gebhart/patrepeval huggingface dataset:
Actin-Containing Sera From Patients With Adult Respiratory Distress Syndrome are Toxic to Sheep Pulmonary Endothelial Cells (2000)

Actin released from damaged cells after a variety of tissue injuries appears to be involved in multiple organ dysfunction syndrome. Under experimental conditions, when the quantity of actin present in plasma is made to exceed the protective capacity of the actin-scavenging mechanism, microembolism and pulmonary vascular angiopathy have been noted in rats. It remains to be determined whether this injury is a result of a direct toxic effect or occurs indirectly via platelet activation or fibrin interactions. We examined the effect of sera from patients with adult respiratory distress syndrome (ARDS), as well as G-actin added to normal serum, on the viability, morphology, and function of cultured sheep pulmonary artery endothelial cells (SPAEC). Both patient sera and normal sera to which actin was added were toxic in the cell culture model; this toxicity could be abrogated, at least partially, by preincubation with gelsolin, which is known to complex with actin. A significant portion of the toxicity of sera from patients with ARDS was sensitive to heat (56 degrees C), suggesting an important role of complement. Sera from patients with ARDS were shown to contain filaments of F-actin by immunoblot and rhodamine phalloidin staining after ultracentrifugation. Thus, saturation of the actin-scavenging system by addition of exogenous G-actin to plasma produces direct pulmonary endothelial cell injury. Furthermore, plasma from patients with ARDS secondary to bacterial pneumonia is toxic to SPAEC, and a small but significant contributory role of actin is apparent in these studies.
Protection against pulmonary oxygen toxicity in rats by the intratracheal administration of liposome-encapsulated superoxide dismutase or catalase. (1985)

To test the feasibility of using liposomes to deliver therapeutic agents to the lungs, the effect of liposome-encapsulated superoxide dismutase (SOD) or catalase on pulmonary oxygen toxicity was studied in rats. The SOD or catalase was encapsulated in negatively changed multilamellar liposomes and administered directly into the trachea of adult rats, which were subsequently exposed to hyperoxia (greater than 95% O2). Response to hyperoxia was examined by studying lung SOD and catalase activities, survival rates, and lung morphology. Rats receiving liposome-encapsulated SOD or catalase showed increased levels of enzyme activities in the lung homogenates compared with those in the control groups after 24 to 72 h of hyperoxic exposure. Elevated enzyme levels in the lungs of rats treated with liposome-encapsulated SOD or catalase were accompanied by a significant improvement in survival rates after 72 h of hyperoxic exposure and less lung injury than in the other control groups.
Rapid, Multiparameter Profiling of Cellular Secretion Using Silicon Photonic Microring Resonator Arrays (2011)

We have developed a silicon photonic biosensing chip capable of multiplexed protein measurements in a biomolecularly complex cell culture matrix. Using this multiplexed platform combined with fast one-step sandwich immunoassays, we perform a variety of T cell cytokine secretion studies with excellent time-to-result. Using 32-element arrays of silicon photonic microring resonators, the cytokines interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5), and tumor necrosis factor alpha (TNFα) were simultaneously quantified with high accuracy in serum-containing cell media. Utilizing this cytokine panel, secretion profiles were obtained for primary human Th0, Th1, and Th2 subsets differentiated from naïve CD4+ T cells, and we show the ability to discriminate between lineage commitments at early stages of culture differentiation. We also utilize this approach to probe the temporal secretion patterns of each T cell type using real-time binding analyses for direct cytokine quantitation down to ∼100 pM with just a 5 min-analysis.
Bioapplications of RAFT Polymerization (2009)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTBioapplications of RAFT PolymerizationCyrille Boyer†, Volga Bulmus‡, Thomas P. Davis*†, Vincent Ladmiral§, Jingquan Liu†, and Sébastien Perrier*§View Author Information Centre for Advanced Macromolecular Design (CAMD), School of Chemical Sciences & Engineering, UNSW, Sydney, NSW 2052, Australia, Centre for Advanced Macromolecular Design (CAMD), School of Biotechnology & Biomolecular Sciences, UNSW, Sydney, NSW 2052, Australia, and Key Centre for Polymers & Colloids, School of Chemistry, Building F11, Eastern Avenue, The University of Sydney, NSW 2006, Australia* E-mail: T.P.D., [email protected]; S.P., [email protected]†Centre for Advanced Macromolecular Design (CAMD), School of Chemical Sciences & Engineering, UNSW.‡Centre for Advanced Macromolecular Design (CAMD), School of Biotechnology & Biomolecular Sciences, UNSW.§The University of Sydney.Cite this: Chem. Rev. 2009, 109, 11, 5402–5436Publication Date (Web):September 18, 2009Publication History Received6 April 2009Published online18 September 2009Published inissue 11 November 2009https://pubs.acs.org/doi/10.1021/cr9001403https://doi.org/10.1021/cr9001403review-articleACS PublicationsCopyright © 2009 American Chemical SocietyRequest reuse permissionsArticle Views22403Altmetric-Citations904LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Copolymers,Monomers,Organic compounds,Polymers,RAFT polymerization Get e-Alerts
A Developmentally Regulated Neuraminidase Activity in Trypanosoma cruzi (1983)

