bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bayesian subset analysis: application to studying treatment‐by‐gender interactions
Authors: Simon Richard 
Published: October 2002

AbstractEvaluating treatment effects within subsets of patients plays a major part of the analysis of many major clinical trials. Clinicians are often impressed by the heterogeneity of patient populations in clinical trials and hence are interested in examining subset effects. Statisticians generally discourage subset analysis or suggest that clinicians ‘do subset analysis but do not believe it’. This advice, however, is a sign of the inadequacy of the analytic methods generally used for subset analysis. Separate analysis of many subsets, and basing conclusions on whether the observed treatment difference achieves significance at the 0.05 level, is likely to yield erroneous conclusions. Making the separate analysis of subsets dependent on demonstration of a statistically significant treatment‐by‐subset interaction is also not an effective analytic strategy because of the limited power of interaction tests. This paper describes a Bayesian approach to subset analysis developed by Simon, Dixon and Freidlin. The method avoids many of the problems of subset analysis because it is not ‘separate’ analysis of subsets. Instead, subset‐specific treatment effects are estimated as an average of observed within‐subset differences and overall differences; the two components are weighted by thea prioriestimate of the likelihood of qualitative treatment by subset interactions. Hence, the Bayesian method proposed permits subset analyses incorporating the assumption that qualitative interactions are unlikely. The methodology is applied to the problem of designing and analysing clinical trials to estimate treatment effects for males and females. Copyright © 2002 John Wiley & Sons, Ltd.
Anti‐stress effect of yoga‐type breathing: modification of salivary cortisol, heart rate and blood pressure following a step‐climbing exercise
Authors: Monnazzi Paola , Leri Oriana , Guizzardi Liliana , Mattioli Domenico , Patacchioli F. R. 
Published: October 2002

AbstractThis paper reports salivary cortisol levels and cardiovascular adjustments monitored after the performance of physical exercise in a subject (healthy man, 58 years old) who had practised and taught yoga techniques for a number of years. The subject performed two different step‐climbing trials which were varied according to the different breathing recovery techniques used. Immediately after the step‐climbing, the subject was asked either to get his breath back spontaneously (as reference) or by 3 min breathing using the ‘Istity Method’, based on the prolongation or amplification of the steps of the breath (breathing in–out) with short regular rest intervals. The measurements of the basal heart rate, blood pressure and cortisol concentration in the saliva were made just before starting, and 5, 15 and 30 min after the end of step‐climbing. Results suggest that the Istity breathing method can induce rapid modification of the cardiovascular function and attenuation of the cortisol level after exposure to physical stress. It might be of interest to pursue further studies of this effect, perhaps not confined to yoga experts, since the ‘Istity Method’ can be implemented by anyone after a short and simple training period. Copyright © 2002 John Wiley & Sons, Ltd.
Structural systems: a marriage of structural engineering and system science
Authors: Skelton Robert E. 
Published: October 2002

AbstractThis research seeks to provide analytical tools and concepts to unify the disciplines of materials, structures, control, and signal processing. Deficiencies are noted in the existing theories of systems science that fails to provide a theory for system design, integrating the design of components. The biggest challenge is the lack of good systems modeling theories, as opposed to the excellent component modeling theories that exist. Mathematical algorithms are suggested to optimally locate the sensing and actuating functions within the structure to enhance the performance of the algorithms looking for faults. These same techniques can be designed to other objectives, such as heating and air conditioning, thermal detection of people movements and security issues. The ‘economic design problem’ discussed herein will determine both the required precision and the best location for sensors to enable the health monitoring or control algorithms to function within a predetermined precision. Copyright © 2002 John Wiley & Sons, Ltd.
Relationship between low‐dose amphetamine‐induced arousal and extracellular norepinephrine and dopamine levels within prefrontal cortex
Authors: Berridge Craig W. , Stalnaker Thomas A. 
Published: October 2002

