bluuebunny/crossref_metadata_2025 huggingface dataset:
An epidemiologic study of trends in prevalence of rheumatoid factor seropositivity in Pima Indians: Evidence of a decline due to both secular and birth‐cohort influences
Authors: Enzer Ian , Dunn Graham , Jacobsson Lennart , Bennett Peter H. , Knowler William C. , Silman Alan
Published: September 2002

Objective

Previous population studies have suggested that both rheumatoid factor (RF) production and rheumatoid arthritis (RA) may be declining in occurrence, and both secular and birth‐cohort influences have been implicated. Since Pima Indians have a very high incidence of RA and also have shown recent evidence of a decline in RA, this study evaluated the relative contributions of age, secular, and birth‐cohort influences on RF seropositivity in the Pima Indian population.

Methods

RF data, as assayed by both the bentonite flocculation test (BFT) and the sheep cell agglutination test (SCAT), were available on 5,345 Pima Indians born between 1886 and 1975, who were surveyed at biennial intervals between 1966 and 1995. An age–period–cohort analysis was conducted using data on 18,295 examinations undertaken during the period of study.

Results

There was a decline in the proportion of positive test results for RF (titer ≥1:32) by both BFT and SCAT, in both male and female subjects from 1966–1975 to the later decades of the study (1976–1985 and 1986–1995). Across all periods, by both assays, the crude proportion of positive titers increased with increasing age of the subjects. There was a very clear birth‐cohort effect: the highest likelihood of seropositivity was in those individuals born around the end of the nineteenth century, with continuing decline in seropositivity up to the most recent birth cohort. A logistic regression analysis, adjusting for Pima heritage and sex, demonstrated a substantially greater influence of birth cohort than of calendar year on the frequency of RF positivity.

Conclusion

In the Pima Indian population, environmental influences in early life are important predictors of the lifelong likelihood of RF positivity. This may have implications for understanding the epidemiology and etiology of RA.
Occupational exposure to crystalline silica and risk of systemic lupus erythematosus: A population‐based, case–control study in the Southeastern United States
Authors: Parks Christine G. , Cooper Glinda S. , Nylander‐French Leena A. , Sanderson Wayne T. , Dement John M. , Cohen Philip L. , Dooley Mary Anne , Treadwell Edward L. , St.Clair E. William , Gilkeson Gary S. , Hoppin Jane A. , Savitz David A.
Published: September 2002

Objective

Crystalline silica may act as an immune adjuvant to increase inflammation and antibody production, and findings of occupational cohort studies suggest that silica exposure may be a risk factor for systemic lupus erythematosus (SLE). We undertook this population‐based study to examine the association between occupational silica exposure and SLE in the southeastern US.

Methods

SLE patients (n = 265; diagnosed between January 1, 1995 and July 31, 1999) were recruited from 4 university rheumatology practices and 30 community‐based rheumatologists in 60 contiguous counties. Controls (n = 355), frequency‐matched to patients by age, sex, and state of residence, were randomly selected from driver's license registries. The mean age of the patients at diagnosis was 39 years; 91% were women and 60% were African American. Detailed occupational and farming histories were collected by in‐person interviews. Silica exposure was determined through blinded assessment of job histories by 3 industrial hygienists, and potential medium‐ or high‐level exposures were confirmed through followup telephone interviews. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression.

Results

More patients (19%) than controls (8%) had a history of medium‐ or high‐level silica exposure from farming or trades. We observed an association between silica and SLE (medium exposure OR 2.1 [95% CI 1.1–4.0], high exposure OR 4.6 [95% CI 1.4–15.4]) that was seen in separate analyses by sex, race, and at different levels of education.

Conclusion

These results suggest that crystalline silica exposure may promote the development of SLE in some individuals. Additional research is recommended in other populations, using study designs that minimize potential selection bias and maximize the quality of exposure assessment.
Increased prevalence of familial autoimmunity in simplex and multiplex families with juvenile rheumatoid arthritis
Authors: Prahalad Sampath , Shear Edith S. , Thompson Susan D. , Giannini Edward H. , Glass David N.
Published: September 2002

Objective

To determine if the prevalence of autoimmunity among relatives of patients with juvenile rheumatoid arthritis (JRA) is greater than that among relatives of healthy volunteer control subjects.

Methods

Interviews were used to obtain histories of the following disorders among living first‐ and second‐degree relatives of 110 patients and 45 controls: alopecia areata, ankylosing spondylitis, dermatomyositis, Graves' disease, Hashimoto thyroiditis, insulin‐dependent diabetes mellitus, inflammatory bowel disease, iritis, JRA, multiple sclerosis, psoriasis, RA, systemic lupus erythematosus, and vitiligo. Chi‐squares, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. Families of 23 JRA affected sibpairs were interviewed subsequently.

Results

There were no significant differences between patients and controls with regard to age, sex, ethnicity, or family size. Patients had 1,228 relatives and controls had 496 relatives. Of all the relatives of the patients, 155 had at least 1 autoimmune disorder, compared with 20 relatives of the controls (12.6% versus 4.0%; OR 3.4 [95% CI 2.1–5.7], P < 0.000001). The prevalence of autoimmunity was increased in first‐degree and in second‐degree relatives of patients (16.1% and 10.6%, respectively). The prevalence of Hashimoto thyroiditis was significantly higher in the relatives of patients (OR 3.5 [95% CI 1.6–7.9], P = 0.0008). The prevalences of other disorders were not significantly different. JRA affected sibpair families had an increased prevalence of autoimmunity (15.0%). A history of arthritis was found significantly more frequently in the JRA affected sibpair families, but not in the simplex families.

