bluuebunny/crossref_metadata_2025 huggingface dataset:
Conformational properties of Rhodobacter capsulatus cytochrome c2 wild‐type and site‐directed mutants using hydrogen/deuterium exchange monitored by electrospray ionization mass spectrometry
Authors: Jaquinod Michel , Halgand Frederic , Caffrey Michael , Saint‐Pierre Christine , Gagnon Jean , Forest Eric , Fitch John , Cusanovich Michael
Published: May 2005

The conformational properties of Rhodobacter capsulatus cytochrome c2 wild‐type and two site‐directed mutants (glycine 34 replaced by serine and proline 35 replaced by alanine) were characterized by their charge state distributions and hydrogen/deuterium (H/D) exchange properties monitored by electrospray ionization mass spectrometry. The results suggest the presence of structural perturbations in the mutated cytochromes, an observation that is in agreement with their decreased conformational stabilities. In addition, a fast enzymatic procedure was developed to identify regions for which the H‐bonding or solvent accessibility properties were perturbed by the mutations. In this procedure, deuterated peptides were separated and analysed by using liquid chromatography directly coupled to the electrospray ionization source in order to minimize the occurrence of back‐exchange during analysis. In the case of G34S, mutational effects were found for peptides 1–26, 38–51, 52–59 and 109–116, which in the Rb. capsulatus cytochrome c2 structure correspond to extensive regions on the same side of the molecule as the proximal histidine, as well as part of the C‐terminal helix. In the case of P35A, mutational effects were found for peptides 1–26, 27–37, 38–51 and 52–59, which in the Rb. capsulatus cytochrome c2 stucture correspond to extensive regions on the same side of the molecule as the proximal histidine. We show that the present set of mass spectrometric experiments is useful as an initial characterization of mutant conformational properties because the analyses require only nanomole quantities of protein and can be performed rapidly.
Fragmentation reactions of Cu+‐cationated α‐amino acids
Authors: Wen Doreen , Yalcin Talat , Harrison Alex G.
Published: May 2005

The Cu+‐cationated species of 12 α‐amino acids have been prepared by fast‐atom bombardment and the unimolecular (metastable ion) fragmentation reactions have been examined by tandem mass spectrometry. The major unimolecular fragmentation reactions observed involve elimination of H2O, elimination of CO2 and elimination of CH2O2. In addition, for Cu+‐cationated asparagine and glutamine, elimination of NH3 is a significant reaction and for Cu+‐cationated proline, elimination of H2 is a major fragmentation reaction. It is concluded that there are three pathways to elimination of (H2, C, O2), direct elimination of CH2O2, direct elimination of (H2O+CO) and elimination of (CO2+H2).
Proton affinity and heat of formation of vinylimine CH2CHCHNH
Authors: Bouchoux Guy , Salpin Jean‐Yves , Leblanc Danielle , Alcaraz Christian , Dutuit Odile , Palm Hartmut
Published: May 2005

The vinylimmonium cation [CH2CHCHNH2]+, [1H]+, originating from cyclopentylamine has been studied by photoionization, ion cyclotron resonance mass spectrometry and ab initio molecular orbital calculations. A heat of formation, ΔH[CH2CHCHNH2]+ of 747±7 kJ/mol has been deduced from photoionization experiments, after correction for the thermal energy of the precursor molecules. The proton affinity of vinylimine, CH2  CHCHNH, 1, (PA(1) = 908±4kJ/mol) has been deduced from proton exchange experiments using the ‘bracketing’ technique. This latter, combined with the previously determined ΔH[CH2CHCHNH2]+ leads to ΔH(CH2CHCHNH)=125kJ/mol with a possible error of ±11 kJ/mol. Molecular orbital calculations, conducted at the MP2/6‐311 ++G**//MP2/6‐31G* + ZPE level, lead to comparable estimates ΔH(CH2  CHCHNH2)+ = 746kJ/mol and ΔH(CH2CHCHNH) = 128–135 (kJ/mol).
Modulation of the gas‐phase reactivity of W+ by carbonyl ligands: Activation of hydrocarbons by W(CO) (x=1–4)
Authors: Mourgues Philippe , Ohanessian Gilles
Published: May 2005

The gas‐phase reactions of W(CO) (x=1–4) with methane, ethane, propane, ethene and propene have been studied in a Fourier transform ion cyclotron resonance mass spectrometer. Virtually all reactions observed involve hydrocarbon dehydrogenation, either single or double, a reactivity similar in type to what is observed with bare W+. The most reactive ion is W(CO) except for this ion, reactivity tends to diminish with increasing number of carbonyl ligands. Whenever there is sufficient internal energy available, CO detachment competes with H2 loss. This is the case for ethene and propene, and in some cases with propane. However, this is strongly dependent upon the number of carbonyl ligands in the reacting ion. In most cases, product ions are themselves reactive with the neutral, leading to reaction sequences of various lengths. These sequences end either because the metal no longer has the appropriate number of non‐bonding electrons for inserting into a CH bond with low activation energy, or because of saturation of the coordination shell around the metal.
Time focusing magnetic wedge‐field sectors for time‐resolved ion momentum spectrometry
Authors: Ioanoviciu Damaschin , Cuna Cornel , Erdélyi BéLa , Yavor Michail I.
Published: May 2005

