bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assay to measure CD59 mutations in CHO AL cells using flow cytometry
Authors: Ross Carley D. , Lim Chang‐Uk , Fox Michael H. 
Published: July 2005

AbstractBackgroundA sensitive mammalian cell mutation assay was developed previously using a Chinese hamster ovary cell line (CHO AL) that stably incorporates human chromosome 11. The assay measures mutations in the CD59 gene on chromosome 11 but it requires the use of rabbit complement and colony growth for mutant selection. We have developed a more rapid flow cytometry‐based mutation assay with CHO AL cells that uses monoclonal antibodies against CD59 to detect mutants and does not require colony formation.MethodsCHO AL cells were treated with γ‐radiation or N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) and then allowed to grow for various times for mutant expression. Cells were labeled with monoclonal antibodies against CD59 and analyzed by flow cytometry.ResultsNegative and positive populations were separated by over 100‐fold. Mixing various proportions of CD59‐positive and ‐negative cells demonstrated that the assay is highly linear (r2 = 0.9999) and sensitive (<0.05% background mutants). The yield of CD59‐inducible mutants was linearly related to dose for a clastogen (γ‐radiation) and point mutagen (MNNG). The mutant yield was time and treatment specific.ConclusionsMutations induced by genotoxic agents can be rapidly and sensitively measured in CHO AL cells using flow cytometry. © 2005 Wiley‐Liss, Inc.
Temporal and spatial expression of liver receptor homologue‐1 (LRH‐1) during embryogenesis suggests a potential role in gonadal development
Authors: Hinshelwood Margaret M. , Shelton John M. , Richardson James A. , Mendelson Carole R. 
Published: July 2005

AbstractLiver receptor homologue‐1 (LRH‐1), an orphan member of the nuclear receptor family highly expressed in adult mouse ovary, is closely related to steroidogenic factor 1 (SF‐1), known to be important in gonadal formation. To analyze the potential role of LRH‐1 in gonadal differentiation, we compared LRH‐1 and SF‐1 expression during mouse embryonic and postnatal development. LRH‐1 expression was first detected in the urogenital ridge before sexual determination, in primordial germ cells and surrounding somatic cells; expression persisted after differentiation into testes and ovaries. Of interest, LRH‐1 expression declined in the developing ovary and testis at embryonic day 15.5 but increased again just after birth in the ovary in granulosa cells and transiently in oocytes of developing follicles. By comparing and contrasting LRH and SF‐1 expression with the two tissue‐specific steroidogenic markers, cytochromes P450 aromatase and P450 17α‐hydroxylase/17,20 lyase, we provide evidence for a potential role for LRH‐1 in gonadal development, the initiation of folliculogenesis and regulation of estrogen biosynthesis within the ovary. Developmental Dynamics 234:159–168, 2005. © 2005 Wiley‐Liss, Inc.
Atom Transfer Radical Additions with the Cationic Half‐Sandwich Complex [Cp*Ru(PPh3)2(CH3CN)]OTf
Authors: Quebatte Laurent , Scopelliti Rosario , Severin Kay 
Published: July 2005

AbstractThe cationic ruthenium half‐sandwich complex [Cp*Ru(PPh3)2(CH3CN)][OTf] (2) (Cp* = η5‐C5Me5, OTf = SO3CF3) was synthesized by reduction of [Cp*RuCl2]2 with zinc in the presence of NaOTf and subsequent reaction with PPh3. When NaOTf was omitted, the corresponding tetrachlorozincate salts were obtained. Complex 2, as well as the salts [Cp*Ru(CH3CN)3]2[ZnCl4] (3) and [Cp*Ru(PPh3)2(CH3CN)]2[ZnCl4] (4), were characterized by single‐crystal X‐ray analysis. Complex 2 proved to be a potent catalyst for the atom transfer radical addition of CCl4 and CHCl3 to terminal olefins, displaying a performance superior to that of the previously described neutral catalyst [Cp*RuCl(PPh3)2]. For the addition of CHCl3 to styrene, a total turnover number of 890 was achieved. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Stereoselective Synthesis of the 5,5‐Difluoro‐(12R)‐ and ‐(12S)‐Leukotrienes B3
Authors: Lingam Manthati Vijaya , Grée Danielle , Grée René 
Published: July 2005

