bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amphotericin B-Induced Renal Tubular Cell Injury Is Mediated by Na+Influx through Ion-Permeable Pores and Subsequent Activation of Mitogen-Activated Protein Kinases and Elevation of Intracellular Ca2+Concentration
Authors: Yano Takahisa , Itoh Yoshinori , Kawamura Eiko , Maeda Asuka , Egashira Nobuaki , Nishida Motohiro , Kurose Hitoshi , Oishi Ryozo 
Published: January 2009

ABSTRACTAmphotericin B (AMB) is one of the most effective antifungal agents; however, its use is often limited by the occurrence of adverse events, especially nephrotoxicity. The present study was designed to determine the possible mechanisms underlying the nephrotoxic action of AMB. The exposure of a porcine proximal renal tubular cell line (LLC-PK1 cells) to AMB caused cell injury, as assessed by mitochondrial enzyme activity, the leakage of lactate dehydrogenase, and tissue ATP depletion. Propidium iodide uptake was enhanced, while terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was not affected by AMB, suggesting a lack of involvement of apoptosis in AMB-induced cell injury. The cell injury was inhibited by the depletion of membrane cholesterol with methyl-β-cyclodextrin, which lowered the extracellular Na+concentration or the chelation of intracellular Ca2+. The rise in the intracellular Ca2+concentration may be mediated through the activation of the ryanodine receptor (RyR) on the endoplasmic reticulum and the mitochondrial Na+-Ca2+exchanger, since cell injury was attenuated by dantrolene (an RyR antagonist) and CGP37157 (an Na+-Ca2+exchanger inhibitor). Moreover, AMB-induced cell injury was reversed by PD169316 (a p38 mitogen-activated protein [MAP] kinase inhibitor), c-Jun N-terminal kinase inhibitor II, and PD98059 (a MEK1/2 inhibitor). The phosphorylations of these MAP kinases were enhanced by AMB in a calcium-independent manner, suggesting the involvement of MAP kinases in AMB-induced cell injury. These findings suggest that Na+entry through membrane pores formed by the association of AMB with membrane cholesterol leads to the activation of MAP kinases and the elevation of the intracellular Ca2+concentration, leading to renal tubular cell injury.
Use of a Bacteriophage Lysin, PlyC, as an Enzyme Disinfectant againstStreptococcus equi
Authors: Hoopes J. Todd , Stark Caren J. , Kim Han Ah , Sussman Daniel J. , Donovan David M. , Nelson Daniel C. 
Published: January 2009

ABSTRACTStreptococcus equiis the causative agent of the purulent infection equine strangles. This disease is transmitted through shedding of live bacteria from nasal secretions and abscess drainage or by contact with surfaces contaminated by the bacteria. Disinfectants are effective againstS. equi, but inactivation by environmental factors, damage to equipment, and toxicity are of great concern. Bacteriophage-encoded lysins (cell wall hydrolases) have been investigated as therapeutic agents due to their ability to lyse susceptible gram-positive organisms. Here, we investigate the use of one lysin, PlyC, as a narrow-spectrum disinfectant againstS. equi. This enzyme was active against >20 clinical isolates ofS. equi, including bothS. equisubsp.equiandS. equisubsp.zooepidemicus. Significantly, PlyC was 1,000 times more active on a per weight basis than Virkon-S, a common disinfecting agent, with 1 μg of enzyme able to sterilize a 108CFU/ml culture ofS. equiin 30 min. PlyC was subjected to a standard battery of tests including the Use Dilution Method for Testing Disinfectants and the Germicidal Spray Products Test. Results indicate that aerosolized PlyC can eradicate or significantly reduce theS. equiload on a variety of materials found on common stable and horse-related equipment. Additionally, PlyC was shown to retain full activity under conditions that mimic a horse stable, i.e., in the presence of nonionic detergents, hard water, or organic materials. We propose PlyC as the first protein-based, narrow-spectrum disinfectant againstS. equi, which may augment or supplement the use of broad-spectrum disinfectants in barns and stables where equine strangles is prevalent.
Coinfection with Two Closely Related Alphaherpesviruses Results in a Highly Diversified Recombination Mosaic Displaying Negative Genetic Interference
Authors: Muylkens Benoît , Farnir Frédéric , Meurens François , Schynts Frédéric , Vanderplasschen Alain , Georges Michel , Thiry Etienne 
Published: January 2009

