tbuckley/cabot-search huggingface dataset:
Molecular Imaging of Activated Matrix Metalloproteinases in Vascular Remodeling
Authors: Jiasheng Zhang, Lei Nie, Mahmoud Razavian, Masood Ahmed, Lawrence W. Dobrucki, Abolfazl Asadi, D. Scott Edwards, Michael Azure, Albert J. Sinusas, Mehran M. Sadeghi
Journal: Circulation (2008)

Background— Matrix metalloproteinase (MMP) activation plays a key role in vascular remodeling. RP782 is a novel indium 111 In–labeled tracer with specificity for activated MMPs. We hypothesized that RP782 can detect injury-induced vascular remodeling in vivo. Methods and Results— Left common carotid artery injury was induced with a guidewire in apolipoprotein E −/− mice. Sham surgery was performed on the contralateral artery, which served as control for imaging experiments. Carotid wire injury led to significant hyperplasia and expansive remodeling over a period of 4 weeks. MMP activity, detected by in situ zymography, increased in response to injury and was maximal by 3 to 4 weeks after injury. RP782 (11.1 MBq) was injected intravenously into apolipoprotein E −/− mice at 1, 2, 3, and 4 weeks after left carotid injury. MicroSPECT imaging was performed at 2 hours and was followed by CT angiography to localize the carotid arteries. In vivo images revealed focal uptake of RP782 in the injured carotid artery at 2, 3, and 4 weeks. Increased tracer uptake in the injured artery was confirmed by quantitative autoradiography. Pretreatment with 50-fold excess nonlabeled tracer significantly reduced RP782 uptake in injured carotids, thus demonstrating uptake specificity. Weekly changes in the vessel-wall area closely paralleled and correlated with RP782 uptake (Spearman r =0.95, P =0.001). Conclusions— Injury-induced MMP activation in the vessel wall can be detected by RP782 microSPECT/CT imaging in vivo. RP782 uptake tracks the hyperplastic process in vascular remodeling and provides an opportunity to track the remodeling process in vivo.
Decision Making in Pediatric Oncology: Who Should Take the Lead? The Decisional Priority in Pediatric Oncology Model
Authors: Simon N. Whitney, Angela M. Ethier, Ernest Frugé, Stacey Berg, Laurence B. McCullough, Marilyn Hockenberry
Journal: Journal of Clinical Oncology (2005)

Decision making in pediatric oncology can look different to the ethicist and the clinician. Popular ethical theories argue that clinicians should not make decisions for patients, but rather provide information so that patients can make their own decisions. However, this theory does not always reflect clinical reality. We present a new model of decision making that reconciles this apparent discrepancy. We first distinguish decisional priority from decisional authority. The person (parent, child, or clinician) who first identifies a preferred choice exercises decisional priority. In contrast, decisional authority is a nondelegable parental right and duty, in which a mature child may join. This distinction enables us to analyze decisional priority without diminishing parental authority. This model analyzes decisions according to two continuous underlying characteristics. One dominant characteristic is the likelihood of cure. Because cure, when possible, is the ultimate goal, the clinician is in a better position to assume decisional priority when a child probably can be cured. The second characteristic is whether there is more than one reasonable treatment option. The interaction of these two complex continual results in distinctive types of decisional situations. This model explains why clinicians sometimes justifiably assume decisional priority when there is one best medical choice. It also suggests that clinicians should particularly encourage parents (and children, when appropriate) to assume decisional priority when there are two or more clinically reasonable choices. In this circumstance, the family, with its deeper understanding of the child's nature and preferences, is better positioned to take the lead.
Measurement of lung volume and DLCO in acute respiratory failure.
Authors: P D Macnaughton, T W Evans
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

