bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions between pairs of antimalarial drugs studied by experimental and ab initio13C NMR chemical shifts
Authors: Casabianca Leah B. , de Dios Angel C.
Published: February 2006

The interactions between the antimalarial drugs chloroquine (CQ) and amodiaquine (AQ), chloroquine and quinine (QN), and amodiaquine and quinine are studied by 13C NMR. Experimental changes in chemical shift are compared to nucleus‐independent chemical shifts to determine the best structure of the complex formed by each drug pair in solution. Structures of the CQ–AQ and CQ–QN complexes are found to be similar to those found previously for the drug dimers. On the other hand, the best solution structure for the AQ–QN complex suggests that the quinoline rings of the two drugs are at an angle with respect to each other. Copyright © 2006 John Wiley & Sons, Ltd.
Conformational analyses of 2,3‐dihydroxypropanoic acid as a function of solvent and ionization state as determined by NMR spectroscopy
Authors: Drake Michael D. , Harsha Alex K. , Terterov Sergei , Roberts John D.
Published: February 2006

Vicinal 1H1H coupling constants were used to determine the conformational preferences of 2,3‐dihydroxypropanoic acid (1) (DL‐glyceric acid) in various solvents and its different carboxyl ionization states. The stereospecific assignments of J12 and J13 were confirmed through the point‐group substitution of the C‐3 hydrogen with deuterium, yielding rac‐(2SR,3RS)‐[3‐2H]‐1, and the observation of only J13 in the 1H NMR spectra. While hydrogen bonding and steric strain may be expected to drive the conformational equilibrium, their role is overshadowed by a profound gauche effect between the vicinal hydroxyl groups that mimics other substituted ethanes, such as 1,2‐ethanediol and 1,2‐difluoroethane. At low pH, the conformational equilibrium is heavily weighted toward the gauche‐hydroxyl rotamers with a range of 81% in DMSO‐d6 to 92% in tert‐butyl alcohol‐d10. At high pH, the equilibrium exhibits a larger dependence upon the polarity and solvating capability of the medium, although the gauche effect still dominates in D2O, 1,4‐dioxane‐d8, methanol‐d4, and ethanol‐d6 (96, 89, 85, and 83% gauche‐hydroxyls respectively). The observed preference for the gauche‐hydroxyl rotamers is believed to stem primarily from hyperconjugative σCH → σ*COH interactions. Copyright © 2006 John Wiley & Sons, Ltd.
Effect of rapidly relaxed electron spin anisotropically coupled to nearby nuclear partners
Authors: Werbelow Larry
Published: February 2006

In practice, many situations arise when a perturbed nuclear spin relies upon the aid of a rapidly relaxed spin neighbor in order to realize thermal equilibrium. Conventional treatments view the efficiently relaxed spin as part of the ‘lattice’, invoke the secular approximation, and consider the associated time correlation of the lattice variables, phenomenologically. Recently, an ab initio perturbative approach has been proposed for investigation of these spin systems. In this work, a similar formalism is applied to the scenario, in which nuclear spin relaxation is effected via an anisotropically coupled, efficiently relaxed, spin. Interesting conflicts with standard theory are revealed. Furthermore, although left mostly unexplored, this approach lends insight into numerous related aspects of magnetic relaxation including separation of timescales, distinction between spin and spatial averaging, paramagnetic relaxation, Curie spin relaxation, and the dynamic frequency shift. Copyright © 2006 John Wiley & Sons, Ltd.
Calculating protein structures directly from anisotropic spin interaction constraints
Authors: Smurnyy Yegor , Opella Stanley J.
Published: February 2006

Protein structure determination by solid‐state NMR of aligned samples relies on the fundamental characteristics of the anisotropic nuclear spin interactions present in isotopically labeled proteins. Progress in the implementation of algorithms that calculate protein structures from the orientational constraints in the chemical shift and heteronuclear dipolar coupling interactions is described using both simulated and experimental data. Copyright © 2006 John Wiley & Sons, Ltd.
1H/29Si cross‐polarization NMR experiments of silica‐reinforced polydimethylsiloxane elastomers: probing the polymer–filler interface
Authors: Iuliucci Robbie , Taylor Craig , Hollis W. Kirk
Published: February 2006

Polydimethylsiloxane (PDMS) elastomers reinforced with fumed silica exhibit unusual strength characteristics that are necessary for their designed applications. The microscopic details of the surface interaction between the polymer and silica are not well characterized. 1H/29Si cross‐polarization (cp) experiments are used to characterize cured and uncured samples of Dow Corning silastic 745. Changes to the cp dynamics upon curing are evident by the variation in peak intensities in the variable contact‐time spectra of the two samples. Estimates of the cp relaxation parameters are reported for the cured sample. Additional information can be obtained by expanding the 1H/29Si cp to a two‐dimensional heteronuclear correlation experiment. Dramatic differences between the cured and uncured 1H/29Si HetCor spectra are observed that are not visible in the 1D spectra. These changes can be rationalized as a dehydration of the silica surface and an increased hardening of the polymer after the curing process. Furthermore, isolation of the NMR signal corresponding to nuclei at or near the polymer–filler interface may be achieved in the 2D 1H/29Si HetCor spectrum. Copyright © 2006 John Wiley & Sons, Ltd.
Modeling the 13C chemical‐shift tensor in organic single crystals by quantum mechanical methods: finite basis set effects
Authors: Sefzik Travis H. , Fidler Jacqueline M. , Iuliucci Robbie J. , Facelli Julio C.
Published: February 2006

