bluuebunny/crossref_metadata_2025 huggingface dataset:
Increase in flame retardance of glass‐epoxy laminates without halogen or phosphorous compounds by simultaneous use of incombustible‐gas generator and charring promoter
Authors: Kiuchi Yukihiro , Iji Masatoshi , Nagashima Hiroaki , Miwa Takashi
Published: June 2006

Highly flame‐resistant glass‐epoxy laminates without flame‐retarding additives such as halogen and phosphorous compounds have been developed to overcome environmental problems caused by these additives. The laminates consist mainly of a self‐extinguishing epoxy‐resin compound (phenol aralkyl), an incombustible‐gas generator (amino‐triazine‐novolac hardener: ATN hardener), and inorganic materials such as a charring promoter (zinc molybdate on talc: ZMT) and a limited amount of harmless metal hydroxide (aluminum trihydroxide: ATH). They are highly flame‐resistant and have other beneficial characteristics, including soldering‐heat resistance, humidity resistance, electronic properties, and processing advantages. These qualities make them applicable enough to replace the FR‐4 type printed wiring boards (PWBs) that are widely used today. Simultaneously using the ATN hardener and ZMT in the laminates, including the epoxy‐resin compound and ATH, greatly improved their flame retardance. We then reduced the amount of ATH to obtain even better flame retardance in the laminates. This reduction of the ATH, consequently, improved other practical characteristics such as soldering‐heat resistance, humidity resistance, and electronic properties. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3367–3375, 2006
Color evaluation of wool fabric dyed with Rhizoma coptidis extract
Authors: Ke Guizhen , Yu Weidong , Xu Weilin
Published: June 2006

Berberine is the only cationic colorant of natural plant dyes, which lies in the roots of Rhizoma coptidis and stems of phellodendron. In this study, wool fabric was dyed with the extracts of R. coptidis. Color evaluation was characterized with ΔE, L*, a*, b*, c*, H0, K/S. Effects of mordant, extraction concentration, pH value of dye bath, and treatment temperature on color values were studied. Results indicated that wool fabrics dyed with mordant, or at higher temperature, or in alkali solution possessed deeper shades and darker colors. And the wool fabric showed good antibacterial property after dyeing with R. coptidis extracts. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3376–3380, 2006
Effects of various fillers on CEM‐1 laminate punchability
Authors: Chiu Hsien‐Tang , Cheng Ming‐Feng
Published: June 2006

The primary objective of this study is to emphasize the modification of the epoxy resin formulation by implementing falling weight test to discuss reduction of impact energy and apply the thesis to improve the punchability on the CEM‐1 copper clad laminate. Experimental results demonstrate that the core structure can be modified with different phenolic resin; when phenolic resin PF‐440 of a smaller molecular weight is used as the modified agent, the impact energy can be lowered by 17%. In addition, three kinds of inorganic fillers, such as TiO2, Al(OH)3, SiO2, are added and the core and face structure were modified separately. Adding these fillers has a small effect on lowering the impact energy and no clear evidence of tendency, while the phenolic resin has significant effect. When 10 phr TiO2 is added to face, the impact energy can be lowered around 60% and has a visible effect on improving the punchability improvement of CEM‐1 copper clad laminate. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3381–3386, 2006
Rheological properties of PDMS filled with CaCo3: The effect of filler particle size and concentration
Authors: Zhou Yabin , Wang Shifeng , Zhang Yong , Zhang Yinxi , Jiang Xuhua , Yi Dengfeng
Published: June 2006

The effects of filler particle size and concentration on the rheological properties of hydroxyl terminated polydimethylsiloxane (HO‐PDMS) filled with calcium carbonate (CaCO3) were investigated by an advanced rheometric expansion system (ARES). The Casson model was used to describe the relationship between shear stress and shear rate for steady‐state measurement. Micron‐CaCO3 could not afford the CaCO3/HO‐PDMS suspensions obvious shear thinning behavior and a yield stress high enough, whereas nano‐CaCO3 could provide the suspensions with remarkable shear thinning behavior and high yield stress. Incorporation of nano‐CaCO3 into HO‐PDMS resulted in the transformation of HO‐PDMS from a mainly viscous material to a mainly elastic material. With increasing nano‐CaCO3 content, shear thinning behavior of nano‐CaCO3/HO‐PDMS suspensions became more obvious. Remarkable yield stress was observed in nano‐CaCO3/HO‐PDMS suspensions with high filler content, and increased with increasing nano‐CaCO3 content. The degree of thixotropy was quantitatively determined using a thixotropic loop method. It was found that nano‐CaCO3 favored more the buildup of filler network structure in the suspensions than micron‐CaCO3 at the same weight fraction. Furthermore, increasing nano‐CaCO3 content accelerated the establishment of filler network structure in the nano‐CaCO3/HO‐PDMS suspensions. An overshoot phenomenon was observed in the nano‐CaCO3/HO‐PDMS suspensions at high shear rates. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3395–3401, 2006
Poly(1,3‐disila‐1,3‐diphenyl‐2‐oxaindane)‐diphenylsiloxane‐poly(dimethylsiloxane) block copolymers
Authors: Mukbaniani O. , Matsaberidze M. , Achelashvili V. , Mukbaniani N. , Samsonia A.
Published: June 2006

