bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractHuman 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

AbstractBy 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

AbstractAccurate 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

AbstractIn 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

Abstract

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

AbstractMucins 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

AbstractTumour 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

Abstract1158 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

AbstractLiver 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

AbstractCell 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

AbstractGold‐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

AbstractThe 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

AbstractDetails 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

AbstractAnalysis 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

AbstractAn 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.