bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunosuppressive therapy regimen and platelet activation in renal transplant patients
Authors: Graff Jochen , Klinkhardt Ute , Harder Sebastian , Wegert Wolfgang , Lenz Tomas , Scheuermann Ernst‐Heinrich , Gossmann Jan
Published: November 2002

Background

Increased platelet activation caused by an immunosuppressive therapy regimen may contribute to the high incidence of death from cardiovascular disease in renal transplant patients. Cyclosporine (INN, ciclosporin) and azathioprine are reported to activate platelets, but data are rare and controversial for tacrolimus and mycophenolate mofetil.

Methods

This cross‐sectional study assessed markers of platelet degranulation (P‐selectin; CD62), the activated glycoprotein IIb/IIIa receptor (PAC1, indicating the fibrinogen binding site), platelet aggregation, and secretion of platelet‐derived growth factor (PDGFAB) in renal transplant patients treated with 4 different therapy regimens. Immunosuppression was based on low‐dose steroids (5 mg/d prednisone) in combination with a single agent: (1) cyclosporine (n = 16), (2) azathioprine (n = 18), (3) tacrolimus (n = 17), or (4) mycophenolate mofetil (n = 13). Effects were compared with those in an age‐matched control group of patients with hypertension (n = 11).

Results

In all renal transplant patient groups, unactivated platelets exhibited an increased expression of CD62. When stimulated with 2‐μmol/L thrombin receptor‐activating peptide, CD62 expression in platelets from patients treated with azathioprine (63% ± 17%; P < .05), cyclosporine (51% ± 23%; P < .05), and tacrolimus (50% ± 22%; P < .05) was elevated compared with control subjects (33% ± 19%). PAC1 expression was significantly increased in the patient groups that received azathioprine and cyclosporine. PDGFAB secretion was elevated in patients treated with azathioprine only (51 ± 24 ng/109 platelets [versus 35 ± 17 ng/109 platelets for control subjects]; P < .05). Platelet aggregation in response to collagen (0.5 μg/mL) was decreased in patients treated with tacrolimus (49% ± 29%; P < .05) and mycophenolate mofetil (55% ± 32%; P < .05) compared with control subjects (73% ± 25%).

Conclusion

This is the first study to compare the effects on platelet function of different immunosuppressive regimens that are based on monotherapy. All renal transplant patients showed preactivated platelets compared with those of patients with hypertension. However, the “newer” immunosuppressive agents tacrolimus and mycophenolate mofetil seemed to have fewer unfavorable effects on platelet CD62 expression and PAC1 expression and aggregation. Whether this finding is accompanied by fewer cardiovascular events remains to be elucidated.

Clinical Pharmacology & Therapeutics (2002) 72, 411–418; doi: 10.1067/mcp.2002.127115
Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole
Authors: Raaska Kari , Niemi Mikko , Neuvonen Mikko , Neuvonen Pertti J. , Kivistö Kari T.
Published: November 2002

Objective

Our objective was to examine the effects of itraconazole on the pharmacokinetics and cortisol‐suppressant activity of budesonide administered by inhalation.

Methods

In a randomized, double‐blind, 2‐phase crossover study, 10 healthy subjects took 200 mg itraconazole or placebo orally once a day for 5 days. On day 5, 1 hour after the last dose of itraconazole or placebo, 1000 μg budesonide was administered by inhalation. Plasma budesonide and cortisol concentrations were measured up to 23 hours.

Results

Itraconazole increased the mean total area under the plasma concentration‐time curve of inhaled budesonide 4.2‐fold (range, 1.7‐fold to 9.8‐fold; P < .01) and the peak plasma concentration 1.6‐fold (P < .01) compared with placebo. The mean terminal half‐life of budesonide was prolonged from 1.6 to 6.2 hours (ie, 3.7‐fold; range, 1.5‐fold to 9.3‐fold; P < .001) by itraconazole. The suppression of cortisol production after inhalation of budesonide was significantly increased by itraconazole as compared with placebo, as shown by a 43% reduction in the area under the plasma cortisol concentration‐time curve from 0.5 to 10 hours (P < .001) and a 12% decrease in the cortisol concentration measured 23 hours after administration of budesonide, at 8 am (P < .05).

