bluuebunny/crossref_metadata_2025 huggingface dataset:
Melt processable and biodegradable aliphatic polycarbonate derived from carbon dioxide and propylene oxide
Authors: Li X. H. , Meng Y. Z. , Zhu Q. , Xu Y. , Tjong S. C.
Published: July 2003

Alternating poly(propylene carbonate)s (PPC)s were successfully synthesized from carbon dioxide and propylene oxide in higher yield than previously reported. Such thermally stable and high molecular weight copolymers were achieved by optimizing the reaction conditions. The molecular structural change and mechanical properties of the alternating copolymer subjected to melt extrusion were examined by means of modulated differential scanning calorimetry (MDSC), thermogravimetric analysis (TGA), NMR, and tensile tests. The MDSC and TGA results showed that the alternating copolymer generally exhibits a high glass‐transition temperature of above 40°C and a decomposition temperature of above 250°C. These PPCs can be readily melt processed under conditions similar to those for commercial polyolefins. For instance, they can be melt extruded in a temperature range from 150 to 170°C under varying extrusion pressures. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3301–3308, 2003
Formation and inhibition of free radicals in electrically stressed and aged insulating polymers
Authors: Li Z. , Yin Y. , Wang X. , Tu D. M. , Kao K. C.
Published: July 2003

Previous work has shown that prebreakdown, electrical aging, and breakdown phenomena are directly associated with charge carriers injected from electrical contacts and their subsequent dissociative trapping and recombination. In addition, the energy released from each trapping or recombination event is dissipated in the breaking of the bonds of macromolecules, thus forming free radicals and new traps in the electrically stressed insulating polymers, as predicted by Kao's model. It is this gradual degradation process that leads to electrical aging and destructive breakdown. New experimental results are presented to confirm previous findings and a new approach to inhibit the degradation process by the incorporation of suitable dopants into the polymer. The concentration of free radicals in the polymer increases with an increasing electric field at a fixed stress time of 250 h and with increasing stress time at a fixed electric field of 833 kV cm−1. The concentration of free radicals is directly related to the concentration of new traps created by stress. However, when suitable dopants are incorporated, the initiation voltage for the occurrence of electrical treeing and the breakdown strength are both increased. The dopants tend to create shallow traps and have little effect on the deep trap concentration. This implies that the dopants act as free‐radical scavengers that tend to satisfy the unpaired electrons of the broken bonds, which create new acceptor‐like electron traps and new shallow traps. By doing so, the shallow traps screen the deep traps, thereby reducing the energy released during trapping and recombination and the probability of breaking the macromolecular bonds and causing structural degradation. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3416–3425, 2003
Effects of poly(vinyl acetate) and poly(vinyl chloride‐co‐vinyl acetate) low‐profile additives on properties of cured unsaturated polyester resins. II. glass‐transition temperatures and mechanical properties
Authors: Huang Yan‐Jyi , Chen Tzong‐Shyang , Huang Jyh‐Gau , Lee Fuh‐Huah
Published: July 2003

Three series of self‐synthesized poly(vinyl acetate)‐based low‐profile additives (LPAs), including poly(vinyl acetate), poly(vinyl chloride‐co‐vinyl acetate), and poly(vinyl chloride‐co‐vinyl acetate‐co‐maleic anhydride), with different chemical structures and molecular weights were studied. Their effects on the glass‐transition temperatures and mechanical properties for thermoset polymer blends made from styrene, unsaturated polyester, and LPAs were investigated by an integrated approach of the static phase characteristics, cured sample morphology, reaction kinetics, and property measurements. Based on Takayanagi mechanical models, the factors that control the glass‐transition temperature in each phase region of the cured samples and the mechanical properties are discussed. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3347–3357, 2003
Specific heat and thermal diffusivity of vinylidene fluoride/trifluoroethylene copolymers
Authors: Wong Y. W. , Hui N. M. , Ong E. L. , Chan H. L. W. , Choy C. L.
Published: July 2003

The specific heat (C) and thermal diffusivity (D) of vinylidene fluoride (VDF)/trifluoroethylene copolymers with 70 and 56 mol % of VDF were measured between 200 and 390 K, and the thermal conductivity (K) was calculated from these data. C, D, and K were rather insensitive to the VDF content but varied significantly with the crystallinity. At room temperature, as the crystallinity increased from about 55 to 85%, C decreased by 17%, and D and K increased by 60 and 40%, respectively. For the copolymer with 70 mol % VDF, C exhibited a broad peak, whereas D showed an abrupt drop at the ferroelectric–paraelectric transition near 370 K on heating. The transition temperature on cooling was about 40 K below that observed in the heating run, thus revealing a large thermal hysteresis. For the copolymer with 56 mol % VDF, the transition temperature was much lower, the transition region was narrower, and the thermal hysteresis was barely observable. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3160–3166, 2003
Self‐immobilization of methylaluminoxane in metallocene‐induced olefin polymerization reactions
Authors: Denner Christine E. , Alt Helmut G.
Published: July 2003

Metallocene complexes carrying one or two ω‐alkenyl ligands were activated with methylaluminoxane (MAO) to give homogeneous catalyst solutions. The reaction with ethylene formed heterogeneous catalysts by self‐immobilization. In the activation step, the ω‐alkenyl groups were transferred from the metal of the metallocene complex to the activating MAO agent and then underwent copolymerization reactions with ethylene induced by other active sites. This method is a universal approach to the heterogenization of homogeneous catalysts by copolymerization with ω‐alkenyl functionalized cocatalysts. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3379–3382, 2003
Structure‐mechanical properties relationship of poly(ethylene terephthalate) fibers
Authors: Šujica Milena Žiberna , Smole Majda Sfiligoj
Published: July 2003

