bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cloning and characterization of WMSU1, a Williopsis saturnus var. mrakii gene encoding a new yeast SUN protein involved in the cell wall structure
Authors: Guyard Cyril , Cailliez Jean‐Charles , Tissier Jean‐Pierre , Dei‐Cas Eduardo , Mercenier Annick , Menozzi Franco D. 
Published: October 2002

AbstractSUN proteins of Saccharomyces cerevisiae have been defined on the basis of high homologies in their C‐terminal domain. Recently, two of these four proteins were shown to be involved in cell wall morphogenesis (Mouassite et al., 2000a). In the present study, we have isolated WMSU1 (Accession No. AF418983), a new SUN‐related gene, from W. saturnus var. mrakii MUCL 41968. Sequencing of the gene revealed an open reading frame coding for 402 amino acids. The predicted amino acid sequence of WMSU1 is closely related to the S. cerevisiae SUN proteins and to other yeast proteins involved in cell wall metabolism. WMSU1 is proposed to encode a cell wall protein since its predicted product contains a signal sequence, a Kex2p cleavage site and a serine/threonine‐rich N‐terminal domain. Southern blot analysis of the W. saturnus var. mrakii MUCL 41968 genome using the highly conserved domain of WMSU1 as a probe suggested that the isolated gene belongs to a multigenic family. Expression of WMSU1 in E. coli led to a 45 kDa protein, which appeared to be toxic to this host. Scanning electron microscopy analysis of a recombinant S. cerevisiae producing Wmsu1p showed that this strain exhibited an altered cell wall, thus pointing to a probable role of this protein in the cell wall structure. Copyright © 2002 John Wiley & Sons, Ltd.
A case‐control study of the impact of WBC reduction on the cost of hospital care for patients undergoing coronary artery bypass graft surgery
Authors: Volkova Natalia , Klapper Ellen , Pepkowitz Samuel H. , Denton Timothy , Gillaspie Glenn , Goldfinger Dennis 
Published: October 2002

BACKGROUND : WBC reduction of blood components may reduce the incidence of transfusion reactions. The cost of this intervention might be offset by a reduction in the incidence of postoperative infection, thereby reducing the length of hospital stay and thus the cost of care for patients receiving transfusion. Cedars‐Sinai Medical Center provided WBC‐reduced blood components to all patients for a period of 2 years, creating an opportunity to compare the incidence of postoperative infection, length of hospital stay, and total hospital costs for patients undergoing coronary artery bypass graft surgery, before, during, and after WBC reduction. STUDY DESIGN AND METHODS : Data were obtained by examining hospital records of patients who received transfusion and control patients who did not receive transfusion for the years 1991 (before WBC reduction), 1992 to 1993 (during WBC reduction), and 1994 (following discontinuation of WBC reduction). Comparisons were made by use of ANOVA following log or square root transformation of the data. RESULTS : Length of hospital stay for patients who received transfusion decreased over time. Mean hospital stays were 15.9, 14.1, and 12.1 days before, during, and after WBC reduction, respectively. A similar trend was seen in the patients who did not receive transfusion. There was no indication that WBC reduction functioned as an independent variable that was responsible for the observed decrease. The rate of postoperative infection stayed constant during WBC reduction and only dropped when WBC reduction was stopped. Mean hospital cost showed no significant change over time for either the tranfusion group or the nontransfusion group. CONCLUSION : The cost of providing a totally WBC‐reduced blood supply may not be offset by immediate savings related to decreased postoperative infections, reduced length of hospital stay, and cost of hospital care.
Overanticoagulation associated with combined use of antifungal agents and coumarin anticoagulants*
Authors: Visser Loes E. , Penning‐van Beest Fernie J. A. , Kasbergen A. A. Harrie , De Smet Peter A. G. M. , Vulto Arnold G. , Hofman Albert , Stricker Bruno H. Ch. 
Published: October 2002