Conclusions

Itraconazole markedly increased systemic exposure to inhaled budesonide, probably by inhibiting the cytochrome P4503A4‐mediated metabolism of budesonide during both the first‐pass and the elimination phases. This interaction resulted in enhanced systemic effects of budesonide, as shown by suppression of cortisol production. Long‐term coadministration of budesonide and a potent CYP3A4 inhibitor may be associated with an increased risk of adverse effects of budesonide.

Clinical Pharmacology & Therapeutics (2002) 72, 362–369; doi: 10.1067/mcp.2002.127397
The impact of the CYP2D6 polymorphism on haloperidol pharmacokinetics and on the outcome of haloperidol treatment
Authors: Brockmöller Jürgen , Kirchheiner Julia , Schmider Jürgen , Walter Silke , Sachse Christoph , Müller‐Oerlinghausen Bruno , Roots Ivar
Published: November 2002

Objectives

The genetically polymorphic enzyme cytochrome P450 (CYP) 2D6 contributes to the biotransformation of the antipsychotic drug haloperidol. The impact of the polymorphism on haloperidol pharmacokinetics, adverse events, and efficacy was prospectively evaluated under naturalistic conditions in 172 unselected psychiatric inpatients with acute psychotic symptoms.

Methods

Serum trough levels of haloperidol and reduced haloperidol of patients receiving clinically adjusted doses were analyzed on days 3, 14, and 28 after hospital admission. Adverse events such as extrapyramidal symptoms were assessed by standardized rating scales. Efficacy was documented by recording the change in positive and negative schizophrenic symptoms. These parameters were correlated with the CYP2D6 genotype determined by polymerase chain reaction analysis for alleles *1 to *15 and *17.

Results

The serum concentrations showed wide interindividual variation. Reduced haloperidol trough levels and haloperidol total clearance correlated significantly with the number of active CYP2D6 genes. In addition, body weight and smoking had significant effects on haloperidol kinetics, whereas age, gender, and comedication showed only slight effects. The ratings for pseudoparkinsonism were significantly higher in poor metabolizers of substrates of CYP2D6. On the other hand, there was a trend toward lower therapeutic efficacy with increasing number of active CYP2D6 genes.

Conclusions

Treatment with haloperidol should be avoided in extremely slow and extremely rapid metabolizers of CYP2D6 substrates. Both genotyping and blood concentration measurement explained only a fraction of the adverse events; about 20 patients would have to be genotyped to achieve a significant benefit in 1 patient. It is interesting that genotyping was at least as good a predictor of adverse events as the measured drug concentrations.

Clinical Pharmacology & Therapeutics (2002) 72, 438–452; doi: 10.1067/mcp.2002.127494
Development of an optimal furosemide infusion strategy in infants with modeling and simulation
Authors: Schoemaker Rik C. , van der Vorst Maria M. J. , van Heel Isabelle Ruijs‐Dudok , Cohen Adam F. , Burggraaf Jacobus ,   on behalf of the Pediatric Pharmacology Network
Published: November 2002

Background

The optimal dosing strategy for continuous intravenous furosemide infusion is unknown in pediatric patients. Eighteen patients less than 1 year old were studied after cardiac surgery during routine clinical care. The current strategy starts with a continuous infusion of 0.1 mg/kg · h, which may be adapted.

Methods

A pharmacokinetic‐pharmacodynamic model was developed that linked furosemide dose to furosemide serum concentrations, renal function (creatinine clearance), and urine output. Various regimens were simulated that adapt according to urine production. The modified dosing schedule was prospectively tested in a subsequent population of 18 pediatric patients after cardiac surgery.

Results

Data from the follow‐up study suggest that urine production is more controlled for the proposed regimen.