The correlation between the fiber structure and mechanical properties of two different poly(ethylene terephthalate) fiber types, that is, wool and cotton types produced by three producers, was studied. Fiber structure was determined using different analytical methods. Significant differences in the suprastructure of both types of conventional textile fibers were observed, although some slight variations in the structure existed between those fibers of the same type provided by different producers. A better‐developed crystalline structure composed of bigger, more perfect, and more axially oriented crystallites was characterized for the cotton types of PET fibers. Crystallinity is higher, long periods are longer, and amorphous domains inside the long period cover bigger parts in this fiber type in comparison with the wool types of fibers. In addition, amorphous and average molecular orientation is higher. The better mechanical properties of cotton PET fiber types, as demonstrated by a higher breaking tenacity and modulus accompanied by a lower breaking elongation, are due to the observed structural characteristics. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3383–3389, 2003
Heart development in the spotted dolphin (Stenella attenuata)
Authors: Sedmera David , Misek Ivan , Klima Milan , Thompson Robert P.
Published: July 2003

Marine mammals show many deviations from typical mammalian characteristics due to their high degree of specialization to the aquatic environment. In Cetaceans, some of the features of limbs and dentition resemble very ancestral patterns. In some species, hearts with a clearly bifid apex (a feature normally present during mammalian embryogenesis prior to completion of ventricular septation) have been described. However, there is a scant amount of data regarding heart development in Cetaceans, and it is not clear whether the bifid apex is the rule or the exception. We examined samples from a unique collection of embryonic dolphin specimens macroscopically and histologically to learn more about normal cardiac development in the spotted dolphin. It was found that during the dolphin's 280 days of gestation, the heart completes septation at about 35 days. However, substantial trabecular compaction, which normally occurs in chicks, mice, and humans at around that time period, was delayed until day 60, when coronary circulation became established. At that time, the apex still appeared bifid, similarly to early fetal mouse or rat hearts. By day 80, however, the heart gained a compacted, characteristic shape, with a single apex. It thus appears that the bifid apex in the adult Cetacean heart is probably particular to certain species, and its significance remains unclear. Anat Rec Part A 273A:687–699, 2003. © 2003 Wiley‐Liss, Inc.
EBAG9/RCAS1 expression and its prognostic significance in prostatic cancer
Authors: Takahashi Satoru , Urano Tomohiko , Tsuchiya Fujiko , Fujimura Tetsuya , Kitamura Tadaichi , Ouchi Yasuyoshi , Muramatsu Masami , Inoue Satoshi
Published: July 2003

Estrogen receptor‐binding fragment‐associated gene 9 (EBAG9) has been identified as a primary estrogen‐responsive gene from MCF‐7 human breast cancer cells (Watanabe T, et al., Mol Cell Biol 1998;18:442–9). EBAG9 is identical with RCAS1 (receptor‐binding cancer antigen expressed on SiSo cells), which has been reported as a cancer cell surface antigen implicated in immune escape ( M, et al., Nat Med 1999;5:938–42). In our present study, we examined EBAG9 expression in human prostatic tissues and investigated its prognostic significance in patients with prostatic cancer. EBAG9 expression in normal prostatic epithelial cells and PC‐3, DU145 and LNCaP cancer cells was determined by Western blot analysis. Immunohistochemic analysis was performed in 21 benign and 81 malignant prostatic specimens, and patients' charts were reviewed for clinical, pathologic and survival data. EBAG9 was abundantly expressed in the prostate cancer cells compared to the normal epithelial cells. Strong and diffuse immunostaining in the cytoplasm of EBAG9 was found in 44 of 81 (54%) cancerous tissue samples. EBAG9 expression significantly correlated with advanced pathologic stages and high Gleason score (p = 0.0305 and < 0.0001, respectively). EBAG9 was more frequently expressed at sites of capsular penetration (79%) and lymph node metastasis (100%) compared to intracapsular primary tumors (54%) (p = 0.0264 and 0.0048, respectively). Positive EBAG9 immunoreactivity significantly correlated with poor PSA failure‐free survival (p = 0.0059). EBAG9/RCAS1 may play a significant role in cancer progression via an immune escape system. Immunodetection of EBAG9/RCAS1 expression can be a negative prognostic indicator for patients with prostatic cancer. © 2003 Wiley‐Liss, Inc.
Active stromelysin‐3 (MMP‐11) increases MCF‐7 survival in three‐dimensional Matrigel culture via activation of p42/p44 MAP‐kinase
Authors: Fromigué Olivia , Louis Krystel , Wu Erxi , Belhacène Nathalie , Loubat Agnès , Shipp Margaret , Auberger Patrick , Mari Bernard
Published: July 2003