AbstractThe first synthesis of the 5,5‐difluoro‐(12R)‐ and ‐(12S)‐leukotrienes B3 is reported which uses a flexible and convergent strategy. The key steps involve a Sonogashira coupling between the bromodienone 4 and the propargylic difluoride 5; this is followed by a CBS type reduction to establish the (12R) or (12S) stereocenters. A final semihydrogenation, under controlled conditions, affords the required E,E,Z trienic system. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Matrix‐degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas
Authors: Held‐Feindt Janka , Paredes Elke Bernedo , Blömer Ulrike , Seidenbecher Constanze , Stark Andreas M. , Mehdorn H. Maximilian , Mentlein Rolf 
Published: July 2005

AbstractBrain tumors, in particular glioblastomas, have a high morbidity and mortality, mainly due to their invasive nature. A prerequisite for this invasiveness is cell migration based on increased expression of proteases digesting the extracellular matrix. Brevican, an important extracellular proteoglycan that is upregulated in glioblastomas, can be degraded by certain proteases. We demonstrate that in human glioblastomas secretory proteases like ADAMTS4 and ADAMTS5 (aggrecanases 1 and 2; ADAMTS = a disintegrin and metalloproteinase with thrombospondin motifs) are expressed on the mRNA and protein levels in considerable amounts. Real‐time RT‐PCR shows a higher levels of ADAMTS4 and 5 expressions in glioblastomas in situ, compared to cultured human glioblastoma cells. The upregulation of these proteases in vivo by cytokines may explain this difference. In vitro, transforming growth factor‐β induces ADAMTS4, but less ADAMTS5, and interleukin‐1β ADAMTS5, but not ADAMTS4. As demonstrated by immunohistochemistry and confocal microscopy in situ, ADAMTS5 expression is confined to proliferating glioblastoma cells of surgical tumor sections and with lower intensity to astroglial cells in normal brain sections, as opposed to brevican. In vitro, glioblastoma‐derived ADAMTS5 degrades recombinant human brevican to several smaller fragments. Our results show that ADAMTS4 and 5 are upregulated on proliferating glioblastoma cells and these proteases may contribute to their invasive potential. © 2005 Wiley‐Liss, Inc.
Cisplatin‐dependent upregulation of death receptors 4 and 5 augments induction of apoptosis by TNF‐related apoptosis‐inducing ligand against esophageal squamous cell carcinoma
Authors: Kondo Kan , Yamasaki Seiji , Sugie Tomoharu , Teratani Naoki , Kan Takatsugu , Imamura Masayuki , Shimada Yutaka 
Published: July 2005

