bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protodynamic therapy for bladder cancer: in vitro results of a novel treatment concept
Authors: Laihia Jarmo K. , Pylkkänen Liisa , Laato Matti , Boström Peter J. , Leino Lasse 
Published: May 2009

OBJECTIVETo present a novel treatment approach for urinary bladder cancer, protodynamic therapy, which comprises inhibition of cancer cell proliferation by intracellular acidification; cis‐urocanic acid (cis‐UCA) was investigated as a protodynamic drug in bladder cancer cell cultures and compared with conventional chemotherapeutic agents.MATERIALS AND METHODSThe moderately differentiated cell line 5637 and the poorly differentiated T24 cell line were exposed to cis‐UCA for 0.25–2 h, and to epirubicin, doxorubicin, cisplatin and paclitaxel for 2 h, to simulate drug exposure on intravesical instillation. The combination of cis‐UCA and chemotherapeutic agents was also studied. Cell viability was measured with a colorimetric assay.RESULTS cis‐UCA inhibited proliferation and suppressed the survival of cells at an extracellular pH ≤ pKa2 of 6.65 but to a lesser degree at pH > pKa2, as suggested by the protodynamic theory. cis‐UCA caused dose‐dependent, irreversible termination of cell proliferation. The number of viable surviving BC cells decreased by >85% with 2%cis‐UCA (P < 0.001). Viable cells disappeared completely with 4% and 6%cis‐UCA after a 2‐h treatment, and by 90% with 6%cis‐UCA within a 15‐min exposure. These effects were associated with distinct morphological changes. The other drugs tested had a clearly lower effect on cell survival. Interestingly, when combined, cis‐UCA markedly enhanced the cytotoxic effect of epirubicin.CONCLUSION cis‐UCA is a potent antiproliferative agent in bladder cancer cell cultures. As our previous non‐clinical studies showed that cis‐UCA is locally and systemically well tolerated, protodynamic therapy with cis‐UCA is a promising intravesical treatment for bladder cancer.
Adenosine receptor expression in Escherichia coli‐infected and cytokine‐stimulated human urinary tract epithelial cells
Authors: Säve Susanne , Mjösberg Jenny , Poljakovic Mirjana , Mohlin Camilla , Persson Katarina 
Published: May 2009

OBJECTIVETo assess the expression and regulation of adenosine receptors in unstimulated, uropathogenic Escherichia coli (UPEC)‐infected and cytokine‐stimulated human urinary tract epithelial cells, and to examine the regulation of interleukin (IL)‐6 secretion in response to A2A receptor activation.MATERIALS AND METHODSHuman urinary tract epithelial cells (A498, T24 and RT4) were grown in cell culture and stimulated with a mixture of pro‐inflammatory cytokines (CM) or UPEC. The expression of adenosine receptors was evaluated using semiquantitative reverse transcription‐polymerase chain reaction (RT‐PCR), Western blot analysis and immunocytochemistry. IL‐6 secretion was measured with an enzyme‐linked immunosorbent assay.RESULTSRT‐PCR analysis showed the presence of transcripts for the A1, A2A and A2B receptor subtypes but not for the A3 receptor in A498 kidney epithelial cells. The expression of A2A receptor mRNA increased in A498 epithelial cells exposed to CM and UPEC, while A1 and A2B receptor transcripts decreased or remained unchanged. Up‐regulation of A2A receptors was confirmed at the protein level using Western blot analysis and immunocytochemistry. There was also an increase in A2A receptor mRNA in human bladder epithelial cells (T24 and RT4) and in mouse bladder uroepithelium in response to cytokines and UPEC. IL‐6 secretion in UPEC‐infected A498 cells was decreased by 38% when exposed to the A2A receptor agonist CGS 21680.CONCLUSIONOur data showed a subtype‐selective plasticity among adenosine receptors in urinary tract epithelial cells in response to UPEC‐infection and cytokines. There was a consistent up‐regulation of A2A receptors in kidney and bladder epithelial cells. Functionally, A2A receptor activation reduced UPEC‐induced IL‐6 secretion. These findings suggest that adenosine might be a previously unrecognized regulator of the mucosal response in urinary tract infection.
Do Firms Learn from Alliance Terminations? An Empirical Examination
Authors: Pangarkar Nitin 
Published: May 2009

