bluuebunny/crossref_metadata_2025 huggingface dataset:
Complementation of Vaccinia Virus Lacking the Double-Stranded RNA-Binding Protein Gene E3L by Human Cytomegalovirus
Authors: Child Stephanie J. , Jarrahian Sohail , Harper Victoria M. , Geballe Adam P.
Published: July 2002

The cellular response to viral infection often includes activation of pathways that shut off protein synthesis and thereby inhibit viral replication. In order to enable efficient replication, many viruses carry genes such as the E3L gene of vaccinia virus that counteract these host antiviral pathways. Vaccinia virus from which the E3L gene has been deleted (VVΔE3L) is highly sensitive to interferon and exhibits a restricted host range, replicating very inefficiently in many cell types, including human fibroblast and U373MG cells. To determine whether human cytomegalovirus (CMV) has a mechanism for preventing translational shutoff, we evaluated the ability of CMV to complement the deficiencies in replication and protein synthesis associated with VVΔE3L. CMV, but not UV-inactivated CMV, rescued VVΔE3L late gene expression and replication. Thus, complementation of the VVΔE3L defect appears to depend on de novo CMV gene expression and is not likely a result of CMV binding to the cell receptor or of a virion structural protein. CMV rescued VVΔE3L late gene expression even in the presence of ganciclovir, indicating that CMV late gene expression is not required for complementation of VVΔE3L. The striking decrease in overall translation after infection with VVΔE3L was prevented by prior infection with CMV. Finally, CMV blocked both the induction of eukaryotic initiation factor 2α (eIF2α) phosphorylation and activation of RNase L by VVΔE3L. These results suggest that CMV has one or more immediate-early or early genes that ensure maintenance of a high protein synthetic capacity during infection by preventing activation of the PKR/eIF2α phosphorylation and 2-5A oligoadenylate synthetase/RNase L pathways.
Caveolar Endocytosis of Simian Virus 40 Is Followed by Brefeldin A-Sensitive Transport to the Endoplasmic Reticulum, Where the Virus Disassembles
Authors: Norkin Leonard C. , Anderson Howard A. , Wolfrom Scott A. , Oppenheim Ariella
Published: July 2002

Simian virus 40 (SV40) enters cells by atypical endocytosis mediated by caveolae that transports the virus to the endoplasmic reticulum (ER) instead of to the endosomal-lysosomal compartment, which is the usual destination for viruses and other cargo that enter by endocytosis. We show here that SV4O is transported to the ER via an intermediate compartment that contains β-COP, which is best known as a component of the COPI coatamer complexes that are required for the retrograde retrieval pathway from the Golgi to the ER. Additionally, transport of SV40 to the ER, as well as infection, is sensitive to brefeldin A. This drug acts by specifically inhibiting the ARF1 GTPase, which is known to regulate assembly of COPI coat complexes on Golgi cisternae. Moreover, some β-COP colocalizes with intracellular caveolin-1, which was previously shown to be present on a new organelle (termed the caveosome) that is an intermediate in the transport of SV40 to the ER (L. Pelkmans, J. Kartenbeck, and A. Helenius, Nat. Cell Biol. 3:473-483, 2001). We also show that the internal SV40 capsid proteins VP2 and VP3 become accessible to immunostaining starting at about 5 h. Most of that immunostaining overlays the ER, with some appearing outside of the ER. In contrast, immunostaining with anti-SV40 antisera remains confined to the ER.
Highly Pathogenic Simian Immunodeficiency Virus mne Variants That Emerge during the Course of Infection Evolve Enhanced Infectivity and the Ability To Downregulate CD4 but Not Class I Major Histocompatibility Complex Antigens
Authors: Patel Parul G. , Yu Kimata Monica T. , Biggins Julia E. , Wilson Joelle M. , Kimata Jason T.
Published: July 2002

The replicative, cytopathic, and antigenic properties of simian immunodeficiency virus (SIV) variants influence its replication efficiency in vivo. To further define the viral properties and determinants that may be important for high-level replication in vivo and progression to AIDS, we compared a minimally pathogenic SIVmne molecular clone with two highly pathogenic variants cloned from late stages of infection. Both variants had evolved greater infectivity than the parental clone due to mutations in
nef
. Interestingly, a
pol
determinant in one of the highly pathogenic variants also contributed to its increased infectivity. Furthermore, because replication in vivo may also be influenced by the ability of a virus to evade the cellular immune response of the host, we examined whether the variants were more capable of downregulating surface expression of class I major histocompatibility complex (MHC). Decreased MHC class I expression was not observed in cells infected with any of the viruses. Furthermore, the Nef proteins of the highly pathogenic variants only slightly reduced surface MHC class I expression in transfected cells, although they efficiently downregulated CD4. Together, these data demonstrate that mutations which can enhance viral infectivity, as well as CD4 downregulation, may be important for efficient replication of SIV in the host. However, Nef-mediated reduction of MHC class I expression does not appear to be critical for the increased in vivo replicative ability of highly pathogenic late variants.
Human T-Cell Leukemia Virus Type 2 (HTLV-2) Tax Protein Transforms a Rat Fibroblast Cell Line but Less Efficiently than HTLV-1 Tax
Authors: Endo Keiichi , Hirata Akira , Iwai Kousuke , Sakurai Mamoru , Fukushi Masaya , Oie Masayasu , Higuchi Masaya , Hall William W. , Gejyo Fumitake , Fujii Masahiro
Published: July 2002

Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are retroviruses with similar biological properties. Whereas HTLV-1 is the causative agent of an aggressive T-cell leukemia, HTLV-2 has been associated with only a few cases of lymphoproliferative disorders. Tax1 and Tax2 are the transcriptional activators of HTLV-1 and HTLV-2, respectively. Here we show that Tax2 transformed a Rat-1 fibroblast cell line to form colonies in soft agar, but the size and number of the colonies were lower than those of Tax1. Use of a chimeric Tax protein showed that the C-terminal amino acids 300 to 353 were responsible for the high transforming activity of Tax1. Activation of cellular genes by Tax1 through transcription factor NF-κB is reportedly essential for the transformation of Rat-1 cells. Tax2 also activated the transcription through NF-κB in Rat-1 cells, and such activity was equivalent to that induced by Tax1. Thus, the high transforming activity of Tax1 is mediated by mechanisms other than NF-κB activation. Our results showed that Tax2 has a lower transforming activity than Tax1 and suggest that the high transforming activity of Tax1 is involved in the leukemogenic property of HTLV-1.
Identification of Neutralizing and Nonneutralizing Epitopes in the Porcine Reproductive and Respiratory Syndrome Virus GP5 Ectodomain
Authors: Ostrowski M. , Galeota J. A. , Jar A. M. , Platt K. B. , Osorio F. A. , Lopez O. J.
Published: July 2002

After infection of swine with porcine reproductive and respiratory syndrome virus (PRRSV), there is a rapid rise of PRRSV-specific nonneutralizing antibodies (NNA), while neutralizing antibodies (NA) are detectable not sooner than 3 weeks later. To characterize neutralizing epitopes, we selected phages from a 12-mer phage display library using anti-PRRSV neutralizing monoclonal antibody (MAb) ISU25-C1. In addition, phages carrying peptides recognized by swine antibodies with high seroneutralizing titer were isolated after subtracting from the library those clones binding to swine anti-PRRSV serum with no neutralizing activity. Two epitopes located in the ectodomain of PRRSV GP5 were identified. One of these epitopes, which we named epitope B, was recognized both by neutralizing MAb ISU25-C1 and swine neutralizing serum (NS) but not by swine nonneutralizing serum (NNS), indicating that it is a neutralizing epitope. Epitope B is sequential, conserved among isolates, and not immunodominant. Antibodies directed against it are detected in serum late after infection. In contrast, the other epitope, which we named epitope A, is hypervariable and immunodominant. Antibodies against it appear early after infection with PRRSV. This epitope is recognized by swine NNA but is not recognized by either neutralizing MAb ISU25-C1 or swine NA, indicating that it is not involved in PRRSV neutralization. During infection with PRRSV, epitope A may act as a decoy, eliciting most of the antibodies directed to GP5 and delaying the induction of NA against epitope B for at least 3 weeks. These results are relevant to the design of vaccines against PRRSV.
Highly Stable Trimers Formed by Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Fused with the Trimeric Motif of T4 Bacteriophage Fibritin
Authors: Yang Xinzhen , Lee Juliette , Mahony Erin M. , Kwong Peter D. , Wyatt Richard , Sodroski Joseph
Published: July 2002

The envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) function as a trimer composed of three gp120 exterior glycoproteins and three gp41 transmembrane proteins. Soluble gp140 glycoproteins composed of the uncleaved ectodomains of gp120 and gp41 form unstable, heterogeneous oligomers, but soluble gp140 trimers can be stabilized by fusion with a C-terminal, trimeric GCN4 motif (X. Yang et al., J. Virol. 74:5716-5725, 2000). To understand the influence of the C-terminal trimerization domain on the properties of soluble HIV-1 envelope glycoprotein trimers, uncleaved, soluble gp140 glycoproteins were stabilized by fusion with another trimeric motif derived from T4 bacteriophage fibritin. The fibritin construct was more stable to heat and reducing conditions than the GCN4 construct. Both GCN4- and fibritin-stabilized soluble gp140 glycoproteins exhibited patterns of neutralizing and nonneutralizing antibody binding expected for the functional envelope glycoprotein spike. Of note, two potently neutralizing antibodies, immunoglobulin G1b12 and 2G12, exhibited the greatest recognition of the stabilized, soluble trimers, relative to recognition of the gp120 monomer. The observed similarities between the GCN4 and fibritin constructs indicate that the HIV-1 envelope glycoprotein ectodomains dictate many of the antigenic and structural features of these fusion proteins. The melting temperatures and ligand recognition properties of the GCN4- and fibritin-stabilized soluble gp140 glycoproteins suggest that these molecules assume conformations distinct from that of the fusion-active, six-helix bundle.
Study of Activity Distribution for Consecutive Reactions
Authors: Letková Zuzana , Brunovská Alena , Markoš Josef
Published: July 2002

The optimal pellet activity distribution for a system of consecutive reactions is analyzed numerically. Two cases are studied: the case of unconstrained activity (without predescribed maximal concentration of active component) leading to a Dirac delta activity distribution and the case with upper bound for the activity distribution (concentration of active component can not exceed given maximal value) which leads to a step function profile. As the objective function global selectivity is chosen. Examples of both cases are given. The reaction kinetics is described by Langmuir-Hinshelwood type of equations.
Preparation of Dimethyl Carbonate from Methanol and Carbon Dioxide in the Presence of Sn(IV) and Ti(IV) Alkoxides and Metal Acetates
Authors: Kizlink Juraj , Pastucha Ivan
Published: July 2002