Conclusions

Both the modeling and simulation results and the follow‐up study indicated that a bolus dose of 1 mg/kg followed 6 hours later with a 1‐ or 2‐mg/kg loading dose and a 0.2‐mg/kg · h intravenous infusion provides a rational starting point for furosemide therapy after cardiac surgery in pediatric patients less than 1 year old. Adjustment of this regimen every 12 hours in steps of 0.1 mg/kg · h on the basis of clinical assessment should lead to adequate control over urinary output.

Clinical Pharmacology & Therapeutics (2002) 72, 383–390; doi: 10.1067/mcp.2002.127608
Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole
Authors: Furuta Takahisa , Shirai Naohito , Watanabe Fumitoshi , Honda Satoru , Takeuchi Ken , Iida Takayuki , Sato Yoshihiko , Kajimura Masayoshi , Futami Hajime , Takayanagi Shigekazu , Yamada Masami , Ohashi Kyoichi , Ishizaki Takashi , Hanai Hiroyuki
Published: November 2002

Background and Objectives

The acid‐inhibitory effect of lansoprazole depends on differences in cytochrome P450 (CYP) 2C19 genotypes. We assessed whether therapeutic effects of lansoprazole on gastroesophageal reflux disease (GERD) depended on the CYP2C19 genotype status in relation to the grade of GERD.

Methods

A total of 65 patients with GERD (grades A‐D) completed treatment with lansoprazole, by taking 30 mg orally once a day for 8 weeks. The CYP2C19 genotype status of patients was determined by polymerase chain reaction‐restriction fragment length polymorphism analysis. Before and after treatment, esophageal endoscopy was performed. GERD was considered to be cured on the basis of endoscopic findings at the end of treatment. Plasma lansoprazole levels could be determined at 3 hours after the last 30‐mg dose of lansoprazole in the 27 genotyped patients.

Results

Cure rates for GERD depended significantly on the CYP2C19 genotype status, as well as the grade of GERD before treatment. Cure rates in the homozygous extensive, heterozygous extensive, and poor metabolizer groups were 45.8%, 67.9%, and 84.6%, respectively. Cure rates in the groups with GERD grade A, grade B, and grade C or D were 85.0%, 60.0%, and 45.0%, respectively. The cure rate in patients with the homozygous extensive metabolizer genotype of CYP2C19 with a GERD grade of C or D was very low (16.7%). Plasma lansoprazole levels in patients with the homozygous extensive metabolizer genotype were the lowest of the 3 groups.

Conclusions

CYP2C19 genotype status, as well as the grade of GERD before treatment, is one of the determinants for the success or failure of treatment of GERD with lansoprazole. The low cure rate in patients with the homozygous extensive metabolizer genotype appeared to be a result of these patients having the lowest plasma lansoprazole levels among the 3 genotype groups.

Clinical Pharmacology & Therapeutics (2002) 72, 453–460; doi: 10.1067/mcp.2002.127637
Concentration‐effect relationships of two rilmenidine single‐dose infusion rates in hypertensive patients
Authors: de Visser Saco J. , van der Post Jeroen‐Paul , Nanhekhan Loyd , Schoemaker Rik C. , Cohen Adam F. , van Gerven Joop M. A.
Published: November 2002

Objectives

This study was designed to assess the concentration‐effect relationships for the antihypertensive effects of rilmenidine in patients to aid in the design of an optimized concentration profile of a sustained‐release formulation.

Methods

A placebo‐controlled, randomized, double‐blind, 2‐way partial crossover study was performed in subjects with hypertension. Patients were randomized to receive 2 of 3 possible 12‐hour infusion regimens, each consisting of a loading phase (2 hours) and a maintenance phase (10 hours): low‐profile infusion (total dose of rilmenidine, 1.45 mg), high‐profile infusion (total dose, 3.3 mg), or placebo. Drug plasma concentrations, adverse events, blood pressure, heart rate, and visual analog scales were measured frequently, up to 24 hours after dosing. Salivary flow was determined for up to 15 hours.

