bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterophilic interactions of platelet factor 4 and RANTES promote monocyte arrest on endothelium
Authors: von Hundelshausen Philipp , Koenen Rory R. , Sack Markus , Mause Sebastian F. , Adriaens Wencke , Proudfoot Amanda E. I. , Hackeng Tilman M. , Weber Christian 
Published: January 2005

AbstractThe chemokines platelet factor 4 (PF4) and RANTES (regulated on activation normal T cell expressed and secreted) are secreted by activated platelets and influence multiple cell types and biologic processes. For instance, PF4 inhibits progenitor cell proliferation and angiogenesis, while platelet-derived RANTES is involved in vascular recruitment of monocytes. However, little is known about functional interactions of PF4 and RANTES. Here we show that the presence of PF4 enhanced the arrest of RANTES-stimulated monocytes and monocytic cells on activated endothelial cells under flow conditions, while binding of PF4 to the monocyte surface was increased by RANTES. Both RANTES-triggered arrest and PF4 binding involved monocytic chondroitin sulfate. Ligand blots and surface plasmon resonance revealed a robust heterophilic interaction of PF4 with RANTES but not with RANTES variants defective in higher order oligomerization. The tetrameric mutant E26A bound to the monocyte surface without increasing PF4 binding, and monocyte arrest induced by E26A-RANTES was not enhanced by PF4. Stimulation of monocytes with supernatants of activated platelets triggered arrest involving RANTES and PF4, as shown by inhibition studies. Our results suggest that heterophilic interactions with PF4 require structural motifs important in RANTES oligomerization and amplify RANTES-triggered effects on monocyte adhesion. This may have implications for the modulation of inflammatory recruitment by platelet-derived chemokines.
Phosphorylation of RasGRP3 on threonine 133 provides a mechanistic link between PKC and Ras signaling systems in B cells
Authors: Zheng Yong , Liu Huaizhi , Coughlin Jason , Zheng Jing , Li Liang , Stone James C. 
Published: January 2005

AbstractB-cell receptor (BCR) signaling activates a number of intracellular signaling molecules including phospholipase C–γ2 (PLC-γ2), which generates membrane diacylglycerol (DAG). DAG recruits both protein kinase C (PKC) and RasGRP family members to the membrane and contributes to their activation. We have hypothesized that membrane colocalization facilitates activation of RasGRP3 by PKC. Here we demonstrate that PKCθ phosphorylates RasGRP3 on Thr133 in vitro, as determined by mass spectrometry. RasGRP3 with a Thr133Ala substitution is a poor PKC substrate in vitro and a poor Ras activator in vivo. Antiphosphopeptide antibodies recognize Thr133-phosphorylated RasGRP3 in B cells after BCR stimulation or DAG analog treatment, but much less so in resting cells. PKC inhibitors block RasGRP3 Thr133 phosphorylation and Ras–extracellular signal-related kinase (Erk) signaling with a similar pattern. After stimulation of T-cell receptor (TCR) or DAG analog treatment of T cells, PKC-catalyzed phosphorylation of RasGRP1 occurs on the homologous residue, Thr184. These studies shed light on the proposed “PKC-Ras pathway” and support the hypothesis that RasGRP phosphorylation by PKC is a mechanism that integrates DAG signaling systems in T and B cells. PKC-mediated regulation of RasGRPs in lymphocytes may generate cooperative signaling in response to increases in DAG. The mast- and myeloid-selective family member RasGRP4 is regulated by different means.
cAMP response element binding protein (CREB) activates transcription via two distinct genetic elements of the human glucose-6-phosphatase gene
Authors: Thiel Gerald , Al Sarraj Jude , Stefano Luisa 
Published: January 2005

Abstract
Background
The enzyme glucose-6-phosphatase catalyzes the dephosphorylation of glucose-6-phosphatase to glucose, the final step in the gluconeogenic and glycogenolytic pathways. Expression of the glucose-6-phosphatase gene is induced by glucocorticoids and elevated levels of intracellular cAMP. The effect of cAMP in regulating glucose-6-phosphatase gene transcription was corroborated by the identification of two genetic motifs CRE1 and CRE2 in the human and murine glucose-6-phosphatase gene promoter that resemble cAMP response elements (CRE).