The heterofunctional condensation of 1,3‐dichloro‐1,3‐disila‐1,3‐diphenyl‐2‐oxaindane with dihydroxydiphenylsilane at various ratios of initial compounds in the presence of amines was carried out, and α,ω‐dihydroxy(1,3‐disila‐1,3‐diphenyl‐2‐oxaindane)‐diphenylsiloxane oligomers with various degrees of condensation were obtained. Corresponding block copolymers were obtained by heterofunctional polycondensation of synthesized α,ω‐dihydroxy(1,3‐disila‐1,3‐diphenyl‐2‐oxaindane)‐diphenylsiloxane oligomers with α,ω‐dichlorodimethylsiloxanes in the presence of amines. Thermogravimetry, gel permeation chromatography, differential scanning calorimetry, and wide‐angle X‐ray analysis were carried out on the synthesized block coplymers. Differential scanning calorimetry and wide‐angle X‐ray studies of these copolymers showed that their properties were determined by the ratio of the lengths of the flexible linear poly(dimethylsiloxane) and rigid poly(1,3‐disila‐1,3‐diphenyl‐2‐oxaindane)‐diphenylsiloxane fragments in the main macromolecular chain. Two‐phase systems were obtained with specific flexible and rigid fragment length values in synthesized block copolymers. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3462–3467, 2006
Encapsulation of titanium dioxide in styrene/n‐butyl acrylate copolymer by miniemulsion polymerization
Authors: Al‐Ghamdi Ghurmallah H. , Sudol E. David , Dimonie Victoria L. , El‐Aasser Mohamed S.
Published: June 2006

Miniemulsion copolymerization of styrene/n‐butyl acrylate was investigated as a means of encapsulating hydrophilic titanium dioxide (TiO2) in a film‐forming polymer. Dispersion studies of the TiO2 were first carried out to determine the choice of stabilizer, its concentration, and the dispersion process conditions for obtaining stable TiO2 particles with minimum particle size. Through screening studies of various functional stabilizers and shelf‐life stability studies at both room and polymerization temperatures, Solsperse 32,000 was selected to give relatively small and stable TiO2 particles at 1 wt % stabilizer and with 20–25 min sonification. The subsequent encapsulation of the dispersed TiO2 particles in styrene/n‐butyl acrylate copolymer (St/BA) via miniemulsion polymerization was carried out and compared with a control study using styrene monomer alone. The lattices resulting from the miniemulsion encapsulation polymerizations were characterized in terms of the encapsulation efficiencies (via density gradient column separations; DGC) and particle size (via dynamic light scattering). Encapsulation efficiencies revealed that complete encapsulation of all of the TiO2 by all of the polymer was not achieved. The maximum encapsulation efficiencies were 79.1% TiO2 inside 61.7% polystyrene and 63.6% TiO2 inside 38.5% St/BA copolymer. As the density of the particles collected from the DGC increased from one layer to another, both the average particle size and the number of the TiO2 particles contained in each latex particle increased. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3479–3486, 2006
Preparation and electroresponsive property of poly(vinyl alcohol)/sodium alginate composite hydrogel
Authors: Li R. X. , Zhang X. Z. , Zhao J. S. , Wu J. M. , Guo Y. , Guan J.
Published: June 2006

Poly(vinyl alcohol) (PVA)/sodium alginate composite hydrogel was prepared by solidifing the blending solution of PVA and sodium alginate, then freezing and thawing repeatedly. In the direct current electric field, the composite hydrogel in aqueous NaCl solution swelled, contracted, and bent. The gel's bending speed and maximum bending degree increased with increase in the electric field intensity and the concentration of NaCl solution. The maximum bending degree increased with increase in the sodium alginate content in the composition hydrogel. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3493–3496, 2006
Structure and processability of iodinated poly(vinyl alcohol) (III)‐structure of films iodinated in solution before casting
Authors: Joo Shin Eun , Hun Lee Yang , Chul Choi Suk
Published: June 2006

Films iodinated at solution before casting (IBC films) were prepared by casting aqueous solutions of 10 wt % poly(vinyl alcohol) (PVA) containing selected quantities of I2/KI. The quantity of I2/KI was controlled to obtain 15.2, 39.8, 83.2, 117.0, and 140.1%. The Thermogravimetry (TG) curves of the IBC film exhibited three distinct zones corresponding to the evaporation of H2O and I2 molecules (zone I), evaporation of I2 and partial decomposition of side groups (OH) (zone II), degradation of the remaining side groups and partial degradation of the main chain (zone III‐1), and degradation of the remaining main chain and the char zone corresponding to KI. The crystalline structure of the film with a weight gain of 15.2% was almost the same as that of the pure PVA, and the film with the weight gain of 140% was almost amorphous. The differential scanning calorimetry (DSC) thermograms of the IBC films with a weight gain of 15.2% and 39.8% indicated endothermic single or double peaks at around 180°C, corresponding to the crystal melting and degradation of side groups; those with weight gains of 83.2% and above indicated exothermic peaks at around 170°C, corresponding to crystallization, and broad endothermic peak at around 180–200°C, corresponding to the crystal melting and degradation of side groups. The dynamic mechanical αa transition of the IBC film with the weight gain of 140.1% appeared at around 20°C. X‐ray diffraction and DSC analysis of deiodinated films show that the crystal structure, on deiodination of all the IBC films, regardless of crystallinity, returned to that of the pure PVA. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3497–3502, 2006
Mechanical and morphological properties of carbon fiber reinforced–modified epoxy composites
Authors: Guduri B. R. , Luyt A. S.
Published: June 2006

