bluuebunny/crossref_metadata_2025 huggingface dataset:
A Top-Down Approach to Protein Structure Studies Using Chemical Cross-Linking and Fourier Transform Mass Spectrometry
Authors: Novak Petr , Young Malin M. , Schoeniger Joseph S. , Kruppa Gary H.
Published: March 2004

In a preliminary communication we described a top-down approach to the determination of chemical cross-link location in proteins using Fourier transform mass spectrometry (FT-MS). We have since extended the approach to use a series of homobifunctional crosslinkers with the same reactive functional groups, but different cross-linker arm lengths. Correlating cross-linking data across a series of related linkers allows the distance constraint derived from a cross-link between two reactive side chains to be determined more accurately and increases the confidence in the assignment of the cross-links. In ubiquitin, there are seven lysines with primary amino groups and the amino terminus. Disuccinimidyl suberate (DSS, cross-linker arm length = 11.4 Å), disuccinimidyl glutarate (DSG, cross-linker arm length = 7.5 Å) and disuccinimidyl tartrate (DST, cross-linker arm length = 5.8 Å) are homobifunctional cross-linking reagents that react specifically with primary amines. Using tandem mass spectrometry (MS/MS) on the singly, internally crosslinked precursor ion of ubiquitin, we found cross-links with DSS and DSG between the amino terminus and Lys 6, between Lys 6 and Lys 11, and between Lys 63 and Lys 48. Using disuccinimidyl tartrate (DST), the shortest cross-linker in the series, only the cross-links between the amino terminus and Lys 6, and between Lys 6 and Lys 11 were observed. The observed cross-links are consistent with the crystal structure of ubiquitin, if the lysine side chains and the amino terminus are assumed to have considerable flexibility. In a separate study, we probed the reactivity of the primary amino groups in ubiquitin using the amino acetylating reagent, N-hydroxy succinimidyl acetate (NHSAc), and a top-down approach to localize the acetylated lysine residues. The reactivity order obtained in that study (M1 ≈ K6 ≈ K48 ≈ K63) > K33 > K11 > (K27, K29), shows that the cross-link first formed in ubiquitin by reaction with DSS and DSG occurs between the most reactive residues.
Estimation of the Molecular Mass Range of the Tar from Pyrolysis of Casein by Gas Chromatography-Mass Spectrometry, Probe Mass Spectrometry and Size-Exclusion Chromatography with 1-methyl-2-pyrrolidinone as Eluent
Authors: Purevsuren B. , Avid B. , Davaajav Ya. , Herod A.A. , Kandiyoti R. , Morgan T.J.
Published: March 2004

Casein has been pyrolysed to obtain a biochar (28.3% yield), with mostly meso- and macro-pore structure, and a liquid tar product of high yield (37.5%) with the balance as gas (20.9%) and water (13.3%). The elemental composition of the casein tar was: C 66.7%, H 8.3%, N 12.1% and O 12.9% (by difference). The tar sample has been characterised by mass spectrometry, gas chromatography (GC)/MS and heated-probe MS, to give molecular mass distributions for comparison with molecular mass ranges indicated by analytical-scale size-exclusion chromatography (SEC). The tar appeared to be completely soluble in 1-methyl-2-pyrrolidinone (NMP), the solvent used for SEC. It appeared to consist mostly of lower molecular mass fractions with elution times at 18–26 min. GC/MS analysis showed the presence of both aliphatic and aromatic nitrogen-containing components. Neither GC/MS nor heated-probe MS were able to detect more than about half the tar components.
Mass Spectrometric Detection of Protein, Lipid and Heme Components of Cytochrome c Oxidase from R. Sphaeroides and the Stabilization of Non-Covalent Complexes from the Enzyme
Authors: Distler Anne M. , Allison John , Hiser Carrie , Qin Ling , Hilmi Yasmin , Ferguson-Miller Shelagh
Published: March 2004

The cytochrome c oxidase enzyme from Rhodobacter sphaeroides bacteria exists as a complex of four peptide subunits, two hemes and a variety of lipids and metal ions held together by non-covalent forces. Although the native enzyme functions as an associated unit, this complex usually dissociates during matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectrometry analysis. Through the use of matrix additives such as sucrose, the complete complex and partial complexes can be stabilized in the MALDI-ToF experiment. The dissociation of the complex allows the detection of the components of the enzyme. The direct detection of associated lipids from an aqueous solution of the intact enzyme may eliminate the need for enzyme disruption and lipid extraction. The partial dissociation of multi-subunit enzymes in such experiments may allow the determination of subunit–subunit and subunit–lipid interactions.
Cyclization of N,N-Dialkyldithiocarbamate and Alkylxanthate Derivatives of Polyhalogenated Pyridines in Gas and Liquid Phases
Authors: Samguina Tatiana Yu. , Lobodin Vladislav V. , Karakhanova Nadezhda K. , Lebedev Albert T. , Sipyagin Aleksey M.
Published: March 2004

The intramolecular cyclization of 31 polyhalogen-substituted pyridines containing N,N-dialkyldithiocarbamate or alkylxanthate groups has been compared as a reaction in solution with sodium N,N-dialkyldithiocarbamates or potassium carbethoxydithiolate and as a gas-phase reaction under electron ionization (EI) conditions. A scheme of fragmentation for the studied compounds has been proposed. The influence of the nature of leaving groups (Cl, F, CF3, CN, COOEt), of the presence of electron-withdrawing groups (Cl, F, CN, CCl3, CF3, COOEt) that are ortho, meta or para to the leaving halogen, of the position of a dithio group with respect to the pyridine nitrogen atom and of the role of oxygen and nitrogen in the corresponding alkylxanthates and N,N-dialkyldithiocarbamates on the cyclization process has been investigated.
Trace Analysis of Organics in Air by Corona Discharge Atmospheric Pressure Ionization Using an Electrospray Ionization Interface
Authors: Nikolaev Eugene , Riter Leah S. , Laughlin Brian C. , Handberg Eric , Cooks R. Graham
Published: March 2004