The influence of using finite basis sets to calculate 13C magnetic shieldings were explored using the Hartree‐Fock and the B3LYP hybrid density functional methods. The shielding values were compared in a linear least‐squares fashion for a test group of 102 13C complete chemical‐shift tensors determined from 14 organic single crystals. Pople's basis sets allow for the addition of polarization and diffuse functions in a straightforward way, allowing the examination of 81 combinations at the double and triple zeta level. Dunning's correlation‐consistent basis sets were explored as well. The errors associated with predicting the shielding values were found to be largely systematic as revealed by the analysis of the determined regression parameters between calculated chemical shieldings and experimental chemical shifts. Expansion of the basis set leads to a convergence of these regression parameters to their ideal values. The random errors, however, do not decrease by employing larger basis sets; therefore, given the appropriate regression parameters, a small basis description such as 3‐21G can be adequate in predicting the relative magnetic‐shielding values, i.e. the chemical shifts. Furthermore, in certain cases the inclusion of unbalanced diffuse and polarization functions can significantly degrade the predicted shielding rmsd. Unless employed carefully, these functions do not justify their computational expense. The chemical‐shift distance is used to evaluate shielding predictions in individual tensor components. The analysis of the chemical‐shift's distance between calculated and experimental data indicates an orientational dependence on the magnitude of errors and suggests the use of the shift anisotropy as a useful fiduciary mark to optimize model chemistries for magnetic‐shielding calculations. Copyright © 2006 John Wiley & Sons, Ltd.
Solid‐state 14N MAS NMR of ammonium ions as a spy to structural insights for ammonium salts
Authors: Jakobsen Hans J. , Hove Anders R. , Hazell Rita G. , Bildsøe Henrik , Skibsted Jørgen
Published: February 2006

The high resolution offered by magic‐angle spinning (MAS), when compared to the static condition in solid‐state NMR of powders, has been used to full advantage in a 14N MAS NMR study of some ammonium salts: CH3NH3Cl, (NH4)2(COO)2·H2O, (CH3)3(C6H5CH2)NCl, (CH3)3(C6H5)NI, [(n‐C4H9)4N]2Mo2O7, (NH4)2HPO4, and NH4H2PO4. It is shown that the high‐quality 14N MAS NMR spectra, which can be obtained for these salts, allow determination of the 14N quadrupole coupling parameters, i.e. CQ (the quadrupole coupling constant) and ηQ (the asymmetry parameter), with very high precision. In particular, it is shown that precise CQ, ηQ parameters can be determined for at least two different 14N sites in case the individual spinning‐sideband (ssb) intensities arise from a single manifold of ssbs, i.e. the ssbs for the two sites cannot be resolved. This feature of 14N MAS NMR, which is the first demonstration for manifolds of ssb in MAS NMR without the potential information from a central transition, becomes especially useful at the slow spinning frequencies (νr = 1000–1500 Hz) applied to some of the ammonium salts studied here. The detection of the number of sites has been confirmed by the corresponding crystal structures determined from single‐crystal X‐ray diffraction (XRD), either in this work for the unknown structure of benzyl trimethylammonium chloride or from reports in the literature. The magnitudes of the 14N quadrupole coupling constants for the ammonium salts studied here are in the range from CQ ∼ 20 kHz to 1 MHz while the asymmetry parameters span the full range 0 ≤ ηQ ≤ 1. Clearly, the 14N quadrupole coupling parameters (CQ, ηQ) for ammonium ions appear highly sensitive toward crystal structure and therefore appreciably more informative for the characterization of ammonium salts in comparison to the isotropic 14N (or 15N) chemical shifts. Copyright © 2006 John Wiley & Sons, Ltd.
FGF Ligand Family mRNA Expression Profile for Mouse Preimplantation Embryos, Early Gestation Human Placenta, and Mouse Trophoblast Stem Cells
Authors: Zhong W. , Wang Q.T. , Sun T. , Wang F. , Liu J. , Leach R. , Johnson A. , Puscheck E.E. , Rappolee D.A.
Published: February 2006

Signaling by fibroblast growth factor (FGF) is essential is for trophoblast stem (TS) cells and preimplantation embryos. FGF4 provides essential signaling, but the expression of the complete set of 23 FGF family members has not been analyzed. Here, semi‐quantitative RT‐PCR and microarray analyses were used to define expression of all FGF ligand mRNA. RT‐PCR was done for developmentally important FGF subfamilies, FGF10/FGF22 and FGF8/FGF17/FGF18 as well as FGF11. FGF4 and FGF18 are detected at highest levels by RT‐PCR and microarrays. FGF10 was detected at low levels in both assays. FGF11 was detected at moderate levels by microarray, but not by RT‐PCR. FGF17 was detected at low levels by array and moderate levels by RT‐PCR. FGF8 and FGF22 were detected by RT‐PCR, but not by microarrays during late cleavage divisions. FGF8, FGF5, and FGF9 were detected in the oocyte by microarray. FGF2, FGF3, and FGF7 were not detected by RT‐PCR or microarrays and FGF13, FGF14, and FGF23 were not detected by microarray. Since a major role of FGF is to maintain TS cells, we tested human and mouse placental cell lines and early gestation human placenta for expression of FGF ligands. Expression in mouse TS cells was compared with preimplantation embryos, and human placental cell line expression was compared with human placenta, to infer which ligands are expressed in placental lineage vs. other cell lineages. The data suggest that human and mouse placenta share FGF18 and its high expression suggests preimplantation and early placental function. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Improved neuronal tract tracing using manganese enhanced magnetic resonance imaging with fast T1 mapping
Authors: Chuang Kai‐Hsiang , Koretsky Alan
Published: February 2006