Epoxy, prepared through aminomethyl 3,5,5‐trimethylcyclohexylamine hardening of diglycidylether of bisphenol‐A (DGEBA) prepolymer, toughened with polycarbonate (PC) in different proportions, and reinforced with carbon fiber, was investigated by differential scanning calorimetry, tensile and interlaminar shear strength testing, and scanning electron microscopy (SEM). A single glass transition temperature was found in all compositions of the epoxy/PC blend system. The tensile properties of the blend were found to be better than that of the pure epoxy matrix. They increased with PC content up to 10%, beyond which they decreased. The influence of carbon fiber orientation on the mechanical properties of the composites was studied, where the fiber content was kept constant at 68 wt %. Composites with 45° fiber orientation were found to have very weak mechanical properties, and the mechanical properties of the blend matrix composites were found to be better than those of the pure epoxy matrix composites. The fracture and surface morphologies of the composite samples were characterized by SEM. Good bonding was observed between the fiber and matrix for the blend matrix composites. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3529–3536, 2006
A comparison of chemical systems for luminometric determination of antioxidant capacity towards individual reactive oxygen species
Authors: Komrskova Daniela , Lojek Antonin , Hrbac Jan , Ciz Milan
Published: June 2006

The aim of the study was to investigate the reactive oxygen species (ROS) production in the hypoxanthine–xanthinoxidase (HX–XO), hydrogen peroxide–ferrous sulphate (H2O2–FeSO4) and hydrogen peroxide (H2O2) systems by using various concentrations of ROS scavengers, such as superoxide dismutase (SOD), dimethylthiourea (DMTU) or catalase (CAT). Luminol (0.8 mmol/L) was dissolved in a borate buffer, pH 9.0, and was used as a luminophor in the chemiluminescence (CL) measurements. In the HX–XO system SOD, CAT and DMTU deepened the CL signal, whereas in the H2O2–FeSO4 system, only CAT and DMTU deepened the CL signal, and in the H2O2 system SOD and CAT increased and DMTU deepened the CL signal. Electron spin resonance (ESR) measurements were performed only in the H2O2–FeSO4 system. 5,5‐dimethyl‐pyrroline‐N‐oxide (DMPO) was used as a spin trap. According to typical ESR spectra, .OH was produced in this chemical system. It can be concluded that the chemical systems do not produce single reactive oxygen species but a mixture of them. Copyright © 2006 John Wiley & Sons, Ltd.
Fiber type composition and maximum shortening velocity of muscles crossing the human shoulder
Authors: Srinivasan R.C. , Lungren M.P. , Langenderfer J.E. , Hughes R.E.
Published: June 2006

A study of the fiber type composition of fourteen muscles spanning the human glenohumeral joint was carried out with the purpose of determining the contribution of fiber types to overall muscle cross‐sectional area (CSA) and to estimate the maximum shortening velocity (Vmax) of those muscles. Muscle biopsies were procured from 4 male cadavers (mean age 50) within 24 hr of death, snap frozen, mounted, and transversely sectioned (10 μm). Slides were stained for myofibrillar ATPase after alkaline preincubation. Photoimages were taken of defined areas (100 fibers) using the Bioquant system, and fiber type and CSA were measured from these images. Staining for mATPase produced three different fiber types: slow‐oxidative (SO), fast‐oxidative‐glycolytic (FOG), and fast‐glycolytic (FG). On average, the muscle fiber type composition ranged from 22 to 40% of FG, from 17 to 51% of FOG, and from 23 to 56% of SO. Twelve out of the 14 muscles had average SO proportions ranging from 35 to 50%. Vmax was calculated from the fiber type contribution relative to CSA and shortening velocity values taken from the literature. The maximum velocities of shortening presented here provide a physiological basis for the development of human shoulder musculoskeletal models suitable for predicting muscle forces for functionally relevant tasks encompassing conditions of muscle shortening and lengthening. Clin. Anat. 20:144–149, 2007. © 2006 Wiley‐Liss, Inc.
Three‐dimensional CT angiography: A new technique for imaging microvascular anatomy
Authors: Tregaskiss Ashley P. , Goodwin Adam N. , Bright Linda D. , Ziegler Craig H. , Acland Robert D.
Published: June 2006

To date there has been no satisfactory research method for imaging microvascular anatomy in three dimensions (3D). In this article we present a new technique that allows both qualitative and quantitative examination of the microvasculature in 3D. In 10 fresh cadavers (7 females, 3 males, mean age 68 years), selected arteries supplying the abdominal wall and back were injected with a lead oxide/gelatin contrast mixture. From these regions, 30 specimens were dissected free and imaged with a 16‐slice spiral computed tomographic (CT) scanner. Using three‐dimensional CT (3D‐CT) angiography, reconstructions of the microvasculature of each specimen were produced and examined for their qualitative content. Two calibration tools were constructed to determine (1) the accuracy of linear measurements made with CT software tools, and (2) the smallest caliber blood vessel that is reliably represented on 3D‐CT reconstructions. Three‐dimensional CT angiography produced versatile, high quality angiograms of the microvasculature. Correlation between measurements made with electronic calipers and CT software tools was very high (Lin's concordance coefficient, 0.99 (95% CI 0.99–0.99)). The finest caliber of vessel reliably represented on the 3D‐CT reconstructions was 0.4 mm internal diameter. In summary, 3D‐CT angiography is a simple, accurate, and reproducible method that imparts a much improved perception of anatomy when compared with existing research methods. Measurement tools provide accurate quantitative data to aid vessel mapping and preoperative planning. Further work will be needed to explore the full utility of 3D‐CT angiography in a clinical setting. Clin. Anat. 20:116–123, 2007. © 2006 Wiley‐Liss, Inc.
A case of a cilioretinal artery supplying the entire retina
Authors: Hegde V. , Deokule S. , Matthews T.
Published: June 2006

The cilioretinal artery commonly supplies a small area of the retina, usually the macula. It can serve a valuable purpose in preserving the central vision in central retinal artery occlusion. We describe a case, where the total retinal circulation is from the cilioretinal artery in one eye and an abnormal central retinal artery branching in the other eye. The clinical relevance of cilioretinal artery in the eye is discussed. Clin. Anat. 19:645–647, 2006. © 2006 Wiley‐Liss, Inc.
Promoter methylation of the secreted frizzled‐related protein 1 gene SFRP1 is frequent in hepatocellular carcinoma
Authors: Shih Yu‐Lueng , Shyu Rong‐Yuan , Hsieh Chung‐Bao , Lai Hung‐Cheng , Liu Kuo‐Yu , Chu Tang‐Yuan , Lin Ya‐Wen
Published: June 2006

BACKGROUND.

