bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative response of plasma VWF in dogs to up-regulation of VWF mRNA by interleukin-11 versus Weibel-Palade body release by desmopressin (DDAVP)
Authors: Olsen Eva H. N. , McCain Arlene S. , Merricks Elizabeth P. , Fischer Thomas H. , Dillon Ivy M. , Raymer Robin A. , Bellinger Dwight A. , Fahs Scot A. , Montgomery Robert R. , Keith James C. , Schaub Robert G. , Nichols Timothy C. 
Published: March 2003

AbstractRecombinant human interleukin-11 (rhIL-11), a glycoprotein 130 (gp130)–signaling cytokine approved for treatment of thrombocytopenia, also raises von Willebrand factor (VWF) and factor VIII (FVIII) by an unknown mechanism. Desmopressin (1-deamino-8-d-arginine vasopressin [DDAVP]) releases stored VWF and FVIII and is used for treatment of VWF and FVIII deficiencies. To compare the effect of these 2 agents, heterozygous von Willebrand disease (VWD) and normal dogs were treated with either rhIL-11 (50 μg/kg/d subcutaneously × 7 days) or DDAVP (5 μg/kg/d intravenously × 7 days). The rhIL-11 produced a gradual and sustained elevation of VWF and FVIII levels in both heterozygous VWD and normal dogs while DDAVP produced a rapid and unsustained increase. Importantly, rhIL-11 treatment produced a 2.5- to 11-fold increase in VWF mRNA in normal canine heart, aorta, and spleen but not in homozygous VWD dogs, thus identifying a mechanism for elevation of plasma VWF in vivo. Moreover, dogs pretreated with rhIL-11 retain a DDAVP-releasable pool of VWF and FVIII, suggesting that rhIL-11 does not significantly alter trafficking of these proteins to or from storage pools. The half-life of infused VWF is unchanged by rhIL-11 in homozygous VWD dogs. These results show that rhIL-11 and DDAVP raise plasma VWF by different mechanisms. Treatment with rhIL-11 with or without DDAVP may provide an alternative to plasma-derived products for some VWD and hemophilia A patients if it is shown safe in clinical trials.
Developmental Expression of Genes Involved in Neurosteroidogenesis: 3β-Hydroxysteroid Dehydrogenase/Δ5-Δ4 Isomerase in the Rat Brain
Authors: Ibanez Chrystelle , Guennoun Rachida , Liere Philippe , Eychenne Bernard , Pianos Antoine , El-Etr Martine , Baulieu Etienne-Emile , Schumacher Michael 
Published: March 2003

AbstractIn the central nervous system, neurosteroids, in particular progesterone, have neurotrophic and neuroprotective effects. We thus decided to study the developmental expression of 3β-hydroxysteroid-dehydrogenase/Δ5-Δ4 isomerase (3βHSD), an enzyme that converts pregnenolone to progesterone, in the male rat brain at 0, 7, 14, and 70 d after birth.3βHSD mRNA was widely distributed throughout the brain, as shown by in situ hybridization. At all ages, the same cerebral structures were labeled, but the intensity of the hybridization signal constantly decreased during postnatal development. As the hippocampus is of particular interest because of its neuronal plasticity, we chose to quantify the changes in 3βHSD mRNA levels as well as progesterone and pregnenolone concentrations in this structure. Quantitative in situ hybridization confirmed a decrease in the expression of 3βHSD mRNA with progressing age, as revealed by a significant reduction in the density of silver grains per cell in the CA1 layer. This decrease was confirmed by semiquantitative RT-PCR on hippocampal samples. Concentrations of hippocampal pregnenolone and progesterone measured by gas chromatography/mass spectrometry were highest on the day of birth and lower at the other ages. Plasma concentrations of these steroids were lower than those in the hippocampus, suggesting that they may have been mostly synthesized in situ since the day of birth. These results demonstrate variations in the expression of a gene coding for an enzyme critically involved in progesterone synthesis in the hippocampus throughout postnatal development.
Phosphodiesterase Regulation Is Critical for the Differentiation and Pattern of Gene Expression in Granulosa Cells of the Ovarian Follicle
Authors: Park Jy-Young , Richard Francois , Chun Sang-Young , Park Jeong-Hoh , Law Evelyn , Horner Kathleen , Jin S-L Catherine , Conti Marco 
Published: March 2003

