bluuebunny/crossref_metadata_2025 huggingface dataset:
Monodispersed Spherical Colloids of Titania: Synthesis, Characterization, and Crystallization
Authors: Jiang X. , Herricks T. , Xia Y.
Published: July 2003

The generation of spherical colloids of titania with uniform diameters (see Figure for an SEM image) has been achieved using a new precursor. By varying the concentration of titanium glycolate in acetone the diameter of these spherical colloids could be controlled in the 200–500 nm range. The as‐synthesized colloids could also be readily assembled into 3D crystalline lattices with qualities sufficiently good for optical characterization.
Creating aesthetics and functional values in cotton fabrics through the introduction of thermobonding amorphous polyester fibers into blends
Authors: Ghosh Subhas , Villarreal Lila
Published: July 2003

Low‐melting thermobonding PET (copolymer) fibers were used to produce heather effects in fabrics blended with cotton, which could be classified as natural 100% cotton fabrics. PET (copolymer) fibers produced at relatively low molecular weights with intrinsic viscosities of 0.57 and 0.47 were used in this investigation. These were mostly amorphous fibers that showed a low specific gravity at 1.27 g cm−3. The fibers were blended with cotton to produce open‐ended spun yarns without the PET component being melted. These yarns were knit into fabrics and cured. The curing was based on the thermal behavior of these fibers as observed in differential scanning calorimetry thermograms. The amount of pigmented PET copolymer needed to achieve the required heather effect was optimized by variations of the blend ratios. This approach provided another avenue for introducing additional functional properties, such as antibacterial and soil‐resistance properties, to the fabric. Both the fibers and resultant fabric properties were studied extensively, along with the finishing of these fabrics. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3747–3756, 2003
Preparation and characterization of siliconized epoxy‐1,2‐bis(maleimido)ethane intercrosslinked matrix materials
Authors: Kumar A. Ashok , Dinakaran K. , Alagar M.
Published: July 2003

Novel intercrosslinked networks of siliconized epoxy‐1,2‐bis(maleimido)ethane matrix systems are developed. The siliconization of epoxy resin is carried out by using 5–15% hydroxyl‐terminated poly(dimethylsiloxane) with γ‐aminopropyltriethoxysilane as a crosslinking agent and dibutyltin dilaurate as a catalyst. The siliconized epoxy systems are further modified with 5–15% 1,2‐bis(maleimido)ethane and cured by using diaminodiphenylmethane. The prepared neat resin castings are characterized for their mechanical properties. Mechanical studies indicate that the introduction of siloxane into these epoxy resins improves the toughness with a reduction in the stress–strain values, whereas incorporation of bismaleimide (BMI) into the epoxy resin improves the stress–strain properties with a lowering of the toughness. The introduction of both siloxane and BMI into the epoxy resin influences the mechanical properties according to their content percentages. Differential scanning calorimetry (DSC), thermogravimetry, and heat distortion temperature analyses are also carried out to assess the thermal behavior of the matrix materials that are developed. DSC thermograms of the BMI modified epoxy systems show unimodal reaction exotherms. The glass‐transition temperature, thermal degradation temperature, and heat distortion temperature of the cured BMI modified epoxy and siliconized epoxy systems increase with increasing BMI content. The water absorption behavior of the matrix materials is also studied. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3808–3817, 2003
Preparation of molecularly imprinted Fe3O4/P(St‐DVB) composite beads with magnetic susceptibility and their characteristics of molecular recognition for amino acid
Authors: Lu Shulai , Cheng Guoxiang , Pang Xingshou
Published: July 2003

Tyrosine and phenylalanine imprinted Fe3O4/P(St‐DVB) composite beads with magnetic susceptibility were prepared by suspension polymerization using Fe3O4 as the magnetically susceptible component, methacrylic acid and acrylamide as functional monomers, styrene and divinylbenzene as polymeric matrix components, stearic acid as porogen, and poly(ethylene glycol) 4000 as dispersant. Scanning electron microscopy examination of the composite beads showed macropores on the surface of spherical beads. The diameters of the composite beads and the macropores were in the ranges ∼ 400–450 and 4–20 μm, respectively. The average content of Fe3O4 inside the composite beads was 3.78%, and Fe3O4 was unevenly distributed. The mechanism of macropore formation and the concept of “intellectual cavity” of molecularly imprinted composite beads were proposed. The recognition selectivity of the composite beads was investigated using tyrosine and phenylalanine as both templates and comparative molecules. Tyrosine‐imprinted composite beads exhibited a good recognition selectivity for tyrosine, and the separation factor was up to 3.67. In contrast, phenylalanine‐imprinted composite beads had little recognition selectivity for phenylalanine and the separation factor was only 1.12. It was confirmed that the three‐site interaction between tyrosine and functional monomers was stronger than the two‐site interaction between phenylalanine and functional monomers. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3790–3796, 2003
Effect of fillers on curing of wood surfaces with polyester oligomers by ultraviolet radiation
Authors: Beg M. D. H. , Khan Mubarak A. , Abedin M. Z.
Published: July 2003

A set of formulations was prepared with polyester acrylate (oligoester M‐9050) oligomers in combination with reactive diluents of different functionalities such as ethylhexyl acrylate, tripropylene glycol diacrylate , and trimethylol propane triacrylate (TMPTA). The thin films were prepared with these formulated solutions under UV radiation on a glass plate, and their physical properties such as pendulum hardness and gel content were studied. The formulation containing TMPTA showed the greatest pendulum hardness and gel content. The polished wood surfaces were cured with these formulated solutions. Physical properties such as pendulum hardness gloss at 20° and 60° angles, adhesion, abrasion resistance, and scratch hardness of UV‐cured surfaces of the wood were characterized. The formulation containing TMPTA had the best physical properties. Two types of filler, sand and talc, were used in the base coat to obtain these better properties. Both fillers improved the properties; however, the 1% sand– and 4% talc–containing formulations performed better. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3826–3834, 2003
Lifetime prediction of the epoxy system DGEBA (n = 0)/1,2‐DCH modified with an epoxy reactive diluent by thermogravimetric analysis
Authors: Núñez Lisardo , Villanueva M. , Núñez M. R. , Rial B.
Published: July 2003

