bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emmprin, a cell surface inducer of matrix metalloproteinases (MMPs), is expressed in T‐cell lymphomas
Authors: Nabeshima Kazuki , Suzumiya Junji , Nagano Mitsuyuki , Ohshima Koichi , Toole Bryan P , Tamura Kazuo , Iwasaki Hiroshi , Kikuchi Masahiro 
Published: February 2004

AbstractDegradation of the extracellular matrix by matrix metalloproteinases (MMPs) is a crucial step in tumour invasion and metastasis. In human carcinomas, tumour cell–fibroblast interactions (TFIs) have been demonstrated to play a role in the up‐regulation of MMP levels in tumours, and emmprin is a surface molecule on tumour cells that stimulates nearby fibroblasts to produce MMP‐1, 2, and 3. T‐cell lymphomas frequently show extranodal organ involvement and skin invasion, but a role for TFIs in their invasion has not been examined in detail. This study investigated TFIs in T‐cell lymphomas with special reference to emmprin expression and MMP production. Immunohistochemically, only germinal centre cells and some histiocytes expressed emmprin in non‐neoplastic lymph nodes (ten cases), while all T‐cell lymphomas [14 cases of adult T‐cell leukaemia/lymphoma (ATLL), six cases of lymphoblastic lymphoma, seven cases of anaplastic large cell lymphoma, and nine cases of angio‐immunoblastic T‐cell lymphoma] expressed emmprin strongly and diffusely. FACS analysis of peripheral blood from normal individuals revealed that small fractions of B‐cells, T‐cells, and monocytes expressed emmprin, whereas emmprin‐expressing T‐cells were much increased in number, and expressed this protein to a higher level, in ATLL patients. In vitro co‐cultures of emmprin‐positive HTLV‐1‐transformed lymphocytes (MT‐2) and emmprin‐negative human fibroblasts enhanced the production of pro‐MMP‐2 (gelatinase A) and active MMP‐2, compared with cultures of either cell type alone. This stimulation was inhibited by an activity‐blocking peptide against emmprin. Moreover, in histopathological sections from patients with ATL skin involvement, MMP‐2 was demonstrated in fibroblasts around infiltrating ATL cells, but not in fibroblasts in non‐diseased areas. In conclusion, emmprin is overexpressed by T‐lymphoma cells, when compared with normal counterparts, and facilitates MMP‐2 production via interactions with fibroblasts, which could play a role in stromal invasion by lymphoma cells. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Increased expression of Met protein is associated with up‐regulation of hypoxia inducible factor‐1 (HIF‐1) in tumour cells in papillary carcinoma of the thyroid
Authors: Scarpino Stefania , Cancellario d'Alena Francesca , Di Napoli Arianna , Pasquini Anna , Marzullo Antonella , Ruco Luigi P 
Published: February 2004

AbstractMet protein, the high affinity receptor for hepatocyte growth factor (HGF), was highly expressed by the tumour cells of 64 well‐differentiated papillary carcinomas of the thyroid. The p145 mature form and the p170 precursor form of the protein were both isolated from the tumours. Enhanced expression of Met protein was associated with a 9.5 ± 5‐fold increase in MET RNA transcript levels, suggesting increased transcription of the gene. In the same tumours, the levels of RNA transcripts for hypoxia inducible factor‐1 (HIF‐1), a potent stimulator of met gene transcription, were 4.5 ± 3‐fold higher than those present in the surrounding normal thyroid tissues. HIF‐1 is generally induced by hypoxia. Histological features suggestive of a hypoxia were observed in 37 of 50 tumours and included coagulative necrosis, psammoma bodies, cystic changes, intratumoural haemorrhage, and hyalinization of the fibrous stroma. Immunostaining for Met protein was particularly intense in some cells located at the tumour periphery which were characterized by an invasive phenotype. Microdissection of tumour cell nests from the invading front revealed that the levels of RNA transcripts for MET/HIF were higher than in the centre of the tumour in four of nine cases. Taken together, the findings of this study suggest that HIF‐1, perhaps driven by hypoxia, may be one of the factors leading to the increased transcription of met gene in papillary carcinoma and that this event is often more pronounced at the tumour periphery. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Reduced selenium‐binding protein 1 expression is associated with poor outcome in lung adenocarcinomas
Authors: Chen Guoan , Wang Hong , Miller Charles T , Thomas Dafydd G , Gharib Tarek G , Misek David E , Giordano Thomas J , Orringer Mark B , Hanash Samir M , Beer David G 
Published: February 2004

