bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and clinical effects of mono‐l‐aspartyl chlorin e6 (NPe6) photodynamic therapy in adult patients with primary or secondary cancer of the skin and mucosal surfaces
Authors: Chan Andrew L. , Juarez Maya , Allen Roblee , Volz William , Albertson Timothy 
Published: March 2005

Background/Purpose: Mono‐l‐aspartyl chlorin e6 (NPe6) is a photosensitizer that exhibits chemical purity, absorption at 664 nm wavelength and may be useful in photodynamic therapy (PDT).Methods: This open label phase I clinical trial at the University of California, Davis Medical Center examined the pharmacokinetic properties of Npe6 and clinical response to PDT with this photosensitizer. A single intravenous dose of Npe6 was administered to 14 cancer patients with superficial malignancies (basal cell carcinoma=22 lesions, squamous cell cancer=13 lesions, papillary carcinoma=14 lesions). Patients received one of five ascending doses (0.5 mg/kg (n=4), 1.0 mg/kg (n=3), 1.65 mg/kg (n=3), 2.5 mg/kg (n=3), or 3.5 mg/kg (n=1)) 4–8 h prior to light activation. The total light dose (range 25–200 J/cm2) depended on the tumor shape and size. Light was delivered using an argon‐pumped tunable dye laser. Serum NPe6 concentrations were measured over a 28‐day period. The toxicity and cutaneous clinical efficacy of NPe6 were observed.Results: Four weeks post‐PDT, 20 of 22 basal cell carcinoma tumors (91%) showed a complete response. Eighteen of 27 other malignant cutaneous tumors showed a complete (n=15/27, 56%) or partial (n=3/27, 11%) response. Fewer non‐responders were seen at an Npe6 dose level of 1.65 mg/kg or higher. Only 2 of 14 patients experienced an adverse event that was definitely related to NPe6 administration. Photosensitivity resolved within 1 week of NPe6 dosing in 12 of 14 patients. Analysis of serum levels of 11 individual patients indicated that a two‐compartment model with a residual phase best fits the data. The mean α, β, and terminal half‐lives were 8.63±2.92, 105.90±37.59 and 168.11±53.40 h (±1 SD), respectively. The observed mean volume of distribution was 5.94±2.55 l, and the mean clearance was 0.0394±0.0132 l/h. These values were independent of the dose administered.Conclusion: The photosensitizer, NPe6, was well tolerated with minimal phototoxic side effects, and demonstrated preliminary efficacy against cutaneous malignancies.
Self-regulated active galactic nuclei heating in elliptical galaxies
Authors: Kawata D. , Gibson B. K. 
Published: March 2005

Abstract
We study the effect of active galactic nuclei (AGN) heating on the chemodynamical evolution of elliptical galaxies and their X-ray and optical properties using high-resolution Λ-dominated cold dark matter cosmological simulations. Our model considers an AGN as being ‘active’ when a convergent gas inflow condition exists within the nucleus of a galaxy; otherwise, the AGN is assumed to remain dormant. This induces a self-regulated activity for the AGN, the result of which leads to a stable hot corona and the suppression of significant late-time star formation – characteristics not encountered in traditional chemodynamical models of ellipticals. These properties of our AGN heating model lead to a system consistent with both the X-ray and optical properties of comparable elliptical galaxies.
Specific Inhibitory Action of Anisodamine against a Staphylococcal Superantigenic Toxin, Toxic Shock Syndrome Toxin 1 (TSST-1), Leading to Down-Regulation of Cytokine Production and Blocking of TSST-1 Toxicity in Mice
Authors: Nakagawa Saori , Kushiya Koji , Taneike Ikue , Imanishi Ken'ichi , Uchiyama Takehiko , Yamamoto Tatsuo 
Published: March 2005