Thermogravimetric analysis was used to predict the lifetime of two three‐component systems of diglycidyl ether of bisphenol A (n = 0)/1,2‐diamine cyclohexane [DGEBA (n = 0)/1,2‐DCH] modified with different concentrations of an epoxy reactive diluent, vinylcyclohexene dioxide (VCHD). Experimental results were treated using two methods. The first method was independent of the degradation mechanism, and the second was based on the thermodegradation kinetic mechanism. The activation energies of the reaction were determined using the Flynn–Wall–Ozawa method. These values were compared with those obtained using Kissinger's method. From experimental results it was found that the optimum temperature of service for these materials were different, so one or the other must be selected, depending on the application temperature considered. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3835–3839, 2003
Structure and properties of nitrile rubber (NBR)–clay nanocomposites by co‐coagulating NBR latex and clay aqueous suspension
Authors: Wu You‐Ping , Jia Qing‐Xiu , Yu Ding‐Sheng , Zhang Li‐Qun
Published: July 2003

Nitrile rubber (NBR)–clay nanocomposites were prepared by co‐coagulating the NBR latex and clay aqueous suspension. Transmission electron microscopy showed that the silicate layers of clay were dispersed in the NBR matrix at the nano level and had a planar orientation. X‐ray diffraction indicated that there were some nonexfoliated silicate layers in the NBR–clay nanocomposites. Stress–strain curves showed that the silicate layers generated evident reinforcement, modulus, and tensile strength of the NBR–clay nanocomposites, which were significantly improved with an increase in the amount of clay, and strain‐at‐break was higher than that of the gum NBR vulcanizate when the amount of clay was more than 5 phr. The NBR–clay nanocomposites exhibited an excellent gas barrier property; the reduction in gas permeability in the NBR–clay nanocomposites can be described by Nielsen's model. Compared with gum NBR vulcanizate, the oxygen index of the NBR–clay nanocomposites increased slightly. The feasibility of controlling rubber flammability via the nanocomposite approach needs to be evaluated further. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3855–3858, 2003
Dimensional stability of oriented, rigid poly(vinyl chloride)
Authors: Hitt David J. , Gilbert Marianne
Published: July 2003

Oriented PVC has enhanced properties, but on heating it begins to shrink and eventually reverts to its original dimensions. Thermomechanical analysis was used to study the effects of orientation variables and subsequent annealing or aging on the shrinkage of rigid PVC. The thermal history of the oriented PVC affected its crystallinity and the free volume in the oriented structure. These changes modified the temperature at which the oriented samples began to shrink (i.e., their dimensional stability.) Higher draw and annealing temperatures can be used to improve dimensional stability; however, their effective use is limited because PVC has a peak elongation at 90°C. Increased annealing time also increases dimensional stability. Aging greatly improves the dimensional stability of the material; this process can be accelerated at temperatures up to 60°C. The shrinkage onset temperature can be increased without compromising the enhancement of mechanical properties achieved by orientation. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3859–3867, 2003
Modeling of moisture sorption isotherms of poly(vinyl alcohol)/starch films
Authors: Raj Baldev , Eugene Raj A. , Madan P. , Siddaramaiah
Published: July 2003

Studies on the moisture sorption characteristics of poly(vinyl alcohol)/starch blends for water activity (aw) values of 0.1–0.9 were performed at 27°C. The equilibrium moisture content at different aw values was used to fit different sorption isotherm models proposed in the literature. The ranges of aw applicable for the different sorption isotherms were reported. The model constants of the sorption equations were determined by linear fitting. The value of the coefficient of determination (0.98 ± 0.01) confirmed the goodness of fit of the equations studied. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3874–3881, 2003
Fe2+ and Fe3+ adsorption on 2‐vinylpyridine–divinylbenzene copolymers and acrylonitrile–methyl methacrylate–divinylbenzene terpolymers
Authors: Rabelo D. , Silva V. J. , Alcântara E. F. C. , Faria L. C. , Martins G. A. V. , Garg V. K. , Oliveira A. C. , Morais P. C.
Published: July 2003

The adsorption of Fe2+ and Fe3+ ions on 2‐vinylpyridine–divinylbenzene copolymer and acrylonitrile–methyl methacrylate–divinylbenzene terpolymer was investigated. In general, the adsorption of Fe2+ and Fe3+ in both resins increased with the enhancement of hydrochloric acid and metal concentration. The metal adsorption on the terpolymer increased sharply with the addition of small portions of ethanol, whereas the adsorption on the copolymer practically was not affected by the presence of the alcohol. An increase in temperature produced a small increase in iron adsorption for both resins. Fourier transform infrared spectra showed that nitrile and ester groups of the terpolymer did not suffer hydrolysis during metal adsorption, even for the highest HCl concentration and the highest temperature applied. A mechanism of iron adsorption through the ion exchange of chloride anions by tetrahedral [FeCl4]2− or [FeCl4]− anions is proposed. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3905–3912, 2003
Preparation and the properties of PMR‐type polyimide composites with aluminum nitride
Authors: Wang Jiajun , Yi Xiao‐Su
Published: July 2003