BackgroundSeveral case reports have associated combined use of coumarins and antifungal agents with overanticoagulation. However, we are not aware of epidemiologic studies that quantify the risk of overanticoagulation caused by antifungal agents. We conducted a follow‐up study in a large population‐based cohort to investigate the antifungal agents that are associated with overanticoagulation during therapy with coumarins.MethodsAll patients in the Rotterdam Study who were treated with acenocoumarol or phenprocoumon in the study period from April 1, 1991, through Dec 31, 1998, and for whom international normalized ratio data were available were followed up until an INR ≥6.0, the end of their treatment, death, or the end of the study period. Proportional hazards regression analysis was used to estimate the risk of an INR ≥6.0 in relation to concomitant use of an oral anticoagulant and antifungal agents, after adjustment for several potentially confounding factors such as age, gender, hepatic dysfunction, malignancies, and heart failure.ResultsOf the 1124 patients in the cohort, 351 had an INR ≥6.0. The incidence rate was 6.9 per 10,000 treatment days. Oral miconazole most strongly increased the risk of overanticoagulation with an adjusted relative risk of 36.6 (95% confidence interval [CI], 12.4‐108.0).ConclusionsIn this study among outpatients of an anticoagulant clinic who were on a regimen of coumarins, oral miconazole was especially strongly associated with overanticoagulation. Awareness of these drug interactions and more frequent monitoring of INR values during the initial stages of treatment with some antifungal drugs in patients taking coumarins may minimize the risk of bleeding complications. The concurrent use of miconazole and coumarins should be discouraged.Clinical Pharmacology & Therapeutics (2002) 71, 496–502; doi: 10.1067/mcp.2002.124470
Enantiospecific effects of cytochrome P450 2C9 amino acid variants on ibuprofen pharmacokinetics and on the inhibition of cyclooxygenases 1 and 2
Authors: Kirchheiner Julia , Meineke Ingolf , Freytag Georg , Meisel Christian , Roots Ivar , Brockmöller Jürgen 
Published: October 2002

ObjectiveAccording to in vitro data, the polymorphic cytochrome P450 enzyme 2C9 (CYP2C9) may be the major S‐ibuprofen hydroxylase. In humans, there are 2 variants of CYP2C9 with a high population frequency. We studied their impact on ibuprofen pharmacokinetics and on the inhibition of cyclooxygenases 1 and 2.MethodsKinetics of an oral dose of 600 mg racemic ibuprofen were studied in 21 healthy volunteers with all combinations of the CYP2C9 variants *2 (arginine144cysteine) and *3 (isoleucine359leucine). Blood concentrations of racemic ibuprofen and of S‐(+)‐ibuprofen and R‐(−)‐ibuprofen were measured by HPLC, and thromboxane B2 and prostaglandin E2 were measured with use of an enzyme immunoassay. Data were evaluated witha population pharmacokinetic model that integrated pharmacogenetic information.ResultsThe pharmacokinetics of racemic and of S‐ibuprofen depended on the CYP2C9 isoleucine359leucine amino acid polymorphism: population mean S‐ibuprofen clearances were 3.25 L/h (95% confidence interval [CI], 2.84 to 3.73), 2.38L/h (95% CI, 2.09 to 2.73), and 1.52 L/h (95% CI, 1.33 to 1.74) in carriersof the CYP2C9 genotypes *1/*1, *1/*3, and *3/*3, respectively. The CYP2C9 variant *2 exhibited no significant effect. Ex vivo formation of thromboxane B2, reflecting cyclooxygenase type 1 inhibition, depended significantly on the CYP2C9 polymorphism. The maximal inhibition ofthromboxane B2 formation and the area under the effect‐time curve were larger in carriers of the slow CYP2C9 genotypes *1/*3, *2/*3, and *3/*3 than in *1/*1 carriers; the same trend was observed for prostaglandin E2, reflecting cyclooxygenase type 2 inhibition.ConclusionsThe reduced S‐ibuprofen total clearance accompanied by increased pharmacodynamic activity may have medical impact in patients receiving ibuprofen.Clinical Pharmacology & Therapeutics (2002) 72, 62–75; doi: 10.1067/mcp.2002.125726
The relationship of hepatic tissue oxygenation with nitric oxide metabolism in ischemic preconditioning of the liver
Authors: Koti Rahul S. , Seifalian Alexander M. , McBride Alan G. , Yang Wenxuan , Davidson Brian R. 
Published: October 2002