Results
The cAMP response element is a point of convergence for many extracellular and intracellular signals, including cAMP, calcium, and neurotrophins. The major CRE binding protein CREB, a member of the basic region leucine zipper (bZIP) family of transcription factors, requires phosphorylation to become a biologically active transcriptional activator. Since unphosphorylated CREB is transcriptionally silent simple overexpression studies cannot be performed to test the biological role of CRE-like sequences of the glucose-6-phosphatase gene. The use of a constitutively active CREB2/CREB fusion protein allowed us to uncouple the investigation of target genes of CREB from the variety of signaling pathways that lead to an activation of CREB. Here, we show that this constitutively active CREB2/CREB fusion protein strikingly enhanced reporter gene transcription mediated by either CRE1 or CRE2 derived from the glucose-6-phosphatase gene. Likewise, reporter gene transcription was enhanced following expression of the catalytic subunit of cAMP-dependent protein kinase (PKA) in the nucleus of transfected cells. In contrast, activating transcription factor 2 (ATF2), known to compete with CREB for binding to the canonical CRE sequence 5'-TGACGTCA-3', did not transactivate reporter genes containing CRE1, CRE2, or both CREs derived from the glucose-6-phosphatase gene.

Conclusions
Using a constitutively active CREB2/CREB fusion protein and a mutant of the PKA catalytic subunit that is targeted to the nucleus, we have shown that the glucose-6-phosphatase gene has two distinct genetic elements that function as bona fide CRE. This study further shows that the expression vectors encoding C2/CREB and catalytic subunit of PKA are valuable tools for the study of CREB-mediated gene transcription and the biological functions of CREB.
Rituximab Therapy for Patients With Newly Diagnosed, Advanced-Stage, Follicular Grade I Non-Hodgkin's Lymphoma: A Phase II Trial in the North Central Cancer Treatment Group
Authors: Witzig Thomas E. , Vukov Allen M. , Habermann Thomas M. , Geyer Susan , Kurtin Paul J. , Friedenberg William R. , White William L. , Chalchal Haji I. , Flynn Patrick J. , Fitch Thomas R. , Welker Debra A. 
Published: January 2005

Purpose Patients with newly diagnosed, advanced-stage, follicular grade 1 non-Hodgkin's lymphoma (NHL) are often asymptomatic and can be observed without immediate chemotherapy. The goals of this study were to assess the overall response rate (ORR) to rituximab in this patient population and to determine the time-to-progression (TTP) and time-to-subsequent-chemotherapy (TTSC). Patients and Methods Eligible patients had untreated follicular grade 1 NHL, and measurable stage III/IV disease. Patients received rituximab 375 mg/m2 intravenous weekly × 4 doses and were then followed for response and progression; no maintenance therapy was provided. Results Thirty-seven patients were accrued; one patient was ineligible. The median age was 59 years (range, 29 to 83 years). Six patients (18%) had elevated lactate dehydrogenase levels. The ORR was 72%, with 36% complete remissions. Fourteen (39%) of 36 patients remain in unmaintained remission, two died without disease progression, and three died with disease progression. Twenty (56%) of 36 patients have disease progression. The median TTP was 2.2 years (95% CI, 1.3 to not yet reached). Eighteen patients have subsequently been treated with chemotherapy, with a median TTSC of 2.3 years (95% CI, 1.6 to not yet reached). Patients with a high lactate dehydrogenase level had a lower ORR of 33% and a short TTP of only 6 months. Conclusion Rituximab can be safely administered to patients with advanced-stage follicular grade 1 NHL with efficacy and minimal toxicity. This therapy is highly active and offers an acceptable alternative to observation in this patient population. Patients with high LDH should not be considered for rituximab monotherapy.
Cost-Effectiveness of Adherence-Enhancing Interventions: A Quality Assessment of the Evidence
Authors: Elliott Rachel A , Barber Nick , Horne Rob 
Published: January 2005

