bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization of Patched‐associated rhabdomyosarcoma
Authors: Kappler Roland , Calzada‐Wack Julia , Schnitzbauer Udo , Koleva Milena , Herwig Astrid , Piontek Guido , Graedler Florian , Adamski Jerzy , Heinzmann Ulrich , Schlegel Jürgen , Hemmerlein Bernhard , Quintanilla‐Martinez Leticia , Hahn Heidi 
Published: July 2003

AbstractMutations in the human homologue of Drosophila Patched1 (PTCH1) have been found in several common tumours including basal cell carcinoma, medulloblastoma, and rhabdomyosarcoma (RMS). Medulloblastoma and RMS are also present in the murine model for Ptch1 deficiency. Tumours in heterozygous Ptch1neo67/+ mice consistently exhibit elevated transcript levels of the proto‐oncogene Gli1, of Ptch1 itself, and of the insulin‐like growth factor 2 (Igf2). The present study has investigated additional molecular changes in RMSs of Ptch1 mutant mice by means of microarray analysis and protein expression analysis. The data show activation of the cell survival‐promoting Akt/protein kinase B (Pkb). Furthermore, RMSs express increased levels of the anti‐apoptotic protein Bcl‐2 and of genes and proteins known to inhibit cell proliferation, including Gadd45a and p27kip1. Taken together, the data suggest that the formation of RMSs in Ptch1 mutants is associated with the ability of tumour cells to resist apoptosis. Copyright © 2003 John Wiley & Sons, Ltd.
Discriminating expression of differentiation markers evolves in transplants of benign and malignant human skin keratinocytes through stromal interactions
Authors: Tomakidi Pascal , Stark Hans‐Juergen , Herold‐Mende Christel , Bosch Franz Xaver , Steinbauer Heinrich , Fusenig Norbert E. , Breitkreutz Dirk 
Published: July 2003

AbstractAccumulating evidence indicates a decisive role for the adjacent stroma in tumour growth and dissemination. However, it is not clear how far altered differentiation such as expression of aberrant keratins and vimentin, common in invasive human carcinomas, may reflect intrinsic cell properties or a response to the tumour environment. We have addressed this by transplanting benign and malignant human HaCaT‐ras keratinocytes, seeded on collagen matrix, onto nude mice. Initially, epithelia derived from benign and malignant cells, being separated from host stroma by collagen, were poorly organized and exhibited the same differentiation markers, as identified by immunofluorescence and in situ hybridization. Epidermal basal and suprabasal keratins were expressed persistently even upon contact with newly formed stroma and malignant cell invasion. In contrast, non‐epidermal keratins (K4/K13, K8/18, K19), which were similarly synthesized by benign and malignant cells in culture and in early transplants, were differentially regulated with increasing stromal vicinity. While both proteins and mRNAs were downregulated in benign epithelia, the malignant, invasive tumour cells continuously expressed these non‐epidermal keratins throughout (K19), suprabasally (K4/13) or at invasive sites (K8/18). Furthermore, the mesenchymal protein vimentin was expressed de novo in invasive areas confronting tumour stroma. Thus, atypical tissue markers, similarly synthesized in isolated cells in vitro, are downregulated in benign but maintained and upregulated in malignant epithelia. This is presumably caused by the neighbouring stroma being permanently activated by malignant epithelia. Copyright © 2003 John Wiley & Sons, Ltd.
Extracellular matrix remodelling: the role of matrix metalloproteinases
Authors: Stamenkovic Ivan 
Published: July 2003

AbstractMatrix metalloproteinases (MMPs) are a growing family of metalloendopeptidases that cleave the protein components of the extracellular matrix and thereby play a central role in tissue remodelling. For many years following their discovery, MMPs were believed to function primarily as regulators of ECM composition and to facilitate cell migration simply by removing barriers such as collagen. It is becoming increasingly clear, however, that MMPs are implicated in the functional regulation of a host of non‐ECM molecules that include growth factors and their receptors, cytokines and chemokines, adhesion receptors and cell surface proteoglycans, and a variety of enzymes. MMPs therefore play an important role in the control of cellular interactions with and response to their environment in conditions that promote tissue turnover, be they physiological, such as normal development, or pathological, such as inflammation and cancer. This review summarizes some of the recent discoveries that have shed new light on the role of MMPs in physiology and disease. Copyright © 2003 John Wiley & Sons, Ltd.
The myofibroblast in wound healing and fibrocontractive diseases
Authors: Gabbiani G 
Published: July 2003