AbstractFeedback regulations are integral components of the cAMP signaling required for most cellular processes, including gene expression and cell differentiation. Here, we provide evidence that one of these feedback regulations involving the cyclic nucleotide phosphodiesterase PDE4D plays a critical role in cAMP signaling during the differentiation of granulosa cells of the ovarian follicle. Gonadotropins induce PDE4D mRNA and increase the cAMP hydrolyzing activity in granulosa cells, demonstrating that a feedback regulation of cAMP is operating in granulosa cells in vivo. Inactivation of the PDE4D by homologous recombination is associated with an altered pattern of cAMP accumulation induced by the gonadotropin LH/human chorionic gonadotropin (hCG), impaired female fertility, and a markedly decreased ovulation rate. In spite of a disruption of the cAMP response, LH/hCG induced P450 side chain cleavage expression and steroidogenesis in a manner similar to wild-type controls. Morphological examination of the ovary of PDE4D−/− mice indicated luteinization of antral follicles with entrapped oocytes. Consistent with the morphological finding of unruptured follicles, LH/hCG induction of genes involved in ovulation, including cyclooxygenase-2, progesterone receptor, and the downstream genes, is markedly decreased in the PDE4D−/− ovaries. These data demonstrate that PDE4D regulation plays a critical role in gonadotropin mechanism of action and suggest that the intensity and duration of the cAMP signal defines the pattern of gene expression during the differentiation of granulosa cells.
Screening Men for Prostate and Colorectal Cancer in the United States
Authors: Sirovich Brenda E. , Schwartz Lisa M. , Woloshin Steven 
Published: March 2003

ContextThe debate about the efficacy of prostate-specific antigen (PSA) screening for prostate cancer has received substantial attention in the medical literature and the media, but the extent to which men are actually screened is unknown. If practice were evidence-based, PSA screening would be less common among men than colorectal cancer screening, a preventive service of broad acceptance and proven efficacy.ObjectiveTo compare the prevalences of PSA and colorectal cancer screening among US men.Design, Setting, and PopulationThe 2001 Behavioral Risk Factor Surveillance System, an annual population-based telephone survey of US adults conducted by the Centers for Disease Control and Prevention, was used to gather data on a representative sample of men aged 40 years or older from all 50 states and the District of Columbia (n = 49 315).Main Outcome MeasuresProportions of men ever screened and up to date on screening for prostate cancer (with PSA testing) and colorectal cancer (with fecal occult blood testing, flexible sigmoidoscopy, or colonoscopy).ResultsOverall, men are more likely to report having ever been screened for prostate cancer than for colorectal cancer; 75% of those aged 50 years or older have had a PSA test vs 63% for any colorectal cancer test (risk ratio [RR], 1.20; 95% confidence interval [CI], 1.18-1.21). Up-to-date PSA screening is also more common than colorectal cancer screening for men of all ages. Among men aged 50 to 69 years (those for whom there is the greatest consensus in favor of screening), 54% reported an up-to-date PSA screen, while 45% reported up-to-date testing for colorectal cancer (RR, 1.19; 95% CI, 1.16-1.21). In state-level analyses of this age group, men were significantly more likely to be up to date on prostate cancer screening compared with colorectal cancer screening in 27 states, while up-to-date colorectal cancer screening was more common in only 1 state.ConclusionAmong men in the United States, prostate cancer screening is more common than colorectal cancer screening. Physicians should ensure that men who choose to be screened for cancer are aware of the known mortality benefit of colorectal cancer screening and the uncertain benefits of screening for prostate cancer.
Probabilistic advisory systems for data‐intensive applications
Authors: Quinn A. , Ettler P. , Jirsa L. , Nagy I. , Nedoma P. 
Published: March 2003

AbstractReal‐world, multidimensional, dynamic, non‐linear processes typically exhibit many distinct modes of operation. Mixtures of dynamic models improve greatly on traditional one‐component linear models in this context. Improved prediction then points the way to effective adaptive control design. This paper presents the experience gained under the EU Project, ProDaCTool, in designing and implementing advisory systems, based on dynamic mixtures, in diverse domains: urban traffic regulation, therapy recommendations in nuclear medicine, and operator support for metal‐strip rolling mills. Efficient, recursive estimation of the dynamic mixtures from archive data is accomplished using the quasi‐Bayes (QB) algorithm, implemented with dedicated software developed within ProDaCTool. The advisory systems are designed using the probabilistic control design technique presented in the previous paper. Highly encouraging prediction and performance enhancements are reported for the applications considered. Copyright © 2003 John Wiley & Sons, Ltd.
Acquired von Willebrand's syndrome: A single institution experience
Authors: Kumar Shaji , Pruthi Rajiv K. , Nichols William L. 
Published: March 2003