Conclusion

These data demonstrate that the prevalence of autoimmunity is significantly higher among first‐ and second‐degree relatives of JRA patients. This suggests that clinically different autoimmune phenotypes may share common susceptibility genes, which may act as risk factors for autoimmunity.
Avoidance of activity and disability in patients with osteoarthritis of the knee: The mediating role of muscle strength
Authors: Steultjens M. P. M. , Dekker J. , Bijlsma J. W. J.
Published: September 2002

Objective

Avoidance of activity is hypothesized to lead to muscle weakness and consequently, to physical disability. This study was undertaken to validate the avoidance model by providing evidence for the mediating role of muscle weakness in the relationship between avoidance of activity and physical disability in patients with osteoarthritis (OA) of the knee.

Methods

Data on avoidance of activity, observed physical disability, and muscle strength of the knee in 107 patients with knee OA were analyzed. A series of regression analyses was performed to establish the mediating role of muscle weakness. First, the effect of avoidance of activity on the level of disability was assessed. Next, the relationship between avoidance of activity and muscle strength was established. Finally, the mediating role of muscle strength could be established if the effect of avoidance of activity on disability decreased when muscle strength was taken into account.

Results

Initially, avoidance of activity accounted for 21.5% of variance in disability. Avoidance of activity also accounted for 3.9% of variance in muscle strength. After muscle strength was taken into account, the variance in disability accounted for by avoidance of activity was reduced from 21.5% to 15.7%. Thus, the criteria for establishing the mediating role of muscle strength were met.

Conclusion

The results of this study provide evidence for the mediating role of muscle weakness in the relationship between avoidance of activity and disability in patients with knee OA.
In vitro cytokine production and proliferation of T cells from patients with anti‐proteinase 3‐ and antimyeloperoxidase‐associated vasculitis, in response to proteinase 3 and myeloperoxidase
Authors: Popa E. R. , Franssen C. F. M. , Limburg P. C. , Huitema M. G. , Kallenberg C. G. M. , Cohen Tervaert J. W.
Published: September 2002

Objective

To investigate in vitro proliferative responses of CD4+ T cells and generation of specific cytokines induced by stimulation of peripheral blood mononuclear cells (PBMCs) from patients with antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis with the autoantigens proteinase 3 (PR3) and myeloperoxidase (MPO).

Methods

PBMCs from vasculitis patients with PR3 ANCA or MPO ANCA and from healthy controls were stimulated for 7 days with PR3, MPO, or control stimuli. Proliferation of CD4+ T cells was assessed by flow cytometry, using the proliferation marker Ki‐67. Levels of the pro‐proliferative cytokines interleukin‐2 (IL‐2) and IL‐6 and of the Th1 and Th2 cytokines interferon‐γ (IFNγ) and IL‐10 in culture supernatants were determined.

Results

PR3 and MPO induced proliferative responses in CD4+ T cells from individual patients with ANCA‐associated vasculitides and healthy controls in vitro. Neither PR3 nor MPO elicited significant IL‐2 production. Levels of IL‐6 were highest after stimulation with PR3 but low after stimulation with MPO, independent of study group. Stimulation with PR3, and to a lesser extent with MPO, induced a Th2 cytokine milieu, characterized by high production of IL‐6 and IL‐10 and low production of IFNγ in patients and controls.

Conclusion

PR3 and MPO promote proliferation of CD4+ T cells from patients with ANCA‐associated vasculitides, but also cross‐stimulate T cells from healthy individuals. Strong IL‐10 production elicited by PR3 in vitro may act as an inhibitory signal for T cell proliferation and may have an important immunoregulatory function in vivo.
A subset of natural killer cells is greatly expanded within inflamed joints
Authors: Dalbeth Nicola , Callan Margaret F. C.
Published: September 2002

Objective

To determine whether natural killer (NK) cells are present within inflamed joints and whether they might play a role in amplifying the inflammatory process.

Methods

Paired samples of peripheral blood and synovial fluid were obtained from 22 patients with inflammatory arthritis. The frequency and phenotype of the peripheral and synovial NK cells were analyzed using a panel of monoclonal antibodies. Further experiments were performed to investigate the functional capacity of the synovial NK cells.

Results

The study showed that the CD3−, CD56bright subset of NK cells was greatly expanded within inflamed joints. Our experiments suggested that this subset of cells was preferentially recruited from the periphery and that NK cells may be further activated by cytokines present within the joint. Furthermore, synovial NK cells responded to a combination of interleukin‐12 (IL‐12) and IL‐15, cytokines that are secreted by cells of the monocyte/macrophage lineage, by rapidly secreting interferon‐γ, a cytokine that can, in turn, activate macrophages.

