bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene expression profiling of tumor xenografts: In vivo analysis of organ‐specific metastasis
Authors: Lee Hyerim , Lin Emme C. K. , Liu Limin , Smith Jeffrey W.
Published: September 2003

Mammary carcinoma frequently metastasizes to specific organs, including the regional lymph nodes, the lung and bone marrow. The mechanisms that guide organ‐specific metastasis and the molecular players that are involved remain to be established. To gain insight into this problem, we used an orthotopic model of breast cancer in which the MDA‐MB‐435 cells are implanted into the mouse mammary fat pad. Sublines that preferentially metastasized to specific sites were isolated by excising metastatic tumors and growing explants of these tumors in culture. Cells lines that preferentially metastasize to the lymph node and thoracic cavity were obtained. The gene expression profiles of primary tumors from these sublines were then compared with cDNA arrays containing 5,800 known genes. In tumors that preferentially metastasize to the lymph node, several genes encoding adhesion and matrix proteins were upregulated. Genes encoding proteins involved in metabolism were downregulated. One of the upregulated genes in lymph‐homing tumors was CD73. Immunohistochemistry showed that the CD73 protein is also upregulated in primary tumors of this cell line and that its expression is elevated in the lymph node metastases. CD73 is a transmembrane protein that has previously been implicated in the homing of normal lymphocytes to the nodes. This raises the hypothesis that tumors preferentially metastasize to lymph nodes by using CD73 to mimic part of the lymphocyte homing process. © 2003 Wiley‐Liss, Inc.
Occupational exposure to dyes, metals, polycyclic aromatic hydrocarbons and other agents and K‐ras activation in human exocrine pancreatic cancer
Authors: Alguacil Juan , Porta Miquel , Kauppinen Timo , Malats Núria , Kogevinas Manolis , Carrato Alfredo ,   for the PANKRAS II Study Group
Published: September 2003

ras genes are known critical DNA targets for chemical carcinogens. Exocrine pancreatic cancer (EPC) is the human tumor with the highest prevalence of K‐ras mutations at diagnosis. We analyzed the relationship between past occupational exposure to dyes, metals, polycyclic aromatic hydrocarbons (PAHs) and other agents and mutations in codon 12 of the K‐ras gene in 107 incident cases of EPC. Information on occupational and life‐style factors was obtained from personal interviews conducted during hospital stay. Occupational exposures were examined using industrial hygienists (IH) assessment and the Finnish job‐exposure matrix (Finjem). Specific occupational exposures among K‐ras mutated EPC cases (n = 83) were compared to those of K‐ras wild‐type EPC cases (n = 24) (case‐case analysis). Multivariate‐adjusted odds ratios (OR) and their corresponding 95% confidence limits were estimated by unconditional logistic regression. Cases with K‐ras mutations were significantly more likely than wild‐type cases to have been exposed to dyes and organic pigments (OR 4.8; p<0.05). There was some indication of weaker associations between K‐ras mutations and occupational exposure to lead, PAHs, benzo[a]pyrene, gasoline, nickel, inhalatory exposure to chromium and sedentary work. The association with chromium compounds was stronger for G to T transversions, a finding compatible with experimental studies on mutation spectra for chromium. Results lend moderate support to the hypothesis of indirect relationships between occupational exposure to dyes and organic pigments and the activation of the K‐ras gene in the etiopathogenesis of human exocrine pancreatic cancer. © 2003 Wiley‐Liss, Inc.
Use of plasma MMP‐2 and MMP‐9 levels as a surrogate for tumour expression in colorectal cancer patients
Authors: Tutton Matthew G. , George Mark L. , Eccles Suzanne A. , Burton Sarah , Swift R. Ian , Abulafi A. Muti
Published: September 2003

Matrix metalloproteinases, and notably the gelatinases MMP‐2 and MMP‐9, have important roles in tumour invasion, metastasis and angiogenesis. Our study investigates the distribution of MMP‐2 and MMP‐9 in colorectal cancer, the correlation with plasma levels, changes following surgical resection and whether plasma levels reflect clinical staging and disease course. MMP‐2 and MMP‐9 expression in 48 colorectal tumours and 13 adenomatous polyps was analysed by RT‐PCR, immunohistochemistry, and quantified by ELISA of tumour lysates. Concentrations of MMP‐2 and MMP‐9 in plasma samples from these patients and 36 other patients who underwent curative resections were measured by ELISA prior to and 6–12 months after surgery. MMP‐2 expression was significantly increased in colorectal cancer tissues compared to matched normal colon as measured by ELISA. Active MMP‐2 was localised by immunohistochemistry to regions where tumour cells invaded the muscularis with little staining in more superficial areas. Plasma MMP‐2 levels were also significantly elevated in patients with colorectal cancer, with significant reductions following curative resections at all stages. Similarly, MMP‐9 expression was significantly increased in colorectal cancer tissues, predominantly in the tumour stroma. Plasma levels of MMP‐9 were significantly elevated at all stages in colorectal cancer patients and a significant reduction was seen following curative resections. With both MMP‐2 and MMP‐9, the strongest correlation with clinical staging in colorectal cancer was represented by the total plasma concentration of the enzymes, both falling to within the normal range following curative surgery. Plasma levels of these enzymes may therefore have potential as a noninvasive indicator of invasion or metastasis in colorectal cancer or as a marker of disease status during follow‐up. © 2003 Wiley‐Liss, Inc.
Microsatellite instability in hereditary and sporadic breast cancers
Authors: Adem Camilo , Soderberg Cheryl L. , Cunningham Julie M. , Reynolds Carol , Sebo Thomas J. , Thibodeau Stephen N. , Hartmann Lynn C. , Jenkins Robert B.
Published: September 2003