OBJECTIVE: To determine whether the current cost-effectiveness evidence on adherence-enhancing interventions (AEIs) was of sufficient quality to aid in decision-making regarding medication adherence policies. DATA SOURCES: A computerized search of Embase, MEDLINE, Cinahl, Econlit, NHSEED, Psychlit, EPIC, and Cochrane databases (1980–April 2004) was performed. English-language human subject articles were identified using the key words compliance, adherence, concordance, patient assistance, therapeutic alliance, costs, economics, efficiency, resource use/utilization, cost-of illness, cost-effectiveness, cost-minimization, cost-utility, and cost-benefit. STUDY SELECTION AND DATA EXTRACTION: Studies that appeared to assess the cost-effectiveness of medication AEIs were included. Methodologic rigor was assessed using 15 minimum quality criteria. DATA SYNTHESIS: We found 45 comparative studies in 43 publications. Asthma (14 studies) and psychiatric illness (12 studies) were most commonly investigated. In 33 studies, interventions were educational, 18 had multiple components, and 23 did not appear to be linked to proven reasons for nonadherence. Reporting of adherence and outcome results was often unclear. Cost data were poorer quality than outcome data, using average or estimated costs and omitting some cost elements. Nine studies carried out incremental economic analysis. No study met all quality criteria. CONCLUSIONS: We were not able to make definitive conclusions about the cost-effectiveness of AEIs due to the heterogeneity of the studies found and incomplete reporting of results. Important policy decisions need to be made about nonadherence; however, they are currently being made in a vacuum of adequate information. AEIs must be based on reasons for nonadherence and be evaluated using accepted clinical and economic quality criteria.
Expression of Stathmin, a Developmentally Controlled Cytoskeleton-Regulating Molecule, in Demyelinating Disorders
Authors: Liu Aixiao , Stadelmann Christine , Moscarello Mario , Bruck Wolfgang , Sobel Andre' , Mastronardi Fabrizio G. , Casaccia-Bonnefil Patrizia 
Published: January 2005

Understanding the biological relevance of reexpression of developmental molecules in pathological conditions is crucial for the development of new therapies. In this study, we report the increased expression of stathmin, a developmentally regulated tubulin-binding protein, in the brains of patients with multiple sclerosis (MS). In physiological conditions, stathmin immunoreactivity was observed in polysialic acid-neural cell adhesion molecule-positive migratory progenitors in the subventricular zone, and its expression progressively decreased as the cells matured into oligodendrocytes (OLs). In MS patients, however, stathmin levels were elevated in 2′,3′-cyclic nucleotide 3′-phosphodiesterase-positive OLs, in 10 of 10 bioptic samples analyzed. Increased levels of stathmin were confirmed by Western blot analysis of normal-appearing white matter samples from MS brains. In addition, using mass spectrometry, stathmin was identified as the main component of a specific myelin protein fraction consistently increased in MS preparations compared with controls.To test the biological relevance of increased stathmin levels, primary OL progenitors were transfected using a myc-tagged stathmin cDNA and were allowed to differentiate. Consistent with a distinct role played by this molecule in cells of the OL lineage at different developmental stages, transient transfection in progenitors favored the bipolar migratory phenotype but did not affect survival. However, sustained stathmin levels in differentiating OLs, because of overexpression, resulted in enhanced apoptotic susceptibility.We conclude that stathmin expression in demyelinating disorders could have a dual role. On one hand, by favoring the migratory phenotype of progenitors, it may promote myelin repair. On the other hand, stathmin in mature OLs may indicate cell stress and possibly affect survival.
Gaze Control Strategy for Vision-Guided Humanoid Walking (Blickwinkelsteuerung für visuell geführtes humanoides Laufen)
Authors: Seara Javier F. , Schmidt Günther 
Published: January 2005

Abstract
To increase the autonomy of a vision guided walking robot, perception must be controlled such that the humanoid is provided with sufficient information about its environment. This article outlines a modular task-specific and situation-dependent gaze control scheme which selects an optimal view direction allowing the goal-oriented acquisition of the relevant information. The basic idea of the approach rests upon maximization of the predicted visual information content of a view situation. For information management, a hybrid Extended Kalman Filter is proposed considering the peculiarities of legged locomotion. Specific view direction evaluation strategies for obstacle avoidance and self-localization tasks are formulated. For dealing with these conflicting objectives a decision strategy for situation-dependent view direction selection based on Utility Theory is presented. Several references to related published work on simulative validation and real-world experiments with different robot platforms are given. The results demonstrate the relevance and practicality of the proposed gaze control approach in the framework of a system for vision-guided humanoid walking.
Modellierung einer Direkt-Methanol-Brennstoffzelle (Modelling of a Direct-Methanol-Fuel-Cell)
Authors: Schlake Jan C. , Preusse Christian , Winkelhake Jürgen , Konigorski Ulrich 
Published: January 2005

