bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacology, toxicology, and radiation dosimetry evaluation of [123I]5‐I‐A‐85380, a radioligand for in vivo imaging of cerebral neuronal nicotinic acetylcholine receptors in humans
Authors: Vaupel D. Bruce , Tella Srihari R. , Huso David L. , Mukhin Alexey G. , Baum Ira , Wagner Valentine O. , Horti Andrew G. , London Edythe D. , Koren Andrei O. , Kimes Alane S. 
Published: March 2003

Abstract[123I]5‐I‐A‐85380, which selectively binds to α4β2 nicotinic acetylcholine receptors, may be a suitable single photon emission computed tomography (SPECT) ligand for imaging nicotinic receptors in the human brain. In a mutagenicity study, 5‐I‐A‐85380 produced positive effects in one of five bacterial strains in the bacterial reverse mutation assay only with metabolic activation. The ED50 for 5‐I‐A‐85380 to elicit tonic‐clonic convulsions in mice, 7.1 µmol/kg, i.v., was five times that of nicotine (ED50=1.4 µmol/kg, i.v.). A 2‐day acute toxicity study (0.03–150 nmol/kg, i.v.) and a 14‐day chronic toxicity study (0.3–30 nmol/kg, s.c.) in mice revealed no evidence of gross pathology or histopathological changes. Biodistribution and dosimetry studies revealed that the urinary bladder wall and the thyroid gland were the critical organs with respect to radiation exposure. In unanesthetized rats, 5‐I‐A‐85380 (5.2–174 nmol/kg, i.v.) and nicotine (20–400 nmol/kg, i.v.) produced similar increases in systolic and diastolic blood pressure, heart rate, and locomotor activity. Doses of 5‐I‐A‐85380 that elevated blood pressure and heart rate by 10% ranged from 5–10 nmol/kg, i.v. The highest doses tested, which produced near maximal increases in blood pressure and heart rate, did not affect the PR, QRS, or QTc intervals of the electrocardiogram. Based on these preclinical data, initial SPECT imaging studies in humans (Fujita et al. [2002] Eur J Nucl Med 29:183–190) used a mass dose of 8.6 pmol/kg [123I]5‐I‐A‐8380, estimated to be 1/580th of the dose that elevates blood pressure and heart rate by 10%. Importantly, no clinical pharmacological effects were observed. Drug Dev. Res. 58:149–168, 2003. Published 2003 Wiley‐Liss, Inc.
Solubilized candida cell Wall β‐glucan, CSBG, is an epitope of natural human antibody
Authors: Masuzawa Shinya , Yoshida Masaharu , Ishibashi Ken‐ichi , Saito Nakaya , Akashi Masakazu , Yoshikawa Noriko , Suzuki Tatsuya , Nameda Sachiko , Miura Noriko N. , Adachi Yoshiyuki , Ohno Naohito 
Published: March 2003

AbstractWe have recently developed a protocol to obtain a soluble Candida spp. β1, 3‐glucan (CSBG) by sodium hypochlorite (NaClO) oxidation and subsequent dimethyl sulfoxide (DMSO) extraction. CSBG is composed mainly of β‐1,3 and β‐1,6‐glucosidic linkages with a small amount of branching. Antibody to β‐glucan is generally difficult to produce. In the present study, the specificity of the human sera to CSBG was examined by ELISA. Using CSBG‐coated plates, sera from normal human volunteers showed high reactivity that was neutralized by adding soluble CSBG as a competitor. However, the reactivity could not be neutralized by a β‐1,6 branched β‐1,3‐glucan, grifolan. Similar specificity of the immunoglobulin (Ig) was detected in commercially available γ‐globulin prepared from pooled human sera. Comparing various standard glucans, a major epitope was present on β‐1,6 glucan segment. Drug Dev. Res. 58:179–189, 2003. © 2003 Wiley‐Liss, Inc.
Antithrombotic effects of YM466, a synthesized direct inhibitor of factor Xa, in an arterio‐venous shunt thrombosis model in squirrel monkeys
Authors: Iwatsuki Yoshiyuki , Kaku Seiji , Moritani Yumiko , Taniuchi Yuta , Hirayama Fukushi , Koshio Hiroyuki , Matsumoto Yuzo , Mano Yuji , Kawasaki Tomihisa 
Published: March 2003