The human pathogen Trypanosoma cruzi (Y strain) contains a neuraminidase activity that varies widely in the different developmental stages of the parasite. The specific neuraminidase activity of infective trypomastigotes obtained from tissue culture and from the bloodstream of infected mice is 7 to 15 times higher than that of the acellular culture forms. Amastigotes were devoid of enzyme activity. The enzyme has a pH optimum of 6.0 to 6.5. Live trypanosomes released sialic acid from human erythrocytes and plasma glycoproteins. Several sialyl compounds were hydrolyzed by the parasite, but the best substrate was the protein orosomucoid. Erythrocytes from infected mice with T. cruzi parasitemia were agglutinated by peanut lectin and the hemagglutination titer was correlated with the degree of parasitemia.
In Vivo Amplification of the PAX3-FKHR and PAX7-FKHR Fusion Genes in Alveolar Rhabdomyosarcoma (1996)

In the pediatric cancer alveolar rhabdomyosarcoma, characteristic t(2;13)(q35;q14) or variant t(1;13)(p36;q14) chromosomal translocations generate PAX3-FKHR or PAX7-FKHR fusion genes. Using fluorescence in situ hybridization, reverse transcriptase-polymerase chain reaction and quantitative Southern blot analyses, we demonstrate that these fusion genes are amplified in 20% of fusion-positive tumors. In particular, we found in vivo amplification of these fusions in one of 22 PAX3-FKHR-positive cases and five of seven PAX7-FKHR-positive cases. These findings indicate that translocation and amplification can occur sequentially in a cancer to alter both the structure and copy number of a gene and thereby activate oncogenic activity by complementary mechanisms.
Efficacy, safety and survival with ruxolitinib in patients with myelofibrosis: results of a median 2-year follow-up of COMFORT-I (2013)

COMFORT-I is a randomized, double-blind, placebo-controlled trial of the Janus kinase 1/Janus kinase 2 inhibitor ruxolitinib in 309 patients with intermediate-2 or high-risk myelofibrosis. This analysis of COMFORT-I describes the long-term efficacy and safety of ruxolitinib (median follow-up, 2 years). Spleen volume was measured by magnetic resonance imaging, and quality of life was evaluated using the EORTC QLQ-C30. Overall survival was determined according to randomized treatment group. At the time of this analysis, 100 of 155 patients randomized to ruxolitinib were still receiving treatment. All patients randomized to placebo crossed over to ruxolitinib or discontinued within 3 months of the primary analysis (median time to crossover, 41 weeks). Mean spleen volume reductions in the ruxolitinib group were 31.6% at week 24 and 34.9% at week 96; improvements in quality of life measures were also maintained. Improved survival was observed for ruxolitinib (n=27 deaths) versus placebo (n=41 deaths) (hazard ratio=0.58; 95% confidence interval: 0.36, 0.95; P=0.03). The incidence of new-onset grade 3 or 4 anemia and thrombocytopenia decreased over time to levels observed in patients receiving placebo. These data indicate that ruxolitinib treatment provides durable reductions in spleen volume and improvements in quality of life and suggest a continued survival advantage for ruxolitinib over placebo.
Improved Outcome When B-Cell Lymphoma Is Treated with Combinations of Immunoliposomal Anticancer Drugs Targeted to Both the CD19 and CD20 Epitopes (2004)