Conclusion

A subset of NK cells was expanded within inflamed joints. The functional properties of these NK cells rendered them good candidates for a role in interacting with the macrophage/monocyte population within the joint, thus amplifying the production of proinflammatory cytokines.
Benefit of an extract of Tripterygium Wilfordii Hook F in patients with rheumatoid arthritis: A double‐blind, placebo‐controlled study
Authors: Tao Xuelian , Younger Jean , Fan Fred Z. , Wang Betty , Lipsky Peter E.
Published: September 2002

Objective

To examine the safety and efficacy of an extract of Tripterygium wilfordii Hook F (TWHF) in the treatment of patients with rheumatoid arthritis (RA).

Methods

An ethanol/ethyl acetate extract from the roots of TWHF was prepared and used in a prospective, double‐blind, placebo‐controlled study in patients with longstanding RA in whom conventional therapy had failed. Patients were randomly assigned to receive either placebo or low‐dose (180 mg/day) or high‐dose (360 mg/day) extract for 20 weeks, followed by an open‐label extension period. Clinical responses were defined as 20% improvement in disease activity according to the American College of Rheumatology criteria. Side effects were actively queried and recorded at each visit.

Results

A total of 35 patients were enrolled in the trial; 21 patients completed the 20‐week study. One patient from each group withdrew because of side effects. Twelve, 10, and 10 patients in the placebo, low‐dose, and high‐dose groups, respectively, completed at least 4 weeks of treatment. Of these patients, 8 and 4 in the high‐dose and low‐dose groups, but none in the placebo group, met criteria for clinical response. Four, 4, and 7 patients in the placebo, low‐dose, and high‐dose groups, respectively, were enrolled in the open‐label extension; of these, 2, 4, and 5 patients, respectively, met criteria for clinical response. The most common side effect was diarrhea, which caused 1 patient in the high‐dose group to withdraw from the trial. No patients withdrew because of adverse events during the open‐label extension.

Conclusion

The ethanol/ethyl acetate extract of TWHF shows therapeutic benefit in patients with treatment‐refractory RA. At therapeutic dosages, the TWHF extract was well tolerated by most patients in this study.
Calibrating software reliability models when the test environment does not match the user environment
Authors: Zhang Xuemei , Jeske Daniel R. , Pham Hoang
Published: September 2002

Software failures have become the major factor that brings the system down or causes a degradation in the quality of service. For many applications, estimating the software failure rate from a user's perspective helps the development team evaluate the reliability of the software and determine the release time properly. Traditionally, software reliability growth models are applied to system test data with the hope of estimating the software failure rate in the field. Given the aggressive nature by which the software is exercised during system test, as well as unavoidable differences between the test environment and the field environment, the resulting estimate of the failure rate will not typically reflect the user‐perceived failure rate in the field.

The goal of this work is to quantify the mismatch between the system test environment and the field environment. A calibration factor is proposed to map the failure rate estimated from the system test data to the failure rate that will be observed in the field. Non‐homogeneous Poisson process models are utilized to estimate the software failure rate in both the system test phase and the field.

For projects that have only system test data, use of the calibration factor provides an estimate of the field failure rate that would otherwise be unavailable. For projects that have both system test data and previous field data, the calibration factor can be explicitly evaluated and used to estimate the field failure rate of future releases as their system test data becomes available. Copyright © 2002 John Wiley & Sons, Ltd.
Teaching cooperative play to typical children utilizing a behavior modeling approach: a systematic replication
Authors: Jahr Erik , Eldevik Sigmund
Published: September 2002

This study investigated the acquisition of cooperative play in three typical children. The differential effectiveness of two different modeling conditions was compared, where in the first condition the children were trained to observe and imitate modeled cooperative play. In the second condition the children observed and described the modeled play prior to imitation. During training, modeled play episodes varied across play topics. The criterion for mastery in training was correct responding on first trial with new modeled play episodes. The results showed that the children became able to take turns in novel episodes of cooperative play and to show play variability only after including verbal description as part of the modeling procedure. Copyright © 2002 John Wiley & Sons, Ltd.
Solution structure of a pentasaccharide representing the repeating unit of the O‐antigen polysaccharide from Escherichia coli O142: NMR spectroscopy and molecular simulation studies
Authors: Landersjö Clas , Widmalm Göran
Published: September 2002

Conformational studies have been performed of a pentasaccharide derived from the O‐polysaccharide from Escherichia coli O142. The polymer was selectively degraded by anhydrous hydrogen fluoride and reduced to yield an oligosaccharide model of its repeating unit, which in the branching region consists of four aminosugars. A comparison of 1H and 13C chemical shifts between the pentasaccharide and the polymer showed only minor differences, except where the cleavage had taken place, indicating that the oligomer is a good model of the repeating unit. Langevin dynamics and molecular dynamics simulations with explicit water molecules were carried out to sample the conformational space of the pentasaccharide. For the glycosidic linkages between the hexopyranoside residues, small but significant changes were observed between the simulation techniques. One‐dimensional (1D) 1H,1H double pulsed field gradient spin echo (DPFGSE) transverse rotating‐frame Overhauser effect spectroscopy (T‐ROESY) experiments were performed, and homonuclear cross‐relaxation rates were obtained. Subsequently, a comparison of interproton distances from NMR experiment and the two simulation approaches showed that in all cases the use of explicit water in the simulations resulted in better agreement. Hydrogen‐bond analysis of the trajectories from the molecular dynamics simulation revealed interresidue interactions to be important as a cluster of different hydrogen bonds and as a distinct highly populated hydrogen bond. NMR data are consistent with the presence of hydrogen bonding within the model of the repeating unit. © 2002 Wiley Periodicals, Inc. Biopolymers 64: 283–291, 2002
In vitro protein–polysaccharide conjugation: Tyrosinase‐catalyzed conjugation of gelatin and chitosan
Authors: Chen Tianhong , Embree Heather D. , Wu Li‐Qun , Payne Gregory F.
Published: September 2002