Abstract
Direkt-Methanol-Brennstoffzellen (DMFC) werden als eine interessante Alternative für die mobile Energieversorgung im unteren Leistungsbereich betrachtet. In diesem Beitrag wird eine Möglichkeit aufgezeigt, die auftretenden dynamischen Effekte der DMFC unter systemtheoretischen Gesichtspunkten zu untersuchen. Die am Institut für Chemische Verfahrenstechnik der TU Clausthal entwickelte Beschreibung durch partielle Differentialgleichungen und Randwertaufgaben wird hierfür mittels der Methode der gewichteten Reste, einer Diskretisierungsmethode zur Lösung von Randwertaufgaben, in ein Zustandsraummodell überführt. Dieses Modell der DMFC gestattet eine Optimierung bezüglich des dynamischen Systemverhaltens durch die Verwendung regelungstechnischer Standardverfahren.
Extraction Distribution of 2-Nitroso-1-Naphthol in the Two-Phase Water-Nitrobenzene System
Authors: Makrlík E. 
Published: January 2005

Abstract
General relations among the thermodynamic parameters, which characterize dissociation equilibria of an acid HA in both phases of a two-phase extraction system and ion transfers across the interface of this system, was formulated. Moreover, dissociation constant of 2-nitroso-1-naphthol in nitrobenzene saturated with water was calculated as pK
d
nb(HA) = −logK
d
nb(HA) = 16.48.
Functional relationships among selenium concentrations in the diet, target tissues, and nondestructive tissue samples of two species of snakes
Authors: Hopkins William A. , Snodgrass Joel W. , Baionno Jennifer A. , Roe John H. , Staub Brandon P. , Jackson Brian P. 
Published: January 2005

Abstract
Nondestructive sampling methods, such as removal of feathers for contaminant analysis, are desirable in ecological monitoring programs that seek to minimize the impacts of harvesting organisms. Although many reptiles are declining worldwide, nondestructive sampling techniques seldom have been employed for assessing contaminant exposure in these organisms. In this study, we examined the utility of nondestructive tissue sampling for assessing Se exposure in reptiles. We describe the functional relationships among dietary Se concentrations, target tissue Se concentrations, and Se concentrations in nondestructive tissue samples (blood and tail tissue biopsy) in two species of snakes that had been exposed to Se under very different experimental protocols. Using nonlinear regression, we found strong positive correlations (r2 &gt; 0.92) in all comparisons among Se concentrations in nondestructive tissues, diet, and target tissues. Moreover, equations describing these relationships can be used to estimate concentrations of Se in diet and target organs, from known concentrations of Se in nondestructive tissue samples. Although the current paucity of toxicity data on reptiles precludes tests of our models, we demonstrate how the equations describing these relationships might be used to make predictions about Se accumulation in target organs for risk assessment. Future studies on reptiles that examine these relationships under different Se exposure conditions, and those that document physiological responses of reptiles to various concentrations of Se, will help to refine our models and test their efficacy for predicting health risk.
Impact of imposed anaerobic conditions and microbial activity on aqueous-phase solubility of polycyclic aromatic hydrocarbons from soil
Authors: Pravecek Tasha L. , Christman Russell F. , Pfaender Frederic K. 
Published: January 2005

Abstract
The influence of anaerobic conditions on aqueous-phase polycyclic aromatic hydrocarbon (PAH) bioavailability was investigated in laboratory microcosms. Highly aged (&gt;70 years), PAH-contaminated soil was incubated under anaerobic conditions by using various anaerobic headspaces, anaerobic headspaces with an oxygen-scavenging complex (titanium(III) citrate) in the aqueous phase, or anaerobic headspaces with electron-acceptor amendments in the aqueous phase. Incubation of soil solely under anaerobic conditions resulted in increased aqueous concentrations of all PAHs tested (fluoranthene, pyrene, benz[a]anthracene, and benzo[a]pyrene). Benz[a]anthraoene and benzo[a]pyrene extractable concentrations were above aqueous solubility, by as much as an order of magnitude for the latter. The degree of solubility increase observed was a function of molecular weight of the PAH regardless of initial soil concentration, suggesting formation of stable PAH-soluble organic matter associations. The soil samples incubated aerobically for 90 d before imposition of anaerobic conditions did not release PAHs to the aqueous phase. Methanogenic organisms and sulfate-reducing bacteria were seen to have the most significant effect on increases in aqueous-phase PAHs. Polycyclic aromatic hydrocarbons made more soluble under anaerobic conditions was available to be degraded or transformed under aerobic conditions.
A
lagille Syndrome
Authors: Kamath Binita M. , Krantz Ian D. 
Published: January 2005

