gebhart/patrepeval huggingface dataset:
Adenosine deaminase and adenylate deaminase: comparative kinetic studies with transition state and ground state analog inhibitors (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAdenosine deaminase and adenylate deaminase: comparative kinetic studies with transition state and ground state analog inhibitorsCarl Frieden, Linda C. Kurz, and Helen R. GilbertCite this: Biochemistry 1980, 19, 23, 5303–5309Publication Date (Print):November 11, 1980Publication History Published online1 May 2002Published inissue 11 November 1980https://pubs.acs.org/doi/10.1021/bi00564a024https://doi.org/10.1021/bi00564a024research-articleACS PublicationsRequest reuse permissionsArticle Views279Altmetric-Citations88LEARN 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 Get e-Alerts
Lowering Risk without Lowering Cholesterol: Implications for National Cholesterol Policy (1996)

Current recommendations for the treatment of hypercholesterolemia include drug therapy for persons at sufficiently elevated risk for coronary heart disease. However, no guidelines incorporate the effects of alternative interventions that decrease risk for coronary heart disease but are not used specifically to alter blood lipids. We did a simulation study to estimate the number of hypercholesterolemic adults who would continue to exceed a high-risk threshold after receiving aspirin, antihypertensive medication, and estrogen-replacement therapy. We found that of all persons who are currently candidates for hypolipidemic medication because they are at high risk for coronary heart disease, 6 to 8 million would no longer have this therapy recommended if the abilities of alternative interventions to reduce risk were considered. Pharmaceutical cost savings associated with alternative interventions range from $3 to $4 billion per year. Current guidelines should be revised to account for this effect.
131I Radioconjugated Antibodies for the Locoregional Radioimmunotherapy of High-grade Malignant Glioma: Phase I and II Study (1999)

Locoregional radioimmunotherapy (LR-RIT) was administered to 111 patients (20 were recruited in a phase I and 91 in a phase II study) with malignant gliomas: 1 patient with oligodendroglioma, 7 patients with anaplastic oligodendroglioma, 2 with grade II astrocytoma, 10 with anaplastic astrocytoma and 91 with glioblastoma, amounting to 58 newly diagnosed and 53 recurrent tumours. The 131I-labelled monoclonal antibodies BC-2 and BC-4 were used in order to recognize stromal and intracellular glycoprotein tenascin, an antigen present particularly in glioblastoma. The patients were enrolled between February 1990 and December 1997 after conventional therapy. The radiopharmaceutical was injected directly into the tumour site. Sequential scintigraphies demonstrated a high and enduring uptake in the tumour. The mean irradiation dose in the tumour was 300 Gy per cycle. In the group of 74 phase II glioblastoma patients the clinical responses were as follows: 10 patients with stable disease (SD), 9 with partial responses (PR), 23 with no evidence of disease (NED) and 1 patient with complete response (CR). The median survival was 19 months. The response rate (CR + PR + NED) was 17.8% for those patients with bulky lesions, with a median survival of 17 months, but 66.6% for patients with small lesions, with a median survival of 25 months. Better outcomes were recorded in cases with less aggressive diseases: oligodendroglioma, anaplastic oligodendroglioma and anaplastic astrocytoma. We conclude that fractionated LR-RIT can be safely performed, with promising results especially in patients with minimal disease.
Polymeric Systems for Controlled Drug Release (1999)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolymeric Systems for Controlled Drug ReleaseKathryn E. Uhrich, Scott M. Cannizzaro, Robert S. Langer, and Kevin M. ShakesheffView Author Information Department of Chemistry, Rutgers University, Piscataway, New Jersey 08854-8087 Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Department of Pharmaceutical Science, University of Nottingham, Nottingham NG7-2RD, U.K. Cite this: Chem. Rev. 1999, 99, 11, 3181–3198Publication Date (Web):October 26, 1999Publication History Received3 February 1999Revised30 June 1999Published online26 October 1999Published inissue 10 November 1999https://pubs.acs.org/doi/10.1021/cr940351uhttps://doi.org/10.1021/cr940351uresearch-articleACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views24537Altmetric-Citations2235LEARN 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:Drug delivery,Monomers,Peptides and proteins,Pharmaceuticals,Polymers Get e-Alerts
Aberrant Cell Cycle and Apoptotic Changes Characterise Severe Influenza A Infection – A Meta-Analysis of Genomic Signatures in Circulating Leukocytes (2011)