AbstractThe demonstration that fibroblastic cells acquire contractile features during the healing of an open wound, thus modulating into myofibroblasts, has open a new perspective in the understanding of mechanisms leading to wound closure and fibrocontractive diseases. Myofibroblasts synthesize extracellular matrix components such as collagen types I and III and during normal wound healing disappear by apoptosis when epithelialization occurs. The transition from fibroblasts to myofibroblasts is influenced by mechanical stress, TGF‐β and cellular fibronectin (ED‐A splice variant). These factors also play important roles in the development of fibrocontractive changes, such as those observed in liver cirrhosis, renal fibrosis, and stroma reaction to epithelial tumours. Copyright © 2003 John Wiley & Sons, Ltd.
Functional structure and composition of the extracellular matrix
Authors: Bosman Fred T , Stamenkovic Ivan 
Published: July 2003

AbstractIn this brief introductory paper the general structure and the molecular composition of the extracellular matrix are outlined. Ultrastructural morphology of the extracellular matrix is introduced and subsequently the molecular structure of each of the main protein families, which together make up the extracellular matrix, is reviewed. Collagens, laminins, tenascins, and proteoglycans are addressed. An important common feature is the domain structure of these in general very large proteins. Several families have domains in common, which favours extensive interactions. Integrins play an important role in these interactions and also in the communication between cells and the matrix. The extracellular matrix appears to be a very dynamic structure, which has a prominent role in normal development as well as in a variety of disease processes. Matrix metalloproteinases are essential actors in this complex interplay between cells and the extracellular matrix. Copyright © 2003 John Wiley & Sons, Ltd.
The clinical pathology of severe acute respiratory syndrome (SARS): a report from China
Authors: Ding Yanqing , Wang Huijun , Shen Hong , Li Zhuguo , Geng Jian , Han Huixia , Cai Junjie , Li Xin , Kang Wei , Weng Desheng , Lu Yaodan , Wu Dehua , He Li , Yao Kaitai 
Published: July 2003

AbstractIn order to investigate the clinical pathology of severe acute respiratory syndrome (SARS), the autopsies of three patients who died from SARS in Nan Fang Hospital Guangdong, China were studied retrospectively. Routine haematoxylin and eosin (H&E) staining was used to study all of the tissues from the three cases. The lung tissue specimens were studied further with Macchiavello staining, viral inclusion body staining, reticulin staining, PAS staining, immunohistochemistry, ultrathin sectioning and staining, light microscopy, and transmission electron microscopy. The first symptom was hyperpyrexia in all three cases, followed by progressive dyspnoea and lung field shadowing. The pulmonary lesions included bilateral extensive consolidation, localized haemorrhage and necrosis, desquamative pulmonary alveolitis and bronchitis, proliferation and desquamation of alveolar epithelial cells, exudation of protein and monocytes, lymphocytes and plasma cells in alveoli, hyaline membrane formation, and viral inclusion bodies in alveolar epithelial cells. There was also massive necrosis of splenic lymphoid tissue and localized necrosis in lymph nodes. Systemic vasculitis included oedema, localized fibrinoid necrosis, and infiltration of monocytes, lymphocytes, and plasma cells into vessel walls in the heart, lung, liver, kidney, adrenal gland, and the stroma of striated muscles. Thrombosis was present in small veins. Systemic toxic changes included degeneration and necrosis of the parenchyma cells in the lung, liver, kidney, heart, and adrenal gland. Electron microscopy demonstrated clusters of viral particles, consistent with coronavirus, in lung tissue. SARS is a systemic disease that injures many organs. The lungs, immune organs, and systemic small vessels are the main targets of virus attack, so that extensive consolidation of the lung, diffuse alveolar damage with hyaline membrane formation, respiratory distress, and decreased immune function are the main causes of death. Copyright © 2003 John Wiley & Sons, Ltd.
Application of atmospheric pressure chemical ionisation mass spectrometry in the analysis of barbiturates by high‐speed analytical countercurrent chromatography
Authors: Jones Jonathan J. , Kidwell Huw , Games David E. 
Published: July 2003