We have undertaken rebreathing measurements of functional residual capacity (FRC), carbon monoxide diffusing capacity (DLCO), and diffusing coefficient (KCO) during positive pressure ventilation in 15 patients with adult respiratory distress syndrome (ARDS). Measurements of oxygenation (PaO2:FIO2 ratio) and lung injury score (LIS) were also recorded. Eight patients subsequently died (mortality of 53%). There was no significant difference in mean FRC, PaO2:FIO2, or LIS at presentation between survivors and nonsurvivors. However, both DLCO and KCO at presentation were significantly greater in survivors than nonsurvivors. In a separate study of nine patients with less severe lung injury, pulmonary capillary blood volume, derived from values of DLCO measured at two different values of FIO2, correlated with invasive pulmonary vascular resistance (PVR) measurements (r = 0.84, p < 0.01). DLCO measurements can be successfully undertaken in patients being ventilated with acute lung injury and may be a useful, noninvasive method of assessing the pulmonary circulation. The lowest values of DLCO were recorded in patients who subsequently did not survive.
Prevention of Bone Loss in Renal Transplant Recipients
Authors: Maria Coco, Daniel Glicklich, Marie Claude Faugere, Larry Burris, Istvan Bognar, Peter Durkin, Vivian Tellis, Stuart Greenstein, Richard Schechner, Katherine Figueroa, Patricia McDonough, Guodong Wang, Hartmut Malluche
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Renal transplant recipients are at risk of developing bone abnormalities that result in bone loss and bone fractures. These are related to underlying renal osteodystrophy, hypophosphatemia, and immunosuppressive treatment regimen. Although bisphosphonates are useful in ameliorating bone mineral loss after transplantation, it is not known whether their use in renal transplant patients leads to excessive suppression of bone turnover and increased incidence of adynamic bone disease. A randomized, prospective, controlled, clinical trial was conducted using the bisphosphonate pamidronate intravenously in patients with new renal transplants. Treatment subjects (PAM) received pamidronate with vitamin D and calcium at baseline and at months 1, 2, 3, and 6. Control (CON) subjects received vitamin D and calcium only. During months 6 to 12, the subjects were observed without pamidronate treatment. Biochemical parameters of bone turnover were obtained monthly and, bone mineral density (BMD) was obtained at baseline and months 6 and 12. Bone biopsies for mineralized bone histology were obtained at baseline and at 6 mo in a subgroup of subjects who underwent scheduled living donor transplantation. PAM preserved bone mass at 6 and 12 mo as measured by bone densitometry and histomorphometry. CON had decreased vertebral BMD at 6 and 12 mo (4.8 ± 0.08 and 6.1 ± 0.09%, respectively). Biochemical parameters of bone turnover were similar in both groups at 6 and 12 mo. Bone histology revealed low turnover bone disease in 50% of the patients at baseline. At 6 mo, all of PAM had adynamic bone disease, whereas 50% of CON continued to have or developed decreased bone turnover. Pamidronate preserved vertebral BMD during treatment and 6 mo after cessation of treatment. Pamidronate treatment was associated with development of adynamic bone histology. Whether an improved BMD with adynamic bone histology is useful in maintaining long-term bone health in renal transplant recipients requires further study. E-mail: [email protected]
Apoptotic Cells with Oxidation-specific Epitopes Are Immunogenic and Proinflammatory
Authors: Mi-Kyung Chang, Christoph J. Binder, Yury I. Miller, Ganesamoorthy Subbanagounder, Gregg J. Silverman, Judith A. Berliner, Joseph L. Witztum
Journal: The Journal of Experimental Medicine (2004)

Oxidation of low density lipoprotein (LDL) generates a variety of oxidatively modified lipids and lipid-protein adducts that are immunogenic and proinflammatory, which in turn contribute to atherogenesis. Cells undergoing apoptosis also display oxidized moieties on their surface membranes, as determined by binding of oxidation-specific monoclonal antibodies. In the present paper, we demonstrated by mass spectrometry that in comparison with viable cells, membranes of cells undergoing apoptosis contain increased levels of biologically active oxidized phospholipids (OxPLs). Indeed, immunization of mice with syngeneic apoptotic cells induced high autoantibody titers to various oxidation-specific epitopes of oxidized LDL, including OxPLs containing phosphorylcholine, whereas immunization with viable thymocytes, primary necrotic thymocytes, or phosphate-buffered saline did not. Reciprocally, these antisera specifically bound to apoptotic cells through the recognition of oxidation-specific epitopes. Moreover, splenocyte cultures from mice immunized with apoptotic cells spontaneously released significant levels of T helper cell (Th) 1 and Th2 cytokines, whereas splenocytes from controls yielded only low levels. Finally, we demonstrated that the OxPLs of apoptotic cells activated endothelial cells to induce monocyte adhesion, a proinflammatory response that was abrogated by an antibody specific to oxidized phosphatidylcholine. These results suggest that apoptotic cell death generates oxidatively modified moieties, which can induce autoimmune responses and a local inflammatory response by recruiting monocytes via monocyte–endothelial cell interaction.
Impairment of BRCA1-Related DNA Double-Strand Break Repair Leads to Ovarian Aging in Mice and Humans
Authors: Shiny Titus, Fang Li, Robert Stobezki, Komala Akula, Evrim Unsal, Kyungah Jeong, Maura Dickler, Mark Robson, Fred Moy, Sumanta Goswami, Kutluk Oktay
Journal: Science Translational Medicine (2013)

