bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated serum vascular endothelial growth factor and decreased survival in advanced laryngeal carcinoma
Authors: Teknos Theodoros N. , Cox Claudell , Yoo Sirius , Chepeha Douglas B. , Wolf Gregory T. , Bradford Carol R. , Carey Thomas E. , Fisher Susan G.
Published: October 2002

Purpose.

The purpose of this study was to determine whether serum vascular endothelial growth factor (s‐VEGF) levels at the time of diagnosis correlate with any known tumor variables and overall survival in patients with advanced laryngeal squamous cell carcinoma. Comparisons with a cohort of normal healthy controls were also performed to determine the potential usefulness of s‐VEGF as a screening tool.

Experimental Design.

Serum from patients enrolled in the VA Laryngeal Cooperative Study #258 (n = 183), as well as normal healthy controls (n = 40) was used in this analysis. Quantitative enzyme‐linked immunosorbent assays (ELISA) for VEGF were performed in duplicate on each serum sample. Demographic and survival data were available for each patient enrolled in the study. Univariate analyses, multivariate Cox regression analyses, and Kaplan‐Meier survival analysis were used.

Results.

The mean serum concentration of s‐VEGF for the healthy control group was 47.83 ± 0.13 pg/mL. For all patients enrolled in the VA Cooperative Study, regardless of treatment group, the mean s‐VEGF level was 317.22 ± 25.46 pg/mL. The patients randomly assigned to the surgical arm (n = 97) had a mean value of 315.44 ± 30.44 pg/mL. Those randomly assigned to the induction chemotherapy arm (n = 86) had a mean s‐VEGF level of 319.22 ± 42.11 pg/mL. Serum VEGF levels were significantly elevated in patients with laryngeal carcinoma compared with healthy controls (p < .001). The serum VEGF levels in each arm of the trial were also elevated versus the healthy controls (p < .001, surgery arm plus radiotherapy; p < .001, chemotherapy plus radiotherapy). In a univariate analysis, elevated s‐VEGF correlated with poor Karnofsky performance status for all patients with advanced laryngeal carcinoma (p < .008). High s‐VEGF levels also correlated with a poor performance score in patients on the chemotherapy arm of the VA Laryngeal Trial (p < .004). Elevated s‐VEGF levels in the surgical plus radiotherapy arm correlated with node‐positive disease (p = .047) and supraglottic location of the tumor (p = .022). In a multivariate analysis using all known tumor variables and s‐VEGF levels, elevated s‐VEGF levels and infiltrating growth pattern correlated with decreased survival for all evaluated patients with advanced laryngeal carcinoma (p = .065, and p = .018, respectively).

Conclusions.

Serum VEGF levels are significantly elevated in patients with advanced laryngeal carcinoma versus healthy controls. Elevated pretreatment s‐VEGF levels tended to indicate a more aggressive disease state and a poorer overall survival in advanced laryngeal carcinoma. © 2002 Wiley Periodicals, Inc. Head Neck 24: 1004–1011, 2002
Correlation of biochemical parameters with single parathyroid adenoma weight and volume
Authors: Bindlish Vinita , Freeman Jeremy L. , Witterick Ian J. , Asa Sylvia L.
Published: October 2002

Objective.

To determine the relationship of the biochemical parameters serum phosphate, serum calcium, and serum parathyroid hormone levels with respect to parathyroid adenoma weight and volume in primary hyperparathyroidism.

Study Design.

Retrospective review of 63 cases of primary hyperparathyroidism from 1992 to 1998.

Methods.

Single parathyroid adenomas were identified from surgical pathology reports. Preoperative calcium, phosphate, and parathyroid hormone levels were collected from charts. The volume of the adenoma was calculated using a mathematical equation for the volume of an ellipsoid object. The data were analyzed using a multiple analysis of variance, and a correlation coefficient was calculated. The level of significance was set at p ≤ .05.

Results.

With respect to adenoma volume, there was a significant correlation with serum calcium and parathormone levels (p = .0001 and p = .0001, respectively). There was no significant correlation between serum phosphate and adenoma volume. With respect to adenoma weight, there was a significant correlation with serum calcium and parathormone levels (p = .0001 and p = .0001, respectively). There was no significant correlation between serum phosphate and adenoma weight.

Conclusions.

Preoperative serum calcium and parathormone levels may be able to predict adenoma weight and volume in primary hyperparathyroidism for a single adenoma. © 2002 Wiley Periodicals, Inc. Head Neck 24: 1000–1003, 2002
The effect of sodicity on the strength of a soil surface
Authors: Rycroft David William , Kyei‐Baffour Nicholas , Tanton Trevor
Published: October 2002

Concern that sodicity developing at a soil surface might increase soil strength, and thus have an indirect adverse effect on germination, stimulated this investigation. The aim was to investigate the link between the strength developing at a soil surface and rising salinity and sodicity.

A soil containing small amounts of a swelling clay, of a type known to suffer from capping, was deliberately salinised in order to impose a range of salinities and sodicities at the soil surface. It was found that the strength at the surface increased during the actual salinisation process, but this was almost exclusively related to the rise in sodicity, and was not influenced to any great extent by the rising salinity.