AbstractFour barbiturates (barbital, allobarbital, phenobarbital and butalbital) were analysed using high‐speed analytical countercurrent chromatography (HSACCC) and high‐performance liquid chromatography (HPLC) interfaced with mass spectrometry, using negative mode atmospheric pressure chemical ionisation (APCI). The polar biphasic solvent system of butyronitrile/acetonitrile/water (1:1:1) was used, in the upper‐stationary, lower‐mobile mode of operation, at a flow rate of 1 mL/min and a rotational speed of 1200 rpm, equating to an applied ‘g’‐field of 177 g. The fractional stationary phase retention (SF) was 0.58. Representative mass spectral data are presented from the HPLC and the HSACCC analyses. Structural information was obtained using source‐induced fragmentation at increased source block voltages. The effect of increasing g‐field on chromatographic resolution is illustrated using the binary base system of butyronitrile/water (1:1), under electrospray ionisation. Copyright © 2003 John Wiley & Sons, Ltd.
Electrochemical oxidation and cleavage of peptides analyzed with on‐line mass spectrometric detection
Authors: Permentier Hjalmar P. , Jurva Ulrik , Barroso Begoña , Bruins Andries P. 
Published: July 2003

AbstractAn on‐line electrochemistry/electrospray mass spectrometry system (EC/MS) is described that allows fast analysis of the oxidation products of peptides. A range of peptides was oxidized in an electrochemical cell by application of a potential ramp from 0 to 1.5 V during passage of the sample. Electrochemical oxidation of peptides was found to occur readily when tyrosine was present. Tyrosine was found to be oxidized between 0.5 and 1.0 V to various oxidation products, including peptide fragments formed by hydrolysis at the C‐terminal side of tyrosine. The results confirm earlier knowledge on the mechanisms and reaction products of chemical and electrochemical peptide oxidation. Methionine residues are also readily oxidized, but do not induce peptide cleavage. At potentials higher than about 1.1 V, additional oxidation products were observed in some peptides, including loss of 28 Da from the C‐terminus and dimerization. The tyrosine‐specific cleavage reaction suggests a possible use of the EC/MS system as an on‐line protein digestion and peptide mapping system. In addition, the system can be used to distinguish phosphorylated from unphosphorylated tyrosine residues. Four forms of the ZAP‐70 peptide ALGADDSYYTAR with both, either or neither tyrosine phosphorylated were subjected to a 0–1.5 V potential ramp. Oxidation of, and cleavage adjacent to, tyrosine was observed exclusively at unphosphorylated tyrosine residues. Copyright © 2003 John Wiley & Sons, Ltd.
Proton affinity of proline and modified prolines using the kinetic method: role of the conformation investigated by ab initio calculations
Authors: Mezzache S. , Afonso C. , Pepe C. , Karoyan P. , Fournier F. , Tabet J.‐C. 
Published: July 2003

AbstractThe proton affinities of proline, cis‐3‐methylproline and cis‐3‐ethylproline have been measured by the kinetic method using an ion trap instrument; the values obtained are 936, 940.5, and 943 kJ mol−1, respectively. The experimental values are consistent with those obtained by high‐level ab initio calculations (B3LYP/6−31+G*//B3LYP/6−31G* and B3P86/6−31+G*//B3LYP/6−31G*). Several conformations of neutral and protonated proline were considered, in particular the endo and exo ring structure and the position of the carboxyl group. These results show the importance of the position of the hydrogen atom of the carboxyl group in determining the most stable protonated proline structure. Copyright © 2003 John Wiley & Sons, Ltd.
Mass spectral fragmentation of (S,S)‐2‐substituted 4,4‐diphenyl‐3,1‐oxazabicyclo[3.3.0]octanes: ring contraction of pyrrolidine and 1,3‐oxazolidine in mass spectrometry
Authors: Xu Jiaxi , Zuo Gang 
Published: July 2003

AbstractThe mass spectral behaviour of (S,S)‐2‐substituted 4,4‐diphenyl‐3,1‐oxazabicyclo[3.3.0]octanes has been studied with the aid of mass‐analyzed ion kinetic energy spectrometry and accurate mass measurements under fast atom bombardment (FAB) and electron impact (EI) ionization conditions. Under FAB ionization, all compounds show a tendency to form protonated aldehyde or benzophenone ions and to form protonated 1‐azabicyclo[3.1.0]hexane ions, which can further lose an ethylene or cyclopropane from the pyrrolidine ring to produce protonated 1‐azabicyclo[1.1.0]butane ions and 3H‐azirine ions, respectively. Under EI ionization, a similar fragmentation to that under FAB ionization was observed. The title compounds also show a tendency to yield oxirane ions and oxirenium ions by loss of pyrrolidine and pyrrolidine plus H. Ring contractions of 1,3‐oxazolidine by loss of an aldehyde or ketone and of pyrrolidine by loss of an ethylene or cyclopropane were observed under both FAB and EI ionization conditions. Copyright © 2003 John Wiley & Sons, Ltd.
Identification of an unknown β‐agonist in feed by liquid chromatography/bioassay/quadrupole time‐of‐flight tandem mass spectrometry with accurate mass measurement
Authors: Nielen M. W. F. , Elliott C. T. , Boyd S. A. , Courtheyn D. , Essers M. L. , Hooijerink H. H. , Bennekom E. O. van , Fuchs R. E. M. 
Published: July 2003