ABSTRACTPhylogenetic studies of the emergence and spread of natural recombinants in herpesviruses infecting humans and animals have been reported recently. However, despite an ever-increasing amount of evidence of recombination in herpesvirus history, the recombination process and the consequences on the genetic diversity of the progeny remain poorly characterized. We addressed this issue by using multiple single-nucleotide polymorphisms (SNPs) differentiating the two subtypes of an alphaherpesvirus, bovine herpesvirus 1 (BoHV-1). Analysis of a large sample of progeny virions obtained in a single growth cycle of coinfected BoHV-1 strains provided a prospective investigation of the recombination dynamics by using SNPs as recombination markers. We found that the simultaneous infection with two closely related herpesviruses results in a highly diversified recombination mosaic. From the analysis of multiple recombinants arising in the progeny, we provide the first evidence of genetic interference influencing the recombination process in herpesviruses. In addition, we report striking differences in the levels of recombination frequency observed along the BoHV-1 genome. With particular emphasis on the genetic structure of a progeny virus population rising in vitro, our data show to which extent recombination participates to the genetic diversification of herpesviruses.
Eosinophilia-associated muscle disorders: an immunohistological study with tissue localisation of major basic protein in distinct clinicopathological forms
Authors: Cantarini L , Volpi N , Carbotti P , Greco G , Aglianò M , Bellisai F , Giannini F , Alessandrini C , Grasso G , Galeazzi M 
Published: January 2009

Aims:(a) To evaluate tissue eosinophil density, location of eosinophil cytotoxic products, histopathological muscle changes and inflammatory cell types in different eosinophilia-associated myopathies that are clinicopathologically heterogeneous. (b) To determine the immunohistological range of tissue eosinophil density in non-eosinophilic inflammatory myopathies.Methods:Muscle biopsy specimens from seven patients with blood and/or tissue eosinophilia and clinicolaboratory myopathic signs (five chronic course myopathies, one subacute onset fasciitis/myositis, one acute myositis), and from 18 non-eosinophilic inflammatory myopathies, underwent routine staining, inflammatory infiltrate immunophenotyping, immunostaining for eosinophil major basic protein (MBP) and transmission electron microscopy examination. Eosinophil and total inflammatory cell counts were statistically analysed.Results:Histological examination showed occasional or no infiltrating eosinophils in all cases. MBP staining showed that tissue eosinophil density and percentages in eosinophilia-associated myopathies were significantly higher than in idiopathic myositides. Extracellular MBP diffusion, the hallmark of eosinophil cytotoxicity, was recurrent on sarcolemma and endothelium. Electron microscopy showed eosinophils close to sarcolemma, abundant mast cells, and capillary endothelial swelling. Immunostaining detected a higher mean eosinophil density in idiopathic myositides than previously assessed histologically.Conclusions:MBP immunohistology on skeletal muscle, previously performed only for acute eosinophilic polymyositis, suggests that eosinophil-mediated injury of muscle cells may occur in a wider spectrum of less aggressive eosinophilia-associated myopathies than previously thought. As conventional histology is likely to underestimate this leucocyte subset, MBP staining may be a useful tool in the analysis of tissue infiltration of eosinophils as a possible treatment target.
Morphological and molecular evidence of natural interspecific hybridization in the diploid potatoSolanum kurtzianumfrom Argentina
Authors: Bedonni María Cecilia , Camadro Elsa Lucila 
Published: January 2009

The common potato, Solanum tuberosum L. subsp. tuberosum , is a tetrasomic tetraploid. This subspecies has approximately 220 related tuber-bearing species that constitute a genetic pool of enormous breeding value. The diploid species Solanum kurtzianum Bitter et Wittm., described as resistant to drought and nematodes, grows in northwestern and western Argentina and can naturally hybridize with the related diploids Solanum chacoense Bitter, Solanum spegazzinii Bitter, and Solanum maglia Schltdl., in areas of sympatry. In this species, the variability for morphological phenotypes and pollen–pistil relations in intra- and interspecific crosses is large. To investigate whether S. kurtzianum accessions available at the Germplasm Bank in Argentina belong to one taxon with great morphological plasticity or are hybrid and (or) segregant populations, these and accessions of the other three species were characterized using morphological and molecular (SSR) markers. Data were statistically analyzed with ANOVAs and AMOVA. With univariate ANOVA, only 11 characters out of 33 evaluated were statistically significant among species. With multivariate analyses, the grouping did not reflect a priori taxonomic assignments; when population averages were used, a tendency was observed towards grouping by geographical origin. With the AMOVA, only individuals within accessions were separated. Interspecific hybridization and introgression in areas of sympatry can explain these results.
A multivariate morphometric analysis of Solidago subsect. Glomeruliflorae (Asteraceae: Astereae)
Authors: Cook Rachel E. , Semple John C. , Baum Bernard R. 
Published: January 2009