There has been growing interest in using manganese‐enhanced MRI (MEMRI) to detect neuronal activation, neural architecture, and neuronal connections. Usually Mn2+ produces a very wide range of T1 change. In particular, in neuronal tract tracing experiments the site of Mn2+ injection can have very short T1 while distant regions have small T1 reductions, primarily due to dilution of Mn2+. Most MEMRI studies use T1‐weighted sequences, which can only give optimal contrast for a narrow range of T1 changes. To improve sensitivity to the full extent of Mn2+ concentrations and to optimize detection of low concentrations of Mn2+, a fast T1 mapping sequence based on the Look and Locker technique was implemented. Phantom studies demonstrated less than 6.5% error in T1 compared to more conventional T1 measurements. Using center‐out segmented EPI, whole‐brain 3D T1 maps with 200‐μm isotropic resolution were obtained in 2 h from rat brain. Mn2+ transport from the rat olfactory bulb through appropriate brain structures could be detected to the amygdala in individual animals. The method reliably detected less than 7% reductions in T1. With this quantitative imaging it should be possible to study more extensive pathways using MEMRI and decrease the dose of Mn2+ used. Magn Reson Med, 2006. Published 2006 Wiley‐Liss, Inc.
Passive staining: A novel ex vivo MRI protocol to detect amyloid deposits in mouse models of Alzheimer's disease
Authors: Dhenain Marc , Delatour Benoît , Walczak Christine , Volk Andreas
Published: February 2006

Amyloid plaques are one of the hallmarks of Alzheimer's disease (AD). This study evaluated a novel μMRI strategy based on “passive staining” of brain samples by gadoteric acid. The protocol was tested at 4.7T on control animals and APP/PS1 mice modeling AD lesions. T1 was strongly decreased in passively stained brains. On high‐resolution 3D gradient echo images, the contrast between the cortex and subcortical structures was highly improved due to a T2* effect. The brains of APP/PS1 mice revealed plaques as hypointense spots. They appeared larger in long compared to short TE images. This suggests that, after passive staining, plaques caused a susceptibility effect. This easily performed protocol is a complementary method to classic histology to detect the 3D location of plaques. It may also be used for the validation of in vivo MRI protocols for plaque detection by facilitating registration with histology via post mortem MRI. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Bunched phase encoding (BPE): A new fast data acquisition method in MRI
Authors: Moriguchi Hisamoto , Duerk Jeffrey L.
Published: February 2006

A new fast data acquisition method, “Bunched Phase Encoding” (BPE), is presented. In conventional rectilinear data acquisition, only a readout gradient (and no phase encoding gradient) is applied when k‐space data are acquired. Reduction of the number of phase encoding lines by increasing the phase encoding step size often leads to aliasing artifacts. Papoulis's generalized sampling theory asserts that in some cases aliasing artifact‐free signals can be reconstructed even if the Nyquist criterion is violated in some regions of the Fourier domain. In this study, Papoulis's theoretical construct is exploited to reduce the number of acquired phase encoding lines. To achieve this, k‐space data are sampled along a “zigzag” trajectory during each readout; samples are acquired at a sampling frequency higher than that of the normal rectilinear acquisition. The total number of TR cycles and, hence, the total scan time can be reduced. The resultant signal‐to‐noise ratio (SNR) often varies across the reconstructed image when using the BPE technique, and the image SNR depends on the reconstruction method. This work is comparable to a gradient based version of parallel imaging. Evidence suggests it may serve as the basis for new opportunities for fast data acquisition in MRI. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Effects of d.c. potential patterns on the performance of ion‐exchange polymer based molecular actuators
Authors: Shoji Eiichi , Hirayama Daisuke , Kusakabe Masahiro , Inoue Tamotsu
Published: February 2006

The dynamic performance (i.e. displacement, current, velocity, and force) of ion‐exchange polymer based actuators (the Nafion™/platinum electrodes) have been examined by developing instrumentation. The CCD imaging technique was examined to evaluate the displacement under the various d.c. potential patterns. Two different d.c. potential patterns with or without a rest were applied to the electrodes at 0.1 Hz. It was better to take a rest at 0 V for the polarization back and forth between +2 and −2 V to give lower current consumption and longer displacement. The actuator produced the force of ca. 0.95 g at 3.25 V in air. The result also demonstrated that higher overpotential has to be avoided to maintain the maximum force. The generative force is in inverse proportion to the length of the actuators. The dimension of the film strongly governs the force production and its performance. Copyright © 2006 John Wiley & Sons, Ltd.
Polarization processes in electrorheological fluids based on conductive polymers
Authors: Krztoń‐Maziopa A. , Ciszewska M. , Płocharski J.
Published: February 2006

Electrorheological (ER) fluids are composed of dielectric particles dispersed in an inert liquid of low electric permittivity. Upon the application of an electric field ER fluids rapidly solidify, or increase their viscosity. Characteristic increase of the viscosity of ER fluids is due to the formation of particle chains that bridge the electrodes. This process is greatly affected by polarization processes within the solid phase and at the surface of the grains. These phenomena are governed by dopants, functional groups, structure of the solid particles and the solid/liquid interface. To find relations between parameters of the ER effect and material properties of components of ER fluids, two main types of the materials were investigated: conjugated polymers [polyphenylene (PPP), pyrolyzed polyacrylonitrile (PAN) and polythiophene] and solid electrolytes based on polyacrylonitrile complexed with inorganic salts. It was found that the ER activity resulted from surface polarization processes due to the presence of polar species (PAN) or bulk polarization related to mobile ions (PPP). Polythiophene, despite the presence of a conjugated system of multiple bonds, showed only residual ER effect. Solid electrolyte‐based fluids exhibited relatively high activity originated from ionic polarization. Copyright © 2006 John Wiley & Sons, Ltd.
Mechanism of Romascone® release from hydrolyzed vinyl acetate nanoparticles: thermogravimetric method
Authors: Ouali L. , Léon G. , Normand V. , Johnsen H. , Dyrli A. , Schmid R. , Benczedi D.
Published: February 2006