Results

The high concentration profile was well tolerated and continued to produce a significant blood pressure reduction of 10.4 mm Hg (systolic)/5.8 mm Hg (diastolic) after 24 hours. The low concentration profile showed no significant effects on blood pressure compared with placebo after 24 hours. Decreases in salivary flow were −36% for the high‐profile infusion and −20% for the low‐profile infusion compared with placebo. Pharmacokinetic‐pharmacodynamic analyses showed infusion rate‐independent, linear concentration‐dependent reductions in diastolic blood pressure and salivary flow up to the maximum observed rilmenidine concentration for both types of infusion.

Conclusions

The high concentration profile was well tolerated and still produced a significant blood pressure reduction after 24 hours. Pharmacokinetic‐pharmacodynamic relationships were linear and unaffected by the rate of infusion. These results should aid in the design of an optimal slow‐release profile.

Clinical Pharmacology & Therapeutics (2002) 72, 419–428; doi: 10.1067/mcp.2002.127638
Pharmacodynamics of active site‐inhibited factor VIIa in endotoxin‐induced coagulation in humans
Authors: Jilma Bernd , Marsik Claudia , Mayr Florian , Graninger Monika T. , Taylor Fletcher B. , Ribel Mette C. , Erhardtsen Elisabeth , Handler Sylvia , Eichler Hans Georg
Published: November 2002

Background

Inhibition of the tissue factor‐factor VIIa pathway attenuated the activation of coagulation and prevented death in a gram‐negative bacteremia primate model of sepsis. This lethal animal model suggested that tissue factor also influences inflammatory cascades.

Methods

This trial examined the pharmacodynamic effects of active site‐inhibited factor VIIa (FFR‐recombinant factor VIIa [rFVIIa]; ASIS) on endotoxin‐induced procoagulant, fibrinolytic, and inflammatory responses in healthy humans. A double‐blind, randomized, placebo‐controlled, parallel‐group study was conducted in 12 healthy male volunteers. Subjects received a bolus infusion of 2‐ng/kg endotoxin, followed by a bolus infusion of ASIS (400 μg/kg) or placebo 10 minutes later.

Results

Endotoxin injection induced inflammation, activation of coagulation, and activation and subsequent inhibition of fibrinolysis. ASIS infusion completely blocked thrombin and fibrin generation, as measured by plasma levels of prothrombin fragment (no increase in the ASIS group, as compared with a 13‐fold increase in the placebo group at 4 hours; P < .01), soluble fibrin, and fibrin split product D‐dimer. ASIS did not alter endotoxin‐induced changes in the fibrinolytic system, cytokine levels, or markers of endothelial (E‐selectin, thrombomodulin) or platelet (P‐selectin) activation.

Conclusions

In summary, ASIS effectively and selectively attenuates tissue factor‐induced thrombin generation. Because ASIS was well tolerated, this study provides seminal data to further characterize its anticoagulant and putative anti‐inflammatory effects in critically ill patients.

Clinical Pharmacology & Therapeutics (2002) 72, 403–410; doi: 10.1067/mcp.2002.127740
Simvastatin‐induced lactic acidosis: A rare adverse reaction?
Authors: Goli Anil K. , Goli Sujatha A. , Byrd Ryland P. , Roy Thomas M.
Published: November 2002