Further strengthening occurred on leaching, and this was also strongly linked to the sodicity at the soil surface immediately before leaching. The strength of the surface increased with rising sodicity up to a maximum consistent with values indicated in the literature as being likely to cause problems due to swelling and dispersion. Above these critical sodicity levels, the strength of the surface remained constant but at a high value. It was concluded that these processes could account for the observed poor germination on similar soil textures under long‐term irrigation. Copyright © 2002 John Wiley & Sons, Ltd.
Air temperature effect on spray evaporation in sprinkler irrigation
Authors: Lorenzini Giulio
Published: October 2002

The temperature effect of the surrounding environment on mean steady aerial water evaporation in sprinkler irrigation is investigated. An experimental set‐up was designed and built to work at opportune operating conditions holding all the other variables constant to minimise the experimental error. One hundred and thirty‐seven tests were performed for this work, of which 81 were considered valid for a statistical analysis of the data measured. Evaporation ranged from 4.15 to 7.73% as the air temperature varied from 21.0 to 27.0° C. Results show a clear dependence of sprinkler water evaporation on air temperature with a logarithmic relation. Further investigations will examine broader temperature intervals to improve the assessment and will consider the effects due to other parameters affecting the phenomenon. Copyright © 2002 John Wiley & Sons, Ltd.
Early estrogen exposure induces abnormal development of Fundulus heteroclitus
Authors: Urushitani Hiroshi , Shimizu Akio , Katsu Yoshinao , Iguchi Taisen
Published: October 2002

Many chemicals released into the environment exhibit estrogenic activity, having the potential to disrupt development and the functioning of the endocrine system. In order to establish a model system to study the effects of such environmental chemicals on aquatic animals, we examined the effects of a natural estrogen, 17β‐estradiol (E2), on early development of Fundulus heteroclitus. Embryos of F. heteroclitus were reared in seawater containing 10−10, 10−8, and 10−6 M E2 throughout the experiment. Hatching and survival rates decreased in a dose‐dependent manner, and fry treated with 10−6 M E2 and 10−8 M E2 were dead by two weeks and 12 weeks after hatching, respectively. More than 85% of fry treated with 10−8 M E2 showed malformations: i.e., eye extrusion, crooked vertebral column, faded lateral‐stripe pattern eight weeks after hatching. Body weight and head and body lengths were significantly reduced in E2‐treated fry when compared to controls. Ossification was not completed in vertebrae, cranial bones, and other bones in fry treated with 10−8 M E2 even 12 weeks after hatching. Sex ratio of control fry was 57% male and 43% female, whereas fry treated with 10−8 M E2 were 100% female eight weeks after hatching. The present results demonstrate that exogenous estrogen induced death of embryos and fry, malformations, sex reversal, and incomplete ossification of vertebrae and cranial bones, which would result in shorter body and head lengths and in malformed vertebrae leading to a hunchback condition. J. Exp. Zool. 293: 693–702, 2002. © 2002 Wiley‐Liss, Inc.
Effects of prenyl pyrophosphates on the binding of S‐ras proteins with KSR
Authors: Chen Chau‐huei , Fan Junn‐huei , Chuang Nin‐nin
Published: October 2002

BALB/3T3 cells were transformed by transfection with DNA encoding the mutated ras(Q61K) from shrimp Penaeus japonicus (Huang et al., 2001. J. Exp. Zool. 289:441–448). On a Western blot, the kinase suppressor of Ras (KSR) in the membrane fraction was expressed at slightly reduced level as compared to that of the untransformed cells. To understand this in more detail, the interaction of the bacterially expressed shrimp Ras (S‐Ras) with KSR was investigated using KSR purified from mice brains. SDS‐polyacrylamide gel electrophoresis and Western blot analysis revealed that the monomers of the purified KSR have a relative molecular mass of 60,000. Purified KSR was found to bind with digoxigenylated S‐ras‐encoding fusion protein (Dig‐S‐Ras) with high affinity in the absence of ATP, and the binding activity of KSR was sustained upon phosphorylation of Dig‐S‐Ras with mitogen‐activated protein kinase (MAPK). The association of purified KSR with S‐Ras was confirmed. Differences between the effects of farnesyl pyrophosphate and geranylgeranyl pyrophosphate on the binding of S‐Ras with the purified KSR were assessed. Densitometer analysis revealed that at nanogram concentration, farnesyl pyrophosphate inhibited the binding of S‐Ras with KSR competently, but geranylgeranyl pyrophosphate did not. The present study provides the evidence that decrease of the concentration of farnesyl pyrophosphate to sub‐microgram levels lower the affinity of Ras proteins with KSR in the signaling pathway. J. Exp. Zool. 293:551–560, 2002. © 2002 Wiley‐Liss, Inc.
Ejaculate of sneaker males is pheromonally inconspicuous in the black goby, Gobius niger (Teleostei, Gobiidae)
Authors: Locatello L. , Mazzoldi C. , Rasotto M.B.
Published: October 2002

The black goby, Gobius niger, shows alternative male mating tactics, i.e., parental and sneaker males. Males release a sexual pheromone that attracts females and stimulates aggressive displays in males. This pheromone is produced by the mesorchial gland, a structure well developed in parental males but markedly undeveloped in sneakers. We measured the behavioral response of parental males to the ejaculates of males performing different reproductive tactics. Parental males reacted to the ejaculate of other parental males, with stereotypic aggressive behaviors, but not to the ejaculate of sneakers; consequently sneaker male ejaculate appears to be pheromonally inconspicuous. J. Exp. Zool. 293:601–605, 2002. © 2002 Wiley‐Liss, Inc.
Oxidative, heat and anthelminthic stress responses in four species of Trichinella: comparative study
Authors: Martinez Javier , Perez‐Serrano Jorge , Bernadina W.E. , Rodriguez‐Caabeiro Filomena
Published: October 2002