The synthesis of dimethyl carbonate by the reaction of methanol with carbon dioxide in the presence of metal alkoxides and metal carboxylates was studied. The best results have been achieved with Ti(IV) and Sn(IV) alkoxides which at 130 to 180 °C and low CO2 pressures yield dimethyl carbonate in 30 to 100 mole % or 40 to 130 mole % yields with respect to the metal alkoxides, depending on the carbon dioxide (gaseous and solid one, respectively). The yields can be further increased up to 70 - 190 mole % and 90 - 270 mole %, respectively, by the use of chemical scavengers of the reaction water.
Phase Stability of Hydrogen-Bonded Polymer Mixtures: Application of the Quasichemical Theory
Authors: Pouchlý Julius , Živný Antonín , Sikora Antonín
Published: July 2002

Expressions for the second derivative of Gibbs energy of mixing with respect to composition and/or the corresponding Flory-Huggins interaction parameter are derived using the Barker-Guggenheim quasichemical theory. The calculation is performed first for a system of compounds with a homogeneous molecular surface, then for a binary mixture of molecules the surface of which consists of various kinds of contact sites. The result is expressed in terms of "indexes of nonrandomness", the factors which characterize deviations of individual types of contact pairs from random mixing at a given composition. Main attention is paid to a mixture of substances, each of which contains a different type of polar groups and a nonpolar residue which is similar for both components. Translucent relations are obtained in two limit cases, namely for small deviations from random mixing and for small attraction between polar and nonpolar groups. The effect of the relative size of the polar groups and of the affinity to formation of various heterocontacts is illustrated using the limit relations derived, as well as by means of model calculations.
Effect of Enzymically Generated Electronic-Excited Species on Membrane-Bound Na+,K+-ATPase
Authors: Obšil Tomáš , Amler Evžen , Pavlíček Zdeněk
Published: July 2002

The effect of electronic-excited species generated by systems 2-methylpropanal (MPAL) plus horse-radish peroxidase (HRP) and glyceraldehyde (GCA) plus HRP on Na+,K+-ATPase activity was investigated. For the system MPAL-HRP (which generates triplet acetone) Na+,K+-ATPase activity, the concentration of malondialdehyde, the membrane lateral pressure and the collisional quenching of protein tryptophan residues by NaI were determined. The enzyme activity decreased by 70% during the incubation. Lipid peroxidation products were increased to a steady state level from 5.5 ± 0.5 to 22.6 ± 0.7 nmol malondialdehyde mg-1 protein after 60 min. The membrane lateral pressure was increased from 83.6 ± 0.4 to 90 ± 0.9 mN m-1. In peroxidized membranes, the fluorescence intensity of tryptophan residues was decreased and the fluorescence intensity of bityrosine adducts was increased. Changes of conformation of Na+,K+-ATPase were observed by the collisional quenching of protein tryptophan residues by NaI. For the system GCA-HRP the Na+,K+-ATPase activity decreased by 20% after incubation with GCA and by 30% with GCA-HRP. Changes of conformation of Na+,K+-ATPase were detected both after the incubation with GCA and GCA-HRP. These results demonstrate that electronic-excited species inhibit the activity of membrane-bound Na+,K+-ATPase both by an increase of membrane lateral pressure of the lipid microenvironment of the ATPase molecules and by a direct effect of oxidation of protein residues, i.e. tryptophan, tyrosine.
Conductimetric Gas Separation-Flow Injection Determination of Ammonia in Gaseous Process Streams
Authors: Kubáň Vlastimil
Published: July 2002

Ammonia (up to 0.3 vol.%) can be determined (RSDs < 2%) after separation from a process gas stream containing (vol.%): carbon dioxide (0.3-20), hydrogen sulfide (< 0.4), hydrogen cyanide (< 1.5 . 10-4), sulfur dioxide (1), carbon monoxide (< 3) in 50-90 vol.% nitrogen and hydrocarbons. The ammonia content in sample is determined through changes in the conductivity of an acceptor stream (3 mM boric acid) caused by absorption of the analyte passed through a Nafion capillary membrane.
Gas/Diffusion Flow Injection Determination of Ammonium Ions in River and Waste Waters by Conductometry
Authors: Vlček Jiří , Kubáň Vlastimil
Published: July 2002

An FIA conductometric method for monitoring of ammonium ions in river and waste waters is proposed. A very good detection limit (xD 5.6 μmol l-1) was obtained at 100/20 s preconcentration/rinsing times and 2 ml sample consumption per analysis at the flow rate 0.8 ml min-1. The detection limit xD can be further improved at longer preconcentration/ rinsing times. Precipitation of polyvalent metal ions (mainly Fe(III)) was eliminated by addition of 0.5 mmol l-1 EDTA prior to injection. The results are comparable with those obtained by spectrophotometry (Nessler's reagent).
Synthesis and Biological Evaluation of New Antiinflammatory 1-Benzothiophene-2-carboxanilides
Authors: Svoboda Jiří , Štádler Michal , Jandera Antonín , Panajotová Vladimíra , Kuchař Miroslav
Published: July 2002

3-Substituted 1-benzothiophene-2-carboxanilides 2-5 and their corresponding sulfones 6-8 were synthesized. The antiinflammatory effect of compounds 2-8 was evaluated in tests of LTB4 biosynthesis, carrageenin edema and ear inflammation. With the exception of 3-hydroxyamides 5a-5c, low inhibitory activities against COX and LT biosynthesis were observed.
Pattern Formation in the Methylene Blue-Fructose-Oxygen System in Aqueous Solution and in Gel Systems
Authors: Adamčíková Ľubica , Hupková Mária , Ševčík Peter
Published: July 2002