Influenza A infection is a global disease that has been responsible for four pandemics over the last one hundred years. However, it remains poorly understood as to why some infected individuals succumb to life threatening complications whilst others recover and are relatively unaffected. Using gene-expression analysis of circulating leukocytes, here we show that the progression towards severe influenza A infection is characterised by an abnormal transcriptional reprogramming of cell cycle and apoptosis pathways. In severely infected humans, leukocyte gene-expression profiles display opposing cell cycle activities; an increased aberrant DNA replication in the G(1)/S phase yet delayed progression in the G(2)/M phase. In mild infection, cell cycle perturbations are fewer and are integrated with an efficient apoptotic program. Importantly, the loss of integration between cell cycle perturbations and apoptosis marks the transition from a mild viral illness to a severe, life threatening infection. Our findings suggest that circulating immune cells may play a significant role in the evolution of the host response. Further study may reveal alternative host response factors previously unrecognized in the current disease model of influenza.
PSMA expression in the neo-vasculature of solid tumors (2008)

2181 Background:  Prostate Specific Membrane Antigen (PSMA) is a type II transmembrane metallo-peptidase overexpressed in prostate cells. Initially thought to be highly specific for prostate and cancer, recent evidence suggest that PSMA is also expressed in endothelial cells associated with non-prostatic solid tumors. Thus far only a limited number of solid tumors have been investigated in detail for PSMA expression in the neovasculature. Because of its potential use as a vascular targeting molecule we determined the expression of PSMA in a representative collection of a variety of solid tumor entities including gastric, colo-rectal, renal-cell and urothelial carcinoma.  Experimental design:  PSMA expression was determined by immunohistochemistry in formalin-fixed paraffin-embedded tissue sections of 119 cases of primary gastric cancer, 130 cases of primary colorectal cancers, 19 cases of renal cell carcinoma (RCC), 18 cases of urothelial carcinoma of the bladder and 23 urothelial carcinoma of the renal pelvis. Immunoreactivity was scored semiquantitatively based on staining intensity and distribution. Expression data were correlated with clinicopathological information.  Results: PSMA expression was detected in tumor-associated neo-vasculature of 79 of 119 (66.4%) of gastric and 110 of 130 (84.6%) of colorectal cancers. Interestingly, 15 (12%) colorectal cancer samples showed also a strong epithelial PSMA staining. There was a trend for high grade tumors to higher PSMA expression (Spearman r = 0.18, P = 0.046) and men generally had higher PSMA level than women (Spearman r = 0.23, P = 0.009) in colorectal cancers. 17 of 19 (89 %) samples of RCC showed strong staining for PSMA in tumor-associated endothelial cells. Non-clearcell carcinoma samples showed no PSMA expression. Thirty-six of fourty-two (88%) urothelial carcinomas exhibited detectable PSMA expression.  Conclusions:  We confirm previous reports on the tumor specific expression of PSMA in neo-vasculature in a large sample collection of solid malignancies. PSMA is frequently expressed in the tumorvasculature but expression levels vary significantly within one tumor entity and between different entities. Further studies investigating the biological significance and regulation of PSMA expression are therefore needed. Because of its highly tumor-specific expression and its unique biological characteristics PSMA represents an interesting target for anti-angiogenic therapies in solid tumors.
Metabolic shifts do not influence the glycosylation patterns of a recombinant fusion protein expressed in BHK cells (2000)

BHK-21 cells expressing a human IgG-IL2 fusion protein, with potential application in tumor-targeted therapy, were grown under different nutrient conditions in a continuous system for a time period of 80 days. At very low-glucose (< 0.5 mM) or glutamine (< 0.2 mM) concentrations, a shift toward an energetically more efficient metabolism was observed. Cell-specific productivity was maintained under metabolically shifted growth conditions and at the same time an almost identical intracellular ATP content, obtained by in vivo 31P NMR experiments, was observed. No significant differences in the oligosaccharide structures were detected from the IgG-IL2 fusion protein preparations obtained by growing cells under the different metabolic states. By using oligosaccharide mapping and MALDI/TOF-MS, only neutral diantennary oligosaccharides with or without core α1-6-linked fucose were detected that carried no, one or two β1-4-linked galactose. Although the O-linked oligosaccharide structures that are present in the IL2 moiety of the protein were studied with less detail, the data obtained from the hydrazinolysis procedure point to the presence of the classical NeuAcα2-3Galβ1-3GalNAc structure. Here, it is shown that under different defined cellular metabolic states, the quality of a recombinant product in terms of O- and N-linked oligosaccharides is stable, even after a prolonged cultivation period. Moreover, unaffected intracellular ATP levels under the different metabolic states were observed. © 2000 John Wiley & Sons, Inc. Biotechnol Bioeng 69: 129–139, 2000.
Immortalization and Transformation of Human Cells (2002)

The disruption of homeostatic mechanisms that regulate normal cell growth and proliferation is a hallmark of cancer. Experimentally, many of the same genetic changes that lead to abnormal cell proliferation conspire to confer replicative immortality upon cells in culture. Correspondingly, several lines of evidence implicate cellular immortalization as a prerequisite for cell transformation. Recently much progress has been made in elucidating the cellular machinery that regulates cell lifespan. This review summarizes these recent advances in our understanding of these molecular mechanisms that contribute to human cell immortalization and transformation.
Clinical significance of low expression of Prostasin mRNA in human gastric cancer (2008)