The evaporation kinetics of pure Romascone® (methyl 2,2‐dimethyl‐6‐methylene‐1‐cyclohexanecarboxylate) and Romascone® when mixed with vinyl acetate (VAc) nanoparticles have been determined by using thermogravimetric analysis. For pure Romascone®, the evaporation rate follows an Arrhenius dependence with temperature. When Romascone® is mixed with VAc nanoparticles, two evaporation mechanisms are identified depending on the presence of comonomer and crosslinking degree. (a) Evaporation limited by the presence of non‐interactive nanoparticles. The evaporation rate is governed by the evolution of the equilibrium vapor pressure that depends on the volume fraction of volatile molecules. (b) Evaporation limited by the diffusion of volatile molecules through a polymeric particle wall.

Since the diffusion depends on the physical state or structure of the polymeric nanoparticle phase, the volume fraction of volatile molecules is a determinant parameter. Furthermore, a sudden modification in the evolution of the diffusion coefficient with volatile volume fraction gives rise to discussion on phase transition. Copyright © 2006 John Wiley & Sons, Ltd.
Electrorheological effect in hybrid fluids with liquid crystalline additives
Authors: Ciszewska M. , Krztoń‐Maziopa A. , Płocharski J.
Published: February 2006

Conventional electrorheological (ER) fluids consist of electrically polarizable particles dispersed in an inert insulating liquid. They are characterized by a development of a yield stress upon application of an external electric field. They resemble Bingham fluids with yield stress value depending on electric field. A viscosity increase in the presence of an electric field has been also found in homogeneous solutions of liquid crystalline polymers with no yield stress observed. In this study these two types of fluids and combined dispersions of the solid particles in the liquid crystalline matrix were investigated. A lyotropic liquid crystalline polymer—poly(n‐hexyl isocyanate) (PHIC)—dissolved in xylene was chosen as the active matrix. The dispersed solid phase was comprised of two kinds of polymers: pyrolyzed polyacrylonitryle (PAN) showing electron conductivity, and PAN doped with two salts (KSCN, NaSCN), resulting in ionic conductivity. The rheological measurements under an electric field were performed. The pristine xylene solution of PHIC was characterized first as well as the 15% m/m dispersions of PAN powders in silicone oil. Then the dispersions in the liquid crystalline matrix were investigated showing a strong ER effect whose magnitude was considerably enhanced in comparison to both ER active components measured separately. Copyright © 2006 John Wiley & Sons, Ltd.
Regulated release of VWF and FVIII and the biologic implications
Authors: Haberichter S.L. , Shi Q. , Montgomery R.R.
Published: February 2006

von Willebrand factor (VWF) performs a critical function in platelet binding at the site of vascular injury and also serves as the carrier protein for coagulation factor FVIII (FVIII), protecting it from proteolytic degradation in plasma. Both proteins undergo rapid, regulated release in response to DDAVP administration in patients with mild hemophilia A or von Wille‐brand disease. Here, we attempt to summarize our current understanding of the establishment of the regulated storage pool of VWF and FVIII. The data presented indicate that regulated secretion of both proteins occurs only if there is endogenous synthesis of FVIII together with VWF. © 2006 Wiley‐Liss, Inc.
Central nervous system‐related permanent consequences in patients with Langerhans cell histiocytosis
Authors: Mittheisz Edda , Seidl Rainer , Prayer Daniela , Waldenmair Marion , Neophytou Birgit , Pötschger Ulrike , Minkov Milen , Steiner Manuel , Prosch Helmut , Wnorowski Martha , Gadner Helmut , Grois Nicole
Published: February 2006

Background

Permanent consequences in Langerhans cell histiocytosis (LCH) are irreversible late sequelae related to the disease that may severely impair the quality of life of survivors. The frequency and pattern of permanent consequences affecting the central nervous system (CNS) remains to be determined.

Procedure

In this single center study, 25 LCH patients observed for a median time of 10 years 3 months underwent a uniform thorough follow‐up program including neuropsychological testing and electrophysiological evaluation.

Results

Overall permanent consequences were seen in 9 of 25 patients. Intracranial abnormalities were the most frequent including diabetes insipidus (DI) in seven patients, anterior pituitary deficiencies in five patients, and neurodegenerative CNS disease in five patients. No patient had overt neurological symptoms upon neurological evaluation, but psychological testing revealed subtle deficits in short‐term auditory memory (STAM) in 14 patients. Brain stem evoked potentials showed abnormalities in four of nine tested patients, all of these four had neurodegeneration on MRI.