Spatial patterns in methylene blue-catalyzed oxidation of fructose at alkaline pH were found in aqueous solution and in gel systems. In a thin liquid layer (thickness >2.4 mm) a mixture of spots and stripes was formed by interaction of a nonlinear reaction and the Rayleigh or Maragoni instabilities. The pattern formation was affected by initial reactant concentrations and by the thickness of the reaction mixture layer. Long-lasting structures were formed in gel systems (polyacrylamide, agar, gelatin). These patterns also arise primarily from hydrodynamic processes.
Kinetics and Mechanism of the Quinolinium Fluorochromate Oxidation of Some Primary, Secondary and Unsaturated Alcohols in Acetonitrile
Authors: Meenakshisundaram Subbiah , Sockalingam Ramanathan
Published: July 2002

Quinolinium fluorochromate (QFC) in MeCN readily oxidises primary and secondary alcohols to the corresponding carbonyl compounds. Solvent effect on reactivity is quite significant. The reaction can be characterized by the rate equationv=k3K1K2[Alc][TsOH][QFC]t/ {1 + [TsOH](K1+K1K2[Alc])}. The ρ* valueca-1.6 is indicative of a partial bonding in the linear transition state envisaged. Large primary kinetic isotope effect (kH/kD> 10) in this study suggests a concerted, two-electron hydride transfer mechanism. Mechanistic studies on the oxidation of unsaturated alcohols with QFC in acetonitrile medium described by the rate equationk0=k2K1[TsOH]2+k4K3K1[Alc][TsOH] is verified. Product analysis studies rule out the possibility of attack on the double bond. Linear relation in the Exner plots implies the operation of a common mechanism in all the alcohols studied. The high reactivity observed in the cinnamyl alcohol oxidation can be ascribed to resonance interaction through conjugated double bonds.
A Simple Numerical Method for Calculating Gaussian NMR Spectral Line Shapes Partially Narrowed Due to a Motion with the Exponential Spectral Autocorrelation Function
Authors: Jakeš Jaromír
Published: July 2002

A simple numerical method for calculating NMR spectral line shapes resulting from a Gaussian line by a partial narrowing due to a motion with the exponential spectral autocorrelation function of the form exp (-|τ|/τc) was developed. It was found that the partially narrowed line is narrower not only than the parent Gaussian line with the second moment of ωp2 but also than the Lorentzian line with the half-width of 2ωp2τc obtained from the extreme narrowing approximation. The central intensity increase compared with the closer of these two lines is less than 50.2%. Asymptotic developments for large values of ω - ω0 and for large values of ωpτc were derived. Two-term approximation applied to the extreme narrowing case led to a very simple modification of the Lorentzian line having the correct second moment ωp2. Analysis of this modified Lorentzian line showed that attempts to estimate ωp2 from truncated second moments of Lorentzian lines without knowledge of τc are hopeless. The case of the polyexponential spectral autocorrelation function with all but one correlation times fast enough to allow for the extreme narrowing, modelling the case of an anisotropic motion, is also considered.
The trunk muscles of elite oarsmen
Authors: McGregor A H , Anderton L , Gedroyc W M W
Published: July 2002

Objectives:To investigate the trunk strength of elite rowers and the impact of low back pain on these measures in order to determine if asymmetries or weakness were present.

Methods:Twenty two elite rowers were recruited: 13 reported previous low back pain, five current low back pain, and the remainder had no history of low back pain. All subjects were scanned during simulated rowing in an interventional open magnetic resonance imaging scanner. In each simulated rowing position, axial scans were obtained at the level of the L4–5 and L5–S1 disc interspace to determine the cross sectional area of the posterior trunk muscles.

Results:Considerable differences were observed between the three groups of rowers. In contrast with expectations and previous literature, the trunk muscles of rowers with low back pain had significantly larger cross sectional areas (p<0.001). No left/right asymmetries were observed and no differences between oarside and non-oarside in terms of muscle cross sectional area.

Conclusion:These findings suggest that low back pain in rowers does not arise as a result of muscle weakness.
The prognostic value of quality of life scores during treatment for oesophageal cancer
Authors: Blazeby J M , Brookes S T , Alderson D
Published: July 2002

BACKGROUND

Quality of life (QL) data are useful to evaluate the effectiveness of treatment. Accumulating evidence suggests that QL data may predict survival.

AIMS

In this study we investigated if baseline QL scores and changes in QL scores before and after intervention are prognostic for patients with oesophageal cancer.

PATIENTS

Between 1993 and 1995, 92 consecutive new patients with oesophageal cancer were studied; 89 were followed until death or the end of the study period (survival of seven patients was censored in May 1999).

METHODS

All patients completed the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire (EORTC QLQ-C30) and the dysphagia scale of the oesophageal module (EORTC QLQ-OES24) before treatment and at regular intervals throughout the study. Cox's proportional hazards models assessed the impact of baseline QL variables and changes in QL scores on survival.

RESULTS

Cox's proportional hazards models, adjusting for associations between QL scores, age, and TNM stage, found that physical function at baseline was significantly associated with survival (p=0.002). An increase in physical function score of 10 points corresponded to a 12% reduction in the likelihood of death at any given time (95% confidence intervals 4–18%). Further exploratory multivariable analyses suggested that improvement in emotional function six months after treatment was significantly related to longer survival (p<0.0001).