ABSTRACTIschemic preconditioning (IPC) may increase the hepatic tolerance of ischemic injury during liver surgery and transplantation via nitric oxide (NO) formation. This study investigates the effect of IPC on hepatic tissue oxygenation and the role of NO stimulation and inhibition on the preconditioning effect in the rat liver. Study groups had 1) sham laparotomy; 2) 45‐min lobar liver ischemia and 2‐h reperfusion (IR); 3) IPC with 5‐min ischemia and 10‐min reperfusion before IR; 4) L‐arginine before IR; and 5) Nω‐Nitro‐L‐arginine methyl ester (L‐NAME) + IPC before IR. Hepatic tissue oxygenation was monitored by near‐infrared spectroscopy. Plasma alanine aminotransferase and plasma nitrite/nitrate were measured. Following IR there was significant decrease in oxyhemoglobin and cytochrome oxidase and an increase in deoxyhemoglobin (P<0.05 vs. Sham). IPC produced a significant increase in intracellular oxygenation at the end of the reperfusion period (cytochrome oxidase CuA redox state, P<0.05 vs IR). NO stimulation with L‐arginine did not attenuate the impairment in hepatic tissue oxygenation after IR (P>0.05 vs IR). In contrast, inhibition of NO synthesis blocked the effect of IPC and further impaired tissue oxygenation (decreased cytochrome oxidase CuA redox state and increased deoxyhemoglobin, both P<0.05 vs IR), suggesting an aggravation of ischemia reperfusion injury. Hepatocellular injury was reduced by IPC and L‐arginine and increased by NO blockade with L‐NAME (Plasma ALT, all P< 0.05 vs IR). Hepatic tissue oxygenation correlated significantly with ALT and plasma nitrite/nitrate. Ischemic preconditioning significantly improved hepatic intra cellular oxygenation and reduced hepatocellular injury. NO stimulation reduced hepatocellular injury, whereas inhibition of nitric oxide synthesis blocked the effect of IPC and reduced tissue oxygenation and increased hepatocellular injury.
Codon 12 and codon 13 mutations at the K‐ras gene induce different soft tissue sarcoma types in nude mice
Authors: Guerrero Sílvia , Figueras Agnès , Casanova Isolda , Farré Lourdes , Lloveras Belen , Capellà Gabriel , Trias Manuel , Mangues Ramon 
Published: October 2002

ABSTRACTK‐ras codon 12 mutation is more oncogenic in in vitro and in vivo experimental systems than Kras codon 13 mutation. Moreover, human colorectal tumors bearing a codon 12 mutation are more aggressive, invasive, and metastatic than the same tumor types carrying a codon 13 mutation. However, despite the association between specific sarcoma types and codon 12 or codon 13 mutations, the relationship between the position of the mutated codon at ras genes and tumor aggressiveness has not been studied in this tumor type. Here, we used a nude mice model to evaluate the tumorogenic capacity of stable transfectants of NIH3T3 fibroblasts, expressing Kras mutated at codon 12 (K12) or 13 (K13), and morphologically, functionally, and molecularly compared these tumors. We found histopathological differences between them, K12‐derived tumors showing fibrosarcoma‐like features, whereas K13‐derived tumors resembled malignant fibrous histiocytomas. Moreover, K12 tumors showed shorter latency of appearance, lower apoptotic and mitotic rates, and higher expression of markers for sarcoma aggressiveness (Ki67, p53 and c‐myc) than K13 tumors. They also showed differences in the expression or activation of Ras, Ras downstream pathways [c‐Jun N‐terminal kinase (JNK), MAPK and AKT], and apoptotic [AKT, Bcl‐2, Focal adhesion kinase (FAK)] and mitotic (cyclin B1) regulators, which could explain their functional differences. Most remarkably, the significantly diminished apoptotic rate observed in K12‐derived tumors was associated with enhanced antiapoptotic signaling through the AKT pathway. These morphological, functional, and molecular differences demonstrate that codon 12 and codon 13 mutations in the K‐ras oncogene can induce two different soft tissue sarcoma types in our in vivo model.
MEK and ERK inhibitors enhance the antiproliferative effect of interferon‐α2b
Authors: Romerio Fabio , Zella Davide 
Published: October 2002

ABSTRACTInterferon (IFN)‐α, initially characterized as an antiviral cytokine, affects several cellular functions. It is used in clinical practice for the treatment of several tumors, including hematopoietic malignancies, due to its antiproliferative effects. To better characterize the molecular mechanism(s) underlying this property, we conducted our studies in purified primary CD4+ T cells stimulated with anti‐CD3 and interleukin (IL)‐2. Upon treatment with IFN‐α, the cells were blocked in the G0/G1 phase of the cell cycle and exhibited impaired entry into S phase and reduced proliferation. Moreover, we detected short‐ and long‐term inhibition of extracellular signal‐regulated kinase (ERK) and mitogen‐activated ERK‐regulating kinase (MEK) function, known to control cellular proliferation. The activity of the upstream regulators, Ras and Raf‐1, was not affected. Analysis of downstream events controlled by the MEK/ERK pathway showed reduced activity of cyclin‐dependent kinase (Cdk)‐2 and ‐4, high levels of the mitotic inhibitors, p21Waf1 and p27Kip1, and decreased cyclin D and E expression. When IFN‐α was used in combination with MEK and ERK inhibitors, we observed a dose‐dependent additive effect in reducing cellular proliferation. Our data demonstrate that IFN‐α may be associated with other molecules to inhibit cellular growth by targeting the MEK/ERK pathway. This may eventually lead to new clinical strategies to strengthen its anticancer effect.
The involvement of mitogen‐activated protein (MAP) kinase in the regulation of amyloid precursor protein processing by novel cholinesterase inhibitors derived from rasagiline
Authors: Yogev‐Falach Merav , Amit Tamar , Bar‐Am Orit , Weinstock Marta , Youdim Moussa B.H. 
Published: October 2002