DNA double-strand break repair has a central role in oocyte aging.
The Dipeptidyl Peptidase-4 Inhibitor Vildagliptin Improves β-Cell Function and Insulin Sensitivity in Subjects With Impaired Fasting Glucose
Authors: Kristina M. Utzschneider, Jenny Tong, Brenda Montgomery, Jayalakshmi Udayasankar, Fernando Gerchman, Santica M. Marcovina, Catherine E. Watson, Monica A. Ligueros-Saylan, James E. Foley, Jens J. Holst, Carolyn F. Deacon, Steven E. Kahn
Journal: Diabetes Care (2007)

To evaluate the effect of treatment with the dipeptidyl peptidase (DPP)-4 inhibitor vildagliptin on insulin sensitivity and beta-cell function in subjects with impaired fasting glucose (IFG).A total of 22 subjects with IFG (11 female and 11 male, mean +/- SD age 59.6 +/- 11.5 years) were treated orally with 100 mg vildagliptin once daily in a single-blind study. Subjects received placebo for 2 weeks (run-in) followed by vildagliptin for 6 weeks (treatment) and then placebo for 2 weeks (washout). A frequently sampled intravenous glucose tolerance test (FSIGT), followed by a 2-h meal tolerance test (MTT), was performed at 2, 8, and 10 weeks. From the FSIGT, the acute insulin response to glucose (AIR(g)) and insulin sensitivity index (S(I)) were determined and used to compute the disposition index (AIR(g) x S(I)) as a measure of beta-cell function.Fasting plasma glucose did not change after 6 weeks of vildagliptin treatment. With treatment, mean +/- SEM AIR(g) increased from 224 +/- 44 to 286 +/- 52 pmol/l (P < 0.05), and S(I) improved from 2.8 +/- 0.5 to 3.5 +/- 0.5 x 10(-5) x min(-1) x pmol(-1) x l (P < 0.01), resulting in an increase in the disposition index from 688 +/- 180 to 1,164 +/- 318 x 10(-5)/min (P < 0.05). These effects were not sustained after washout. During the MTT, the incremental area under the glucose curve was significantly decreased after treatment (240 +/- 15 vs. 191 +/- 14 mmol x l(-1) x min(-1); P = 0.002), but this effect was not sustained after washout.The DPP-4 inhibitor vildagliptin improves insulin sensitivity and beta-cell function, leading to improved postprandial glycemia in subjects with IFG, who are known to have beta-cell dysfunction. Thus, vildagliptin may prevent progression to diabetes in high-risk subjects.
MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes
Authors: Thomas Vogl, Stephan Ludwig, Matthias Goebeler, Anke Strey, Irmgard S. Thorey, Rudolf Reichelt, Dirk Foell, Volker Gerke, Marie P. Manitz, Wolfgang Nacken, Sabine Werner, Clemens Sorg, Johannes Roth
Journal: Blood (2004)
IL-29 is the dominant type III interferon produced by hepatocytes during acute hepatitis C virus infection
Authors: Heiyoung Park, Elisavet Serti, Onyinyechi Eke, Brian Muchmore, Ludmila Prokunina-Olsson, Stefania Capone, Antonella Folgori, Barbara Rehermann
Journal: Hepatology (2012)

Early, vigorous intrahepatic induction of interferon (IFN)-stimulated gene (ISG) induction is a feature of hepatitis C virus (HCV) infection, even though HCV inhibits the induction of type I IFNs in vitro. To identify the cytokines and cells that drive ISG induction and mediate antiviral activity during acute HCV infection, type I and III IFN responses were studied in (1) serial liver biopsies and plasma samples obtained from 6 chimpanzees throughout acute HCV infection and (2) primary human hepatocyte (PHH) cultures upon HCV infection. Type I IFNs were minimally induced at the messenger RNA (mRNA) level in the liver and were undetectable at the protein level in plasma during acute HCV infection of chimpanzees. In contrast, type III IFNs, in particular, interleukin (IL)-29 mRNA and protein, were strongly induced and these levels correlated with ISG expression and viremia. However, there was no association between intrahepatic or peripheral type III IFN levels and the outcome of acute HCV infection. Infection of PHH with HCV recapitulated strong type III and weak type I IFN responses. Supernatants from HCV-infected PHH cultures mediated antiviral activity upon transfer to HCV-replicon-containing cells. This effect was significantly reduced by neutralization of type III IFNs and less by neutralization of type I IFNs. Furthermore, IL-29 production by HCV-infected PHH occurred independently from type I IFN signaling and was not enhanced by the presence of plasmacytoid dendritic cells.
Natural Resistance to Intracellular Infections
Authors: Nada Jabado, Andrzej Jankowski, Samuel Dougaparsad, Virginie Picard, Sergio Grinstein, Philippe Gros
Journal: The Journal of Experimental Medicine (2000)