A corona discharge ion source operating at atmospheric pressure in the point-to-plane configuration was constructed by reconfiguring the ion source of a commercial electrospray ionization (ESI) quadrupole mass spectrometer. This new source allows direct air analysis without modification to the mass spectrometer. Detection and quantitation of semi-volatile compounds in air is demonstrated. The analytical performance of the system was established using the chemical warfare agent simulants methyl salicylate and dimethyl methylphosphonate. Limits of detection are 60 pptr in the negative-ion mode and 800 pptr in the positive-ion mode for methyl salicylate and 800 pptr in the negative-ion mode and 3.6 ppb in the positive-ion mode for dimethyl methylphosphonate. A linear response was observed from 60 pptr to 8 ppb for methyl salicylate in air in the negative-ionization mode. Cluster ion formation versus production of analyte ions was investigated and it was found that dry air or an elevated capillary interface temperature (130°C) was needed to avoid extensive clustering, mostly of water. Reagent gases are not needed as proton sources, as is usually the case for atmospheric pressure chemical ionization, and this, together with the simplicity, sensitivity and speed of the technique, makes it promising for miniaturization and future field studies.
Derivatization in Mass Spectrometry– 3. Alkylation (Arylation)
Authors: Halket John M. , Zaikin Vladimir G.
Published: March 2004

The review is devoted to alkylation (arylation) as a widely employed derivatization procedure for the protection of OH (carboxylic acids, phosphoric acids, sulfonic acids, alcohols, polyols, phenols, enols), SH (thiols) and NH (amines, amides) groups in order to increase volatility, to improve the chromatographic properties and, if possible, mass spectral properties of derivatives. Chemical aspects of derivatization and various alkylation (arylation) reagents and reaction procedures are described. Specific mass spectral (electron ionization, chemical ionization) features of derivatives helpful in identification, structure elucidation, profiling and quantitative determination of the above-mentioned polar compounds by coupled gas chromatography or high-performance liquid chromatography are discussed. Some common analytical applications of the procedures in organic chemistry, clinical chemistry, environmental chemistry etc. are briefly summarized.
MICRA: A Compact Permanent Magnet Fourier Transform Ion Cyclotron Resonance Mass Spectrometer
Authors: Mauclaire G. , Lemaire J. , Boissel P. , Bellec G. , Heninger M.
Published: March 2004

MICRA,1 a compact Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer is described. The amount of miniaturisation in this device, based on a 1.24 T permanent magnet, remains compatible with genuine FT-ICR performance and analytical power in the mass range 2–1000 m/z, with a mass resolving power of 73,000 at mass 132. A first application of the transportability is the repetitive coupling of MICRA with a large-scale source of IR photons, the free electron laser CLIO.
High-Energy Collision-Induced Dissociation of Oxosteroids Derivatised to Girard Hydrazones
Authors: Griffiths William J. , Alvelius Gunvor , Liu Suya , Sjövall Jan
Published: March 2004

Neutral oxosteroids have been derivatised with Girard T and P hydrazine reagents to give the corresponding Girard hydrazone quaternary ammonium salts. Both Girard T (GT) and Girard P (GP) hydrazones of oxosteroids give very intense [M]+ ion signals in electrospray (ES) mass spectra and fragment within the ES interface and collision cell to give characteristic fragment ions. GT and GP derivatives give informative high-energy collision-induced dissociation spectra, from which the structure of the precursor oxosteroid can be determined. Both charge-remote and charge-mediated mechanisms are responsible for the formation of the fragment ions at high collision-energy.
Investigation of Methods Suitable for the Matrix-Assisted Laser Desorption/Ionization Mass Spectrometric Analysis of Proteins from Ribonucleoprotein Complexes
Authors: Suh Moo-Jin , Limbach Patrick A.
Published: March 2004

A variety of protein isolation and purification techniques for ribonucleoprotein (RNP) complexes were investigated for their compatibility with downstream analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Ribosomal proteins from Escherichia coli 70S ribosomes were obtained using methods such as phenol extraction and precipitation by organic solvents or acids. Under optimal conditions, more than 90% of the expected ribosomal proteins were detected in a single MALDI-MS experiment. The most effective approach combined ribosome denaturation by buffer exchange with acid precipitation of the ribosomal ribonucleic acids. An improved acid precipitation approach, involving the sequential additions of acetic and trifluoroacetic acid, yielded more complete protein coverage while minimizing loss of ion signal from lower molecular weight proteins. With phenol extraction, substantial gains in ion abundance of higher molecular weight proteins are noted, although some of the lower molecular weight proteins were not efficiently extracted. These results illustrate several effective approaches for protein isolation from protein complexes such as RNPs that are MALDI-MS compatible, and these approaches should extend the use of MALDI-MS for proteomics-based analyses of other protein–nucleic acid complexes.
Excitation of Ions by High-Harmonic Frequency Components in Paul and Penning Traps and Ion Guides. I. Selective Simultaneous Dipolar Excitation of High Charge States with Clipped Sinusoidal and Non-Harmonic Waveforms in a Linear Quadrupole Ion Guide
Authors: Rakov V. Sergey , Whitehouse Craig M.
Published: March 2004