Abstract

Alagille syndrome, also known as syndromic bile duct paucity or arteriohepatic dysplasia, is a multisystem, autosomal‐dominant, developmental disorder with highly variable expression. It is characterized by abnormalities of the liver, heart, eye, skeleton, and a characteristic facial appearance. The kidney and central nervous system are also affected in a smaller percentage of individuals. The disease causing gene has been identified as
JAG1.
An even wider spectrum of clinical involvement (including intestinal abnormalities, orofacial clefts, hearing loss, and mental retardation) may be seen in those individuals with Alagille syndrome and a deletion of chromosome 20p12.
Charge Association
Authors: Oley Christine A. 
Published: January 2005

AbstractThe CHARGE association is a nonrandom occurrence of congenital malformations including coloboma, congenital heart defects, choanal atresia, retardation of growth, developmental delay, genital abnormalities, ear abnormalities, and deafness. The cause remains unknown. Various genetic mechanisms have been proposed, but there has not been any consistent cytogenetic or molecular defect described. Most cases are sporadic.
Coffin‐Lowry Syndrome
Authors: Hunter Alasdair G.W. 
Published: January 2005

AbstractCoffin‐Lowry syndrome is a distinctive X‐linked dominantly inherited condition that has a birth prevalence of about 1/50,000 and is caused by mutations in theRDS6KA3gene. The hemizygous male presents with significant mental retardation and a facial appearance characterized by a prominent forehead and supraorbital ridges; down‐slanting palpebrae and hypertelorism; a distinctive nose with a low bridge, thick septum, small and anteverted nares; and full and patulous lips with the lower lip everted. The hands are soft and hyperextensible with tapering fingers, and there are a number of minor and nonspecific radiographic changes that may aid in the diagnosis. Progressive kyphoscoliosis can be an important complication. Clinical expression in the heterozygous female can range from completely normal intelligence and appearance, through mild degrees of intellectual impairment and facial dysmorphia, to expression equaling that in the male. There is evidence to suggest a significant risk of premature death, primarily related to pulmonary and cardiac complications but in some cases remaining unexplained.
Deletion 22
q
13 Syndrome (
P
helan‐
M
c
D
ermid Syndrome)
Authors: Phelan Mary C. , Stapleton Gail A. , Rogers R. Curtis 
Published: January 2005

Abstract
The deletion 22q13 syndrome results from loss of a segment of the distal long arm of chromosome 22. Simple deletions, rings, unbalanced translocations, and other less common structural chromosome abnormalities have been associated with this deletion syndrome. The major clinical features are neonatal hypotonia, global developmental delay, absent or severely delayed speech, and normal to accelerated growth. Facial features include dolichocephaly, full brow, flat midface, wide nasal bridge, bulbous nose, deep‐set eyes, ptosis, long eyelashes, puffy eyelids, full cheeks, and prominent ears. Other common features are large fleshy hands, dysplastic toenails, high tolerance to pain, and mouthing or chewing behaviors. Less common features are arachnoid cysts, lymphedema, and hearing loss. There are no apparent life‐threatening defects of the organ systems. Therapies to improve muscle tone, coordination, strength, cognitive skills, and communication skills are beneficial to many individuals. Haploinsufficiency for the gene SHANK3/PROSAP2 is the most likely cause for the neurological deficits associated with deletion 22q13. The eponym for deletion 22q13 is Phelan‐McDermid Syndrome
Kabuki Syndrome
Authors: Hudgins Louanne 
Published: January 2005

AbstractKabuki syndrome (Kabuki makeup syndrome, Niikawa‐Kuroki syndrome) is a multiple‐malformation syndrome characterized by distinctive facial features (long palpebral fissures, eversion of the lower lateral eyelid, arched eyebrows with sparse or dispersed lateral one third, depressed nasal tip, and large, prominent ears), mental retardation, and postnatal growth deficiency. The etiology is unknown, however, it is suspected to be an autosomal dominant disorder. Malformations involving almost every system have been described. The various manifestations of this disorder are described and suggested evaluations and treatment are reviewed.