A multivariate morphometric study of Solidago subsection Glomeruliflorae (Torr. & A. Gray) Nesom was undertaken on a matrix of 45 characters by 368 plants to assess the morphological differences among the members of the complex and to determine their appropriate taxonomic ranks. The numbers of a priori groups tested were based on taxa recognized in floristic literature, examination of type specimens and 3214 herbarium specimens, and observations of plants in the field and greenhouse. Analyses were performed to determine statistical support for eight a priori species level groups: Solidago albopilosa E.L. Braun, Solidago caesia L., Solidago curtisii Torr. & A. Gray, Solidago flexicaulis L., Solidago glomerata Michx., Solidago lancifolia (Torr. & A. Gray) Chapm., Solidago macrophylla Pursh, and Solidago ouachitensis C.E.S Taylor & R.J. Taylor. Additional analyses were preformed to determine statistical support for varietal level a priori groups within S. caesia and S. curtisii. Statistical support for recognizing all 10 a priori groups varied, although in all analyses, the P values were always well below α of 0.05. Based on the results of the discriminant analyses, the following taxa are recognized: S. albopilosa, S. caesia var. caesia , S. caesia var. zedia , S. curtisii var. curtisii , S. curtisii var. flaccidifolia , S. flexicaulis, S. glomerata, S. lancifolia, S. macrophylla, and S. ouachitensis.
Best Proximity Sets and Equilibrium Pairs for a Finite Family of Multimaps
Authors: Al-Thagafi M. A. , Shahzad Naseer 
Published: January 2009

AbstractWe establish the existence of a best proximity pair for which the best proximity set is nonempty for a finite family of multimaps whose product is either an "Equation missing"-multimap or a multimap "Equation missing" such that both "Equation missing" and "Equation missing" are closed and have the KKM property for each Kakutani multimap "Equation missing". As applications, we obtain existence theorems of equilibrium pairs for free 1-person games as well as for free 1-person games. Our results extend and improve several well-known and recent results.
Expression and prognostic significance of kallikrein-related peptidase 8 protein levels in advanced ovarian cancer by using automated quantitative analysis
Authors: Scorilas Andreas , Markakis Sonia , Kowalski Diane , Camp Robert L. , Diamandis Eleftherios P. , Dimopoulos Meletios A. , Kountourakis Panteleimon , Psyrri Amanda 
Published: January 2009

SummaryKallikrein-related peptidases, a subgroup of the serine protease enzyme family, are considered to be important prognostic biomarkers in cancer. In this study we sought to determine the prognostic value of kallikrein-related peptidase 8 (KLK8,hK8,KLK-8) in ovarian cancer using a novel method of compartmentalised in situ protein analysis. A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For the evaluation of kallikrein-related peptidase 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred twenty-six of 150 cases had sufficient tissue for AQUA analysis. There were significant correlations between tumour mask KLK8 protein expression levels and clinicopathological variables, including grade (p=0.0011), residual disease (p=0.0063) and clinical response to chemotherapy(p=0.0346). In univariate survival analysis there was a significant correlation between KLK8 tumour mask expression and five years progression-free survival, meanwhile it was not associated with five-year overall survival (p =0.0694). Specifically, low KLK8 expression correlated with better outcome (top vs. bottom quartile, p=0.0319). In multivariate survival analysis, adjusting for well-characterised prognostic variables, tumour KLK8 expression level retained its prognostic significance for progression-free survival (95%CI: 0.341–1.027, p=0.045). The possibility that KLK8 may be a suitable candidate as a diagnostic and prognostic marker warrants further investigation.
How useful is determination of anti-factor Xa activity to guide bridging therapy with enoxaparin?
Authors: Omran Heyder , Tripp Christian , Poetzsch Bernd , Hammerstingl Christoph 
Published: January 2009