The aim of this study was to compare levels of stress proteins in four Trichinella species when exposed to different stressors. Heat shock protein (HSP) 60, 70 and 90 responses were evaluated in infective larvae (L1) of four classic Trichinella species following exposure to oxidative, anthelminthic and thermal stress. Larvae of T. nativa, T nelsoni, T. pseudospiralis and T. spiralis were exposed to peroxide shock (0.2%, 1%, or 2% H2O2for 2h), high temperatures (40°C or 45°C for 2h), or 0.1µg/ml of the benzimidazole anthelminthics: mebendazole (MBZ), albendazole (ALB) or thiabendazole (TBZ) for 4h. Following exposures, the L1 were tested for induced morphological changes. Those observed were: (i) no change (in all species exposed to 40° C) (ii) aberrant forms (in all species exposed to anthelminthics, in T. nativa, T. nelsoni and T. spiralis exposed to 45°C, and in T. spiralis and T. nelsoni exposed to 0.2% H2O2) and (iii) severe degradation or death (in T. nativa and T. pseudospiralis exposed to 0.2% H2O2, and in all species at 1% and 2% H2O2). In Western blot analyses, L1 proteins were probed with monoclonal antibodies (mAbs) specific for the three HSPs. Greater changes in HSP levels occurred following H2O2 exposure than with other stresses in all Trichinella species, while accumulation of a 50 kDa HSP was only observed in T. spiralis and T. pseudospiralis. Anthelminthic stress only caused decreased HSP levels in T. nativa. Thermal stress caused no significant changes in the HSP response of any species. It is suggested that other stress proteins (e.g., glucose‐regulated proteins) may be involved in adaptation to thermal stress. J. Exp. Zool. 293:664–674, 2002. © 2002 Wiley‐Liss, Inc.
Distribution and gene expression of cytoskeletal proteins in two‐cell rat embryos and developmental arrest
Authors: Matsumoto Hiromichi , Jiang Jin‐yi , Mitani Disuke , Sato Eimei
Published: October 2002

Previous observations in rat two‐cell embryos suggested that distribution of microfilaments and microtubules are involved in developmental arrest. Therefore, we examined the distribution of cytoskeletal proteins, actin binding proteins, and microtubule‐associated proteins in rat two‐cell embryos. We also examined gene expression of β‐actin, α‐tubulin, and cytoskeletal proteins that showed changes in their distributions. Distribution of cytoskeletal proteins was examined by immunocytochemistry. Although distributions of α‐actinin, MAP1A, MAP1B/MAP5, and MAP2 were disturbed in arrested embryos, these abnormal distributions occurred following the initiations of developmental arrest and marked damage of microfilaments and microtubules. Gene expression of cytoskeletal proteins was examined by RT‐PCR. Beta‐actin and α‐actinin mRNA was detected in normal late two‐cell stage but not in arrested embryos. The difference occurred after zygotic gene activation. Expression of α‐tubulin was detected in neither normal late two‐cell stage nor arrested embryos. No MAP1A, MAP1B/MAP5, or MAP2 expression was detected in embryos during the two‐cell stage. In conclusion, both distributions of microfilaments and microtubules are closely involved in rat developmental arrest, but other distributions of cytoskeletal proteins, actin binding proteins, and microtubule‐associated proteins do not appear to have major roles in two‐cell arrest. Furthermore, mRNA expression patterns are different between microfilaments and microtubules. Both distribution and mRNA transcription of microfilaments are involved in rat developmental arrest, whereas only distribution of maternal microtubules is disturbed in arrested embryos. J. Exp. Zool. 293:641–648, 2002. © 2002 Wiley‐Liss, Inc.
Effect on growth and reproduction of hormone immersed and masculinized fighting fish Betta splendens
Authors: Kirankumar Santhakumar , Pandian Thavamani Jegajothivel
Published: October 2002

To produce all‐male progenies in the fighting fish, Betta splendens, six groups of fry were subjected to discrete immersion treatment at different 17α‐methyltestosterone (MT) doses (viz. 100, 200, 500, 700, 900, and 1,000 µg/l) for a constant duration (3 hr/day) and frequency (second, fifth, and eighth day after hatching). The treatment at 900 µg/l led to 98% masculinization and 71% survival at sexual maturity. Treated groups, which showed significant deviation from the 1:1 sex ratio, were classified into two different series: S1 and S2. The groups that showed nearly cent‐percent masculinization were classified as S1, and the other groups were classified as S2. The S1 males showed remarkably slower growth and attained 3.5 cm total length compared to 6.0 cm attained by a normal male. The S2 males attained 5.4 cm total length. Apart from these morphological defects, both S1 and S2 males suffered functional (decreased sperm count and sperm motility) and behavioral defects (incomplete embracing during mating) in their reproductive ability, leading to approximately 50% and 30% reduction in fecundity per mating, respectively. The cumulative fecundity loss suffered by the S1 male during its active reproductive phase is discussed. When normal and sex‐reversed males were presented, a female preferred the former. Progeny testing of the sex‐reversed males showed the occurrence of 12.75% males, indicating the possible role of autosomal genes in the sex determination mechanism of this species. Discrete immersion treatment at optimal/super‐optimal doses ensured not only a higher percentage of masculinization, but also a higher frequency of homogametic males (XX). J. Exp. Zool. 293:606–616, 2002. © 2002 Wiley‐Liss, Inc.
Experimentally induced anhydrobiosis in the tardigrade Richtersius coronifer: phenotypic factors affecting survival
Authors: Jönsson K. Ingemar , Rebecchi Lorena
Published: October 2002

The ability of some animal taxa (e.g., nematodes, rotifers, and tardigrades) to enter an ametabolic (cryptobiotic) state is well known. Nevertheless, the phenotypic factors affecting successful anhydrobiosis have rarely been investigated. We report a laboratory study on the effects of body size, reproductive condition, and energetic condition on anhydrobiotic survival in a population of the eutardigrade Richtersius coronifer. Body size and energetic condition interacted in affecting the probability of survival, while reproductive condition had no effect. Large tardigrades had a lower probability of survival than medium‐sized tardigrades and showed a positive response in survival to energetic condition. This suggests that energy constrained the possibility for large tardigrades to enter and to leave anhydrobiosis. As a possible alternative explanation for low survival in the largest specimens we discuss the expression of senescence. In line with the view that processes related to anhydrobiosis are connected with energetic costs we documented a decrease in the size of storage cells over a period of anhydrobiosis, showing for the first time that energy is consumed in the process of anhydrobiosis in tardigrades. J. Exp. Zool. 293:578–584, 2002. © 2002 Wiley‐Liss, Inc.
Computer simulation tools as applied to radioisotope production target design
Authors: Alvord C. W.
Published: October 2002