Conclusion

Psychoneuroendocrine sequelae were found in an unexpectedly high number of patients in this single center study. Long‐term follow‐up focusing on such sequelae are important in LCH survivors, in order to detect early deficits, to monitor the evolution of the disease, and to provide specific support. Pediatr Blood Cancer 2007;48:50–56. © 2006 Wiley‐Liss, Inc.
Adolescents with acute lymphoblastic leukaemia: Emerging from the shadow of paediatric and adult treatment protocols
Authors: Ramanujachar Ramya , Richards Sue , Hann Ian , Webb David
Published: February 2006

Adolescents and young adults (AYA) with acute lymphoblastic leukaemia (ALL) constitute a distinct population from children and older adults. Based on patterns of referral, they may be treated by either paediatric or adult oncologists. As a group, AYA with ALL have a worse survival and event‐free survival (EFS) compared to that achieved by younger children. A systematic review of all published clinical trials, which provide data on treatment and outcome of adolescents with ALL, has been summarised in an effort to determine whether they should be treated on paediatric or adult type protocols. Adolescents appear to have a consistent survival advantage when treated on paediatric regimens. Pediatric Blood Cancer 2006;47:748–756. © 2006 Wiley‐Liss, Inc.
Secondary pseudotumor cerebri in pediatric oncology and hematology: An unpredictable condition of varying etiology
Authors: Distelmaier Felix , Göbel Ulrich , Vandemeulebroecke Nicola , Mayatepek Ertan , Rosenbaum Thorsten , Laws Hans‐Jürgen
Published: February 2006

Secondary pseudotumor cerebri (PTC) in pediatric oncology and hematology is an unpredictable and under‐recognized condition. It is characterized by increased cerebrospinal fluid (CSF) pressure of more than 25 cm H2O in the absence of underlying structural causes. Numerous conditions and medications have been implicated in the etiology of secondary PTC. Patients may suffer from incapacitating headaches and permanent visual loss, if they are not managed properly. We retrospectively analyzed the records of eight children, diagnosed with secondary PTC with an underlying hematological or oncological disease. Our study highlights the clinical features, contributing factors, and treatment options of this syndrome in children. Pediatr Blood Cancer 2007;49:1029–1033. © 2006 Wiley‐Liss, Inc.
Prenatal counselling of small bowel atresia:watch the fluid!
Authors: Iacobelli Barbara D. , Zaccara Antonio , Spirydakis Ioannis , Giorlandino Claudio , Capolupo Irma , Nahom Antonella , Bagolan Pietro
Published: February 2006

Objective

To evaluate polyhydramnios as a sign of extreme disproportion of atretic segments in small bowel atresia (SBA).

Methods

Twenty‐eight patients with a prenatal diagnosis (PD) of SBA undergoing neonatal surgical treatment were reviewed retrospectively. Parameters recorded were gestational age, birth weight, surgical procedure, rate of complications, parenteral nutrition (PN) days and length of stay (LOS). Patients were divided into two groups: Group A with delayed anastomosis and Group B with direct anastomosis.

Results

Seventeen subjects were in Group A while 11 were in Group B. The two groups did not differ with regard to gestational age at diagnosis, birth weight and obstetrical management. Polyhydramnios was present in both Group A (64.7%) and Group B (9%) (p < 0.05). Patients in Group A needed a longer period on PN, had a longer LOS and exhibited significantly higher rates of complication.

Conclusion

In the absence of other malformations, association of dilated bowel loops and polyhydramnios is highly predictive of severe SBA, which can in no instance be amenable to one‐stage reconstruction. Because of its consequences on postnatal treatment, such information should be conveyed to the prospective parents at the time of counselling. Copyright © 2006 John Wiley & Sons, Ltd.
Laboratory monitoring of potassium and creatinine in ambulatory patients receiving angiotensin converting enzyme inhibitors and angiotensin receptor blockers
Authors: Raebel Marsha A. , McClure David L. , Simon Steven R. , Chan K. Arnold , Feldstein Adrianne , Andrade Susan E. , Lafata Jennifer Elston , Roblin Douglas , Davis Robert L. , Gunter Margaret J. , Platt Richard
Published: February 2006

Purpose

Serum potassium and creatinine monitoring is recommended for patients prescribed angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). Much has been written about hyperkalemia associated with these drugs; little is known about laboratory monitoring patterns. The purpose of this retrospective cohort study was to assess creatinine and potassium monitoring and characteristics associated with monitoring among patients dispensed ACEi or ARB.

Methods

This study was conducted in 10 United States health maintenance organizations. Study patients (n = 52 906) were aged 18 or older with dispensings of ACEi or ARB for at least 1 year. Serum potassium and creatinine monitoring were assessed from administrative data and medical records.

Results

More than two‐thirds (68.4%) of patients received laboratory monitoring. Likelihood of monitoring increased with age (adjusted odds ratio [OR] 2.10; 95% confidence interval [95%CI] 1.93, 2.28 [individuals ≥ 80 compared to <50 years]), >9 outpatient visits (OR 1.46; 95%CI 1.39, 1.54), hospitalization (OR 1.15; 95%CI 1.06, 1.25), concomitant medications (potassium [OR 2.01; 95%CI 1.84, 2.20], diuretics [OR 1.54; 95%CI 1.47, 1.61], digoxin [OR 1.15; 95%CI 1.01, 1.30]), and comorbidities (diabetes [OR 1.68; 95%CI 1.61, 1.75], heart failure [OR 1.73; 95%CI 1.57, 1.90], chronic kidney disease [OR 2.95; 95%CI 2.48. 3.51]).