The enzyme tyrosinase was used for the in vitro conjugation of the protein gelatin to the polysaccharide chitosan. Tyrosinases are oxidative enzymes that convert accessible tyrosine residues of proteins into reactive o‐quinone moieties. Spectrophotometric and dissolved oxygen studies indicate that tyrosinase can oxidize gelatin and we estimate that 1 in 5 gelatin chains undergo reaction. Oxidized tyrosyl residues (i.e., quinone residues) can undergo nonenzymatic reactions with available nucleophiles such as the nucleophilic amino groups of chitosan. Ultraviolet/visible, 1H‐NMR, and ir provided chemical evidence for the conjugation of oxidized gelatin with chitosan. Physical evidence for conjugation was provided by dynamic viscometry, which indicated that tyrosinase catalyzes the sol‐to‐gel conversion of gelatin/chitosan mixtures. The gels formed from tyrosinase‐catalyzed reactions were observed to differ from gels formed by cooling gelatin. In contrast to gelatin gels, tyrosinase‐generated gels had different thermal behavior and were broken by the chitosan‐hydrolyzing enzyme chitosanase. These results demonstrate that tyrosinase can be exploited for the in vitro formation of protein–polysaccharide conjugates that offer interesting mechanical properties. © 2002 Wiley Periodicals, Inc. Biopolymers 64: 292–302, 2002
Dimer structure of magainin 2 bound to phospholipid vesicles
Authors: Wakamatsu Kaori , Takeda Akemi , Tachi Tomoya , Matsuzaki Katsumi
Published: September 2002

Magainin 2 from African clawed frog Xenopus laevis is an antimicrobial peptide with broad spectra and action mechanisms considered to permeabilize bacterial membranes. CD, vibration, and solid‐state NMR spectroscopies indicate the peptide adopts an α‐helical conformation on binding to phospholipid bilayers, and its micelle‐bound conformation, being monomeric and α‐helical, is well detailed. We showed, however, that the peptide dimerizes on binding to phospholipid bilayers. This difference in the conformation and aggregation state between micelle‐ and bilayer‐bound states prompted us to analyze the conformation of an equipotent analog of magainin 2 (F5Y,F16W magainin 2) bound to phosphatidylcholine vesicles using transferred nuclear Overhauser enhancement (TRNOE) spectroscopy. While observed medium‐range TRNOE cross peaks were characteristic of α‐helix, many long‐range cross peaks were not compatible with the peptide's monomeric state. Simulated annealing calculations generated dimer structures indicating (1) two peptide molecules have a largely helical conformation in antiparallel orientation forming a short coiled‐coil structure, (2) residues 4–20 are well converged and residues 9–20 are in an α‐helical conformation, and (3) the interface of the two peptide molecules is formed by well‐defined side chains of hydrophobic residues. Finally, determined structures are compatible with numerous investigations examining magainin–phospholipid interactions. © 2002 Wiley Periodicals, Inc. Biopolymers 64: 314–327, 2002
Screening of various glycosidases for the synthesis of octyl glucoside
Authors: Ducret Amélie , Trani Michael , Lortie Robert
Published: September 2002

Thirteen glycosidases of microbial origin and almond β‐glycosidase were assayed in octanol/DMF (80:20, v/v), using a combination of hydrolysis, transglycosylation, and condensation reactions, in order to assess their potential for the production of alkyl glucosides. The two mesophile enzymes were highly impaired by the organic media. Three of the 11 thermophile enzymes gave interesting results in the hydrolysis and transglycosylation reactions, but they were highly inhibited by glucose. This made their use in a condensation reaction less interesting than the use of almond β‐glucosidase, which has a lower activity but shows less inhibition by the glucose. © 2002 Government of Canada. Exclusive worldwide publication rights in this article have been transferred to John Wiley & Sons, Inc. Biotechol Bioeng 77: 752–757, 2002; DOI 10.1002/bit.10156
Biokinetics in acidogenesis of highly suspended organic wastewater by adenosine 5′ triphosphate analysis
Authors: Yu Youngseob , Hansen Conly L. , Hwang Seokhwan
Published: September 2002