The time‐of‐flight properties of magnetic wedge‐field sectors have been derived in a second‐order approximation. The following quantities were included: source slit width, radial and axial opening angles of the ion beam and relative energy spread. The transfer matrix elements of the time‐of‐flight (longitudinal) row were derived in terms of the initial and final angles and of K‐parameter dependence on the ion momentum and magnetic field. The longitudinal mass dispersion coefficient required in the time resolution formula was derived. The time‐of‐flight ion optical properties of a 60° symmetric, homogeneous magnetic sector mass spectrometer, already employed for time‐resolved ion momentum spectrometry studies, were compared with those of a wedge‐field, 180° deflecting stigmatic arrangement with K=0.7423. The time‐of‐flight aberrations were calculated from transfer matrix multiplications. The advantages of the wedge‐field geometry are: independence, up to second order, of the ion packet length upon the ion source slit width, independence to first order of the ion energy spread and stigmatic focusing in space. These factors ensure both improved sensitivity and time resolution.
A simple method for differentiating Leu and Ile in peptides. The negative‐ion mass spectra of [M  h]− ions of phenylthiohydantoin Leu and Ile
Authors: Ramsay Steven L. , Steinborner Simon T. , Waugh Russell J. , Dua Suresh , Bowie John H.
Published: May 2005

Phenylthiohydantoin (PTH) amino acid derivatives are formed during sequential Edman degradation of peptides and proteins. Isomeric Leu and Ile (which differ only in respectively having iso‐butyl and sec‐butyl chains, and are often difficult to distinguish by conventional mass spectrometric techniques) may be readily identified by the characteristic decompositions of the [M  H]− ions of their PTH derivatives. The Leu spectrum shows major loss of propane, while that of the Ile derivative shows elimination of both methane and ethane. This method may be used routinely with 10 μg quantities of peptide material.
Quantification of 7‐dehydrocholesterol in plasma and amniotic fluid by liquid chromatography/particle beam‐mass spectrometry as a biochemical diagnostic marker for the smith‐lemli‐opitz syndrome
Authors: Sattler Wolfgang , Kostner Gerhard M. , Malle Ernst , Leis Hans‐JÖRg
Published: May 2005

The qualitative and quantitative determination of cholesterol and 7‐dehydrocholesterol (7‐DHC) in plasma as a biochemical diagnostic marker for the Smith‐Lemli‐Opitz syndrome by liquid chromatography/particle beam interface‐mass Spectrometry (LC/PB‐MS) is presented. Baseline separation of cholesterol arid 7‐DHC is achieved on a silica column with hexane + ethanol (99:1 v/v) as mobile phase within a 10 min analysis. Recoveries of cholesterol and 7‐DHC in a simple two‐phase extraction system are nearly 100%. The absolute limit of detection using LC/PB‐MS is ≈10 ng. The method presented allows extraction, analysis and quantification of cholesterol and 7‐DHC within 15 min without the necessity of sample derivatization.
Mass spectrometry of derivatives of dicyclopentadienyltitanium dichloride II. Comparison of chemical ionization and liquid secondary ion mass spectrometric behaviour
Authors: Wang Fu , Fang Ming , Wu Wannian , Chen Xuehua , Huang Jielin
Published: May 2005

Positive/negative chemical ionization (PI/NI CI) and liquid secondary ion mass spectrometry (LSIMS) of ten derivatives of dicyclopentadienyltitanium (IV) dichloride were investigated. The major ions detected were M + NHU4, M − CI]+, [M − 2Cl]+, [M − R1CpR3]+ and [M − R2CpR4]+ in PICI (ammonia) mass spectra, M−, [M + CI]−, [M − CI]−, [M + CI − R1CpR3]+ and [M + CI − R1CpR3]+ in NICI (ammonia) mass spectra, and [M − CI]+, [M − 2CI]+, [M − 2CI + (NBA − H)]+ (where NBA = m‐nitrobenzyl alcohol), [M − R1CpR3]+, [M − R2CpR4+, [M − R1CpR3 − HCI]+ and [M − R2CpR4 − HCI]+ (where R1CpR3 and R2CpR4 are both mixed alkyl‐aryl substituted cyclopentadienyl groups) in LSIMS. Although the mass spectrometric behaviours are quite different due to the different ionization mode, adduct ions were observed in all mass spectra and molecular ions were only observed in NICI mass spectra. The cleavage pathways were confirmed using tandem mass spectrometry methods.
Ion dissociation reactions induced in a high‐pressure quadrupole collision cell
Authors: Whalen Kevin , Grossert J. Stuart , Boyd Robert K.
Published: May 2005

This work concerns a new high‐pressure quadrupole collision cell, designed for tripie‐quadrupole mass spectrometers. This new collision cell operates at pressures up to 10 mTorr, an order of magnitude higher than conventional cells of this type. Previous investigations have concentrated upon the significant increases in transmission efficiency and in resolving power for fragment ions which result from the use of this new design. The present work reports an investigation into the nature of the dissociation reactions which can be induced by collisions in this high‐pressure cell. Charge‐site‐remote fragmentations of a simple precursor ion were chosen as a test case, and were found to be observable at laboratory collision energies lower by a factor of 4–5 than those found previously to be necessary when using conventional low‐pressure quadrupole collision cells. It was also shown that the charge‐site‐remote reactions were accompanied by the mixed‐site‐fragmentation reactions described by Tuinman and Cook (J. Am. Soc. Mass Spectrom). Vol. 1, p. 85 (1989). Ionization of collision gas was observed in the case of xenon. Efforts to observe charge‐site‐remote fragmentations of peptide ions were marginally successful. Highly basic peptides, which have been problematic for sequencing by low‐energy tandem mass spectrometry, did not yield useful fragment‐ion spectra in the new cell. The fragmentation behaviour of protonated Leu‐enkephalin, for which fragmentation pathways have been thoroughly studied previously, suggested that the observed spectra reflected integration of the fragmentation kinetics over a considerably longer time, thus involving many more reaction steps. These combined observations are considered in terms of a qualitative model based on a rapid decrease of ion kinetic energy during passage through the cell, with much longer residence times than for conventional quadrupole cells.
An improved method for clenbuterol screening using high resolution selected ion recording
Authors: Kingston R. , Ordsmith N. , Williams E. , Thieme D.
Published: May 2005