A new polyimide composite was developed relying on the concept of in situ polymerization of monomer reactants polyimide. High thermal conductive, low dielectric constant and dielectric loss, and thermal‐stable composites were successfully demonstrated by incorporating aluminum nitride powder into the polyimide. The weight percent of aluminum nitride was up to 80%. The thermal and dielectric properties follow the classic composite theories. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3913–3917, 2003
The study of polymerization kinetics of methacrylamide by oxidation: Reduction system using potassium permanganate/glycine in aqueous medium
Authors: Mirzaei A. A. , Shaterian H. R. , Habibi S. M.
Published: July 2003

The polymerization kinetic of methacrylamide with the KMnO4/glycine redox system has been investigated volumetrically at 35±0.1°C under nitrogen atmosphere in aqueous sulfuric acid medium in a dimethylsulfoxide/H2O mixture (5% v/v). The rates of polymerization were found to obey the following equation: Rp ∝ [Methacrylamide]1.08[Glycine]0.44[KMnO]0.46. A glycine end group containing polymethacrylamide was prepared by the MnO/glycine redox system under mild conditions. The reaction proceeded with radical mechanism and the overall energy of activation (Ea) was calculated to be 29.87 kJ/mol from the Arrhenius plot in the temperature range 25–50°C. Molecular weight of the polymer was determined by viscometry. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3918–3924, 2003
Theoretical evaluation and the effect of thermal degradation on the Time–Temperature–Transformation (TTT) diagram of bisphenol A epoxies
Authors: Stutz Herbert
Published: July 2003

A brief discussion about the Time–Temperature–Transformation (TTT) diagram is presented. Using diamino diphenylsulfone‐cured diglycidyl bisphenol A as a representative example, its TTT diagram is completed by including the thermal degradation. The theoretical diagram as obtained from the kinetics of curing and thermal degradation is compared with experimental data. The agreement is good, slight deviations are observed only in the time to vitrify above 150°C and the maximum available glass temperature, which is due to side reactions and onset of thermal degradation during curing. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3894–3896, 2003
Studies on acrylic acid–grafted polyester fabrics by electron beam preirradiation method. II. Novel intelligent immersion‐resistant and moisture‐permeable fabrics
Authors: He Changcheng , Gu Zhenya , Tian Junying
Published: July 2003

Moisture regain, water vapor permeability, and water‐impermeable ability of polyester fabrics before and after grafting by acrylic acid (AA) were investigated. The results showed that the AA‐grafted fabric presents novel properties. When it is dry it possesses a higher water vapor transmission rate. Once it comes into contact with water, the grafted poly(acrylic acid) layer on the fibers' surface begins to swell and seals the intervals between fibers and yarns to prevent water from penetrating, a phenomenon known as immersion resistance. This kind of immersion‐resistant and moisture‐permeable fabrics might be a suitable candidate for the immersion‐resistant layer fabrics of Type B immersion‐resistant suits. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3939–3943, 2003
Porous cellulose acetate membrane prepared by thermally induced phase separation
Authors: Matsuyama Hideto , Ohga Kazuhiro , Maki Taisuke , Tearamoto Masaaki , Nakatsuka Shuji
Published: July 2003

Microporous cellulose acetate membranes were prepared by a thermally induced phase separation (TIPS) process. Two kinds of cellulose acetate with acetyl content of 51 and 55 mol % and two kinds of diluents, such as 2‐methyl‐2,4‐pentandiol and 2‐ethyl‐1,3‐hexanediol, were used. In all polymer‐diluent systems, cloud points were observed, which indicated that liquid–liquid phase separation occurred during the TIPS process. The growth of droplets formed after the phase separation was followed using three cooling conditions. The obtained pore structure was isotropic, that is, the pore size did not vary across the membrane. In addition, no macrovoids were formed. These pore structures were in contrast with those usually obtained by the immersion precipitation method. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3951–3955, 2003
Socioeconomic effects on the risk of having a recognized pregnancy with Down syndrome
Authors: Torfs Claudine P. , Christianson Roberta E.
Published: July 2003

BACKGROUND

Appoximately 95% of Down syndrome (DS) cases are caused by an error in germ cell division (meiosis), resulting in an extra chromosome 21. The meiotic error, predominantly of maternal origin, occurs either during the mother's fetal life (meiosis I) or at ovulation (meiosis II). Because maternal‐age‐specific DS prevalence rates vary between and within populations, it has been hypothesized that environmental factors can affect the risk for a DS pregnancy.

METHODS

In a population‐based case‐control study of 997 clinically recognized DS cases (including fetal losses) and 1007 controls without a birth defect, we examined the mother's socioeconomic status (SES) from the time of her fetal life to the time of conception. SES variables were considered as proxies for environmental factors. We used multiple logistic regression for the analyses.

RESULTS

We found associations with low levels of each SES variable examined: mother's education less than high school (OR, 1.29; 95% CI, 1.01–1.65), father's low occupation (OR, 1.23; 95% CI, 0.95–1.60), father's low education (OR, 1.28; 95% CI, 0.99–1.64), mother's father's low occupation (OR, 1.35; 95% CI, 1.06–1.71), and family income $820,000 (OR, 1.31; 95% CI, 1.02–1.68). The risk for DS increased as the number of low socioeconomic factors present throughout the mother's life increased. With four factors present, the risk (adjusted for confounders) almost doubled (OR, 1.98; 95% CI, 1.30–3.01). Those associations persisted among young (<30) and old (≥30) maternal age groups.