Sporadic cancers and familial breast cancers are characterized by an increase in genetic instability. Little is known about whether mismatch repair defects accompany this genetic instability. We investigated invasive and/or in situ breast cancers from 30 women with deleterious BRCA1/2 mutations and unclassified variant BRCA1/2 alterations. Forty cases of sporadic breast cancers were also investigated, including 7 medullary carcinomas. Malignant and benign lesions were examined from all cases to better understand tumor progression. Automated immunohistochemistry, with antibodies directed against hMLH1 and hMSH2, was used to screen cases for possible mismatch repair defects. When loss of expression was noted, DNA ploidy was performed by cytomorphometry. DNA, after laser microdissection, was extracted from a majority of familial cases and their corresponding controls, and microsatellite instability analysis was performed. None of the familial or sporadic cases had loss of hMSH2 expression. All but one lesion, a DCIS arising in a deleterious BRCA2 mutation carrier, had loss of hMLH1 expression and a tetraploid profile by image cytomorphometry. There was no MSI in any explored lesions (n = 34), as determined by molecular analysis, including the DCIS with loss of hMLH1 expression. We conclude that DNA mismatch repair defects involving hMLH1 and hMSH2 underexpression are extremely rare events in sporadic and familial breast cancer. Mismatch repair gene mutations may be secondary random events in breast cancer progression. © 2003 Wiley‐Liss, Inc.
Increased expression of the mannose 6‐phosphate/insulin‐like growth factor‐II receptor in breast cancer cells alters tumorigenic properties in vitro and in vivo
Authors: Lee Jason S. , Weiss Jocelyn , Martin Janet L. , Scott Carolyn D.
Published: September 2003

The mannose 6‐phosphate/insulin‐like growth factor‐II receptor (M6P/IGF‐IIR) is thought to act as a suppressor of tumor growth by binding the mitogenic peptide IGF‐II and modulating its extracellular levels via degradation. This receptor has been found to be absent or nonfunctional in a high proportion of breast tumors as a result of LOH and mutation of the gene. In our study, we have examined the effect of increasing expression of M6P/IGF‐IIR on breast cancer cell tumorigenicity. MDA‐MB‐231 breast cancer cells stably transfected with M6P/IGF‐IIR cDNA exhibited not only a greatly reduced ability to form tumors but also a markedly reduced growth rate in nude mice. In vitro, increased M6P/IGF‐IIR expression resulted in 2‐fold reduced uptake of IGF‐II and was associated with reduced cellular invasiness and motility. Cells with increased M6P/IGF‐IIR expression exhibited reduced phosphorylation of IGF‐I receptor and p44/42 MAPK compared to vector transfectants, or wild‐type MDA‐MB‐231 cells. These results therefore suggest that M6P/IGF‐IIR levels can modulate breast cancer cell tumorigenicity by a mechanism that may involve altered IGF‐I receptor signaling. © 2003 Wiley‐Liss, Inc.
Suppression of peritoneal dissemination through protecting mesothelial cells from retraction by cancer cells
Authors: Hashimoto Shigenari , Takeoka Michiko , Taniguchi Shun'ichiro
Published: September 2003

In a previous study, we demonstrated that calponin h1 suppressed tumor growth of transformed cells and that the peritonitis carcinomatosa induced by mouse B16‐F10 melanoma (F10) cells was more extensive in calponin h1‐deficient (CN−/−) mice with fragility of mesothelial (MS) cells than in their calponin h1‐wild (CN+/+) counterparts. In our study, we assessed the therapeutic effect of calponin h1 on peritoneal dissemination. F10 cells were overlaid on the cultured CN+/+ or CN−/− MS cells and the effect of calponin h1 on retraction of MS cells was evaluated. Then, an adenoviral vector with the calponin h1 gene (AdGFP‐CN) inserted was constructed and was applied to CN−/− MS cells or CN−/− mouse peritoneum to investigate its suppressive effect on the peritoneal dissemination caused by F10 cells. Greater retraction and invasion of F10 cells were observed in CN−/− MS than in CN+/+ cells in vitro, while down‐regulation of calponin h1 was observed in CN+/+ MS cells prior to the invasion of F10 cells. Infecting CN−/− MS cells with AdGFP‐CN prevented their retraction and the invasion of F10 cells. Peritoneal dissemination was prominently suppressed in AdGFP‐CN‐infected CN−/− mice, and the survival of those mice was significantly prolonged. Thus, calponin h1 functioned to protect host MS cells from the invasion of F10 cells. © 2003 Wiley‐Liss, Inc.
Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers
Authors: Zöchbauer‐Müller Sabine , Lam Stephen , Toyooka Shinichi , Virmani Arvind K. , Toyooka Kiyomi O. , Seidl Sonja , Minna John D. , Gazdar Adi F.
Published: September 2003