A method has been developed using reliable GC derivatization techniques interfaced with a high resolution mass spectrometer. The method has proved successful for the detection of low levels (less than 1 ppm) of clenbuterol in complex biological matrices. Selected ion recording of two characteristic isotopic fragment ions provides a specific mode of detection by verifying the GC retention time of these ions and also by comparing their relative abundance. Analysis of urine samples demands higher mass spectrometric resolution, and 40000 (10% valley) was found to be a prerequisite for accurate integration of the drug‐related chromatographic peaks. The method developed is suitable for adaptation to a completely unattended automated routine incorporating sample injection, storage and retrieval of source tuning parameters, and data processing.
The characterization of the metabolites of ranolazine in man by liquid chromatography mass spectrometry
Authors: Penman A. D. , Eadie J. , Herron W. J. , Reilly M. A. , Rush W. R. , Liu Y.
Published: May 2005

The metabolism of ranolazine (RS‐43285) or (+)N‐(2,6‐dimethylphenyl)‐4‐[2‐hydroxy‐3‐(2‐methoxyphenoxy)‐propyl]‐1‐piperazine acetamide dihydrochloride was investigated in man using plasma samples obtained from four different clinical studies. The metabolite profiles following single and multiple doses of 342 mg instant release (IR) ranolazine, following multiple doses of 1000 mg sustained release (SR) ranolazine and following dosing with both ranolazine (IR) and a potentially co‐administered drug, diltiazem, were compared. Metabolism of ranolazine in man was shown by LC/MS analysis to be extensive with up to seven primary routes of metabolism identified. N‐dealkylation by hydrolysis at the piperazine ring produced three metabolites whilst O‐demethylation and O‐dearylation at the methoxyphenoxy moiety produced a further two compounds. Additionally, hydrolysis of the amide group formed one other species. Oxygenation at various points in the molecule produced a further four metabolites. Direct conjugation of ranolazine with glucuronic acid and with an uncharacterized adduct were also identified as a route of elimination. Ten other biotransformation products were formed as a result of multiple metabolic steps. Conjugation was also associated with the desmethyl metabolite (glucuronide and unidentified conjugates) of hydroxylated ranolazine. In a previous publication (Journal of Chromatography, 1995, accepted for publication) semi‐quantitative analyses of pooled plasma from the study where ranolazine was dosed at 1000 mg twice daily showed that of the twelve metabolites studied only four accounted for AUC's in excess of 10% of the ranolazine AUC.
A reconciliation of mass ranges from matrix‐assisted laser desorption/ionization mass spectrometry and size exclusion chromatography for coal‐derived materials
Authors: Herod Alan A. , Kandiyoti Rafael , Johnson Barry R. , Bartle Keith D. , Carter David M. , Cocksedge Mike J. , Domin Mark
Published: May 2005

Size exclusion chromatography (SEC) has been used extensively in the characterization of coal‐derived liquids to estimate molecular masses (MM), indicating the presence of considerably greater upper mass ranges compared to mass spectrometric methods based on heated probes and field ionization. In the present study, the use of tetrahydrofuran (THF), a solvent commonly used in SEC, has been shown to lead to partial loss of sample on column packings and to allow some separation by an adsorption mechanism rather than by size exclusion. In this paper, we have compared these results with data from SEC, where 1‐methyl 2‐pyrrolidinone was used as the mobile phase, indicating that the largest molecules (not observed in THF‐based work) appear at the exclusion limit, with a continuum of material down to the total permeation limit of the column. In terms of polystyrene standard masses, this is equivalent to a range from 100 u, at the lower limit, up to in excess of 30–40 000 u and possibly over 2 000 000 u. Our results from SEC in NMP suggest that limitations exist in much solution‐based work attempting to identify distributions of MMs in coal‐derived liquids. Matrix‐assisted laser desorption/ionization (MALDI) spectra of the fractions show similar features to those seen by SEC in NMP, with a continuum from high to low mass, and a significant shift to higher mass in the insoluble fraction compared with the soluble fraction. The new data are in line with observations by laser desorption mass spectrometry (LD‐MS) and MALDI‐MS, which have shown much greater upper‐MM limits than either SEC (in THF) or mass spectrometric techniques relying on thermal evaporation of coal‐derived materials from heated probes. The work would appear to have implications for other polydispersed natural polymer systems.
The development and validation of a high performance liquid chromatography (HPLC)/tandem mass spectrometry assay for fenticonazole in human plasma and comparison with an HPLC‐UV method
Authors: Speed William , Long Jeffrey M. , Simmonds Roger J. , Enos Trevor A.
Published: May 2005