The secreted frizzled‐related protein 1 gene (SFRP1) encodes a Wnt/β‐catenin signaling antagonist and frequently is inactivated by promoter methylation in many tumors. However, the role of SFRP1 in hepatocellular carcinoma (HCC) is not clear. Therefore, the authors investigated whether methylation of the SFRP1 promoter is common in HCC and whether it may influence SFRP1 expression.

METHODS.

Four HCC cell lines, 54 HCCs, 42 cirrhotic livers, 21 livers with chronic hepatitis, and 15 normal control tissues were analyzed for 1) SFRP1 promoter methylation by using methylation‐specific polymerase chain reaction analysis and bisulfite sequencing, 2) SFRP1 messenger RNA expression by using quantitative reverse transcriptase‐polymerase chain reaction analysis, and 3) loss of heterozygosity (LOH) by using microsatellite markers flanking the SFRP1 locus. HCC cells were treated with the demethylating agent 5‐aza‐2′‐deoxycytidine to determine whether it could restore SFRP1 expression.

RESULTS.

SFRP1 promoter methylation was observed in 75%, 48.2%, 21.4%, 14.3% and 0% in HCC cell lines, primary HCCs, cirrhotic livers, livers with chronic hepatitis, and normal control tissues, respectively. Methylation of the SFRP1 promoter region in HCCs increased significantly compared with control tissues. All samples with SFRP1 methylation showed down‐regulation of SFRP1 expression. Demethylation treatment with 5‐aza‐2′‐deoxycytidine in HCC cells restored SFRP1 expression. Moreover, LOH of markers D8S505 and D8S1722 was found in 25% and 27.6% of the informative samples, respectively.

CONCLUSIONS.

The current results suggested that promoter hypermethylation of SFRP1 is a common event in HCC and plays an important role in the regulation of SFRP1 expression. In addition to methylation‐mediated down‐regulation of SFRP1, LOH also may play a role. Cancer 2006. © 2006 American Cancer Society.
T‐cell large granular lymphocyte leukemia
Authors: Osuji Nnenna , Matutes Estella , Tjonnfjord Geir , Grech Henri , Del Giudice Ilaria , Wotherspoon Andrew , Swansbury John G. , Catovsky Daniel
Published: June 2006

BACKGROUND.

To the authors' knowledge, there is no standard treatment for patients with T‐cell large granular lymphocyte (LGL) leukemia. Available data are limited by patient numbers and coexisting pathologies.

METHODS.

The authors report on the use of immunosuppressants (cyclosporin A [CSA] and low‐dose oral methotrexate [MTX] given continuously) and cytotoxic agents in the treatment of 29 patients with T‐cell LGL leukemia age over the past 20 years.

RESULTS.

The overall response rate (ORR) to MTX (n = 8 patients) was 85.7% (complete hematologic response [CHR] rate, 14.3%; partial response [PR] rate, 71.4%) with dose‐dependent responses observed and safe usage of doses >10 mg/m2 per week in 2 patients. The ORR to CSA (n = 23 patients) was 78.2% (CHR rate, 30.4%; PR rate, 47.8%). The median time to response for both agents was 1 month. Toxicity, although it was minor in most patients and was more common in the CSA group, included second malignancies in 5 patients. An ORR of 67% (all CHR) was attained with pentostatin (n = 4 patients); recurrences developed after a median of 4.6 years. Successful retreatment with pentostatin was possible but with increasing drug resistance. Cyclophosphamide induced CHR that lasted >7 years with bone marrow clearance in 1 of 4 patients. Alemtuzumab induced a PR in 1 patient who had refractory disease.

CONCLUSIONS.

Both MTX and CSA were efficacious in the treatment of T‐cell LGL leukemia but generally required long‐term maintenance therapy. The authors highlight the risks of second malignancies and persistence of bone marrow disease. Although MTX and CSA were effective as first‐line therapy, alemtuzumab and pentostatin merit further investigation, particularly for refractory disease. Cancer 2006 © 2006 American Cancer Society.
Emerging implications of nanotechnology on cancer diagnostics and therapeutics
Authors: Cuenca Alex G. , Jiang Huabei , Hochwald Steven N. , Delano Matthew , Cance William G. , Grobmyer Stephen R.
Published: June 2006

Nanotechnology is multidisciplinary field that involves the design and engineering of objects <500 nanometers (nm) in size. The National Cancer Institute has recognized that nanotechnology offers an extraordinary, paradigm‐changing opportunity to make significant advances in cancer diagnosis and treatment. In the last several decades, nanotechnology has been studied and developed primarily for use in novel drug‐delivery systems (e.g. liposomes, gelatin nanoparticles, micelles). A recent explosion in engineering and technology has led to 1) the development of many new nanoscale platforms, including quantum dots, nanoshells, gold nanoparticles, paramagnetic nanoparticles, and carbon nanotubes, and 2) improvements in traditional, lipid‐based nanoscale platforms. The emerging implications of these platforms for advances in cancer diagnostics and therapeutics form the basis of this review. A widespread understanding of these new technologies is important, because they currently are being integrated into the clinical practice of oncology. Cancer 2006. © 2006 American Cancer Society.
Pilot trial of bone‐targeted therapy with zoledronate, thalidomide, and interferon‐γ for metastatic renal cell carcinoma
Authors: Tannir Nizar , Jonasch Eric , Pagliaro Lance C. , Mathew Paul , Siefker‐Radtke Arlene , Rhines Laurence , Lin Patrick , Tibbs Rita , Do Kim‐Anh , Lin Sue‐Hwa , Tu Shi‐Ming
Published: June 2006

BACKGROUND.