Simvastatin, a hydroxymethylglutaryl coenzyme A (HMG‐CoA) reductase inhibitor, is a commonly used cholesterol‐lowering agent. The long‐term safety profile of simvastatin, established over 10 years of clinical use, is excellent. HMG‐CoA reductase inhibitors block 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase, the rate‐limiting enzyme in cholesterol synthesis. However, other important nonsterol compounds, such as coenzyme Q10 (CoQ10), are also derived from the same synthetic pathway. CoQ10 is an essential carrier in the mitochondrial respiratory chain that participates in oxidative phosphorylation. Simvastatin and other HMG‐CoA reductase inhibitors have been documented to lower serum concentrations of CoQ10. It has been suggested that the adverse effect of myopathy caused by HMG‐CoA reductase inhibitors is due to CoQ10 deficiency in the tissue mitochondria. Documentation of this cause‐and‐effect phenomenon, however, has been lacking. We offer evidence that lactic acidosis may develop as a complication of simvastatin therapy. Our patient also manifested the well‐known HMG‐CoA reductase inhibitor drug toxicities of rhabdomyolysis and hepatitis. The occurrence of these known adverse events with lactic acidosis in our patient suggests that interference of the mitochondrial respiratory chain may play a role in the toxicity of this class of drugs.

Clinical Pharmacology & Therapeutics (2002) 72, 461–464; doi: 10.1067/mcp.2002.127943
Pharmacokinetic and pharmacodynamic interactions between diltiazem and methylprednisolone in healthy volunteers
Authors: Booker Brent M. , Magee Mindy He , Blum Robert A. , Lates Christian D. , Jusko William J.
Published: November 2002

Objectives

The pharmacokinetics and pharmacodynamics after administration of methylprednisolone alone, diltiazem alone, and both drugs jointly were assessed in healthy volunteers.

Methods

An unblinded, controlled, fixed‐sequence, 2‐period study was carried out in 5 healthy white men who received a single dose of intravenous methylprednisolone, 0.3 mg/kg, on day 2, followed by diltiazem alone, 180 mg, on days 5, 6, and 7, with joint dosing of both drugs on day 8. Methylprednisolone and diltiazem disposition was assessed from plasma concentrations. Pharmacodynamic factors were assessed by plasma cortisol and T‐helper and T‐suppressor lymphocytes by means of extended indirect response models.

Results

The clearance of methylprednisolone was significantly reduced in the presence of diltiazem (25.2 L/h versus 16.8 L/h), resulting in a longer half‐life (2.28 hours versus 3.12 hours) and increased area under the plasma concentration‐time curve (AUC) (871 ng · h/mL versus 1299 ng · h/mL). The AUC of diltiazem was unchanged in the presence of methylprednisolone. No significant intrinsic pharmacodynamic differences were observed for methylprednisolone versus methylprednisolone‐diltiazem. The 50% inhibitory concentration values were 0.446 ng/mL versus 0.780 ng/mL for cortisol, 9.20 ng/mL versus 10.7 ng/mL for T‐helper cells, and 18.5 ng/mL versus 20.9 ng/mL for T‐suppressor cells (P > .05). Greater net suppression, as indicated by the area between the effect curve and suppression ratios, was observed for the methylprednisolone‐diltiazem combination versus methylprednisolone alone, which was attributed to reduced elimination of methylprednisolone.

Conclusions

Controlled‐delivery diltiazem, 180 mg, significantly increased methylprednisolone AUC and half‐life and reduced clearance, lending to greater systemic exposure to the steroid. However, significant differences between 50% inhibitory concentration values for methylprednisolone when given alone and for methylprednisolone in combination with diltiazem were not seen, which implies no change in cortisol or cell‐trafficking sensitivity in the presence of diltiazem.

Clinical Pharmacology & Therapeutics (2002) 72, 370–382; doi: 10.1067/mcp.2002.127944
Pharmacokinetic‐pharmacodynamic analysis of drotrecogin alfa (activated) in patients with severe sepsis
Authors: Macias William L. , Dhainaut Jean‐Francois , Yan Sau Chi Betty , Helterbrand Jeffrey D. , Seger Mary , Johnson Gerald , Small David S.
Published: November 2002

Objective

We aimed to characterize the pharmacokinetics and pharmacodynamics of drotrecogin alfa (activated) (recombinant human activated protein C) in patients with severe sepsis.