AbstractDespite the well‐known and potent arousal‐enhancing effects of amphetamine (AMPH)‐like stimulants, the neurobiological substrates of AMPH‐induced arousal have rarely been examined explicitly. Available evidence suggests the possible participation of noradrenergic and/or dopaminergic systems in the arousal‐enhancing actions of AMPH‐like stimulants. The current studies examined the extent to which low‐dose AMPH‐induced increases in waking are related to AMPH‐induced increases in extracellular norepinephrine (NE) and dopamine (DA) levels within the prefrontal cortex (PFC), as measured by in vivo microdialysis. Vehicle injections elicited brief epochs of waking. Vehicle‐induced waking was closely associated with a brief and moderate (50% above baseline) increase in NE levels. DA levels were less sensitive to the arousing actions of vehicle injections, with maximal increases of approximately 25% above baseline observed. 0.15 mg/kg and 0.25 mg/kg AMPH increased time spent awake, which resulted primarily from increases in quiet waking. Although the magnitude of the waking response did not differ substantially between the two doses across time, a trend for a more rapid recovery to baseline waking levels was observed at the higher dose, possibly suggesting the development of a relatively rapid‐onset tolerance to the wake‐promoting actions of AMPH at this dose. At the 0.15 mg/kg dose, AMPH elicited maximum increases of approximately 175% and 125% above baseline levels for NE and DA, respectively. The time course of AMPH‐induced increases in waking closely paralleled the time course of AMPH‐induced increases in both NE and DA efflux. These observations are consistent with the hypothesis that both increased DA and NE efflux contribute to the low‐dose behavioral effects of AMPH‐like stimulants, including the arousal‐enhancing actions of these drugs. Additionally, these observations also suggest a possibly greater sensitivity of NE efflux, relative to DA, to moderately arousing conditions including low‐dose AMPH‐like stimulant administration. Synapse 46:140–149, 2002. © 2002 Wiley‐Liss, Inc.
Role of maternal smoking and maternal reproductive history in the etiology of hypospadias in the offspring
Authors: Källén Karin 
Published: October 2002

AbstractBackgroundThis study was undertaken to evaluate some possible risk factors for hypospadias with special regard to parity, subfertility and maternal smoking.MethodsWith the use of the Swedish health registries, 3,262 infants with a diagnosis of hypospadias were identified among 1,413,811 infants born in 1983–96 with prospectively collected smoking exposure during pregnancy. Odds ratios (OR) and 95% confidence intervals (CI) were calculated after adjustment for various possible confounders.ResultsA negative association between hypospadias and maternal smoking was found (OR: 0.83 95% CI: 0.76–0.90), but this association was only observed among mothers of Parity 1 or 4+, and the possibility of the results being due to confounding was suspected. Primiparity (vs. Parity 2) was positively associated with hypospadias (OR: 1.29 95% CI: 1.19–1.40), and so was subfertility (defined here as at least 1 year of attempts to conceive) (OR for subfertility: 1.16 95% CI: 1.01–1.33). The OR for smoking and primiparity, respectively, were of the same magnitude irrespective of whether subfertility was present or not, and no evidence was found that subfertility in the parents of infants with hypospadias seriously confounded the analyses.ConclusionsNo explanation was found for the negative association between maternal smoking and hypospadias or the positive association between primiparity and hypospadias. Possible causal mechanisms are discussed. Teratology 66:185–191, 2002. © 2002 Wiley‐Liss, Inc.
The influence of microcystin‐LR and hepatotoxic cyanobacterial extract on the water plantSpirodela oligorrhiza
Authors: Romanowska‐Duda Zdzisława , Tarczyńska Małgorzata 
Published: October 2002

AbstractThe eutrophication of the Sulejów Reservoir dam in Poland is related to toxicity from cyanobacterial blooms. The main species responsible for hepatotoxic bloom formation isMicrocystis aeruginosa. The aim of this study was to evaluate the influence of toxic cyanobacterial extract on the growth and morphology of the water plantSpirodela oligorrhiza, compared with commercial‐grade microcystin‐LR (MC‐LR). It was found that after 96 h of incubation the highest concentration of cyanobacterial extract, containing 0.344 mg MC‐LR/L, reduced the number of fronds by about 50% in comparison with the control. The extract effected a reduction in the frond mass and a decrease in chlorophyll (a+b) concentration. A reduction in the number of fronds was also observed after the first 24 h of incubation in the presence of 0.2 and 0.1 μg/L of commercial‐grade MC‐LR. Changes in activity of constitutive acid phosphatase and RNase after 7 days of incubation with commercial‐grade MC‐LR were observed. The results confirm the toxicity of cyanobacterial hepatotoxins toSpirodela oligorrhiza, which can be used as a sensitive bioindicator. © 2002 Wiley Periodicals, Inc. Environ Toxicol 17: 434–440, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/tox.10076
Acute toxicity, mutagenicity, and estrogenicity of biodegradation products of bisphenol‐A
Authors: Ike Michihiko , Chen Min‐Yu , Jin Chang‐Suk , Fujita Masanori 
Published: October 2002