SummaryLow-molecular-weight heparins (LMWH) are commonly used as peri-procedural bridging anticoagulants. The usefulness of measurement of anti-factor Xa activity (anti-Xa) to guide bridging therapy with LMWH is unknown. It was the objective of this study to determine levels of anti-Xa during standard bridging therapy with enoxaparin, and to examine predictors for residual anti-Xa. Consecutive patients receiving enoxaparin at a dosage of 1 mg/kg body weight/12 hours for temporary interruption of phenprocoumon were prospectively enrolled to the study. Blood-samples were obtained 14 hours after LMWH-application immediately pre- procedurally. Procedural details, clinical and demographic data were collected and subsequently analyzed. Seventy patients were included (age 75.2 ± 10.8 years, Cr Cl 55.7 ± 21.7ml/min, body mass index [BMI] 27.1 ± 4.9). LMWH- therapy was for a mean of 4.2 ± 1.6 days; overall anti-Xa was 0.58 ± 0.32 U/ml. In 37 (52.8%) of patients anti-Xa was ≥0.5 U/ml, including 10 (14.3%) patients with anti-Xa > 1U/ml. Linear regression analysis of single variables and logistic multivariable regression analysis failed to prove a correlation between anti-Xa and single or combined factors. No major bleeding, no thromboembolism and four (5.7%) minor haemorrhages were observed. When bridging OAC with therapeutic doses of enoxaparin a high percentage of patients undergo interventions with high residual anti-Xa. The levels of anti-Xa vary largely and are independent of single or combined clinical variables. Since the anti-Xa-related outcome of patients receiving bridging therapy with LMWH is not investigated, no firm recommendation on the usefulness of monitoring of anti-Xa can be given at this stage.
Increased plasma von Willebrand factor antigen levels but normal von Willebrand factor cleaving protease (ADAMTS13) activity in preeclampsia
Authors: Rigó Jr János , Bõze Tamás , Derzsy Zoltán , Cervenak László , Makó Veronika , Gombos Tímea , Udvardy Miklós László , Hársfalvi Jolán , Prohászka Zoltán , Molvarec Attila 
Published: January 2009

SummaryThe activity of ADAMTS13, the von Willebrand factor (VWF) cleaving protease is low in several conditions, including HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome. As HELLP syndrome develops in most cases on the basis of preeclampsia, our aim was to determine whether plasma ADAMTS13 activity is decreased in preeclampsia. Sixty-seven preeclamptic patients, 70 healthy pregnant women and 59 healthy non-pregnant women were involved in this case-control study. Plasma ADAMTS13 activity was determined with the FRETS-VWF73 assay, while VWF antigen (VWF:Ag) levels with an enzyme-linked immunosorbent assay. The multimeric pattern of VWF was analyzed by SDS-agarose gel electrophoresis. There was no significant difference in plasma ADAMTS13 activity between the preeclamptic and the healthy pregnant and non-pregnant groups (median [25–75 percentile]: 98.8 [76.5–112.8] %, 96.3 [85.6–116.2] % and 91.6 [78.5–104.4] %, respectively; p>0.05). However, plasma VWF:Ag levels were significantly higher in preeclamptic patients than in healthy pregnant and non-pregnant women (187.1 [145.6–243.1] % versus 129.3 [105.1–182.8] % and 70.0 [60.2–87.3] %, respectively; p<0.001). The multimeric pattern of VWF was normal in each group. Primiparas had lower plasma ADAMTS13 activity than multi-paras (92.6 [75.8–110.6] % versus 104.2 [92.1–120.8] %; p=0.011). No other relationship was found between clinical characteristics, laboratory parameters and plasma ADAMTS13 activity in either study group. In conclusion, plasma ADAMTS13 activity is normal in preeclampsia despite the increased VWF:Ag levels. However, further studies are needed to determine whether a decrease in plasma ADAMTS13 activity could predis-pose preeclamptic patients to develop HELLP syndrome.
Factor XIII-A subunit Val34Leu polymorphism is associated with the risk of thrombosis in patients with antiphospholipid antibodies and high fibrinogen levels
Authors: Red Gloria de la , Tàssies Dolores , Espinosa Gerard , Monteagudo Joan , Bové Albert , Plaza Joan , Cervera Ricard , Reverter Joan-Carles 
Published: January 2009