In this paper, we pointed out the problems of using conventional volatile suspended solids (VSS) and chemical oxygen demand (COD) to evaluate biokinetic coefficients, especially for the treatment of highly suspended organic wastewater. We also introduced a novel approach to evaluate biokinetic coefficients by measurement of adenosine 5′‐triphosphate (ATP) of microorganisms. The concept of using ATP analysis in biokinetic evaluations with highly suspended wastewater was shown to be effective. This study also showed that the conventional VSS and COD methods were strongly affected by incoming suspended organics in the wastewater and by biokinetics of microorganisms. A cheese‐processing wastewater was used in evaluating the biokinetics of mesophilic acidogens. The concentration of COD and total suspended solids in the wastewater was 63.3 g/L and 12.4 g/L, respectively. The TSS was 23.6% of total solids concentration. A high ratio of VSS to total suspended solids of 96.7% indicated that most of the suspended particles were organic materials. Lactose and protein were the major organic components contributing COD in the wastewater, and a total of 94.2% of the COD in the wastewater was due to the presence of lactose and protein. Two different physiological conditions where the maximum rates of acetate and butyrate production occurred were tested. These were pH 7 (condition A for acetate production) and pH 7.3 (condition B for butyrate production) at 36.2°C, respectively. Based on the molecular structures of the major organic substances and microbial ATP analysis, the residual substrate and microbial concentrations were stoichiometrically converted to substrate COD (SuCOD) and microbial VSS (MVSS), respectively, using correlation coefficients reported previously. These SuCOD and MVSS were simultaneously used to evaluate the biokinetic coefficients using Monod‐based mathematical equations. The nonlinear least squares method with 95% confidence interval was used to evaluate biokinetic coefficients. The maximum microbial growth rate, μmax and half saturation coefficient, Ks, for conditions A and B were determined to be 9.9 ± 0.3 and 9.3 ± 1.0 day−1 and 134.0 ± 58.3 and 482.5 ± 156.5 mg SuCOD/L, respectively. The microbial yield coefficient, Y, and microbial decay rate coefficient, kd for conditions A and B were determined to be 0.29 ± 0.03 and 0.20 ± 0.05 mg MVSS/mg SuCOD, and 0.14 ± 0.05 and 0.25 ± 0.05 day−1, respectively. Specific substrate utilization rate at condition B was 43.8 ± 20.6 mg SuCOD/mg MVSS/day, which was 31% higher than that at condition A. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 147–156, 2002; DOI 10.1002/bit.10164
Monitoring of temperature effects on animal cell metabolism in a packed bed process
Authors: Ducommun P. , Ruffieux P.‐A. , Kadouri A. , von Stockar U. , Marison I. W.
Published: September 2002

Animal cell (Chinese Hamster Ovary) concentration was determined on‐line in a packed bed process using dielectric spectroscopy. This enabled the evaluation of the effect of temperature on specific metabolic rates during 3 months of continuous culture. The effect of low cultivation temperature on cell growth and metabolism was monitored, and the data were used for process development. At 37°C cells grew exponentially with a specific growth rate of 0.038 d−1 and specific glucose uptake and lactate production rates increased continually. Reduction of the temperature to 33.5°C resulted in a lowering of these metabolic rates while having no effect on cell proliferation. Subsequent reduction of the temperature to 32°C resulted in stabilization of the cell concentration at a high density (3.6 × 107 cell per mL of packed bed). In addition, the specific production rate of the protein of interest increased by a factor of 6 compared to the value at 37°C. During the stationary phase at 32°C, all other specific metabolic rates could be controlled to low and constant levels. © 2002 John Wiley & Sons, Inc. Biotechnol Bioeng 77: 838–842, 2002; DOI 10.1002/bit.10185
Understanding viral partitioning in two‐phase aqueous nonionic micellar systems: 1. Role of attractive interactions between viruses and micelles
Authors: Kamei Daniel T. , Liu Chia‐li , Haase‐Pettingell Cameron , King Jonathan A. , Wang Daniel I. C. , Blankschtein Daniel
Published: September 2002

The partitioning behavior of viruses in the two‐phase aqueous nonionic n‐decyl tetra(ethylene oxide) (C10E4) micellar system cannot be fully explained by considering solely the repulsive, steric, excluded‐volume interactions that operate between the viruses and the nonionic C10E4 micelles. Specifically, an excluded‐volume theory developed recently by our group is not able to quantitatively predict the observed viral partition coefficients, even though this theory is capable of providing reasonable quantitative predictions of protein partition coefficients. To shed light on the discrepancy between the theoretically predicted and the experimentally measured viral partition coefficients, a central assumption underlying the excluded‐volume theory that the viruses and the C10E4 micelles interact solely through repulsive, excluded‐volume interactions was challenged in this study. In particular, utilizing bacteriophage P22 as a model virus, a competitive inhibition test and a partitioning study of the capsids of bacteriophage P22 were conducted. Based on the results of these two experimental studies, it was concluded that any attractive interactions between the tailspikes of bacteriophage P22 and the C10E4 micelles are negligible. Another experimental study was carried out wherein the partition coefficients of the model viruses, bacteriophages P22 and T4, were measured at various temperatures, and compared with those previously obtained for bacteriophage ϕX174. This comparison also indicated that possible attractive, electromagnetic‐induced interactions between the bacteriophage particles and the C10E4 micelles cannot be invoked to rationalize the observed discrepancy between the theoretically predicted and the experimentally measured viral partition coefficients. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 190–202, 2002; DOI 10.1002/bit.10193
Optimization of carbohydrate fatty acid ester synthesis in organic media by a lipase from Candida antarctica
Authors: Degn Peter , Zimmermann Wolfgang
Published: September 2002