AbstractBiodegradation of bisphenol‐A (BPA), which is known as an estrogenic chemical, proceeds via complicated metabolic routes and leads to formation of several kinds of biodegradation products. Through the major route BPA can be completely mineralized; however, p‐hydroxyacetophenone (p‐HAP), p‐hydroxybenzaldehyde (p‐HBAL), and p‐hydroxybenzoic acid (p‐HBA) are transiently accumulated at relatively high concentrations. On the other hand, degradation of BPA through the minor route tends to cause the accumulation of 2,3‐bis(4‐hydroxyphenyl)‐1,2‐propanediol and p‐hydroxyphenacyl alcohol as the dead‐end products. To fully assess the impact of BPA discharge into the environment, the considerable BPA degradation products p‐HAP, p‐HBAL, and p‐HBA and the mixture of the dead‐end products were examined for their acute toxicity, mutagenicity, and estrogenicity using the Daphtoxkit (Creasel Ltd.), umu test system, and yeast two‐hybrid system, respectively. BPA was moderately toxic to Daphnia magna (48‐h EC50 was 10 mg/L) and weakly estrogenic, with activity that was 5 orders of magnitude lower than that of 17β‐estradiol in the yeast screen, though no mutagenicity was observed. All the tested BPA biodegradation products showed very low acute toxicity compared with BPA, and none was mutagenic. A slight estrogenic activity was detected only for p‐HAP among the tested degradation products. It was concluded that biodegradation can remarkably reduce the toxic effects of BPA. © 2002 Wiley Periodicals, Inc. Environ Toxicol 17: 457–461, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/tox.10079
Maintenance of cell integrity in the gas1 mutant of Saccharomyces cerevisiae requires the Chs3p‐targeting and activation pathway and involves an unusual Chs3p localization
Authors: Carotti Cristina , Ferrario Laura , Roncero Cesar , Valdivieso M‐Henar , Duran Angel , Popolo Laura 
Published: October 2002

AbstractChitin synthase III is essential for the increase in chitin level and for cell integrity in cells lacking Gas1p, a β(1,3)‐glucanosyltransferase. In order to discover whether the upregulation of chitin synthesis proceeds through the canonical transport and activation pathway of Chs3p or through an alternative one, here we studied the effects of the inactivation of the GAS1 and CHS4‐5‐6‐7 genes. All the double‐null mutants showed a temperature‐sensitive cell lysis phenotype that could be suppressed by the presence of an osmotic stabilizer. In liquid YEPD at 30 °C, chs4Δ gas1Δ, chs5Δ gas1Δ, chs6Δgas1Δ and chs7Δgas1Δ mutants were unable to grow, whereas they grew very slowly in minimal medium and showed low viability. High osmolarity suppressed the defective phenotype and restored growth. In chs4 gas1, chs5 gas1 and chs7 gas1, chitin levels did not increase and were reduced to only 10%, while in chs6 gas1 the value of gas1 was reduced to 20–40%. To investigate at which level the upregulation of chitin synthesis could occur, mRNA levels were monitored. The expression of CHS4‐5‐6‐7 did not change significantly in gas1Δ. In strains expressing HA‐tagged forms, the localization of Chs3p and Chs5p was examined. In the gas1 mutant the fluorescence pattern was affected and the proteins appeared abnormally present in the bud. The results indicate that: (a) the function of the CHS4–7 genes is required for chitin hyperaccumulation in gas1 mutant and for cell integrity; (b) homologous genes do not replace their function; (c) the regulation of CHS4–7 genes does not occur at transcriptional level. Control of the position of chitin synthesis could be important in protecting the bud from lysis. Copyright © 2002 John Wiley & Sons, Ltd.
Molecular cloning and sequence analysis of the Zygosaccharomyces bailii HIS3 gene encoding the imidazole glycerolphosphate dehydratase
Authors: Branduardi Paola 
Published: October 2002