Computer simulations have been applied to many isotope target design problems with mixed results. At best, computer simulations provide rapid evaluation of design alternatives with high accuracy and without the cost in time and material of ‘cut‐and‐try’ methods. However, models are only helpful when well posed, well validated, and theoretically sound. In this context, the growing availability of commercial simulation packages provides an opportunity for the development of more advanced target systems. Copyright © 2002 John Wiley & Sons, Ltd.
Preparation of 18O‐labelled nicotinamide
Authors: Kołodziejska‐Huben Magdalena , Kamiński Zbigniew , Paneth Piotr
Published: October 2002

A method of preparing 18O‐labelled nicotinamide, involving cyanopyridine, H2 18O, and 1,1′3,3′‐tetramethylguanidine as a catalyst is described. The desired product is produced in 91% chemical yield and 97.5% isotopic incorporation. Copyright © 2002 John Wiley & Sons, Ltd.
Preparation, characterization and biodistribution of a new technetium‐99 m nitrido complex with 2‐methoxyisobutylisonitrile and comparison with 99mTc–MIBI
Authors: Zhang X. Zh. , Wang X. B. , Jia F. , Tang Z. G. , Zhang J. B. , Liu B. L. , Wang X. Y.
Published: October 2002

The preparation of complex 99mTcN–MIBI was carried out using two alternative procedures that led to the formation of the complex with high radiochemical purity (>90%). The partition coefficient, electrophoresis and cationic resin exchange experiments showed that the 99mTcN–MIBI is a lipophilic and neutral complex, the structure of this complex is six‐coordinate distorted octahedral, its composition may be [99mTcNCl2(MIBI)3], and the optimized geometry of this complex was calculated by using Gaussian 98 for Window (G98W) program. The biodistribution of 99mTcN–MIBI shows high myocardial uptake and good target/non‐target ratios in mice at early post‐injection time, for 5 min post‐injection the heart‐to‐blood, heart‐to‐lungs and heart‐to‐liver ratios are 3.18, 1.72 and 1.42, respectively. In respect of the relatively good rations after 5 min and the rapid clearance from non‐target, the complex 99mTcN–MIBI may be suitable for instant myocardial imaging. In addition, the lyophilized kit enables the convenient preparation of this complex for clinical use. Based on these promising properties, 99mTcN–MIBI should be a new potential myocardial perfusion‐imaging agent. Copyright © 2002 John Wiley & Sons, Ltd.
Hydroacylation of 4‐[18F]fluorobenzaldehyde: a novel method for the preparation of 4′‐[18F]phenylketones
Authors: Khan Noor‐Ul Hasan , Lee Byung Chul , Lee Sang‐Yoon , Choe Yearn Seong , Jun Chul‐Ho , Chi Dae Yoon
Published: October 2002

To assess the potential of intermolecular hydroacylation reactions as a new fluorine‐18 labeling method, model reactions of [18F]fluorobenzaldehyde with three different olefins (1‐hexene (2a), allylbenzene (2b), and 3‐phenoxypropene (2c)) in the presence of Wilkinson's catalyst were performed. The procedure gave high radiochemical yields (38–62%) of [18F]fluorophenylketones with short reaction times (15 min). The intermolecular hydroacylation reaction provides a new method for the preparation of fluorine‐18 labeled compounds. Copyright © 2002 John Wiley & Sons, Ltd.
Syntheses of stable‐isotope labeled [M+7] and [M+6] 2‐(methylamino)imidazole
Authors: Zhang Yinsheng
Published: October 2002

Stable isotope‐labeled 2‐methylaminoimidazole (M+7 and M+6) was required as an intermediate in the synthesis of mass labeled drug candidates. These two isotopomers were synthesized with total yields of 24 and 36%, respectively. Labeled 2‐aminoimidazole (M+4) was prepared from labeled isothiourea (M+3) and 2‐aminoacetaldehyde dimethyl acetal (M+1 and M+2). The (M+1) version of 2‐aminoacetaldehyde dimethyl acetal was obtained in two steps starting with potassium [15N]phthalimide, while the (M+2) version was prepared from the reduction of diethoxyacetamide with LiAlD4. Two different approaches for the preparation of 2‐methylaminoimidazole from aminoimidazole were explored. Attempts to prepare protected 2‐aminoimidazole to couple with CH3I (M+4) to form the desired labeled 2‐methyl‐aminoimidazole failed. However, methylation was achieved by applying N‐formamidation followed by deutero‐reduction. These successful syntheses allowed us to selectively label with nitrogen, carbon or hydrogen isotopes at most of the positions of 2‐methylaminoimidazole. Copyright © 2002 John Wiley & Sons, Ltd.
Preparation of the iodine‐124 derivative of the Bolton–Hunter reagent ([124I]I‐SHPP) and its use for labelling a VEGF antibody as a PET tracer
Authors: Glaser Matthias , Carroll Veronica A. , Collingridge David R. , Aboagye Eric O. , Price Pat , Bicknell Roy , Harris Adrian L. , Luthra Sajinder K. , Brady Frank
Published: October 2002