ABSTRACTToxic shock syndrome toxin 1 (TSST-1), produced byStaphylococcus aureus(including methicillin-resistantS. aureus), is a superantigenic toxin responsible for toxic shock syndrome as well as neonatal TSS-like exanthematous disease. TSST-1 exhibits its deleterious effects by leading to the abnormal proliferation of, e.g., Vβ2+T cells and overproduction of proinflammatory cytokines. In the present study we examined the inhibitory effect of a Chinese herbal extract, anisodamine, on TSST-1 using human peripheral blood mononuclear cells (PBMCs). Anisodamine inhibited the production of proinflammatory cytokines better than interleukin-10 (an anti-inflammatory cytokine). The inhibitory effect of anisodamine was greater than that of any tropane alkaloid examined. Anisodamine acted directly on both monocytes and T cells in human PBMCs, and the effect was confirmed at the transcriptional level. Inhibition of NF-κB activation was also demonstrated. In contrast, no significant inhibition of Vβ2+T-cell proliferation was observed. In mice injected with TSST-1, anisodamine treatment significantly decreased serum proinflammatory cytokine levels and prevented TSST-1-induced death. These results suggest that anisodamine specifically acts against the production of cytokines (inflammatory cytokines in particular) and not against Vβ2+T-cell proliferation and that anisodamine may have a beneficial effect on TSST-1-associated disease.
Interleukin-18 Primes the Oxidative Burst of Neutrophils in Response to Formyl-Peptides: Role of Cytochrome b558 Translocation and N-Formyl Peptide Receptor Endocytosis
Authors: Elbim Carole , Guichard Cécile , Dang Pham M. C. , Fay Michèle , Pedruzzi Eric , Demur Hélène , Pouzet Cécile , El Benna Jamel , Gougerot-Pocidalo Marie-Anne 
Published: March 2005

ABSTRACTUsing flow cytometry, we observed that interleukin-18 (IL-18) primed human neutrophils (PMNs) in whole blood to produce superoxide anion (O2°−) in response to N-formyl peptide (fMLP) stimulation, whereas IL-18 alone had no significant effect. In contrast to tumor necrosis factor alpha (TNF-α), which is a cytokine known to strongly prime O2°−production, IL-18 did not induce either p47phoxphosphorylation or its translocation from the cytosol to the plasma membrane. However, IL-18 increased PMN degranulation, as shown by increased levels of cytochrome b558 and CD11b expression at the PMN surface. Moreover, addition of IL-18 to whole blood for 45 min reduced the ability of PMNs to bind to fMLP, suggesting endocytosis of fMLP receptors, as visualized by confocal microscopy. 2,3-Butanedione 2-monoxime, which inhibits endosomal recycling of plasma membrane components back to the cell surface, concomitantly accentuated the diminution of fMLP binding at the PMN surface and increased IL-18 priming of O2°−production by PMNs in response to fMLP. This suggests that fMLP receptor endocytosis could account, at least in part, for the priming of O2°−production. In addition, genistein, a tyrosine kinase inhibitor, and SB203580, a p38 mitogen-activated protein kinase (p38MAPK) inhibitor, completely reversed the decreased level of fMLP binding and increased the level of CD11b expression after IL-18 treatment. Flow cytometric analysis of intact PMNs in whole blood showed that IL-18 increased p38MAPK phosphorylation and tyrosine phosphorylation. In particular, IL-18 induced phosphorylation of focal adhesion kinase (p125FAK), which has been implicated in cytoskeleton reorganization. Taken together, our findings suggest several mechanisms that are likely to regulate cytokine-induced priming of the oxidative burst in PMNs in their blood environment.
Impaired Accessory Cell Function in a Human Dendritic Cell Line after Human Immunodeficiency Virus Infection
Authors: Beuria Prarthana , Chen Houchu , Timoney Michael , Sperber Kirk 
Published: March 2005

ABSTRACTWe generated human dendritic cell (DC) hybridoma cell lines by fusing HGPRT-deficient promonocytic U937 cells with immature DCs obtained by culturing peripheral blood monocytes with interleukin-4 (IL-4; 1,000 U/ml) and granulocyte-macrophage colony-stimulating factor (100 U/ml) for 7 days and mature DCs by treatment with tumor necrosis factor alpha (12.5 μg/ml) for 3 days. Only one fusion with immature DCs was successful and yielded four cell lines—HB-1, HB-2, HB-3, and HB-9—with an overall fusion efficiency of 0.0015%. The cell lines were stable in long-term culture, displayed morphological features typical of DCs, and expressed distinct class I and class II molecules not present on U937 (A*031012, B*51011, Cw*0701, DRB3*01011 52, and DR5*01011). A representative cell line, HB-2, that expressed DC markers including CD83, CD80 and CD86 could be induced to produce IL-12 through CD40 stimulation. After human immunodeficiency virus (HIV) infection, there was impairment of antigen-presenting cell (APC) function, which was manifested by an inability to stimulate allogeneic T-cell responses. There was no change in expression of major histocompatibility complex class I and class II antigens, CD83, CD40, CD4, CD11c, CD80, CD86, CD54, and CD58, or IL-12 production in the HIV-infected HB-2 cells. The HIV-infected HB-2 cells induced T-cell apoptosis in the cocultures. T-cell proliferation could be partially restored by using ddI, indinivir, and blocking anti-gp120 and anti-IL-10 antibodies. Our data suggest that there are multiple mechanisms that DCs use to inhibit T-cell responses in HIV-infected patients. The HB-2 cell line could be a useful model system to study APC function in HIV-infected DCs.
Use of the COOH Portion of the Nucleocapsid Protein in an Antigen-Capturing Enzyme-Linked Immunosorbent Assay for Specific and Sensitive Detection of Severe Acute Respiratory Syndrome Coronavirus
Authors: Qiu Maofeng , Wang Jin , Wang Hongxia , Chen Zeliang , Dai Erhei , Guo Zhaobiao , Wang Xiaoyi , Pang Xin , Fan Baoxing , Wen Jie , Wang Jian , Yang Ruifu 
Published: March 2005