AbstractAcquired von Willebrand's disease or syndrome (AVWS) is a rare bleeding disorder distinguished from congenital von Willebrand's disease by age at presentation and absence of personal and family history of bleeding disorders. We report on 22 patients with AVWS seen over 25 years. Mean age at diagnosis was 61.3 years (range 38–86 years); most patients had a spontaneous or a post‐operative hemorrhage at presentation. Gastrointestinal bleeding and epistaxis were the most common spontaneous symptoms. Bleeding time was prolonged in most patients, associated with marked reductions in plasma von Willebrand factor antigen and ristocetin cofactor activity. Plasma VWF multimer distribution was normal (type 1 pattern) in 5 patients, indeterminate (no multimers detectable) in 6 patients (type 3 pattern), and abnormal (decreased higher‐molecular‐weight multimers, type 2 pattern) in 11 patients. None of 17 patients tested had an inhibitor of ristocetin cofactor activity. An underlying malignant or benign hematologic disease was found in 18 patients, and 1 patient had Crohn's disease. Desmopressin was effective in only half the patients so treated, but all patients responded to treatment with VWF‐containing concentrates. Resolution of AVWS occurred with therapy of lymphoma (1 patient) and chronic lymphocytic leukemia (1 patient). Sixteen patients were alive at last follow‐up; no deaths were related to bleeding. AVWS may be more prevalent than has been appreciated; we estimate up to 0.04%. Awareness of the existence of AVWS is essential for diagnosis and appropriate management. Therapy of associated diseases may improve the bleeding disorder. Am. J. Hematol. 72:243–247, 2003. © 2003 Wiley‐Liss, Inc.
Relationship between the Structure and Antimycobacterial Activity of Substituted Salicylanilides
Authors: Waisser Karel , Bureš Otakar , Holý Pavel , Kuneš Jiří , Oswald Radek , Jirásková Lucie , Pour Milan , Klimešová Věra , Kubicová Lenka , Kaustová Jarmila 
Published: March 2003

AbstractA series of 143 salicylanilides substituted in positions 4 and 5 and in positions 3′ and 4′ was synthesized. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii, and Mycobacterium avium. To describe the structure‐antimycobacterial activity relationships (QSARs), an approach based on the combination of the Free‐Wilson and Hansch methods was employed (the substituent constants were used in the case of the substituents on the phenyl ring; indicator parameters were used for the substituents on the acyl moiety). The relationships between the antimycobacterial activity and physico‐chemical parameters of all substituents were also explored. The quadratic representation of lipophilicity parameters did not lead to significant correlations.
Promoting social initiation in children with autism using video modeling
Authors: Nikopoulos Christos K. , Keenan Michael 
Published: March 2003

AbstractA large number of studies have shown that children and youths with autism can improve their social skills when provided with appropriate and well planned treatment strategies. Here, a video modeling procedure was implemented with seven developmentally delayed children, using a multiple‐treatment design. Each child watched a videotape showing a model and the experimenter engaged in a simple social interactive play in an adapted play setting. Afterwards each child's behavior was assessed in this setting, while the experimenter's behavior remained the same as that shown in the videotape. The video modeling training enhanced the social initiation skills of four children. It also facilitated appropriate play engagement, which generalized across settings, peers, and toys. These changes maintained after a 1‐ and 2‐month follow‐up period. The intervention was evaluated as a time‐efficient teaching tool as well as a means of enhancing appropriate play skills. Copyright © 2003 John Wiley & Sons, Ltd.
Combination of extinction and protective measures in the treatment of severely self‐injurious behavior
Authors: Yang Lizen J. 
Published: March 2003