CONCLUSIONS

These data provide evidence to support a relationship between patient rated scores of QL and survival. Further understanding of the associations between QL and clinical variables is needed.
Cell proliferation in type C gastritis affecting the intact stomach
Authors: Mac Dowall J E , Willis P , Prescott R , Lamonby S , Lynch D A F
Published: July 2002

Aims—Type C gastritis caused by bile reflux has a characteristic appearance, similar to that seen in other forms of chemical gastritis, such as those associated with NSAIDs or alcohol. An increase in mucosal cell proliferation increases the likelihood of a neoplastic clone of epithelial cells emerging, particularly where there is chronic epithelial injury associated with bile reflux. It has been shown previously that type C gastritis is associated with increased cell proliferation in the postsurgical stomach. The aim of this study was to determine cell proliferation in type C gastritis caused by bile reflux affecting the intact stomach.

Methods—Specimens from 15 patients with a histological diagnosis of type C gastritis on antral biopsy were obtained from the pathology archives between 1994 and 1997. A control group of nine normal antral biopsies was also selected and all underwent MIB-1 immunostaining. The gastric glands were divided into three zones (zone 1, gastric pit; zone 2, isthmus; and zone 3, gland base) and the numbers of positively staining nuclei for 500 epithelial cell nuclei were counted in each zone to determine the percentage labelling index (LI%).

Results—Cell proliferation was significantly higher in all three zones of the gastric glands with type C gastritis compared with controls as follows: zone 1, median LI% in type C gastritis 64.7 (range, 7.8–99.2), controls 4.7 (range, 2.0–11.3); zone 2, median LI% in type C gastritis 94.7 (range, 28.8–98.7), controls 40.2 (range, 23.1–70.3); and zone 3, median LI% in type C gastritis 20.0 (range, 1.3–96.0), controls 2.6 (range, 0.9–8.7).

Conclusions—Bile reflux is thought to act as a promoter of gastric carcinogenesis in the postsurgical stomach. The same may be true in the intact stomach.
Evaluation of B cell lymphoid infiltrates in bone marrow biopsies by morphology, immunohistochemistry, and molecular analysis
Authors: Maes B , Achten R , Demunter A , Peeters B , Verhoef G , De Wolf-Peeters C
Published: July 2002

Aims—Morphological criteria to distinguish between reactive and neoplastic B cell lymphocytoid infiltrates in trephines have been defined but are not always reliable. Polymerase chain reaction (PCR) analysis of the CDR3 region of the immunoglobulin heavy chain (IgH) gene which, by demonstrating monoclonality, can provide additional arguments in favour of lymphoid malignancy is now frequently used for the detection and follow up of B cell lymphoma (NHL). The aim of this study was to investigate the usefulness of morphological findings in bone marrow biopsies in comparison with data obtained by PCR analysis.

Methods—Eighty nine bone marrow biopsies displaying lymphoid infiltrates were evaluated by morphology and immunohistochemistry as well as by CDR3-PCR using consensus framework 3 (FRW3) and JH primers.

Results—The presence of a clonal B cell proliferation was demonstrated by PCR analysis in 45 biopsies, including 21 samples considered to be positive, 17 to be suspicious, and seven to be negative by morphology. In the remaining 44 trephines we found no evidence of clonality, although 12 of these trephines were thought to be positive by morphology.

Conclusions—These results, revealing an incomplete correlation between CDR3-PCR data and immunomorphological findings, indicate that molecular analysis may be more sensitive and specific in general. However, false negative PCR results do occur, which emphasises the necessity to combine both diagnostic tools in the evaluation of lymphoid infiltrates.
Methadone deaths: a toxicological analysis
Authors: Milroy C M , Forrest A R W
Published: July 2002

Aims—To perform a toxicological analysis of deaths involving methadone and to determine the fatal concentration of methadone in such deaths.

Methods—Deaths in which methadone was mentioned in the cause of death were identified. Deaths were divided into those associated with methadone only and deaths in which the cause of death was a combination of methadone and other drugs. Toxicological findings in these deaths were analysed and compared with previously published data.

Results—One hundred and eleven cases were analysed. In 55 cases, methadone poisoning was given as the sole cause of death. Fifty victims were adults, age range 17–51 years (median, 23), with five victims under 14 years of age. The mean methadone concentration in the adult deaths was 584 μg/litre (median, 435; range, 84–2700). In 56 cases, age range 15–49 years, (median, 28), death was ascribed to a combination of methadone and other drugs. The mean methadone concentration in these deaths was 576 μg/litre (median, 294; range, 49–2440). In 26 cases, multiple site sampling was performed. This revealed that there could be a 100% discrepancy between methadone concentrations, and other drugs, in samples collected in different sites in the same body.

Conclusions—There is an overlap between quoted therapeutic methadone concentrations and methadone concentrations seen in fatalities. However, those dying from methadone poisoning might not be the same as those in a methadone programme. A degree of caution must be exercised in determining a fatal concentration because of the phenomenon of postmortem redistribution. Pathologists and toxicologists need to examine all the available postmortem findings in identifying the cause of death.
Methodological quality and reporting of ethical requirements in clinical trials
Authors: Ruiz-Canela Miguel , de Irala-Estevez Jokin , Martínez-González Miguel Ángel , Gómez-Gracia Enrique , Fernández-Crehuet Joaquín
Published: July 2002

Objectives—To assess the relationship between the approval of trials by a research ethics committee (REC) and the fact that informed consent from participants (ICP) was obtained, with the quality of study design and methods.