AbstractThe effects of selenium, an essential nutrient with anti‐carcinogenic properties, are mediated by selenium‐binding proteins. The protein expression status of human selenium‐binding protein 1 (SBP1) in human tumours and the exact function of this protein are not known. In this study, quantitative two‐dimensional polyacrylamide gel electrophoresis (2‐D PAGE) was used on 93 lung adenocarcinomas and ten uninvolved lung samples. Two likely isoforms of a 56 kD protein that showed a significantly decreased abundance in lung adenocarcinomas were observed. Tandem mass spectrometry and 2‐D western blot analysis identified these two proteins as human SBP1. Tumour tissue microarrays were utilized to examine the cellular expression patterns of SBP1 using immunohistochemistry. The same tissue samples were examined for SBP1 mRNA expression using oligonucleotide microarrays. Two major SBP1 isoforms were detected, with an acidic isoform (457) being significantly down‐regulated in lung adenocarcinomas compared with normal lung (p = 0.02). Two additional more acidic SBP1 isoforms were only observed in normal lung. SBP1 protein isoforms and SBP1 mRNA levels were significantly decreased in poorly differentiated (versus moderately and well‐differentiated), T2–T4 (versus T1), and bronchus‐derived (versus bronchioloalveolar) tumours. Low levels of SBP1 protein (native form, 460) correlated significantly with poor survival (p = 0.007). The lack of SBP1 expression was not due to gene deletion. Treatment of A549 lung adenocarcinoma cells with the methylation inhibitor 5‐azacytidine did not affect expression of the SBP1 protein. Analysis of the tumour proliferation status using Ki‐67 suggests that down‐regulated expression of SBP1 may reflect increased cell proliferation and decreased differentiation in lung adenocarcinomas. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Western blot analysis of a limited number of cells: a valuable adjunct to proteome analysis of paraffin wax‐embedded, alcohol‐fixed tissue after laser capture microdissection
Authors: Martinet Wim , Abbeloos Vanessa , Van Acker Nathalie , De Meyer Guido RY , Herman Arnold G , Kockx Mark M 
Published: February 2004

AbstractIn recent years, laser capture microdissection (LCM) has been used successfully to obtain distinct populations of cells for subsequent molecular analysis. Because of the limited sample availability and the absence of in vitro amplification steps for proteins, the use of LCM for proteome analysis largely depends on highly sensitive protein detection methods. In this study, a western blot protocol was developed and validated for the detection of β‐actin and the moderately expressed cell death protein caspase‐3 in small numbers of cells. Initially, cultured human U937 monocytes and whole sections of paraffin wax‐embedded, alcohol‐fixed human tonsils were used to optimize protein electrophoresis and western blotting conditions. High‐performance NuPAGE Bis‐Tris gels in combination with high‐quality transfer membranes, optimized antibody concentrations, and a sensitive chemiluminescent substrate provided a strong signal for β‐actin with ∼500 U937 cells. In the same way, procaspase‐3 could be identified with ∼1000 cells. Similar results were obtained with germinal centre cells that were procured from paraffin wax‐embedded, alcohol‐fixed human tonsils by LCM. Treatment of U937 cells with etoposide rapidly induced cell death and allowed the detection of active caspase‐3 with ∼2500 cells (0.8 pg of protein). The findings of this study suggest that western blotting is a valuable adjunct to proteome analysis of LCM procured cells. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Linkage of angiotensin I‐converting enzyme gene insertion/deletion polymorphism to the progression of human prostate cancer
Authors: Medeiros Rui , Vasconcelos André , Costa Sandra , Pinto Daniela , Lobo Francisco , Morais Antonio , Oliveira Jorge , Lopes Carlos 
Published: February 2004