ABSTRACT
Antibody detection with a recombinant COOH portion of the severe acute respiratory syndrome (SARS) coronavirus nucleocapsid (N) protein, N13 (amino acids 221 to 422), was demonstrated to be more specific and sensitive than that with the full-length N protein, and an N13-based antigen-capturing enzyme-linked immunosorbent assay providing a convenient and specific test for serodiagnosis and epidemiological study of SARS was developed.
Modulation of endothelial cell migration by extracellular nucleotides
Authors: Erb Laurie , Koziak Katarzyna , Jarzyna Robert , Wink Marcia R. , Guckelberger Olaf , Blusztajn Krzysztof J. , Trinkaus-Randall Vickery , Weisman Gary A. , Robson Simon C. , Kaczmarek Elzbieta 
Published: March 2005

SummaryExtracellular nucleotides bind to type-2 purinergic/pyrimidinergic (P2) receptors that mediate various responses, such as cell activation, proliferation and apoptosis, implicated in inflammatory processes. The role of P2 receptors and their associated signal transduction pathways in endothelial cell responses has not been fully investigated. Here, it is shown that stimulation of human umbilical vein endothelial cells (HUVEC) with extracellular ATP or UTP increased intracellular free calcium ion concentrations ([Ca2+]i), induced phosphorylation of focal adhesion kinase (FAK), p130cas and paxillin, and caused cytoskeletal rearrangements with consequent cell migration. Furthermore, UTP increased migration of HUVEC in a phosphatidylinositol 3-kinase (PI3-K)-dependent manner. BAPTA or thapsigargin inhibited the extracellular nucleotide-induced increase in [Ca2+]i, a response crucial for both FAK phosphorylation and cell migration. Furthermore, long-term exposure of HUVEC to ATP and UTP, agonists of the G protein-coupled P2Y2 and P2Y4 receptor subtypes, caused upregulation of αv integrin expression, a cell adhesion molecule known to directly interact with P2Y2 receptors. Our results suggest that extracellular nucleotides modulate signaling pathways in HUVEC influencing cell functions, such as cytoskeletal changes, cellular adhesion and motility, typically associated with integrin-activation and the action of growth factors. We propose that P2Y2 and possibly P2Y4 receptors mediate those responses that are important in vascular inflammation, atherosclerosis and angiogenesis.
Transcriptional control of cell density dependent regulation of matrix metalloproteinase and TIMP expression in breast cancer cell lines
Authors: Vené Roberta , Iancu Cristina M. , Pfeffer Ulrich , Mayer Barbara , Noonan Douglas , Albini Adriana , Jochum Marianne , Nerlich Andreas G. , Bachmeier Beatrice E. 
Published: March 2005