This article presents a method for simultaneous excitation of multiple high charge states of a molecular ion in Paul or Penning trap. Using a linear quadrupolar ion guide we validate the method by using a variety of time-domain excitation waveforms with high harmonics of the first charge state's resonant frequency. The proposed way of inducing harmonics is the deliberate distortion of the excitation waveform from its sinusoidal form. In order to facilitate interference of the harmonics, a superposition of two sinusoids different by a frequency factor of two is used. The simplest form of distortion – amplitude restriction – of such waveform produces interference of the harmonics and results in selective excitation of charge states. Multiple protonation states of melittin were used as a model in this study.
Gas-Phase Ion–Molecule Reactions of Small Nitroalkanes and Their Deprotonated Anions
Authors: Kato Shuji , Carrigan Kathleen E. , DePuy Charles H. , Bierbaum Veronica M.
Published: March 2004

Gas-phase reactions of nitromethane (1), nitroethane (2), 2-nitropropane (3), 2-methyl-2-nitropropane (4) and nitrocyclopropane (5) were studied at 300 K using the flowing afterglow technique. These nitroalkanes react with gas-phase bases HO−, CH3O− and HOO− very rapidly with rate coefficients of (2.5–4.3) × 10−9 cm3 s−1 and reaction efficiencies of 60–100%, for example, k = 3.2 × 10−9 cm3 s−1 (86%) for 5 reacting with hydroperoxide anion. Proton transfer (PT) is the only reaction observed for 1 while elimination (E2) is the exclusive pathway for 4 yielding isobutene and NO2−. Both PT and E2 reactions are observed for 2, 3 and 5, the former being the major pathway. Deprotonated anions of 1, 2, 3 and 5 were subjected to reactivity studies with CH3I, CO2, CS2 and SO2. Nucleophilic substitution (SN2) reaction occurs with CH3I, while characteristic products CS2O− and SO3− are formed from CS2 and SO2, respectively, along with competing adduct formation. The SN2 rate is greater, whereas the reactivities with the triatomic reagents are smaller for deprotonated nitrocyclopropane than for the other acyclic anions. These observations strongly suggest that the reactions of nitroalkane [M – H]− anions occur through initial attack from the terminal oxygen; the nitrocyclopropane carbanion is more strained and, thus, less stabilized by resonance [R2C−−NO2 ↔ R2C=NO2−] resulting in the greater basicity/nucleophilicy and the less negative charge on the oxygen site.
Analysis of Sugar Epimers Using Mass Spectrometry: N-Acetyllactosamine-6,6′-Disulfate and the 2′-Epimer
Authors: Ohashi Yoko , Itoh Yoshiyuki , Kubota Masayuki , Hamada Kensaku , Ohashi Mamoru , Hirano Takashi , Niwa Haruki
Published: March 2004

Galβ1–4GlcNAc-6,6′-disulfate and 2′-epimer corresponding to Galβ1–4ManNAc-6,6′-disulfate were distinguished by mass spectrometry by utilizing fast atom bombardment (FAB), electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) methods. As for the steric information, negative-ion ESI mass spectrometry/mass spectrometry (MS/MS) provides the most extensive data, but FAB MS/MS also reveals detailed structural information of interest in our case, where MALDI MS is not yet fully equipped with post-source decay.
Optimization of Conditions for Studies of Protein Unfolding by Hydrogen Exchange/Mass Spectrometry
Authors: Raza A.S. , Smith D.L.
Published: March 2004

Understanding the forces driving protein folding and aggregation is an essential step in developing means for controlling these important processes. Amide hydrogen exchange, coupled with mass spectrometry, has become an important method for studying protein unfolding and refolding. To extend procedures developed to study unfolding of relatively soluble proteins to less soluble, aggregation-prone proteins requires special considerations. This publication describes a general strategy developed using yeast transaldolase, which aggregates easily under conditions required to study its unfolding. Results presented here show that reducing the protein concentration to the nanomolar range is essential for managing aggregation of transaldolase. In addition, the present results point to use of relatively high concentrations of denaturants and short incubation times to minimize aggregation. These results also show how amide hydrogen exchange, coupled with mass spectrometry, can be used to study soluble aggregates.
Design, Setup and First Results of a Miniaturized Time-of-Flight Mass Spectrometer with a Simple Reflector of a New Design
Authors: Uphoff Andreas , Muskat Tassilo , Grotemeyer Jürgen
Published: March 2004

A new kind of reflector with only one element has been constructed and used in a miniaturized time-of-flight mass spectrometer. Details from the simulation of the instrument with SIMION and its design are presented and discussed. The instrumental setup is displayed and some first results from measurements are presented. Laser-generated electron ionization (LEI) and resonance-enhanced multi-photon ionization (REMPI) are used for ion production. While both methods yield good mass spectra, the mass resolving power of the instrument is different for both methods. The results of the measurements are compared and discussed with respect to the design. It is found that the resolution of the new instrument is satisfactory for mass spectrometric measurements of small molecules and not limited by the reflector.
Mass Spectrometric Differentiation of α- and β-Aspartic Acid in a Pseudo-Tetrapeptide Thrombosis Inhibitor and its Isomer
Authors: Luu Nganha C. , Robinson Scott , Zhao R. , McKean R. , Ridge Douglas P.
Published: March 2004