An important method for silencing tumor suppressor genes in cancers is by aberrant methylation (referred to as methylation) of CpG islands in gene promoter regions. In lung cancer, methylation of the genes retinoic acid receptor β‐2 (RARβ‐2), CDH13 (H‐cadherin), p16INK4a (p16), RASSF1A (RAS association domain family I) is frequent. Thus, we investigated methylation of these genes in 4 different types of specimens (oropharyngeal brushes, sputum samples, bronchial brushes and bronchioloalveolar lavage [BAL] samples) of the upper aerodigestive tract epithelium from heavy smokers without evidence of cancer but with morphometric evidence of sputum atypia and compared the frequencies of methylation in the different types of specimens. In addition, we also analyzed sputum samples from 30 never smokers for methylation of these genes. Our major findings are: (i) At least one gene was methylated in one or more specimens from 48% of the smokers. However, methylation was statistically significant less frequently in never smokers compared to smokers. (ii) In general, methylation occurred more frequently in samples from the central airways (sputum, bronchial brushes) compared to the peripheral airways (BAL) and only occasionally in the oropharynx. (iii) RARβ‐2 was the most frequently methylated gene, whereas the frequency of methylation for the other genes was lower. (iv) Data from sputum samples and bronchial brushes were comparable. Our findings suggest that detection of methylation should be investigated as an intermediate marker for lung cancer risk assessment and response to chemopreventive regimens. © 2003 Wiley‐Liss, Inc.
Reproductive and anthropometric factors in relation to the risk of lobular and ductal breast carcinoma among women 65–79 years of age
Authors: Li Christopher I. , Malone Kathleen E. , Porter Peggy L. , Weiss Noel S. , Tang Mei‐Tzu C. , Daling Janet R.
Published: September 2003

Use of combined estrogen‐progestin hormone replacement therapy appears to be associated with an increased risk of invasive lobular breast carcinomas (ILC) and, to a lesser degree, with risk of invasive ductal carcinoma (IDC). Conceivably, ILCs are more hormonally responsive and so may be more strongly associated than IDCs with reproductive and anthropometric characteristics that can influence hormone levels. However, few epidemiologic studies of breast cancer have evaluated these factors by histologic type. We conducted a population‐based case‐control study of women aged 65–79 years in western Washington State. Responses from 975 women diagnosed with breast cancer during 1997–1999 were compared to those of 1,007 controls. Associations between various reproductive and anthropometric factors and risks of IDC (n = 656) and ILC (n = 196) were evaluated using polytomous logistic regression. Earlier age at menarche, later age at menopause and obesity were more strongly associated with elevated risks of IDC than ILC. Alternatively, oral contraceptive use was associated with an increased risk of ILC but not IDC. Thus, the pattern of results that we observed suggest that factors influencing endogenous hormones and duration of ovarian function may be more strongly associated with IDC risk, while exogenous hormones may be more strongly associated with ILC risk. © 2003 Wiley‐Liss, Inc.
Increase of AKT/PKB expression correlates with gleason pattern in human prostate cancer
Authors: Liao Yongde , Grobholz Rainer , Abel Ulrich , Trojan Lutz , Michel Maurice Stephan , Angel Peter , Mayer Doris
Published: September 2003

AKT/PKB is a central signaling molecule related to stimulation of cell proliferation and inhibition of apoptosis. Perturbations of AKT expression and function play an important role in tumor development and progression. We wanted to determine (a) whether AKT is overexpressed in human prostatic tumors, (b) whether AKT expression is correlated with tumor grade, and (c) whether AKT expression correlates with clinicopathological parameters. AKT expression was investigated by immunohistochemistry in sections from 56 paraffin‐embedded prostate specimens displaying benign prostatic tissue (BPT), prostatic intraepithelial neoplasia (PIN), and primary tumors graded 2–5 according to Gleason. The staining intensity for AKT was significantly more pronounced in tumors compared to BPT, with PIN ranging between BPT and carcinomas. Similarly, the fraction of AKT‐positive cells was higher in tumors than in BPT. A score of AKT expression (calculated as product from intensity and fraction of positive cells) ranging from 0–6 was also significantly higher in tumors than in BPT. Furthermore, the intensity of AKT expression in tumors showed a positive correlation with high preoperative serum levels of prostate specific antigen (PSA ≥ 10 ng/ml, p = 0.0325). These data show that AKT is upregulated in prostate cancer and that expression is correlated with tumor progression. © 2003 Wiley‐Liss, Inc.
Modular approach for novel nanostructered polycondensates enabled by the unique selectivity of carbonyl biscaprolactam
Authors: Loontjens Ton
Published: September 2003

New enabling chemistries have been developed to produce novel well‐defined polymeric materials through the additions of small amounts of reactive functional compounds to standard polymers during regular processing steps. We found that carbonyl biscaprolactam and its derivatives couple polymer chains in a strictly linear fashion. The requirements for fast and well‐controlled coupling reactions, a prerequisite to apply this modular concept, were met. The breakthrough to produce a wide variety of novel polymers came when we found that many building blocks, provided with functional groups and blocked isocyanate groups, could be made on the basis of this chemistry. Blocked isocyanate groups are very suitable coupling units to fix desired functions onto polymer backbones. In one example, antifouling coatings were prepared by introducing fluorine groups. In another case, blocked isocyanate functional acrylates were built into a polyacrylate to make self‐crosslinkable coatings. In another illustration, the concept was demonstrated by a novel route to prepare polyrotaxanes from rotaxane monomers provided with blocked isocyanates as polymerizable stopper groups. These reactive functional compounds gave, in a controlled manner, polymeric materials with substantially improved properties. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3198–3205, 2003
Photoinitiated cationic polymerization of monofunctional benzoxazine
Authors: Kasapoglu Fatmanur , Cianga Ioan , Yagci Yusuf , Takeichi Tsutomu
Published: September 2003

The photoinitiated ring‐opening cationic polymerization of a monofunctional benzoxazine, 3‐phenyl‐3,4‐dihydro‐2H‐1,3‐benzoxazine, with onium salts such as diphenyliodonium hexafluorophosphate and triphenylsulfonium hexafluorophosphate as initiators was examined. The structures of the polymers thus formed were complex and related to the ring‐opening process of the protonated monomer either at the oxygen or nitrogen atoms. The phenolic mechanism also contributed, but its influence decreased with decreasing monomer concentration. Thermal properties of the polymers were also investigated by differential scanning calorimetry and thermogravimetric analysis. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3320–3328, 2003
Design and synthesis of highly photopolymerizable styrenyl compounds in solid‐state photoinitiated polymerization
Authors: Furukawa Akira , Imanishi Yukio , Tanihara Masao
Published: September 2003