CONCLUSIONS

A mother's low SES during any period before conception increases her risk for a recognized pregnancy with DS. Because of the high birth prevalence of DS, the public health impact of maternal SES may be considerable. Birth Defects Research (Part A) 67:522–528, 2003. © 2003 Wiley‐Liss, Inc.
Trichloroethylene effects on gene expression during cardiac development
Authors: Collier J. Michael , Selmin Ornella , Johnson Paula D. , Runyan Raymond B.
Published: July 2003

BACKGROUND

Halogenated hydrocarbon exposure is associated with changes in gene expression in adult and embryonic tissue. Our study was undertaken to identify differentially expressed mRNA transcripts in embryonic hearts from Sprague‐Dawley rats exposed to trichloroethylene (TCE) or potential bio‐transformation products dichloroethylene (DCE) and trichloroacetic acid (TCAA).

METHODS

cDNA subtractive hybridization was used to selectively amplify expressed mRNA obtained from control or halogenated hydrocarbon exposed rat embryos. The doses used were 1100 and 110 ppm (8300 and 830 μM) TCE, 110 and 11 ppm (1100 and 110 μM) DCE, and 27.3 and 2.75 mg/ml (100 and 10 mM) TCAA. Control animals were given distilled drinking water throughout the period of experiments.

RESULTS

Sequencing of over 100 clones derived from halogenated hydrocarbon exposed groups resulted in identification of numerous differentially regulated gene sequences. Up‐regulated transcripts identified include genes associated with stress response (Hsp 70) and homeostasis (several ribosomal proteins). Down‐regulated transcripts include extracellular matrix components (GPI‐p137 and vimentin) and Ca2+ responsive proteins (Serca‐2 Ca2+‐ATPase and β‐catenin). Two possible markers for fetal TCE exposure were identified: Serca‐2 Ca2+‐ATPase and GPI‐p137, a GPI‐linked protein of unknown function. Differential regulation of expression of both markers by TCE was confirmed by dot blot analysis and semi‐quantitative RT‐PCR with levels of TCE exposure between 100 and 250 ppb (0.76 and 1.9 μM) sufficient to decrease expression.

CONCLUSIONS

Sequences down‐regulated with TCE exposure appear to be those associated with cellular housekeeping, cell adhesion, and developmental processes, while TCE exposure up‐regulates expression of numerous stress response and homeostatic genes. Birth Defects Research (Part A) 67488–495, 2003. © 2003 Wiley‐Liss, Inc.
Vascular endothelial growth factor rescues 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin inhibition of coronary vasculogenesis
Authors: Ivnitski‐Steele Irena D. , Walker Mary K.
Published: July 2003

BACKGROUND

We previously demonstrated that the environmental pollutant 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) reduces coronary vascular development in chick embryos in vivo. In the current study, we assessed whether TCDD inhibits early events in coronary endothelial tube formation and outgrowth, and whether this inhibition occurs through a vascular endothelial growth factor (VEGF)‐dependent mechanism.

METHODS

Fertile chicken eggs were treated with control (corn oil) or TCDD (0.3 pmol TCDD/g) on incubation day 0. On embryonic day 6, cardiac ventricle explants were cultured on a three‐dimensional collagen gel, when coronary angioblasts are present, but prior to their assembly into endothelial tubes. Endothelial cells migrating out from explants were identified by immunohistochemistry, and endothelial tube number and length were quantitated. In addition, on incubation days 6 and 8, cardiac VEGF mRNA and protein were measured by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA), respectively.

RESULTS

Endothelial tube length and number were significantly reduced (40% ± 1.7% and 36% ± 3%, respectively) in TCDD explants, compared to controls. Recombinant exogenous VEGF, as well as hypoxic stimulation with CoCl2 or 10% O2, significantly increased the length and number of outgrowing tubes in TCDD cultures, and this stimulation was prevented by a VEGF neutralizing antibody. In contrast, VEGF neutralizing antibody reduced the length and number of tubes only in control cultures, and had no inhibitory effect on tube outgrowth from TCDD explants. Finally, hearts from TCDD‐treated embryos exhibited a significant reduction in both VEGF mRNA and protein, compared to controls.

CONCLUSIONS

These data suggest that TCDD inhibits early coronary vascular outgrowth via a VEGF‐dependent mechanism. Birth Defects Research (Part A) 67:496–503, 2003. © 2003 Wiley‐Liss, Inc.
Classifying Two‐Year Colleges: Purposes, Possibilities, and Pitfalls
Authors: McCormick Alexander C. , Cox Rebecca D.
Published: July 2003

A credible and reliable classification system for two‐year colleges will advance our understanding of this important sector of higher education. But developing such a system involves a number of challenges and may lead to unintended and largely unforseeable consequences.
College Size as the Major Discriminator
Authors: Cohen Arthur M.
Published: July 2003

College size is a valid, readily available, easily understood, and nonjudgmental criterion that relates directly to other important college characteristics. Therefore, size should be considered the main criterion in the classification of community colleges.
Using IPEDS to Develop a Classification System for Two‐Year Postsecondary Institutions
Authors: Merisotis Jamie P. , Shedd Jessica M.
Published: July 2003

This chapter explores the development of a classification system for two‐year institutions that can provide a framework for analysis and contribute to the discourse in public policy. The proposed classification system is based on cluster analyses using data from the National Center for Education Statistics' Integrated Postsecondary Education Data System (IPEDS).
On Markets and Other Matters: A Price Model for Public Two‐Year Colleges
Authors: Shaman Susan M. , Zemsky Robert
Published: July 2003

Community colleges are often thought to constitute a separate sphere in higher education, one that is unique and largely self‐contained. This chapter calls into question that basic assumption, demonstrating that the price an individual community college charges is a function of the role and place that the institution occupies in the overall market for postsecondary education. The analysis suggests a classification that distinguishes colleges with respect to their emphasis on formal degree programs versus delivery of courses.
The Perspective of the American Association of Community Colleges
Authors: Phillippe Kent A. , Boggs George R.
Published: July 2003