The pseudo-tetrapeptide designated here as RGD (N-ethyl-N-[1-oxo-4-(4-piperidinyl) butyl] glycyl-L-α-aspartyl-3-cyclohexyl-L-alaninamide) and its isomer with β-aspartic acid rather than α-aspartic acid were examined using electrospray ionization (ESI) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). RGD has potential as a thrombosis inhibitor and the isomer, designated here as isopeptide, is an inactive instability product; hence, means were sought to distinguish the two. Both isomers give a protonated parent on ESI and fragments typical of peptides on sustained off resonance irradiation collision-induced decomposition (SORI-CID). Cleavage at the aspartic acid (b3) is the dominant process in both isomers, although a significant b2 and smaller a2 “and c2” peaks are also observed. More distinctive are peaks observed at b3 – H2O, b3 – (CO + CO2) and, only in the case of the RGD, b3 – (H2O + CO). SORI CID on the b3 ion indicates that, of these distinctive peaks, only the b3 – (CO + CO2) comes from decomposition of the b3 ion. On this basis, a mechanism is suggested for b3 formation, involving proton transfer from a back-bone carbonyl to the aspartic acid side-chain carboxyl group. Such an intramolecular proton transfer involves rings of different sizes for the two isomers, providing a basis for the different SORI energy dependences. A mechanism suggested for the formation of the b3 – H2O fragments also involves proton transfer to the aspartic acid side chain carboxyl group. This leads to concomitant H2O loss and amide bond cleavage, giving the b3 – H2O ions with ketene moieties resulting from the water loss. According to the suggested mechanism, the observed loss of CO (verified by SORI-CID on the b3 – H2O ion) from the RGD b3 – H2O peak results in a secondary carbocation stabilized by an adjacent nitrogen. The unobserved loss of CO from the b3 – H2O ion, formed by the suggested mechanism from the isopeptide, would give an unstable primary carbocation lacking a neighboring nitrogen. The mechanism, thus, only rationalizes the observation of a b3 – (H2O + CO) fragment in RGD and not in the isopeptide. The isomers can be distinguished on the basis of this unique peak or on the basis of the different SORI energy dependence of the formation of the b3 ions.
Kinetic Energy Release of Protonated Methanol Clusters Using the Low-Temperature Fast-Atom Bombardment: Experiment and Theory Combined
Authors: Gömöry Ágnes , Végh Péter , Sztáray Judit , Drahos László , Vékeya Károly
Published: March 2004

Low-temperature fast-atom bombardment was found to be an excellent method for generating large protonated methanol clusters, (CH3OH) nH+ ( n = 2 to 15). Metastable dissociations of these clusters, involving elimination of one methanol molecule, were studied using mass-analyzed ion kinetic energy spectra (MIKES). From metastable peak profiles kinetic energy release (KER) distributions were obtained, even for clusters as large as (CH3OH)15H+. The results were analyzed by a simple thermal model, by the finite heat bath theory (FHBT) and by the RRKM-based MassKinetics algorithm. The KER distribution was shown to correspond to a three-dimensional translational energy distribution, implying statistical energy partitioning in the transition state. The mean KER values and transition state temperatures were found to increase with cluster size, reaching 25 meV and ∼210 K for large clusters ( n = 10).
Influential Characteristics of Physician/Pharmacist Collaborative Relationships
Authors: Zillich Alan J , McDonough Randal P , Carter Barry L , Doucette William R
Published: March 2004

BACKGROUND

A theoretical model of physician/pharmacist collaborative relationships, driven by 3 groups of relationship characteristics termed participant, context, and exchange, has been developed. There are no studies that have examined the types of characteristics which most influence development of collaborative relationships between physicians and pharmacists.

OBJECTIVE

To test the model and determine which drivers most influence physician/pharmacist collaboration.

METHODS

Data on the relationship drivers and collaborative practice were collected via a mailed survey of a random sample of 1000 primary care physicians in Iowa. Participant variables include demographics; context drivers refer to the practice environment and professional interactions between physicians and pharmacists. Exchange characteristics describe the nature of social exchange and were elicited using scores from 3 domains (relationship initiation, trustworthiness, role specification) of the Physician/Pharmacist Collaboration Instrument (PPCI). Five additional questions asked about the physician's collaborative practice with a pharmacist. Hierarchical linear regression analysis was performed with collaborative practice as the dependent variable and measures of participant, context, and exchange drivers as independent variables.

RESULTS

Three hundred forty usable surveys (34%) were returned. Almost 70% of the respondents were male and aged 45.8 ± 9.9 years (mean ± SD). The majority were family practice physicians (72.1%) in private practice (67.3%). Regression analyses produced an R2 = 0.804 (p < 0.001). Significant predictors in the model were internal medicine physicians, professional interaction with a pharmacist, and the 3 domains of exchange drivers from the PPCI (p < 0.05).

CONCLUSIONS

Although participant and context factors influenced physician/pharmacist collaborative relationships, exchange characteristics were the most influential relationship drivers. Role specification, trustworthiness, and relationship initiation were positively associated with physician/pharmacist collaborative practice. Recognition of these drivers may help pharmacists who are developing collaborative working relationships with physicians. But, studies are needed to delineate other factors that may influence physician/pharmacist relationships.
Lichenoid Drug Eruption Probably Associated with Rofecoxib
Authors: Abu-Shraie Nada A , Alfadley Abdullah A
Published: March 2004

OBJECTIVE

To report a case of lichenoid drug eruption (LDE) probably induced by rofecoxib.