SummaryOur recent studies on breast carcinoma cell lines with differing tumorigenicity / invasiveness (MCF-7< MDA-MB-468< MDAMB-231< MDA-MB-435) had shown significantly decreasing expression levels of MMPs-1,-2,-3,-8,-9,-10,-11 and –13 with increasing cell density while the levels of TIMP-1 and –2 increased. This correlated well with a lower invasiveness of confluent cells. In the present study, we extend our in vitro studies on three-dimensional cultures of breast cancer cell lines MCF-7 and MDAMB-435 and the transcriptional control of MMP and TIMP-expression in two-dimensional cultures of MDA-MB-231 and –435 cells. The tumor spheroid model showed that MMP expression and proteolytic activity were considerably higher in loosely structured tumor groups as compared to densely growing “compact” cell complexes. These data suggested that cell density regulates MMP and TIMP transcription and therefore, we tested whether AP-1, NFκB and CRE are involved in this process. Gene silencing of c-jun in sparse cultures had an inhibitory effect on MMP-3,–9 and –13 expression, on proteolytic activity as well as on the invasive potential of the cells, thus confirming a role for AP-1. TIMP-1, and –2 expression was up-regulated as compared to control cells. Consistent with this, overexpression of c-jun and c-fos in confluent breast cancer cell lines leads to up-regulation of MMP expression, proteolytic activity and invasion as well as down-regulation of TIMP-1. In summary, we provide evidence that cell density influences the invasive potential of tumor cells via regulation of MMPs and TIMPs by AP-1, NFκB and CRE transcription factors. Overexpression of MMPs in sparse cultures could help explain early dissemination of potentially metastatic cells.
Thrombolytic agents
Authors: Lijnen Roger H. , Collen Désiré 
Published: March 2005

SummaryThrombolytic agents are plasminogen activators that convert the zymogen plasminogen to the active enzyme plasmin, which degrades fibrin. Elucidation of the molecular mechanism of physiological fibrinolysis opened up a new era of fibrin-specific thrombolysis. Fibrin-specific plasminogen activators, including tissue-type plasminogen activator (t-PA), single-chain urokinase-type plasminogen activator (scu-PA) and staphylokinase (Sak), preferentially activate fibrin-associated plasminogen. Generated plasmin remains associated with fibrin, where it is protected from rapid inhibition and can efficiently degrade fibrin, avoiding systemic activation of the fibrinolytic system. Following a decade of clinical investigation t-PA and variants thereof are routinely used for treatment of patients with thromboembolic disease.
Transcriptional and posttranscriptional regulation of the plasminogen activator system
Authors: Medcalf Robert L. , Muñoz-Cánoves Pura , Nagamine Yoshikuni 
Published: March 2005

SummaryThe core protein components of the plasminogen activator (PA) system are two plasminogen activators, two plasminogen activator inhibitors and a urokinase type plasminogen activator-specific cell surface receptor. Various types of biological regulation are exerted through the interplay of these components mutually and with extracellular matrix proteins and cell membrane proteins, with or without involving proteolytic activity. Reflecting these diverse biological roles, the level and activity of each component of the PA system is under the control of a variety of regulatory mechanisms. The expression level of a protein reflects the level of the corresponding mRNA, which is essentially the net result of de novo synthesis, i.e. transcription, and degradation. Many recent studies have shown that the regulation of mRNA stability is dynamic and cell specific. Accordingly, we are learning that the mRNAs of the PA system are also the subject of diverse regulatory mechanisms. In this short review, we summarize current understanding of the transcriptional and mRNA-stability regulation of the PA system.
Structure and function of the plasminogen/plasmin system
Authors: Ploplis Victoria A. , Castellino Francis J. 
Published: March 2005

SummaryActivation of the fibrinolytic system is dependent on the conversion of the plasma zymogen, plasminogen (Pg), to the serine protease plasmin (Pm) by the physiological activators urokinase-type Pg activator (uPA) or tissue-type plasminogen activator (tPA). The primary in vivo function of Pm is to regulate vascular patency by degrading fibrin-containing thrombi. However, the identification of Pg/Pm receptors and the ability of Pm to degrade other matrix proteins have implicated Pm in other functions involving degradation of protein barriers, thereby mediating cell migration, an important event in a number of normal e.g., embryogenesis, wound healing, angiogenesis, and pathological, e.g., tumor growth and dissemination, processes. Prior to the development of Pg-deficient mice, much of the evidence for its role in other biological events was based on indirect studies. With the development and characterization of these mice, and ability to apply challenges utilizing a number of animal models that mimic the human condition, a clearer delineation of Pg/Pm function has evolved and has contributed to an understanding of mechanisms associated with a number of pathophysiological events.
Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease
Authors: Dellas Claudia , Loskutoff David J. 
Published: March 2005