We designed a new type of styrenyl compound applicable to conventional photopolymerization systems, aiming at the production of polymers with improved mechanical properties, resistance to chemicals, and elevated glass‐transition temperatures (Tg's). A series of styrenyl monomers bearing 2,5‐dithio‐1,3,4‐thiadiazole groups were prepared, and their reactivity was studied in solid‐state photopolymerization initiated by 2‐(4′‐methoxystyryl)‐4,6‐bis(trichloromethyl)‐1,3,5‐triazine. These monomers exhibited much higher polymerization rates than usual, and the final conversion nearly reached completion, despite the relatively high Tg of the solid‐state photopolymerization system. Even at temperatures below Tg, the polymerization proceeded without a ceiling phenomenon. These features were explained by intermolecular interactions between the monomers that induced monomer alignments effective for solid‐state polymerization, large excess free volumes arising from rotation around the methylthio groups, and intramatrix radical migration leading to encounters with the remaining monomers. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3227–3242, 2003
Morphology of poly(p‐oxybenzoyl) crystal prepared by direct polycondensation of p‐hydroxybenzoic acid with p‐toluenesulfonyl chloride in pyridine
Authors: Kimura Kunio , Horii Toshiyuki , Yamashita Yuhiko
Published: September 2003

Poly(p‐oxybenzoyl) (POB) crystals were prepared with the reaction‐induced crystallization of oligomers during the direct polycondensation of p‐hydroxybenzoic acid (HBA) with p‐toluenesulfonyl chloride (TsCl) and N,N‐dimethylformamide in pyridine. Sheaflike lozenge‐shaped POB crystals were obtained, of which the longer diagonal was 7.0–8.0 μm. The influence of the polymerization condition on the morphology was examined to optimize the preparative condition for the crystals exhibiting the clearest habit, and the favorable condition was determined as the molar ratio of TsCl to HBA of 1.3 and polymerization concentration of 3.0%. The crystals possessed extremely high crystallinity and outstanding thermal stability. The formation mechanism of the crystal was proposed as follows. When the number‐average degree of polymerization of the oligomers exceeded a critical value of about 4, they were precipitated to form the hexagonal lamellae. The crystals were grown very quickly to lozenge‐shaped crystal through screw dislocation with the continuous precipitation of oligomers from the solution. Finally, the further polymerization occurred in the precipitated crystal with developing polymer‐chain packing. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3275–3282, 2003
Crosslinking polymerization leading to interpenetrating polymer network formation. II. Polyaddition crosslinking reactions of poly(methyl methacrylate‐co‐2‐methacryloyloxyethyl isocyanate) with various diols
Authors: Kiguchi Tadahiro , Aota Hiroyuki , Matsumoto Akira
Published: September 2003

As part of our continuing studies concerned with the elucidation of the crosslinking polymerization mechanism leading to interpenetrating polymer network (IPN) formation, in which IPNs consist of both polymethacrylates and polyurethane (PU) networks, this article explores the polyaddition crosslinking reactions of multifunctional poly(methyl methacrylate‐co‐2‐methacryloyloxyethyl isocyanate) [poly(MMA‐co‐MOI)] [MMA/MOI = 90/10] with various diols leading to PU network formation. Thus, the equimolar polyaddition crosslinking reactions of poly(MMA‐co‐MOI) with ethylene glycol (EG), 1,6‐hexane diol, and 1,10‐decane diol (DD) were carried out in N‐methyl pyrrolidone at a 0.25 mol/L isocyanate group concentration at 80 °C. The second‐order rate constants decreased from EG to DD. The deviation of the actual gel point from the theoretical one was smaller from EG to DD. The intrinsic viscosity of resulting prepolymer demonstrated almost no variation with progressing polymerization for the EG system, whereas it gradually increased with conversion for the DD system. Close to the gel point conversion it increased rather drastically for both systems. The swelling ratio of resulting gel was higher from EG to DD. These are discussed mechanistically in terms of the significant occurrence of intramolecular cyclization and intramolecular crosslinking reactions leading to shrinkage of the molecular size. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3243–3248, 2003
Polyimides from isomeric oxydiphthalic anhydrides
Authors: Li Qingxuan , Fang Xingzhong , Wang Zhen , Gao Lianxun , Ding Mengxian
Published: September 2003

2,2′,3,3′‐Oxydiphthalic dianhydride (2,2′,3,3′‐ODPA) and 2,3,3′,4′‐ODPA were synthesized from 3‐chlorophthalic anhydride with 2,3‐xylenol and 3,4‐xylenol, respectively. Their structures were determined via single‐crystal X‐ray diffraction. A series of polyimides derived from isomeric ODPAs with several diamines were prepared in dimethylacetamide (DMAc) with the conventional two‐step method. Matrix‐assisted laser desorption/ionization time‐of‐flight spectra showed that the polymerization of 2,2′,3,3′‐ODPA with 4,4′‐oxydianiline (ODA) has a greater trend to form cyclic oligomers than that of 2,3,3′,4′‐ODPA. Both 2,2′,3,3′‐ODPA and 2,3,3′,4′‐ODPA based polyimides have good solubility in polar aprotic solvents such as DMAc, dimethylformamide, and N‐methylpyrrolidone. The 5% weight‐loss temperatures of all polyimides were obtained near 500 °C in air. Their glass‐transition temperatures measured by dynamic mechanical thermal analysis or differential scanning calorimetry decreased according to the order of polyimides on the basis of 2,2′,3,3′‐ODPA, 2,3,3′,4′‐ODPA, and 3,3′,4,4′‐ODPA. The wide‐angle X‐ray diffraction of all polyimide films from isomeric ODPAs and ODA showed some certain extent of crystallization after stretching. Rheological properties revealed that polyimide (2,3,3′,4′‐ODPA/ODA) has a comparatively lower melt viscosity than its isomers, which indicated its better melt processability. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3249–3260, 2003
Effects of clay‐modifying agents on the morphology and properties of poly(methyl methacrylate)/clay nanocomposites synthesized via γ‐ray irradiation polymerization
Authors: Zhang Wei'an , Liang Ying , Luo Wei , Fang Yue'e
Published: September 2003