AbstractA new approach to the search for residues of unknown growth promoting agents such as anabolic steroids and β‐agonists in feed is presented. Following primary extraction and clean‐up, samples are separated using gradient liquid chromatography (LC). The effluent is split towards two identical 96‐well fraction collectors and an optional electrospray quadrupole time‐of‐flight mass spectrometry (QTOFMS) system for accurate mass measurement. One 96‐well plate is used for a bioassay (enzyme‐immuno assay, receptor assay) and will detect the bioactivity and position of the relevant peak in the chromatogram. The positive well in the second 96‐well plate is used for identification by LC/QTOFMS/MS. The value of this LC/bioassay/QTOFMS/MS methodology is highlighted by the finding and structure elucidation of a new β‐agonist in a feed extract. Copyright © 2003 John Wiley & Sons, Ltd.
An approach to quantitative proteome analysis by labeling tryptophan residues
Authors: Kuyama Hiroki , Watanabe Makoto , Toda Chikako , Ando Eiji , Tanaka Koichi , Nishimura Osamu 
Published: July 2003

AbstractThis report describes a method for quantification and sequence identification of individual proteins in complex mixtures. The method is based on labeling with the chemical reagent 2‐nitrobenzenesulfenyl chloride (NBSCl) in conjunction with tandem mass spectrometry. In this method, selective introduction of the 2‐nitrobenzenesulfenyl (NBS) moiety onto tryptophan residues is achieved, and a 6 Da mass differential is generated using 13C6‐labeled NBSCl (NBSCl‐13C6) and 12C6‐labeled NBSCl (NBSCl‐12C6). The 6 Da mass differential between the NBS‐12C6‐labeled and the NBS‐13C6‐labeled peptides assigns a mass signature to all tryptophan‐containing peptides in any pool of proteolytic digests for protein identification through peptide mass mapping. Using this strategy, we compared the protein expression in rat sera using a normal (control) rat (Crj:Wistar) and a hyperglycemic rat (GK/Crj). The stable isotope dilution techniques used in this method provide highly accurate relative quantification. The NBS approach offers a widely applicable means of analyzing protein mixtures derived from biological samples, and the method described here presents an effective and simplified approach to proteome analysis. Copyright © 2003 John Wiley & Sons, Ltd.
Blurred affinities: tracing the influence of North Indian classical music in Keith Jarrett's solo piano improvisations
Authors: Blume Gernot 
Published: July 2003

In the first forty years of his career, American pianist Keith Jarrett has established a reputation in multiple stylistic directions. Jarrett has typically incorporated influences as varied as bebop, country, rock, gospel, minimalism, baroque and classical styles into his often lengthy improvisations. Vital to his musical persona, but less obvious, is the influence North Indian classical music has had in shaping Jarrett's improvisatory strategies. Although he never formally studied Indian music, and although his instrument – the piano – is far removed from the conceptual backdrop of North Indian raga performance, Indian music was a central component in the artistic climate out of which his improvised solo recitals grew.A cultural climate of global influences was the backdrop to the development of Jarrett's solo concerts. Therein, perhaps, lies one key to understanding the spell that this music has cast on large and international audiences. With this format, Jarrett tapped into the ambiance of a particular historic moment, which combined a desire for change with the discovery of spiritual and musical traditions outside the Western world.In this paper I will demonstrate how explicit and implicit references to classical Indian principles of music making helped shape Jarrett's unique free solo concerts.
Where in the world is the hip hop nation?
Authors: Templeton Inez H. 
Published: July 2003