CASE SUMMARY

A 73-year-old woman was prescribed rofecoxib 25 mg/day for rheumatoid arthritis in addition to other medications on which the patient had been stabilized. Six months after initiation of rofecoxib, linear plaques over the infra-orbital and bitemporal areas of both eyes were observed. Several itchy violaceous papules also developed on her right wrist and dorsum of the left foot. She also had a hyperpigmented macule on her right buccal mucosa. As the skin rash was localized and the patient was initially unwilling to undergo skin biopsy, rofecoxib was continued and a topical steroid was started. One month later, the patient was seen in the dermatology clinic, and the improvement of her skin reaction was significant. A skin biopsy performed during this visit was consistent with LDE. On the next day, her rheumatologist decided to discontinue the offending drug, rofecoxib. Two months later, all skin lesions had completely resolved. No rechallenge with rofecoxib was attempted.

DISCUSSION

LDE is a rare skin reaction that can be associated with several drugs. Rofecoxib, a cyclooxygenase-2 inhibitor, has never before been reported to cause LDE. An objective causality assessment indicates that rofecoxib was the probable cause of the skin reaction.

CONCLUSIONS

As of this writing, to our knowledge, this is the first case report in the English literature in which rofecoxib had led to the development of LDE.
Tibolone: A Unique Version of Hormone Replacement Therapy
Authors: Swegle John M , Kelly Michael W
Published: March 2004

OBJECTIVE

To review the pharmacology, pharmacokinetics, efficacy, and safety of tibolone in the treatment of menopausal symptoms and the prevention of osteoporosis.

DATA SOURCES

Information was obtained from a MEDLINE search (1966–July 2003) and from Organon International. The bibliographies of reviewed literature were searched for additional studies.

STUDY SELECTION AND DATA EXTRACTION

Studies and review articles evaluating tibolone were evaluated. Since tibolone has been available for many years in Europe and has an extensive literature base, this review emphasizes information from studies published after 1995.

DATA SYNTHESIS

Tibolone possesses estrogenic activity and is effective for treating the symptoms and osteoporosis associated with menopause. While the impact of tibolone on the risk of breast cancer or cardiovascular and thromboembolic events is not well defined, its unique pharmacologic profile may provide a safer alternative to traditional hormone replacement therapy. Although widely used for many years in other countries, tibolone has not been approved for use in the US.

CONCLUSIONS

Results of recent trials have led to questions regarding the safety of established hormone replacement therapies in peri- and postmenopausal women. Tibolone appears to be an attractive alternative to these traditional regimens. Additional studies will determine whether the promise of increased safety with tibolone will be realized.
Possible Association of Acute Lateral-Wall Myocardial Infarction and Bitter Orange Supplement
Authors: Nykamp Diane L , Fackih Majed N , Compton Anthony L
Published: March 2004

OBJECTIVE

To report a possible incidence of acute lateral-wall myocardial infarction (MI) coinciding with the use of a Citrus aurantium L. (bitter orange)—containing dietary supplement in a patient with undetected coronary vascular disease.

CASE SUMMARY

A 55-year-old white woman presented to the emergency department with symptoms of dull aching shoulder and chest pain. A review of medications during cardiac rehabilitation revealed the patient had ingested a multicomponent dietary supplement for weight loss containing 300 mg of bitter orange (Edita's Skinny Pill) for the past year. Although the patient's past medical history did not include hypertension, coronary disease, or hyperlipidemia, an arteriogram revealed a lesion in the left main coronary artery. She did have a smoking history. She was diagnosed with acute lateral-wall MI and hospitalized for 4 days.

DISCUSSION

Consumers generally consider dietary supplements safe. However, some supplements taken for weight loss contain ingredients that have been associated with cardiovascular events. Although consumers are becoming more aware of the serious adverse effects secondary to products containing ingredients such as Ma huang and ephedra, reports involving other ingredients are increasing. Bitter orange or synephrine, found in bitter orange, has been associated with adverse cardiovascular reactions. Based on the Naranjo probability scale, C. aurantium is possibly associated with this cardiovascular event.

CONCLUSIONS

The use of C. aurantium—containing supplements may present as a risk for cardiovascular toxicity; however, additional studies/case reports are needed to validate this conclusion.
Assessing the Clinical Impact of Prostate-Specific Antigen Assay Variability and Nonequimolarity: A Simulation Study Based on the Population of the United Kingdom
Authors: Roddam Andrew W , Price Christopher P , Allen Naomi E , Ward Anthony Milford ,   the National Health Service Prostate Cancer Risk Management Programme
Published: March 2004

Background: Prostate-specific antigen (PSA) is the most widely used serum biomarker to differentiate between malignant and benign prostate disease. Assays that measure PSA can be biased and/or nonequimolar and hence report significantly different PSA values for samples with the same nominal amount. This report investigates the effects of biased and nonequimolar assays on the decision to recommend a patient for a prostate biopsy based on age-specific PSA values.

Methods: A simulation model, calibrated to the distribution of PSA values in the United Kingdom, was developed to estimate the effects of bias, nonequimolarity, and analytical imprecision in terms of the rates of men who are recommended to have a biopsy on the basis of their assay-reported PSA values when their true PSA values are below the threshold (false positives) or vice versa (false negatives).

Results: False recommendation rates for a calibrated equimolar assay are 0.5–0.9% for analytical imprecision between 5% and 10%. Positive bias leads to significant increases in false positives and significant decreases in false negatives, whereas negative bias has the opposite effect. False-positive rates for nonequimolar assays increase from 0.5% to 13% in the worst-case scenario, whereas false-negative rates are almost always 0%.