Via γ‐ray irradiation polymerization, poly(methyl methacrylate) (PMMA)/clay nanocomposites were successfully prepared with reactive modified clay and nonreactive clay. With reactive modified clay, exfoliated PMMA/clay nanocomposites were obtained, and with nonreactive clay, intercalated PMMA/clay nanocomposites were obtained. Both results were confirmed by X‐ray diffraction and high‐resolution transmission electron microscopy. PMMA extracted from PMMA/clay nanocomposites synthesized by γ‐ray irradiation had higher molecular weights and narrow molecular weight distributions. The enhanced thermal properties of the PMMA/clay nanocomposites were characterized by thermogravimetric analysis and differential scanning calorimetry. The improved mechanical properties of PMMA/clay were characterized by dynamic mechanical analysis. In particular, the enhancement of the thermal properties of the PMMA/clay nanocomposites with reactive modified clay was much more obvious than that of the PMMA/clay nanocomposites with nonreactive clay. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3218–3226, 2003
Synthesis of poly(tetrahydrofuran)‐b‐polystyrene block copolymers from dual initiators for cationic ring‐opening polymerization and atom transfer radical polymerization
Authors: Bernaerts Katrien V. , Schacht Etienne H. , Goethals Eric J. , Du Prez Filip E.
Published: September 2003

A dual initiator (4‐hydroxy‐butyl‐2‐bromoisobutyrate), that is, a molecule containing two functional groups capable of initiating two polymerizations occurring by different mechanisms, has been prepared. It has been used for the sequential two‐step synthesis of well‐defined block copolymers of polystyrene (PS) and poly(tetrahydrofuran) (PTHF) by atom transfer radical polymerization (ATRP) and cationic ring‐opening polymerization (CROP). This dual initiator contains a bromoisobutyrate group, which is an efficient initiator for the ATRP of styrene in combination with the Cu(0)/Cu(II)/N,N,N′,N″,N″‐pentamethyldiethylenetriamine catalyst system. In this way, PS with hydroxyl groups (PS‐OH) is formed. The in situ reaction of the hydroxyl groups originating from the dual initiator with trifluoromethane sulfonic anhydride gives a triflate ester initiating group for the CROP of tetrahydrofuran (THF), leading to PTHF with a tertiary bromide end group (PTHF‐Br). PS‐OH and PTHF‐Br homopolymers have been applied as macroinitiators for the CROP of THF and the ATRP of styrene, respectively. PS‐OH, used as a macroinitiator, results in a mixture of the block copolymer and remaining macroinitiator. With PTHF‐Br as a macroinitiator for the ATRP of styrene, well‐defined PTHF‐b‐PS block copolymers can be prepared. The efficiency of PS‐OH or PTHF‐Br as a macroinitiator has been investigated with matrix‐assisted laser desorption/ionization time‐of‐flight spectroscopy, gel permeation chromatography, and NMR. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3206–3217, 2003
Synthesis and characterization of liquid‐crystalline epoxy and its blend with conventional epoxy
Authors: Sadagopan K. , Ratna D. , Samui A. B.
Published: September 2003

Terephthaloyl chloride was reacted with 4‐hydroxy benzoic acid to get terephthaloylbis(4‐oxybenzoic) acid, which was characterized and further reacted with epoxy resin [diglycidyl ether of bisphenol A (DGEBA)] to get a liquid‐crystalline epoxy resin (LCEP). This LCEP was characterized by Fourier transform infrared spectrometry, 1H and 13C NMR spectroscopy, differential scanning calorimetry (DSC), and polarized optical microscopy (POM). LCEP was then blended in various compositions with DGEBA and cured with a room temperature curing hardener. The cured blends were characterized by DSC and dynamic mechanical analysis (DMA) for their thermal and viscoelastic properties. The cured blends exhibited higher storage moduli and lower glass‐transition temperatures (tan δmax, from DMA) as compared with that of the pure DGEBA network. The formation of a smectic liquid‐crystalline phase was observed by POM during the curing of LCEP and DGEBA/LCEP blends. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3375–3383, 2003
Simplified synthesis of carbohydrate‐functional siloxanes via transacetalation. I. Glucose‐functional siloxanes
Authors: Ogawa Takuya
Published: September 2003

Carbohydrate‐functional siloxanes (CHFSs) that exhibit high intermolecular interactions and good environmental friendliness have successfully been synthesized by acid‐catalyzed transacetalation between an acetal‐functional siloxane and glucose in dimethylformamide/dioxane mixed solvents. Activated clay has proven to be a good catalyst because of its high activity and its easy removal from the product. Acetal‐functional siloxanes as starting materials can be easily synthesized in good yields by hydrosilylation between SiH‐functional siloxanes and acrolein diethyl acetal. This method has the following advantages: (1) the inexpensive materials used, (2) the simplified process employed, and (3) the high yield achieved. Because the carbohydrate moieties in these materials have the nature of strong intermolecular interactions and are highly hydrophilic, CHFSs exhibit very high bulk viscosities in comparison with the corresponding acetal‐functional siloxanes and good solubilities in polar solvents such as dimethylformamide and dimethyl sulfoxide. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3336–3345, 2003
Thermosensitive polyalcohols: Synthesis via living cationic polymerization of vinyl ethers with a silyloxy group
Authors: Sugihara Shinji , Hashimoto Kiyotaka , Matsumoto Yuko , Kanaoka Shokyoku , Aoshima Sadahito
Published: September 2003