ABSTRACTTwo novel neuroprotective cholinesterase (ChE) inhibitors, TV3326, (N‐propargyl‐(3R) aminoindan‐5‐yl)‐ethyl methyl carbamate, and TV3279, (N‐propargyl‐(3S) aminoindan‐5‐yl)ethyl methyl carbamate, were derived from rasagiline for the treatment of Alzheimer's disease (AD). TV3326 also inhibits monoamine oxidase (MAO)‐A and ‐B, whereas its S‐isomer, TV3279, lacks MAO inhibitory activity. The action of these drugs in the regulation of amyloid precursor protein (APP) processing, using rat PC12 and human SH‐SY5Y neuroblastoma cells, was examined. Both isomers stimulated the release of the non‐amyloidogenic α‐secretase form of soluble APP (sAPPα) from these cell lines. The increases in sAPPα, induced by TV3326 and TV3279, were dose‐dependent (0.1–100 μM) and blocked by the hydroxamic acid‐based metalloprotease inhibitor, Ro31–9790, suggesting mediation via α‐secretase activity. Using several signal transduction inhibitors, we identified the involvement of protein kinase C (PKC), mitogen‐activated protein (MAP) kinase, and tyrosine kinase‐dependent pathways in the enhancement of sAPPα release by TV3326 and TV3279. In addition, both drugs directly induced the phosphorylation of p44 and p42 MAP kinase, which was abolished by the specific inhibitors of MAP kinase activation, PD98059 and U0126. These data suggest a novel pharmacological mechanism whereby these ChE inhibitors regulate the secretory processes of APP via activation of the MAP kinase pathway.
Real-Time Imaging of Fluorescent Flagellar Filaments of
Rhizobium lupini
H13-3: Flagellar Rotation and pH-Induced Polymorphic Transitions
Authors: Scharf Birgit 
Published: October 2002

ABSTRACT

The soil bacterium
Rhizobium lupini
H13-3 has complex right-handed flagellar filaments with unusual ridged, grooved surfaces. Clockwise (CW) rotation propels the cells forward, and course changes (tumbling) result from changes in filament speed instead of the more common change in direction of rotation. In view of these novelties, fluorescence labeling was used to analyze the behavior of single flagellar filaments during swimming and tumbling, leading to a model for directional changes in
R
.
lupini
. Also, flagellar filaments were investigated for helical conformational changes, which have not been previously shown for complex filaments. During full-speed CW rotation, the flagellar filaments form a propulsive bundle that pushes the cell on a straight path. Tumbling is caused by asynchronous deceleration and stops of individual filaments, resulting in dissociation of the propulsive bundle.
R
.
lupini
tumbles were not accompanied by helical conformational changes as are tumbles in other organisms including enteric bacteria. However, when pH was experimentally changed, four different polymorphic forms were observed. At a physiological pH of 7, normal flagellar helices were characterized by a pitch angle of 30°, a pitch of 1.36 μm, and a helical diameter of 0.50 μm. As pH increased from 9 to 11, the helices transformed from normal to semicoiled to straight. As pH decreased from 5 to 3, the helices transformed from normal to curly to straight. Transient conformational changes were also noted at high viscosity, suggesting that the
R
.
lupini
flagellar filament may adapt to high loads in viscous environments (soil) by assuming hydrodynamically favorable conformations.
The Gene
yjfQ
Encodes the Repressor of the
yjfR-X
Regulon (
ula
), Which Is Involved in
l
-Ascorbate Metabolism in
Escherichia coli
Authors: Campos Evangelina , Aguilar Juan , Baldoma Laura , Badia Josefa 
Published: October 2002

ABSTRACT

Mutations in
yjfQ
allowed us to identify this gene as the regulator of the operon
yjfS-X
(
ula
operon), reported to be involved in
l
-ascorbate metabolism. Inactivation of this gene renders constitutive the expression of the
ula
operon, indicating that YjfQ acts as a repressor. We also demonstrate that this repressor regulates the nearby
yjfR
gene, which in this way constitutes a regulon with the
ula
operon.
A Gene Encoding a Homologue of Dolichol Phosphate-β-
d
-Mannose Synthase Is Required for Infection of
Streptomyces coelicolor
A3(2) by Phage φC31
Authors: Cowlishaw Deborah A. , Smith Margaret C. M. 
Published: October 2002