AbstractTNF‐related apoptosis‐inducing ligand (TRAIL) is a member of the TNF superfamily known to induce apoptosis in a variety of cancers. The purpose of our study was to examine the effects of TRAIL in combination with cisplatin against esophageal squamous cell carcinoma (ESCC) cell lines in vitro and in vivo, and to elucidate underlying molecular mechanisms. Expression profiles of TRAIL receptors were investigated in 19 ESCC (KYSE) cell lines using RT‐PCR. Crystal violet staining assays were performed to reveal the sensitivity against TRAIL. Flow cytometric analyses of apoptosis induction and TRAIL receptor expression were performed. Furthermore, Western blot was used to clarify the apoptosis pathway involved, and a nude‐mouse xenograft model was used to show effects in vivo. Results show that death receptors (DR) 4 and 5 were expressed in 100% of the cell lines, and 79% (15/19) expressed 4 TRAIL receptors. There was only 1 cell line without decoy receptor expression. Eighteen cell lines were resistant to TRAIL, but in some, the combination treatment with cisplatin could overcome this resistance. They underwent apoptosis via activation of caspase‐8 and ‐3, and cisplatin‐dependent upregulation of DR4 and 5 was detected. Furthermore, pretreatment with cisplatin followed by TRAIL resulted in significant tumoricidal effects. Finally, systemic administration of TRAIL with cisplatin synergistically suppressed tumor growth of ESCC xenografts in nude mice. These results provide a significance of cisplatin‐induced upregulation of death receptors as apoptosis‐inducing machinery, and it was suggested that sequential administration of cisplatin and TRAIL might be a feasible chemotherapeutic regimen against ESCC. © 2005 Wiley‐Liss, Inc.
Gender‐specific polygenic control of ethylnitrosourea‐induced oncogenesis in the rat peripheral nervous system
Authors: Koelsch Bernd U. , Fischer Christine , Neibecker Markus , Schmitt Nina , Schmidt Ortrud , Rajewsky Manfred F. , Kindler‐Röhrborn Andrea 
Published: July 2005

AbstractThe inbred BD rat strains constitute a model system for analysis of the genetic basis of susceptibility or resistance to the development of neural tumors, as they exhibit distinct strain‐specific differences regarding the sensitivity to tumor induction by the alkylating carcinogen N‐ethyl‐N‐nitrosourea (EtNU). Among the different BD strains, BDIX and BDIV rats, respectively, are either highly susceptible or entirely resistant to the development of EtNU‐induced malignant schwannomas of the peripheral nervous system (PNS), predominantly of the trigeminal nerves. We have previously mapped one locus associated with susceptibility/resistance to schwannoma induction to the telomeric third of chromosome 10 (Mss1) in segregating (BDIX × BDIV) crosses. We report on the genetic mapping of 6 further loci controlling tumor incidence or survival time on chromosomes 1 (Mss2), 3 (Mss3), 6 (Mss4), 13 (Mss5) and 15 (Mss6) as well as on chromosome 10 (Mss7) close to the centromere. Interestingly, most of these loci mediate gender‐specific effects of variable strength ranging from minor influences on tumor development to complete tumor resistance. The gender specificity is reflected by the fact that male (BDIX × BDIV) F2 rats exhibit a 2‐fold higher incidence of EtNU‐induced schwannomas than females as well as a shorter survival time. A number of human nervous system tumors too arise with a marked gender bias. Genes mediating gender‐specific predisposition of developing malignant schwannomas in the rat may be relevant for the human individual risk of developing nervous system tumors. © 2005 Wiley‐Liss, Inc.
Targeted chemotherapy with cytotoxic bombesin analogue AN‐215 inhibits growth of experimental human prostate cancers
Authors: Stangelberger Anton , Schally Andrew V. , Letsch Markus , Szepeshazi Karoly , Nagy Attila , Halmos Gabor , Kanashiro Celia A. , Corey Eva , Vessella Robert 
Published: July 2005