The authors examine and discuss the utility of the classification systems proposed for community colleges from the perspective of the American Association of Community Colleges. Each proposed system has its strengths and limitations, and the discussion provides insights for understanding the differences among community colleges.
A Practitioner's Perspective
Authors: de los Santos Alfredo G.
Published: July 2003

Each scheme described in the first part of this volume has strengths and weaknesses, which are identified and discussed in this chapter.
A Researcher's Perspective
Authors: Bailey Thomas R.
Published: July 2003

The diversity of community colleges justifies a more subtle system of categorization than the traditional Carnegie system, but the large number of missions taken on by community colleges complicates this goal. Any system must be based on a clear understanding of the goals of the categorization. This chapter makes a distinction between a characteristics‐based system and an output‐based system and uses that distinction to discuss the proposed classification schemes.
Caspase‐dependent and ‐independent apoptosis of mast cells induced by withdrawal of IL‐3 is prevented by Toll‐like receptor 4‐mediated lipopolysaccharide stimulation
Authors: Yoshikawa Hideshi , Tasaka Kachio
Published: July 2003

IL‐3‐dependent mucosal‐like mast cells undergo apoptosis upon withdrawal of IL‐3. Generally, the apoptosis is mediated by the activation of caspases and inhibited by addition of the pan‐caspase inhibitors z‐VAD‐FMK or BOC‐D‐FMK. However, DNA fragmentation, a typical characteristic of apoptosis, is not inhibited by z‐VAD‐FMK or BOC‐D‐FMK in mast cell apoptosis. In this study, we demonstrate that the apoptosis of mast cells is mediated by both caspase‐dependent and ‐independent mechanisms. The caspase‐independent apoptosis is mediated by the translocation of endonuclease G from mitochondria into nuclei. Withdrawal of IL‐3 caused down‐regulation of Bcl‐xL, resulting in a drop in mitochondrial membrane transition potential followed by the release of cytochrome c and endonuclease G from mitochondria. However, stimulation of mast cells through Toll‐like receptor 4 (TLR4) by lipopolysaccharide prevented mast cell apoptosis by inducing expression of Bcl‐xL. Moreover, the activation of mast cells by LPS is enhanced in the presence of IFN‐γ, which up‐regulates the expression of cell surface TLR4. Taken together, these observations provide evidence that mast cells play importantroles not only in allergic reactions but also in innate immunity recognizing enterobacteria through TLR4, and are regulated differently from allergic inflammation by Th1 cytokines.
Reduced transforming growth factor‐β1‐producing T cells in the duodenal mucosa of children with food allergy
Authors: Pérez‐Machado Miguel A. , Ashwood Paul , Thomson Michael A. , Latcham Frances , Sim Rosalind , Walker‐Smith John A. , Murch Simon H.
Published: July 2003

Infant food allergies are increasing, and many breast‐fed infants now sensitize to maternally‐ingested antigens. As low‐dose oral tolerance requires generation of suppressor lymphocytes producing TGF‐β1 (Th3 cells), we studied these cells in duodenal biopsies after diagnostic endoscopy. Spontaneous production of Th1, Th2 and Th3 cytokines by duodenal lymphocytes was studied using flow cytometry in 20 children with no eventual clinico‐pathological diagnosis (controls), 30 children with multiple food allergy, nine with celiac disease and six with inflammatory enteropathies. Immunohistochemistry and in situ hybridization were used to localize TGF‐β1 protein and mRNA in matched biopsies. We found no significant Th1/Th2 skewing amongst mucosal lymphocytes in allergic children compared to controls, although celiac and inflammatory enteropathy patients showed increased Th1 responses. By contrast, the allergic children showed reduction of TGF‐β1+ lymphocytes in both epithelial and lamina propria compartments. Reduction of TGF‐β1 expression was also seen in mononuclear cells and epithelium in food allergy by immunohistochemistry and in situ hybridization. The dominant mucosal abnormality in food allergic children was, thus, not Th2 deviation but impaired generation of Th3 cells. As generation of these cells requires innate immune response to enteric bacteria, we suggest that changing infectious exposures may inhibit primary establishment of basic oral tolerance mechanisms.
Human NK cells express Fc receptors for IgA which mediate signal transduction and target cell killing
Authors: Mota Gabriela , Manciulea Mioara , Cosma Ecaterina , Popescu Iulia , Hirt Mirela , Jensen‐Jarolim Erika , Calugaru Ana , Galatiuc Cecilia , Regalia Teodor , Tamandl Dietmar , Spittler Andreas , Boltz‐Nitulescu George
Published: July 2003

Receptors for the Fc region of IgG (FcγRIIIa, FcγRIIc) and IgM (FcμR) were previously described on NK cells. In this work the expression of Fc receptors for IgA (FcαR) on humanNK cells and the signaling events were investigated. The FcαR was demonstrated by flow cytometry using secretory IgA (sIgA) and anti‐human IgA antibody. The percentage of NK cells (CD3–CD56+CD16+) expressing FcαR ranged between 55.7% and 95.7%, with a mean ± SD of 75.2±11.8. The association constant and the number of 125I‐labeled sIgA (125I‐sIgA) molecules bound per cell, calculated by Scatchard analysis, were 2×107 M–1 and 1.7×104, respectively. The binding specificity was proved by inhibition experiments. Cold sIgA but not IgA Fab fragments were able to inhibit 125I‐sIgA binding in a concentration‐dependent manner. Binding of sIgA to NK cells was neither inhibited by anti‐mannose receptor antibody, nor by L‐fucose, D‐galactose, D‐glucose, D‐mannose or N‐acetyl‐D‐glucosamine. Pretreatment of NK cells with polymeric IgA inhibited their capacity to kill 51Cr‐labeled K562 target cells by 34.8%, whereas with monomeric IgA only by 13.1%. Ligand‐induced clustering of the FcαR resulted in activation of tyrosine kinases Lck, Syk and phosphatidylinositol 3‐kinase. The present studies support the concept that human NK cells bind preferentially sIgA and polymeric IgA with moderate affinity via FcαR, which is different from the FcαRI/CD89 and other carbohydrate‐recognizing receptors like mannose receptor/CD206. This novel structure mediates signal transduction and cell killing.
ME3738 protects from concanavalin A‐induced liver failure via an IL‐6‐dependent mechanism
Authors: Klein Christian , Wüstefeld Torsten , Heinrich Peter C. , Streetz Konrad L. , Manns Michael P. , Trautwein Christian
Published: July 2003