Conclusions: Biased and nonequimolar assays can have major detrimental effects on both false-negative and false-positive rates for recommending biopsy. PSA assays should therefore be calibrated to the International Standards and be unbiased and equimolar in response to minimize the likelihood of incorrect clinical decisions, which are potentially detrimental for both patient and healthcare provider.
Coriolis-Massedurchflussmesser mit direkter Viskositätsmessung (Coriolis-mass-flowmeter with Direct Viscosity Measurement)
Authors: Drahm Wolfgang , Fuchs Michael , Bjönnes Hege , Matt Christian , Wenger Alfred , Sprich Hans-Jörg
Published: March 2004

Massedurchfluss-Messgeräte nach dem Coriolisprinzip haben sich schon seit langem als präzise und robuste Feldgeräte bewährt. Diese Geräte lieferten schon bisher Prozessinformationen über Durchfluss, Dichte und Temperatur. Nun ist es gelungen, auch noch den wichtigen Prozessparameter Viskosität gleichzeitig und unabhängig zu erfassen. Damit steht ein wirklich „multivariables“ Prozessmessgerät zur Verfügung.
Fahrzeugumfelderfassung mit mehrzeiligen Laserscannern (The Use of Multi-Layer Laser Scanners for Monitoring the Environment of Driving Vehicles)
Authors: Fürstenberg Kay Ch. , Dietmayer Klaus C. J.
Published: March 2004

Es werden Methoden zur Fahrzeugumfelderfassung, basierend auf einem neuartigen mehrzeiligen Laserscanner als Sensor, vorgestellt. Mithilfe eines Sensormodell- und Objektmodell-gestützten Ansatzes zur Messsignalverarbeitung ist es möglich, andere Verkehrsteilnehmer wie Fußgänger, Radfahrer oder Kraftfahrzeuge zu detektieren, zu klassifizieren und in ihrem Bewegungsverhalten zu modellieren. Derartige Algorithmen bilden die Grundlage zum Aufbau eines konsistenten Fahrzeugumfeldmodells, das für zukünftige Sicherheits- und Komfortsysteme im Kraftfahrzeug benötigt wird.
Bedeutung der Informationsverarbeitung in Sensorsystemen (Importance of Signal Processing in Sensor Systems)
Authors: Kanoun Olfa , Tränkler Hans-Rolf
Published: March 2004

Innovationen bei künftigen Sensorsystemen sind durch gleichzeitige Fortschritte bei den Herstellungstechnologien und bei der Signalverarbeitung charakterisiert. Erst durch ein abgestimmtes Zusammenspiel zwischen Herstellungstechnologie und Signalverarbeitung lassen sich Synergien für besonders erfolgreiche Lösungen erzielen. Ziel dieses Beitrags ist es, einen Überblick über die besondere Bedeutung der Informationstechnik in der heutigen Sensorik zu geben. Eine spezielle Betrachtung wird den Methoden der digitalen Signalverarbeitung zur Verbesserung der Sensoreigenschaften und Kompensation von unerwünschten Effekten gewidmet. Am Ende des Beitrags werden einige Entwicklungstendenzen für Sensorsysteme angeführt.
Immunological Aspects and Affections of Rubbish Collectors Caused by Bioaerosols
Authors: Becher Stephan , Lichtnecker Herbert
Published: March 2004

Immunological Aspects and Affections of Rubbish Collectors Caused by Bioaerosols: Stephan Becher, et al. Rheinischer Gemeindeunfallversicherungsverband—From the point of view of industrial medicine, the maintenance of industrial health and safety standards to minimize health hazards for staff is the most important item in dealing with biological materials at work. With regard to the rubbish industry, it is therefore mandatory to recognize every possible health hazard in order to supplement preventive measures and to increase industrial medical prevention. In a cross‐sectional study of industrial medicine, 83 trash collectors were medically examined, their case history having been taken by means of a standardized questionnaire. The immunobiological examination consisted of the measurement of specific IgE and IgG antibodies to Aspergillus fumigatus. An immunoblot was used to supplement the investigation and to illustrate individual epitopes of allergens of Aspergillus fumigatus. In 16 trash collectors (19%) there was a specific sensitization against Aspergillus fumigatus Type I and Type III simultaneously, as proven by the standards of Coombs and Gell. Specific antibodies to Aspergillus fumigatus were discovered in 27 employees. Neither the information given by the dust collectors nor medical examination results allowed the deduction of the presence of an allergy in the sense of typical health disturbances. Based on the results of this study, however, the immunological parameters may indicate a possible sensitization of the employees in the rubbish industry.
Relationships between Some Individual Characteristics and Occupational Accidents in the Construction Industry
Authors: Chau Nearkasen , Mur Jean‐Marie , Benamghar Lahoucine , Siegfried Christian , Dangelzer Jean‐Louis , Français Martine , Jacquin Régis , Sourdot Alain
Published: March 2004