A method is described for the determination of fenticonazole in human female plasma. The method utilizes high performance liquid chromatography coupled to atmospheric pressure positive‐ion chemical ionization triple quadrupole mass spectrometry. Multiple reaction monitoring is employed for selectivity and sensitivity which enables quantification over the range 0.5–20 ng mL−1 with acceptable precision and accuracy. A comparison is made with an existing HPLC‐UV assay and the utility of the technology of combined liquid chromatography and tandem mass spectrometry for subnanogram per mL assays is discussed.
Matrix‐assisted laser desorption/ionization combined with quadrupole ion‐trap mass spectrometry for the direct analysis of colour couplers adsorbed on solid substrates
Authors: Bristow Anthony W. T. , Creaser Colin S.
Published: May 2005

A method has been developed for the study of samples adsorbed on solid substrates using matrix‐assisted laser desorption/ionization combined with quadrupole ion‐trap mass spectrometry. The introduction of ions generated externally to the ion trap facilitates the direct analysis of molecules contained on substrates without the need for a lengthy extraction procedure. The method is demonstrated for the analysis of colour coupler compounds separated by thin‐layer chromatography and present on a photographic substrate.
Ebrotidine and its metabolites studied by mass spectrometry with electrospray ionization. Comparison of tandem and in‐source fragmentation
Authors: Rozman E. , Albet C. , Galcerán M. T.
Published: May 2005

Electrospray ionization was used for the analysis of ebrotidine and its potential metabolites. Since standard electrospray gave only the quasi‐molecular ions for most of the compounds, two collision‐induced dissociation (CID) experiments were carried out in order to obtain structural information: tandem mass spectrometry (MS/MS) and in‐source fragmentation by increasing the cone voltage (CVF, cone voltage fragmentation). CVF produced more fragmentation than MS/MS, and the intensities of the fragments formed were also greater. Unlike MS/MS spectra, CVF spectra gave ions which showed retention of the bromine isotope pattern, adducts with acetate and dehydration. The general fragmentation pathways observed for ebrotidine and its derivatives were basically the same for the CVF and MS/MS experiments. Most of the fragments were formed by the breaking of bonds to heteroatomics. In order to analyse biological samples containing ebrotidine and its biotransformation products, an HPLC/MS separation procedure with simultaneous UV detection was developed, allowing the identification of ebrotidine and its metabolites in human urine.
The effect of addition of carbon powder to samples in liquid secondary ion mass spectrometry: Improved ionization of apolar compounds
Authors: Rozenski Jef , Herdewijn Piet
Published: May 2005

Addition of carbon or graphite powder, to either the matrix or the sample if no matrix is used, facilitates the formation of sample ions. For most of the compounds investigated, [M + H]+ ions are observed. For long‐chain alcohols, [M − 1]+ ions are formed. This new analysis method allows mass spectra of compounds, that hitherto were difficult or impossible to ionize, using liquid secondary mass spectrometry to be obtained and enhances the signal intensity of poorly ionizable compounds. Using this technique in the negative ion mode, a spectrum of Fomblin® can be obtained which is suitable for calibration purpose over a mass range of 1400 u. The observed effect is possibly due to enhancement of the field strength at the sample surface in the presence of carbon powder. No evidence of contamination of the ion source was visible after four weeks of intensive use of this technique.
A comparison of femtosecond and nanosecond multiphoton ionization and dissociation for some nitro‐molecules
Authors: Ledingham Kenneth W. D. , Deas Robert M. , Marshall Archibald , McCanny Thomas , Singhal Ravi P. , Kilic Hamdi S. , Kosmidis Costantine , Langley Andrew J. , Shaikh Waseem
Published: May 2005

Resonance‐enhanced multiphoton ionization spectrometry (REMPI), using time‐of‐flight mass spectrometers and tuned lasers, has proved an important ultra‐sensitive analytical technique. Nevertheless, conventional nanosecond REMPI suffers from a number of shortcomings: most importantly, REMPI often fails through rapidly (pre)dissociating states. In the case of thermally labile molecules, which include the nitro‐molecules, either no or very small parent or high/mass fragment ion peaks exist, making the interpretation of the mass spectra ambiguous at best and often impossible. Femtosecond laser mass spectrometry (FLMS) can often ‘defeat’ these dissociative states, resulting in large parent or high‐mass fragment ion peaks which make the interpretation less ambiguous. In the present paper, nanosecond and femtosecond multiphoton ionization and fragmentation are compared using time‐of‐flight mass spectrometry for NO2 gas and a number of different nitro‐molecules: nitromethane, nitrobenzene, m‐nitrotoluene, dinitrotoluene and trinitrotoluene.
Molecular weight determination of megadalton DNA electrospray ions using charge detection time‐of‐flight mass spectrometry
Authors: Fuerstenau Stephen D. , Benner W. Henry
Published: May 2005

We present results obtained with a novel mass spectrometer capable of determining the mass of multiply charged electrospray ions generated from samples of macromolecules in the megadalton (MDa) size range. The instrument utilizes a sensitive amplifier which can detect the charge on a single ion as it passes through a tube detector. A velocity measurement of an ion with known electrostatic energy provides the ion's mass‐to‐charge ratio. Simultaneous detection of the ion charge permits a mass assignment to be made for each ion. Electrospray ions of DNA and polymer molecules with masses greater than 1 × 106 Da and charge numbers (z) in excess of 425 e− are readily detected in this mass spectrometer. The weights of small particles were also measured. The on‐axis single‐ion detection configuration provides a duty cycle of nearly 100% and extends the practical application of electrospray mass spectrometry to the analysis of very large molecules with relatively inexpensive instrumentation.
Plasma desorption time‐of‐flight mass spectrometric elucidation of the mechanisms of adhesion enhancement between plasma‐treated PEEK–carbon composite and an epoxyamine adhesive
Authors: Nsouli B. , Allali H. , Debre O. , Oladipo A. A. , Thomas J. P. , Rumeau P. , Chabert B. , Soulier J. P.
Published: May 2005

