bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of bronchial responsiveness to histamine in asthma, allergic rhinitis and allergic sensitization at the age of 7 years
Authors: Nickel R. , Lau S. , Niggemann B. , Sommerfeld C. , Wahn U. ,   the German Multicenter Allergy Study Group
Published: October 2002

SummaryBackground Bronchial responsiveness (BR) to histamine or methacholin is a common finding in adult non‐asthmatic patients with allergic rhinitis.Objective We tested whether BR is also present in children with a comparatively short history of allergic rhinitis in a paediatric cohort.Methods We performed pulmonary function tests and histamine challenges in a total of 654 children (age 7 years, participants of the German Multicenter Allergy Study) and compared PC20 FEV1 values in children with asthma, allergic rhinitis, asymptomatic allergic sensitization and non‐atopic controls.Results Most pronounced BR to histamine was observed in allergic asthmatics (n = 28), irrespective of the presence or absence of allergic rhinitis. Furthermore, PC20FEV1 values in non‐asthmatic children with allergic rhinitis (n = 24) were not significantly different from those seen in asymptomatic atopic (n = 54) or non‐atopic controls (n = 92).Conclusions In contrast to adult study populations, 7‐year‐old non‐asthmatic children with allergic rhinitis do not show a higher degree of BR than asymptomatic atopic or non‐atopic controls. Therefore, secondary preventive measures in non‐asthmatic children with allergic rhinitis (such as regular local anti‐inflammatory therapy or specific immunotherapy) should be studied and applied more intensely to prevent bronchial hyper‐responsiveness (BHR) and asthma in this high‐risk group.
Use of a flow‐cell system to investigate virucidal dimethylmethylene blue phototreatment in two RBC additive solutions
Authors: Wagner Stephen , Skripchenko Andrey , Thompson‐Montgomery Dedeene 
Published: October 2002

BACKGROUND: Limited photoinactivation kinetics, use of low‐volume 30 percent Hct RBCs, and hemolysis have restricted the practicality of the use of dimethylmethylene blue (DMMB) and light for RBC decontamination. A flow‐cell system was developed to rapidly treat larger volumes of oxygenated 45 percent Hct RBCs with high‐intensity red light.MATERIALS AND METHODS: CPD‐whole blood was WBC reduced, RBCs were diluted in additive solutions (either Adsol or Erythrosol), and suspensions were subsequently oxygenated by gas overlay. Intracellular or extracellular VSV and DMMB were sequentially added. VSV‐infected RBC suspensions (45% Hct) were passed through 1‐mm‐thick flow cells and illuminated. Samples were titered for VSV, stored for up to 42 days, and assayed for Hb, supernatant potassium, ATP, and MCV.RESULTS: The use of oxygenated RBCs resulted in rapid and reproducible photoinactivaton of ≥6.6 log extracellular and approximately 4.0 log intracellular VSV independent of additive solution. Phototreated Adsol RBCs exhibited more than 10 times greater hemolysis and 30 percent greater MCV during storage than identically treated Erythrosol RBCs. Phototreatment caused RBC potassium leakage from RBCs in both additive solutions. ATP levels were better preserved in Erythrosol than Adsol RBCs.CONCLUSION: A rapid, reproducible, and robust method for photoinactivating model virus in RBC suspensions was developed. Despite improved hemolysis and ATP levels in Erythrosol‐phototreated RBCs, storage properties were not maintained for 42 days.
Probability of receiving testing in a national lookback program: the English HCV experience
Authors: The English National Blood Service HCV Lookback Collation Co  
Published: October 2002

BACKGROUND : The HCV lookback program was designed to trace and offer testing to recipients who received transfusion of blood components from donors subsequently found to be anti‐HCV positive. Only approximately 20 percent of transfusable components entering lookback did result in a recipient obtaining testing through this program. STUDY DESIGN AND METHODS : Data from English blood centers were collated to describe the outcomes of the HCV lookback program. The data were used to assess factors affecting the likelihood that recipients of lookback components received testing by the program. RESULTS : In total, 4424 recipients of 6687 blood components that had been issued for transfusion were identified. The lookback resulted in a tested recipient for 1067 components. Factors positively associated with receiving testing in identified recipients were younger age at transfusion, more recent year of transfusion, certain component types, and transfusion under the care of certain medical specialties; these effects were largely explained by the association of these factors with survival after transfusion. CONCLUSION S: Not accepting testing through this program was largely due to death before the lookback and partly due to inability to access information from records and to decisions that testing was not in recipients' best interests. The probability of obtaining testing through this lookback was associated with several factors that could be used to focus the efforts of similar lookbacks in the future.
Effect of WBC reduction of transfused RBCs on postoperative infection rates in cardiac surgery
Authors: Wallis J.P. , Chapman C.E. , Orr K.E. , Clark S.C. , Forty J.R. 
Published: October 2002