This study describes the radioiodination of an antibody specific to the vascular endothelial growth factor (VEGF), VG76e, with [124I]iodine to obtain a novel PET tracer for measurement of angiogenesis. In vitro binding assays showed a significantly higher immunoreactive fraction with the protein labelling reagent N‐succinimidyl 3‐(4‐hydroxy‐5‐[125I]iodophenyl) propionate ([125I]Bolton–Hunter reagent, [125I]I‐SHPP) (34.0±4.0%) as compared with N‐succinimidyl 3‐[125I]iodobenzoate (10.9±6.4%) or direct radioiodination using [125I]iodide and IodoGen (3.1±3.0%). Consequently, the cyclotron–produced positron–emitting [124I]iodine (T1/2=4.2 days) was employed to prepare [124I]I‐SHPP. Using an improved radioiodination methodology, [124I]I‐SHPP was prepared from sodium [124I]iodide with IodoGen at pH 6.5. The [124I]Bolton–Hunter reagent was isolated with 25–58% (n=3) radiochemical yield and 88–95% (n=3) radiochemical purity by the conventional extraction procedure. The conjugate of VG76e with [124I]I‐SHPP was prepared with 17–18% (n=3) labelling efficiency and 98% radiochemical purity. The immunoreactive fraction was determined to be 33.5% (n=2). Copyright © 2002 John Wiley & Sons, Ltd.
Thymic model for examining BRCA2 expression and function
Authors: Flores Kristina G. , McAllister Kimberly A. , Greer Paula K. , Wiseman Roger W. , Hale Laura P.
Published: October 2002

Mutations in the human BRCA2 breast cancer susceptibility gene are associated with increased risks of breast, ovarian, and other cancers. BRCA2 has been hypothesized to function in processes of DNA damage/breakage repair, cell proliferation, and apoptosis. These processes continually occur in the thymus during thymocyte development, and BRCA2 mRNA is highly expressed in thymus relative to most other organs. We therefore used the thymus as a model system to study BRCA2 expression and function. Quantitative reverse transcription polymerase chain reaction experiments showed that highly activated immature CD4+ CD8+ double‐positive human thymocytes that exhibited high levels of proliferation and apoptosis had increased BRCA2 mRNA levels relative to other thymocyte subsets. BRCA2 mRNA levels were upregulated in thymocytes treated with the DNA‐damaging agent etoposide. Only modest increases were associated with proliferation in human peripheral lymphocytes in response to concanavalin A (ConA) mitogen. Mice homozygous for a targeted mutation in Brca2 exon 27 (Brca2Δ27/Δ27) showed normal thymic architecture but had 18% decreased thymocyte cellularity compared with wild‐type mice. Thymocytes from these Brca2Δ27/Δ27 mice displayed decreased apoptosis in response to etoposide‐induced DNA damage compared with wild‐type thymocytes. These studies suggest that BRCA2 mRNA levels are modulated during DNA damage and may be important during apoptosis. © 2002 Wiley‐Liss, Inc.
Induction of marked apoptosis in mammalian cancer cell lines by antisense DNA treatment to abolish expression of DENN (differentially expressed in normal and neoplastic cells)
Authors: Lim K. M. , Chow Vincent T. K.
Published: October 2002

We previously reported the isolation of the novel human DENN gene, which is differentially expressed in normal and neoplastic cells. DENN is identical to MADD (mitogen‐activated protein kinase–activating death domain), which interacts with tumor necrosis factor receptor 1 through their death domains. DENN is also homologous to Rab3 GEP, a rat Rab3 GDP/GTP exchange protein. Real‐time reverse transcription–polymerase chain reaction analysis showed that DENN expression in cancer cell lines was 26–50 times that in normal cells. The Jurkat human leukemia, PLC/PRF/5 human hepatoma, and NS‐1 mouse myeloma cell lines as well as the MRC‐5 human fetal lung and Vero monkey kidney cell lines were treated successfully with four separate DENN‐targeted antisense oligodeoxynucleotides (ODNs) to abrogate DENN expression. Quantitative assessment of cell viability and apoptosis by flow cytometry via fluorescein diacetate and propidium iodide membrane‐integrity tests, terminal deoxynucleotidyl transferase–mediated deoxyuridine 5‐triphosphate–biotin nick end‐labeling, and annexin V assays showed that antisense silencing of DENN resulted in markedly more pronounced cell death in cancer cells compared with nonmalignant cells. Antisense‐treated cell lines exhibited extensive loss of DNA content, forming distinct sub‐G1 peaks, while cell proliferation diminished significantly. Ultrastructural features of programmed cell death in cells subjected to antisense ODNs were authenticated by electron microscopy. In contrast, transfection of cell lines with a plasmid construct to achieve DENN overexpression augmented cellular proliferation and could reverse the apoptotic effect of antisense and staurosporine treatment. Our findings suggest that DENN is intimately involved in anti‐apoptotic and cell‐survival processes. © 2002 Wiley‐Liss, Inc.
Determinants of non‐compliance with lipid‐lowering therapy in hyperlipidemic patients
Authors: Sik Kim Young , Sunwoo Sung , Ree Lee Hye , Mi Lee Keun , Woo Park Yong , Cheol Shin Ho , Hwan Kim Cheol , Hyun Kim Dae , Sung Kim Byung , Soo Cha Hyeong , Yul Huh Bong
Published: October 2002

Purpose

In order to assess the determinants of non‐compliance with a lipid‐lowering therapy, a prospective study of the hyperlipidemic Korean subjects was carried out.

Methods

A total of 1019 patients was observed by 46 family physicians for the period of 1 year from January 1999 to January 2000. To ascertain the compliance associated with a lipid lowering drug (Simvastatin), we regularly followed up the hyperlipidemic patients at intervals of 4, 12 and 24 weeks. The criterion for evaluating compliance is to measure clinic attendance. Using a structured questionnaire, patients and physicians were asked about risk factors for the compliance.