ABSTRACT

We have shown previously that a gene encoding a homologue to the eukaryotic dolichol-phosphate-
d
-mannose, protein
O
-
d
-mannosyltransferase, was required for φC31 infection of
Streptomyces coelicolor
. Here we show that a gene encoding the homologue to dolichol-phosphate-mannose synthase is also essential for phage sensitivity. These data confirm the role of glycosylation in the phage receptor for φC31 in
S. coelicolor
.
Behaviour of Young Growing Pigs in a Resident‐Intruder Test Designed to Measure Aggressiveness
Authors: D'Eath Richard B. , Pickup Helena E. 
Published: October 2002

AbstractA total of 125 growing pigs (47 days old) were tested for aggressive responses on two occasions using a resident‐intruder (R‐I) design. Our aims were twofold: (1) to attempt to replicate earlier work on pigs showing that resident aggression is a consistent individual characteristic, unaffected by weight or sex of the resident or intruder and (2) to develop behavioural measures to characterise the wide range of aggressive responses in the test. Resident pigs, housed since birth with littermates, were placed individually in a divided‐off portion of their home pen, and a smaller, unfamiliar intruder (approximately 66% of the resident's weight) was introduced. The test ended 5 min after the first investigation of the intruder by the resident or when one of the pigs began to attack the other (by delivering a sudden, rapid series of bites). On days 1 and 2, 33.6% and 43.2% of tests, respectively, ended in an attack by a resident. Intruder attacks were rare. Pigs were consistent in whether they attacked or not over the two tests, although attack latencies for pigs attacking in both tests were not correlated. Females were more likely to attack and attacked more quickly than males on the first test day but not in the second test or overall. Intruder sex had some effect on the test outcome (males were attacked more rapidly in the second test only). Resident and intruder weight had no effect. Aggressive pigs (meaning pigs that attacked vs. pigs that did not and fast‐attacking pigs vs. slow‐attacking pigs) showed a number of differences in behaviour during the R‐I test: (1) they took longer to make initial contact with the intruder in their first test; (2) they showed a higher frequency of aggressive acts (single head knocks, bites, and shoves); (3) they spent a greater proportion of the test engaging in social contact with the intruder rather than non‐social behaviours; (4) their social behaviour involved more postures directed toward the head as opposed to flank‐ or rear‐directed postures or re‐establishing social contact; and (5) they showed closer physical contact with intruders during social encounters, as characterised by their lower head positions. Some of these behavioural measures could be used to improve the measuring power of the test in the future. Improved behavioural measures would enable aggressiveness scoring among pigs that did not attack instead of classifying them all together as “non‐attacking.” Aggr. Behav. 28:401–415, 2002. © 2002 Wiley‐Liss, Inc.
Natural gradient algorithm for neural networks applied to non‐linear high power amplifiers
Authors: Abdulkader H. , Langlet F. , Roviras D. , Castanie F. 
Published: October 2002

AbstractThis paper investigates the processing techniques for non‐linear high power amplifiers (HPA) using neural networks (NNs). Several applications are presented: Identification and Predistortion of the HPA. Various Neural Network structures are proposed to identify and predistort the HPA.Since a few decades, NNs have shown excellent performance in solving complex problems (like classification, recognition, etc.) but usually they suffer from slow convergence speed. Here, we propose to use the natural gradient instead of the classical ordinary gradient in order to enhance the convergence properties. Results are presented concerning identification and predistortion using classical and natural gradient. Practical implementations issues are given at the end of the paper. Copyright © 2002 John Wiley & Sons, Ltd.
A forward‐only recursion algorithm for MAP decoding of linear block codes
Authors: Zepernick Hans‐Jürgen 
Published: October 2002

AbstractThe evolution of digital mobile communications along with the increase of integrated circuit complexity has resulted in frequent use of error control coding to protect information against transmission errors. Soft decision decoding offers better error performance compared to hard decision decoding but on the expense of decoding complexity. The maximum
a posteriori (MAP) decoder is a decoding algorithm which processes soft information and aims at minimizing bit error probability. In this paper, a matrix approach is presented which analytically describes MAP decoding of linear block codes in an original domain and a corresponding spectral domain. The trellis‐based decoding approach belongs to the class of forward‐only recursion algorithms. It is applicable to high rate block codes with a moderate number of parity bits and allows a simple implementation in the spectral domain in terms of storage requirements and computational complexity. Especially, the required storage space can be significantly reduced compared to conventional BCJR‐based decoding algorithms. Copyright © 2002 John Wiley & Sons, Ltd.