Methods

Patients (N = 1690) in a randomized, double‐blind, placebo‐controlled phase 3 trial received a 96‐hour infusion of placebo (n = 840) or drotrecogin alfa (activated) (n = 850), 24 μg · kg−1 · h−1. Plasma samples from 680 patients were collected for pharmacokinetic assessment. Pharmacodynamic effects on activated partial thromboplastin time, D‐dimer, protein C, and interleukin 6 were analyzed by drotrecogin alfa (activated) steady‐state plasma concentration (Css) quartile.

Results

Transient endogenous activated protein C concentrations above 10 ng/mL were observed in 11 placebo‐treated patients (3.3%). In drotrecogin alfa (activated)‐treated patients, the median Css was 44.9 ng/mL and the median plasma clearance (CLp) was 40.1 L/h. Css was reached within 2 hours after the infusion was started. Plasma concentrations were below the assay quantitation limit of 10 ng/mL within 2 hours after the infusion was stopped in 92% of patients. CLp increased with increasing body weight, so infusion rates should be based on predose body weight. Mean CLp associated with age, sex, or baseline hepatic or renal function differed by less than 30% from the mean CLp in all patients and resided within the interquartile range of CLp in all patients. Dose adjustment is not required on the basis of these factors alone or in combination. No correlation was detected between Css quartile and bleeding risk or the magnitudes of effect on biomarkers of coagulopathy (D‐dimers and protein C) and inflammation (interleukin 6).

Conclusions

Plasma concentrations of drotrecogin alfa (activated) attain steady state rapidly after the infusion is started and decline rapidly after the infusion is stopped. The infusion rate should be based on predose body weight and not on any other demographic or baseline clinical covariate.

Clinical Pharmacology & Therapeutics (2002) 72, 391–402; doi: 10.1067/mcp.2002.128148
Dimensions of work satisfaction as predictors of commitment type
Authors: Jernigan I.E. , Beggs Joyce M. , Kohut Gary F.
Published: November 2002

This study of hospital nurses (n = 154) examined the influence of dimensions of work satisfaction on types of organizational commitment. Significant results were found for the two affective commitment types tested but not for the instrumental type evaluated. The results indicate that satisfaction with professional status was a significant predictor of moral commitment. Dissatisfaction with organizational policies, autonomy, and professional status were significant predictors of alienative commitment. None of the dimensions of work satisfaction were predictors of calculative commitment. The results of this study suggest that understanding how various factors impact the nature and the form of an individual’s organizational commitment is worth the effort. If managers do not know what causes an attitude to take on a particular form, they cannot accurately predict what behavior might follow.
Reinforcement learning and the prevention of data catastrophes
Authors: Yechiam Eldad , Haruvy Ernan , Erev Ido
Published: November 2002

Companies incur immense losses due to employee neglect to save and back up data and failure to frequently update anti‐virus protections. This problem appears perplexing as such oversights are clearly neither in the organization’s nor in the employees’ best interest. We review the possible reasons for this phenomenon arising from studies of social dilemmas, unrealistic optimism, and reinforcement learning. We follow with three examples of “under‐saving” behavior. The results reveal that in all three cases computer users, novices and experts, feel that they do not save enough. This feeling is consistent with the reinforcement learning account. People think that they are less careful than they wish to be. The implications of this observation are discussed.
The effects of managerial influence behavior on the transition to self‐directed work teams (SDWTs)
Authors: Douglas Ceasar
Published: November 2002

A growing number of organizations are adopting self‐directed work teams (SDWTs), but many firms experience trouble with the transition – the time needed for SDWT development. The addition of a SDWT represents a change in the organization and requires that managers adjust their use of influence behaviors. In this article I examine the impact that managerial influence behaviors have on SDWT development.
A preliminary study for evaluation of skirt asymmetric drape
Authors: Sidabraite V. , Masteikaite V.
Published: November 2002