AbstractThe antithrombotic effects of YM466, a synthetic direct inhibitor of human factor Xa (FXa), were evaluated in an arterio‐venous shunt thrombosis model in squirrel monkeys. YM466 significantly inhibited thrombus formation after continuous IV zx infusion at doses of 3–30 µg/kg/h. Although prothrombin time (PT) was significantly prolonged at doses of 10 and 30 µg/kg/h, this effect was small (1.2‐ and 1.4‐fold of the control, respectively). Furthermore, YM466 had no effect on template bleeding time and activated partial thromboplastin time at any dose. Plasma anti‐FXa activity increased in a dose‐dependent manner correlating with the antithrombotic effect of YM466. Thrombin‐antithrombin III complex levels decreased to less than normal levels at 30 µg/kg/h of YM466. Mean plasma concentrations of YM466 measured by LC/MS/MS were 2.5, 10.5, 27.4, and 75.5 ng/ml at doses of 1, 3, 10, and 30 µg/kg/h, respectively. These results suggest that YM466 is a safe antithrombotic agent with low bleeding risk, and that plasma anti‐FXa activity may be a suitable parameter for monitoring its antithrombotic effect. Drug Dev. Res. 58:190–195, 2003. © 2003 Wiley‐Liss, Inc.
Mechanism of carvedilol‐induced block of delayed rectifier K+ current in the NG108‐15 neuronal cell line
Authors: Liu Chun‐Peng , Chiang Hung‐Ting , Jan Chung‐Ren , Wu Sheng‐Nan 
Published: March 2003

AbstractThe effects of the β‐adrenoceptor antagonist carvedilol on delayed rectifier K+ current (IK (DR)) were examined in NG108‐15 neuronal cells. Carvedilol (1–100µM) reversibly blocked IK (DR) with an IC50 value of 5 µM. IK (DR) in response to depolarizing pulses was sensitive to inhibition by quinidine or dendrotoxin, but not by iberiotoxin, 5‐hydroxydecanoate sodium, or linopiridine. The carvedilol‐induced inhibition of IK (DR) could not be reversed by further application of t‐butyl hydroperoxide or diazoxide. The inhibition of IK (DR) by carvedilol could still be observed in cells preincubated with t‐butyl hydroperoxide (1 mM), ruthenium red (30 µM), or carbonyl cyanide m‐chlorophenyl hydrazone (10 µM). The presence of carvedilol enhanced both the rate and extent of IK (DR) inactivation. Recovery from block by carvedilol (3 µM) could be fitted by a single exponential with a value of 1.64 s. Crossover of tail currents in the presence of carvedilol was also observed. Cell‐attached single‐channel recordings revealed that carvedilol suppressed channel activity without altering single‐channel amplitude. With the aid of the binding scheme, a quantitative description of the carvedilol actions on IK (DR) was also developed that clearly showed that in addition to being an antioxidative agent, carvedilol can block delayed rectifying K+ channel of neurons in an open‐ and state‐dependent manner. Drug Dev. Res. 58:196–208, 2003. © 2003 Wiley‐Liss, Inc.
Haptic intramodal comparison of texture in human neonates
Authors: Molina Michèle , Jouen François 
Published: March 2003

AbstractWe investigated neonates' capacity to haptically compare objects varying in texture property. Right‐hand manual activity, assessed by holding time and hand‐pressure frequency, was recorded for objects in the presence (test period) or absence (pretest and post‐test periods) of an object simultaneously held in the left hand. Thirty‐two babies were assigned to four experimental conditions according to the texture density of the object held in each hand: Objects had either the same (matching conditions) or different (non‐matching conditions) texture density. Although holding time decreased during test period in both conditions, hand‐pressure frequency changed according to the matching and non‐matching conditions. In the matching condition, hand‐pressure frequency of the right hand did not differ from hand‐pressure frequency of the left hand. In the non‐matching condition, hand‐pressure frequency recorded from the right hand was significantly higher than hand‐pressure frequency recorded from the left hand. These results point to neonates' capacity to compare information between simultaneously held objects. These results are interpreted in relation to existing data on the early capacity for intermodal exploration of objects. © 2003 Wiley‐Liss, Inc. Dev Psychobiol 42: 378–385, 2003.
Rat pups reduce ultrasonic vocalization after exposure to an adult male rat
Authors: Wiedenmayer Christoph P. , Lyo Donggon , Barr Gordon A. 
Published: March 2003