The effect of solvents and solvent mixtures on the synthesis of myristic acid esters of different carbohydrates with an immobilized lipase from C. antarctica was investigated. The rate of myristyl glucose synthesized by the enzyme was increased from 3.7 to 20.2 μmol min−1 g−1 by changing the solvent from pure tert‐butanol to a mixture of tert‐butanol:pyridine (55:45 v/v), by increasing the temperature from 45°C to 60°C, and by optimizing the relative amounts of glucose, myristic acid, and the enzyme preparation. Addition of more than 2% DMSO to the tert‐butanol:pyridine system resulted in a reduction of enzyme activity. Lowering the water content of the enzyme preparation below 0.85% (w/w) resulted in significant decreases in enzyme activity, while increasing the water content up to 2.17% (w/w) did not significantly affect the enzyme activity. The highest yields of myristyl glucose were obtained when an excess of unsolubilized glucose was present in the reaction system. In this case, all of the initially solubilized and a significant amount of the initially unsolubilized glucose was converted to the ester within 24 h of incubation, resulting in a myristyl glucose concentration of 34 mg/mL−1. Myristic acid esters of fructose (22.3 μmol min−1 g−1), α‐D‐methyl‐glucopyranoside (26.9 μmol min−1 g−1) and maltose (1.9 μmol min−1 g−1) could also be prepared using the tert‐butanol:pyridine solvent system. No synthesis activity was observed with maltotriose, cellobiose, sucrose, and lactose as substrate. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 74: 483–491, 2001.
Biocatalysis of isomerization of 1,2‐benzisoxazole by bovine serum albumin in an organic solvent
Authors: Liu Xiao‐Chuan , Lemma‐Gray Patrizia
Published: September 2002

The catalytic properties of bovine serum albumin (BSA) have been studied rather extensively. The protein has shown catalytic activities toward a variety of reactions in aqueous media. However, there appears to be no reports of reactions catalyzed exclusively in organic media. In this study, we report the catalytic property of BSA on the isomerization of 1,2‐benzisoxazole in an organic solvent. Kinetics were performed using a continuous flow system in a spectrophotometer at 330 nm. The catalysis showed a Michaelis‐Menten behavior with an estimated catalytic efficiency (kcat/KM) of 8.77 M−1S−1. The influence of water content and inhibitors was also studied. The activity of BSA in acetonitrile is approximately 20% of that in water under similar conditions. Inhibition studies show that the active site may be the pyridoxal binding site involving Lys‐220. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 74: 524–527, 2001.
Nano‐HPLC–mass spectrometry and MEKC for the analysis of oligosaccharides from human milk
Authors: Schmid Dietmar , Behnke Beate , Metzger Jörg , Kuhn Reinhard
Published: September 2002

The separation of oligosaccharides derivatized with various esters of aminobenzoic acid by means of reversed‐phase nano‐HPLC (nHPLC) with on‐line ESI mass spectrometry and off‐line MALDI‐TOF mass spectrometry as well as MEKC is described. For this purpose methyl, ethyl and butyl aminobenzoates and heptyloxyaniline were used as derivatization agents for homologous maltodextrins and oligosaccharides from human milk. Four different C18 stationary phases were tested for this purpose because the type of stationary phase was shown to have a dramatic effect on the performance of the separation. Optimal results were obtained using n‐butyl aminobenzoate as label and an encapsulated ODS stationary phase. The on‐line coupling of nHPLC to ESI MS allowed to separate and identify various oligosaccharides from human milk. This technique enabled the exact attribution of the molecular structure to a signal in the chromatogram. In a second approach oligosaccharides were separated by nHPLC and subsequently fractionated. The fractions were analyzed by MALDI‐TOF mass spectrometry. The results obtained by this approach confirmed the ESI MS data. An analogous separation profile was obtained by using sodium dodecyl sulfate in MEKC, which proves that the retention mechanisms of both techniques are identical. Copyright © 2002 John Wiley & Sons, Ltd.
Separation of naturally occurring triterpenoidal saponins by capillary zone electrophoresis
Authors: Emara Samy , Mohamed Khaled M. , Masujima Tsutomu , Yamasaki Kazuo
Published: September 2002

A high‐performance capillary electrophoresis (HPCE) was successfully applied to the separation and quantitation of naturally occurring oleanene triterpenoidal saponins. The HPCE adapted to the separation of two pairs of disteriomeric saponins (1–2) or (3–4), obtained from Trifolium alexandrinum seeds, was based on capillary zone electrophoresis (CZE) in borate buffer with UV detection at 195 nm. An usual technique for isolation and group separation of saponins was developed as an appropriate purification step prior to determination of individual saponins by CZE. The separation parameters such as borate concentration, pH and applied voltage were varied in order to find the best compromise that complied with demands for high separation, short duration and sufficiently high detector response. The optimum running conditions were found to be 60 mM borate buffer, pH 10 and 12 kV. Under the alkaline borate electrolyte, no resolution was achieved for the saponins (1 and 3) or (2 and 4) in a single mixture, except when 20 mM β‐cyclodextrin was added to the running electrolyte. With the combined techniques of group separation, purification and CZE, a rapid and efficient method for the determination of naturally occurring diasteriomeric saponins is now available. Copyright © 2001 John Wiley & Sons, Ltd.