Thermosensitive homopolymers and copolymers with hydroxy groups were synthesized via the living cationic polymerization of Si‐containing vinyl ethers. The cationic homopolymerization and copolymerization of five vinyl ethers with silyloxy groups, each with a different spacer length, were examined with a cationogen/Et1.5AlCl1.5 initiating system in the presence of an added base. When an appropriate base was added, the living cationic polymerization of Si‐containing monomers became feasible, giving polymers with narrow molecular weight distributions and various block copolymers. Subsequent desilylation gave well‐defined polyalcohols, in both water‐soluble and water‐insoluble forms. One of these polyalcohols, poly(4‐hydroxybutyl vinyl ether), underwent lower‐critical‐solution‐temperature‐type thermally induced phase separation in water at a critical temperature (TPS) of 42 °C. This phase separation was quite sensitive and reversible on heating and cooling. The phase separation also occurred sensitively with random copolymers of thermosensitive and hydrophilic or hydrophobic units, the TPS values of which in water could be controlled by the monomer feed ratio. The thermal responsiveness of this polyalcohol unit made it possible to prepare novel thermosensitive block and random copolymers consisting solely of alcohol units. One example prepared in this study was a 20 wt % aqueous solution of a diblock copolymer consisting of thermosensitive poly(4‐hydroxybutyl vinyl ether) and water‐soluble poly(2‐hydroxyethyl vinyl ether) segments, which transformed into a physical gel above 42 °C. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3300–3312, 2003
Macrocycles 27: Cyclic aliphatic polyesters of isosorbide
Authors: Kricheldorf Hans R. , Chatti Saber , Schwarz Gert , Krüger Ralf‐P.
Published: September 2003

Numerous polycondensations of isosorbide and suberoyl chloride or other aliphatic dicarboxylic acid dichlorides were performed with pyridine as a catalyst and HCl acceptor. The reaction conditions were varied to optimize both the molecular weight and the fraction of cyclic oligo‐ and polyesters. Furthermore, we attempted to obtain the cyclic monomer by catalyzed back‐biting degradation of the molten cyclic polyesters above 220 °C in vacuo. The polyesters were characterized by viscosity and size exclusion chromatographic measurements as well as matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. In selected cases, mixtures of linear and cyclic polyesters were treated with a hot solution of partially methylated β‐cyclodextrin in methanol. This treatment allowed for a selective extraction of the linear chains up to approximately 5000 Da. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3414–3424, 2003
Synthesis and crosslinking of biphenyl and naphthalene liquid‐crystalline polyethers with pendant full‐saturated and vinyl‐terminated aliphatic chains
Authors: Callau Lourdes , Reina José Antonio , Mantecón Ana
Published: September 2003

Two series of vinyl‐terminated, side‐chain liquid‐crystalline polyethers containing 4,4′‐biphenyl and 2,6‐naphthalene moieties as mesogenic cores with several contents of vinyl crosslinkable groups were synthesized by chemically modifying poly(epichlorohydrin) with mixtures of saturated and vinyl‐terminated mesogenic acids. In most cases the degree of modification was over 90%. The polymers were characterized by chlorine analysis, IR and 1H and 13C NMR spectroscopies, viscometry, size exclusion chromatography/multi‐angle laser light scattering, and thermogravimetric analysis. The liquid‐crystal behavior of all the synthesized polymers was examined by differential scanning calorimetry, polarized optical microscopy (POM), and X‐ray diffraction on mechanically oriented samples. The crosslinking of most polymers was done by peroxide‐type initiators, which generally led to liquid‐crystal elastomers. The mesophase organization was maintained on the crosslinked materials, as confirmed by POM and X‐ray diffraction. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3384–3399, 2003
Living radical polymerization of vinyl chloride initiated with iodoform and catalyzed by nascent Cu0/tris(2‐aminoethyl)amine or polyethyleneimine in water at 25 °C proceeds by a new competing pathways mechanism
Authors: Percec Virgil , Popov Anatoliy V. , Ramirez‐Castillo Ernesto , Weichold Oliver
Published: September 2003

The first example of living radical polymerization of vinyl chloride carried out in water at 25 °C is reported. This polymerization was initiated by iodoform and catalyzed by nascent Cu0 produced by the disproportionation of CuI in the presence of strongly CuII binding ligands such as tris(2‐aminoethyl)amine or polyethyleneimine. The resulting poly(vinyl chloride) was free of structural defects, had controlled molecular weight and narrow molecular weight distribution, contained two ∼CHClI active chain ends, and had a higher syndiotacticity (62%) than the one obtained by conventional free‐radical polymerization at the same temperature (56%). This novel polymerization proceeds, most probably, by a combination of competitive pathways that involves activation by single electron transfer mediated by nascent Cu0 and degenerative chain transfer. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3283–3299, 2003
Metalization of polypropylene. I. Synthesis and melt free‐radical grafting of novel maleimides and methacrylates containing chelating moieties
Authors: Knaus Simone , Liska Alexander , Sulek Peter
Published: September 2003