Design—Systematic review using a standardised checklist.

Main measures—Methodological and ethical issues of all trials published between 1993 and 1995 in theNew England Journal of Medicine,theLancet,theJournal of the American Medical Associationand theBritish Medical Journalwere studied. In addition, clinical trials conducted in Spain and published by at least one Spanish author during the same period in any other journal were also included.

Results—We studied the published articles of 767 trials and found the following indicators of lower methodological quality to be independent predictors for failure to disclose REC approval or ICP: absence of concealment of allocation, lack of justification for unblinded trials, not using a treatment for the patients in the control group, absent information on statistical methods, not including sample size estimation, not establishing the rules to stop the trial, and omitting the presentation of a baseline comparison of groups

Conclusion—Trials of higher methodological and scientific quality were more likely to provide information about their ethical aspects.
Musculoskeletal dysfunction in physical education teachers
Authors: Sandmark Hélène
Published: July 2002

OBJECTIVES

To investigate the prevalence of musculoskeletal disorders, especially symptomatic osteoarthrosis (OA) of the knee and hip, health and lifestyle factors among physical education (PE) teachers, and whether they differed from the general population in these respects.

METHODS

The study base was all Swedish men (n=290) and women (n=281) who graduated from the only training college for PE teachers in Sweden, between the years 1957 and 1965, and age matched referents, 255 men and 257 women, randomly selected from the Swedish population register. A postal questionnaire was sent to the subjects with questions on occupational history, participation in sports, musculoskeletal disorders, height, weight, smoking habits, and general health.

RESULTS

The PE teachers had a higher prevalence ratio (PR) of symptomatic OA of the knee (men: 2.8 95% confidence interval (95% CI) 1.6 to 4.8; women: 3.2 95% CI 1.8 to 5.5) and knee injury compared with the referents. The PE teachers reported more absence from work, and the women had had to change jobs more often because of knee disorders. The prevalence ratio for symptomatic OA of the hip was 2.7 (95% CI 1.0 to 7.1) for the female PE teachers. At the age of 25 the body mass index (BMI) of male PE teachers was higher than the male referents, but at an older age both the female and male PE teachers had lower BMI than the referents. The participation in sports activities was considerably higher in the group of PE teachers. They also smoked less, reported less serious diseases, and better health than the referents.

CONCLUSIONS

The PE teachers had a high risk of developing knee disorders, which entailed difficulties in continuing their work as PE teachers. They differed from the referents in lifestyle factors as they smoked less, were less overweight, and had a higher lifelong sports exposure.
Reported incidence of occupational asthma in the United Kingdom, 1989–97
Authors: McDonald J C , Keynes H L , Meredith S K
Published: July 2002

OBJECTIVES

To examine trends in estimated population based incidence of occupational asthma by age, sex, occupation, geographical region, and causal agents based on 9 years of the Surveillance of Work Related and Occupational Respiratory Disease (SWORD) data.

METHODS

In January 1989 the SWORD scheme for the surveillance of occupational respiratory disease was established in the United Kingdom to make good the lack of epidemiological information on the incidence of these diseases in the United Kingdom. Between 80% and 90% of chest and occupational physicians report voluntarily all new cases they see, on a monthly or random sampling basis. During the 9 years 1989–97, an estimated 25 674 new cases of occupational respiratory disease, including 7387 of occupational asthma, were reported. Suspected causal agents were classified into 44 categories and estimated annual incidences of asthma were calculated with denominators from the labour force survey.

RESULTS

Overall, a third of the suspected causes of asthma were organic, a third chemical, 6% metallic, and the rest miscellaneous, or in 8%, unknown. There was evidence of an increase since 1989 in cases due to latex, and possibly glutaraldehyde, and an apparent drop since 1991 in the proportion of cases attributed to isocyanates. Incidences were higher in men than women and the disparity was especially marked in the population aged 45 years or more in which rates for men were at least twice those for women. Average annual rates per million workers for 1992–7 ranged from 7 (95% confidence interval (95% CI) 5 to 9) for the lowest risk group of professional, clerical, and service workers to 1464 (95% CI 968 to 2173) for coach and other spray painters. Except for laboratory technicians, all other occupations with rates over 100 were concerned with manufacturing and processing that used chemicals, metals, and organic materials. Incidences were two to three times higher in the north and midlands than in East Anglia and the south. The introduction of a sampling scheme in 1992 doubled estimates of reported incidence of occupational asthma, but there was little evidence of other temporal changes.

CONCLUSIONS

The SWORD scheme has produced consistent estimates of the causes and incidence of occupational asthma as seen by chest and occupational physicians. It has allowed the epidemiology of occupational asthma in the population to be studied and high risk occupations to be identified. There is certainly more occupational asthma in the population than that which reaches specialists in occupational and chest medicine; therefore the incidence rates presented here are underestimates, but by how much remains unknown.
Hypoparathyroidism unmasked by alendronate
Authors: Kashyap A S , Kashyap Surekha
Published: July 2002

The case of an elderly woman is reported in whom alendronate, given for osteoporosis, led to severe hypocalcaemia a few days after starting the drug treatment. This was caused by the unmasking of previously unrecognised hypoparathyroidism.
Dataandmodels determine treatment proposals—an illustration from meta-analysis
Authors: Helfenstein U
Published: July 2002