Abbreviations used:

CD

Cyclodextrins.
Partnerships, management systems and the search for innovative regulation in the vehicle body shop industry
Authors: Gunningham Neil , Sinclair Darren
Published: September 2002

This article examines innovative approaches to regulating the environmental performance of vehicle body shops, in the state of Victoria, Australia. Based on field research, this provides a useful opportunity to not only identify the limitations of the environmental management practices (including regulatory resistance, a lack of resources and cultural obstacles), but also the failure of conventional regulatory approaches to adequately address and overcome problematic characteristics typical of small and medium sized enterprises (numerous, geographically dispersed, environmentally unsophisticated and, collectively, a substantial source of pollution). Particular focus is given to cleaner production, partnerships and environmental management systems in improving environmental performance. We also consider the potential role of ‘regulatory surrogates’ as an adjunct to a mix of government regulatory initiatives. Copyright © 2002 John Wiley & Sons, Ltd. and ERP Environment.
Strategic inter‐organizational environmentalism in the US: A multi‐sectoral perspective of alternating eco‐policy roles
Authors: Starik Mark , Heuer Mark
Published: September 2002

During the last several decades, numerous policies and programs intended to advance environmental goals have been formulated in the US by governmental bodies and implemented by businesses and nongovernmental organizations. This article forwards a multi‐sectoral perspective that business and nonprofit organizations have also been significantly involved in environmental policy and program formulation, as well as implementation, and that governments have also fulfilled the latter strategic role in US environmental policy. In this article, nine US environmental initiatives are described and categorized according to which of the three sectors' organizations were significant formulators of the programs and which were significant implementors. Implications for future research include investigation of other environmental dyadic program combinations in addition to those presented, extension of the present analysis beyond dyads into environmental policy networks, inclusion of the strategic environmental program evaluation stage to complement formulation and implementation and exploration of effectiveness variables in cross‐sectoral, inter‐organizational collaborations. Implications for educators and practitioners are also presented. Copyright © 2002 John Wiley & Sons, Ltd. and ERP Environment.
Current analysis of theTarasoffduty: an evolution towards the limitation of the duty to protect
Authors: Walcott Damon Muir , Cerundolo Pat , Beck James C.
Published: September 2002

In 1976, theTarasoffcase established a new legal duty to protect third parties from a psychiatric patient's foreseeable violence. After theTarasoffcase, courts expanded the scope and role of a clinician's duty to protect, sometimes in novel ways. Later interpretations ofTarasoffbegan to limit significantly the situations in which a duty to protect would attach. RecentTarasoff‐type cases in which courts have rejected the clinician's duty to warn suggest thatTarasoffis declining in significance. The advent of state statutes that codify the establishment and discharge ofTarasoffduty have contributed to a further limitation of the duty to protect. Lastly, when faced with the management of dangerous patients, we advocate for a thorough, well documented assessment of risk of violence as the best means for addressing concern about potential legal liability. Copyright © 2001 John Wiley & Sons, Ltd.
Genetic risk: the new frontier for the duty to warn*
Authors: Petrila John
Published: September 2002

Mental health professionals usually think of the “duty to warn” in the context of mental illness. However, two state appellate courts have endorsed a duty to warn when children of a patient may be at risk genetically for acquiring the disease of their parents. In these cases, the courts held that a physician's legal obligations extended beyond his or her patient to the patient's children. This article discusses these cases, as well as issues regarding implementation of such a duty and the implications for the physician–patient relationship in a health care environment that will be dominated increasingly by genetics issues. The article concludes that it is premature to apply a duty to warn to the treatment of mental illness and to concerns regarding future criminal behavior. Copyright © 2001 John Wiley & Sons, Ltd.
To warn and to control: two distinct legal obligations or variations of a single duty to protect?
Authors: Felthous Alan R. , Kachigian Claudia
Published: September 2002

Prior to the Tarasoff decisions, jurisprudence pertaining to the duty to warn, or inform, to prevent violence to third persons, was separate from that pertaining to the duty to control to prevent such violence. The Tarasoff Principle consolidated preventive obligations in the face of foreseeable violence under a single “duty to protect.” Even as courts adopted divergent rules for establishing foreseeability, many held to a single duty to protect with warnings as one possibility for fulfilling this option. Particularly over the past decade, courts have again disengaged the duty to warn and the duty to control, each requiring different legal predicates to occur. In recent years, courts have upheld or rejected a duty to warn, upheld or rejected a duty to control; and several courts have, within a single opinion, articulated fundamental distinctions between these two separate protective duties. Copyright © 2001 John Wiley & Sons, Ltd.
An improved spreadsheet toolbox for simulating digital networks
Authors: El‐Hajj Ali , Kabalan Karim Y. , El‐Haj Mahmoud Samer
Published: September 2002

This paper presents an improved toolbox for simulating digital logic networks using spreadsheets. This simulation uses advanced spreadsheet features such as: toolbars, menus, controls, graphics, and online help. Instead of writing lengthy formulas that are spread all around the worksheet, the user can draw a complete logical network by mere mouse clicks. This simulation can be applied to all types of combinational, sequential, synchronous, and asynchronous networks. Many examples are given for illustration. © 2001 John Wiley & Sons, Inc. Comput Appl Eng Educ 9: 78–86, 2001
Macrophages transfer [14C]‐labelled fatty acids to pancreatic islets in culture
Authors: Garcia J. R. , Curi R. , Martins E. F. , Carpinelli A. R.
Published: September 2002

