bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of glycyrrhizin in normal and albumin‐deficient rats
Authors: Koga Kenjiro , Tomoyama Michiko , Ohyanagi Kazuo , Takada Kanji 
Published: June 2008

AbstractThe pharmacokinetics of glycyrrhizin (GZ) was compared in albumin‐deficient rats (NAR) and normal rats (SDR) after intravenous administration. The study sought to clarify the relationship between GZ concentration and its elimination rate in serum, liver and bile when the serum protein binding of GZ decreased. Serum protein binding in SDR and NAR, respectively, was 99.7% and 68.2% for a GZ concentration of 2.5 µg/ml. At steady‐state conditions after i.v. infusion of GZ (0.5–2.0 mg/h), the relationship between the GZ concentration in serum and liver was linear in the SDR but nonlinear in the NAR. For both NAR and SDR, the GZ liver level and the elimination rate was nonlinear, indicating that the elimination of GZ from liver into bile was the rate‐limiting step regardless of serum protein binding, and that the liver GZ level was extremely high when serum protein binding was decreased. It is concluded that a typical dose of GZ in chronic hepatitis patients whose serum albumin level is low will not cause a decrease of therapeutic effect compared with patients with a normal serum albumin level. Copyright © 2008 John Wiley & Sons, Ltd.
Case study and application of process analytical technology (PAT) towards bioprocessing: II. Use of ultra‐performance liquid chromatography (UPLC) for making real‐time pooling decisions for process chromatography
Authors: Rathore Anurag S. , Wood Rebecca , Sharma Ashutosh , Dermawan Shinta 
Published: June 2008

AbstractProcess analytical technology (PAT) has been gaining a lot of momentum in the biopharmaceutical community due to the potential for continuous real‐time quality assurance resulting in improved operational control and compliance. Two of the key goals that have been outlined for PAT are “variability is managed by the process” and “product quality attributes can be accurately and reliably predicted over the design space established for materials used, process parameters, manufacturing, environmental, and other conditions”. Recently, we have been examining the feasibility of applying different analytical tools for designing PAT applications for bioprocessing. We have previously shown that a commercially available online high performance liquid chromatography (HPLC) system can be used for analysis that can facilitate real‐time decisions for column pooling based on product quality attributes (Rathore et al., 2008). In this article we test the feasibility of using a commercially available ultra‐ performance liquid chromatography (UPLC) system for real‐time pooling of process chromatography columns. It is demonstrated that the UPLC system offers a feasible approach and meets the requirements of a PAT application. While the application presented here is of a reversed phase assay, the approach and the hardware can be easily applied to other modes of liquid chromatography. Biotechnol. Bioeng. 2008;101: 1366–1374. © 2008 Wiley Periodicals, Inc.
Stabilization of α‐chymotrypsin upon PEGylation correlates with reduced structural dynamics
Authors: Rodríguez‐Martínez José A. , Solá Ricardo J. , Castillo Betzaida , Cintrón‐Colón Héctor R. , Rivera‐Rivera Izarys , Barletta Gabriel , Griebenow Kai 
Published: June 2008

AbstractProtein stability remains one of the main factors limiting the realization of the full potential of protein therapeutics. Poly(ethylene glycol) (PEG) conjugation to proteins has evolved into an important tool to overcome instability issues associated with proteins. The observed increase in thermodynamic stability of several proteins upon PEGylation has been hypothesized to arise from reduced protein structural dynamics, although experimental evidence for this hypothesis is currently missing. To test this hypothesis, the model protein α‐chymotrypsin (α‐CT) was covalently modified with PEGs with molecular weights (MW) of 700, 2,000 and 5,000 and the degree of modification was systematically varied. The procedure did not cause significant tertiary structure changes. Thermodynamic unfolding experiments revealed that PEGylation increased the thermal transition temperature (Tm) of α‐CT by up to 6°C and the free energy of unfolding [ΔGU (25°C)] by up to 5 kcal/mol. The increase in stability was found to be independent of the PEG MW and it leveled off after an average of four PEG molecules were bound to α‐CT. Fourier‐transformed infrared (FTIR) H/D exchange experiments were conducted to characterize the conformational dynamics of the PEG‐conjugates. It was found that the magnitude of thermodynamic stabilization correlates with a reduction in protein structural dynamics and was independent of the PEG MW. Thus, the initial hypothesis proved positive. Similar to the thermodynamic stabilization of proteins by covalent modification with glycans, PEG thermodynamically stabilizes α‐CT by reducing protein structural dynamics. These results provide guidance for the future development of stable protein formulations. Biotechnol. Bioeng. © 2008 Wiley Periodicals, Inc.
Enzymatic hydrolysis of cellulose coupled with electricity generation in a microbial fuel cell
Authors: Rezaei Farzaneh , Richard Tom L. , Logan Bruce E. 
Published: June 2008