A relevant problem in meta-analysis concerns the possible heterogeneity between trial results. If a test of heterogeneity is not significant the trials are often considered to be “homogeneous” and the individual trial results are replaced by an overall mean effect size and its confidence interval (“equal effects model”). If the trials are heterogeneous the individual trial effect sizes are conserved (“fixed effects model”). In a more flexible approach (“random effects model”), each trial makes use of knowledge from the other trials so individual effect sizes are “shrunken” towards an overall mean effect size. The more flexible tool may be useful for doctors involved in a trial when the outcome of their individual trial differs markedly from the overall mean effect size. Where a particular trial result is opposite in direction to the overall mean result, a conflict may arise: should a new patient be treated with the new method or not? The more flexible position and a graphical comparison of the three approaches are likely to be helpful in guiding the decision. Applying different models to the same data may lead to apparently paradoxical results: an individual trial result may be interpreted to be beneficial or harmful depending on the choice of model.
Application of consumer protection authority in preventing tobacco sales to minors
Authors: Krevor B S , Lieberman A , Gerlach K
Published: July 2002

In the USA, the enforcement of state sales of tobacco products to minors laws has had only limited impact upon reducing youth access. The application of consumer protection authorities by state attorneys general to alter the sales and promotion practices of tobacco retailers provides a complementary and highly leveraged strategy to increase compliance with tobacco sales to minors laws
Genes for multicopper proteins and laccase activity: common features in plant-associatedFusariumisolates
Authors: Kwon Sun-Il , Anderson Anne J
Published: July 2002

Eight Fusarium isolates from diverse plant habitats produced laccase activities when cultured on low-carbon medium. Three sequences with high homology to laccase genes were detected in the genome of Fusarium proliferatum, NRRL 31071, an opportunistic pathogen of wheat (Triticum spp.). The sequences aligned with laccase genes from Ascomycetes, whereas genes from other fungal taxonomic groups and from plants grouped separately. Sequences for related multicopper oxidases with ascorbate oxidase activity were also separated discretely. A fourth sequence from NRRL 31071 had highest homology to genes for multicopper proteins associated with ferrooxidase activities in yeasts. Each of the four sequences had high homology to sequences within the genome of a ligninolytic F. proliferatum from forest soil. RFLP analysis of the genomes of three other F. proliferatum isolates and a phylogenetically closely related isolate, Fusarium fujikuroi, showed that fragments hybridizing with the four multicopper oxidase genes were similar in size to those from the NRRL 31071 genome. Weaker hybridization was observed with the phylogenetically more distant Fusarium anthophilum. No hybridization was observed with an isolate of Fusarium culmorum, a wheat pathogen, from a different section of the genus Fusarium, although this isolate produced laccases.Key words: ferrooxidase, Fusarium proliferatum, laccase, multicopper oxidase.
Deformation of Upper Carboniferous coal measures in the Sydney Basin: evidence for late Alleghanian tectonism in Atlantic Canada
Authors: Gibling M R , Langenberg W , Kalkreuth W D , Waldron J WF , Courtney R , Paul J , Grist A M
Published: July 2002

Upper Carboniferous (Stephanian) coal measures of the Sydney Basin are deformed by reverse faults and folds with dips of up to 50° on the limbs. These structures represent compressional or transpressional events (Donkin Episode) of unknown sequence and timing. Offshore swath-bathymetry data indicate that northwest-striking reverse faults are folded by prominent northeast-trending folds. Vitrinite reflectance patterns of oriented coal samples from the fold limbs are uniaxial negative, with minimum reflectance axes (Rmin) near-normal to bedding and fanning across fold axes. This pattern implies that the bulk of coalification took place through burial compaction without directed horizontal stress, prior to the deformation that produced the folds. Slight divergence between Rminaxes and poles to bedding may reflect slight tilting, associated with differential subsidence or early reverse faulting, before or during coalification, or may lie within analytical error. One moderately biaxial sample suggests that some deformation accompanied coalification locally. Available apatite fission-track data for the Sydney Basin indicate that cooling of the coal measures to below 100 ± 20°C was underway by the Middle to Late Triassic or earlier. Because cooling implies that coalification was largely complete, the fission-track results are compatible with latest Paleozoic or early Mesozoic deformation. We infer that the Donkin Episode represents late Alleghanian (Permian?) compression within the Appalachian Orogen. If so, the Sydney structures are manifestations of a little-known tectonic episode in Atlantic Canada. However, MesozoicCenozoic deformation cannot be ruled out.
Probing electrostatic interactions in cytochromecusing site-directed chemical modification
Authors: Blouin Christian , Guillemette J Guy , Wallace Carmichael JA
Published: July 2002

This communication reports the generation of an electrostatic probe using chemical modification of methionine side chains. The alkylation of methionine by iodoacetamide was achieved in a set of Saccharomyces cerevisiae iso-1-cytochrome c mutants, introducing the nontitratable, nondelocalized positive charge of a carboxyamidomethylmethionine sulfonium (CAMMS) ion at five surface and one buried site in the protein. Changes in redox potential and its variation with temperature were used to calculate microscopic effective dielectric constants operating between the probe and the heme iron. Dielectric constants (ε) derived from ΔΔG values were not useful due to entropic effects, but εΔΔHgave results that supported the theory. The effect on biological activity of surface derivatization was interpreted in terms of proteinprotein interactions. The introduction of an electrostatic probe in cytochrome c often resulted in marked effects on activity with one of two physiological partners: cytochrome c reductase, especially if introduced at position 65, and cytochrome c oxidase, if at position 28.Key words: protein engineering, chemical modification, cytochrome c, electron transport, protein electrostatics, redox potential control.
Activity and conformational changes of horseradish peroxidase in trifluoroethanol
Authors: Zhou Hong-Wei , Xu Yan , Zhou Hai-Meng
Published: July 2002