Plasma desorption time‐of‐flight mass spectrometry (PD‐TOFMS) using accelerated argon ions (9 MeV) has been successfully used for characterizing the surface modifications induced at the surface of poly(ether etherketone) (PEEK) by cold plasma treatments. While the intact polymer structure leads to the emission of negative ions from fragmentation of the repeat unit, the degradation of such a structure under plasma exposure gives rise to production of oxidized fragments. It is demonstrated that this production is highest for a plasma using a mixture of O2 and N2 (20:80), and that as a function of treatment duration, the rate of oxidation of the modified surface layer correlates with adhesive strength, at least in a first step. PD‐TOFMS is used for analysis of the failure patterns of epoxyamine adhesive/PEEK/carbon composite in order to localize the fracture position. It is concluded that the increase of the cohesion of the interphase layer as a function of the plasma treatment duration leads to a shift from the interphase/PEEK interface to the bulk of the matrial.
Characterization of a recombinant antihaemophilia‐a factor (factor VIII‐δII) by matrix‐assisted laser desorption/ionization mass spectrometry
Authors: Bihoreau N. , Veillon J. F. , Ramon C. , Scohyers J. M. , Schmitter J. M.
Published: May 2005

Factor VIII‐ΔII is a genetically engineered deletion variant of factor VIII, expressed by recombinant Chinese hamster ovary cells. This 1436‐residues‐long protein has a molecular mass, calculated from its sequence, of 164 954 Da and exhibits seven potential glycosylation sites. The glycoprotein, secreted as a single polypeptide chain, can be cleaved after Arg740 to generate a heavy‐light chain complex of 90‐80 kDa as revealed by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) analysis. Due to its high mass range and excellent senstitivity, matrix‐assisted laser desorption/ionization‐mass spectrometry (MALDI‐MS) has been chosen to play a key role in the precise determination of the molecular masses of recombinant factor VIII and the localization of the post‐translational modifications within the protein. Native factor VIII‐ΔII displays a molecular mass of 178 kDa. The masses measured by MALDI for the heavy and light chains are respectively 89 900 Da and 87 100 Da. These mass values, found reproducible from batch to batch, are used to characterize factor VIII‐ΔII during the course of preclinical studies. The difference from the theoretical molecular masses and the observation of broad molecular peaks suggest that recombinant FVIII‐ΔII has been effectively glycosylated by the host cell on both heavy and light chains. Similarly to plasma‐derived factor VIII, the recombinant protein is proteolyzed by thrombin to generate the A1/A2/A3‐C1‐C2 trimer that is the active form of factor VIII in the coagulation pathway. MALDI‐MS analysis of activated factor VIII‐ΔII suggested the presence of N‐linked oligosaccharides in the proteolyzed light chain (A3‐C1‐C2 of 77 750 Da) and in the A1 domain (46 400 Da) of the heavy chain. By contrast, the similarity between the experimental and theoretical masses of the A2 domain indicated that its single potential glycosylation site has not been utilized.
Neurophysiological investigation of effects of the D‐1 agonist SKF 38393 on tonic activity of substantia nigra dopamine neurons
Authors: Carlson Joanne H. , Bergstrom Debra A. , Weick Barton G. , Walters Judith R.
Published: May 2005

The effects of the D‐1 agonist SKF 38393 on tonic activity of rat substantia nigra pars compacta dopamine neurons were studied using extracellular, single‐unit recording techniques. Unlike nonselective D‐1/D‐2 dopamine agonists or the D‐2 agonist quinpirole, SKF 38393 did not inhibit dopamine neuronal activity when applied iontophoretically or when administered intravenously in doses up to 20 mg/kg to chloral hydrateanesthetized rats. Moreover, pretreatment with SKF 38393 did not alter the inhibitory response of these neurons to apomorphine or the D‐2 agonist quinpirole. However, in locally anesthetized, gallamine‐treated, artificially respired rats, dopamine cell activity was significantly altered by i.v. administration of SKF 38393; firing rate increases and decreases were observed. Administration of the inactive enantiomer of SKF 38393, S‐SKF 38393, did not induce similar changes in parallel experiments. These results support the idea that unlike D‐2 autoreceptor stimulation, D‐1 receptor stimulation does not exert a direct local effect on dopamine neurons in the substantia nigra pars compacta and suggest that D‐1 receptor stimulation at sites postsynaptic to the dopamine cells may indirectly affect the activity of some dopamine neurons through long‐loop feedback mechanisms.
Human brain receptor autoradiography using whole hemisphere sections: A general method that minimizes tissue artefacts
Authors: Quirion Rémi , Robitaille Yves , Martial Johanne , Chabot Jean‐Guy , Lemoine Pierrette , Pilapil Carmencita , Dalpé Michel
Published: May 2005