AbstractWe examined how the experience of a threatening stimulus alters subsequent behavior in a situation where the immediate threat is absent. A small huddle of 12‐day‐old rats was exposed to a potentially infanticidal adult male rat for 5 min. During male exposure, pups were significantly more immobile than control pups. Thirty, 60, and 180 min after male exposure, the pups were isolated for 5 min from litter and dam in an unfamiliar environment. When isolated, pups that had been previously exposed to the male emitted significantly fewer ultrasonic vocalizations than controls, but did not differ in immobility. Low levels of vocalization were apparent 30 and 60 min after male exposure and were not evident at 180 min. The pups seemed to have adjusted their behavior to a potential male threat in a different context for a limited period of time. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 42: 386–391, 2003.
A study of the flywheel capacity of the power compensator for the wind turbine generator
Authors: Nakamura Hirokazu , Koyanagi Akihiro , Suzuki Yasunori , Eguchi Naoya , Sato Yoshihisa , Shimada Ryuichi 
Published: March 2003

AbstractNowadays, the Wind Turbine Generator (WTG) system is remarkably increasing as a renewable energy resource in Japan. But in the WTG, the power fluctuations caused by the wind speed fluctuation are the most crucial issue in providing their energy to the utility. It was found that a power compensation system (PCS) of suitable capacity is not yet available. In this paper, the time range and standardized wind speed including fluctuations are discussed. We estimated the storage capacity of PCS at different wind profiles by standardization of wind speed and verified the validity of their capacities using a computer simulation. In this way we determined the suitable capacity of the power compensation system. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(4): 64–71, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10122
Voltage stability preventive and emergency‐preventive control using VIPI sensitivity
Authors: Takehara Arisa , Tanaka Yoshiyuki , Iwamoto Shinichi 
Published: March 2003

AbstractRecently, power systems have become larger and more complicated, and the rate of occurrence of constant power loads has increased. Under a situation like this, concerns about voltage instability phenomena have been raised. Therefore, in addition to the conventional local voltage control, the necessity of a global on‐line voltage control scheme has risen.In this paper, we propose a method of on‐line voltage stability control including preventive and emergency‐preventive controls to retain voltage stability even if a severe fault occurs. According to the result of contingency analysis for severe faults, we consider operation of control equipment as preventive control. And in the case that the fault seems severe still after preventive control, we consider load curtailment as emergency‐preventive control. When we select the control equipment and loads to curtail, we use voltage stability index VIPI sensitivity. And we determine the amount of control and load curtailment using Optimal Power Flow calculation. The effectiveness of the proposed method is verified by simulations using a 28‐bus system. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(4): 22–30, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10128
Proposal of a high‐performance solid oxide fuel cell combined power generation system with carbon dioxide recovery
Authors: Inui Yoshitaka , Yanagisawa Shin , Ishida Taichi 
Published: March 2003

AbstractA new fossil‐fuel‐utilized high‐performance combined power generation system with liquefaction recovery of carbon dioxide is proposed. In the system, pure oxygen is used as the oxidant gas to prevent the mixture of nitrogen in the exhaust gas and to make the liquefaction recovery of carbon dioxide possible. Solid oxide fuel cell is selected as the topping cycle. The exhaust fuel gas of the solid oxide fuel cell is afterburned with its exhaust oxidant gas of pure oxygen and the heat of the combustion gas is utilized in the bottoming cycle. Nonequilibrium MHD/noble gas turbine cycle is selected as the bottoming cycle because the temperature of the combustion gas reaches about 2300 K. It is made clear through detailed examination of energy balance that the total thermal efficiency of the system using natural gas (methane) as the fuel reaches 63.24% (HHV) or 70.18% (LHV). This efficiency is very high as for the system with carbon dioxide recovery. The proposed system, therefore, has excellent performance, and further research and development is warranted. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(4): 12–21, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10146
Facial identification system based on a high‐speed matching algorithm for isodensity lines
Authors: Hirano Teruaki , Ikeda Misuzu , Nakamura Osamu 
Published: March 2003