AbstractAngiotensin‐converting enzyme (ACE) degrades vasodilator kinins and generates angiotensin II (Ang II). It has been reported that ACE is synthesized by the prostate and that the AT‐1 receptor subtype is the predominant prostatic Ang II receptor. A polymorphism in the human ACE gene has been described and the highest levels of circulating and tissue ACE activity are found in carriers of the DD genotype. In the present study, ACE genotypes were determined in 170 patients with prostate cancer and their association with disease progression was analysed. It was found that the DD genotype was present in 31 of 78 (39.8%) patients with advanced disease and in 19 of 82 (23.2%) with localized disease: this difference was statistically significant (OR = 2.18, 95% CI = 1.11–4.03; p = 0.024). Step‐wise logistic regression analysis was used to identify predictive parameters of advanced disease and it was observed that the DD genotype (p = 0.002, OR = 5.4, 95% CI = 1.84–16.06), high‐grade tumour (p < 0.001, OR = 8.04, 95% CI = 3.03–21.33), and high serum PSA (p < 0.001, OR = 10.87, 95% CI = 4.06–29.13) were significantly associated with advanced disease. The results of this study support the hypothesis that genetic factors related to ACE may influence the behaviour of human prostate cancer. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Arzneimittelwechselwirkungen mit H1‐Antihistaminika: Worauf sollte bei der Abgabe von Antihistaminika geachtet werden?
Authors: Haen Ekkehard 
Published: February 2004

AbstractH1‐Antihistaminika sind im allgemeinen gut verträgliche Substanzen, die auch nur zu wenigen Arzneimittelinteraktionen Anlass geben. Am relevantesten sind die pharmakodynamische Verstärkung der sedierenden Wirkung anderer ZNS‐aktiver Substanzen und der pharmakokinetisch bedingte Anstieg der Wirkstoffkonzentration bei Hemmung des Cytochrom‐P450‐Enzymsystems durch Arznei‐ und Lebensmittel mit der Folge potenziell lebensbedrohlicher Herzrhythmusstörungen. Werden H1‐Antihistaminika zur Behandlung von Allergien eingenommen, so sollten β‐Blocker nur mit großer Vorsicht angewendet werden.
H1‐Antihistaminika‐Medikation: Wie sieht die richtige Pharmazeutische Betreuung aus?
Authors: Teerling Ulrike 
Published: February 2004

AbstractH1‐Antihistaminika verfügen über das Potenzial, die Lebensqualität von Patienten zu verbessern [31]. Durch die sedierenden Eigenschaften, insbesondere der älteren H1‐Antihistaminika, ergeben sich oftmals schwerwiegende Folgen: So zeigten sich H1‐Antihistaminika sowohl als Ursache von Autounfällen als auch als eine der häufigsten Arzneimittel in Autopsieberichten von Piloten, deren Flugzeug abgestürzt war. Auch wenn Patienten sich nicht schläfrig fühlen, kann die Gehirnfunktion gelegentlich beeinträchtigt sein [32]. Aber auch die anderen diskutierten Neben‐ und Wechselwirkungen machen diese Substanzen zu einer sehr beratungsintensiven Arzneimittelgruppe.Die Auswahl des jeweils günstigsten H1‐Antihistaminikums sollte unter Berücksichtigung des Zulassungsstatuses (Indikation, Kinder, Schwangere) und der individuellen Erfordernisse des jeweiligen Individuums Patient (Sedierung erwünscht, kardiale Risikofaktoren, Begleitmedikation, Alter, Leber‐ oder Niereninsuffizienz) erfolgen.Das ideale H1‐Antihistaminikum existiert zur Zeit noch nicht, aber neue Substanzen befinden sich in der klinischen Erprobung [12].Zur richtigen Zeit, am richtigen Ort mit den richtigen Hinweisen eingenommen stellen sie ohne Frage eine wichtige, sichere Therapieoption bei den verschiedenen, genannten Krankheitsbildern dar.Dem Fazit von Herrn Prof. Mutschler bleibt auch in diesem Fall nichts hinzuzufügen:Eine unkritische Empfehlung für die Selbstmedikation ist entschieden abzulehnen! (H1‐Antihistaminika als freiverkäufliche Hypnotika
Ausgezeichnet!
Authors: Dingermann Theo , Zündorf Ilse 
Published: February 2004