The purpose of the study was to evaluate the efficacy and safety of a bone‐targeted regimen consisting of zoledronate, thalidomide, and interferon‐γ in patients with renal cell carcinoma and bone metastases.

METHODS.

Eligible patients had radiographic evidence of bone metastasis. Impending pathologic fractures or spinal cord compressions must have been controlled by surgery or radiation therapy before enrollment. Zoledronate (4 mg) was given intravenously every 4 weeks, thalidomide (300 mg) was given orally once a day, and interferon‐γ (100 μg) was given subcutaneously once a week. Patients were evaluated for time to skeletal‐related events, the appearance of calcification in osteolytic metastases, and levels of the bone formation/resorption markers.

RESULTS.

Fifteen patients were treated between November 2002 and November 2003; 12 had previously undergone surgery, radiation, or embolization for their bone metastases; 11 had more than 3 sites of bone involvement; and 9 also had nonosseous metastases in the lung, liver, lymph node, pancreas, or adrenal gland. The median time to progression was 8.3 weeks (range, 2.1–48 weeks). The median time to a skeletal‐related event was 12.0 weeks (range, 3.9–46.4 weeks). Two patients discontinued treatment because of adverse drug reactions (1 deep venous thrombosis and 1 myocardial infarction). Two patients experienced pain improvement and developed calcification in osseous metastases; these patients also showed favorable changes in bone marker levels.

CONCLUSIONS.

In this pilot study a bone‐targeted regimen combining zoledronate, thalidomide, and interferon‐γ was well tolerated and might provide clinical benefit for a small subset of patients with renal cell carcinoma and bone metastases. Cancer 2006. © 2006 American Cancer Society.
Study of Pax6 mutant rat revealed the association between upper incisor formation and midface formation
Authors: Kriangkrai Rungarun , Chareonvit Suconta , Yahagi Koichi , Fujiwara Michio , Eto Kazuhiro , Iseki Sachiko
Published: June 2006

In this study, we investigated the process of supernumerary upper incisor formation in the Pax6 mutant rat, rSey2/rSey2, which exhibits a facial cleft between the medial nasal and maxillary processes. Histological investigation and epithelial labeling studies of wild type rat embryos indicated that the upper incisor develops by fusion of two primary dental placodes (PDPs) in the medial nasal process with a contribution from the epithelium of the maxillary process. In the rSey2/rSey2 embryo, both PDPs are formed but they stay apart, then subsequently these PDPs independently develop into upper incisor tooth buds. In order to examine if the failure of the two placodes to fuse is due to the cleft between the maxillary and medial nasal processes, maxillary and medial nasal process fusion was inhibited with a barrier in wild type embryos. This resulted in the maintenance of the two distinct PDPs. These results demonstrate that fusion of the facial processes reduces the number of odontogenic placodes and is required to assemble all components at one site for rat upper incisor formation. The results also provide further insight into the mechanism of supernumerary incisor formation in human cleft lip conditions. Developmental Dynamics 235:2134–2143, 2006. © 2006 Wiley‐Liss, Inc.
A mouse carrying the green fluorescent protein gene targeted to the Pdx1 locus facilitates the study of pancreas development and function
Authors: Holland Andrew M. , Micallef Suzanne J. , Li Xueling , Elefanty Andrew G. , Stanley Edouard G.
Published: June 2006

The pancreatic and duodenal homeobox gene 1 (Pdx1) has multiple roles in the specification and development of foregut endoderm‐derived tissues. We report the characterization of a mouse line in which the gene encoding green fluorescent protein (GFP) has been targeted to the Pdx1 locus, allowing the visualization of Pdx1 expressing cells. Analysis of GFP expression during development showed that the reporter faithfully reproduced the known expression pattern of Pdx1. We demonstrate the utility of this mouse line for the isolation of Pdx1+ cells by fluorescence‐activated cell sorting and for the real‐time observation of Pdx1+ cells in an ex vivo embryonic pancreas culture system. This mouse model should prove useful for the study of pancreas development and regeneration. genesis 44:304–307, 2006. © 2006 Wiley‐Liss, Inc.
Immunosuppressive role of semaphorin‐3A on T cell proliferation is mediated by inhibition of actin cytoskeleton reorganization
Authors: Lepelletier Yves , Moura Ivan Cruz , Hadj‐Slimane Réda , Renand Amédée , Fiorentino Susana , Baude Cédric , Shirvan Anat , Barzilai Ari , Hermine Olivier
Published: June 2006

Timely negative regulation of the immune system is critical to allow it to perform its duty while maintaining it under tight control to avoid overactivation. We previously reported that the neuronal receptor neuropilin‐1 (NP‐1) is expressed in human lymph nodes. However, the role of NP‐1 interaction with its physiological ligand semaphorin‐3A (Sema‐3A) on immune cells remains elusive. Here we show that Sema‐3A is expressed by activated DC and T cells, and that its secretion in DC/T cell cocultures is delayed. Sema‐3A/NP‐1 interaction down‐modulated T cell activation since addition of Sema‐3A in DC/T cell cocultures dramatically inhibited allogeneic T cell proliferation. More importantly, neutralization by blocking antibodies or by antagonist peptide of endogenous Sema‐3A produced by DC/T cell cocultures resulted in a 130% increase in T cell proliferation. Sema‐3A acted directly on T cells, since it could block anti‐CD3/CD28‐stimulated proliferation of T cells. Finally, immunomodulatory functions of Sema‐3A relied on the blockage of actin cytoskeleton reorganization, affecting TCR polarization and interfering with early TCR signal transduction events such as ZAP‐70 or focal adhesion kinase phosphorylation. Therefore, we propose that Sema‐3A secretion and the resulting NP‐1/Sema‐3A interaction are involved in a late negative feedback loop controlling DC‐induced T cell proliferation.
Higher‐order CpG‐DNA stimulation reveals distinct activation requirements for marginal zone and follicular B cells in lupus mice
Authors: Brummel Rachel , Roberts Tara L. , Stacey Katryn J. , Lenert Petar
Published: June 2006