AbstractZygosaccharomyces bailii is a spoilage yeast belonging to the Zygosaccharomyces genus. In recent years these yeasts, due to their exceptional resistance to several stresses, have become more and more interesting as model organisms to study the molecular basis of the said resistance. A Z. bailii cDNA library has been built and the 672 bp nucleotide sequence coding for the HIS3 gene was cloned by complementation of a Saccharomyces cerevisiae his3 mutant strain. The deduced 223 amino acid sequence shares a high degree of homology with His3p homologues in other non‐conventional yeast species. The GeneBank Accession No. is AY050224. Copyright © 2002 John Wiley & Sons, Ltd.
The kex2 gene from the dimorphic and human pathogenic fungus Paracoccidioides brasiliensis
Authors: Venancio Emerson J. , Daher Bruno S. , Andrade Rosângela V. , Soares Célia M. A. , Pereira Ildinete Silva , Felipe Maria Sueli S. 
Published: October 2002

AbstractKexin‐like protein is a component of the subtilase family of proteinases involved in the processing of proproteins to their active forms. Kexin‐like proteins are also synthesized as a propeptide and this is involved in (auto)inhibition, correct folding and subcellular sorting of proteins. The kexin‐like protein was described as the product of the kex2 gene for Aspergillus niger, Candida albicans, Saccharomyces cerevisiae, Yarrowia lipolytica and other fungi. Disruption of the kex2 gene in C. albicans and Y. lipolytica affects hyphae production and induces morphological cell defects, strongly suggesting a possible role of kexin‐like proteins in dimorphism of human pathogenic fungi. In this work, we report the nucleotide sequence of the kex2 gene cloned from the dimorphic and human pathogenic fungus Paracoccidioides brasiliensis (Pbkex2). An open reading frame (ORF) of 2622 bp was identified in the complete sequence, interrupted by only one intron of 93 bp. The 5′ non‐coding region contains consensus sequences such as canonical TATA, CAAT boxes and putative motifs for transcriptional factors binding sites, such as HSE‐like regulating genes involved in thermo‐dependent processes; Xbp1, reported as a transcriptional factor that may control genes involved in cell morphology; and StuAp, which may regulate spore differentiation and pseudohyphal growth in fungi. In the 3′ non‐coding region were observed the canonical motifs necessary for correct mRNA processing and polyadenylation. The deduced protein sequence consists of 842 amino acid residues, showing identity to kexin‐like proteinases from A. niger (55%), Emericella nidulans (53%) and C. albicans (48%). Comparative sequence analysis of P. brasiliensis kexin‐like protein reveals the presence of homologous regions related to a signal peptide, a propeptide, a subtilisin‐like catalytic domain, a P domain, a S/T rich region and a transmembrane domain. A putative Golgi retrieval signal (YEFEMI) has also been found in the cytoplasmic tail. The complete nucleotide sequence of Pbkex2 and its flanking regions have been submitted to GenBank database under Accession No. AF486805. Copyright © 2002 John Wiley & Sons, Ltd.
Liver pathology in compound heterozygous patients for hemochromatosis mutations
Authors: Schöniger‐Hekele Maximilian , Müller Christian , Polli Claudia , Wrba Friedrich , Penner Edward , Ferenci Peter 
Published: October 2002