Several chelating monomers with methacrylate and maleimide residues as polymerizable groups and diketone and aspartic acid residues as metal‐bonding groups were synthesized. A long‐chain aliphatic spacer was introduced to increase the solubility of the monomers in the polymer melt and to enhance the compatibility of grafted side chains and homopolymers with polypropylene (PP). PP was functionalized by melt free‐radical grafting, and some properties of the modified polymer were investigated. The grafting of a chelating methacrylic ester by injection molding afforded grafting yields of 30–50%. A comparison with products obtained by the grafting of commercially available acetoacetoxy methyl methacrylate showed the beneficial effect of the aliphatic spacer with respect to the grafting yield as well as the tensile strength and flexural modulus. The grafting of an aspartic acid based maleimide in an extruder afforded grafting yields of 80–95% and a significant increase in the surface wettability, as shown by contact‐angle measurements. A comparative study using samples obtained by the grafting of maleimidobenzoic acid indicated that the homogeneity‐increasing effect of the spacer was neutralized by the detrimental effect of the dicarboxylic chelating group. Nevertheless, the results showed that the maleimides were well suited for grafting by reactive extrusion because of their low susceptibility to homopolymerization under melt‐processing conditions. Preliminary metalization experiments showed the feasibility of plating without the use of corrosive etchants. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3400–3413, 2003
Graft copolymerization of butyl acrylate and 2‐ethyl hexyl acrylate from labile chlorines of poly(vinyl chloride) by atom transfer radical polymerization
Authors: Bicak Niyazi , Ozlem Mesut
Published: September 2003

Trace amounts of labile chlorines present in poly(vinyl chloride) (PVC) were found to act as initiation sites for the preparation of graft copolymers of PVC by copper‐mediated atom transfer radical polymerization (ATRP). High grafting yields were attained during the graft copolymerizations of n‐butyl acrylate (161.8%) and 2‐ethyl hexyl acrylate (51.2%) in 7.5 h. In both cases, the grafting proceeded with first‐order kinetics with respect to the monomer concentrations, this being typical for ATRP. Gel permeation chromatography traces of the resulting products did not exhibit additional peaks attributable to the formation of free homopolymers. The presented procedure offers an efficient means of preparing self‐plasticized PVC structures. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3457–3462, 2003
Perspectives of patients with cystic fibrosis on preventive counseling and transition to adult care
Authors: Zack Julie , Jacobs Carolyn P. , Keenan Peter M. , Harney Kathy , Woods Elizabeth R. , Colin Andrew A. , Emans S. Jean
Published: September 2003

The purpose of this study was to investigate how adolescents and adults with cystic fibrosis (CF) view preventive counseling and their transition to adult‐centered care within a children's hospital. Thirty‐two patients ≥16 years old diagnosed with CF were recruited from a pediatric tertiary care setting. During face‐to‐face interviews, patients were asked 27 structured questions and completed a 30‐item self‐administered questionnaire on preventive counseling by healthcare providers and on transition issues. The median age of patients was 25.5 years (range, 16–43 years); 69% of patients identified a pulmonologist as their “main doctor,” even though 78% had a primary care provider. Participants felt that 13–16 years of age was the best time for them to begin spending time alone with their main doctor. Less than half of the participants recalled receiving preventive counseling during the previous 12 months, and more patients wanted to discuss issues than actually did. Qualitative data emphasized the importance of independence in making decisions in healthcare and establishing relationships with providers, and many patients did not desire to transfer care to an adult hospital. Participants identified adult‐focused services such as inpatient rooms, discussion groups, work options, and social service support that would enhance care. In conclusion, the majority of adolescent/young adult patients with CF receiving care in a pediatric institution reported satisfaction with their healthcare. However, patients identified preventive issues that they desired to be more regularly addressed, starting in early adolescence, and changes in the delivery of services to enhance transition to adult‐oriented care. This study underscored the understanding of the integration of transition planning into the facilitation of healthcare decision‐making by the adolescent in issues of self‐care, sexuality, education, and finances. Future initiatives to enhance the care of patients with CF should provide training of pulmonologists in preventive care and increased attention to helping patients utilize appropriate primary‐care services during the adult years. In addition, prospective studies are needed to compare outcomes of CF patients who have transitioned and transferred to adult hospitals and those transitioning to adult‐oriented services in a pediatric institution. Pediatr Pulmonol. 2003; 36:376–383. © 2003 Wiley‐Liss, Inc.
Dornase alfa in the treatment of cystic fibrosis in Europe: A report from the Epidemiologic Registry of Cystic Fibrosis
Authors: Hodson M.E. , McKenzie S. , Harms H.K. , Koch C. , Mastella G. , Navarro J. , Strandvik B.
Published: September 2003

Dornase alfa (Pulmozyme®) treatment for patients with cystic fibrosis (CF) has been shown to improve pulmonary function and reduce exacerbations of infection in a number of placebo‐controlled double‐blind studies. Data in the Epidemiologic Registry of Cystic Fibrosis (ERCF) in November 1998 were used to assess the long‐term effectiveness in routine clinical practice of dornase alfa in terms of pulmonary function and frequency of acute pulmonary exacerbations in CF. At that time, the ERCF contained data on 13,684 CF patients, with a mean observation period of 2.3 years. To be included in the analysis, patients had to have 2 years of data in the Registry in appropriate detail. Overall, untreated patients showed a decline in forced expiratory volume in 1 sec over a 2‐year period of −2.3% predicted, but treated patients were stable, showing a change of 0.3% predicted, i.e., a treatment benefit of 2.5%. Compared to untreated patients, there were 25 fewer exacerbations per 100 treated patients per year. The analysis suggested that younger patients were likely to benefit more from treatment. The findings of randomized clinical trials were supported by the data collected in routine clinical practice. Pediatr Pulmonol. 2003; 36:427–432. © 2003 Wiley‐Liss, Inc.
Exhaled nitric oxide is age‐dependent in asthma
Authors: Avital Avraham , Uwyyed Kamal , Berkman Neville , Bar‐Yishay Ephraim , Godfrey Simon , Springer Chaim
Published: September 2003