Results

During the first 24 weeks of treatment, the lipid‐lowering medication was continued by 52.3% and discontinued by 19.7%. The remaining 28% dropped out. Patient‐related factors for non‐compliance were young age, current smoker, lack of low fat diet and exercise, new user, no concomitant medication, and occurrence of adverse reactions. Physician‐related factors for non‐compliance were low patients' satisfaction with the physician, small number of hyperlipidemic patients per month and working in a relatively small hospital.

Conclusions

Compliance with the lipid‐lowering therapy was relatively low and several factors for non‐compliance were detected. Copyright © 2002 John Wiley & Sons, Ltd.
Amiodarone‐induced thyroid dysfunction associated with cumulative dose
Authors: Bouvy Marcel L. , Heerdink Eibert R. , Hoes Arno W. , Leufkens Hubert G. M.
Published: October 2002

Purpose

To obtain risk estimates of thyroid disorder in patients starting amiodarone.

Methods

We followed a cohort of 5522 patients with a first prescription for an anti‐arrhythmic drug and no previous use of thyroid drugs. Within this cohort we conducted a nested case–control analysis. Cases were defined as all patients who started a thyreomimetic or thyreostatic drug no sooner than 3 months after the start of an anti‐arrhythmic drug. Controls were patients with a comparable follow‐up period not receiving any thyroid drugs during the observation period.

Results

We identified 123 cases who had started thyreostatic drugs and 96 cases who had started a thyreomimetic drug. In users of amiodarone we found an adjusted odds ratio of 6.3 (3.9–10.2) for hyperthyroidism and 6.6 (3.9–11.1) for hypothyroid disease compared to users of other antiarrhythmics. Patients who were exposed to a cumulative dose exceeding 144 g of amiodarone had an adjusted odds ratio of 12.9 (6.1–27.3) for the development of hyperthyroid disease. The dose response for development of hypothyroidism was less pronounced.

Conclusions

We observed an increased risk for thyroid disorder at the high end of that reported in the literature. The risk of thyroid disorder increased with exposure to higher cumulative doses. Clinicians should keep in mind the possibility of development of thyroid disorders in patients on treatment with amiodarone even after several years of use. Copyright © 2002 John Wiley & Sons, Ltd.
The safety of drugs for OTC use: what evidence is required for an NSAID switch?
Authors: MacDonald Thomas M. , Beard Keith , Bruppacher Rudolf , Hasford Joerg , Lewis Michael , Logan Richard F. , McNaughton David , Tubert‐Bitter Pascale , Van Ganse Eric , Moore Nicholas
Published: October 2002

In recent years there has been a growing demand for safe and effective over‐the‐counter (OTC) drugs. The demonstration of the safety of OTC products in actual conditions of use is crucial for their wide distribution, since the circumstances of their use may be different from the prescription‐only setting. A group of experts met in Geneva, Switzerland, with the aim of exploring the criteria required to show safety equivalence of OTC medications, with specific reference to low‐dose non‐steroidal anti‐inflammatory drugs (NSAIDs) used for analgesia. It was agreed that an acceptable surrogate marker for safety as the primary endpoint in a study designed to show that a new NSAID was not inferior to a current NSAID would be any adverse event leading the patient to consult a physician. A sample size of 10 000 patients in each arm of a two‐arm study would be sufficient to show non‐inferiority with acceptable relative risk equal to 1.2 with at least 90% power for an event rate of 5%. An example of a possible pharmacy‐based randomized study design to demonstrate safety equivalence of OTC analgesics is given. Copyright © 2002 John Wiley & Sons, Ltd.
A framework for describing the impact of antidepressant medications on population health status
Authors: Patten Scott B.
Published: October 2002

Background

In the absence of strategies for primary prevention, public health initiatives for major depression have generally focused on secondary and tertiary strategies such as case‐finding, public and professional education and disease management. Much emphasis has been placed on low reported rates of antidepressant utilization. In principle, increased rates of treatment utilization should lead to improved mental health status at the population level. However, methods for relating antidepressant utilization to population health status have not been described.

Methods

An incidence–prevalence model was developed using data from a Canadian national survey, supplemented by parameter estimates from literature reviews. The lifetime sick‐day proportion (LSP) was used to approximate point prevalence.

Results

Mathematical simulations using this model produced reasonable approximations of point prevalence for major depression. The model suggests that an improved rate of treatment utilization may not, in itself, lead to substantially reduced prevalence. Reducing the rate of relapse in those with highly recurrent disorders, which can be accomplished by long‐term antidepressant treatment, is predicted to have a more substantial impact on population health status.

Conclusions

The model presented here offers a framework for describing the impact of antidepressant treatment on population health status. Mathematical models may assist with decision‐making and priority setting in the public health sphere, as illustrated by the model presented here, which challenges some commonly held assumptions. Copyright © 2002 John Wiley & Sons, Ltd.
Diene/olefin/polar monomer copolymerisation: unprecedented functional polymers from a rare earth catalyst
Authors: Bonnet Fanny , Barbier‐Baudry Denise , Dormond Alain , Visseaux Marc
Published: October 2002

An ansasamarocene allyl system is an efficient initiator which polymerises 1,3‐dienes, copolymerises dienes and long‐chain α‐olefins or α,ω‐dienes to give functionalisable polymers. It also polymerises caprolactone and allows the controlled diblock copolymerisation of isoprene or isoprene/α‐olefin copolymer and caprolactone.