Prostasin mRNA expression was frequently down-regulated in gastric cancer. Loss of expression might be regulated by epigenetic factors, contributing to the shorter survival. Reduced Prostasin mRNA expression might be a novel indicator for biological aggressiveness in gastric cancer.
LC2, theChlamydomonasHomologue of thetComplex-encoded Protein Tctex2, Is Essential for Outer Dynein Arm Assembly (1999)

Tctex2 is thought to be one of the distorter genes of the mouse t haplotype. This complex greatly biases the segregation of the chromosome that carries it such that in heterozygous +/t males, the t haplotype is transmitted to >95% of the offspring, a phenomenon known as transmission ratio distortion. The LC2 outer dynein arm light chain of Chlamydomonas reinhardtii is a homologue of the mouse protein Tctex2. We have identified Chlamydomonas insertional mutants with deletions in the gene encoding LC2 and demonstrate that the LC2 gene is the same as the ODA12 gene, the product of which had not been identified previously. Complete deletion of the LC2/ODA12 gene causes loss of all outer arms and a slow jerky swimming phenotype. Transformation of the deletion mutant with the cloned LC2/ODA12 gene restores the outer arms and rescues the motility phenotype. Therefore, LC2 is required for outer arm assembly. The fact that LC2 is an essential subunit of flagellar outer dynein arms allows us to propose a detailed mechanism whereby transmission ratio distortion is explained by the differential binding of mutant (t haplotype encoded) and wild-type dyneins to the axonemal microtubules of t-bearing or wild-type sperm, with resulting differences in their motility.
Structural determinants of the partial agonist‐inverse agonist properties of 6′‐azidohex‐2′‐yne‐Δ8‐tetrahydrocannabinol at cannabinoid receptors (1999)

1. We have extended previous investigations of four analogues of Delta8-tetrahydrocannabinol (Delta8-THC): 6'-azidohex-2'-yne-Delta8-THC (O-1184), 6'-azidohex-cis-2'-ene-Delta8-THC (O-1238) and octyl-2'-yne-Delta8-THC (O-584) and its 1-deoxy-analogue (O-1315). 2. O-1184, O-1238 and O-584 displaced [3H]-CP55940 from specific binding sites on Chinese hamster ovary (CHO) cell membranes expressing CB1 or CB2 cannabinoid receptors, with pKi values of 8.28 to 8.45 (CB1) and 8.03 to 8.13 (CB2). The pKi values of O-1315 were significantly less, 7.63 (CB1) and 7.01 (CB2). 3. All the analogues inhibited forskolin-stimulated cyclic AMP production by CB1-transfected CHO cells (pEC50=9.16 to 9.72). Only O-1238 behaved as a full agonist in this cell line. 4. In mouse vasa deferentia, O-1238 inhibited electrically-evoked contractions (pEC50=10.18 and Emax=70.5%). Corresponding values for O-1184 were 9.08 and 21.1% respectively. At 1 nM, O-1184 produced surmountable antagonism of the cannabinoid receptor agonist, CP55940. However, at 0.1 nM, O-1184 did not attenuate CP55940-induced inhibition of cyclic AMP production by CB1-transfected CHO cells. 5. In CB2-transfected CHO cells, cyclic AMP production was inhibited by CP55940 (pEC50=8.59), enhanced by O-1184 and O-584 (pEC50=8.20 and 6.86 respectively) and not significantly affected by O-1238 or O-1315. 6. At 100 nM, O-1184 and O-1238 produced surmountable antagonism of CP55940 in CB2 cells, decreasing the pEC50 of CP55940 from 8.61 to 7.42 (O-1184) or from 8. 54 to 7.44 (O-1238). 7. These data support the hypothesis that increasing the degree of unsaturation of the aliphatic side-chain of Delta8-THC analogues has little effect on CB1 or CB2 receptor affinity but can reduce CB1 receptor efficacy and reverse the direction of responses elicited at CB2 receptors.
Dynamic Contrast-Enhanced Magnetic Resonance Imaging Rapidly Indicates Vessel Regression in Human Squamous Cell Carcinomas Grown in Nude Mice Caused by VEGF Receptor 2 Blockade with DC101 (2004)