Mouse follicular B cells express TLR9 and respond vigorously to stimulation with single‐stranded CpG‐oligodeoxynucleotides (ODN). Surprisingly, follicular B cells do not respond to direct stimulation with other TLR9 ligands, such as bacterial DNA or class A(D) CpG‐ODN capable of forming higher‐order structures, unless other cell types are present. Here, we show that priming with interferons or with B cell‐activating factor, or simultaneous co‐engagement of the B cell receptor for antigen (BCR), can overcome this unresponsiveness. The effect of interferons occurs at the transcriptional level and is mediated through an autocrine/paracrine loop, which is dependent on IRF‐1, IL‐6 and IL‐12 p40. We hypothesize that the lack of bystander activation of follicular B cells with more complex CpG ligands may be an important safety mechanism for avoiding autoimmunity. This will prevent resting B cells from responding to foreign or self‐derived hypomethylated double‐stranded CpG ligands unless these ligands are either delivered through the B cell receptor or under conditions where B cells are simultaneously co‐engaged by activated plasmacytoid dendritic cells or TH1 cells. A corollary is that the heightened responsiveness of lupus B cells to TLR9‐induced stimulation cannot be ascribed to unprimed follicular B cells, but is rather mediated by hypersensitive marginal zone B cells.
TCR ligand avidity determines the modeof B‐Raf/Raf‐1/ERK activation leading to the activationof human CD4+ T cell clone
Authors: Tsukamoto Hirotake , Irie Atsushi , Chen Yu‐Zhen , Takeshita Kumiko , Kim Jeong‐Ran , Nishimura Yasuharu
Published: June 2006

The interactions between peptide/MHC complexes and their cognate TCR are essential for various T cell responses. However, the relationship between the avidity of TCR ligand and the subsequent intracellular signaling through the TCR is still unclear. To investigate the effects of TCR ligand avidity on TCR‐mediated signaling, we established L cells expressing HLA‐DR4 molecules covalently linked with agonistic peptide (high‐affinity ligand) or altered peptide ligand (APL; low‐affinity ligand) at various densities as APC for a cognate human CD4+ T cell clone. Using this system, we demonstrated that the T cell clone stimulated with APL/HLA‐DR4 complexes presented at an excessive density provoked the up‐regulation of CD69, IL‐2 production and proliferation, but no detectable phosphorylation of ZAP‐70/LAT/SLP‐76. Furthermore, in contrast to the high‐affinity stimulation, the low‐affinity stimulation evoked delayed and sustained activation of the B‐Raf/extracellular signal‐regulated kinase (ERK) pathway without Raf‐1 activation. The strength and duration of B‐Raf/ERK activations closely correlated with the density of the TCR ligand. A knockdown approach confirmed that B‐Raf activation was indispensable for the APL‐induced T cell responses. These observations suggest that the differences in TCR‐peptide/MHC interactions reflect the strength and duration of B‐Raf/Raf‐1/ERK activation in the human CD4+ T cells.
Immunoglobulin promotes the diversity and the function of T cells
Authors: João Cristina , Ogle Brenda M. , Geyer Susan
Published: June 2006

It is generally accepted in immunology that while T and B cells collaborate for the production of antibodies in response to protein antigens, T cells develop and function in the absence of B cells. However, B cell‐deficient subjects and mice have unexplained cellular immune defects. Here, we examined the contribution of B cells/Ig to the generation of diversity and function of T cells. Mice lacking B cells and Ig (JH–/–) or having oligoclonal B cells (QM) had a profoundly contracted T cell receptor (TCR) Vβ repertoire: 0.08 and 1.3% of wild type, respectively. Rejection of H‐Y‐incompatible skin grafts in QM and JH–/– mice was significantly delayed (median, 43 and 22 days, respectively) compared to wild‐type mice (median, 16 days). Furthermore, reduction of the TCR Vβ diversity by thymectomy in wild‐type mice significantly increased survival of H‐Y‐incompatible skin grafts, and reconstitution of the T cell diversity in QM mice with Ig Fab fragments significantly decreased survival of the skin grafts. These results indicate that B cells and/or Ig "help" T cells through the generation and maintenance of T cell diversity, improving T cell function. Our results may have important implications for therapy and immune reconstitution in the context of AIDS, cancer, autoimmunity and post‐myeloablative treatments.
BAFF costimulation of Toll‐like receptor‐activatedB‐1 cells
Authors: Ng Lai Guan , Ng Chee‐Hoe , Woehl Blanche , Sutherland Andrew P. R. , Huo Jianxin , Xu Shengli , Mackay Fabienne , Lam Kong‐Peng
Published: June 2006