The ‘Hood Comes First: Race, Space and Place in Rap and Hip-Hop. By Murray Forman. Middletown: Wesleyan University Press, 2002. 400 pp.Global Noise: Rap and Hip-Hop Outside the USA. Edited by Tony Mitchell. Middletown: Wesleyan University Press, 2001. 352 pp.
Calcineurin inhibitors exert rapid reduction of inflammatory pain in rat adjuvant‐induced arthritis
Authors: Magari Katsue , Miyata Susumu , Ohkubo Yoshitaka , Mutoh Seitaro , Goto Toshio 
Published: July 2003

FK506 and cyclosporin A (CsA) are immunosuppressive drugs, that specifically inhibit T‐cell activation via calcineurin inhibition. This study was undertaken to investigate whether calcineurin inhibitors exert analgesic actions in rat adjuvant‐induced arthritis (AIA), an animal model of rheumatoid arthritis (RA).
AIA was induced in female Lewis rats. Single doses of FK506 and CsA were orally administered to arthritic rats 17 days after arthritis induction. Intensity of hyperalgesia was assessed by measuring the pain threshold of hind paws. Tumor necrosis factor (TNF)‐α, IL‐1β and PGE2 levels in paw extracts were determined by ELISA. TNF activity was measured by L929 cell cytotoxicity assay. IL‐1β and cyclooxygenase (COX) mRNA expression in arthritic paws were measured by RT–PCR.
Single doses of FK506 and CsA markedly reduced joint hyperalgesia 24 h after drug administration, without affecting inflammation in an advanced stage of AIA.
The calcineurin inhibitors partially reduced the elevated level of TNF‐α in arthritic paws, however, the analgesic effects of these drugs were not associated with the reduction in TNF‐α level.
Moreover, treatment with anti‐rat TNF‐α antibody did not affect the hyperalgesia, when TNF‐α activity was suppressed in arthritic paws by that treatment.
Both calcineurin inhibitors reduced the elevated level of IL‐1β in arthritic paws to a normal level, 24 h after drug administration.
FK506 reduced IL‐1β and COX‐2 mRNA expression and PGE2 level in arthritic paws.
In conclusion, calcineurin inhibitors rapidly reduce joint hyperalgesia probably by downregulating IL‐1β, but not TNF‐α, in AIA. Our findings may provide a new strategy for the treatment of pain in RA.

British Journal of Pharmacology (2003) 139, 927–934. doi:10.1038/sj.bjp.0705310
Changes in functional and histological distributions of nitric oxide synthase caused by chronic hypoxia in rat small pulmonary arteries
Authors: Shirai Mikiyasu , Pearson James T , Shimouchi Akito , Nagaya Noritoshi , Tsuchimochi Hirotsugu , Ninomiya Ishio , Mori Hidezo 
Published: July 2003

Chronic hypoxia (CH) increases lung tissue expression of all types of nitric oxide synthase (NOS) in the rat. However, it remains unknown whether CH‐induced changes in functional and histological NOS distributions are correlated in rat small pulmonary arteries.
We measured the effects of NOS inhibitors on the internal diameters (ID) of muscular (MPA) and elastic (EPA) pulmonary arteries (100–700 μm ID) using an X‐ray television system on anaesthetized rats. We also conducted NOS immunohistochemical localization on the same vessels.
Nonselective NOS inhibitors induced ID reductions in almost all MPA of CH rats (mean reduction, 36±3%), as compared to ∼60% of control rat MPA (mean, 10±2%). The inhibitors reduced the ID of almost all EPA with similar mean values (∼26%) in both CH and control rats. On the other hand, inducible NOS (iNOS)‐selective inhibitors caused ID reductions in ∼60% of CH rat MPA (mean, 15±3%), but did so in only ∼20% of control rat MPA (mean, 2±2%). This inhibition caused only a small reduction (mean, ∼4%) in both CH and control rat EPA. A neuronal NOS‐selective inhibitor had no effect.
The percentage of endothelial NOS (eNOS)‐positive vessels was ∼96% in both MPA and EPA from CH rats, whereas it was 51 and 91% in control MPA and EPA, respectively. The percentage for iNOS was ∼60% in both MPA and EPA from CH rats, but was only ∼8% in both arteries from control rats.
The data indicate that in CH rats, both functional and histological upregulation of eNOS extensively occurs within MPA. iNOS protein increases sporadically among parallel‐arranged branches in both MPA and EPA, but its vasodilatory effect is predominantly observed in MPA. Such NOS upregulation may serve to attenuate hypoxic vasoconstriction, which occurs primarily in MPA and inhibit the progress of pulmonary hypertension.

British Journal of Pharmacology (2003) 139, 899–910. doi:10.1038/sj.bjp.0705312