Stromelysin‐3 (ST3) has the characteristic structure of matrix metalloproteinases (MMP), but its substrate specificity and pattern of expression differ markedly from that of other MMP family members. ST3 was originally isolated on the basis of its expression in primary breast cancers and has been shown to be overexpressed in virtually all primary carcinomas, suggesting that ST3 participates in the initial development of epithelial malignancies. Recent data using murine models reported that ST3 expression was able to increase tumor take by suppressing cell apoptosis. Our present goal was to set up an in vitro model in which we could study this new function. For this purpose, we analyzed survival of MCF‐7 transfectants expressing either wild‐type or catalytically inactive ST3 (ST3wt or ST3cat‐) in three‐dimensional (3‐D) culture conditions by inclusion in Matrigel. In such conditions, that mimic the in vivo microenvironment, we found a marked decrease in the percentage of cell death when active ST3 was expressed (ST3wt transfectants vs. ST3cat‐ or vector only transfectants) as assessed by FACS and TUNEL analysis. The addition of batimastat, a broad spectrum MMP inhibitor, reversed the increased cell survival in ST3wt transfectants, confirming that ST3 enzymatic activity was required for this effect. Finally, we analyzed the expression of anti‐ and pro‐apoptotic proteins as well as activation of cell survival pathways and we found that ST3‐mediated cell survival was accompanied by activation of both p42/p44 MAPK and AKT. Our data confirm and extend the anti‐apoptotic function of ST3 and provide a useful model to dissect this new role and identify new physiological substrates. © 2003 Wiley‐Liss, Inc.
Tartrate‐resistant acid phosphatase isoform 5b: A novel serum marker for monitoring bone disease in multiple myeloma
Authors: Terpos Evangelos , de la Fuente Josu , Szydlo Richard , Hatjiharissi Evdoxia , Viniou Nora , Meletis John , Yataganas Xenophon , Goldman John M , Rahemtulla Amin
Published: July 2003

Tartrate‐resistant acid phosphatase isoform‐5b (TRACP‐5b), a new marker reflecting osteoclast activity, and osteoprotegerin (OPG) were measured in 121 patients with multiple myeloma (MM) at diagnosis, and in 63 of them during pamidronate administration, to define their correlation with the extent of bone disease and disease activity in MM. Radiographic evaluation of the skeleton, measurement of other markers of bone remodelling, including N‐terminal cross‐linking telopeptide of type‐I collagen (NTX), bone alkaline phosphatase and osteocalcin and of markers of disease activity (beta2‐microglobulin, paraprotein, interleukin‐6 (IL‐6), were also performed. Levels of TRACP‐5b were increased (p < .0001), while OPG was decreased in MM patients compared to controls (p < .01). TRACP‐5b levels were associated with the radiographically assessed severity of bone disease (p < .0001) as well as with levels of NTX, IL‐6 and beta2‐microglobulin (p < .001, for each biochemical parameter, respectively). The combination of pamidronate with VAD‐chemotherapy produced a reduction in TRACP‐5b, NTX, IL‐6, paraprotein and beta2‐microglobulin levels from the 2nd month of treatment, with no effect on bone formation and OPG. A strong correlation was observed between changes in TRACP‐5b and changes in NTX, IL‐6 and beta2‐microglobulin, while TRACP‐5b predicted the disease progression in 5 patients. These findings suggest that TRACP‐5b is increased in MM, reflects the extent of myeloma bone disease and may have a predictive value. TRACP‐5b has also proved to be very useful for monitoring antimyeloma treatment, which had no effect on OPG levels. © 2003 Wiley‐Liss, Inc.
Dosage, duration and timing of nonsteroidal antiinflammatory drug use and risk of prostate cancer
Authors: Perron Linda , Bairati Isabelle , Moore Lynne , Meyer François
Published: July 2003

Experimental studies suggest that NSAIDs could reduce prostate cancer risk. Results of observational studies on the relation between NSAIDs and prostate cancer risk have, however, been inconsistent. Moreover, none has addressed the issues of dosage, duration and timing of exposure. In a population‐based, age‐matched case‐control study, we measured the association between prostate cancer risk and NSAIDs defined in terms of mean daily dose, cumulative duration and timing of exposure. Eight‐year drug exposure history was obtained from the Quebec health insurance system database. Parallel analyses were performed for aspirin and NSAIDs other than aspirin. We controlled for detection bias and assessed the potential impact of protopathic bias. Analyses were performed with conditional logistic regression. Among the 2,221 cases and 11,105 controls, there was a negative trend between cumulative duration of aspirin use and prostate cancer risk (p = 0.0009). Also, exposure to a mean daily dose of aspirin of at least 80 mg, maintained throughout the entire 8 years of follow‐up, was associated with an 18% reduction in prostate cancer risk (OR = 0.82, 95% CI 0.71–0.95). In more recent users of such a dose, the risk reduction was 7%. However, 1 year after the end of a 7‐year regular aspirin exposure, no residual protective effect persisted. No association was observed between prostate cancer risk and exposure to NSAIDs other than aspirin. The results suggest that long‐term and regular use of aspirin, at a dosage beneath that usually recommended for an anti‐inflammatory effect, may prevent prostate cancer. © 2003 Wiley‐Liss, Inc.
Incidence and survival of Swedish patients with differentiated thyroid cancer
Authors: Lundgren Catharina Ihre , Hall Per , Ekbom Anders , Frisell Jan , Zedenius Jan , Dickman Paul W.
Published: July 2003