Macrophages are able to produce, export, and transfer fatty acids to lymphocytes in culture. The purpose of this study was to examine if labelled fatty acids could be transferred from macrophages to pancreatic islets in co‐culture. We found that after 3 h of co‐culture the transfer of fatty acids to pancreatic islets was: arachidonic ≫ oleic > linoleic = palmitic. Substantial amounts of the transferred fatty acids were found in the phospholipid fraction; 87.6% for arachidonic, 59.9% for oleic, 53.1% for palmitic, and 36.9% for linoleic acids. The remaining radioactivity was distributed among the other lipid fractions analysed (namely polar lipids, cholesterol, fatty acids, triacylglycerol and cholesterol ester), varying with the fatty acid used. For linoleic acid, a significant proportion (63.1%) was almost equally distributed in these lipid fractions. Also, it was observed that transfer of fatty acids from macrophages to pancreatic islets is time‐dependent up to 24 h, being constant and linear with time for palmitic acid and remaining constant after 12 h for oleic acid. These results lead us to postulate that in addition to the serum, circulating monocytes may also be a source of fatty acids to pancreatic islets, mainly arachidonic acid. Copyright © 2001 John Wiley & Sons, Ltd.
Telomerase activity is repressed during differentiation along the hepatocytic and biliary epithelial lineages: verification on immortal cell lines from the same origin
Authors: Fukutomi Marie , Enjoji Munechika , Iguchi Haruo , Yokota Masaki , Iwamoto Hiroaki , Nakamuta Makoto , Sakai Hironori , Nawata Hajime
Published: September 2002

Recent investigations indicate that telomerase activity regulates the life span of cells by compensating for telomere shortening during DNA replication. In addition, as differentiation progresses, telomerase activity is reduced in several different cell lineages. These findings lend support to the theory that more immature cells have greater remaining proliferative capacity and longer life span. However, it has not been directly demonstrated that the differentiation along a hepatocytic or a bile ductal lineage is accompanied by reduction of telomerase activity. In this study, we present direct evidence that telomerase activity is reduced during hepatocytic and biliary epithelial differentiation by using our unique cell lines including a stem‐like cell line, ETK‐1. When hepatocytic differentiation was induced in ETK‐1 by 5‐azacytidine, telomerase activity decreased significantly. Similarly, when we compared the telomerase activity on SSP‐25 and RBE cell lines from the same origin but representing different maturation stages of cholangiocarcinoma, more mature cells were found to possess significantly lower activity. These results indicate that the generally accepted relationship between telomerase activity and differentiation stage also applies in the hepatocytic and biliary epithelial lineages. Copyright © 2001 John Wiley & Sons, Ltd.
Effects of retinoids and thiazolidinediones on proliferation, insulin release, insulin mRNA, GLUT 2 transporter protein and mRNA of INS‐1 cells
Authors: Blumentrath J. , Neye H. , Verspohl E. J.
Published: September 2002

Both 9‐cis‐retinoic acid (9cRA) and all‐trans‐retinoic acid (ATRA) are active metabolites of vitamin A (retinol). There exists an interaction between retinoid receptors and peroxisome proliferator‐activated receptors (PPARγ). To define their functions in an insulin secreting system the effects of ATRA, 9cRA and the PPARγ agonist rosiglitazone on cell proliferation, insulin release and glucose transporter (GLUT) 2 of INS‐1 cells were tested. Retinoic acid receptor (RAR‐α and ‐γ) and retinoid X receptor (RXR‐α and ‐β) proteins are present (immunoblots). Both 9cRA and ATRA inhibit INS‐1 cell proliferation ([3H]‐thymidine assay) in a concentration dependent manner. Both 9cRA and ATRA increased insulin release, but only ATRA ralsed the GLUT 2 mRNA in a bell‐shaped concentration response curve after 48 h. The insulinotropic effect of one compound is not significantly superimposed by the other indicating that the same binding sites are used by 9cRA and ATRA. The acute and chronic effects of the PPARγ agonist rosiglitazone on insulin release were additionally determined since glitazones act as transcription factors together with RXR agonists. At high concentrations (100 μm) rosiglitazone inhibited glucose (8.3 mm) stimulated insulin secretion (acute experiment over 60 min). Insulin secretion, however, was increased during a 24 h treatment at a concentration of 10 μm and again inhibited at 100 μm. Changes in preproinsulin mRNA expression were not observed. Rosiglitazone (100 μm) increased GLUT 2 mRNA paralleled by an increase of GLUT 2 protein, but only after 24 h of treatment. This data indicate that RAR and RXR mediate insulin release. The changes in GLUT 2 have no direct impact on insulin release; the inhibition seen at high concentrations of either compound is possibly the result of the observed inhibition of cell proliferation. Effects of rosiglitazone on preproinsulin mRNA and GLUT 2 (mRNA and protein) do not play a role in modulating insulin secretion. With the presence of an RXR receptor agonist the effect of rosiglitazone on insulin release becomes stimulatory. Thus the effects of RAR‐, RXR agonists and rosiglitazone depend on their concentrations, the duration of their presence and are due to specific interactions. Copyright © 2001 John Wiley & Sons, Ltd.