Undesirable effect of asymmetric drape often occurs when cutting patterns of flared skirt on cross. Out of this reason garment seams twist toward the front or back or folds form different shapes on each side of the garment and this lowers garment aesthetic appearance. The new measuring procedure for asymmetric skirt drape near the side seam, based on bottom traces geometry, was developed in this paper. The experiment with four‐gored skirts of six lightweight fabrics was made. It was found that asymmetric drape depends on combination of grain lines directions of front and back panels of a skirt. There were made general conclusions relating skirt asymmetric drape with various fabric characteristics, such as bending rigidity, extensibility, shear rigidity, fabric weight and drape coefficient in this article. According to developed measuring procedure a final objective evaluation of skirt asymmetric drape rate will be done further.
Garment's pressure sensation (1): subjective assessment and predictability for the sensation
Authors: You F. , Wang J.M. , Luo X.N. , Li Y. , Zhang X.
Published: November 2002

In order to study the wearing comfort of pressure for tight‐fit clothing, the sensation of wearing pressure and the other related sensations have been assessed for knit garments, which have different sizes and fabrics which have different extensibilities, by developing a wearing experimental procedure. Using factor analysis with principal factor solutions and rotated by the Varimax method, we obtained relevant factor matrices about the subjective assessment. At the same time, objective clothing pressure, fabric extensibility and garment fitness have been measured. Regression analysis showed that the garment fitness and fabric extensibility had great predictive power for the subjective pressure assessment.
Optimal marking of garment patterns using rectilinear polygon approximation
Authors: Hwan Sul In , Jin Kang Tae
Published: November 2002

Pattern marking is the allocation of garment patterns on the cloth roll minimizing the fabric loss, and thus very important for the cost reduction in garment manufacturing industries. But automatic marking is very difficult because it is a non‐deterministic in polynomial time problem. Most previous pattern marking methods needed collision detection routine to lay out patterns without interfering each other, which was the bottle neck of nesting speed. In this study, rectilinear polygon approximation technique was used to reduce the overall calculation time because the garment patterns are usually in non‐convex shape that can effectively be approximated by rectangles. Additionally, we adapted stochastic simulated annealing to search the optimal pattern marking.
Identifying antecedents of information exchange within supply chains
Authors: Moberg Christopher R. , Cutler Bob D. , Gross Andrew , Speh Thomas W.
Published: November 2002

Although information exchange among trading partners is consistently mentioned as a key requirement of successful supply chain management implementation, research on information exchange is scarce. This lack of research provides little guidance and support for those managers interested in improving their logistics operations through increased information exchange. The main goal of this paper is to identify potential antecedents of information exchange. Questionnaires were sent to logistics managers at manufacturing firms in several industries. The results of this exploratory study are detailed and the implications for logistics managers discussed.
The importance of technology trust in Web services security
Authors: Ratnasingam Pauline
Published: November 2002

The Internet is changing the way businesses operate today. Firms are using the Web for procurement, to find trading partners, and to link existing applications to other applications. Web services are rapidly becoming the enabling technology of today’s e‐business, and e‐commerce systems. We are having a massive impact on the way businesses think about designing, developing, and deploying Web‐based applications. Web services may be an evolutionary step in designing distributed applications, however, they are not without problems. There are issues relating to security, transactions and scalability that need to be addressed. This paper addresses security concerns in Web services and the role of technology trust.
A methodology for developing integrated information systems based on ERP packages
Authors: Stirling Mark , Petty David , Travis Leigh
Published: November 2002

This paper describes a methodology for the structured development of manufacturing information systems based on a collaborative action research project. The methodology starts from the premise that a company has an enterprise resource planning (ERP) system in place. It can then be used to determine the optimal method for achieving a particular business requirement. The methodology has seven decision points, each of which relates to a different outcome. The methodology is supported by a series of questions to assist users in making appropriate decisions. The paper also describes a series of structured interviews with practitioners from industry. These were undertaken in order to verify the usefulness of the methodology. These interviews show that there is a requirement for tools to assist in the ongoing development of information systems in manufacturing industry. Furthermore, the interviews suggest that the methodology is a useful tool, particularly for relatively inexperienced manufacturing information system practitioners.
Construction of an RAPD linkage map and localization of QTLs for oleic acid level using recombinant inbreds in mustard (Brassica juncea)
Authors: Sharma R , Aggarwal R AK , Kumar R , Mohapatra T , Sharma R P
Published: November 2002