BACKGROUND : WBC‐replete blood transfusion has been suggested as an independent cause of increased postoperative infection. STUDY DESIGN AND METHODS : A total of 597 patients undergoing elective coronary artery or heart valve surgery were randomly assigned to receive plasma‐ reduced (PR), buffy coat‐depleted (BCD), or WBC‐ filtered (WCF) RBCs in the event of requiring blood transfusion. Details of postoperative course were recorded. Further information was collected from the patient's general practitioner 3 months after discharge. RESULTS
: No significant difference in inpatient infection rates was observed among patients randomly assigned to receive PR, BCD, or WCF RBCs. When only those receiving transfusion were analyzed (n = 509), use of PR RBCs was associated with more events coded as infections (p ≤ 0.05) compared with BCD or WCF RBCs. However, when events coded as urinary tract infections were excluded, there was no significant difference among the three groups. Follow‐up performed after discharge showed no difference in readmission rates, but a higher reported rate of infection in those randomly assigned to receive WCF RBCs (p
< 0.02). CONCLUSION : No evidence has been found, analyzed by intention to treat, that use of WBC‐reduced, BCD, or WCF RBCs reduces postoperative inpatient infection in patients undergoing cardiac bypass surgery.
Hepatic but not intestinal CYP3A4 displays dose‐dependent induction by efavirenz in humans
Authors: Mouly Stéphane , Lown Kenneth S. , Kornhauser David , Joseph Jeffrey L. , Fiske William D. , Benedek Irma H. , Watkins Paul B. 
Published: October 2002

ObjectiveThe capacity of the non‐nucleoside reverse transcriptase inhibitor efavirenz to induce either liver CYP3A4 or intestinal CYP3A4, or both, as well as intestinal P‐glycoprotein, was evaluated in healthy volunteers during and after a 10‐day treatment course with two different daily doses.MethodsCohorts of 12 healthy subjects were randomized (2:1) to receive eitherefavirenz or placebo orally for 10 days. The first cohort received 200 mg efavirenz and the second cohort received 400 mg efavirenz daily. Liver CYP3A4 activity was evaluated on 9 different occasions with use of the erythromycin breath test (ERMBT). Intestinal biopsyspecimens were obtained before the first dose of efavirenz and on the day after administration of the last dose to measure intestinal CYP3A4 and P‐glycoprotein contents by immunoblotting. Efavirenz plasma levels were measured by HPLC, and pharmacokinetic parameters were determined by standard noncompartmental methods.ResultsEfavirenz significantly increased the mean ERMBT result in a dose‐ andtime‐dependent manner, with a 55% mean induction at 400 mg and a 33% mean induction at 200 mg (P < .01, compared with placebo for each treatment). The efavirenz AUC on day 10 correlated with the magnitude of induction (day 11/day 1 ERMBT ratio) when the two dose groups were combined (r = 0.509; P = .04). In contrast, efavirenz treatment had no detectable effect on intestinal CYP3A4 or P‐glycoprotein.ConclusionsEfavirenz is an inducer of liver CYP3A4 in healthy volunteesrs, and interpatient differences in magnitude of induction is partly explained by variation in systemic drug exposure. However, efavirenz did not appear to induce intestinal CYP3A4 or intestinal P‐glycoprotein. These results suggest that drug interactions caused by induction of CYP3A4 can be liver specific.Clinical Pharmacology & Therapeutics (2002) 72, 1–9;doi: 10.1067/mcp.2002.124519
Angiotensin‐converting enzyme inhibitor‐induced syndrome of inappropriate secretion of antidiuretic hormone: Case report and review of the literature
Authors: Izzedine Hassane , Fardet Laurence , Launay‐Vacher Vincent , Dorent Richard , Petitclerc Thierry , Deray Gilbert 
Published: October 2002