SummaryAlthough plasminogen activator inhibitor 1 (PAI-1) is one of the primary regulators of the fibrinolytic system, it also has dramatic effects on cell adhesion, detachment and migration. PAI-1 also differs from other serine protease inhibitors (serpins) in that it is a trace protein in plasma, it has a short half-life in vivo, its synthesis is highly regulated, and it binds to the adhesive glycoprotein vitronectin (VN) with high affinity and specificity. These unique and diverse properties of PAI-1 probably account for the many observations in the literature that correlate abnormalities in PAI-1 gene expression with a variety of pathological conditions. In this review, we discuss the discovery, origin, properties and regulation of PAI-1, and then speculate about its potential role in vascular disease, fibrosis, obesity and the metabolic syndrome, and cancer.
The Scaling and Structure of the Estuarine Bottom Boundary Layer
Authors: Stacey Mark T. , Ralston David K. 
Published: March 2005

Abstract
A two-week dataset from a partially and periodically stratified estuary quantifies variability in the turbulence across the tidal and spring–neap time scales. These observations have been fit with a two-parameter model of the Reynolds stress profile, which produces estimates of the time variation of the bottom boundary layer height and the friction velocity. Conditions at the top of the bottom boundary layer indicate that the dynamics governing the development of the estuarine bottom boundary layer are different on ebb tides than on flood tides. The asymmetry in the flow is explained by consideration of the strain-induced buoyancy flux, which is stabilizing on ebb tides and destabilizing on flood tides. Based on these observations, a scaling approach to estimating estuarine bottom boundary layer parameters (height and friction velocity) is presented, which includes a modified Monin–Obukhov length scale to account for the horizontal buoyancy flux created by the sheared advection. Comparison with the observations of boundary layer height and friction velocity suggests that this approach may be successful in predicting bottom boundary layer parameters in estuaries and coastal regions with significant horizontal buoyancy fluxes. Comparison between the strain-induced buoyancy flux and shear production indicates that the straining of the density field is an important contributor to the turbulent kinetic energy budget and creates an asymmetry in turbulent energy between ebb and flood tides. It appears that the structure of the turbulence, specifically the ratio of the Reynolds stress to the turbulent energy, is also modified by tidal straining, further accentuating the ebb–flood asymmetries.
High Temporal Resolution Path-Average Rain Gauge with 50-GHz Band Microwave
Authors: Minda Haruya , Nakamura Kenji 
Published: March 2005

Abstract
Rain radar measures instantaneous spatial-average rainfall, while conventional rain gauges directly measure point rainfall with low temporal resolution. Thus differences in the resolution of the sensors create difficulties for rain radar validation, especially for spaceborne rain radar. Accordingly, rainfall measurement by microwave link has been proposed for several decades, as it estimates instantaneous path-average rainfall. Thus it is expected that the microwave link rain gauge will overcome, at least partly, the problems in the rain radar validation, toward which a 50-GHz band microwave link [the path-averaged rain gauge (PRG)] was developed that has been in operation since September 2000. In this paper, the authors show the potential of the PRG system by a simple model and rainfall comparison with a disdrometer and a tipping-bucket rain gauge. Differences observed by the instruments were within 15% (within 10% in half of the cases) during actual rain events in 2003. This confirmed that the PRG system displayed good performance as a rain gauge. Finally, the possibility of the PRG system being applied for spaceborne rain radar validation is considered.
The West Texas Mesonet: A Technical Overview
Authors: Schroeder J. L. , Burgett W. S. , Haynie K. B. , Sonmez I. , Skwira G. D. , Doggett A. L. , Lipe J. W. 
Published: March 2005

Abstract
The West Texas Mesonet originated in 1999 as a project of Texas Tech University. The mesonet consists of 40 automated surface meteorological stations, two atmospheric profilers, and one upper-air sounding system. Each surface station measures up to 15 meteorological and 10 agricultural parameters over an observation period of 5 and 15 min, respectively. The mesonet uses a combination of radio, cell phone, landline phone, and serial server (Internet) communication systems to relay data back to the base station at Reese Technology Center (formerly Reese Air Force Base), Texas. Data are transmitted through the radio network every 5 min for most meteorological data and every 15 min for agricultural data. For stations located outside of the radio network, phone systems transmit data every 30–60 min. The archive includes data received through the various communication systems, as well as data downloaded in the field from each station during regularly scheduled maintenance visits. Quality assurance/control (QA/QC) tests effectively flag data for manual review from a decision maker. The QA/QC flags and review decisions are then added to the database. All data are available free of charge; real-time data are available on the West Texas Mesonet Web page, and an interface to access the data archive is currently being developed.