abstractIn this paper, drawing from the learning from failure perspective, we argue that firms that have experienced prior terminations are less likely to have their future alliance terminated. Our key argument is that prior terminations will enable firms to design better alliances and adopt more appropriate alliance management strategies to avoid future terminations. We also suggest a more nuanced view of learning by hypothesizing that termination experience will mediate the relationship between alliance formation experience and likelihood of termination. We used the case–control methodology to select a sample of 198 alliances (consisting of 99 terminations and an equal number of surviving alliances) from the global biotechnology industry, and deployed logistic regression analysis to test the hypotheses in a multivariate setting. Our analysis strongly supports both hypotheses.
LARGE AND LATECOMER FIRMS: THE TAIWAN SEMICONDUCTOR MANUFACTURING COMPANY AND TAIWAN'S ELECTRONICS INDUSTRY
Authors: LEE CHIA‐WEN , HAYTER ROGER , EDGINGTON DAVID W. 
Published: May 2009

ABSTRACTThis paper focuses on the role of Taiwan's ‘latecomer firms’ that are also large firms in developing technological capability within the electronics industry. Taiwan illustrates a latecomer country that has industrialised in the late twentieth century through export‐based industrialisation and latecomer firms are indigenous influences shaping this process. Large firms comprise a business segment distinctive from small firms and giant MNCs, and are characterised by strong commitments to innovation. Conceptually, a framework is outlined that connects latecomer firms with the triad business segmentation model, local technology learning as summarised by reverse product cycle dynamics and clustering. Empirically, the study focuses on the evolutionary dynamics of a latecomer case study, the Taiwan Semiconductor Manufacturing Company, to reveal important insights regarding the development of Taiwan's internationally competitive technological capabilities. The case study reveals the significance of large latecomer firms to the technology learning process, and in reducing technology gaps with global leaders.
FROM JACKBOOTS TO BIRKENSTOCKS: THE CIVILIANISATION OF GERMAN GEOPOLITICS IN THE TWENTIETH CENTURY
Authors: BACHMANN VEIT 
Published: May 2009

ABSTRACTGerman geopolitical claims have changed from two phases of aggressive, military expansionism (Jackboots) at the beginning of the twentieth century to a civilianised foreign policy (Birkenstocks) at its end. This paper describes this transition during the second half of the twentieth century in light of a changing international system and the geopolitical constellations of the Cold War and European integration. As part of such historical experiences, external circumstances and internal preferences the civilian power concept became the foundation for the Berlin Republic's grand strategy of promoting civilianised structures in the international system. Unlike at the beginning of the twentieth century, German foreign policy after reunification in 1990 was not based on a deliberately pursued strategy of militaristic power politics to attain world power status. It reflected a foreign policy identity into which Germany ‘grew’ during the Cold War in a process of adapting and becoming part of European integration and American hegemony. Even though Germany did not completely abandon its power ambitions, their articulations and claims were radically transformed. A civilianised international system thereby became the objective and medium of German foreign policy. Such a system is characterised by multilateralism, supranational integration, strong international institutions, rule of law, free trade, human rights, good governance and restrictions of the use of force.
In vitro and in vivo pharmacological role of TLQP‐21, a VGF‐derived peptide, in the regulation of rat gastric motor functions
Authors: Severini C , La Corte G , Improta G , Broccardo M , Agostini S , Petrella C , Sibilia V , Pagani F , Guidobono F , Bulgarelli I , Ferri GL , Brancia C , Rinaldi AM , Levi A , Possenti R 
Published: May 2009

Background and purpose:  Vgf gene expression has been detected in various endocrine and neuronal cells in the gastrointestinal tract. In this study we investigated the pharmacological activity of different VGF‐derived peptides. Among these, TLQP‐21, corresponding to the 556–576 fragment of the protein was the unique active peptide, and its pharmacological profile was further studied.Experimental approach:  The effects of TLQP‐21 were examined in vitro by smooth muscle contraction in isolated preparations from the rat gastrointestinal tract and, in vivo, by assessing gastric emptying in rats. Rat stomach tissues were also processed for immunohistochemical and biochemical characterization.Key results:  In rat longitudinal forestomach strips, TLQP‐21 (100 nmol·L−1–10 µmol·L−1) concentration‐dependently induced muscle contraction (in female rats, EC50 = 0.47 µmol·L−1, Emax: 85.7 ± 7.9 and in male rats, 0.87 µmol·L−1, Emax: 33.4 ± 5.3; n = 8), by release of prostaglandin (PG)E2 and PGF2a from the mucosal layer. This effect was significantly antagonized by indomethacin and selective inhibitors of either cyclooxygenase‐1 (S560) or cyclooxygenase‐2 (NS398). Immunostaining and biochemical studies confirmed the presence of VGF in the gastric neuronal cells. TLQP‐21, injected i.c.v. (2–32 nmol per rat), significantly decreased gastric emptying by about 40%. This effect was significantly (P < 0.05) blocked by i.c.v. injection of indomethacin, suggesting that, also in vivo, this peptide acts in the brain stimulating PG release.Conclusions and implications:  The present results demonstrate that this VGF‐derived peptide plays a central and local role in the regulation of rat gastric motor functions.
The interaction of ibuprofen and diclofenac with aspirin in healthy volunteers
Authors: Schuijt MP , Huntjens‐Fleuren HWHA , De Metz M , Vollaard EJ 
Published: May 2009