Conclusions

Nearly one‐third of patients dispensed ACEi or ARB did not undergo laboratory monitoring at least yearly. Though patients at increased risk of hyperkalemia were more likely to be monitored, many remained unmonitored. Copyright © 2006 John Wiley & Sons, Ltd.
Comparative proteome approach to characterize the high‐pressure stress response of Lactobacillus sanfranciscensis DSM 20451T
Authors: Hörmann Sebastian , Scheyhing Carsten , Behr Jürgen , Pavlovic Melanie , Ehrmann Matthias , Vogel Rudi F.
Published: February 2006

High hydrostatic pressure (HHP) exerts diverse effects on microorganisms, leading to stress response and cell death. While inactivation of microorganisms by lethal HHP is well investigated in the context of food preservation and the hygienic safety of minimal food processes, sublethal HHP stress response and its effect on adaptation and cross‐protection is less understood. In this study, the HHP stress response of Lactobacillus sanfranciscensis was characterized and compared with cold, heat, salt, acid and starvation stress at the proteome level by using 2‐DE so as to provide insight into general versus specific stress responses. Sixteen proteins were found to be affected by HHP and were identified by using N‐terminal amino acid sequencing and MS. Only one slightly increased protein was specific to the HHP response and showed homology to a clp protease. The other proteins were influenced by most of the investigated stresses in a similar way as HHP. The highest similarity in the HHP proteome was found to be with cold‐ and NaCl‐stressed cells, with 11 overlapping proteins. At the proteome level, L. sanfranciscensis appears to use overlapping subsets of stress‐inducible proteins rather than stereotype responses. Our data suggest that a specific pressure response does not exist in this bacteria.
MapQuant: Open‐source software for large‐scale protein quantification
Authors: Leptos Kyriacos C. , Sarracino David A. , Jaffe Jacob D. , Krastins Bryan , Church George M.
Published: February 2006

Whole‐cell protein quantification using MS has proven to be a challenging task. Detection efficiency varies significantly from peptide to peptide, molecular identities are not evident a priori, and peptides are dispersed unevenly throughout the multidimensional data space. To overcome these challenges we developed an open‐source software package, MapQuant, to quantify comprehensively organic species detected in large MS datasets. MapQuant treats an LC/MS experiment as an image and utilizes standard image processing techniques to perform noise filtering, watershed segmentation, peak finding, peak fitting, peak clustering, charge‐state determination and carbon‐content estimation. MapQuant reports abundance values that respond linearly with the amount of sample analyzed on both low‐ and high‐resolution instruments (over a 1000‐fold dynamic range). Background noise added to a sample, either as a medium‐complexity peptide mixture or as a high‐complexity trypsinized proteome, exerts negligible effects on the abundance values reported by MapQuant and with coefficients of variance comparable to other methods. Finally, MapQuant's ability to define accurate mass and retention time features of isotopic clusters on a high‐resolution mass spectrometer can increase protein sequence coverage by assigning sequence identities to observed isotopic clusters without corresponding MS/MS data.
Proteomic profiling of cell envelope‐associated proteins from Staphylococcus aureus
Authors: Gatlin Christine L. , Pieper Rembert , Huang Shih‐Ting , Mongodin Emmanuel , Gebregeorgis Elizabeth , Parmar Prashanth P. , Clark David J. , Alami Hamid , Papazisi Leka , Fleischmann Robert D. , Gill Steven R. , Peterson Scott N.
Published: February 2006

The emergence of highly virulent community acquired Staphylococcus aureus and continued progression of resistance to multiple antimicrobials, including methicillin and vancomycin, marks the reemergence of S. aureus as a serious health care threat. Investigation of proteins localized to the cell surface could help to elucidate mechanisms of virulence and antibiotic resistance in S. aureus. In this study, proteomic profiling methods were developed to solubilize, display, and evaluate abundance levels of proteins present in the supernatants of the lysostaphin‐digested cell envelope from cultured vancomycin‐intermediate S. aureus (VISA) cells. Combining approaches of 2‐DE or chromatographic separation of proteins with MS analyses resulted in the identification of 144 proteins of particular interest. Of these proteins, 48 contained predicted cell wall localization or export signal motifs, including 14 with distinct covalent peptidoglycan‐anchor sites, four of which are uncharacterized to date. One of the two most abundant cell envelope proteins, which showed remarkably high variations in MW and pI in the 2‐DE gel display, was the S. aureus surface protein G. The display of numerous secreted proteins that are not covalently cell wall‐anchored, suggests that, in the exponential growth phase, secreted proteins can be retained physiologically in the cell envelope and may interact with cell wall‐anchored proteins and carbohydrate structures in a manner yet to be determined. The remaining 96 proteins, devoid of recognizable motifs, were repeatedly profiled in the VISA cell envelope fractions. We describe a novel semiquantitative method to determine abundance factors of such proteins in 2‐DE gels of cell envelope fractions relative to whole cell lysates and discuss these data in the context of true cell envelope localization versus experimentally caused cell lysis.
The identification and characterization of xenoantigenic nonhuman carbohydrate sequences in membrane proteins from porcine kidney
Authors: Kim Yun‐Gon , Kim Sun‐Young , Hur Young‐Mi , Joo Hwang‐Soo , Chung Junho , Lee Dong‐Sup , Royle Louise , Rudd Pauline M. , Dwek Raymond A. , Harvey David J. , Kim Byung‐Gee
Published: February 2006

The immunogenic nonhuman carbohydrate sequences in membrane proteins from porcine kidney were identified and characterized using MALDI‐TOF MS and ESI‐QTOF‐MS. The MALDI profile, investigated by incubation with exoglycosidases, showed a series of about 40 carbohydrates that were identified as high mannose glycans (Man3–9GlcNAc2) and complex bi‐, tri‐, and tetra‐antennary glycans with and without core fucose. The antennae of many of the complex glycans were terminated with α‐galactose residues, with the numbers of these residues ranging from one up to the number of antennae. Negative ion ESI‐MS/MS spectra confirmed the location of the α‐galactose residues on the ends of the antennae. This total glycan profile of the membrane proteins from porcine kidney will thus provide important information for the study of molecular interactions between antigenic carbohydrates and proteins in xenotransplantation.
Analysis of aromatic catabolic pathways in Pseudomonas putida KT 2440 using a combined proteomic approach: 2‐DE/MS and cleavable isotope‐coded affinity tag analysis
Authors: Kim Young Hwan , Cho Kun , Yun Sung‐Ho , Kim Jin Young , Kwon Kyung‐Hoon , Yoo Jong Shin , Kim Seung Il
Published: February 2006