Mutations at the natural resistance–associated macrophage protein 1 (Nramp1) locus cause susceptibility to infection with antigenically unrelated intracellular pathogens. Nramp1 codes for an integral membrane protein expressed in the lysosomal compartment of macrophages, and is recruited to the membrane of phagosomes soon after the completion of phagocytosis. To define whether Nramp1 functions as a transporter at the phagosomal membrane, a divalent cation-sensitive fluorescent probe was designed and covalently attached to a porous particle. The resulting conjugate, zymosan–FF6, was ingested by macrophages and its fluorescence emission was recorded in situ after phagocytosis, using digital imaging. Quenching of the probe by Mn2+ was used to monitor the flux of divalent cations across the phagosomal membrane in peritoneal macrophages obtained from Nramp1-expressing (+/+) and Nramp1-deficient (−/−) macrophages. Phagosomes from Nramp1+/+ mice extrude Mn2+ faster than their Nramp−/− counterparts. The difference in the rate of transport is eliminated when acidification of the phagosomal lumen is dissipated, suggesting that divalent metal transport through Nramp1 is H+ dependent. These studies suggest that Nramp1 contributes to defense against infection by extrusion of divalent cations from the phagosomal space. Such cations are likely essential for microbial function and their removal from the phagosomal microenvironment impairs pathogenesis, resulting in enhanced bacteriostasis or bactericidal activity.
Ethical Challenges in Cell-Based Interventions for Neurological Conditions: Some Lessons To Be Learnt from Clinical Transplantation Trials in Patients with Parkinson's Disease
Authors: Elisabeth Hildt
Journal: The American Journal of Bioethics (2009)

"Ethical Challenges in Cell-Based Interventions for Neurological Conditions: Some Lessons To Be Learnt from Clinical Transplantation Trials in Patients with Parkinson's Disease." The American Journal of Bioethics, 9(5), pp. 37–38
Static mechanical properties and chemical composition of the aorta of spontaneously hypertensive rats: a comparison with the effects of induced hypertension
Authors: S. E. GREENWALD, C. L. BERRY
Journal: Cardiovascular Research (1978)

The static elastic properties and medial scleroprotein content of the aorta have been examined in spontaneously hypertensive rats (AS strain) aged 6 and 20 weeks (group SH). The results are compared with data from two previous studies on normal (group N) and induced hypertensive animals (group H). Spontaneous hypertension is associated with a relative increase in elastin and decrease in collagen when compared with the normal aorta. These changes are similar to, although smaller in magnitude than, those associated with induced hypertension. Elasticity measurements show that the functional stiffness (incremental strain) of the aorta in group SH is greater than normal. However, this difference diminishes with age, suggesting an adaptive response which tends to maintain the functional stiffness near to normal levels.
Orbital development in long-term survivors of retinoblastoma.
Authors: S C Kaste, G Chen, J Fontanesi, D B Crom, C B Pratt
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine the effects of enucleation, irradiation, and age at diagnosis on bony orbital growth in long-term survivors of retinoblastoma using measurements based on computed tomographic (CT) imaging. PATIENTS AND METHODS We used CT obtained at a median age of 13 years to measure orbital volume and configuration in 54 patients who had been treated for retinoblastoma a minimum of 5 years previously. RESULTS Enucleation and high-dose orbital irradiation (&gt; 35 Gy) both independently adversely affected orbital development (P = .014 and P = .022, respectively). Orbital volume differences for children treated when &lt; or = 1 year old were no greater than those for children treated when older than 1 year of age. In children treated for bilateral retinoblastoma, the impact of enucleation on orbital development was not statistically different from that of irradiation (P = .13). Small implants (12 to 14 mm in diameter) were more commonly associated with smaller orbital volumes. Migration of orbital implants was associated with the smaller orbital sphere size in children &lt; or = 1 year of age (P &lt; .035). CONCLUSION Treatment for retinoblastoma compromises orbital development. Resulting orbital asymmetry seems to be at least partially related to the size of the implant. Detailed imaging-based measurements of orbital volume and configuration may aid the planning for cosmetic and reconstructive surgery in those who develop orbital asymmetry.
Fast and Slow Implementations of Relaxed-Clock Methods Show Similar Patterns of Accuracy in Estimating Divergence Times
Authors: Fabia U. Battistuzzi, Paul Billing-Ross, Aditya Paliwal, Sudhir Kumar
Journal: Molecular Biology and Evolution (2011)