Background and purpose:  Aspirin reduces the risk of myocardial infarction and stroke by inhibiting thromboxane production in platelets. This inhibition can be competitively antagonized by some non‐steroidal anti‐inflammatory drugs (NSAIDs).Experimental approach:  By measuring thromboxane B2 production in healthy volunteers, we investigated whether ibuprofen (800 mg three times daily for 7 days) or diclofenac (50 mg three times daily for 7 days) taken concurrently with aspirin 80 mg (once daily for 7 days) influenced the inhibitory effect of aspirin. The effects were compared with aspirin 30 mg (once daily for 7 days), which is the lowest dose of aspirin with a proven thromboprophylactic effect.Key results:  The median percentage inhibition of thromboxane B2 levels by 30 mg or 80 mg aspirin was 90.3% (range 83.1–96.0%) and 98.0% (range 96.8–99.2%) respectively. The inhibition by concurrent administration of slow release diclofenac and 80 mg aspirin was 98.1% (range 97.2–98.9%), indicating no interference between aspirin and diclofenac. The inhibition decreased significantly by concurrent administration of immediate release ibuprofen and 80 mg aspirin (86.6%; range 77.6–95.1%) to a level less than 30 mg aspirin.Conclusions and implications:  As alternatives are easily available, NSAIDs such as diclofenac should be preferred to ibuprofen for combined use with aspirin.
Oligonucleotide microarray analysis of apoptosis induced by 15‐methoxypinusolidic acid in microglial BV2 cells
Authors: Choi Y , Lim SY , Jeong HS , Koo KA , Sung SH , Kim YC 
Published: May 2009

Background and purpose:  We conducted a genome wide gene expression analysis to explore the biological aspects of 15‐methoxypinusolidic acid (15‐MPA) isolated from Biota orientalis and tried to confirm the suitability of 15‐MPA as a therapeutic candidate for CNS injuries focusing on microglia.Experimental approach:  Murine microglial BV2 cells were treated with 15‐MPA, and their transcriptome was analysed by using oligonucleotide microarrays. Genes differentially expressed upon 15‐MPA treatment were selected for RT‐PCR (reverse transcription‐polymerase chain reaction) analysis to confirm the gene expression. Inhibition of cell proliferation and induction of apoptosis by 15‐MPA were examined by bromodeoxyuridine assay, Western blot analysis of poly‐ADP‐ribose polymerase and flow cytometry.Key results:  A total of 514 genes were differentially expressed by 15‐MPA treatment. Biological pathway analysis revealed that 15‐MPA induced significant changes in expression of genes in the cell cycle pathway. Genes involved in growth arrest and DNA damage [gadd45α, gadd45γ and ddit3 (DNA damage‐inducible transcript 3)] and cyclin‐dependent kinase inhibitor (cdkn2b) were up‐regulated, whereas genes involved in cell cycle progression (ccnd1, ccnd3 and ccne1), DNA replication (mcm4, orc1l and cdc6) and cell proliferation (fos and jun) were down‐regulated. RT‐PCR analysis for representative genes confirmed the expression levels. 15‐MPA significantly reduced bromodeoxyuridine incorporation, increased poly‐ADP‐ribose polymerase cleavage and the number of apoptotic cells, indicating that 15‐MPA induces apoptosis in BV2 cells.Conclusion and implications:  15‐MPA induced apoptosis in murine microglial cells, presumably via inhibition of the cell cycle progression. As microglial activation is detrimental in CNS injuries, these data suggest a strong therapeutic potential of 15‐MPA.
Human immunodeficiency virus‐1 genotypic drug resistance among volunteer blood donors in Yunnan, China
Authors: Tu Yuan‐Quan , Wang Min‐Jie , Yao Jun , Zhu Xiang‐Ming , Pan Pin‐Liang , Xing Wen‐Ge , Zhang Gao‐Hong , Yang Rong‐Ge , Zheng Yong‐Tang , Jiang Yan 
Published: May 2009