Abstract: Background: While hepatic pathology of homozygous carriers of the C282Y mutation of the HFE haemochromatosis gene is well defined, the impact of the C282Y/H63D compound heterozygous carrier state is unknown.Aims: To evaluate the range of hepatic pathology in C282Y/H63D compound heterozygous patients.Patients: 25 C282Y/H63D compound heterozygous patients with and without known underlying liver disease underwent liver biopsies for evaluation or abnormal liver tests. Eleven cadaveric liver donors with HFE wild type served as controls.Methods: Mutations in the HFE gene were detected by polyacrylamide gel electrophoresis (PAGE) separation of digested polymerase chain reaction (PCR)‐amplificates. The extent of light microscopic changes of liver architecture were studied on haematoxylin, eosin (H. E.) stains. In addition, the extent and the distribution of iron deposition was graded on Prussian blue‐stained sections and hepatic iron was quantified by atom absorption spectroscopy. Serum ferritin concentration and the transferrin saturation index were measured using routine laboratory methods.Results: Patients without underlying liver disease (n = 15): Hepatic inflammation was seen in only 8% but fibrosis was found in 36% of compound heterozygous patients. Eighty six percent of those patients had stainable iron predominantly found in Rappaport's zone 1 and 2, but all had a liver iron‐index < 1.9. Transferrin saturation was found elevated in 36% of compound heterozygous patients. Patients with liver fibrosis showed significantly higher ferritin levels than patients without liver fibrosis (1110 ng/mL versus 307 ng/mL, p < 0.05). Patients with underlying disease (n = 10): In compound heterozygous patients, 77% had hepatic inflammation and 88% fibrosis. Stainable iron (44%) was less frequently found than in patients without underlying liver disease. Hepatic iron‐index in patients with underlying liver disease was always below 1.17; transferrin saturation was elevated in only 22% of the compound heterozygous patients. Histologic hepatic iron‐index was significantly lower in patients with underlying disease (median 0.047) as compared to patients without underlying liver disease (median 0.274, P < 0.05).Conclusions: The underlying liver disease determines the extent of hepatic pathology seen in livers of compound heterozygous patients. However, considerable histologic fibrosis can also be found in compound heterozygous patients without underlying liver disease.
Comparative positions of kinetoplasts in Trypanosoma musculi and Trypanosoma lewisi during development in vitro
Authors: Ashraf M. , Nesbitt R. A. , Humphrey P. A. , Siewe M. , Lee C. M. 
Published: October 2002

Abstract. The development of Trypanosoma musculi and Trypanosoma lewisi were studied in vitro in the presence of adherent splenic cells. Both parasites developed only when attached by their flagellar tips to adherent splenic cells. During the proliferation of T. musculi, the kinetoplast migrated towards the nucleus, and once in the vicinity of the nucleus, the nuclear division was triggered. The kinetoplast of T. lewisi did not migrate towards the nucleus, but remained at its original location. The nucleus and kinetoplast divided at the same time in both parasites, and parasites started dividing from their flagellar ends and T. musculi and T. lewisi daughter cells were formed within 48 h. The unavailability of the adherent splenic cells in vitro led the parasites to transform into round/oval nonviable forms.
Evidence for the genetic control of immunoglobulin E reactivity to the allergens of Alternaria alternata
Authors: Karihaloo C. , Tovey E. R. , Mitakakis T. Z. , Duffy D. L. , Britton W. J. 
Published: October 2002

SummaryBackground The fungus Alternaria alternata contains potent allergens, and sensitization to these allergens is associated with a high risk of respiratory disease. The influence of genetic regulation on sensitization to Alternaria is unknown.Objective To determine the influence of genetic factors on IgE responses to specific allergens of Alternaria.Methods The concordance of skin prick test (SPT), radioallergosorbent test (RAST) and IgE‐binding profiles of sera were examined from a large cohort of monozygotic and dizygotic twins.Results Casewise concordance for a positive SPT response was monozygous (MZ) 66%: dizygous (DZ) 40% (P = 0.002). Logistic regression confirmed that casewise concordance was significantly stronger between MZ than DZ pairs. Immunoblotting against an Alternaria extract revealed 19 allergenic bands. The differences in concordance between the different bands were not significant for either the MZ (P = 0.97) or DZ (P = 0.84) groups. The pooled MZ : DZ difference in concordance was just significant (P = 0.049), suggesting an overall genetic effect on the response to Alternaria. This was reinforced by the comparison of the MZ and DZ correlations for total number of bands recognized (MZ r = 0.65; DZ r = 0.37, P = 0.015). Overall, there was a moderate correlation between the individual SPT weal size and RAST score (r2 = 0.41) and a substantial correlation between the number of immunoblotted bands and RAST scores (r2 = 0.79).Conclusion There is a strong genetic influence on IgE response to the mixture of Alternaria allergens and a lesser effect on IgE response to individual allergens.