Proteomic analysis of Pseudomonas putida KT2440 cultured in monocyclic aromatic compounds was performed using 2‐DE/MS and cleavable isotope‐coded affinity tag (ICAT) to determine whether proteins involved in aromatic compound degradation pathways were altered as predicted by genomic analysis (Jiménez et al., Environ Microbiol. 2002, 4, 824–841). Eighty unique proteins were identified by 2‐DE/MS or MS/MS analysis from P. putida KT2440 cultured in the presence of six different organic compounds. Benzoate dioxygenase (BenA, BenD) and catechol 1,2‐dioxygenase (CatA) were induced by benzoate. Protocatechuate 3,4‐dixoygenase (PcaGH) was induced by p‐hydroxybenzoate and vanilline. β‐Ketoadipyl CoA thiolase (PcaF) and 3‐oxoadipate enol‐lactone hydrolase (PcaD) were induced by benzoate, p‐hydroxybenzoate and vanilline, suggesting that benzoate, p‐hydroxybenzoate and vanilline were degraded by different dioxygenases and then converged in the same β‐ketoadipate degradation pathway. An additional 110 proteins, including 19 proteins from 2‐DE analysis, were identified by cleavable ICAT analysis for benzoate‐induced proteomes, which complemented the 2‐DE results. Phenylethylamine exposure induced β‐ketoacyl CoA thiolase (PhaD) and ring‐opening enzyme (PhaL), both enzymes of the phenylacetate (pha) biodegradation pathway. Phenylalanine induced 4‐hydroxyphenyl‐pyruvate dioxygenase (Hpd) and homogentisate 1,2‐dioxygenase (HmgA), key enzymes in the homogentisate degradation pathway. Alkyl hydroperoxide reductase (AphC) was induced under all aromatic compounds conditions. These results suggest that proteome analysis complements and supports predictive information obtained by genomic sequence analysis.
Analysis of the wheat and Puccinia triticina (leaf rust) proteomes during a susceptible host‐pathogen interaction
Authors: Rampitsch Christof , Bykova Natalia V. , McCallum Brent , Beimcik Eva , Ens Werner
Published: February 2006

Wheat leaf rust is caused by the fungus Puccinia triticina. The genetics of resistance follows the gene‐for‐gene hypothesis, and thus the presence or absence of a single host resistance gene renders a plant resistant or susceptible to a leaf rust race bearing the corresponding avirulence gene. To investigate some of the changes in the proteomes of both host and pathogen during disease development, a susceptible line of wheat infected with a virulent race of leaf rust were compared to mock‐inoculated wheat using 2‐DE (with IEF pH 4–8) and MS. Up‐regulated protein spots were excised and analyzed by MALDI‐QqTOF MS/MS, followed by cross‐species protein identification. Where possible MS/MS spectra were matched to homologous proteins in the NCBI database or to fungal ESTs encoding putative proteins. Searching was done using the MASCOT search engine. Remaining unmatched spectra were then sequenced de novo and queried against the NCBInr database using the BLAST and MS BLAST tools. A total of 32 consistently up‐regulated proteins were examined from the gels representing the 9‐day post‐infection proteome in susceptible plants. Of these 7 are host proteins, 22 are fungal proteins of known or hypothetical function and 3 are unknown proteins of putative fungal origin.
Proteases and chaperones are the most abundant proteins in the parasitophorous vacuole of Plasmodium falciparum‐infected erythrocytes
Authors: Nyalwidhe Julius , Lingelbach Klaus
Published: February 2006

After invasion of erythrocytes, the human malaria parasite Plasmodium falciparum resides within a parasitophorous vacuole (PV) which forms an interface between the host cell cytosol and the parasite surface. This vacuole protects the parasite from potentially harmful substances, but allows access of essential nutrients to the parasite. Furthermore, the vacuole acts as a transit compartment for parasite proteins en route to the host cell cytoplasm. Recently we developed a strategy to biotin label soluble proteins of the PV. Here, we have paired this strategy with a high‐throughput MALDI‐TOF‐MS analysis to identify 27 vacuolar proteins. These proteins fall into the following main classes: chaperones, proteases, and metabolic enzymes, consistent with the expected functions of the vacuole. These proteins are likely to be involved in several processes including nutrient acquisition from the host cytosol, protein sorting within the vacuole, and release of parasites at the end of the intraerythrocytic cycle.
Analysis of the interacting partners of the neuronal calcium‐binding proteins L‐CaBP1, hippocalcin, NCS‐1 and neurocalcin δ
Authors: Haynes Lee P. , Fitzgerald Daniel J. , Wareing Brian , O'Callaghan Dermott W. , Morgan Alan , Burgoyne Robert D.
Published: February 2006