B cell‐activating factor belonging to the TNF family (BAFF) and its receptor BAFF‐R play critical roles in the maturation and survival of conventional peripheral B cells. However, they appeared to be dispensable for the generation and maintenance of CD5+ B‐1 cells as BAFF–/– and BAFF‐R–/– mice have normal B‐1 cell populations. Hence, it is presently unclear if B‐1 cells are responsive to BAFF and if BAFF regulates some aspects of B‐1 cell function. We show here that BAFF‐R and transmembrane activator and CAML interactor (TACI) are the major receptors expressed by B‐1 cells. Specifically, we show that BAFF treatment of B‐1 cells leads to increased NF‐κB p100 processing and CD21/CD35 expression. Interestingly, toll‐like receptor (TLR) engagement of B‐1 cells augmented the surface expression of BAFF receptors and rendered them responsive to BAFF costimulation, as evidenced by their increased proliferation, expression of cell surface activation markers and secretion of the pro‐inflammatory cytokine IL‐6 and the anti‐inflammatory cytokine IL‐10. This costimulatory effect is achieved primarily through BAFF‐R as BAFF failed to costimulate B‐1 cells obtained from A/WySnJ mice which have defective BAFF‐R signaling. Thus, as TLR are innate immune receptors and B‐1 cells are "innate‐like" lymphocytes, our data provide evidence that BAFF plays a role in innate immunity.
Coy decoy with a new ploy: Interceptor controls the levels of homeostatic chemokines
Authors: Haraldsen Guttorm , Rot Antal
Published: June 2006

A new subfamily of chemokine receptors is emerging that do not signal along classical G‐protein‐mediated pathways. Instead, these “silent” receptors efficiently internalize their cognate chemokine ligands, hence their suggested name, “chemokine interceptors”, for internalizing receptors. Two of these interceptors, DARC and D6, possess intriguing patterns of tissue expression and are believed to be involved in controlling the local levels of proinflammatory chemokines. In this issue of the European Journal of Immunology, the biochemical properties of a third silent chemokine receptor, CCX‐CKR, have been characterized and it is suggested that it may act as a scavenger for homeostatic chemokines, pointing to a broad and significant role for this group of chemokine binding molecules in chemokine biology.

See accompanying article http://www.dx.doi.org/10.1002/eji.200535716
Exposure to wood smoke, HPV infection, and genetic susceptibility for cervical neoplasia among women in Colombia
Authors: Sierra‐Torres Carlos H. , Arboleda‐Moreno Yexania Y. , Orejuela‐Aristizabal Leonora
Published: June 2006

Cervical cancer is the second leading cause of death from cancer among women in Colombia (16/100,000). Infection with high‐risk human papillomavirus (HPV) plays a major role in the etiology of high‐grade squamous intraepithelial lesions (HSILs). Exposure to chemical agents may be a cofactor for tumor induction, and individual genetic differences in the metabolism of these chemical agents may affect the susceptibility of individuals towards the development of HSIL. In this case–control study, a total of 91 cases with HSIL and 92 healthy controls, frequency‐matched by age and place of origin, were recruited, and their frequencies of CYP2E1, GSTM1, and GSTT1 polymorphism were determined. We then evaluated the association of these polymorphisms, by themselves and in combination with wood smoke exposure and HPV‐infection status, with the risk of HSIL. The results indicate that GSTM1 and GSTT1 polymorphism were not associated with HSIL, although a small increase in risk was observed for individuals who were GSTT1 null (OR = 1.4, 95% CI = 0.57–3.44). Contrary to other investigations, the c2/c2 variant of the CYP2E1 gene was associated with a significant increase in risk after adjusting for wood smoke exposure (OR = 6.3, 95% CI = 1.10–36.38) or wood smoke exposure and HPV‐infection status (OR = 10.7, 95% CI = 1.76–65.58). Wood smoke exposure also increased the risk of HSIL among CYP2E1 c2/c2 HPV‐positive women (OR = 3.3, CI = 0.50–22.50); however, the increase did not achieve statistical significance. Our study provides tantalizing evidence that genetic differences in the metabolism of wood smoke carcinogens, particularly metabolism by CYP2E1, may confer susceptibility for HSIL development. Further investigations with larger populations will be needed to confirm this association, which may provide important information for improving cervical cancer prevention programs. Environ. Mol. Mutagen., 2006. © 2006 Wiley‐Liss, Inc.
Evaluation of micronucleus frequencies and DNA damage in glass workers exposed to arsenic
Authors: Vuyyuri Saleha B. , Ishaq Mohamed , Kuppala Danadevi , Grover Paramjit , Ahuja Y.R.
Published: June 2006

Arsenic (As) is a known human carcinogen; however, very little is known about the health consequences of occupational exposure to As. In the present study, we assessed the genotoxic damage in the blood cells and in the buccal cells of south Indian glass factory workers who are occupationally exposed to As. The As content in the whole blood of 200 workers and 165 controls was evaluated with inductively coupled plasma mass spectrometry. Blood leukocytes from the subjects were monitored for the level of DNA damage using the Comet assay (mean comet tail length); buccal cells were used to determine the frequency of micronuclei (MN). The mean As concentration was significantly higher in the workers (56.76 μg/L) than in the controls (11.74 μg/L) (P < 0.001). The workers also had increased frequencies of MN in the buccal cells and increased levels of DNA damage in leukocytes compared to the controls (P < 0.001). There were significant correlations between the genotoxicity endpoints that were evaluated and blood As concentration, smoking, age, and the duration of working in the factory. Also, a significant correlation was observed between the frequency of MN and comet tail‐length for the worker samples. Our findings indicate that chronic occupational exposure to As is genotoxic and that the Comet assay and micronucleus test are useful assays for evaluating genotoxicity in humans occupationally exposed to As. Environ. Mol. Mutagen., 2006. © 2006 Wiley‐Liss, Inc.
Innate immune response to human bone marrow fibroblastic cell implantation in CB17 scid/beige mice
Authors: Xia Zhidao , Taylor Philip R. , Locklin Rachel M. , Gordon Siamon , Cui Zhanfeng , Triffitt James T.
Published: June 2006