ME3738 is a new compound that attenuates liver disease in several models of acute and chronic liver inflammation. We used the concanavalin A (Con A) model to elucidate the molecular mechanismsof ME3738 to block liver cell damage. Pretreatment of BALB/c mice with ME3738 prior to Con A injection resulted in a significant reduction in liver injury. The protective effect of ME3738 prior to Con A injection was associated with a reduction in IL‐6 serum levels and NF‐κB DNA binding in liver nuclear extracts. However, STAT3 DNA binding was induced via ME3738 prior to Con A injection. Further analysis showed that ME3738 induces IL‐6 serum levels and activates STAT3 DNA binding and target gene transcription. The relevance of this finding was assessed in IL‐6–/– mice. Inthese animals, ME3738 induced no increase in IL‐6 serum expression, and activation of IL‐6‐dependent pathways was not found. In addition, ME3738 did not protect IL‐6–/– animals from Con A‐induced liver failure, while IL‐6 injection was still effective. Therefore, we demonstrate that ME3738 triggers IL‐6 expression, which activates pathways that are relevant to protect from Con A‐induced liver failure.
Vav exchange factor counteracts the HIV‐1 Nef‐mediated decrease of plasma membrane GM1 and NF‐AT activity in T cells
Authors: Tuosto Loretta , Marinari Barbara , Andreotti Mauro , Federico Maurizio , Piccolella Enza
Published: July 2003

Several findings support the importance of GM1‐enriched lipid microdomains of plasma membrane and of Vav, an essential regulator of actin cytoskeletal rearrangement, in the regulation of T cell activation. Moreover, a functional link among lipid microdomains, Vav and the HIV product Nef has been described. These observations suggest that Nef can modify plasma membrane GM1, affecting the behavior of HIV‐infected cells towards antigen recognition and Vav towards counteracting such an effect. We observed that Nef expression, either following viral infection or ectopic expression, significantly decreased the level of plasma membrane GM1 in unstimulated T cells. This down‐regulation was associated with the inhibition of NF‐AT activation, but not with NF‐κB activation inducedby TCR engagement. Dissecting the signaling pathway that regulates NF‐AT activation, we found that Nef inhibited exclusively the Ca2+/calcineurin cascade, whereas the JNK cascade and AP‐1 transcriptional activity were not affected. Our evidence that Vav overexpression counteracted both the Nef‐induced decrease of GM1 expression and the inhibition of NF‐AT activity, suggests a novel mechanism by which Nef may interfere with TCR‐mediated activation through the modulation of intracellular trafficking and clustering of GM1‐enriched microdomains at the cell surface.
Lysophosphatidic acid induces human natural killer cell chemotaxis and intracellular calcium mobilization
Authors: Jin Yixin , Knudsen Eirunn , Wang Ling , Maghazachi Azzam A.
Published: July 2003

We have investigated the effects of the bioactive lipid lysophosphatidic acid (LPA) on several functions of activated human natural killer (NK) cells. Flow cytometric and immunoblot analyses show that these cells express LPA1, LPA2 and LPA3. LPA but not its precursor phosphatidic acid (PA) induces the chemotaxis of NK cells, an activity that is inhibited by prior treatment of the cells with pertussis toxin (PTX). In addition, LPA induces the mobilization of intracellular calcium, an effect that is markedly inhibited by PTX, but is not inhibited by the addition of EGTA. PA also induces calcium flux in NK cells, but with much lower efficacy than LPA. Cross‐desensitization experiments demonstrate that LPA and PA utilize different receptors. Moreover, LPA or PA but not sphingosine 1‐phosphate, enhances IFN‐γ secretion by activated NK cells. Our results may shed some light on the findings that activated NK cells are found at the sites of tumor growth.
Sensitivity of IL‐5 production to the cAMP‐dependent pathway in human T cells is reduced by exogenous IL‐2 in a phosphoinositide 3‐kinase‐dependent way
Authors: Heijink Irene H. , Kauffman Henk F. , Postma Dirkje S. , de Monchy Jan G. R. , Vellenga Edo
Published: July 2003