The success of immunoliposomal therapy in combination regimens varies with the type of encapsulated drug and the nature of the target epitopes.
Field Dependence of the Spin Relaxation Within a Film of Iron Oxide Nanocrystals Formed via Electrophoretic Deposition (2010)

The thermal relaxation of macrospins in a strongly interacting thin film of spinel-phase iron oxide nanocrystals (NCs) is probed by vibrating sample magnetometry (VSM). Thin films are fabricated by depositing FeO/Fe(3)O(4) core-shell NCs by electrophoretic deposition (EPD), followed by sintering at 400°C. Sintering transforms the core-shell structure to a uniform spinel phase, which effectively increases the magnetic moment per NC. Atomic force microscopy (AFM) confirms a large packing density and a reduced inter-particle separation in comparison with colloidal assemblies. At an applied field of 25 Oe, the superparamagnetic blocking temperature is T(B) (SP) ≈ 348 K, which is much larger than the Néel-Brown approximation of T(B) (SP) ≈ 210 K. The enhanced value of T(B) (SP) is attributed to strong dipole-dipole interactions and local exchange coupling between NCs. The field dependence of the blocking temperature, T(B) (SP)(H), is characterized by a monotonically decreasing function, which is in agreement with recent theoretical models of interacting macrospins.
ICOS-ligand, expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+T cells (2002)

Endothelial cells (EC) play a central role in inflammatory immune responses and efficiently induce effector functions in T cells, despite lacking the classical costimulatory ligands CD80 and CD86. By using the mAb HIL-131 we now demonstrate that human inducible costimulator-ligand (ICOS-L), a molecule related to CD80/CD86, is constitutively expressed on human EC in vivo. In vitro, ICOS-L expression was strongly enhanced on human umbilical vein EC and microvascular EC by the inflammatory cytokines tumor necrosis factor alpha and IL-1beta, and to a lower extent by stimulation of EC by CD40 or lipopolysaccharide. Coculture of MHC class II(+) EC with resting memory CD4(+) T cells in the presence of superantigen led to a marked up-regulation of ICOS on T cells and to the production of Th1 (IFN-gamma, IL-2) and Th2 cytokines (IL-4, IL-10, IL-13). When these cocultures were performed in the presence of the inhibitory mAb HIL-131, secretion of all cytokines was reduced by about 50-80%, indicating that ICOS-L is a major costimulator in EC-mediated T cell activation. Taken together, our data suggest an important physiological role of ICOS-L in the reactivation of effector/memory T cells on the endothelium controlling the entry of immune cells into inflamed tissue.
Nitroxides block DNA scission and protect cells from oxidative damage (1991)

The protective effect of cyclic stable nitroxide free radicals, having SOD-like activity, against oxidative damage was studied by using Escherichia coli xthA DNA repair-deficient mutant hypersensitive to H2O2. Oxidative damage induced by H2O2 was assayed by monitoring cell survival. The metal chelator 1,10-phenanthroline (OP), which readily intercalates into DNA, potentiated the H2O2-induced damage. The extent of in vivo DNA scission and degradation was studied and compared with the loss of cell viability. The extent of DNA breakage correlated with cell killing, supporting previous suggestions that DNA is the crucial cellular target of H2O2 cytotoxicity. The xthA cells were protected by catalase but not by superoxide dismutase (SOD). Both five- and six-membered ring nitroxides, having SOD-like activity, protected growing and resting cells from H2O2 toxicity, without lowering H2O2 concentration. To check whether nitroxides protect against O2.(-)-independent injury also, experiments were repeated under hypoxia. These nitroxides also protected hypoxic cells against H2O2, suggesting alternative modes of protection. Since nitroxides were found to reoxidize DNA-bound iron(II), the present results suggest that nitroxides protect by oxidizing reduced transition metals, thus interfering with the Fenton reaction.
Antigen-Specific IgG Elicited in Subjects with Prostate Cancer Treated with Flt3 Ligand (2005)