AbstractElectricity can be directly generated by bacteria in microbial fuel cells (MFCs) from a variety of biodegradable substrates, including cellulose. Particulate materials have not been extensively examined for power generation in MFCs, but in general power densities are lower than those produced with soluble substrates under similar conditions likely as a result of slow hydrolysis rates of the particles. Cellulases are used to achieve rapid conversion of cellulose to sugar for ethanol production, but these enzymes have not been previously tested for their effectiveness in MFCs. It was not known if cellulases would remain active in an MFC in the presence of exoelectrogenic bacteria or if enzymes might hinder power production by adversely affecting the bacteria. Electricity generation from cellulose was therefore examined in two‐chamber MFCs in the presence and absence of cellulases. The maximum power density with enzymes and cellulose was 100 ± 7 mW/m2 (0.6 ± 0.04 W/m3), compared to only 12 ± 0.6 mW/m2 (0.06 ± 0.003 W/m3) in the absence of the enzymes. This power density was comparable to that achieved in the same system using glucose (102 ± 7 mW/m2, 0.56 ± 0.038 W/m3) suggesting that the enzyme successfully hydrolyzed cellulose and did not otherwise inhibit electricity production by the bacteria. The addition of the enzyme doubled the Coulombic efficiency (CE) to CE = 51% and increased COD removal to 73%, likely as a result of rapid hydrolysis of cellulose in the reactor and biodegradation of the enzyme. These results demonstrate that cellulases do not adversely affect exoelectrogenic bacteria that produce power in an MFC, and that the use of these enzymes can increase power densities and reactor performance. Biotechnol. Bioeng. © 2008 Wiley Periodicals, Inc.
Increasing yeast secretion of heterologous proteins by regulating expression rates and post‐secretory loss
Authors: Huang Dagang , Gore Patrick R. , Shusta Eric V. 
Published: June 2008

AbstractHeterologous protein secretion involves the coupled processes of protein synthesis, protein folding, and secretory trafficking. A more complete understanding of how these processes interrelate could help direct optimization of secretion systems. Here we provide a detailed study regarding the dynamics of heterologous protein secretion from yeast in terms of intracellular protein levels, secreted protein levels, and unfolded protein response (UPR). Three different protein expression induction temperatures (20, 30, and 37°C) were investigated as a means to modulate expression rates and thus cellular responses. Inducing at 20°C yielded the slowest initial secretion rate, but the highest absolute level of product. Correspondingly, the level and the rate of both intracellular protein accumulation and unfolded protein response (UPR) activation were also the lowest at 20°C. In addition, secretion ceased after approximately 22 h at 30 and 37°C, respectively, while it was continuous until nutrient depletion at 20°C. Maxima in secretion levels were observed that were a result of the additive effects of secretion cessation and post‐secretory protein loss. The post‐secretory loss of protein did not appear to result from solution phase proteolysis or aggregation, but required the presence of yeast cells. Refeeding of both yeast nitrogen base and casamino acids successfully prevented the post‐secretory loss of protein at both high (37°C) and low (20°C) temperatures, and further increased secretion levels 1.5‐fold at 20°C where the secretory pathway was still functioning. Taken together, these findings suggest that there exists an appropriate balance between protein synthesis, processing and secretion rates required for secretion optimization. Biotechnol. Bioeng. © 2008 Wiley Periodicals, Inc.
Teleconferencing model for forensic consultation, court testimony, and continuing education
Authors: Miller Thomas W. , Clark James , Veltkamp Lane J. , Burton Deborah C. , Swope Marian 
Published: June 2008