Seventeen cases of severe hyponatremia induced by angiotensin‐converting enzyme (ACE) inhibitor therapy have been reported in the literature. The mechanism of severe hyponatremia induced by ACE inhibitor is not clear. A 60‐year‐old white man with a history of idiopathic dilated cardiomyopathy was treated with enalapril, 20 mg daily, that had been started 2 weeks before heart transplantation. The serum sodium level was 138 mmol/L before initiation of enalapril therapy and 127 mmol/L just before cardiac surgery. In the post‐heart transplantation period, enalapril therapy was withdrawn for the perianesthesia period, and the serum sodium level increased from 127 to 140 mmol/L. One month later, viral myocarditis developed in the patient and enalapril was reintroduced at 20 mg daily. Two weeks later, natremia decreased. Enalapril was discontinued. Three days later the serum sodium level rose to 140 mmol/L. Severe symptomatic hyponatremia induced by the syndrome of inappropriate secretion of antidiuretic hormone should be considered a rare but possible complication associated with ACE inhibitor therapy.Clinical Pharmacology & Therapeutics (2002) 71, 503–507; doi: 10.1067/mcp.2002.124520
Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P‐glycoprotein
Authors: Kurata Yasuo , Ieiri Ichiro , Kimura Miyuki , Morita Toshihiro , Irie Shin , Urae Akinori , Ohdo Shigehiro , Ohtani Hisakazu , Sawada Yasufumi , Higuchi Shun , Otsubo Kenji 
Published: October 2002

ObjectiveOur objective was to quantitate the contribution of the genetic polymorphism of the human MDR1 gene to the bioavailability and interaction profiles of digoxin, a substrate of P‐glycoprotein.MethodsThe pharmacokinetics of digoxin was studied in 15 healthy volunteers, who were divided into 3 groups (n = 5 each) on the basis of genotyping for the MDR1 gene, in a 4‐dose study after single doses of digoxin alone (0.5 mg orally and intravenously) and coadministered with clarithromycin (400 mg orally for 8 days). The dose of digoxin was reduced during the clarithromycin phase (0.25 mg orally and intravenously).ResultsThe bioavailability of digoxin in G/G2677C/C3435, G/T2677C/T3435, and T/T2677T/T3435 subjects were 67.6% ± 4.3%, 80.9% ± 8.9%, and 87.1% ±8.4%, respectively, and the difference betweenG/G2677C/C3435 and T/T2677T/T3435 subjects was statistically significant (P <.05). The MDR1 variants were also associated with differences in disposition kinetics of digoxin, with the renal clearance being almost 32% lower in T/T2677T/T3435 subjects (1.9 ± 0.1 mL/min per kilogram) than G/G2677C/C3435 subjects (2.8 ± 0.3 mL/min per kilogram), and G/T2677C/T3435 subjects having an intermediate value (2.1 ± 0.6 mL/min per kilogram). Coadministration of clarithromycin did not consistently affect digoxin clearance or renal clearance. However, a significant increase in digoxin bioavailability was observed in G/G2677C/C3435subjects (67.6% ± 4.3% versus 85.4% ± 6.1%; P < .05) but not inthe other2 genotype groups.ConclusionThe allelic variants in the human MDR1 gene are likely to be associated with altered absorption and/or disposition profiles of digoxin and P‐glycoprotein‐mediated drug interaction (Clin Pharmacol Ther 2002;72:209‐19.)Clinical Pharmacology & Therapeutics (2002) 72, 209–219; doi: 10.1067/mcp.2002.126177
Effect of coadministration of nelfinavir, indinavir, and saquinavir on the pharmacokinetics of amprenavir
Authors: Pfister Marc , Labbé Line , Lu Jian‐Feng , Hammer Scott M. , Mellors John , Bennett Kara K. , Rosenkranz Susan , Sheiner Lewis B. ,   the AIDS Clinical Trial Group Protocol 398 Investigators
Published: October 2002