© 2002 Society of Chemical Industry
Synthesis and characterization of a polymer–metal complex from bisphenol A polyhydroxy ether with sulfur‐bearing side‐groups
Authors: Zhang Hongwen , Ma Hongyang , Li Hongtu , Wang Jingyuan
Published: October 2002

A novel polymer–metal complex from bisphenol A polyhydroxy ether with dithiocarboxylic side‐groups was synthesized. The structure of the complex was characterized by elemental analysis and infrared and UV–vis spectroscopies. Because the dithiocarboxylic group possesses a strong chelating ability, it gives bisphenol A polyhydroxy ether some new properties such as coordination. At the same time, bisphenol A polyhydroxy ether increases the thermal stability of the complex, as verified by thermogravimetric analysis. The coordination ability of the functional bisphenol A polyhydroxy ether with various cations was investigated using the results of the gel fractions calculated by means of statistical theory. In addition, the electrochemical activity and surface chemical analysis of the complexes were investigated by cyclic voltammetry and X‐ray photoelectron spectroscopy, respectively.

© 2002 Society of Chemical Industry
Bulk and surface modification of silicone rubber for biomedical applications
Authors: Abbasi Farhang , Mirzadeh Hamid , Katbab Ali‐Asgar
Published: October 2002

Attempts have been made to modify the surface and bulk properties of polydimethylsiloxane (PDMS) polymers to improve their properties for biomedical applications. Laser‐induced surface grafting of poly(2‐hydroxyethyl methacrylate) (PHEMA) and a sequential method for preparation of interpenetrating polymer networks (IPNs) of PDMS/PHEMA were used for surface and bulk modifications, respectively. A major difference between these two methods and other modification techniques is their unique potentiality to modify a specific section of a polymeric sample. The modified PDMS samples have been studied by attenuated total reflectance Fourier transform infrared (ATR‐FTIR) spectroscopy, water contact angle measurement, scanning electron microscopy (SEM), dynamic mechanical thermal analysis (DMTA), and platelet adhesion measurement.

© 2002 Society of Chemical Industry
Thermally stable and high molecular weight poly(propylene carbonate)s from carbon dioxide and propylene oxide
Authors: Zhu Q , Meng Y Z , Tjong S C , Zhao X S , Chen Y L
Published: October 2002

The copolymerization of carbon dioxide and propylene oxide was carried out to afford alternating poly(propylene carbonate) in high yield. Thermal stable and high molecular weight copolymers were successfully obtained by optimizing the reaction conditions. The catalyst used was zinc glutarate supported on a perfluorinated compound containing 7–12 carbon atoms. Copolymerization parameters, such as the ratio of propylene oxide to catalyst, stirring strength and purity of propylene oxide, were studied. The alternating copolymer with a molecular weight of 56 100 in a very high yield (126 g polymer per gram of catalyst) was achieved, which is the highest yield ever reported. The thermal and mechanical properties of the alternating PPC copolymer were examined by the means of modulated differential scanning calorimetry (MDSC), thermogravimetric analysis (TGA) and tensile test. MDSC and TGA results showed that the alternating PPC copolymer exhibits an extremely high glass transition temperature (maximum 46.46 °C) and decomposition temperature (255.8 °C) when compared to those values reported in literature. Tensile test revealed that thin film of alternating PPC copolymer exhibits superior mechanical strength.

© 2002 Society of Chemical Industry
Preparation and properties of acrylic polymers/titania hybrid materials prepared by the in situ sol–gel process
Authors: Perrin F X , Nguyen V N , Vernet J L
Published: October 2002

Hybrid inorganic–organic materials based on a methyl methacrylate–n‐butyl methacrylate–methacrylic acid terpolymer have been prepared by the in situ sol–gel process in the presence of tetrabutyltitanate. The whole hydrolysis–condensation process results in homogeneous and semi‐transparent films with amounts of titania ranging from 4.5 to 22%. Infra‐red spectroscopic results show that COO—Ti bonds are formed and that chelating ones are stable up to 200 °C. Thus far, it had not been possible to separate the contributions of the acid groups from the catalyst (acetic acid) and those from the polymer. However, solvent extraction results undoubtedly proved a strong interaction between the polymer and the inorganic phase through COO—Ti bonds. Mechanical properties of the hybrid films have also been investigated through microhardness measurements and dynamic mechanical analysis. The results show that the tensile properties of the composites are strongly enhanced above the glass transition temperature (Tg) of the polymer. Below Tg, the tensile properties are not significantly affected.

© 2002 Society of Chemical Industry
A kinetic study of the copolymerization of substituted anilines by 1H NMR
Authors: Mav Ida , Žigon Majda
Published: October 2002

We investigated the kinetics of oxidative chemical copolymerization of 2‐methoxyaniline (OMA) with the following acidic substituted anilines (ANIAs): 2‐aminobenzoic acid, 3‐aminobenzoic acid, 2‐aminobenzenesulfonic acid and 3‐aminobenzenesulfonic acid by monitoring monomer depletion using 1H NMR spectroscopy. In order to characterize kinetically these new copolymerization systems, a semi‐empirical kinetic model for copolymerization systems with a large difference in monomer reactivities was used, whereas the monomer reactivity ratios were determined by employing the Kelen–Tüdõs (KT) method. Owing to the much higher reactivity of OMA compared to that of ANIA monomers, the conversion of OMA starts before that of ANIA and both the initiation and propagation rates are higher than those for ANIAs. The ANIA end‐conversion is much smaller (from 21 to 31%) than that of OMA (from 75% to 90%).