Identifying appropriate prostate cancer-associated antigens is critical to the development of immunologic treatments for prostate cancer. Flt3 ligand, a growth and differentiation factor for dendritic cells, has shown modest clinical activity in prostate cancer, presumably by eliciting anti-cancer immune responses. The authors previously reported the results of a clinical trial in which some patients with metastatic prostate cancer treated with flt3 ligand developed autoimmune hypothyroidism with thyroid-specific antibodies. Given these findings, the authors hypothesized that anti-prostate immune responses might also have been elicited in some subjects treated with flt3 ligand. The authors now report the identification of prostate-associated proteins immunologically recognized in 13 prostate cancer patients treated with multiple cycles of flt3 ligand. Using a normal prostate cDNA expression library, and sera from subjects before and after treatment with flt3 ligand, a modified SEREX approach was used to identify six proteins to which IgG immune responses were augmented after flt3 ligand treatment compared with pretreatment. IgG responses to one protein, MAD-CaP-5, were not detectable in any of the subjects' sera before treatment but were elicited after therapy in one subject. The authors suggest that MAD-CaP-5 could be explored as a novel prostate cancer antigen, and that this approach can be used to identify immunologically recognized proteins following any specific intervention.
Regulation of human histone gene expression: kinetics of accumulation and changes in the rate of synthesis and in the half-lives of individual histone mRNAs during the HeLa cell cycle. (1983)

We have analyzed the kinetics of accumulation of each of the individual core histone mRNAs throughout the HeLa cell cycle in cells synchronized by sequential thymidine and aphidicolin treatments. These analyses showed that during the S phase there was a 15-fold increase in the levels of histone mRNAs and that this resulted from both an increased rate of synthesis and a lengthening of the half-life of histone mRNAs. A comparison of the kinetics of accumulation of histone mRNA in the total cellular and nuclear RNA populations suggested an increased transcription rate through the S phase. Within 30 min after the inhibition of DNA synthesis in mid-S phase, the steady-state concentration and the rate of synthesis of histone mRNA each declined to their non-S-phase levels. Reactivation of histone mRNA accumulation could occur even after an extended mid-S-phase block in DNA synthesis. These results suggest that the mechanisms responsible for histone mRNA synthesis are not restricted to the G1/S boundary of the HeLa cell cycle, but can operate whenever DNA synthesis is occurring.
Viral hepatitis (1980)

Hepatitis A and hepatitis B are distinguished clinically by differences in onset and serologically by the presence of hepatitis A antigen or of any one of at least three hepatitis B antigens on the virus particle. At present, hepatitis non-A, non-B can be diagnosed only by exclusion of the other two types. Clinically it resembles hepatitis B. Hepatitis A is most often contracted through the fecal-oral route, and preschool children are at particular risk. Hepatitis B usually is transmitted by parenteral inoculation of virus-containing material. Transmission is now known to occur venereally as well. Since all blood donors now are screened for hepatitis B surface antigen, the cases of transfusion-associated hepatitis that do occur are caused mainly by non-A, non-B virus(es).
The Use of a Tropism-Modified Measles Virus in Folate Receptor–Targeted Virotherapy of Ovarian Cancer (2006)

A FR-exclusive ovarian cancer targeted oncolytic virus was generated and shown to be therapeutically effective, thus introducing a new modality for FR targeting and a candidate measles virus for clinical testing.
Pharmacokinetic Profile of μSMIN Plus™, a new Micronized Diosmin Formulation, after Oral Administration in Rats (2015)