Relationships between Some Individual Characteristics and Occupational Accidents in the Construction Industry: A Case‐Control Study on 880 Victims of Accidents Occurred during a Two‐ Year Period: Nearkasen Chau, et al. National Institute for Health and Medical Research (INSERM), Unit 420, Faculte de Medecine—This case‐control study assessed the relationships between certain individual characteristics (age, body mass index, training, length of time in present job, sleep disorders, certain disabilities, smoking habits, sporting activities) and occupational accidents in construction male labourers: 880 cases with at least one occupational accident in 1995‐1996, 880 controls with no occupational accident during the previous five years, matched to cases on the job. A standardised questionnaire, filled in by the occupational physician, was used. The statistical analyses were made by the conditional logistic regression method for paired data. The main causes of accidents were handling or carrying objects, falls to a lower level, construction machinery and devices, falls on the same level, moving objects, hand tools. For all accidents combined, the factors with significant adjusted odds‐ratios (OR) were: age<30 yr (OR 1.30, 95%C11.01‐1.68), sleep disorders (1.97, 1.42‐2.73), and current smoker (1.27, 1.04‐1.54). Sleep disorders were a significant factor in falls to a lower level (OR 2.25, 95%CI 1.14‐4.44), age<30 yr and sleep disorders for accidents caused by moving objects (4.64, 1.48‐14.5 and 13.11, 2.64‐65.2 respectively), and no sporting activity for injuries by handling or carrying objects (1.70, 1.11‐2.60). Sleep disorders were significant for accidents with sick leave lengths of >15 d, whereas age<30 yr and current smoker were significant for the others (<14 d). A relationship was observed between the severity of sleep disorders and accidents. Occupational accidents are mainly due to work conditions, but certain individual characteristics may also play a role; this should be confirmed by further studies.
Hyperexcitability of the Hippocampal CA1 and the Dentate Gyrus in Rats Subchronically Exposed to a Substitute for Chlorofluorocarbons, 1‐Bromopropane Vapor
Authors: Fueta Yukiko , Ishidao Toru , Arashidani Keiichi , Endo Yu taka , Hori Hajime
Published: March 2004

Hyperexcitability of the Hippocampal CA1 and the Dentate Gyrus in Rats Subchronically Exposed to a Substitute for Chlorofluorocarbons, 1‐Bromopropane Vapor: Yukiko Fueta, et al. The First Department of Medical Technology, School of Health Sciences, University of Occupational and Environmental Health—To investigate the effects on the central nervous system of subchronic exposure to 1‐bromopropane (1‐BP), which is a substitute for chlorofluorocarbons, we measured the hippocampal excitability of 1‐BP‐treated rats electrophysiologically. Male Wistar rats were exposed to 1 ‐BP for 6‐h in a day in an exposure chamber (1,500 ppm) for 4 wk. After the 1‐, 3‐ and 4‐wk inhalation, field excitatory postsynaptic potentials (fEPSPs), population spikes (PSs), fEPSP/spike (E/S) curve, paired‐pulse profiles of fEPSP slopes and PS amplitudes recorded from CA1 pyramidal neurons, and dentate granule cells of the hippocampal slice obtained from the rats were analyzed. In 1 ‐BP treated rats, E/S potentiation and a lower subthreshold of PSs were observed in the dentate gyrus (DG) after the 3 and 4‐wk inhalation. Paired‐ pulse inhibition was reduced at 5‐50 ms in the CA1 and at 5‐20 ms in the DG after all of the inhalation. These changes were not associated with paired‐pulse inhibition of fEPSPs. In the DG, the paired‐pulse inhibition at the short interpulse intervals in rats exposed to 1‐BP was pronounced by an application of A type gamma aminobutyric acid (GABA) receptor agonist pentobarbital. Impaired paired‐pulse inhibition of granule cells at the short interpulse intervals was recovered after the application of N‐methyl‐D‐aspartate (NMDA) type glutamate receptor antagonist DL‐2‐amino‐5‐phosphonopentanoic acid. Convulsing rats observed after the 4‐wk inhalation exhibited multiple PSs in the DG, and their second component was abolished by an application of this antagonist. Inhalation of 1‐BP increased the neuronal excitability in the hippocampal CA1 and the DG. The hyperexcitability of the granule cells in the DG was at least due to an over‐activation of NMDA receptors.
Two‐year Study of Carcinogenicity and Chronic Toxicity of Biphenyl in Rats
Authors: Umeda Yumi , Arito Heihachiro , Kano Hirokazu , Ohnishi Makoto , Matsumoto Michiharu , Nagano Kasuke , Yamamoto Seigo , Matsushima Taijiro
Published: March 2004

Two‐year Study of Carcinogenicity and Chronic Toxicity of Biphenyl in Rats: Yumi Umeda, et al. Japan Bioassay Research Center, Japan Industrial Safety and Health Association— Carcinogenicity and chronic toxicity of biphenyl were examined in 50 male and 50 female F344 rats exposed to 0, 500, 1,500 or 4,500 ppm biphenyl in the diet for 105 weeks. Bladder tumors were found in the 4,500 ppm males, as evidenced by significantly increased incidence of carcinoma (24/50) and papilloma (10/50) of the transitional cells as well as one rarely observed case both of carcinoma and papilloma of the squamous cells. The survival rate of the 4500 ppm males significantly decreased, due to the bladder tumors and the hematuria accompanied by bladder calculi. The bladder calculi were found in 43 males in the 4,500 ppm group, but in only 8 females. Urinary pH significantly increased in the males, and occult blood was observed both in males and females in the 4,500 ppm group. The pre‐neoplastic lesions were hyperplasia of transitional epithelium (simple, nodular and papillary hyperplasia) in the bladder of the 4,500 ppm males. Incidences of calculus formation and transitional cell hyperplasia in the renal pelvis also significantly increased in the 4,500 ppm males and females. On the other hand, the incidences of the transitional cell hyperplasia and the calculus formation in the bladder and the renal pelvis were far lower in females than in males, and no bladder tumors were observed in the females. Causative factors of the bladder tumors and their male predominance were discussed with reference to the findings reported in the literature and the previous study of biphenyl metabolism.
Acute and Subchronic Inhalation Toxicity of Chloroform in Rats and Mice
Authors: Kasai Tatsuya , Nishizawa Tomoshi , Arito Heihachiro , Nagano Kasuke , Yamamoto Seigo , Matsushima Taijiro , Kawamoto Toshihiro
Published: March 2004