Immunocompromised mouse models have been extensively used to assess human cell implantation for evaluation of cytotherapy, gene therapy and tissue engineering strategies, as these mice are deficient in T and B lymphoid cells. However, the innate immune response and its effect on human cell xenotransplantation in these mouse models are mainly unknown. The aim of this study is to characterise the myeloid populations in the spleen and blood of CB17 scid beige (CB17 sb) mice, and to study the inflammatory cell responses to xenogeneic implantation of enhanced green fluorescent protein (GFP)‐labelled human bone marrow fibroblastic (HBMF) cells into CB17 sb mice. The results indicate that even though CB17 sb mice are deficient in B‐ and T‐cells, they exhibit some increases in their monocyte (Mo), macrophage (MΦ) and neutrophil (Neu) populations. NK cell and eosinophil populations show no differences compared with wild‐type Balb/C mice. An innate immune response, identified by CR3 (CD11b/CD18)‐positive myeloid inflammatory cells and F4/80‐positive macrophages, was evident in the tissues where HBMF cells were implanted. As a consequence, the majority of implanted HBMF cells were eliminated by 4 weeks after implantation. Interestingly, the mineralised matrix formed by osteogenic HBMF cells was also eroded by multinuclear MΦ‐like giant cells. We conclude that CB17 sb mice retain active innate immune cells, which respond to HBMF cell xenotransplantation. This study highlights the importance of the innate immune cells in the anti‐xenograft response and suggests that strategies to block the activities of these cells may ameliorate the progressive long‐term elimination of xenotransplants. J. Cell. Biochem. 98: 966–980, 2006. © 2006 Wiley‐Liss, Inc.
TGF‐β2 stimulates cranial suture closure through activation of the Erk‐MAPK pathway
Authors: Lee Sang‐Won , Choi Kang‐Young , Cho Je‐Yoel , Jung Sung‐Hwa , Song Kun‐Bae , Park Eui‐Kyun , Choi Je‐Yong , Shin Hong‐In , Kim Shin‐Yoon , Woo Kyung‐Mi , Baek Jeong‐Hwa , Nam Soon‐Hyeun , Kim Young‐Jin , Kim Hyun‐Jung , Ryoo Hyun‐Mo
Published: June 2006

Cranial sutures are important growth sites of the skull. During suture closure, the dura mater is one of the most important sources of various positive and negative regulatory signals. Previous results indicate that TGF‐β2 from dura mater strongly accelerates suture closure, however, its exact regulatory mechanism is still unclear. In this study, we confirmed that removal of dura mater in calvarial organ culture strongly accelerates sagittal suture closure and that this effect is further enhanced by TGF‐β2 treatment. TGF‐β2 stimulated cell proliferation in the MC3T3‐E1 cell line. Similarly, it stimulated the proliferation of cells in the sutural space in calvarial organ culture. Furthermore, TGF‐β2‐mediated enhanced cell proliferation and suture closure were almost completely inhibited by an Erk‐MAPK blocker, PD98059. These results indicate that TGF‐β2‐induced activation of Erk‐MAPK is an important signaling component that stimulates cell proliferation to enrich osteoprogenitor cells, thereby promoting their differentiation into osteoblasts to achieve a rapid calvarial bone expansion. J. Cell. Biochem. 98: 981–991, 2006. © 2006 Wiley‐Liss, Inc.
Osteogenic growth peptide effects on primary human osteoblast cultures: Potential relevance for the treatment of glucocorticoid‐induced osteoporosis
Authors: Spreafico Adriano , Frediani Bruno , Capperucci Caterina , Leonini Alessandra , Gambera Dario , Ferrata Paolo , Rosini Sergio , Di Stefano Anna , Galeazzi Mauro , Marcolongo Roberto
Published: June 2006

The osteogenic growth peptide (OGP) is a naturally occurring tetradecapeptide that has attracted considerable clinical interest as a bone anabolic agent and hematopoietic stimulator. In vivo studies on animals have demonstrated that the synthetic peptide OGP (10–14), reproducing the OGP C‐terminal active portion [H‐Tyr‐Gly‐Phe‐Gly‐Gly‐OH] increases bone formation, trabecular bone density and fracture healing. In vitro studies performed on cellular systems based on osteoblastic‐like cell lines or mouse stromal cells, have demonstrated that OGP (10–14) increases osteoblast proliferation, alkaline phosphatase (ALKP) activity and matrix synthesis and mineralization. In view of a potential application of OGP (10–14) in clinical therapy, we have tested different concentrations of OGP (10–14) on primary human osteoblast (hOB) cultures. We have observed significant increases of hOB proliferation (+35%), ALKP activity (+60%), osteocalcin secretion (+50%), and mineralized nodules formation (+49%). Our experimental model based on mature hOBs was used to investigate if OGP (10–14) could prevent the effects on bone loss induced by sustained glucocorticoid (GC) treatments. A strong decrease in bone formation has been attributed to the effects of GCs on osteoblastogenesis and osteocyte apoptosis, while an increase in bone resorption was due to a transient osteoblastic stimulation, mediated by the OPG/RANKL/RANK system, of osteoclasts recruitment and activation. Moreover, GCs act on hOBs decreasing the release of osteoprotegerin (OPG) a regulator of the RANKL/RANK interaction. Here, we provide evidences that OGP (10–14) inhibits hOB apoptosis induced by an excess of dexamethasone (−48% of apoptotic cells). Furthermore, we show that OGP (10–14) can increase OPG secretion (+20%) and can restore the altered expression of OPG induced by GCs to physiological levels. Our results support the employment of OGP (10–14) in clinical trials addressed to the treatment of different bone remodeling alterations including the GC‐induced osteoporosis. J. Cell. Biochem. 98: 1007–1020, 2006. © 2006 Wiley‐Liss, Inc.