AbstractGleich zwei pharmazeutische Hochschullehrer wurden Ende 2003 mit hoch‐dotierten Preisen ausgezeichnet: Prof. Dr. Bernd Clement aus Kiel erhielt für sein In‐vitro‐Modell zum Fremdstoffmetabolismus den mit 10.000 Euro dotierten Tierschutzpreis Schleswig‐Holstein und Prof. Dr. Michael Karas, Frankfurt, wurde zusammen mit Prof. Dr. Franz Hillenhamp, Münster, der mit 30.000 Euro dotierte Beckurts‐Preis für ihre revolutionierenden Arbeiten auf dem Gebiet der Massenspektrometrie verliehen.
Kampf der Birkenpollenallergie
Authors: Zündorf Ilse 
Published: February 2004

AbstractCa. 100 Millionen Menschen leiden unter einer Birkenpollenallergie. Und immerhin 70 % der Birkenpollen‐Allergiker entwickeln auch Typ‐1‐Hypersensitivitätsreaktionen gegenüber diversen Früchten und Gemüsetypen.
Cadmium ist ein Metalloestrogen
Authors: Götz Regina 
Published: February 2004

AbstractCadmium wirkt wie Estrogen — das ist das Ergebnis einer tierexperimentellen Studie, die im Wissenschaftsmagazin Nature Medicine veröffentlicht wurde. Die Studie wirft die Frage nach einer Neubewertung der Toxizität von Cadmium auf.
Sweet Substitute: A software tool for in silico fragmentation of peptide‐linked N‐glycans
Authors: Clerens Stefan , Van den Ende Wim , Verhaert Peter , Geenen Lieve , Arckens Lutgarde 
Published: February 2004

AbstractA software tool, Sweet Substitute, is described, which assists tandem mass spectrometry (MS/MS)‐based glycosylation characterization from within a tryptic digest. The algorithm creates a virtual nanoelectrospray‐quadrupole time‐of‐flight style‐MS/MS spectrum of any user‐defined N‐linked glycan structure. An empirical peak height modeling routine is implemented in the program. By comparing the theoretical MS/MS data with the deconvoluted and deisotoped experimental MS/MS data, the user is able to quickly assess whether a proposed candidate oligosaccharide structure is a plausible one.
Identification of chromosomally encoded membranal polypeptides of Bacillus anthracis by a proteomic analysis: Prevalence of proteins containing S‐layer homology domains
Authors: Chitlaru Theodor , Ariel Naomi , Zvi Anat , Lion Menahem , Velan Baruch , Shafferman Avigdor , Elhanany Eytan 
Published: February 2004