Papillary (PTC) and follicular (FTC) thyroid cancers are rare disorders but are, nevertheless, among the most common cancers in individuals below 40 years of age. From the population‐based Swedish Cancer Registry we identified 3,588 individuals with PTC and 1,966 with FTC during 1958–87. Histopathology was determined by examining the original histopathology reports. The relative survival ratio (RSR) was used as the measure of patient survival. Incidence of both PTC and FTC was higher among women, especially for PTC and particularly during the fertile part of female life. Incidence of PTC increased significantly over time, a trend that was not observed for FTC. Five‐year relative survival appeared to be higher for patients diagnosed with PTC compared to FTC, although this difference was almost completely explained by the confounding effect of age. Patients with PTC experience lower mortality during the period 7–20 years after diagnosis. Excess mortality was lower among women, although the magnitude of the difference varied with age and histopathology. In contrast to our perceptions based on clinical practice, we observed no difference in excess mortality between patients diagnosed with PTC and FTC during the years immediately after diagnosis (where the majority of deaths occur). Our data suggest that there may exist a subgroup of thyroid tumors with superior prognosis diagnosed in women during the fertile part of female life. Sex hormones may play a role in the etiology of these tumors. © 2003 Wiley‐Liss, Inc.
Anti‐CD30‐IL‐12 antibody‐cytokine fusion protein that induces IFN‐γ secretion of T cells and NK cell‐mediated lysis of Hodgkin's lymphoma‐derived tumor cells
Authors: Heuser Claudia , Diehl Volker , Abken Hinrich , Hombach Andreas
Published: July 2003

Interleukin‐12 (IL‐12) is a disulfide‐linked p40‐p35 heterodimeric cytokine and plays a key role in linking innate cellular immunity to an adaptive Th1 response against pathogens and tumor cells and in counteracting a Th2 immune response. The pathogenesis of Hodgkin's disease (HD) is partially attributed to a Th2 dominance associated with functional anergy of T cells that accumulate in the near vicinity to the malignant Hodgkin/Reed‐Sternberg (H/RS) cells. To revert Th2 polarization in the tumor lesion, we generated an anti‐CD30‐IL‐12 antibody‐cytokine fusion protein that binds to CD30 on H/RS cells and is composed of a CD30 binding domain (HRS3‐scFv) linked to p40‐p35 murine single chain IL‐12. The HRS3‐scFv‐hi‐IL‐12 fusion protein is expressed as a 110 kD polypeptide, can be purified by affinity chromatography, and has binding specificities to both the CD30 antigen and the IL‐12 receptor. After binding to CD30+ H/RS cells, the fusion protein stimulates T cells to secrete IFN‐γ, a predominant Th1 cytokine, and induces NK cells to lyse CD30+ cells with high efficiency. These properties make the HRS3‐scFv‐hi‐IL‐12 fusion protein suitable for the specific immunotherapy of Hodgkin's lymphoma. © 2003 Wiley‐Liss, Inc.
Favorable prognostic value of tissue human kallikrein 11 (hK11) in patients with ovarian carcinoma
Authors: Borgoño Carla A. , Fracchioli Stefano , Yousef George M. , Rigault de la Longrais Irene A. , Luo Liu‐Ying , Soosaipillai Antoninus , Puopolo Manuela , Grass Linda , Scorilas Andreas , Diamandis Eleftherios P. , Katsaros Dionyssios
Published: July 2003

Human kallikrein 11 (hK11/trypsin‐like serine protease/TLSP, encoded by theKLK11gene) is a member of the kallikrein family of secreted serine proteases. Recently, we developed a highly sensitive and specific immunoassay for hK11 and found that this protease is expressed in the prostate, stomach and trachea as well as in amniotic fluid and milk of lactating women. Elevated serum hK11 levels were found in 60% of men with prostate cancer and 70% of women with ovarian cancer. Also, hK11 expression was found to be under the regulation of steroid hormones, particularly estrogens, at the level ofKLK11transcription. We hypothesized that hK11 may be implicated in endocrine‐related malignancies and serve as a novel prostate and ovarian cancer serological marker. The aim of our study was to examine if hK11 expression in ovarian tumors bears any prognostic significance. The concentration of hK11 (ng per mg of total protein) in 104 ovarian tumor cytosolic extracts was quantified and correlated with clinicopathologic variables and outcome over a median follow‐up period of 67 months. Outcome was defined as progression‐free survival (PFS) and overall survival (OS). hK11 concentration in ovarian tumor cytosols ranged from 0–21 ng/mg of total protein, with a median of 0.54 ng/mg. An optimal cutoff value of 0.54 ng/mg was selected to categorize tumors as hK11‐positive or ‐negative. hK11‐positive tumors were more frequently associated with early stage (Stage I/II) disease, pre‐/peri‐menopausal status and patients who exhibited complete or partial response to chemotherapy (p< 0.05). Univariate analysis revealed that patients with hK11‐positive tumors had a significantly decreased risk of relapse with a hazard ratio (HR) of 0.45 (p= 0.007) and death (HR of 0.34,p= 0.005). Cox multivariate analysis indicated that hK11 was an independent prognostic indicator of OS (HR of 0.41,p= 0.025). Kaplan‐Meier survival curves further confirmed that women with hK11‐positive tumors have longer PFS and OS (p= 0.005 andp= 0.003, respectively). Similarly, in the subgroup of patients with grade 1–2 tumors, hK11‐positivity was associated with higher OS in both univariate and multivariate analysis (HR of 0.23 and 0.17,p< 0.05). Finally, in women with optimal debulking after surgery (<1 cm residual tumor), hK11 positivity was associated with a slower disease progression. These results indicate that hK11 is a novel, independent marker of favorable prognosis in patients with ovarian cancer. © 2003 Wiley‐Liss, Inc.
Shape and position of the sarcoplasmic reticulum and the Golgi apparatus in the sole plate and remaining subsarcolemmal muscle region of the mouse using imidazole‐osmium staining
Authors: Voigt Tilman , Dauber Wolfgang , Bensemann‐Ryvkin Irina , Härtel Xenia
Published: July 2003