AbstractA medical center‐based forensic clinic that provides the necessary comprehensive consultation, continuing education, court testimony, and clinical services through an applied model of teleconferencing applications is addressed. Telemedicine technology and services have gained the attention of both legal and clinical practitioners, examining trends and models of health care for underserved populations, and identifying where consultation with a team of professionals may benefit service providers in rural communities. The contribution offered herein provides an understanding of the history of the development of the clinic, a theoretical model that has been applied to a clinical forensic program that employs telepsychiatry services, and the ethical and malpractice liability issues confronted in using teleconferencing services. This model is examined through a child and adolescent forensic evaluation clinic. The goals of this model are offered, as are a number of applications within the broad spectrum of services utilizing telemedicine. Finally, changing patterns are addressed in clinically based health‐care delivery for criminal justice, social services, and forensic mental health. Copyright © 2008 John Wiley & Sons, Ltd.
Forensic telepsychiatry in the United Kingdom
Authors: Saleem Younus , Taylor Mark H. , Khalifa Najat 
Published: June 2008

AbstractForensic telepsychiatry remains in its infancy in the United Kingdom. This article sets out to describe how it can be used within a community forensic service, and the future challenges ahead in the United Kingdom. It looks at relevant academic, governmental, and legal resources and is designed as a scholarly reflection by clinicians rather than as a formal literature review. Copyright © 2008 John Wiley & Sons, Ltd.
Empirical evidence on the use and effectiveness of telepsychiatry via videoconferencing: Implications for forensic and correctional psychiatry
Authors: Antonacci Diana J. , Bloch Richard M. , Saeed Sy Atezaz , Yildirim Yilmaz , Talley Jessica 
Published: June 2008

AbstractA growing body of literature now suggests that use of telepsychiatry to provide mental health services has the potential to solve the workforce shortage problem that directly affects access to care, especially in remote and underserved areas. Live interactive two‐way audio–video communication—videoconferencing—is the modality most applicable to psychiatry and has become synonymous with telepsychiatry involving patient care, distance education, and administration. This article reviews empirical evidence on the use and effectiveness of videoconferencing in providing diagnostic and treatment services in mental health settings that serve child, adolescent, and adult populations. Descriptive reports, case studies, research articles, and randomized controlled trials related to clinical outcomes were identified and reviewed independently by two authors. Articles related to cost‐effectiveness, technological issues, or legal or ethical aspects of telepsychiatry were excluded. The review of the evidence broadly covers mental health service provision in all settings, including forensic settings. Given the sparse literature on telepsychiatry in forensic settings, we discuss implications for mental health care across settings and populations and comment on future directions and potential uses in forensic or correctional psychiatry. Copyright © 2008 John Wiley & Sons, Ltd.
Telepsychiatry with rural American Indians: issues in civil commitments
Authors: Shore Jay H. , Bloom Joseph D. , Manson Spero M. , Whitener Ron J. 
Published: June 2008

AbstractThe use of live interactive videoconferencing to provide psychiatric care, telepsychiatry, has particular relevance for improving mental health treatment to rural American Indian reservations. There is little literature on civil commitments in telepsychiatry and none specifically addressing this topic among American Indians. This article reviews telepsychiatry in the mental health care of American Indians, civil commitments and telepsychiatry in general, and the current state of civil commitments in American Indian communities. We conclude by considering commitment through telepsychiatry in rural reservations and offering guidelines to assist practitioners in navigating this challenging landscape. Civil commitments of American Indian patients residing in rural reservations can be successfully accomplished through videoconferencing by thoughtful and informed clinicians. However, much more work is needed in this area, including research into the cultural attitudes and perspectives towards commitments and further inquiry regarding potential legal precedents, as well as case reports and examples of this work. Copyright © 2008 John Wiley & Sons, Ltd.
Videoconferencing and forensic mental health in Australia
Authors: Sullivan Danny H. , Chapman Murray , Mullen Paul E. 
Published: June 2008

AbstractVideoconferencing is in common use in Australian forensic mental health services. It provides opportunities to link remote prisons, courts, and psychiatric clinics with distant specialist services, and enables a range of activities including assessment, treatment and feedback, expert testimony, education, and inter‐service planning. These functions are acceptable to patients and clinicians, and in Australia videoconferencing minimizes disruption to small services and their patients, who might otherwise face lengthy journeys. In particular, marginalized patient groups, including indigenous people and prisoners, may receive better services. The evidence base supports use of videoconferencing despite a number of practical, legal, and clinical issues that may reduce its effectiveness compared with face‐to‐face assessments. Videoconferencing technologies are critical to effective forensic mental health services in Australia. Copyright © 2008 John Wiley & Sons, Ltd.
Selenoglutaredoxin as a Glutathione Peroxidase Mimic
Authors: Casi Giulio , Roelfes Gerard , Hilvert Donald 
Published: June 2008