AbstractWe developed a powerful cytotoxic analogue of bombesin AN‐215, in which the bombesin (BN)‐like carrier peptide is conjugated to 2‐pyrrolino doxorubicin (AN‐201). Human prostate cancers express high levels of receptors for BN/gastrin releasing peptide (GRP) that can be used for targeted chemotherapy. The effects of targeted chemotherapy with cytotoxic BN analogue AN‐215 were evaluated in nude mice bearing subcutaneous xenografts of DU‐145, LuCaP‐35, MDA‐PCa‐2b and intraosseous implants of C4‐2 human prostate cancers. Intraosseous growth of C4‐2 tumors was monitored by serum PSA. BN/GRP receptors were evaluated by 125I‐[Tyr4]BN binding assays and RT‐PCR. The effects of AN‐215 on apoptosis and cell proliferation were followed by histology, and the expression of Bcl‐2 and Bax protein was determined by Western blot analysis. Targeted analog AN‐215 significantly inhibited growth of subcutaneously implanted DU‐145, LuCaP‐35 and MDA‐PCa‐2b prostate cancers by 81% to 91% compared to controls, while cytotoxic radical AN‐201 was less effective and more toxic. Serum PSA levels of mice bearing intraosseous C4‐2 prostate tumors were significantly reduced. In LuCaP‐35 tumors administration of BN antagonist RC‐3095 prior to AN‐215 blocked the receptors for BN/GRP and inhibited the effects of AN‐215. High affinity receptors for BN/GRP and their m‐RNA were detected on membranes of all 4 tumor models. Therapy with AN‐215, but not with AN‐201, decreased the ratio of Bcl‐2/Bax in DU‐145 and the expression of antiapoptotic Bcl‐2 in LuCaP‐35 tumors. The presence of BN/GRP receptors on primary and metastatic prostate cancers makes possible targeted chemotherapy with AN‐215 for the treatment of this malignancy. © 2005 Wiley‐Liss, Inc.
Supraagonistic, bispecific single‐chain antibody purified from the serum of cloned, transgenic cows induces T‐cell‐mediated killing of glioblastoma cells in vitro and in vivo
Authors: Grosse‐Hovest Ludger , Wick Wolfgang , Minoia Rosa , Weller Michael , Rammensee Hans‐Georg , Brem Gottfried , Jung Gundram 
Published: July 2005

AbstractHere we characterize the antitumor activity of a recombinant bispecific single‐chain antibody isolated from the serum of cloned transgenic cows. The antibody, termed r28M, is directed to a melanoma‐associated proteoglycan, also expressed on glioblastoma cells, and to human CD28. Bound to tumor cells, r28M induced exceedingly efficient supraagonistic T‐cell activation via the CD28 molecule without an additional stimulus via the TCR/CD3 complex. In vitro, T cells and NK cells contributed to tumor cell killing after r28M‐mediated activation of peripheral blood mononuclear cells. However, NK activity depended on T‐cell‐derived cytokines. In vivo, r28M markedly inhibited the growth of human glioblastoma cells in nude mice. The serum half‐life of the protein after i.v. injection was approximately 6 hr. Thus, r28M is unique not only in inducing supraagonistic CD28‐mediated T‐cell activation against tumor cells in vitro and in vivo, it also meets 2 additional requirements that are critical for clinical application: a relatively long serum half‐life and the possibility of obtaining large amounts of active material from cloned transgenic livestock. © 2005 Wiley‐Liss, Inc.
NAT2 slow acetylation and bladder cancer in workers exposed to benzidine
Authors: Carreón Tania , Ruder Avima M. , Schulte Paul A. , Hayes Richard B. , Rothman Nathaniel , Waters Martha , Grant Delores J. , Boissy Robert , Bell Douglas A. , Kadlubar Fred F. , Hemstreet George P. , Yin Songnian , LeMasters Grace K. 
Published: July 2005

AbstractThis study expands a previous study of NAT2 polymorphisms and bladder cancer in male subjects occupationally exposed only to benzidine. The combined analysis of 68 cases and 107 controls from a cohort of production workers in China exposed to benzidine included 30 new cases and 67 controls not previously studied. NAT2 enzymatic activity phenotype was characterized by measuring urinary caffeine metabolite ratios. PCR‐based methods identified genotypes for NAT2, NAT1 and GSTM1. NAT2 phenotype and genotype data were consistent. A protective association was observed for the slow NAT2 genotype (bladder cancer OR = 0.3; 95% CI = 0.1 = 1.0) after adjustment for cumulative benzidine exposure and lifetime smoking. Individuals carrying NAT1wt/*10 and NAT1*10/*10 showed higher relative risks of bladder cancer (OR = 2.8, 95% CI = 0.8–10.1 and OR = 2.2, 95% CI = 0.6–8.3, respectively). No association was found between GSTM1 null and bladder cancer. A metaanalysis risk estimate of case‐control studies of NAT2 acetylation and bladder cancer in Asian populations without occupational arylamine exposures showed an increased risk for slow acetylators. The lower limit of the confidence interval (OR = 1.4; 95% CI = 1.0–2.0) approximated the upper confidence interval for the estimate obtained in our analysis. These results support the earlier finding of a protective association between slow acetylation and bladder cancer in benzidine‐exposed workers, in contrast to its established link as a risk factor for bladder cancer in people exposed to 2‐naphthylamine and 4‐aminobiphenyl. Study findings suggest the existence of key differences in the metabolism of mono‐ and diarylamines. Published 2005 Wiley‐Liss, Inc.
Prospective study of dietary acrylamide and risk of colorectal cancer among women
Authors: Mucci Lorelei A. , Adami Hans‐Olov , Wolk Alicja 
Published: July 2005