Diosmin is a naturally occurring flavonoid present in citrus fruits and other plants belonging to the Rutaceae family. It is used for the treatment of chronic venous insufficiency (CVI) for its pheblotonic and vaso-active properties, safety and tolerability as well. The aim of the current in vivo study was to investigate the pharmacokinetic profile of a branded micronized diosmin (µSMIN Plus™) compared with plain micronized diosmin in male Sprague-Dawley rats. After oral administration by gastric gavage, blood samples were collected via jugular vein catheters at regular time intervals from baseline up to 24 hours. Plasma concentrations were assessed by LC/MS. For each animal, the following pharmacokinetic parameters were calculated using a non-compartmental analysis: maximum plasma drug concentration (Cmax), time to reach Cmax (Tmax), area under the plasma concentration-time curve (AUC0-last), elimination half-life (t½), and relative oral bioavailability (%F). The results of the current study clearly showed an improvement in the pharmacokinetic parameters in animals treated with µSMIN Plus™ compared with animals treated with micronized diosmin. In particular, µSMIN Plus™ showed a 4-fold increased bioavailability compared with micronized diosmin. In conclusion, the results from the current study provided a preliminary pharmacokinetic profile for µSMIN Plus™, which may represent a new tool for CVI management.
Engineering microbial factories for synthesis of value-added products (2011)

Microorganisms have become an increasingly important platform for the production of drugs, chemicals, and biofuels from renewable resources. Advances in protein engineering, metabolic engineering, and synthetic biology enable redesigning microbial cellular networks and fine-tuning physiological capabilities, thus generating industrially viable strains for the production of natural and unnatural value-added compounds. In this review, we describe the recent progress on engineering microbial factories for synthesis of valued-added products including alkaloids, terpenoids, flavonoids, polyketides, non-ribosomal peptides, biofuels, and chemicals. Related topics on lignocellulose degradation, sugar utilization, and microbial tolerance improvement will also be discussed.
Isomorphous binding of mercury-substituted thiosaccharides to pertussis toxin crystals yields crystallographic phases (1994)

An isomorphous derivative of pertussis toxin crystals was prepared using a 2-alpha-mercuric analog of N-acetyl neuraminic acid in a method analogous to the use of inhibitors labelled with heavy atoms to solve crystal structures of enzymes. This derivative exploits the specific binding between pertussis toxin and terminal sialic acid residues on receptor glycoproteins. Difference Patterson maps yielded heavy-atom sites which refined with good statistics, indicating that the protein probably does not undergo a conformational change on receptor binding. Mercuric analogs of other monosaccharides should be easily obtainable using the same synthetic strategy, suggesting a general method for derivatizing crystals of carbohydrate-binding proteins.
Transgenic Modeling of Transforming Growth Factor-β1: Role of Apoptosis in Fibrosis and Alveolar Remodeling (2006)

Inflammation and tissue remodeling with pathologic fibrosis are common consequences of Th2 responses in the lung and other organs. Interleukin (IL)-13 and transforming growth factor-beta1 (TGF-beta(1)) are frequently coexpressed in these responses and are believed to play important roles in the pathogenesis of Th2-induced pathologies. To shed light on the mechanisms of these responses, overexpression transgenic approaches were used to selectively target each of these cytokines to the murine lung. IL-13 proved to be a potent stimulator of eosinophilic inflammation, mucus metaplasia, tissue fibrosis, and alveolar remodeling. CC chemokines, specific chemokine receptors (CCR2, CCR1), adenosine metabolism, vascular endothelial growth factor, and IL-11 contributed to the genesis of these responses. IL-13 also induced tissue fibrosis, at least in part, via its ability to induce and activate TGF-beta(1). In the TGF-beta(1) transgenic mouse, epithelial apoptosis preceded the onset of tissue fibrosis and alveolar remodeling. In addition, chemical (Z-VAD-fmk) and genetic (null mutations of early growth response gene 1) interventions blocked apoptosis and ameliorated TGF-beta(1)-induced fibrosis and alveolar restructuring. These studies define an IL-13-TGF-beta(1) pathway of tissue remodeling that regulates inflammation, mucus metaplasia, apoptosis, vascular responses, and fibrosis in the lung. They also highlight the intimate relationship between apoptosis and fibrosis induced by TGF-beta(1). By defining the complexities of this pathway, these studies highlight sites at which therapies can be directed to control these important responses.