The effect of trifluoroethanol (TFE) on horseradish peroxidase (HRP) was determined using activity assay and spectral analysis including optical absorption, circular dichroism (CD), and intrinsic fluorescence. The enzyme activity increased nearly twofold after incubation with 525% (v/v) concentrations of TFE. At these TFE concentrations, the tertiary structure of the protein changed little, while small changes occurred at the active site. Further increases in the TFE concentration (2540%) decreased the enzyme activity until at 40% TFE the enzyme was completely inactivated. The α-helix content of the protein increased at high TFE concentrations, while near-UV CD, Soret CD, and intrinsic fluorescence indicated that the tertiary structure was destroyed. Polyacrylamide gel electrophoresis results indicated that the surface charge of the enzyme was changed at TFE concentrations greater than 20%, and increasing concentrations of TFE reduced the enzyme molecular compactness. A scheme for the unfolding of HRP in TFE was suggested based on these results. The kinetics of absorption change at 403 nm in 40% TFE followed a two-phase course. Finally, HRP incubated with TFE was more sensitive to urea denaturation, which suggested that the main effect of TFE on HRP was the disruption of hydrophobic interactions.Key words: horseradish peroxidase, trifluoroethanol, unfolding, Soret.
Electromagnetic fields of thin circular loop antenna of arbitrary radius
Authors: Abo-Seida O M
Published: July 2002

The radiation pattern of a circular loop source of alternating current located in the lower half-space of two conductive media is considered. A solution of the linear Maxwell's equations in the frequency domain, using the Hankel transform to modified Helmholtz wave equations, was obtained. This leads to a system of ordinary differential equations with respect to the vertical coordinate, considering initial, boundary, and transition conditions. The solution determines the electromagnetic field in the conductive media which consists of primary and scattered waves. The results obtained from this paper can be used to evaluate numerical solutions of different complexities such as the underlying multilayered media. In addition, the derived formulation would be useful for interpreting airborne electromagnetic systems.

PACS Nos.: 41.20Jb, 42.25Bs, 42.25Gy, 44.05+e
The effect of vacuum polarization on muonproton scattering at small energies and angles
Authors: Gashi A , Rasche G , Woolcock W S
Published: July 2002

We give a compact expression for the unpolarized differential cross section for muonproton scattering in the one-photon exchange approximation. The effect of adding the vacuum polarization amplitude to the no-spin-flip amplitude for one-photon exchange is calculated at small energies and scattering angles and is found to be negligible for present experiments.

PACS No.: 13.6
A new simple system for measuring volume changes in unsaturated soils
Authors: Ng C W.W , Zhan L T , Cui Y J
Published: July 2002

A new simple system for accurately measuring overall total volume changes in unsaturated soil specimens with a triaxial apparatus is introduced in this paper. The basic principle of the measuring system is to record changes in the differential pressure due to changes in the water level inside an open-ended, bottle-shaped inner cell caused by volume change in the specimen and inside a reference tube using an accurate differential pressure transducer. Several important steps were taken to improve the accuracy and sensitivity of the measuring system. Detailed calibrations were carried out to account for apparent volume changes as a result of changes in cell pressure, fluctuation in the ambient temperatures, creep in the inner cell wall, and relative movement between the loading ram and the inner cell. The calibration results demonstrate that the measuring system is reasonably linear, reversible, and repeatable. The estimated accuracy of the measuring system is in the order of 32 mm3 (or 0.04% volumetric strain for a triaxial specimen 38 mm in diameter and 76 mm in height) once the system is properly calibrated.Key words: unsaturated soils, volume-change measurement, open-ended, bottle-shaped, inner cell, differential pressure, calibration.
Effects of defoliation on growth, biomass allocation, and wood properties ofBetula pendulaclones grown at different nutrient levels
Authors: Anttonen Seija , Piispanen Riikka , Ovaska Jari , Mutikainen Pia , Saranpää Pekka , Vapaavuori Elina
Published: July 2002

Three-year old Betula pendula Roth clones were grown at two nutrient levels in a field experiment to investigate the responses and recovery in growth and wood properties to a range of defoliation levels (0100%). No general threshold value of defoliation level for negative effects in growth was found, since the sensitivity of saplings to defoliation varied according to plant traits studied. However, responses were related to defoliation intensity. Saplings compensated for 25% defoliation in terms of height growth and number of current branches and were able to tolerate 50% defoliation without effects on diameter growth 1 year after the defoliation. Nutrient availability was significant only in determining how total biomass responded to defoliation. Fertilized saplings were able to tolerate 25% defoliation without reduction in total biomass, but nonfertilized saplings were not. The interaction between defoliation and fertilization disappeared in the second growing season after the defoliation. Saplings were not able to compensate for 75% defoliation in terms of total biomass or for 100% defoliation in terms of growth and branching even in 2 years' recovery time. In stemwood, complete defoliation reduced growth ring width and vessel diameter simultaneously and also induced a narrow zone of secondary xylem with defects. Our results suggest that defoliation level and recovery time played a crucial role in compensatory growth of birch saplings, while nutrient availability had a minor role.