By means of thin (≤150 nm) and thick (>150 nm) sections, the shape and position of the sarcoplasmic reticulum and of the Golgi apparatus in the sole plate and in the remaining subsarcolemmal sarcoplasmic region were investigated. For this purpose the membranes were stained by means of imidazole‐osmium postfixation and unstained sections analyzed under the electron microscope. Both in the sarcoplasma of the sole plate and around the muscle fiber nuclei, a network of tubules is visible after imidazole‐osmium staining which can be identified as the sarcoplasmic reticulum solely on the basis of its contacts with the perinuclear cistern and the cisterns of the triads. Findings in literature on the position of the Golgi apparatus are confirmed and similar spatial relationships and vesiculations between the perinuclear cisterns and the Golgi apparatus of the sole plate nuclei and the other subsarcolemmal fiber nuclei are also demonstrated using this new staining method. Microsc. Res. Tech. 61:419–422, 2003. © 2003 Wiley‐Liss, Inc.
Three‐dimensional capillary geometry in gut tissue
Authors: Bosan Sorel , Kareco Thoma , Ruehlmann Dietrich , Chen Kevin Y.M. , Walley Keith R.
Published: July 2003

Accurate characterization of capillary geometry is of the utmost importance for physiological tissue studies such as oxygen transport. We show that 3D microscopy can be used to measure tissue capillary geometry both in normal and disease states. We imaged fluorescently labeled gut mucosa capillary beds of three control rats and three rats 4 hours after i.p. injection of 9 mg/kg endotoxin. We used serial optical sectioning microscopy coupled with deconvolution to reconstruct 3D capillary geometry. Theoretical point spread functions accounting for depth into the specimen resulted in better reconstructions than experimentally measured point spread functions. We next derived the distribution of the shortest distances to the nearest capillary from all extravascular tissue voxels. In normal rats the shortest‐distance distributions were remarkably constant despite widely varying capillary geometry. Furthermore, the mean of the shortest‐distance distributions increased significantly for endotoxemic rats (4.8 ± 0.4 μm) compared to controls (4.3 ± 0.3 μm, P < 0.05). Hence, serial sectioning microscopy provides an accurate venue for measuring physiologically relevant 3D capillary structure. Microsc. Res. Tech. 61:428–437, 2003. © 2003 Wiley‐Liss, Inc.
Glycocalyx morphology of Candida albicans
Authors: Krautgartner Wolf Dietrich , Vitkov Ljubomir , Hannig Matthias
Published: July 2003

In this study, we examine new cytochemical aspects of the fimbria‐mediated adhesion of the oral facultative pathogen Candida albicans. A wild‐type strain of the yeast was grown with and without sucrose supplementation for 8 days. Osmium tetroxide, uranyl acetate (UA), ruthenium red (RR), and cupromeronic blue (CB) staining with critical electrolytic concentrations (CECs) and tannic acid‐metal salt technique (TAMST) were applied to specimens separately or in combination for transmission electron microscopy (TEM) examination. Cytochemically, two types of fimbriae of C. albicans were distinguished: RR‐positive fimbriae of polyanionic glycoconjugates and CB‐positive fimbriae with a ceasing point of 0.3 M MgCl2 where no staining of sulfated carboxyl‐rich and/or phospho‐glycoconjugates occurred. Additionally, CB‐positive intercellular fibers were observed, which seemed to be involved in intercellular adhesion. The present protocol enables, for the first time, a partial cytochemical differentiation between at least two kinds of yeast fimbriae. Microsc. Res. Tech. 61:409–413, 2003. © 2003 Wiley‐Liss, Inc.
University business schools 2 business: the changing dynamics of the corporate education market
Authors: Watling Derek , Prince Christopher , Beaver Graham
Published: July 2003

There is a substantial and growing body of evidence to suggest that organizations are increasingly recognising the importance of individual and group learning and knowledge management as ways of attaining competitive advantage.

A consequence of this phenomenon is the growing demand for management education and training and increasingly, this is linked with the imperative of integrating management development with other organizational systems and processes to ensure their effectiveness in delivering business goals.

The purpose of this paper is to analyse this trend from the perspective of a New University Business School, i.e. one of the post 1992 Universities, created by the demise of the Polytechnics and their subsequent transfer to university status.

One of the principal aims of the paper is to suggest and identify potential market development opportunities and to highlight the competences required by business schools to successfully compete is this potentially profitable, yet increasingly competitive market.

The significance of the corporate education market should not be underestimated. As an example, the Association of Business Schools (1997) estimated that this type of activity accounted for up to two‐thirds of the programmes offered by its members in their provision.

Copyright © 2003 John Wiley & Sons, Ltd.
Differential expression of mucins 1–6 in papillary thyroid carcinoma: evidence for transformation‐dependent post‐translational modifications of MUC1 in situ
Authors: Magro Gaetano , Schiappacassi Monica , Perissinotto Daniela , Corsaro Antonella , Borghese Cinzia , Belfiore Antonino , Colombatti Alfonso , Grasso Sebastiano , Botti Carlo , Bombardieri Emilio , Perris Roberto
Published: July 2003