AbstractThere has been considerable discourse about whether exposure to acrylamide in foods could increase the risk of human cancer. Acrylamide is classified as a probable human carcinogen, and animal studies have demonstrated an increased incidence of tumors in rats exposed to very high levels. Still, epidemiologic data of the effect of dietary acrylamide remain scant. We have undertaken the first prospective study of acrylamide in food and risk of colon and rectal cancers using prospective data from the Swedish Mammography Cohort. The cohort comprised 61,467 women at baseline between 1987 and 1990. Through 2003, the cohort contributed 823,072 person‐years, and 504 cases of colon and 237 of rectal cancer occurred. Mean intake of acrylamide through diet was 24.6 μg/day (Q25–70 = 18.7–29.9). Coffee (44%), fried potato products (16%), crisp bread (15%) and other breads (12%) were the greatest contributors. After adjusting for potential confounders, there was no association between estimated acrylamide intake and colorectal cancer. Comparing extreme quintiles, the adjusted relative risks (95% CI; p for trend) were for colorectal cancer 0.9 (0.7–1.3; p = 0.80), colon cancer 0.9 (0.6–1.4; p = 0.83) and rectal cancer 1.0 (0.6–1.8; p = 0.77). Furthermore, intake of specific food items with elevated acrylamide (e.g., coffee, crisp bread and fried potato products) was not associated with cancer risk. In this large prospective study, we found no evidence that dietary intake of acrylamide is associated with cancers of the colon or rectum. Epidemiologic studies play an important role in assessing the possible health effects of acrylamide intake through food. © 2005 Wiley‐Liss, Inc.
Novel strategy for optimal sequential application of clinical criteria, immunohistochemistry and microsatellite analysis in the diagnosis of hereditary nonpolyposis colorectal cancer
Authors: Engel Christoph , Forberg Jochen , Holinski‐Feder Elke , Pagenstecher Constanze , Plaschke Jens , Kloor Matthias , Poremba Christopher , Pox Christian P. , Rüschoff Josef , Keller Gisela , Dietmaier Wolfgang , Rümmele Petra , Friedrichs Nicolaus , Mangold Elisabeth , Buettner Reinhard , Schackert Hans K. , Kienle Peter , Stemmler Susanne , Moeslein Gabriela , Loeffler Markus ,   the German HNPCC Consortium
Published: July 2005