AbstractIn this paper, a high‐speed personal identification system which is adaptable for slant faces is presented.In the proposed method, the 25 facial images which are taken with different angles are registered in the database as reference images. The similarity of an input image is first examined between all registered images and the three facial images, which are similar to the input image, are then extracted as the candidate facial images. The isodensity map, which is expected to have the maximum similarity to the input image, is created by the interpolation between two candidate images and the input facial image is judged identical or not with the interpolated images.A template matching is adopted to obtain a similarity between two isodensity lines. In general, template matching requires a lot of time to obtain maximum similarity, while on the other hand it is very simple to use. To reduce the processing time for the matching efficiently, the techniques which are suited for the line pictures and the Sequential Similarity Detection Algorithm (SSDA) are adopted.Computer simulation using 50 people shows an accuracy of 95.2% correct discrimination. In addition, processing time is reduced to approximately 1/12. From the experimental results, the prospects of using this method are very encouraging. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(4): 31–41, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10147
A method of gene selection that decreases the number of fitness value calculations
Authors: Yamaguchi Satoshi , Itakura Hidekiyo 
Published: March 2003

AbstractThis paper proposes a new selection method of a gene from a population for reducing the number of fitness value calculations in genetic algorithms. The proposed method effectively reduces the computation time required to search for a solution to the optimization of a process involving a large number of such calculations as in robot behavior decisions and neural network learnings. In the proposed method, the use of a special buffer for storing a gene and its associated fitness value is introduced. The gene in the buffer is used as a candidate for the solution to the optimization problem. This gene is compared with a gene selected from the population, and one of the values is used in the next generation depending on the results of the comparison. The proportion of suitable genes in the population is increased in the possible shortest time. The convergence speed of our buffer depends on the population topology, which is introduced for choosing a gene from the population to compare with the buffer gene. Three kinds of topology are applied to our algorithm and they are compared and evaluated. The proposed method is applied to a robot control problem to demonstrate the validity of the technique. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(4): 42–49, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10148
Rosmarinic acid inhibits TCR‐induced T cell activation and proliferation in an Lck‐dependent manner
Authors: Won Jonghwa , Hur Yun‐Gyoung , Hur Eun Mi , Park See‐Hyoung , Kang Mi‐Ae , Choi Youngbong , Park Changwon , Lee Keun‐Hyeung , Yun Yungdae 
Published: March 2003

AbstractLck is a T cell‐restricted Src family protein tyrosine kinase that plays pivotal roles in TCR‐mediated signaling. We aimed to identify novel agents that could disrupt the molecular interactionof the Src homology 2‐domain of Lck (Lck SH2) with its binding partners, with the expectation that this would impair TCR signaling and generate immunosuppression. Large‐scale screening of plant extracts indicated that rosmarinic acid (RosA) in extracts of Prunella vulgaris consistently inhibits the interaction between Lck SH2 and a peptide containing its consensus binding sequence (pYEEI). The inhibitory effect of RosA was specific for SH2 domains of Src family protein tyrosine kinase. RosA inhibited TCR‐induced‐Ca2+ mobilization and IL‐2 promoter activation but not phorbol 12‐myristate 13‐acetate/ionomycin‐induced IL‐2 promoter activation, indicating its point of inhibition at the membrane proximal site of TCR signaling. Furthermore, RosA inhibited TCR‐induced splenocyte proliferation as well as one‐way MLR at an IC50 of 25–50 μM and inhibited cytokine expression such as IL‐2 and IFN‐γ. Here, we first report RosA as an inhibitor of TCR‐signaling and subsequent T cell proliferation.
Activity of human monocytes in IgE antibody‐dependent surveillance and killing of ovarian tumor cells
Authors: Karagiannis Sophia N. , Wang Qin , East Nick , Burke Frances , Riffard Stephane , Bracher Marguerite G. , Thompson Richard G. , Durham Stephen R. , Schwartz Lawrence B. , Balkwill Frances R. , Gould Hannah J. 
Published: March 2003

AbstractWe have previously shown that a chimeric IgE antibody against the folic acid receptor (MOv18 IgE) inhibits tumor growth in a SCID mouse model of ovarian carcinoma. MOv18 IgE gave greater protection than the corresponding chimeric MOv18 IgG1. We have now confirmed these effects in a nude‐mouse model of ovarian carcinoma and have demonstrated for the first time that human monocytes are active in IgE antibody‐dependent cell‐mediated cytotoxicity. Injection of tumor‐bearing mice with PBMC and MOv18 IgE led to infiltration of monocytes into the tumors and prolonged survival of the mice.Incubation of PBMC or purified monocytes and MOv18 IgE with ovarian tumor cells in vitro resulted in tumor cell killing proportional to the expression of unoccupied FcϵRI on monocytes.We observed phagocytosis of tumor cells by the monocytes in vitro. Our results suggest that tumor‐specific IgE antibodies may be exploited for immunotherapy of cancer.
Signaling through HLA‐DR induces PKCβ‐dependent B cell death outside rafts
Authors: Guo Wenyan , Castaigne Jean‐Gabriel , Mooney Nuala , Charron Dominique , Al‐Daccak Reem 
Published: March 2003