The cAMP‐dependent pathway plays an important role in the regulation of T cell‐mediated immune responses by inhibition of T cell proliferation, activation and production of Th1‐like cytokines.Depending on costimulatory signals and on the activation status of T cells, cAMP also regulates the production of Th2‐like cytokines, yet the mechanism is not completely defined. We investigated the effect of costimulation with IL‐2 on cAMP‐mediated inhibition of IL‐5 secretion and the signaling pathways involved in these effects in freshly isolated, α‐CD3/α‐CD28‐stimulated human T lymphocytes. We demonstrate that IL‐2 counteracts the cAMP‐mediated inhibitory effects on IL‐5 secretion by the modulation of phosphoinositide 3‐kinase (PI3‐K)‐dependent signaling. Our results indicate that phosphorylation of cAMP‐responsive element‐binding protein (CREB) and the activity of the small GTPase Rap1 are unlikely involved in the protective effect of IL‐2. Instead, the effect of IL‐2may be mediated by the PI3‐K‐dependent inactivation of the forkhead‐related transcription factor FKHR‐L1, down‐regulation of p27kip and abrogation of the cAMP‐mediated inhibition of activator protein (AP)‐1 binding activity. Together, our results indicate that increased IL‐2‐dependent PI3‐K signaling leads to impaired negative feedback control of the production of Th2‐type cytokine IL‐5 by the cAMP‐dependent pathway.
Essential pathogenic role of endogenous IL‐18 in murine diabetes induced by multiple low doses of streptozotocin. Prevention of hyperglycemia and insulitis by a recombinant IL‐18‐binding protein: Fc construct
Authors: Nicoletti Ferdinando , Marco Roberto Di , Papaccio Gianpaolo , Conget Ignacio , Gomis Ramon , Bernardini Renato , Sims John E. , Shoenfeld Yehuda , Bendtzen Klaus
Published: July 2003

IL‐18 is a cytokine structurally and functionally related to IL‐1 that, in synergy with IL‐12, stimulates the synthesis of IFN‐γ from T lymphocytes and natural killer cells. Because IFN‐γ plays a key pathogenic role in the development of murine immunoinflammatory diabetes induced by multiple low doses of streptozotocin (STZ) we investigated the effect of negating the actions of endogenous IL‐18 in this model by administering recombinant IL‐18‐binding protein:Fc (IL‐18 bp:Fc). C57BL/6 mice were injected once daily with 40 mg/kg STZ for 5 consecutive days, day 0 being the first day of STZ challenge. Relative to control animals treated in parallel with either PBS or human IgG, mice treated from day –3 to day 7 with daily doses of 150 μg of IL‐18 bp:Fc exhibited lowerincidence of diabetes and milder insulitis. In contrast, mice that were treated with IL‐18 bp:Fc from day 7 to day 14 exhibited clinical and histological signs of STZ‐induced diabetes similar to those of control mice treated with IgG. The protective effect of IL‐18 bp:Fc was accompanied by modified ex vivo immune responses, in that spleen cells and peritoneal macrophages contained fewer IFN‐γ secreting cells and released lower amounts of nitrite (an index of nitric oxide production) and IL‐1β. We conclude that intact IL‐18 function is essential for the full diabetogenic effectof low dose STZ in C57BL/6 mice.
TEA regulates local TCR‐Jα accessibility through histone acetylation
Authors: Mauvieux Laurent , Villey Isabelle , de Villartay Jean‐Pierre
Published: July 2003

Enhancer α‐dependent histone acetylation has been proposed as a molecular mechanism underlying the control of accessibility of recombination signal sequences along the TCRα locus. Herewe show that chromatin acetylation along the first Jα segments is under the dependence of the T early α element (TEA), located upstream of TCRJα locus. The targeted deletion of TEA leads to an absence of histones H3 and H4 tail acetylation, while maintaining histone acetylation in the region spanning downstream Jα segments. During thymocyte maturation, TEA‐dependent histone acetylation appears at immature single‐positive stage, known to represent the stage of VαJα initiation. TEA‐dependent histone acetylation of the most upstream Jα segments leads to enhancedDNA accessibility thus optimizing TCRJα usage and increasing Ag receptor diversity potential.
Oxidative‐stress‐induced T lymphocyte hyporesponsiveness is caused by structural modification rather than proteasomal degradation of crucial TCR signaling molecules
Authors: Cemerski Saso , van Meerwijk Joost P. M. , Romagnoli Paola
Published: July 2003

In several human pathologies (e.g. cancer, rheumatoid arthritis, AIDS and leprosy) oxidative stress induces T cell hyporesponsiveness. Hyporesponsive T cells often appear to display impaired expression of some (e.g. TCR‐ζ, p56lck and LAT) but not all (e.g. TCR‐αβ and CD3‐ϵ) crucial TCR‐proximal signaling molecules but the underlying mechanisms have as yet not been identified. Using an in vitro system for oxidative‐stress‐induced T cell hyporesponsiveness we here report two sequential effects of oxidative stress on TCR signaling molecules: protein alterations and proteasomal degradation. We have identified the C‐terminal part of TCR‐ζ and the membrane‐proximal domain of p56lck as potential targets for modifications induced by reactive oxygen species. Oxidative‐stress‐exposed proteins were differentially susceptible to proteasomal degradation: whereas modified TCR‐ζ was relatively resistant, reactive oxygen species (ROS)‐altered LAT and p56lck were much more susceptible. Importantly, we found that T cell hyporesponsiveness best correlated with ROS‐dependent protein alteration since inhibition of proteasomal degradation did not restore function. Finally, our data provide an explanation for the paradox of reduced TCR‐ζ signals combined with unaltered TCR‐αβ and CD3‐ϵexpression levels: the TCR‐ζ chain in hyporesponsive T cells is still expressed but no longer detectable by certain mAb recognizing ROS‐sensitive epitopes.
CRP‐ductin, the mouse homologue of gp‐340/deleted in malignant brain tumors 1 (DMBT1), binds gram‐positive and gram‐negative bacteria and interacts with lung surfactant protein D
Authors: Madsen Jens , Tornøe Ida , Nielsen Ole , Lausen Mette , Krebs Inge , Mollenhauer Jan , Kollender Gaby , Poustka Annemarie , Skjødt Karsten , Holmskov Uffe
Published: July 2003