Mucins are primary glycoproteins of epithelia that are known to undergo major changes in their post‐translational processing during neoplastic transformation. This study has examined the expression pattern of seven primary mucins, ie mucin (MUC) 1, 2, 3, 4, 5AC, 5B and 6, in normal, hyperplastic, benign neoplastic, and papillary‐type carcinoma (PTC) tissues of the thyroid. MUC1 and MUC5B were the only mucins to be widely transcribed in both benign and malignant tissues. In contrast, MUC4 transcripts were undetectable in normal thyroids, and were present in only 40% of the hyperplastic and malignant thyroid tissues. In PTC, MUC1 was identified as a single mRNA transcript, rejecting the idea that this mucin may undergo transformation‐dependent alternative splicing in thyroid tumours. The tissue distribution of MUC1 and MUC4 proteins was highly heterogeneous: this largely paralleled their mRNA expression profiles and supported the conclusion that whereas MUC1 was ubiquitously expressed in PTC, MUC4 was detectable in less than 20% of the cases analysed. In order to determine whether post‐translational modifications of MUC1, putatively associated with malignancy, also occurred in the mucin produced by PTC, immunohistochemistry was performed with a panel of well‐characterized anti‐MUC1 antibodies in conjunction with digestion of the tissue sections with deglycosylating enzymes. These experiments, which were supported by immunochemical analyses of the MUC1 and MUC4 glycoforms extracted from tissues, collectively demonstrated markedly divergent MUC1 glycosylation profiles in normal and benign thyroid tissues when compared with PTC. Characteristically, these latter neoplastic cells produced mucin molecules carrying complex poly‐N‐lactosamine‐type glycans capped with fucose and neuraminic acid residues. The present study also found evidence in PTC for the potential presence of proteolytically processed MUC1 isoforms which differ in their post‐translational traits depending on whether they are retained on the cell surface or secreted into the extracellular space. It is proposed that the observed differences in the glycosylation properties of normal and neoplastic MUC1 may be exploitable as an ancillary tool in the diagnosis of PTC. Copyright © 2003 John Wiley & Sons, Ltd.
Differences in the vascular patterns of basal and squamous cell skin carcinomas explain their differences in clinical behaviour
Authors: Chin Cheryl WS , Foss Alexander JE , Stevens Alan , Lowe James
Published: July 2003

Tumour angiogenesis is essential for tumour growth and appears to play an important role both at the transition from hyperplasia to invasive growth and at a late stage in the dissemination process. Basal cell carcinomas (BCCs) and trichoepitheliomas (TEs) are related tumours that share the properties of invasive growth but without the capacity to metastasize. Squamous cell carcinomas (SCCs) of the skin are derived from a similar cell type and they have both invasive and metastatic potential. The aim of this study was to investigate whether the behaviour of these tumours could be explained by differences in their microvasculature. The study looked both qualitatively and quantitatively at the microvasculature of BCCs (n = 50) and TEs (n = 33) and compared them with normal skin (n = 6) and with SCCs of the skin (n = 22). Vessel counts were performed using a standard graticule count method after immunohistochemical staining for CD31. Counts were made of blood vessels in the stroma surrounding the tumour and also for vessels in the body of the tumour. The stromal counts for all the tumour groups differed significantly from normal skin. The SCC counts differed significantly from the counts for the BCCs and TEs. There was no significant difference between the counts for different subtypes of BCC or TE groups. While vessels could be found in the body of the SCCs, none was seen in the nodular BCC or the TE groups. There was no correlation between the vascular density and the depth of invasion. Overall, invasive growth correlated with an angiogenic response in the stroma, while metastatic potential correlated with microvessels being present in the body of the tumour. Copyright © 2003 John Wiley & Sons, Ltd.
The development of optimal pathological assessment of sentinel lymph nodes for melanoma
Authors: Cook Martin G , Green Margaret A , Anderson Brian , Eggermont Alexander MM , Ruiter Dirk J , Spatz Alain , Kissin Mark W , Powell Barry WEM
Published: July 2003

1158 sentinel lymph nodes (SLNs), excised from patients with primary cutaneous melanoma, were assessed pathologically using histology with immunohistochemistry (IHC) on all nodes, and RT‐PCR for Mart‐1 and tyrosinase on 55 nodes. RT‐PCR was compared with the histology and IHC assessed on the same nodes. The evaluation of progressively more detailed protocols for histology and IHC modulated by the RT‐PCR results led to a procedure that consistently detects metastases in 34% of patients submitted to SLN biopsy for cutaneous melanomas with a vertical growth phase and a mean thickness of 2.02 mm (range 0.25, with regression, to 19 mm). As this technique is virtually free of false positives and produces only a marginally lower detection rate than RT‐PCR, which was subject to false positives of 7% in our study, it is suggested that this extended protocol should be the basis on which further evaluation of the place of RT‐PCR in SLN assessment takes place. The evolved protocol described here has been adopted by the EORTC as the standard procedure for pathological handling of sentinel lymph nodes for melanoma when SLN status is a criterion in their clinical trials or studies. Copyright © 2003 John Wiley & Sons, Ltd.
Liver extracellular matrix in health and disease
Authors: Bedossa Pierre , Paradis Valérie
Published: July 2003

Liver fibrosis is the hallmark of every chronic liver disease. It is also the major factor of morbidity and mortality due to the development of cirrhosis and its complications including hepatocellular carcinoma. But even at the beginning of the process of liver fibrosis and due to the strategic position of the extracellular matrix at the interface between blood flow and epithelial compartment, any quantitative or qualitative modification of extracellular matrix will rapidly affect structure and function of the liver. The development of several animal models of liver fibrosis as well as isolation and cultivation of hepatic stellate cells, the major fibrogenic cell type in the liver, led to the gathering of recent knowledge on the mechanism of liver fibrosis. Activation of hepatic stellate cells is a key event in this process and many details on this finely tuned mechanism are now available. In addition to these experimental data, experience from chronic hepatitis C now allows the development of new concepts and perspectives such as liver fibrosis regression and antifibrotic therapies. Copyright © 2003 John Wiley & Sons, Ltd.
Integrin‐dependent pathologies
Authors: Wehrle‐Haller Bernhard , Imhof Beat A
Published: July 2003