AbstractClinical criteria, microsatellite analysis (MSA) and immunohistochemistry (IHC) are important diagnostic tools for identification of hereditary nonpolyposis colorectal cancer (HNPCC) patients who are likely to carry pathogenic germline mutations in mismatch repair genes. Based on MSA and IHC results and subsequent mutation analyses of 1,119 unrelated index patients meeting the Amsterdam II criteria or the classical Bethesda guidelines, we analyzed the value of these tools to predict MLH1 and MSH2 mutations with the aim of establishing optimal strategies for their most efficient sequential use. The overall prevalence of pathogenic germline mutations in our cohort was 20.6% (95% CI = 18.3–23.0%) and 61.8% (95% CI = 56.8–66.6%), respectively, after MSA/IHC‐based preselection. IHC was highly predictive (99.1%) and specific (99.6%) with regard to MSA. However, 14 out of 230 mutations (6%) escaped detection by IHC. Thus, IHC cannot be recommended to substitute MSA fully. Nonetheless, IHC is important to indicate the gene that is likely to be affected. To combine both methods efficiently, we propose a novel screening strategy that provides 2 alternative ways of sequential IHC and MSA application, either using IHC or MSA in the first place. A logistic regression model based on the age of the index patient at first tumor diagnosis and the number of fulfilled HNPCC criteria is used to allocate individual patients to that alternative pathway that is expected to be least expensive. A cost analysis reveals that about 25% of the costs can be saved using this strategy. © 2005 Wiley‐Liss, Inc.
Migration of Additives in Polymer Coatings: Phosphonated Additives and Poly(vinylidene chloride)‐Based Matrix
Authors: Rixens Bérengère , Severac Romain , Boutevin Bernard , Lacroix‐Desmazes Patrick , Hervaud Yves 
Published: July 2005

AbstractSummary: The living radical terpolymerization of vinylidene chloride (VC2), methyl acrylate (MA), and dimethyl‐2‐methacryloxyethylphosphonate (MAPHOS) was performed at 70 °C in benzene by a reversible addition fragmentation chain transfer (RAFT) process to yield a gradient terpolymer of controlled molecular weight ($\overline M _{\rm n}$ = 5 800 g · mol−1, Ip = 1.53) with a molar composition of 75:14:11 (VC2/MA/MAPHOS). Such terpolymers, hydrolyzed (phosphonic acid groups) or not, were used as polymeric additives in coating formulations based on a poly(VC2‐co‐MA) copolymer matrix ($\overline M _{\rm n}$ = 63 300 g · mol−1, Ip = 1.99, VC2/MA = 80:20 molar ratio). The formulations were spun cast on stainless steel surfaces and the coatings were observed by scanning electron microscopy (SEM) coupled with X‐ray analyses (EDX). The hydrolyzed additive was shown to both segregate and migrate towards the metal interface, leading to a preferential organization of the coating. Hence, the matrix at the air surface acts as a barrier to gas while the additive ensures adhesion at the polymer/metal interface.SEM photograph of a section of the coating with formulation 4 [poly(VC2‐co‐MA‐co‐MAPHOS(OH)2) (75:14:11)].magnified imageSEM photograph of a section of the coating with formulation 4 [poly(VC2‐co‐MA‐co‐MAPHOS(OH)2) (75:14:11)].
Interaction of Surfactant and Initiator Types in Emulsion Polymerisations: A Comparison of Ammonium Persulfate and Hydrogen Peroxide
Authors: Boutti Salima , Zafra Rocio Diez , Graillat Christian , McKenna Timothy F. 
Published: July 2005

AbstractSummary: In emulsion polymerisation all the components of the system have an influence on the nucleation mechanisms and colloidal stability, and therefore on the final particle size distribution (PSD). The impact of the nature of the initiator (charged radicals and electrically neutral radicals) and its interaction with the composition of the surfactant system and the radical flux on dp is studied in this paper. It was demonstrated that the influence of the nature of initiator on dp depends on the composition of the surfactant system. No influence of the nature of the initiator on Np (number of particles per litre) or the rate of reaction could be discerned when even trace amounts of anionic surfactant were present. But for surfactant‐free reactions or when non‐ionic surfactant (TN) was used as sole stabiliser, it was not possible to produce stable latex using electrically neutral radicals (in this case, hydroxyl radicals). Finally, the order of the semi‐continuous addition of ascorbic acid (AscA) and of hydrogen peroxide (HPO) was studied. As expected, a significant influence of the order of addition was observed in terms of the radical flux and reaction kinetics. It was demonstrated that one mole of AscA added to HPO provides more free radicals than are obtained when a mole of HPO is added to AscA.Overall conversion vs. reaction time.magnified imageOverall conversion vs. reaction time.