gans J, van de Beek D, for the European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002;347(20):1549-56. 

Background: Even when bacterial meningitis is diagnosed and treated promptly, it causes significant
ABC of sports and exercise medicine, 3rd edn
Authors: D Robinson
Journal: British Journal of Sports Medicine (2007)

Edited by Gregory P Whyte, Mark Harries, Clyde Williams. Oxford, UK: Blackwell Publishing, 2005, £24.95, US$46.98 (approx), €36.58 (approx), pp 136 (softcover). ISBN 0727918133

The title of this book is a misnomer. “ABC of sports and exercise medicine” suggests that the book covers all subjects within the designated sphere. The foreword also states that there is “no clearer, more compact, comprehensive, authoritative manual of sports and exercise medicine.” How could a comprehensive textbook on sports medicine be compact and how could it exclude almost all discussion on injuries to the body below the neck?

This book is a fascinating dichotomy. It has some excellent components and some rather pedestrian ones. Each chapter has been written by a different author, and it is almost as if the editorial direction each author was given varied in terms of content, degree of detail, and requirement for referencing and further …
Detection of Micrometastatic Disease and Monitoring of Perioperative Tumor Cell Dissemination in Primary Operable Breast Cancer Patients Using Real-Time Quantitative Reverse Transcription-PCR
Authors: Mohamed Saad Ismail, Wim Wynendaele, Joeri L. E. Aerts, Robert Paridaens, Rabab Gaafar, Nayera Shakankiry, Hussein M. Khaled, Marie-Rose Christiaens, Hans Wildiers, Sherif Omar, Philippe Vandekerckhove, Allan T. van Oosterom
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We previously found a statistically significant number of cytokeratin 19 (CK19)+ cells in peripheral blood (PB) of stage IV breast cancer (BC) patients compared with those of healthy volunteers, using a quantitative real-time reverse transcription-PCR. We aimed to apply the technique on bone marrow (BM) of primary operable BC patients. Pre- and postoperative PB samples of these patients were further analyzed to investigate possible shedding of CK19+ cells during the operation. Experimental Design: In 54 primary operable BC patients, we analyzed 50 BM samples taken preoperatively and 297 PB samples. PB samples were collected before surgery; immediately after surgery; on the first, second, and fifth day postoperatively; and one month postoperatively. Results: In BM of controls and BC patients, we detected a median of 28 and 568 CK19+ cells/5 × 106 leukocytes, respectively (P &amp;lt; 0.001). In preoperative blood (B-1) samples, we measured a median of 109 CK19+ cells. Using the upper limit of 95% confidence interval of controls as cutoff, 74% and 52% of BM and (B-1), respectively were considered CK19+. There was no significant correlation between CK19+ cells in BM and (B-1) and classical prognostic factors. We found no significant difference between blood samples at different time points with respect to the average CK19+ cells. Conclusions: In primary BC patients, we detected high numbers of CK19+ cells in BM and PB (B-1) samples compared with controls. However, no significant correlation between the presence of CK19+ cells in BM and PB and classical prognostic factors was found. We detected no statistically significant influence of surgical manipulation on CK19+ cells.
Proinflammatory Activation of Macrophages by Basic Calcium Phosphate Crystals via Protein Kinase C and MAP Kinase Pathways
Authors: Imad Nadra, Justin C. Mason, Pandelis Philippidis, Oliver Florey, Cheryl D.W. Smythe, Geraldine M. McCarthy, Robert C. Landis, Dorian O. Haskard
Journal: Circulation Research (2005)

Basic calcium phosphate (BCP) crystal deposition underlies the development of arterial calcification. Inflammatory macrophages colocalize with BCP deposits in developing atherosclerotic lesions and in vitro can promote calcification through the release of TNF alpha. Here we have investigated whether BCP crystals can elicit a proinflammatory response from monocyte-macrophages. BCP microcrystals were internalized into vacuoles of human monocyte-derived macrophages in vitro. This was associated with secretion of proinflammatory cytokines (TNFα, IL-1β and IL-8) capable of activating cultured endothelial cells and promoting capture of flowing leukocytes under shear flow. Critical roles for PKC, ERK1/2, JNK, but not p38 intracellular signaling pathways were identified in the secretion of TNF alpha, with activation of ERK1/2 but not JNK being dependent on upstream activation of PKC. Using confocal microscopy and adenoviral transfection approaches, we determined a specific role for the PKC-alpha isozyme. The response of macrophages to BCP crystals suggests that pathological calcification is not merely a passive consequence of chronic inflammatory disease but may lead to a positive feed-back loop of calcification and inflammation driving disease progression.