Intracellular Ca2+signals are transduced by the binding of Ca2+ to sensor proteins, which subsequently modify the activity of their target proteins. Identification of these target proteins is, therefore, important for an understanding of cellular signalling processes. We have investigated the binding partners of four EF‐hand Ca2+‐binding proteins. Three proteins of the neuronal calcium sensor (NCS) family, hippocalcin, NCS‐1 and neurocalcin δ were prepared as N‐terminally tagged GST fusion proteins, and the less closely related protein L‐CaBP1 was prepared in both N‐ and C‐terminally tagged forms, the latter requiring generation of a new vector. Immobilised fusion proteins were used to purify binding partners from bovine brain cytosol and membrane extracts in the presence of 1 μM free Ca2+. Bound proteins were eluted with Ca2+‐free and high‐salt buffers and eluted proteins were identified by MALDI‐MS and Western blotting. New protein targets detected included ARF1, Ca2+‐dependent activator protein for secretion 1, cyclic nucleotide 3', 5'‐phosphodiesterase, the vacuolar ATPase, AP1 and AP2 complexes and the type I TGF‐β receptor. While certain of these interactions occurred with more than one of the Ca2+‐binding proteins, others were found to be specific targets for particular Ca2+ sensors, and many of these did not overlap with known calmodulin‐binding proteins. These findings provide new clues to the functional roles of the neuronal calcium sensor proteins.
PRISM: A data management system for high‐throughput proteomics
Authors: Kiebel Gary R. , Auberry Ken J. , Jaitly Navdeep , Clark David A. , Monroe Matthew E. , Peterson Elena S. , Tolić Nikola , Anderson Gordon A. , Smith Richard D.
Published: February 2006

Advanced proteomic research efforts involving areas such as systems biology or biomarker discovery are enabled by the use of high level informatics tools that allow the effective analysis of large quantities of differing types of data originating from various studies. Performing such analyses on a large scale is not feasible without a computational platform that performs data processing and management tasks. Such a platform must be able to provide high‐throughput operation while having sufficient flexibility to accommodate evolving data analysis tools and methodologies. The Proteomics Research Information Storage and Management system (PRISM) provides a platform that serves the needs of the accurate mass and time tag approach developed at Pacific Northwest National Laboratory. PRISM incorporates a diverse set of analysis tools and allows a wide range of operations to be incorporated by using a state machine that is accessible to independent, distributed computational nodes. The system has scaled well as data volume has increased over several years, while allowing adaptability for incorporating new and improved data analysis tools for more effective proteomics research.
Quantitation of protein phosphorylation in pregnant rat uteri using stable isotope dimethyl labeling coupled with IMAC
Authors: Huang Sheng‐Yu , Tsai Mei‐Ling , Wu Chin‐Jen , Hsu Jue‐Liang , Ho Shih‐Hsin , Chen Shu‐Hui
Published: February 2006

Quantitative analysis of protein phosphorylation provides important insights into molecular signaling mechanisms and a better understanding of many cellular processes. In this study, we coupled stable isotope dimethyl labeling with immobilized metal affinity chromatography (IMAC) enrichment to quantify protein phosphorylation at MS‐determined phosphorylation sites. The proposed method was first characterized using α‐ and β‐casein as two model phosphoproteins, and further applied to the analysis of pregnant rat uteri with and without treatment with 8‐bromo‐cGMP. Dimethyl labeling has several significant advantages: global, fast (within 5 min) and complete (near 100%). Our results indicate that the labeling has no adverse effect on the IMAC enrichment for tryptic peptides having single and multiple phosphorylation sites. Moreover, the enhanced a1 signal and the complete reaction by dimethyl labeling provide unequivocal identification of both the N‐terminal amino acid and the number of the labeling site. Using these two criteria in data validation, which is particularly important for identifying phosphoproteins, we found that the confidence in interpreting dimethyl‐labeled peptides had greatly increased. In the analysis of late gestation rat uteri, the abundance ratio between treated and un‐treated phosphopeptide signals ranged from 0.51 to 1.69 with an average of around 1.01 ± 0.25. The obtained ratio of the phosphorylation levels at Ser 15 of HSP27 was further confirmed by the consistent results obtained from Western blot analyses. Based on the analysis of the results, it is interesting to note that the activated cGMP dependentt protein kinase G (PKG) seems to affect the phosphorylation of proteins associated with the inhibition of cell migration and proliferation, redistribution of actin‐associated proteins, and the increase of protein synthesis in late‐gestation uteri. These observations provide important evidence suggesting that activated PKG may play a critical role in the shift of pregnant uteri from proliferative to hypertrophic states.
Comparative proteome analysis of Staphylococcus aureus biofilm and planktonic cells and correlation with transcriptome profiling
Authors: Resch Alexandra , Leicht Stefan , Saric Marc , Pásztor Linda , Jakob Andreas , Götz Friedrich , Nordheim Alfred
Published: February 2006

Pathogenic staphylococci can form biofilms in which they show a higher resistance to antibiotics and the immune defense system than their planktonic counterparts, which suggests that the cells in a biofilm have an altered metabolic activity. Here, 2‐D PAGE was used to identify secreted, cell wall‐associated and cytoplasmic proteins expressed in Staphylococcus aureus after 8 and 48 h of growth. The proteins were separated at pH ranges of 4–7 or 6–11. The protein patterns revealed significant differences in 427 protein spots; from these, 258 non‐redundant proteins were identified using ESI‐MS/MS. Biofilm cells expressed higher levels of proteins associated with cell attachment and peptidoglycan synthesis, and in particular fibrinogen‐binding proteins. Enzymes involved in pyruvate and formate metabolism were upregulated. Furthermore, biofilm cells expressed more staphylococcal accessory regulator A protein (SarA), which corroborates the positive effect of SarA on the expression of the intercellular adhesion operon ica and biofilm growth. In contrast, proteins, such as proteases and particularly immunodominant antigen A (IsaA) and staphylococcal secretory antigen (SsaA), were found in lower amounts. The RNA expression profiling largely supports the proteomic data. The results were mapped onto KEGG pathways.