A general method for the preparation of high‐quality, mostly ice‐crystal‐artefact‐free whole human brain hemisphere sections is described. Upon receipt, hemispheres are divided; one is then fixed in buffered 10% formalin for neuropathological analysis while the other is cut in 8–10‐mm‐thick coronal slices that are then rapidly frozen in 2‐methylbutane at −40°C (10–15 sec) before being placed in the brain bank at −80°C. Such rapid freezing markedly decreases the formation of ice‐crystal artefacts. Whole‐hemisphere 20‐μm thick sections are then cut and mounted onto lantern‐type gelatin‐coated slides. These sections are subsequently used for both qualitative and quantitative in vitro receptor autoradiography. Examples of data obtained are given by using various radioligands labelling “classical” neutrotransmitter, neuropeptide, enzyme, and ion channel receptor binding sites. This method should be useful for the obtention of various receptor maps in human brain. Such information could be most useful for in vivo receptor visualization studies using positron emission tomography (PET) scanning. It could also indicate if a given receptor population is specifically and selectively altered in certain brain diseases, eventually leading to the development of new therapeutic approaches.
Effects of dopamine depletion on the spontaneous activity of type I striatal neurons: Relation to local dopamine concentration and motor behavior
Authors: Orr William B. , Stricker Edward M. , Zigmond Michael J. , Berger Theodore W.
Published: May 2005

The relation between the electrophysiological activity of Type I striatal neurons, local dopamine (DA) concentration, and motor behavior in rats was investigated using intraventricular administration of the neurotoxin 6‐hydroxydopamine (6‐HDA) and extracellular single‐unit recording. Results are compared with findings of past experiments in which the activity of Type II striatal neurons was examined after comparable 6‐HDA‐induced lesions. Several differences between the present observations and the earlier results were found. First, although large depletions (greater than 50%) of DA local to the site of the recording were required before the spontaneous firing rate of either cell type was increased, the levels necessary for this effect were found to be less for Type I cells than for Type II neurons. Second, although DA depletions of greater than 50% always were associated with increased Type I cell activity, depletions of greater than 95% resulted in spontaneous firing rates that were lower than those observed after depletions of approximately 90%. Thus, the relation between extent of dopaminergic depletion and Type I cell firing rate was biphasic, whereas that relation previously was found to be monophasic for Type II neurons. Finally, whereas increased Type I cell activity in the lateral striatum was associated with the aphagia, adipsia, and akinesia induced by large DA‐depleting brain lesions, increased Type II cell activity in the medial striatum was found to be associated with these impairments. Because accumulating evidence suggests that the functioning of the lateral striatum is more critical for these behaviors, however, it is proposed that the substrate of the behavioral dysfunctions resulting from DA depletion is the Type I cell population in lateral striatum.
Excitation of locus coeruleus neurons by an adenoine 3′,5′‐cyclic monophosphate‐activated inward current: Extracellular and intracellular studies in rat brain slices
Authors: Wang Y.‐Y. , Aghajanian G. K.
Published: May 2005

The firing rate of locus coeruleus (LC) neurons in rat brain slices was increased reversibly by agents that either elevate intracellular levels of adenosine 3′,5′‐cyclic monophosphate (cAMP) or mimic its actions (e.g., forskolin, an activator of adenylate cyclase, 8‐Br‐cAMP, a membrane permeable analog of cAMP, and Ro20‐1724, a preferential inhibitor of cAMP‐phosphodiesterase). Intracellular recordings showed that 8‐Br‐cAMP and forskolin induce a depolarization of LC neurons, accompanied by a decrease in input resistance. The 8‐Br‐cAMP‐ and forskolin‐elicited depolarization persisted in the presence of cobalt, a calcium channel blocker. Steady‐state current‐voltage curves revealed that in the voltage range of –50 to –120 mV, 8‐Br‐cAMP and forskolin induced an inward current, which did not reverse at the potassium equilibrium potential and could not be blocked by tetrodotoxin. Partial replacement of sodium with Tris or choline markedly reduced the depolarization elicited by 8‐Br‐cAMP.

We conclude that 8‐Br‐cAMP and forskolin act through a common mechanism to increase the firing rate of locus coeruleus neurons by inducing a cAMP‐activated inward current, carried out at least in part by sodium ions.
Excitation of K X‐rays for a wide range of elements (25 ⩽ Z ⩽ 82) by direct interaction of beta particles from phosphorus‐32
Authors: LaBrecque J. J. , Rosales P. A.
Published: May 2005

The relative sensitivities of low–medium and high‐Z elements from manganese to lead were investigated via their Kα x‐rays employing 75 μCi of 32P. This was accomplished by preparing various synthetic mixtures of elements in the range 25 ⩽ Z⩽ 82, then simply introducing 32P solution to form source‐samples. The advantages of excitation with 32P, a pure β‐emitter with a βmax. energy at 1709 keV, include the following: excitation of all the Kα x‐rays from manganese to lead; the relative sensitivities of the K x‐rays are all within one order of magnitude; the source itself does not produce any spectral lines; and the background can be greatly reduced by filtering. Excitation with 32P is compared with that of a conventional 109Cd source and some possible applications are discussed.
The value of B‐type natriuretic peptide and big endothelin‐1 for detection of severe pulmonary hypertension in heart transplant candidates
Authors: Kubánek Miloš , Málek Ivan , Kautzner Josef , Hegarová Markéta , Wiendl Martin , Lupinek Petr , Karasová Ludmila , Lánská Věra
Published: May 2005

Background:

Severe pulmonary hypertension (PH) and increased pulmonary vascular resistance (PVR) are important risk factors that predict early postoperative mortality after orthotopic heart transplantation. The aim of our study was to determine the value of B‐type natriuretic peptide (BNP) and big endothelin‐1 (big ET1) for prediction of severe PH in heart transplant candidates.