Cell adhesion and migration are essential for embryonic development, tissue regeneration, and immune defence. The physical link between the extracellular substrate and the actin cytoskeleton is mediated by receptors of the integrin family and a large set of adaptor proteins. During cell migration this physical link is dynamically modified, allowing the cell to sense and adapt to the microenvironment. This includes the formation of integrin clusters at the cell front, their stabilization in the cell body and subsequent disassembly of these clusters at the rear of the cell. The modulation of the adhesion strength of the cell to the substrate is regulated by the affinity switch of integrin molecules and increased avidity through clustering of integrins. Here we explain how integrins mediate cell migration and how genetic defects of integrins and their adaptors lead to cellular dysfunction and generate pathological situations. Copyright © 2003 John Wiley & Sons, Ltd.
Gold‐coated fused‐silica sheathless electrospray emitters based on vapor‐deposited titanium adhesion layers
Authors: Nilsson Stefan , Klett Oliver , Svedberg Malin , Amirkhani Ardeshir , Nyholm Leif
Published: July 2003

Gold‐coated fused‐silica electrospray (ES) emitters based on vapor‐deposited adhesion layers of titanium have been manufactured to investigate the possibilities of producing durable ES emitters applicable in chip‐based analytical devices. The stabilities of the emitters were studied by both electrospray and electrochemical experiments and a marked increase in the emitter lifetime, compared to that for Cr/Au coated emitters, was found for the Ti/Au emitters in the ES durability tests. This indicates that Ti (rather than Cr) adhesion layers should be used in association with large‐scale fabrication of ES emitters by vapor‐deposition techniques. The lifetime of about 500–700 hours also allowed the Ti/Au‐coated emitter to be used as an integrated part of a capillary liquid chromatography column coupled to a mass spectrometer in a series of LC/MS experiments. The Ti/Au coating was further studied by electrochemical techniques and scanning electron microscopy in conjunction with X‐ray spectroscopy. It is shown that the eventual failure of the Ti/Au emitters in ES experiments was due to an almost complete detachment of the gold layer. Experimental evidence suggests that the detachment of the gold coating was due to a reduced adhesion to the titanium layer during oxidation in positive electrospray. Most likely, this was caused by the formation of an oxide layer on the titanium film. It is thus shown that unlimited emitter stabilities are not automatically obtained even if the metallic adhesion layer is stabilized by an oxide formation under positive electrospray conditions. Copyright © 2003 John Wiley & Sons, Ltd.
Micro‐electrospray with stainless steel emitters
Authors: Shui Wenqing , Yu Yanling , Xu Xuejiao , Huang Zhenyu , Xu Guobing , Yang Pengyuan
Published: July 2003

The physical processes underlying micro‐electrospray (micro‐ES) performance were investigated using a stainless steel (SS) emitter with a blunt tip. Sheathless micro‐ES could be generated at a blunt SS tip without any tapering or sanding if ESI conditions were optimized. The Taylor cone was found to shrink around the inner diameter of the SS tubing, which permitted a low flow rate of 150 nL/min for sheathless microspray on the blunt tip (100 μm i.d. × 400 μm o.d.). It is believed that the wettability and/or hydrophobicity of SS tips are responsible for their micro‐ES performance. The outlet orifice was further nipped to reduce the size of the spray cone and limit the flow rate to 50–150 nL/min, resulting in peptide detection down to attomole quantities consumed per spectrum. The SS emitter was also integrated into a polymethylmethacrylate microchip and demonstrated satisfactory performance in the analysis and identification of a myoglobin digest. Copyright © 2003 John Wiley & Sons, Ltd.
Optimization of matrix‐assisted laser desorption/ionization time‐of‐flight collision‐induced dissociation using poly(ethylene glycol)
Authors: Hoteling Andrew J. , Kawaoka Kenji , Goodberlet Mary C. , Yu Wan‐Mo , Owens Kevin G.
Published: July 2003

Details of the optimization of the collision‐induced dissociation (CID) process, using a collision cell on a matrix‐assisted laser desorption/ionization (MALDI) time‐of‐flight (TOF) mass spectrometer, are described using poly(ethylene glycol) 1000 (PEG 1000) as a model analyte. The effects of collision gas identity (helium, air, and argon), as well as collision gas pressure, on the resulting MS/MS data were investigated. With PEG 1000, helium was found to give the best results with respect to signal‐to‐noise (S/N) ratio. The optimum pressure for each gas was found to be in the range where the precursor ion signal was attenuated to approximately 30–50% for helium and 40–60% for argon. The effect of cation choice (Li, Na, and K) on the CID of PEG was also studied. CID spectra were produced for each, but PEG cationized with lithium was found to produce the spectra with the highest S/N ratio. The MALDI‐TOF CID spectra that were generated for PEG were compared with the high‐energy and low‐energy MS/MS spectra obtained from a sector mass spectrometer and from a triple quadrupole mass spectrometer, respectively. The results observed for PEG confirm that CID on a MALDI‐TOF mass spectrometer is a high‐energy MS/MS technique. Copyright © 2003 John Wiley & Sons, Ltd.
Use of doubly protonated molecules in the analysis of cathedulins in crude extracts of khat (Catha edulis) by liquid chromatography/serial mass spectrometry
Authors: Kite Geoffrey C. , Ismail Muna , Simmonds Monique S. J. , Houghton Peter J.
Published: July 2003