BACKGROUND: Drug resistance profiles of human immunodeficiency virus‐1 (HIV‐1) in treatment‐naïve infections have been reported in developed countries. However, little is known in developing countries, including China, especially in treatment‐naïve volunteer blood donors.STUDY DESIGN AND METHODS: Fifty‐two HIV‐1–positive samples of blood donors were collected from 2005 to 2006 in Yunnan, China. Recent and long‐term infections were distinguished by the HIV‐1 subtypes B, E, and D immunoglobulin G‐capture enzyme immunoassay assay. The nucleotide sequences of pol genes were amplified and sequenced. Phylogenetic tree and drug resistance analyses were performed.RESULTS: Of 49 samples successfully analyzed, circulating strains were circulating recombinant form (CRF)08_BC (51.0%), CRF07_BC (24.5%), CRF01_AE (20.4%), and B (4.1%). No protease inhibitors (PI) major drug resistance mutation (DRM) was detected. Six samples (12.2%) displayed seven minor PI DRMs. Nine samples (18.4%) displayed 10 nucleoside reverse transcriptase inhibitor DRMs, and DRMs to nonnucleoside reverse transcriptase inhibitors were present in one sample (2.0%). There was only one sample of the 49 (2.0%) in which the DRMs were of sufficient magnitude to result in a clinical change to drug susceptibility, but even in this sample, the clinical effect of these DRMs was predicted to be low. Significant differences were not observed between the long‐term and recent infected population. Differences in DRMs were not observed between peripheral blood mononuclear cells and plasma within an individual.CONCLUSIONS: CRF_BC was the dominant subtype circulating in HIV‐1–infected donors in Yunnan. Prevalence of genotypic drug resistances among donors in Yunnan was low in this study. Surveillance on HIV‐1 infections among blood donors should be continued in China.
RHCE alleles detected after weak and/or discrepant results in automated Rh blood grouping of blood donors in Northern Germany
Authors: Döscher Andrea , Vogt Claudia , Bittner Rita , Gerdes Ingrid , Petershofen Eduard K. , Wagner Franz F. 
Published: May 2009

BACKGROUND: More than 170 weak or partial RHD alleles are currently known. A similar heterogeneity of RHCE alleles may be anticipated, but a large‐scale systematic analysis of the molecular bases of altered C, c, E, and e antigenicity in European blood donors was lacking.STUDY DESIGN AND METHODS: Between November 2004 and October 2006, samples collected from 567,105 blood donors in the northwest of Germany were surveyed for weakened and/or discrepant serologic reaction patterns of the C, c, E, or e antigens in automated testing. Samples from 187 donors with systematic typing problems were further investigated by manual typing and in 122 donors by DNA typing. The polymorphisms determining C, c, E, and e, as well as three repeatedly found substitutions, M167K, G96S, and L115R, were tested by PCR‐SSP. Further analysis consisted of sequencing of the exons of RHCE. In addition, 13 referred samples were analyzed.RESULTS: RHcE(M167K) known as E variant I was the most frequent allele, found in 70 of 122 analyzed donors. Among 13 referred samples, C typing problems predominated. Overall, 34 different underlying alleles were detected, 23 of which were new. Molecular causes included single‐amino‐acid substitutions, gene conversions, multiple dispersed amino acid substitutions, protein extensions, and in‐frame amino acid deletions.CONCLUSION: In addition to RHcE(M167K), a large number of different alleles are underlying CcEe typing problems. Molecular mechanisms parallel those found in RHD. Elucidation of the molecular bases of variant antigens is important to improve serologic and molecular typing methods.
Adult T‐cell leukemia/lymphoma in the Middle East: first report of two cases from Lebanon
Authors: Bitar Nizar , Hajj Hiba El , Houmani Zaher , Sabbah Ahmad , Otrock Zaher K. , Mahfouz Rami , Zaatari Ghazi , Bazarbachi Ali 
Published: May 2009