AbstractSignals through HLA‐DR molecules contribute to optimal activation of antigen‐presenting cells (APC) during T cell/APC interactions participating in the generation of productive interactions, and to the induction of APC death, which has been postulated to play a role in the termination of the immune response. To understand how these molecules accommodate both cellular responses, we studied the not yet well‐defined signaling events and the biochemical requirements for HLA‐DR‐mediated death. We demonstrate that in B cells the HLA‐DR‐activated protein kinase C (PKC) β is required for HLA‐DR‐mediated death whereas the HLA‐DR‐activated Src family of PTK is redundant. In contrast to HLA‐DR‐mediated activation of Src kinase Lyn, the aggregation of HLA‐DR molecules in lipid rafts is not required for HLA‐DR‐mediated PKCβ activation nor for the induction of cell death. Indeed, the bulk of HLA‐DR‐activated PKCβ reside outside rafts. This is the first report showing that HLA‐DR‐induced PKCβ activation is essential for the induction of B cell death via HLA‐DR, and that these HLA‐DR‐mediated events do not require the integrity of rafts.
The CD4‐related molecule, LAG‐3 (CD223), regulates the expansion of activated T cells
Authors: Workman Creg J. , Vignali Dario A. A. 
Published: March 2003

AbstractThe lymphocyte activation gene‐3 (LAG‐3, CD223) is a CD4‐related, activation‐induced cell surface molecule that binds to MHC class II with high affinity. The function of murine LAG‐3 on T cells is unclear. Here, we show that Vβ7/8+LAG‐3–/– T cells expand poorly following staphylococcal enterotoxin B (SEB) stimulation in vitro. LAG‐3–/– T cells proliferate at a normal rate, but exhibit increased cell death. Similar observations were made with LAG‐3–/–CD4+OT‐II TCR transgenic T cells following peptide stimulation. Despite reduced T cell expansion and increased cell death, LAG‐3–/–OT‐II+ T cells secrete more IL‐2 and IFN‐γ following stimulation. Antigen‐driven expansion of LAG‐3–/– T cells was restored by constitutive expression of LAG‐3 via retroviral‐mediated stem cell gene transfer. We further show that LAG‐3 function is mediated via its cytoplasmic domain, for which a conserved ‘KIEELE’ motif is essential. Our data support a role for LAG‐3 in regulating the expansion of activated T cells.
IL‐10 is crucial for the transition from acute to chronic disease state during infection of mice with Schistosoma mansoni
Authors: Sadler Clare H. , Rutitzky Laura I. , Stadecker Miguel J. , Wilson R. Alan 
Published: March 2003

AbstractAfter infection of mice with Schistosoma mansoni, deposition of eggs in the walls of the intestine and liver provokes an intense (acute) T cell response that peaks at week 8 and, thereafter, down‐modulates as the disease becomes chronic. Egg antigen‐stimulated proliferation of mesenteric lymph node and spleen cells in vitro was intense at week 8 in both IL‐10–/– and wild‐type (WT) mice, while proliferative responses were markedly reduced at week 15 in WT mice, but undiminished in IL‐10–/– animals. Moreover, in the absence of IL‐10 production, levels of both IFN‐γ and IL‐4 remained elevated at week 15. Granulomas around eggs embolized in the livers of WT mice were significantly smaller at week 15 than week 8, whereas those in IL‐10–/ animals were larger at week 8, showed no reduction in size at week 15, and were less sharply demarcated by peripheral collagen. There was also a greater leukocytic infiltration and necrosis of the hepatic parenchyma. These data suggest that in mice IL‐10 regulates not only the intensity of hepatic inflammation, but also granuloma organization and cohesiveness. It is a crucial agent in the down‐modulation of immune responses and immunopathology that defines the transition from acute to chronic disease.