© 2002 Society of Chemical Industry
Grafting on polysilanes using atom transfer radical polymerisation
Authors: dos Santos Cláudio G , Parker James , Jones Richard G , Holder Simon J
Published: October 2002

Atom transfer radical polymerisation (ATRP) was used in an attempt to prepare a graft polymer based on poly(methylphenylsilane) (PMPS). A partially bromomethylated PMPS was subjected to ATRP conditions in order to grow poly(methyl methacrylate) (PMMA) grafts onto that backbone. Following the grafting reaction, a substantial increase in molecular weight was observed by size exclusion chromatography, analysis using refractive index detection. However, a bimodal product molecular weight distribution was observed using a UV detector set at wavelengths at which only the PMPS backbone can be detected. The lower molecular weight fraction was identified as homopolymeric PMPS although it appears to include some material with short grafts, while the higher molecular weight fraction corresponds to PMPS with long grafts. These observations are interpreted as the formation of a substantial amount of PMMA that is not grafted onto PMPS through a radical process initiated independently of the ATRP. However, since MMA is barely susceptible to thermal polymerisation, this is not easily rationalised.

© 2002 Society of Chemical Industry
Hyperbranched macromolecules through donor‐acceptor type copolymerization of allyl–vinylene bifunctional monomers
Authors: Rzaev Zakir M O
Published: October 2002

Present review is an attempt to generalize and systematize the results accumulated in synthesis of cyclolinear and hyperbranched reactive macromolecules via radical alternating copolymerization of various bifunctional monomers containing donor and acceptor type double bonds. Synthesis of hyperbranched reactive macromolecules was carried out using complex‐radical cyclocopolymerization of donor‐acceptor type bifunctional monomers such as monoallyl ester of maleic acid (MAM), allyl acrylate (AA), allyl methacrylate (AM), allyl trans‐cinnamate (AC), methylallylmaleate (MeAM), methylallylfumarate (MAF) and allyl‐α‐(N‐maleimido)acetate (AMI), and maleic anhydride (MA) and styrene (St) as typical acceptor and donor comonomers, respectively. The kinetic parameters of these reactions, constants of cyclization, complex‐formation and copolymerization, as well as the ratios of chain growth rates for the participation of monomeric charge transfer complexes and free monomers, were all determined. It was demonstrated that in the studied systems, copolymerizations predominantly proceed according to alternating mechanism with formation of macromolecules having cyclolinear structure in the steady‐state and hyperbranched structure in the high conversion conditions. It was shown that formation of linear and hyperbranched macromolecules containing allyl or vinylene groups in the side chain occurs selectively carry out and depends on the nature of used comonomer. General schemes and proposed mechanism of hyperbranching and crosslinking reactions were also described. Some useful properties of synthesized reactive copolymers were discussed.

© 2002 Society of Chemical Industry.
Preliminary study of the non‐emissive thermal rearrangement of novel N‐cyanates to rigid rod polymers
Authors: Hay John N , Martin Philip S , Bird Clive W , Hormozi Neda
Published: October 2002

Novel materials, both monomeric and polymeric, were synthesised to study the non‐emissive thermal rearrangement of N‐cyanates. These materials undergo an exothermic rearrangement, at temperatures in the range of 150–300 °C, to fused heterocyclic products. The series of N‐cyanate polymeric materials was characterised by Fourier‐transform infrared spectroscopy (FTIR) and modulated differential scanning calorimetry (DSC) as a preliminary assessment of their use as processable precursors to rigid rod polymers.

© 2002 Society of Chemical Industry
Preparation of N,N‐dilauryl chitosan Langmuir–Blodgett film
Authors: Li Mingchun , Xin Meihua , Miyashita Tokuji
Published: October 2002

N,N‐Dilauryl chitosan pentamer, synthesized by the reacting chitosan and lauryl aldehyde, was spread on a water surface from chloroform solution to investigate its monolayer behaviour. The condensed monolayer formed had collapse pressure of 50 mN m−1 and was transferred successful onto a solid support by the Langmuir–Blodgett (LB) technique giving a chitosan derivative ultrathin LB film with highly ordered layer structure and smooth surface. The characterization of the LB film and the monolayer on the water are discussed.

© 2002 Society of Chemical Industry
Reversible addition‐fragmentation chain‐transfer (RAFT) copolymerization of vinylidene chloride and methyl acrylate
Authors: Severac Romain , Lacroix‐Desmazes Patrick , Boutevin Bernard
Published: October 2002

The reversible addition‐fragmentation chain‐transfer (RAFT) copolymerization of vinylidene chloride and methyl acrylate was investigated at 70 °C in benzene. Three dithioesters were synthesized in high yield by a simple and straightforward transesterification method. These dithioesters were successfully used as reversible chain‐transfer agents, as demonstrated by the increase of molecular weight with conversion, a relatively low polydispersity index (Ip = 1.5) in comparison with a blank experiment (Ip = 1.9), first‐order polymerization kinetics and efficient chain extension. Nevertheless, a transfer reaction to vinylidene chloride monomer was considered to address the limitations of the RAFT process for this system. Moreover, a retardation effect was noticeable on the kinetics, depending on the structure and concentration of the transfer agent, leading to lower rate of polymerization for lower targeted molecular weights.

© 2002 Society of Chemical Industry
Novel hydrogels based on methacrylate‐modified agarose
Authors: Paepe Ilse De , Declercq Heidi , Cornelissen Maria , Schacht Etienne
Published: October 2002

Hydrogels based on agarose were prepared aiming to obtain flexible, firm and transparent materials suitable for biochemical applications. The kinetics of gelation were studied by means of rheology. Agarose was chemically modified by introduction of methacrylate side‐groups. The latter can be crosslinked to result in a network structure. The gel formation of the modified agarose is a combinatioin of physical gelation and chemical crosslinkage. The water‐soluble agarose obtained after derivatization was crosslinked by UV‐irradiation in the presence of a water soluble photoinitiator. The effect of storage time before chemical crosslinking has been examined and has a large influence on the final storage modulus and the contribution of the chemical and physical network strength towards the total network strength. The influence of the degree of modification on the final mechanical properties of the material has been examined by texturometry.

© 2002 Society of Chemical Industry