Methods:

The study population included 43 potential heart transplant candidates (38 males, mean age 52±7 years). All underwent repeated right‐heart catheterizations (2–5 studies) at an interval of 3–4 months, giving a total of 124 examinations, associated with blood sampling for BNP and big ET1 analysis. Severe PH was defined as the mean pulmonary artery pressure (MPAP)>40 mmHg.

Results

Significantly high PVR (PVR>3.0 Wood units and TPG>15 mmHg) was noted on 12 occasions in 10 patients; always in the presence of severe PH. Low BNP levels (<67 pg/ml) ruled out the presence of severe PH with a 100% sensitivity, however, with a low specificity (34%). An increase in plasma BNP>30 pg/ml (>40% of initial value) in subjects with a previous MPAP–40 mmHg detected development of severe PH with a 100% sensitivity and an 80–88% specificity. As a total of 58% of patients presented repeatedly with MPAP≤40mmHg, serial BNP testing could reduce the need for hemodynamic studies in this subgroup down to 12–20%.

Conclusions:

Serial BNP testing in hemodynamically stable heart transplant candidates with MPAP–40 mmHg allows reliable detection of development of severe PH, and may significantly reduce the need for repeated right‐heart catheterizations in these patients.
Functional mitral regurgitation predicts 1‐year mortality in elderly patients with systolic chronic heart failure
Authors: Cioffi Giovanni , Tarantini Luigi , De Feo Stefania , Pulignano Giovanni , Del Sindaco Donatella , Stefenelli Carlo , Di Lenarda Andrea , Opasich Cristina
Published: May 2005

Background and aim:

Mitral regurgitation (MR) has been demonstrated to be a powerful predictor of adverse outcome in middle‐aged patients with chronic heart failure (CHF). In this study, we sought to define the prognostic impact of functional mitral regurgitation in a population of elderly patients with systolic CHF.

Methods:

One hundred seventy‐five outpatients aged >70 years with validated CHF and left ventricular ejection fraction <40% underwent clinical and echocardiographic evaluations at baseline. Mitral regurgitation was diagnosed by Color Doppler and quantified in 5 categorical values using a 0–4+ grading system. Outcome measures included 1‐year mortality and hospitalization for worsening CHF.

Results:

The distribution of patients according to the 5 different degrees of MR detected at baseline was: absent=11%, 1+=31%, 2+=38%, 3+=16%, 4+=4%. The relationship between MR and mortality was direct and approximately linear (r=0.39, p=0.00001). The prevalence of death in the 5 subgroups was 0%, 7%, 15%, 45%, 57%, respectively. Multivariate logistic regression analysis showed that MR was the strongest predictor of death (OR 4.47, 95% CI 1.50–13.0), independently of the presence of diabetes mellitus, older age and larger left ventricular end‐diastolic volume. No association was found between MR and hospitalization for worsening CHF (r=0.08, p=0.41).

Conclusions:

This study establishes the direct and independent relationship between MR severity and one‐year mortality among elders with systolic CHF. Conversely, MR does not provide useful information regarding the risk of subsequent hospitalization for worsening CHF.
Validation of the PAC‐SYM questionnaire for opioid‐induced constipation in patients with chronic low back pain
Authors: Slappendel Robert , Simpson Karen , Dubois Dominique , Keininger Dorothy L.
Published: May 2005

Background The Patient Assessment of Constipation Symptoms (PAC‐SYM) questionnaire is a 12‐item self‐report instrument divided into abdominal, rectal and stool domains.

Aims This study aimed to (1) evaluate the psychometric properties of PAC‐SYM in assessing the symptoms and severity of opioid‐induced constipation; (2) test for differences in opioid‐induced constipation between Durogesic® fentanyl transdermal reservoir (TDF) and oral sustained‐release morphine (SRM) in patients with chronic low back pain (CLBP).

Methods In a 13‐month, open‐label, parallel‐group study, 680 patients were randomised to receive either TDF (n = 338) or SRM (n = 342) for CLBP. Assessments were recorded at Visit 1 (baseline), Visit 5 (Day 29) and Visit 17 (Month 13). Concurrent validity, clinical validity and responsiveness of PAC‐SYM were determined based on patients' confirmation of constipation (CC) scores. Differences in PAC‐SYM scores between treatment groups were also evaluated.

Results The study included 677 patients, of whom 638 were opioid‐naïve. Mean PAC‐SYM scores for constipated patients were substantially higher than for non‐constipated patients, demonstrating good clinical validity for PAC‐SYM. The PAC‐SYM could detect changes in bowel function over the treatment period, indicating responsiveness. Homogeneity of each symptom domain exceeded Cronbach's α coefficient of 0.70, suggesting good internal consistency and reliability. Changes in mean PAC‐SYM scores from baseline to Visit 5 and Visit 17 were significantly lower for the TDF group than for the SRM group, indicating that the TDF group experienced less severe constipation.