ObjectivePharmacokinetic interactions are expected when human immunodeficiency virus (HIV) protease inhibitors are coadministered because many are both substrates forand inhibitors of CYP3A4. The goal of this model‐based pharmacokinetic analysis was to describe the differences observed in amprenavir pharmacokinetics among treatment arms in the Adult AIDS Clinical Trial Group (AACTG) study protocol 398 and to propose mechanisms toaccount for them.MethodsOne hundred seventy‐six HIV‐positive subjects receiving 1200 mg amprenavir twice daily as part of AACTG protocol 398 were included in the pharmacokinetic study. All patients also received background medications efavirenz, adefovir dipivoxil, and abacavir and, depending on the study arm, placebo or one of the following protease inhibitors: nelfinavir, indinavir, or saquinavir. A population pharmacokinetic model was fitted to a total of 565 amprenavir concentration measurements. The blood samples for concentration measurements were drawn at week 2 (12‐hour pharmacokinetic study, approximately 7 samples per study; 46 patients) and at week 24 (6‐hour pharmacokinetic study, approximately 5samples per study; 10 patients). In addition, samples were collected at 1 or more follow‐up visits (population pharmacokinetic study, 1 to 3 occasions per patient; 150 patients).Results and ConclusionAmprenavir intrinsic clearance was significantly reduced relative to placebo by nelfinavir (−41%) and indinavir (−54%)but not by saquinavir. The absolute magnitude of amprenavir intrinsic clearance suggests that CYP3A4 inhibition by nelfinavir and indinavir is balanced by enzymatic induction in the presence of the background drug(s), most likely efavirenz. Amprenavir intrinsic clearance apparently increases by more than 30% between weeks 2 and 24, possibly because of the time course of CYP3A4 induction.Clinical Pharmacology & Therapeutics (2002) 72, 133–141; doi: 10.1067/mcp.2002.126183
Ezrin turnover and cell shape changes catalyzed by proteasome in oxidatively stressed cells
Authors: Grune Tilman , Reinheckel Thomas , North James A. , Li Rui , Bescos Paloma B. , Shringarpure Reshma , Davies Kelvin J. A. 
Published: October 2002

ABSTRACTWe find that ezrin, a cytoskeletal protein involved in anchoring actin to the cell membrane, is preferentially degraded and resynthesized after oxidative stress. Ezrin was identified using 2‐dimensional gels and amino‐terminal microsequencing as one of a select few [35S]methionine prelabeled proteins degraded in clone 9 rat liver cells exposed to hydrogen peroxide (H2O2). Metabolic labeling of cellular proteins with [35S]methionine after oxidative stress showed that resynthesis of ezrin rose dramatically but carboxyl terminus anti‐ezrin monoclonal antibodies revealed constant intracellular ezrin levels; in other words, degradation and resynthesis were exactly matched. Ezrin degradation was blocked by selective inhibitors of the proteasome (lactacystin, NLVS, and epoxomycin) and by an antisense oligonucleotide directed against the proteasome C2 subunit. H2O2 also caused major changes in cell shape, including significant increases in cell diameter, which must require substantial cytoskeletal rearrangement. Peroxide‐induced increases in cell diameter were, however, blocked by the selective proteasome inhibitor lactacystin. The degradation and resynthesis of ezrin may therefore be an underlying mechanism for overall cell shape changes observed during oxidative stress. Oxidative stress induces extensive protein oxidation and degradation and significant increases in cell blebbing, rounding‐up, and overall size. Our results indicate that all these oxidant‐induced changes may actually be catalyzed by the proteasome.—Grune, T., Reinheckel, T., North, J. A., Li, R., Bescos, P. B., Shringarpure, R., Davies, K. J. A. Ezrin turnover and cell shape changes catalyzed by proteasome in oxidatively stressed cells. FASEB J. 16, 1602–1610 (2002)
The role of caspases in cryoinjury: caspase inhibition strongly improves the recovery of cryopreserved hematopoietic and other cells
Authors: Stroh Christopher , Cassens Uwe , Samraj Ajoy K. , Sibrowski Walter , Schulze‐Osthoff Klaus , Los Marek 
Published: October 2002

ABSTRACTCryopreserved cells and tissues are increasingly used for stem cell transplantation and tissue engineering. However, their freezing, storage, and thawing is associated with severe damage, suggesting the need for better cryopreservation methods. Here, we show that activation of caspase‐3 is induced during the freeze‐thaw process. Moreover, we demonstrate that prevention of caspase activation by the caspase inhibitor zVAD‐fmk strongly improves the recovery and survival of several cryopreserved cell types and hematopoietic progenitor cells. A short preincubation with the caspase inhibitor after thawing also enhances the colony‐forming activity of hematopoietic progenitor cells up to threefold. Furthermore, overexpression of Bcl‐2, but not the blockade of the death receptor signaling, confers protection, indicating that cryoinjury‐ associated cell death is mediated by a Bcl‐2‐controlled mitochondrial pathway. Thus, our data suggest the use of zVAD‐fmk as an efficient cryoprotective agent. The addition of caspase inhibitors may be an important tool for the cryopreservation of living cells and advantageous in cell transplantation, tissue engineering, and other genetic technologies.
SAGE transcript profiles of normal primary human hepatocytes expressing oncogenic hepatitis B virus X protein
Authors: Wu Chuan‐Ging , Forgues Marshonna , Siddique Shabina , Farnsworth Julie , Velerie Kristoffer , Wang Xin Wei 
Published: October 2002

ABSTRACTHepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). HBV encodes an oncogenic HBx gene that functions as a transcriptional coactivator of multiple cellular genes. To understand the role(s) of HBx in the early genesis of HCC, we systematically analyzed gene expression profiles by serial analysis of gene expression (SAGE) in freshly isolated human primary hepatocytes infected with a replication‐defective adenovirus containing HBx. A total of 19,501 sequence tags (representing 1443 unique transcripts) were analyzed, which provide a distribution of a transcriptome characteristic of normal hepatocytes and a profile associated with HBx expression. Examples of the targeted genes were confirmed by the Megarray analysis with a significant correlation between quantitative SAGE and Megarray (r = 0.8, P> 0.005). In HBx‐expressing hepatocytes, a total of 57 transcripts (3.9%) were induced, and 46 transcripts (3.3%) were repressed by more than fivefold. Interestingly, most of the HBxup‐regulated transcripts can be clustered into three major classes, including genes that encode ribosomal proteins, transcription factors with zinc‐finger motifs, and proteins associated with protein degradation pathways. These results suggest that HBx may function as a major regulator in common cellular pathways that, in turn, regulate protein synthesis, gene transcription, and protein degradation.
Bioreactors mediate the effectiveness of tissue engineering scaffolds
Authors: Pei Ming , Solchaga Luis A. , Seidel Joachim , Zeng Li , Vunjak‐Novakovic Gordana , Caplan Arnold I. , Freed Lisa E. 
Published: October 2002

ABSTRACTWe hypothesized that the mechanically active environment present in rotating bioreactors mediates the effectiveness of three‐dimensional (3D) scaffolds for cartilage tissue engineering. Cartilaginous constructs were engineered by using bovine calf chondrocytes in conjunction with two scaffold materials (SM) (benzylated hyaluronan and polyglycolic acid); three scaffold structures (SS) (sponge, non‐woven mesh, and composite woven/non‐woven mesh); and two culture systems (CS) (a bioreactor system and petri dishes). Construct size, composition [cells, glycosaminoglycans (GAG), total collagen, and type‐specific collagen mRNA expression and protein levels], and mechanical function (compressive modulus) were assessed, and individual and interactive effects of model system parameters (SM, SS, CS, SM∗CS and SS∗CS) were demonstrated. The CS affected cell seeding (higher yields of more spatially uniform cells were obtained in bioreactor‐grown than dish‐grown 3‐day constructs) and subsequently affected chondrogenesis (higher cell numbers, wet weights, wet weight GAG fractions, and collagen type II levels were obtained in bioreactor‐grown than dish‐grown 1‐month constructs). In bioreactors, mesh‐based scaffolds yielded 1‐month constructs with lower type I collagen levels and four‐fold higher compressive moduli than corresponding sponge‐based scaffolds. The data imply that interactions between bioreactors and 3D tissue engineering scaffolds can be utilized to improve the structure, function, and molecular properties of in vitro‐generated cartilage.
Genetic and pharmacological dissection of pathways involved in the angiotensin II‐mediated depression of baroreflex function
Authors: Wong Liang‐Fong , Polson Jaimie W. , Murphy David , Paton Julian F. R. , Kasparov Sergey 
Published: October 2002

ABSTRACTHeart failure and hypertension are associated with increases in angiotensin II (ANG II) activity. One brain area where ANG II effects may be particularly important in these situations is the nucleus of the solitary tract (NTS). Located in the dorsomedial medulla, the NTS is the termination site of baroreceptor afferents and is essential for mediating the baroreflex. In hypertensive animals the baroreflex is impaired; this may be reversed by antagonizing ANG II AT1 receptors in the NTS. Recently, we showed that the baroreflex depressant action of ANG II in the NTS is mediated by activation of endothelial nitric oxide synthase (eNOS) and enhanced release of GABA. Using conventional pharmacological tools and a range of adenoviral‐mediated expression of dominant negative proteins, we have determined the intracellular pathway(s) in the NTS by which ANG II activates eNOS. Our data indicate that ANG II acting in the NTS depresses the baroreflex via aGq protein‐mediated activation of phospholipase C, which through 1,4,5‐inositol triphosphate causes release of calcium from the IP3‐sensitive intracellular stores and calcium‐calmodulin formation. In contrast, multiple site disruption of a pathway leading to eNOS activation via the serine/threonine kinase Akt was ineffective.—Wong, L.‐F., Polson, J. W., Murphy, D., Paton, J. F. R., Kasparov, S. Genetic and pharmacological dissection of pathways involved in the angiotensin II‐mediated depression of baroreflex function. FASEB J. 16, 1595–1601 (2002)