AbstractTwo female adolescents with profound mental retardation and physical disabilities residing in a state facility exhibited self‐injurious behavior (SIB). They had been wearing restrictive mechanical restraints for more than two years to prevent injuries from occurring. By using an indirect method of functional analysis, social attention was found to be the factor reinforcing and maintaining their behaviors. Extinction in combination with non‐intrusive protective measures was selected as the intervention strategy to reduce SIB. The outcomes of the treatment were evaluated with an AB probe design. Incidents of SIB decreased quickly and sharply after the treatment began. Once the incidents had reached a level of zero for three consecutive sessions, a six‐month follow‐up was started. No SIB was observed or reported during the follow‐up. The advantages of using extinction, especially in conjunction with the non‐intrusive protective measures to treat SIB, are discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Additive concentration effects on enantioselective separations in supercritical fluid chromatography
Authors: Phinney Karen W. , Sander Lane C. 
Published: March 2003

AbstractPolar additive concentration effects in supercritical fluid chromatography were studied on chiral stationary phases having either a macrocyclic glycopeptide or a derivatized polysaccharide as the chiral selector. Two basic additives, isopropylamine and triethylamine, were incorporated into the methanol modifier at various concentrations and the effects on retention, selectivity, and resolution were monitored. Many of the analytes failed to elute from the macrocyclic glycopeptide stationary phase in the absence of an additive and the most noticeable effect of increasing additive concentration was a significant decrease in retention. On the derivatized polysaccharide stationary phase the additives had little effect on retention, but they did foster significant improvements in peak shape and resolution. Chirality 15:287–294, 2003. Published 2003 Wiley‐Liss, Inc.
Enantiospecific disposition of pranoprofen in beagle dogs and rats
Authors: Imai Teruko , Nomura Tadayuki , Aso Mayumi , Otagiri Masaki 
Published: March 2003

AbstractThe pharmacokinetic characteristics of pranoprofen enantiomer were examined and compared with the disposition of the corresponding isomer after the administration of racemic pranoprofen to beagle dogs and rats. The plasma levels of (+)‐(S)‐isomer were significantly higher than those of (–)‐(R)‐isomer in dogs and rats by either intravenous or oral administration. Although the oral bioavailability and absorption rate constant between the (–)‐(R)‐ and (+)‐(S)‐form was the same, the elimination rate constant of the (+)‐(S)‐form was significantly lower than that of the (–)‐(R)‐form in both dogs and rats. This discrepancy can be explained on the basis of differences in protein binding and the metabolism of the two enantiomers. The (–)‐(R)‐isomer was predominantly conjugated depending on its higher free plasma level and its faster metabolic rate than the (+)‐(S)‐form, and thus was excreted more rapidly in the urine and bile in the form of pranoprofen glucuronide. Furthermore, a (–)‐(R)‐ to (+)‐(S)‐inversion occurred to the extent of 14% in beagle dogs, but not in rats. This chiral inversion might be an important factor in the slow elimination of the (+)‐(S)‐form in dogs. The most efficient organ for chiral inversion was the liver, followed by kidney and intestine. Chirality 15:312–317, 2003. © 2003 Wiley‐Liss, Inc.
Convenient method for determining the absolute configuration of chiral alcohols with racemic 1H NMR anisotropy reagent, MαNP acid: Use of HPLC‐CD detector
Authors: Kasai Yusuke , Watanabe Masataka , Harada Nobuyuki 
Published: March 2003

AbstractA convenient method for determining the absolute configuration of chiral secondary alcohols using the racemic NMR anisotropy reagent, (±)‐2‐methoxy‐2‐(1‐naphthyl)propionic acid [(±)‐MαNP acid], and an HPLC‐CD detector was developed. The method was successfully applied to some chiral alcohols derived from (–)‐α‐santonin. Chirality 15:295–299, 2003. © 2003 Wiley‐Liss, Inc.
Chiral inversion of the second generation IMiD™ CC‐4047 (ACTIMID™) in human plasma and phosphate‐buffered saline
Authors: Teo Steve K. , Chen Yong , Muller George W. , Chen Roger S. , D. Thomas Steve , Stirling David I. , Chandula Reddy S. 
Published: March 2003