AbstractBacillus anthracis is the causative agent of anthrax disease. Improvement of existing anthrax vaccines, which are currently based on the administration of Protective Antigen (the highly immunogenic nontoxic subunit of the bacterial toxin) may entail other bacterial immunogenic elements, part of which are predicted to reside on the surface of bacterial cells. In the present study, membranal proteins extracted from a stationary‐phase culture of a nonvirulent B. anthracis strain, devoid of the native virulence plasmids pXO1 and pXO2, were separated by two‐dimensional electrophoresis (2‐DE) and a characteristic protein map was defined. The proteomic analysis allowed matix‐assisted laser desorption/ionization‐time of flight mass spectrometry‐assisted identification of 86 protein spots which represent the product of 30 individual open reading frames (ORF). Among these, a prevalent class of proteins was the S‐layer proteins (which were found to represent more than 75% of the B. anthracis membranal fraction) and proteins containing S‐layer homology (SLH)‐membranal localization domains. Five novel SLH proteins, previously inferred only from bioinformatic ORF analysis (draft genome sequence), were identified and one was shown to be a highly abundant membranal protein. Western blots of the 2‐DE gels were probed with sera from convalescent rabbits and guinea pigs infected with virulent B. anthracis (Vollum strain). This analysis revealed that B. anthracis immune animals exhibit antibodies against at least 14 distinct membranal proteins present in the 2‐DE map, establishing that these proteins are expressed in vivo and are able to elicit an immune response. The identification of the protein components of the B. anthracis membranal fraction, as well as the establishment of their potential immunogenicity, underscore the strength of the proteomic approach for identifying molecules which may serve for further analysis of immune and protective abilities.
Profiling the activity of G proteins in patient‐derived tissues by rapid affinity‐capture of signal transduction proteins (GRASP)
Authors: Berman David M. , Shih Ie‐Ming , Burke Lorri‐Anne , Veenstra Timothy D. , Zhao Yingming , Conrads Thomas P. , Kwon Sung Won , Hoang Van , Yu Li‐Rong , Zhou Ming , Kurman Robert J. , Petricoin Emanuel F. , Liotta Lance A. 
Published: February 2004

AbstractThe next phase in molecular medicine will require the ability to identify signal transduction events inside a cell, in the biologic context of the disease‐host interface and at a given point in time. New technologies are needed to profile the activity of these signaling pathways in patient tissue rather than cultured cell lines since the tumor‐host microenvironment influences the cellular proteome. We introduce such a technology, rapid affinity capture of signaling proteins (GRASP), to investigate the activity of signaling pathways from patient‐derived carcinomas and benign epithelial surfaces and apply it to studying important signaling events in ovarian carcinoma. During the progression from benign ovarian epithelium to invasive carcinoma, there is loss of repression of Rho A as evidenced by its dissociation from its inhibitor, Rho Guanine Nucleotide Dissociation Inhibitor (RhoGDI). GRASP is more informative than simply profiling transcript or protein levels. Furthermore, GRASP coupled with mass spectrometry allowed us to identify a protein‐binding partner of RhoGDI, demonstrating the power of this technology in the discovery of potentially novel protein‐protein interactions. GRASP represents an advance in the field of proteomics as it detects protein interactions present in cells as they exist in their native tissue microenvironment.
Database search post‐processing by neural network: Advanced facilities for identification of components in protein mixtures using mass spectrometric peptide mapping
Authors: Lokhov Petr G. , Tikhonova Olga V. , Moshkovskii Sergei A. , Goufman Eugene I. , Serebriakova Marina V. , Maksimov Boris I. , Toropyguine Ilya Yu. , Zgoda Victor G. , Govorun Vadim M. , Archakov Alexander I. 
Published: February 2004

AbstractDatabase search post‐processing by neural network was employed in peptide mapping experiments. The database search was performed using both the known algorithms and score functions, such as Bayesian, MOWSE, Z‐score, correlations between calculated and actual peptide length fractional abundance, and, in addition, the probability of protein digest pattern in peptide fingerprint, all embedded in locally developed program. The new signal‐processing algorithm based on neural network improves signal‐noise separation and is acceptable for automatic protein identification in mixtures. Its power was tested on Helicobacter pylori protein inventory after preceding protein separation by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE). Increase in protein identification success rate was observed, and about 100 proteins were identified with no need of human participation in database search estimation.
A two‐dimensional liquid‐phase separation method coupled with mass spectrometry for proteomic studies of breast cancer and biomarker identification
Authors: Hamler Rick L. , Zhu Kan , Buchanan Nathan S. , Kreunin Paweena , Kachman Maureen T. , Miller Fred R. , Lubman David M. 
Published: February 2004