BACKGROUND: Adult T‐cell leukemia/lymphoma (ATL) is an aggressive lymphoproliferative disorder caused by human T‐cell leukemia virus type I (HTLV‐I). HTLV‐I is endemic in southern Japan, the Caribbean, Central and South America, certain areas of Africa, and the southeastern United States. In the Middle East, North East Iran, particularly the region of Mashhad, has been recognized as an endemic region.CASE REPORTS: In this report, the first two cases of ATL diagnosed in Lebanon are described. The first patient of Lebanese origin presented with acute ATL. The second patient of Romanian origin developed acute ATL in early relapse after autologous transplantation for ATL. Both patients had lymphocytosis, severe hypercalcemia, and CD25+ T‐cell immunophenotype on peripheral blood. In both patients, HTLV‐I serology was positive by enzyme‐linked immunosorbent assay and confirmed by Western blot and HTLV‐I oncoprotein Tax expression was documented in the leukemic cells. Upon screening, seven direct family members of the first patient were HTLV‐I positive; four of them were regular blood donors.CONCLUSIONS: Screening blood donors for HTLV‐I seropositivity is not currently performed in Lebanon. A large screening study in Lebanon is needed to confirm whether South Lebanon is a new endemic region for HTLV‐I infection and to recommend mandatory screening of blood donors for HTLV‐I infection.
The role of the CCR5 Δ32 polymorphism in abdominal aortic aneurysms
Authors: Sandford B. , Bown M. , London N. , Sayers R. 
Published: May 2009

SummaryBackground  C‐C chemokine receptor 5 (CCR5) is involved in the regulation of the inflammatory response. Abdominal aortic aneurysms (AAA) may arise as the result of a chronic inflammatory process which is influenced by genetic predisposition. The CCR5 gene is associated with a 32 base pair deletion (the Δ32 polymorphism). The aim of this study was to investigate the role of the CCR5 Δ32 polymorphism in the development of AAA.Methods  A case–control study was conducted including 285 patients with AAA and 273 control subjects. A blood sample was taken from each individual and DNA was extracted. CCR5 genotype was determined using the polymerase chain reaction (PCR). Flow cytometry was used to investigate the biological activity of the Δ32 polymorphism.Results  There was no significant difference between the AAA and the control group in relation to the Δ32 allele frequency (AAA group 10%, control group = 12%, P = 0.82, chi‐squared analysis). Genotype analysis revealed no significant difference between the groups (AAA vs. controls, wild‐type homozygotes = 82% vs. 77%, heterozygotes = 16% vs. 21%, vs. Δ32 homozygotes = 2% and 2%, respectively, P = 0.33, chi‐squared analysis). The polymorphism was shown to be biologically active with the number of Δ32 alleles correlating with cell expression of ccr5 as detected with flow cytometry (P ≤ 0.05).Conclusion  This study demonstrates that the ccr5 Δ32 is a biologically active genetic polymorphism; however, there is no association between this polymorphism and AAA.
Genetic susceptibility to haemorrhagic fever with renal syndrome caused by Hantaan virus in Chinese Han population
Authors: Wang M. L. , Lai J. H. , Zhu Y. , Zhang H. B. , Li C. , Wang J. P. , Li Y. M. , Yang A. G. , Jin B. Q. 
Published: May 2009

SummaryWe report a significantly higher occurrence of HLA‐DRB1*09 (51% vs. 23%, P = 0.002, OR = 3.57) and HLA‐B*46‐DRB1*09 (26% vs. 8%, P = 0.018, OR = 3.76) in patients with haemorrhagic fever with renal syndrome (HFRS) compared to the control group, suggesting Hantaan virus‐induced HFRS is associated with a genetic predisposition in the Chinese Han population.
Effects of Logging on the Diversity of Lianas in a Lowland Tropical Rain Forest in Hainan Island, South China
Authors: Ding Yi , Zang Runguo 
Published: May 2009

ABSTRACTLianas are an integral part of tropical forest ecosystems, which usually respond strongly to severe disturbances, such as logging. To compare the effect of different logging systems on the lianas diversity in tropical rain forest, we recorded all lianas and trees ≥1 cm dbh in two 40‐year‐old forest sites after clear cutting (CC) and selective cutting (SC) as well as in an old‐growth (OG) lowland tropical rain forest on Hainan Island in south China. Results showed that OG contained fewer liana stems and lower species richness (stems: 261, richness: 42 in 1 ha) than CC (606, 52) and SC (727, 50). However, OG had the highest Fisher's α diversity index (17.3) and species richness per stem (0.184). Species composition and dbh class distribution of lianas varied significantly with different logging systems. The mean liana dbh in OG (22.1 cm) were higher than those in CC (7.0 cm) and SC (10.4 cm). Stem twining was the most frequent climbing mechanism represented in the forest, as shown by the greatest species richness, abundance, basal area, and host tree number with this mechanism. The percent of host tree stems ≥4 cm dbh hosting at least one liana individual in SC (39%) was higher than CC (23%) and OG (19.5%). Large host trees (dbh≥60 cm) were more likely to be infested by lianas in SC and OG. Our study demonstrated that logging disturbance could significantly change the composition and structure of liana communities in the lowland tropical rain forest of south China.