Conclusion PAC‐SYM is a reliable, valid and responsive measure of the presence and severity of opioid‐induced constipation symptoms.
On the echo interference in sound backscattering by densely aggregated targets
Authors: Gorska Natalia , Chu Dezhang
Published: May 2005

It is important to understand the volume backscattering by dense aggregations of a variety of scattering objects such as bubbles or biological targets. This paper addresses the interference of the echoes from randomly distributed targets. The main motivation of the paper is to understand the conditions under which the echo interference may affect the accuracy of the abundance and/or the biomass estimation in fisheries and zooplankton acoustics significantly. Our approach consists of two parts. The first includes an analytical approach, which describes explicitly the dependence of the echo interference on the pulse shape of the transmitted signals. Because of the limitations of the analytical approach, numerical computations based on Monte Carlo simulations of acoustic backscattering by three-dimensional target distribution were performed as a second approach. The impacts of the echo interference were studied numerically over a wide range of frequencies, for different pulse shapes and directivity patterns of the acoustic systems, and for various spatial distributions of the targets (abundance), as well as the corresponding target strengths. Using analytical and numerical approaches it was demonstrated that for targets that are uniformly distributed in space, the influence of echo interference on the observed volume-backscattering strength is strongly controlled by three main parameters. These are the number of targets in the sampling volume, the product of sound frequency and pulse duration, and the degree of tapering of the applied pulses. A numerical examples of the abundance estimation of marine organisms are presented.
Energy storage and utilization in relation to the reproductive cycle in the razor clam Ensis arcuatus (Jeffreys, 1865)
Authors: Darriba Susana , San Juan Fuencisla , Guerra Alejandro
Published: May 2005

Seasonal changes in condition indices and biochemical components of the digestive gland, anterior adductor muscle, foot, and gonad of Ensis arcuatus (Jeffreys, 1865) were analysed from February 1998 to June 1999 in relation to environmental conditions and reproductive events. During summer, E. arcuatus accumulated lipids, particularly triacylglycerols, in the digestive gland and glycogen in the anterior adductor muscle and foot while the gonad was in sexual rest. Phytoplankton blooms caused by the upwelling of cold waters, rich in nutrients, from offshore are responsible for the high availability of food during reserve storage. In autumn, when gametogenesis started, oceanographic conditions changed to a situation with low temperature throughout the water column because of the vertical mixing, and food became scarce. At that point in time, the energy requirements for basal metabolism and the reproductive process were provided by the mobilization of triacylglycerols and glycogen stored in the digestive gland and muscle tissues, respectively. The pattern exhibited by E. arcuatus based on the accumulation of reserves in summer and the subsequent mobilization during gonadal development seems to follow a conservative pattern.
Late Victorian visual reasoning and Alfred Marshall's economic science
Authors: COOK SIMON
Published: May 2005

Today the economic diagram is employed universally in teaching and research by professional economists. Yet the history of its construction shows that much that has been regarded as distinctive of twentieth-century visual culture was prefigured in the nineteenth. This paper will place the construction of the first economic diagrams by Alfred Marshall in the context both of contemporary visual technologies developed in other moral sciences, and of his wider theory of industrial production. The paper will argue that an understanding of the background to the historical graphs, constructed by the Cambridge political economist from the late 1860s onwards, will necessitate a revision of the narrative of modern visual reasoning, as recently advanced by Lev Manovich.
Isaac Frost's Two Systems of Astronomy (1846): plebeian resistance and scriptural astronomy
Authors: REID FRANCIS
Published: May 2005

In early nineteenth-century London audiences flocked to a variety of lectures and shows on astronomical topics. While the religious and social positions of the lecturers and showmen varied significantly, the vast majority adopted a Newtonian cosmology incorporating a belief in the plurality of worlds. This paper focuses on Isaac Frost's 1846 book Two Systems of Astronomy in an attempt to gain a fuller understanding of how some thinkers in plebeian London responded to and resisted this emergent astronomical orthodoxy. Central to this analysis is research that reveals how changes in the intellectual world of Frost and his Muggletonian co-religionists prompted this formerly non-proselytizing Protestant sect to become increasingly vocal during the nineteenth century. This research is based upon a thorough examination of the Muggletonian archive in the British Library together with a collection of approximately thirty Muggletonian letters deposited in the Oxfordshire Records Office in 1993 and not examined by previous historians. It is concluded that the unorthodox or anti-Newtonian cosmologies advanced by several early nineteenth-century thinkers were often intellectually coherent and embodied in receptive social contexts.
Nutrient (N, P) budgets for the Red River basin (Vietnam and China)
Authors: Quynh Le Thi Phuong , Billen Gilles , Garnier Josette , Théry Sylvain , Fézard Cédric , Minh Chau Van
Published: May 2005

In order to examine the degree of human‐induced alteration of the nitrogen and phosphorus cycles at the scale of a tropical watershed of regional dimension, the budgets of these two elements were estimated in the four main sub‐basins (Da, Lo, Thao, and Delta) of the Red River system (156 448 km2, Vietnam and China). The four sub‐basins differ widely in population density (from 101 inhabitants km−2 in the upstream basins to more than 1000 inhabitants km−2 in the delta), land use, and agricultural practices. In terms of agricultural production, on the one hand, and consumption of food and feed on the other, the upstream sub‐basins are autotrophic systems, exporting agricultural goods, while the delta is a heterotrophic system, depending on agricultural goods imports. The budget of the agricultural soils reveals great losses of nitrogen, mostly attributable to denitrification in rice paddy fields and of phosphorus, mostly caused by erosion. The budget of the drainage network shows high retention/elimination of nitrogen (from 62 to 77% in the upstream basins and 59% in the delta), and of phosphorus, with retention rates as high as 80% in the Da and Lo sub‐basins which have large reservoirs in their downstream course (Hoa Binh on the Da and Thac Ba on the Lo). The total specific delivery estimated at the outlet of the whole Red River System is 855 kg km−2 yr−1 total N and 325 kg km−2 yr−1 total P. Nitrogen rather than phosphorus seems to be the potential limiting factor of algal growth in the plume of the Red River in Tonkin Bay.