We determined whether the exhaled nitric oxide (eNO) level in asthmatics is age‐dependent. Eighty‐seven asthmatic patients aged 2–41 years were studied. Hyperreactivity to adenosine 5′‐monophosphate (AMP) was used to confirm asthma (≤200 mg/ml). In the younger group of children (2–5 years), AMP challenge was performed by the provocation concentration causing wheeze (PCW) method, while in the older groups of patients (6–41 years), regular spirometry was used. Exhaled NO was measured in the younger group by the tidal breathing method (TBm) and in the older subjects by the slow vital capacity method (SVCm). TBm and SVCm were compared in 21 other subjects, and there was a significant correlation between the two values (r = 0.96, P < 0.0001). The equation of correlation between the two methods was eNOTBm = 0.78eNOSVCm − 0.51. Within asthmatic patients, we found a significant increase in eNO with age (P < 0.0001), while there was no significant difference in AMP reactivity (P = 0.35). We conclude that eNO in asthmatic patients is age‐dependent, with lower values in young children. Pediatr Pulmonol. 2003; 36:433–438. © 2003 Wiley‐Liss, Inc.
Does vitamin D administered to children with asthma treated with inhaled glucocorticoids affect short‐term growth or bone turnover?
Authors: Schou Anders J. , Heuck Carsten , Wolthers Ole D.
Published: September 2003

Our objective was to assess whether administration of 25‐OH‐vitamin D to children with asthma treated with inhaled dry‐powder budesonide 400 μg daily affects short‐term growth or markers of bone turnover. We utilized a randomized, double‐blind, two‐period crossover trial with run‐in and washout periods of 2 weeks and treatment periods of 4 weeks duration. The setting was an Outpatient clinic in a secondary referral center. Subjects included 14 boys and 3 girls with a mean age of 11.7 (range, 6.1–14.4) years. Interventions included 15 μg (600 IU) 25‐OH‐vitamin D (cholecalciferol) in one tablet ABCDin® once daily in the morning. Primary outcome measures were: lower leg growth rate, serum osteocalcin, and serum markers of type I collagen turnover, i.e., the amino terminal propeptide of type I procollagen (PINP), the carboxy terminal propeptide of type I procollagen (PICP) (formation markers), and the carboxy terminal pyridinoline cross‐linked telopeptide of type I collagen (ICTP) (degradation markers). Secondary outcome measures were parameters of asthma control and serum 25‐OH‐vitamin D. Lower leg growth rate was 0.22 mm/week during vitamin D and 0.25 mm/week during placebo treatment (NS). Osteocalcin was 59.9 and 57.8 μg/l during vitamin D and placebo treatment, respectively, PINP 574 and 565 μg/l, PICP 381 and 382 μg/l, and ICTP 11.5 and 11.1 μg/l, respectively (NS). Serum 25‐OH‐vitamin D was 76.3 nmol/l and 48.2 nmol/l, respectively (P < 0.001). There were no statistically significant differences in measures of pulmonary function. In conclusion, administration of 25‐OH‐vitamin D does not affect short‐term growth or markers of bone turnover in children with asthma treated with inhaled dry‐powder budesonide 400 μg daily. Pediatr Pulmonol. 2003; 36:399–404. © 2003 Wiley‐Liss, Inc.
Effect of montelukast on time‐course of exhaled nitric oxide in asthma: Influence of LTC4 synthase A−444C polymorphism
Authors: Whelan Glenn J. , Blake Kathryn , Kissoon Niranjan , Duckworth Laurie J. , Wang Jainwei , Sylvester James E. , Lima John J.
Published: September 2003

Leukotrienes (LT) mediate inflammation in asthma. The fraction of exhaled nitric oxide (FENO) is thought to be a sensitive and reproducible method for assessing airway inflammation in asthmatics and the anti‐inflammatory effects of drugs. A number of factors are known to contribute to intrapatient variation in FENO which can confound interpretation. The aims of this study were to characterize the time‐course of FENO, determine the effect of montelukast on the time‐course of FENO, and evaluate the influence of the LTC4 synthase A−444C polymorphism on montelukast‐evoked changes in FENO. Following a 2‐week run‐in, 7 males and 5 females with asthma, 10–16 years old, received 5 or 10 mg of montelukast or an identical placebo at bedtime for 7 days in double‐blind, crossover fashion, followed by a 7‐day washout. FENOwas quantified every 30 min for 3 or 6 hr at baseline and on days 1, 2, 3, and 7 of treatment. A time‐averaged value for FENO was calculated (FENO*), and % changes in FENO* relative to baseline vs. time following placebo and montelukast were compared. The genotype of the A−444C polymorphism was determined by PCR and RFLP. FENO varied markedly as a function of time in each patient. Time‐averaged values of FENO (FENO*) during placebo and montelukast treatment were similar. Montelukast significantly reduced the slope of the % change in FENO* vs. time curve in heterozygotes (n = 4), but not in A/A homozygotes (n = 8). These data suggest that heterozygotes respond better to montelukast compared to A/A homozygotes, at least with respect to changes in FENO. We conclude that assessment of inflammation or the anti‐inflammatory effects of drugs in asthma based on single determinations of FENO can be misleading. We further conclude that the A−444C polymorphism in the LTC4 synthase gene probably contributes to interpatient variability in montelukast‐evoked changes in FENO* and warrants further study. Pediatr Pulmonol. 2003; 36:413–420. © 2003 Wiley‐Liss, Inc.