Acute and Subchronic Inhalation Toxicity of Chloroform in Rats and Mice: Tatsuya Kasai, et al. Japan Bioassay Research Center—In order to better characterize acute and subchronic toxicities of chloroform and to provide its basic toxicity data for risk assessment of humans exposed to chloroform in work and living environments, mice and rats of both sexes were exposed by inhalation to chloroform at different concentrations from 500 to 8,000 ppm for 6 h/d x 5 d/ wk X 2 wk and from 12 to 400 ppm for 6 h/d x 5 d/wk x 13 wk. The kidneys, liver and nasal cavity were primarily damaged by the inhalation exposure. Acute death occurred at 12 ppm in male mice, 1,000 ppm in female mice and 2,000 ppm in male and female rats. The 13‐wk exposures induced renal lesions in male mice, hepatic and nasal lesions in female mice and renal, hepatic and nasal lesions in male and female rats. Susceptibility to the acute and subchronic toxicities was higher in male mice than female mice, and higher in mice than in rats. No‐observed‐adverse‐ effect‐levels (NOAELs) and lowest‐observed‐adverse‐ effect‐levels (LOAELs) were determined for the renal, hepatic and nasal endpoints of animals exposed to chloroform for 13 wk. For the hepatic endpoint, NOAEL was 100 ppm in male mice, 50 ppm in female mice and female rats and 100 ppm in male rats. For the renal endpoint, LOAEL was 12 ppm in male mice, and NOAEL was 25 ppm in male rats and 100 ppm in female rats. For the nasal endpoint, LOAEL was 12 ppm and 25 ppm in the mice and the rats of both sexes, respectively.
Physiological and Psychological Effects of High Speed Driving on Young Male Volunteers
Authors: Uchikune Masashi
Published: March 2004

Physiological and Psychological Effects of High Speed Driving on Young Male Volunteers: Masashi Uchikune, Department of Precision Machinery Engineering, College of Science & Technology, Nihon University—The purpose of this study was to clarify the physiological and psychological effects on car‐drivers and their passengers. Heart rate, respiratory frequency, salivation, and subjective symptoms were measured before, 3 min and 6 min after starting at speeds ranging from 80 to 120 km/h. Vibration frequency and acceleration of the drivers and passengers’ heads were simultaneously determined. The heart rate and respiratory frequency ratios of the drivers travelling at 110 km/h were 1.04, and 1.15 at 6 min after starting, whereas those of the passengers were 1.06 and 1.15, respectively. With respect to the salivation rate ratios, a decrease was noted at all the travelling speeds of both drivers and passengers. In drivers travelling at 110 km/h, a repression value of 0.72 to the baseline of one was noted, and a repression value of 0.91 was noted in the passengers. Pleasant and unpleasant indexes, at 120 km/h was 1.26 times higher than that obtained at 90 km/h. It was considered that in all the measurements the variations were caused by physiological and psychological changes mainly induced by vibration frequency and acceleration of the head.
Low Back Pain and Smoking in a Community Sample in Japan
Authors: Otani Tetsuya , Iwasaki Motoki , Ohta Akiko , Kuroiwa Masaya , Yosiaki Sasazawa , Suzuki Shosuke , Aoki Shigenobu
Published: March 2004

Low Back Pain and Smoking in a Community Sample in Japan: Tetsuya Otani, et al. Department of Public Health, Gunma University School of Medicine—A cross‐sectional study with a self‐administered questionnaire was conducted in order to examine the association between low back pain and smoking. The subjects analyzed were 6,891 adults aged 40‐69 yr, who lived in a downtown district in Isesaki City, Gunma, Japan. There was a positive association between cigarette smoking and low back pain in men. The age‐adjusted odds ratios of low back pain were 1.32 (95% confidence interval (Cl) 1.10,1.57) for 1‐20 cigarettes smoked per day and 1.40 (95% Cl 1.11,1.76) for 21 or more. The association had similar strength after adjustment for alcohol consumption, physical exercise, body mass index, non‐ musculoskeletal disease, education, occupation, and whether living with parents, living with a child or children, or living alone. The multivariate odds ratios for low back pain were 1.29 (95% Cl 1.03, 1.62) for 1‐ 20 cigarettes smoked per day and 1.36 (95% Cl 1.03, 1.80) for 21 or more. In conclusion, smoking was significantly related to low back pain, even if adjusted for other potential risk factors.
Effectiveness of a Participatory Workplace Risk Assessment Team in Reducing the Risk and Severity of Musculoskeletal Injury
Authors: Carrivick Philip J.W. , Lee Andy H. , Yau Kelvin K.W.
Published: March 2004

Effectiveness of a Participatory Workplace Risk Assessment Team in Reducing the Risk and Severity of Musculoskeletal Injury: Philip J.W. Carrivick,et al.Department of Occupational Health, Sir Charles Gairdner Hospital, Australia—This study evaluates the effectiveness of a participatory workplace risk assessment team (the intervention) in reducing the rate and severity of musculoskeletal and non‐musculoskeletal injuries among a cohort of 137 cleaners within a hospital setting. The date, workers’ compensation claims cost and hours lost from work were obtained for each injury occurring during the 4‐yr pre‐intervention and 3‐yr post‐intervention period. The age, gender and hours worked during the study period, were ascertained for every cleaner whether injured or not. For musculoskeletal injuries, the intervention was associated with significant reductions of two‐thirds in injury rate, 65% in workers’ compensation claims cost per hour worked, and 40% in hours lost per hour worked. Cleaners also experienced a significant two‐ third post‐intervention reduction in non‐musculoskeletal injury rate; but the corresponding changes in severity rates were not significant. The intervention supports the adoption of a participatory approach to reducing the rate and consequence of musculoskeletal injuries in the workplace.