AbstractGlutaredoxin (Grx1) from Escherichia coli is a monomeric, 85‐amino‐acid‐long, disulfide‐containing redox protein. A Grx1 variant in which the redox‐active disulfide was replaced with a selenocysteine (C11U/C14S) was prepared by native chemical ligation from three fragments as a potential mimic of the natural selenoenzyme glutathione peroxidase (Gpx). Selenoglutaredoxin, like the analogous C14S Grx1 variant, shows weak peroxidase activity. The selenol provides a 30‐fold advantage over the thiol, but its activity is four orders of magnitude lower than that of bovine Gpx. In contrast, selenoglutaredoxin is an excellent catalyst for thiol–disulfide exchange reactions; it promotes the reduction of β‐hydroxyethyldisulfide by glutathione with a specific activity of 130 units mg−1. This value is 1.8 times greater than that of C14S Grx1 under identical conditions, and >104 greater than the peroxidase activity of either enzyme. Given the facile reduction of the glutathionyl‐selenoglutaredoxin adduct by glutathione, oxidation of the selenol by the alkyl hydroperoxide substrate likely limits catalytic turnover and will have to be optimized to create more effective Gpx mimics. These results highlight the challenge of generating Gpx activity in a small, generic protein scaffold, despite the presence of a well‐defined glutathione binding site and the intrinsic advantage of selenium over sulfur derivatives.
General Synthesis and Aggregation Behaviour of New Single‐Chain Bolaphospholipids: Variations in Chain and Headgroup Structures
Authors: Drescher Simon , Meister Annette , Graf Gesche , Hause Gerd , Blume Alfred , Dobner Bodo 
Published: June 2008

AbstractThe chemical structures of polymethylene‐1,ω‐bis(phosphocholines) that self‐assemble into nanofibres was modified on the one hand in the hydrophobic chain region, by introduction of sulfur and oxygen atoms, and on the other hand by variation of the polar headgroup structure with functionalised tertiary amines. The temperature‐dependent self‐assembly of these novel bolaphospholipids into nanofibres and spherical micelles was investigated by differential scanning calorimetry (DSC) and transmission electron microscopy (TEM). The thermal stabilities of the nanofibres strongly depend on the chemical compositions of the headgroups and of the hydrophobic chains. The insertion of new functionalities in the headgroup region by click chemistry makes these substances interesting for potential applications in bioscience and materials science.
Insights into the Post‐Translational Methylation of Arginine from Studies of Guanidinium–Water Nanodroplets
Authors: McQuinn Keri , McIndoe J. Scott , Hof Fraser 
Published: June 2008

AbstractHighly solvated methylated guanidinium ions ([MenGuan(H2O)m]+; n=0–4 and 6; m=1–>50), which model the various post‐translationally methylated states of arginine, were generated in the electrospray ionization (ESI) source of an unmodified commercial tandem mass spectrometer. The dehydration processes of highly solvated [MenGuan(H2O)21]+ ions were monitored by using energy‐dependent ESI MS. These data, together with supporting calculations, provide a detailed picture of the interplay of methylation and hydration, and both the calculations and the experimental evidence suggest a specific structural basis for the observed effects. The ramifications for biochemical binding events that are controlled by the post‐translational methylation of arginine to give dimethylarginines are discussed.
Expression of the fast twitch troponin complex, fTnT, fTnI and fTnC, in vascular smooth muscle
Authors: Moran Carlos M. , Garriock Robert J. , Miller Melanie K. , Heimark Ronald L. , Gregorio Carol C. , Krieg Paul A. 
Published: June 2008