SummaryRecent reports have described the factor XIII A subunit (FXIII-A) Val34Leu polymorphism as a protective factor against venous and arterial thrombosis. The aim of this study was to investigate the association between the FXIII-A Val34Leu polymorphism, its interaction with fibrinogen concentration, and thrombosis in patients with antiphospholipid antibodies (aPL). We included 172 consecutive patients with aPL: 88 with primary antiphospholipid syndrome (APS), 38 with APS associated with systemic lupus erythematosus (APS-SLE), 32 with SLE and aPL but without APS (SLE-aPL), and 14 asymptomatic individuals with aPL (A-aPL). The FXIII-A Val34Leu polymorphism was assessed by polymerase chain reaction techniques. We found no significant differences in FXIII-A Leu34 allele frequencies between primary APS (allele frequency 0.22), APS-SLE (0.23), SLE-aPL (0.22) and A-aPL (0.32) patients, or between patients with (0.21) and without thrombosis (0.26). FXIII-A Leu34 allele frequencies were significantly lower in patients with thrombosis and those in the upper fibrinogen tertile (>3.40 g/l) (allele frequency 0.07) compared with patients without thrombosis in the upper fibrinogen tertile (0.29) and patients with (0.29) and without (0.25) thrombosis in the mid- and lower fibrinogen tertiles. The FXIII-A Leu34 allele had a protective effect against thrombosis in patients in the upper fibrinogen tertile (odds ratio [OR]=0.20, 95% confidence interval [CI] 0.07–0.60) but not in those in the other tertiles (OR=1.20, 95% CI 0.67–2.16). The FXIII-A Leu34 allele seems to have a protective effect on the development of thrombosis in patients with aPL, but only in those with high plasma fibrinogen values.
Maturation of blood vessels by haematopoietic stem cells and progenitor cells: Involvement of apelin/APJ and angiopoietin/Tie2 interactions in vessel caliber size regulation
Authors: Kidoya Hiroyasu , Takakura Nobuyuki 
Published: January 2009

SummaryApelin is a recently-isolated bioactive peptide from bovine gastric extract. The gene encodes a protein of 77 amino acids, which can generate two active polypeptides, long (42–77) and short (65–77). Both peptides ligate and activate APJ, a G protein-coupled receptor expressed in the cardiovascular and central nervous systems. Although an essential role for the apelin/APJ system in blood vessel formation has been reported in Xenopus, its precise function in mammals is unclear. Blood vessel tube formation is accomplished by two main mechanisms: 1) single cell hollowing, in which a lumen forms within the cytoplasm of a single endothelial cell (EC), and 2) cord hollowing in which a luminal cavity is created de novo between ECs in a thin cylindrical cord. Molecular control of either single cell or cord hollowing has not been precisely determined. Angiopoietin-1 (Ang1) has been reported to induce enlargement of blood vessels. Apelin is produced from ECs upon activation of Tie2, a cognate receptor of Ang1, expressed on ECs. It has been suggested that apelin induces cord hollowing by promoting proliferation and aggregation/assembly of ECs. During angiogenesis, haematopoietic stem cells (HSCs) and progenitor cells (HPCs) are frequently observed in the perivascular region. They produce Ang1 and induce migration of ECs, resulting in a fine vascular network. Moreover, HSCs/HPCs can induce apelin production from ECs. Therefore, this review article posits that HSCs/HPCs regulate caliber size of blood vessels via apelin/APJ and Angiopoietin/Tie2 interactions.
Point-of-care versus central laboratory coagulation testing during haemorrhagic surgery
Authors: Ozier Yves , Ankri Annick , Fléron Marie-Hélène , Leroux Geneviève , Samama Charles Marc , Toulon Pierre 
Published: January 2009

SummaryDelay in collecting coagulation test results from a central laboratory is one of the critical issues to efficiently control haemostasis during surgery. The aim of this multicenter study was to compare the performance of a point-of-care (POC) device (CoaguChek™ Pro DM) with the central laboratory-based coagulation testing during haemorrhagic surgery. For this purpose, 93 patients undergoing major surgical procedure were prospectively included in three centers. Blood was drawn from all patients before surgical incision and from most patients during surgical procedure after a blood loss of 25% or more was observed. When expressed in activity percentage, POC-based prothrombin time (PT) was in good agreement with central laboratory test result with coefficient of correlation in the range from 0.711 to 0.960 in the three centers. Comparison was less conclusive when PT was expressed in seconds or as the patient-to-control ratio and for activated partial thromboplastin time, with significantly shorter clotting times and lower ratios obtained on the POC device. On-site PT (in activity percentage) monitoring would have induced no significant change in fresh frozen plasma (FFP) transfusion in patients when compared to central laboratory monitoring. Test results were obtained in less than 5 minutes when performed using the POC device versus a median turnaround time of 88 minutes (range: 29–235 minutes) when blood collection tubes were sent to the central laboratory. These results suggest that, in providing a rapid answer, POC-based monitoring of PT (in percentage) using the CoaguChek device could be validly used in patients undergoing haemorrhagic surgical procedures.