Phylogenetic analyses are using increasingly larger data sets for estimating divergence times. With this increase in data sizes, the computation time required is becoming a bottleneck in evolutionary investigations. Our recent study of two relaxed-clock programs (BEAST and MultiDivTime [MDT]) showed their usefulness in time estimation; however, they place a significant computational time burden on biologists even for moderately small data sets. Here, we report speed and accuracy of another relaxed-clock program (MCMCTree, MC2T). We find it to be much faster than both MDT and BEAST while producing comparable time estimates. These results will encourage the analysis of larger data sets as well as the evaluation of the robustness of estimated times to changes in the model of evolutionary rates and clock calibrations.
INTERACTIONS BETWEEN RABBIT POLYMORPHONUCLEAR LEUCOCYTES AND STAPHYLOCOCCI
Authors: Zanvil A. Cohn, Stephen I. Morse
Journal: The Journal of Experimental Medicine (1959)

A method has been described for the study in vitro of leucocyte-bacteria interactions which permits the simultaneous evaluation of both phagocytosis and intracellular bacterial inactivation. Employing this technique, the fate and localization of staphylococci in homogeneous suspensions of rabbit polymorphonuclear leucocytes have been studied. Coagulase-positive strains of S. aureus were not efficiently ingested in the presence of normal rabbit serum. In contrast, coagulase-negative strains of S. albus were rapidly engulfed and inactivated. Immune sera prepared against a coagulase-positive strain enhanced the the ingestion of the homologous organism as well as of three heterologous strains of S. aureus. Following phagocytosis, prompt intracellular killing of S. aureus occurred. The thermostable opsonins in immune sera reacted only with strains of S. aureus. A comparison between polymorphonuclear leucocytes obtained from normal and immune animals revealed no differences in their ability either to ingest or kill coagulase-positive staphylococci. Studies with other bacterial species are presented to illustrate: (a) phagocytosis followed by intracellular inactivation; (b) phagocytosis followed by intracellular survival; and (c) the absence of phagocytosis.
Pivotal role of CEACAM1 protein in the inhibition of activated decidual lymphocyte functions
Authors: Gal Markel, Dana Wolf, Jacob Hanna, Roi Gazit, Debra Goldman-Wohl, Yuval Lavy, Simcha Yagel, Ofer Mandelboim
Journal: Journal of Clinical Investigation (2002)

Lymphocytes in direct contact with embryonic extravillous trophoblasts constitute more than 40% of decidual cells and appear to play major roles in implantation and early gestation. A unique subset of NK cells, making up 70–80% of decidual lymphocytes, express high levels of CD56 but lack CD16. We have recently demonstrated a novel class I MHC–independent inhibitory mechanism of NK cell cytotoxicity that is mediated by CEACAM1 homotypic interactions. This mechanism is used by some melanoma cells to avoid attack, mainly by CD16– NK cells. We now demonstrate that CEACAM1 is expressed on primary extravillous trophoblasts and is upregulated on the vast majority of IL-2–activated decidual lymphocytes, including NK, T, and NKT cells. Importantly, we present evidence that CEACAM1 interactions inhibit the lysis, proliferation, and cytokine secretion of activated decidual NK, T, and NKT cells, respectively. In vivo analysis of decidual lymphocytes isolated from cytomegalovirus-infected (CMV-infected) pregnant women revealed a dramatic increase in the expression of CEACAM1. Finally, we suggest that a novel ligand for this adhesion molecule is present on the surface of CMV-infected fibroblasts. These combined results demonstrate a major role for the CEACAM1 protein in controlling local decidual immune responses.