AbstractIt is generally believed that proteins of the troponin complex are not expressed in smooth muscle. We have directly assayed for expression of troponin transcripts in mouse vascular smooth muscle and found that troponin sequences normally associated with fast twitch skeletal muscle (fTnT, fTnI, fTnC) were present at significant levels in the thoracic aorta. In situ hybridization experiments demonstrated that fTnT, fTnI and fTnC transcripts were expressed in the smooth muscle layer of mouse blood vessels of all sizes. Protein blot analysis using rat tissue showed that at least two members of the troponin complex, Troponin T and Troponin I, were translated in vascular smooth muscle of the aorta. Finally, immuno‐fluorescence microscopy of rat aortic smooth muscle revealed that TnT and TnI are localized in a unique pattern, coincident with the distribution of tropomyosin. It seems likely therefore, that a complete troponin complex is expressed in vascular smooth muscle and is associated with the contractile machinery of the cell. These observations raise the possibility that troponins play a role in regulation of smooth muscle function. Cell Motil. Cytoskeleton 2008. © 2008 Wiley‐Liss, Inc.
Up‐regulation of CD40 with juxtacrine activity in human nonsmall lung cancer cells correlates with poor prognosis
Authors: Ishikawa Keidai , Miyamoto Masaki , Yoshioka Tatsuya , Kato Tatsuya , Kaji Mitsuhito , Ohbuchi Toshiro , Hirano Satoshi , Itoh Tomoo , Dosaka‐Akita Hirotoshi , Kondo Satoshi 
Published: June 2008

AbstractBACKGROUND.CD40 and its ligand, CD154, play a regulatory role in several signaling pathways among lymphocytes. Recently, it was reported that CD40 is expressed in several malignant tumors. However, the clinical impact of CD40 expression in nonsmall cell lung cancer has not been studied widely.METHODS.One hundred twenty‐nine surgical specimens of nonsmall cell lung cancer were assessed immunohistochemically for CD40 and CD154 expression, and that expression was correlated with patients' clinicopathologic parameters and outcome. Subsequently, in vitro analysis of CD40‐CD154 signaling was performed.RESULTS.Immunohistochemical staining of tumor cells confirmed that 67 patients (51.9%) were positive for CD40, and 76 patients (58.9%) were positive for CD154. The survival of patients who had tumors that were negative for CD40 was significantly better than the survival of patients who had tumors that were positive for CD40 (P = .0004). Multivariate analysis using a Cox regression model indicated that CD40 expression in cancer cells is an independent, unfavorable prognostic factor (risk ratio, 1.855; P = .0403). By using an in vitro juxtacrine growth factor assay, the growth of LK2 cells (CD40‐positive/CD154‐negative) was accelerated by CD154‐positive cancer cells, such as PC10 cells (CD40‐negative/CD154‐positive), by a juxtacrine mechanism.CONCLUSIONS.The current results suggested that CD40 expression in tumors is associated with a poor prognosis and that the juxtacrine interaction of CD40‐CD154 among cancer cells facilitates the development of malignant potential in nonsmall cell lung cancer. Cancer 2008. © 2008 American Cancer Society.
Intracellular Phospho‐Flow cytometry reveals novel insights into TCR proximal signaling events. A comparison with Western blot
Authors: Haas Anna , Weckbecker Gisbert , Welzenbach Karl 
Published: June 2008

AbstractPhospho‐site specific antibodies become increasingly available, enabling the study of signaling events by Western blotting (WB) or intracellular flow cytometry (Phospho‐Flow). Here we compared data generated by WB or Phospho‐Flow regarding the kinetics and degree of phosphorylation of membrane proximal TCR signaling molecules. Phosphorylation events in Jurkat T cells were triggered by anti‐CD3 stimulation (OKT3) or by oxidative stress (H2O2) and were analyzed by Phospho‐Flow or WB. Both techniques showed that OKT3‐ or H2O2‐induced, transient phosphorylation of ZAP70 or LAT was dependent on functional Lck. Phospho‐Flow data revealed differences in the kinetics and the degree of H2O2‐ or OKT3‐mediated protein phosphorylation compared with WB data. In addition, using Phospho‐Flow we discovered that H2O2‐induced phosphorylation of TCR signaling proteins was inhibited by small molecular weight kinase inhibitors far more potently than OKT3‐triggered protein phosphorylation, despite a superior induction of phosphorylation by H2O2.This finding was confirmed by WB. Interestingly, we identified by Phospho‐Flow that, in P116 Jurkat cells lacking ZAP70 protein expression, H2O2 potently triggered the phosphorylation of ZAP70 residues Y493 and Y292 but not Y319. The phosphorylation of these ZAP70 tyrosine residues cells was blocked by an Lck inhibitor, suggesting the existence of an Lck‐coupled truncated ZAP70 protein or a novel isoform of ZAP70 in P116 cells. Phospho‐Flow is a largely quantitative technology with excellent throughput, highly suited in studying the function or inhibition of TCR signaling pathways and allowing the detection of novel pathway insights. It can serve as a good complement to Western blot analysis. © 2008 International Society for Advancement of Cytometry