The purpose of our study was the investigation of early changes in tumor vascularization during antiangiogenic therapy with the vascular endothelial growth factor (VEGF) receptor 2 antibody (DC101) using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). Subcutaneous heterotransplants of human skin squamous cell carcinomas in nude mice were treated with DC101. Animals were examined before and repeatedly during 2 weeks of antiangiogenic treatment using Gd-DTPA-enhanced dynamic T1-weighted MRI. With a two-compartment model, dynamic data were parameterized in "amplitude" (increase of signal intensity relative to precontrast value) and k(ep) (exchange rate constant). Data obtained by MRI were validated by parallel examinations of histological sections immunostained for blood vessels (CD31). Already 2 days after the first DC101 application, a decrease of tumor vascularization was observed, which preceded a reduction of tumor volume. The difference between treated tumors and controls became prominent after 4 days, when amplitudes of treated tumors were decreased by 61% (P =.02). In line with change of microvessel density, the decrease in amplitudes was most pronounced in tumor centers. On day 7, the mean tumor volumes of treated (153 +/- 843 mm(3)) and control animals (596 +/- 384 mm(3)) were significantly different (P =.03). After 14 days, treated tumors showed further growth reduction (83 +/- 93 mm(3)), whereas untreated tumors (1208 +/- 822 mm(3)) continued to increase (P =.02). Our data underline the efficacy of DC101 as antiangiogenic treatment in human squamous cell carcinoma xenografts in nude mice and indicate DCE MRI as a valuable tool for early detection of treatment effects before changes in tumor volume become apparent.
Direct Alignment and Patterning of Silver Nanowires by Electrohydrodynamic Jet Printing (2014)

Highly aligned and patterned silver nanowires (Ag NWs) are investigated by using electrohydrodynamic (EHD) jet printing. Interaction between the flow field and the electric field as well as the mechanical stretching of the fiber jet can successfully align the Ag NWs inside the jet fiber. This technique can be applied in fabricating 1D nanostructures-based printed micro/nanoscale devices.
Bactericidal Action of the Reactive Species Produced by Gas-Discharge Nonthermal Plasma at Atmospheric Pressure: A Review (2006)

Biological decontamination using a nonthermal gas discharge at atmospheric pressure in air is the subject of significant research effort at this time. The mechanism for bacterial deactivation undergoes a lot of speculation, particularly with regard to the role of ions and reactive gas species. Two mechanisms have been proposed: electrostatic disruption of cell membranes and lethal oxidation of membrane or cytoplasmic components. Results show that death is accompanied by cell lysis and fragmentation in Gram-negative bacteria but not Gram-positive species, although cytoplasmic leakage is generally observed. Gas discharges can be a source of charged particles, ions, reactive gas species, radicals, and radiation (ultraviolet, infrared, and visible), many of which have documented biocidal properties. The individual roles played by these in decontamination are not well understood or quantified. However, the reactions of some species with biomolecules are documented otherwise in the literature. Oxidative stress is relatively well studied, and it is likely that exposure to gas discharges in air causes extreme oxidative challenge. In this paper, a review is presented of the major reactive species generated by nonthermal plasma at atmospheric pressure and the known reactions of these with biological molecules. Understanding these mechanisms becomes increasingly important as plasma-based decontamination and sterilization devices come closer to a wide-scale application in medical, healthcare, food processing, and air purification applications. Approaches are proposed to elucidate the relative importance of reactive species.
Pilot study of nebulized surfactant therapy for neonatal respiratory distress syndrome (2000)

Thirty‐four spontaneously breathing newborns with respiratory distress syndrome (RDS) requiring nasal continuous positive airway pressure (CPAP) and an arterial‐to‐alveolar oxygen tension ratio (a/A PO 2 ) of 0.15‐0.22 were randomized to treatment with nebulized surfactant (Curosurf®) or to serve as controls. All children were first supported by nasal CPAP according to normal clinical routines. Surfactant was administered using a modified Aiolos® nebulizer, and a total of 480 mg was aerosolized in each case. The control group received no nebulized material, but had the same CPAP support. Acid‐base status and a/A PO 2 were determined at regular intervals before, during and after surfactant administration. Both groups included in the study were similar with regard to gestational age, birthweight, steroids given before birth, sex and Apgar scores as well as a/A PO 2 when entering the study. There were no significant differences between the groups in a/A PO 2 1‐12 h after randomization, number of infants needing mechanical ventilation, time on ventilator or CPAP. Two children in the treated group developed bronchopulmonary dysplasia. No side effects of the surfactant therapy were noted. No beneficial effects of aerosolized surfactant were demonstrated in our trial, contrary to data from animal experiments. This finding probably reflects differences in administration techniques. Our findings do not justify large clinical trials with the same protocol. Further work is needed to optimize delivery of aerosolized surfactant to the neonatal lung in clinical practice.
Interleukin‐31: its role in canine pruritus and naturally occurring canine atopic dermatitis (2013)

Canine IL-31 induced pruritic behaviours in dogs. Canine IL-31 was detected in the majority of dogs with naturally occurring AD, suggesting that this cytokine may play an important role in pruritic allergic skin conditions, such as atopic dermatitis, in this species.