AbstractA two‐dimensional liquid‐phase separation scheme coupled with mass spectrometry (MS) is presented for proteomic analysis of cell lysates from normal and malignant breast epithelial cell lines. Liquid‐phase separations consist of isoelectric focusing as the first dimension and nonporous silica reverse‐phase high‐performance liquid chromatography (NPS‐RP‐HPLC) as the second dimension. Protein quantitation and mass measurement are performed using electrospray ionization‐time of flight MS (ESI‐TOF MS). Proteins are identified by peptide mass fingerprinting using matrix‐assisted laser desorption ionization‐time of flight MS (MALDI‐TOF MS) and MALDI‐quadrupole time of flight (QTOF)‐tandem mass spectrometry (MS/MS). Two pH regions with 50–60 unique proteins in each pH range were chosen for analysis. Mass maps were created that allowed visualization of protein quantitation differences between normal and malignant breast epithelial cells. Of the approximately 110 unique proteins observed from mass mapping experiments over the limited pH range, 40 (36%) were positively identified by peptide mass fingerprinting and assigned to bands in the mass maps. Of these 40 proteins, 22 were more highly expressed in one or more of the malignant cell lines. These proteins represent potential breast cancer biomarkers that could aid in diagnosis, therapy, or drug development.
Photoaptamer arrays applied to multiplexed proteomic analysis
Authors: Bock Chris , Coleman Mike , Collins Brian , Davis Jody , Foulds Glenn , Gold Larry , Greef Chad , Heil Jim , Heilig Joseph S. , Hicke Brian , Nelson Hurst Michele , Husar Gregory M. , Miller Darcey , Ostroff Rachel , Petach Helen , Schneider Dan , Vant‐Hull Barry , Waugh Sheela , Weiss Allison , Wilcox Sheri K. , Zichi Dominic 
Published: February 2004

AbstractMultiplexed photoaptamer‐based arrays that allow for the simultaneous measurement of multiple proteins of interest in serum samples are described. Since photoaptamers covalently bind to their target analytes before fluorescent signal detection, the arrays can be vigorously washed to remove background proteins, providing the potential for superior signal‐to‐noise ratios and lower limits of quantification in biological matrices. Data are presented here for a 17‐plex photoaptamer array exhibiting limits of detection below 10 fM for several analytes including interleukin‐16, vascular endothelial growth factor, and endostatin and able to measure proteins in 10% serum samples. The assays are simple, scalable, and reproducible. Affinity of the capture reagent is shown to be directly correlated to the limit of detection for the analyte on the array.
Proteomic analysis of selected prognostic factors of breast cancer
Authors: Roberts Kylie , Bhatia Kiron , Stanton Peter , Lord Roger 
Published: February 2004

AbstractThe incidence of breast cancer is on the rise but as yet there is no guaranteed beneficial treatment for many of the sufferers. The treatments specific for breast and other hormone‐sensitive cancers work well at times, however, the population of women that they will benefit is relatively small. Many are limited to surgical, chemotherapy, and radiotherapy options. Here, using two‐dimensional electrophoresis (2‐DE) in conjunction with a silver stain and Western blotting approach, we attempt to locate selected known prognostic markers for breast cancer. With these results, we can exclude these proteins from the future search for potential pharmaceutical targets, using the same techniques. The proteins that were located include the estrogen receptor‐α, β‐casein, cytokeratin 7, calponin and bax. For each protein an estimated Mr and pI was gained. Each protein was found in multiple variants. By locating these proteins the number of unknown proteins found on the 2‐DE gel has been reduced, helping the future search for novel markers that are shown as being differentially expressed between healthy and cancerous tissue samples.