CRP‐ductin is a protein expressed mainly by mucosal epithelial cells in the mouse. Sequence homologies indicate that CRP‐ductin is the mouse homologue of human gp‐340, a glycoprotein that agglutinates microorganisms and binds the lung mucosal collectin surfactant protein‐D (SP‐D). Here we report that purified CRP‐ductin binds human SP‐D in a calcium‐dependent manner and that the binding is not inhibited by maltose. The same properties have previously been observed for gp‐340 binding of SP‐D. CRP‐ductin also showed calcium‐dependent binding to both gram‐positive and ‐negative bacteria. A polyclonal antibody raised against gp‐340 reacted specifically with CRP‐ductin in Western blots. Immunoreactivity to CRP‐ductin was found in the exocrine pancreas, in epithelial cells throughout the gastrointestinal tract and in the parotid ducts. A panel of RNA preparations from mouse tissues was screened for CRP‐ductin and SP‐D expression by reverse transcription‐PCR. The pancreas was the main site of synthesis of CRP‐ductin, but transcripts were also readily amplified from salivary gland, the gastrointestinal tract, liver, testis, uterus and lung. Lung was the main site of synthesis of SP‐D, but transcripts were also amplified from uterus, salivary gland, thymus, thyroid gland, pancreas and testis. We conclude that CRP‐ductin is the mouse homologue of human gp‐340 and that its capacity to bind SP‐D as well as gram‐negative and gram‐positive bacteria suggests a role in mucosal immune defense.
Oxidative stress stimulates IL‐4 and IL‐6 production in mast cells by an APE/Ref‐1‐dependent pathway
Authors: Frossi Barbara , De Carli Marco , Daniel Kenn Curt , Rivera Juan , Pucillo Carlo
Published: July 2003

Mast cells are exposed to an oxidative environment in the course of allergic and inflammatory reactions. We have examined the effects of H2O2 stimulation in a primary rat basophilic leukemia cell line (RBL‐2H3) and compared with IgE‐dependent stimulation. Like IgE stimulation, H2O2 up‐regulates IL‐4 and IL‐6 gene expression and cytokine secretion, shows a little effect on IL‐5 but does not induce IL‐10 gene expression. Simultaneous H2O2 treatment and FcϵRI triggering of mast cells has additive effects on IL‐4 expression. In addition, we show that both stimuli induce the nuclear translocation of APE/Ref‐1, a bifunctional enzyme that stimulates the DNA‐binding activity of several transcription factors through the reduction of highly reactive cysteines. Conditional inactivation of APE/Ref‐1 expression abolishes H2O2‐induced IL‐4 and IL‐6 gene expression but does not affect that induced by FcϵRI stimulation. Our findings indicate that oxidative stress activates the gene expression of a specific cytokine pattern in mast cells through an APE/Ref‐1‐dependent pathway, which is distinct from theone that is activated by FcϵRI stimulation. Nonetheless, H2O2 and FcϵRI signalings are additive in augmenting IL‐4 production. Most importantly, oxidative stress can induce a pro‐type 2 inflammatory response from mast cells that is independent of FcϵRI stimulation.
4‐1BB enhances CD8+ T cell expansion by regulating cell cycle progression through changes in expression of cyclins D and E and cyclin‐dependent kinase inhibitor p27kip1
Authors: Lee Hyeon‐Woo , Nam Kyung‐Ok , Park Su‐Jung , Kwon Byoung S.
Published: July 2003

The T cell costimulatory receptor 4‐1BB enhances cell cycle progression and proliferation of CD8+ T cells in both an IL‐2‐dependent and ‐independent manner. In these studies, 4‐1BB costimulation was shown to increase cyclin D2, D3, and E expression, and concomitantly down‐regulate the expression of the cyclin‐dependent kinase inhibitor p27kip1. 4‐1BB increases cyclin D2 transcription via mitogen‐activated/extracellular signal‐regulated kinase‐1/2 and LY294002‐sensitive phosphatidylinositol 3‐kinase (PI3K) signaling pathways. In addition, 4‐1BB up‐regulates cyclin D2 translation via PI3K/Akt/mammalian target of rapamycin (mTOR) pathways, presumably triggered by IL‐2/IL‐2 receptor ligation. The enhanced cyclin D2 and D3 expression initiates up‐regulation of cyclin E expression and down‐regulation of p27kip1. Our results suggest a role for cyclin D2, D3, and E, and p27kip1 proteins in the 4‐1BB‐mediated cell cycle progression of CD8+ T cells in vivo.
Anti‐tumor T cell response and protective immunity in mice that received sublethal irradiation and immune reconstitution
Authors: Ma Jun , Urba Walter J. , Si Lüsheng , Wang Yili , Fox Bernard A. , Hu Hong‐Ming
Published: July 2003

To test whether homeostasis‐driven T cell proliferation in reconstituted lymphodepleted hosts would improve the therapeutic efficacy of tumor vaccines, normal mice and reconstituted lymphopenic mice (RLM; C57BL/6 mice rendered lymphopenic with sublethal total‐body irradiation and reconstituted with naive splenocytes) were used in the vaccination and challenge experiments with weakly immunogenic F10 melanoma cells. Only limited protection was observed in vaccinated normal mice (16.7%), whereas significantly greater protection was induced in vaccinated RLM (63.2%). Protective immunity in RLM depended on CD8 T cells. Following vaccination, a significant increase in the percentage of CD44hiCD62Llo T cells was detected in the tumor vaccine‐draining lymph node (TVDLN) of vaccinated RLM compared to that of vaccinated normal mice. After in vitro stimulation, effector T cells generated from TVDLN of vaccinated RLM produced more IFN‐γ than T cells from vaccinated normal mice, and contained more melanoma‐specific T cells, as assessed by ELISA and intracellular cytokine staining. This study suggests that vaccination of reconstituted lymphopenic hosts could elicit superior anti‐tumor immunity compared to normal hosts, highlighting the potential clinical benefit of performing tumor vaccination during immune reconstitution.