Analysis of crude methanolic extracts of fresh khat (Catha edulis) by liquid chromatography/mass spectrometry (LC/MS) revealed the presence of 62 cathedulin alkaloids (compared with 15 published structures). Many cathedulins generated doubly protonated molecules following electrospray ionisation and the ratio of doubly to singly protonated species could be manipulated by adjusting the electrospray capillary position and source conditions. By selecting the doubly protonated species for serial mass spectrometric analysis (MS/MS), it was possible to use an ion trap mass spectrometer to observe singly charged product ions at lower m/z values than ion trap MS/MS analysis of [M+H]+ would have allowed. These spectra were particularly valuable in elucidating the acylation patterns of cathedulins where MS/MS analysis of [M+H]+ resulted in loss of a large neutral species to yield a small singly charged fragment below the lower limit for ion trapping. Acylation patterns for most of the 62 cathedulins are proposed from mass spectrometric analysis, and the data obtained for a major unreported cathedulin of mass 1001 Da suggest that it belongs to a new group of cathedulins having a cathate dilactone bridge but not an evoninate bridge. Copyright © 2003 John Wiley & Sons, Ltd.
Stable isotope labeling of phosphopeptides for multiparallel kinase target analysis and identification of phosphorylation sites
Authors: Glinski Mirko , Romeis Tina , Witte Claus‐Peter , Wienkoop Stefanie , Weckwerth Wolfram
Published: July 2003

An approach for multiparallel target identification and relative quantification of in vitro kinase activities in two different biological samples, using liquid chromatography/mass spectrometry (LC/MS), is described. Synthetic target peptides, containing the putative regulatory phosphorylation sites of sucrose‐phosphate synthase (SPS) isoenzymes from Arabidopsis thaliana, were simultaneously in vitro phosphorylated and their phosphorylation states determined. Quantification was achieved by stable isotope labeling of the phosphoserine moiety with ethanethiol and [2D5]‐ethanethiol. This revealed different kinase activities in extracts of wild‐type (WT) plants and mutant plants lacking plastidic phosphoglucomutase (PGM). The multiparallel assay allowed the determination of favored substrate specificities among the putative phosphorylation sites in SPS. Additionally, we extended the method to unambiguously identify phosphorylation sites in peptides via differential labeling. Copyright © 2003 John Wiley & Sons, Ltd.
Determination of stavudine in human serum by on‐line solid‐phase extraction coupled to high‐performance liquid chromatography with electrospray ionization tandem mass spectrometry: application to a bioequivalence study
Authors: Raices Renata S. L. , Salvadori Myriam C. , Estrela Rita de Cassia E. , Neto Francisco R. de Aquino , Suarez‐Kurtz Guilherme
Published: July 2003

A method based on solid‐phase extraction (SPE) coupled to high‐performance liquid chromatography (HPLC) with positive ion electrospray ionization tandem mass spectrometry (ESI‐MS/MS) detection was developed for the determination of stavudine in human serum, using didanosine as internal standard. The acquisition was performed in multiple reaction monitoring (MRM) mode. The method was linear over the studied range (10–2000 ng/mL), with r2 > 0.99, and the run time was 4 min. The intra‐ and inter‐assay precisions (%) were in the ranges 0.1–13.6 and 2.6–9.9, respectively, and the intra‐ and inter‐assay accuracies were >92%. The absolute recoveries were approximately 100% (10 ng/mL), 98% (30 ng/mL), 105% (750 ng/mL) and 105% (1500 ng/mL). The limits of detection and quantitation were 4 and 10 ng/mL, respectively. The analytical method was applied to a bioequivalence study, in which 24 healthy adult volunteers (12 men) received single oral doses (40 mg) of reference and two test stavudine formulations, in an open, three‐period, randomized, crossover protocol. The 90% confidence interval of the individual ratios (test formulation/reference formulation) for Cmax (peak serum concentration), AUC0–10 and AUC0–inf (areas under the serum concentration vs. time curve from time zero to 10 h and to infinity, respectively), were in the range 80–125%, which supports the conclusion that the two test formulations are bioequivalent to the reference formulation with respect to the rate and extent of stavudine absorption. Copyright © 2003 John Wiley & Sons, Ltd.
Investigations into the use of a reverse scan in a quadrupole ion trap mass spectrometer
Authors: Dobson G. , Murrell J. , Despeyroux D. , Wind F. , Tabet J.‐C.
Published: July 2003

The forward scan (i.e. an increasing RF voltage ramp for the mass‐selective instability scan) is commonly used as an analytical scan for ion detection with quadrupole ion trap instruments. A number of phenomena have been observed while using this scan technique. These include space charge effects resulting in the delayed ejection of ions from the ion trap, and the fragmentation of fragile ions producing very broad peaks. Here the use of a reverse scan (i.e. a decreasing RF voltage ramp) is examined to determine the effect of the above phenomena in this acquisition method. With regard to space charge effects, the apparent reduction of the carbon isotope spacing below one Thomson (for singly charged ions) that is observed with the forward scan is now replaced by an apparent increase in this spacing. The reverse scan, which optimizes at lower axial modulation ejection voltages than the forward scan, allows for the intact ejection of fragile ions under its typical operating conditions whereas the forward scan results in fragmentation. Reducing the axial modulation voltage for the ejection of ions in the forward scan results in less dissociation of the fragile ions during ion ejection, but with the observation of ghost peaks due to incomplete ejection of all of the ions at the resonance ejection condition. While performing the reverse scan experiment, the formation of product ions from dissociation of the MH+ ion has also been observed. Copyright © 2003 John Wiley & Sons, Ltd.