AbstractCC‐4047 is a racemic second‐generation immunomodulatory drug currently in clinical development for various oncologic indications. It has potent effects on key cytokines including tumor necrosis factor‐α, interleukin (IL‐10), and interferon (IFN‐γ). The S‐isomer of CC‐4047 has been reported to be the more potent enantiomer of the racemate. In this article we report on the rapid racemization of the S‐isomer of CC‐4047 in human plasma and phosphate‐buffered saline. These results support the further development of the racemate instead of the S‐isomer. Chirality 15:348–351, 2003. © 2003 Wiley‐Liss, Inc.
A DFT Study of Tin‐ and Crown‐Ether‐Based Host Molecules Capable of Binding Anions and Cations Simultaneously
Authors: Vivas‐Reyes Ricardo , De Proft Frank , Biesemans Monique , Willem Rudolph , Geerlings Paul 
Published: March 2003

AbstractDFT calculations are reported for a series of tin‐ and crown‐ether‐based host compounds {i.e., the trimethyl derivatives [18]‐crown‐6‐C6H3COOSn(CH3)3and [15]‐crown‐5‐C6H3COOSn(CH3)3} capable of binding cations and anions simultaneously. The B3LYP functional together with the 6‐31G* basis set was used for the atoms C, H, N, O, S, Na and K and the 3‐21G* basis set for Sn in order to obtain insights into the factors determining the nature of the interactions of these compounds with the neutral molecules acetone and H2O, the SCN−anion, and the Na+and K+cations. The interaction strength pattern with these molecules was explained by the use of a series of reactivity descriptors such as the Fukui function, hardness, local softness, and the MEP (molecular electrostatic potential). In all cases studied in this paper, the complexes with Na+were more stable than those with K+, correlating with the size of the cation and the volume available in the crown ether. Moreover, this finding is also in accordance with the greater hardness of Na+relative to K+, in combination with the hard environment of the crown ether moiety. This region was also analysed by computation of electrostatic potentials, which showed that highly negative values are associated with the inside region of the cavity of the crown, this region thus being amenable to electrophilic attack. The HSAB principle, characterising the reactive sites on the basis of local softness and the Fukui function, provided a firm explanation of the reactivity of the tin atom of the crown ether benzocarboxylate towards SCN−, acetone and water. The HSAB concept was also successfully used to explain the preference of the tin atoms in both crown ethers to bind with the nitrogen atom rather than the sulfur atom of SCN−. This result is a confirmation that the tin atoms in the compounds under consideration behave as hard atoms. Overall, these results fit remarkably well with previous experimentally measured NMR spectroscopy data and demonstrate that the interactions of this kind of molecules can be predicted and interpreted by the use of DFT calculations and DFT‐based reactivity descriptors, as well as MEP calculations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Direct Synthesis of (PhSe)4Ge and (PhTe)4Ge from Activated Hydrogenated Germanium − Crystal Structure and Twinning of (PhTe)4Ge
Authors: Schlecht Sabine , Friese Karen 
Published: March 2003

AbstractThe germanium chalcogenolates (PhSe)4Ge and (PhTe)4Ge were synthesized from activated hydrogenated germanium (Ge*) and diphenyldiselenide or diphenylditelluride, respectively. (PhTe)4Ge is the first homoleptic organotellurolate of germanium. It was characterized spectroscopically and by X‐ray crystal structure analysis. (PhTe)4Ge crystallizes in the monoclinic space group P21/c with a = 12.8018(14), b = 9.1842(9), c = 23.690(3) Å and β = 105.458(8)°. The molecules show a tetrahedral GeTe4 core. Weak Te‐Te interactions connect neighbouring tetrahedra to infinite helices along [010]. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Web usage mining approaches to page recommendation and restructuring
Authors: Ishikawa Hiroshi , Ohta Manabu , Yokoyama Shohei , Nakayama Junya , Katayama Kaoru 
Published: March 2003

AbstractAs an increasing number of Web sites such as e‐businesses consist of an increasing number of pages, users find it more difficult to rapidly reach their own target pages. Ill‐structured design of Web sites also prevents the users from rapidly accessing the target pages. In this paper, we describe two complementary approaches to Web usage mining as a key solution to these issues. First, we describe an adaptable recommendation system called the L‐R system, which constructs user models by classifying the Web access logs and by extracting access patterns based on the transition probability of page accesses and recommends the relevant pages to the users based on both the user models and the Web structures. We have evaluated the prototype system and have obtained the positive effects. Second, we describe another approach to constructing user models, which clusters Web access logs based on access patterns. The user models also help to discover unexpected access paths corresponding to ill‐formed Web site design. Copyright © 2003 John Wiley & Sons, Ltd.