RAPD markers were employed for construction of a linkage map and localization of QTLs for oleic acid level using a set of 94 recombinant inbred lines (RILs) of mustard (Brassica juncea L.) as a mapping population. Only 30% of the 235 random primers used were useful in terms of polymorphism detected and the reproducibility of those patterns. Normal Mendelian segregation was observed for the majority of the 130 markers obtained with 71 informative primers; only 13.1% deviated (P < 0.01) from the expected 1:1 ratio. One-hundred and fourteen markers were assigned to 21 linkage groups (LGs) covering a total length of 790.4 cM with an average distance of 6.93 cM between markers. Two quantitative trait loci (QTL) for oleic acid level were mapped to 14- and 10.6-cM marker intervals on two different LGs. Both loci together explained 32.2% of phenotypic variance. One major QTL explained 28.5% of the trait variance observed in this species.Key words: Brassica juncea, linkage map, oleic acid, quantitative trait loci, RAPD, recombinant inbred line.
Genetic diversity in European and Argentinian cultivated potatoes (Solanum tuberosumsubsp.tuberosum) detected by inter-simple sequence repeats (ISSRs)
Authors: Bornet B , Goraguer F , Joly G , Branchard M
Published: November 2002

In this study, the use of inter-simple sequence repeats (ISSR) to assess genetic diversity between cultivated potatoes (Solanum tuberosum subsp. tuberosum) is reported. ISSR technology rapidly reveals high polymorphic fingerprints and thus determines the genetic diversity among potato cultivars. Nine primers were selected according to the number of amplified markers and the level of polymorphism detected. Three primers (GAG(CAA)5, CTG(AG)8, and (AG)8) were used to cluster the 28 potato accessions and 77 polymorphic markers were sufficient to identify all of the accessions. Among the 15 simple sequence repeat (SSR) motifs tested, the most abundant were CAA and AG. Argentinian- and European-grown potatoes were easily distinguished, with a higher level of genetic diversity among potatoes from Argentina. An ISSR study using a limited number of cultivars and very few primers clearly differentiated between all cultivars, thus ISSR was revealed to be a good tool for the genetic identification of potato and for future germplasm-management programs.Key words: Solanum tuberosum subsp. tuberosum, potato, ISSR, genetic diversity.
Genetic diversity in cultivars and landraces of Oryza sativa subsp. indica as revealed by AFLP markers
Authors: Prashanth S R , Parani M , Mohanty B P , Talame V , Tuberosa R , Parida A
Published: November 2002

Genetic diversity among 49 Indian accessions of rice (Oryza sativa subsp. indica), including 29 landraces from Jeypore, 12 modern cultivars, and 8 traditional cultivars from Tamil Nadu, was investigated using AFLP markers. In total, nine primer combinations revealed 664 AFLPs, 408 of which were found to be polymorphic. The percentage of polymorphic AFLPs was approximately the same within the cultivars and landraces. Similar results were obtained when genetic diversity values were estimated using the ShannonWeiner index of diversity. Genetic diversity was slightly higher in the modern cultivars than in the traditional cultivars from Tamil Nadu. Among the landraces from Jeypore, the lowland landraces showed the highest diversity. The present study showed that the process of breeding modern cultivars did not appear to cause significant genetic erosion in rice. Cluster analysis and the first component of principle component analysis (PCA) both showed a clear demarcation between the cultivars and landraces as separate groups, although the genetic distance between them was narrow. The modern cultivars were positioned between the landraces from Jeypore and the traditional cultivars from Tamil Nadu. The second component of PCA further separated medium and upland landraces from lowland landraces, with the lowland landraces found closest to the traditional and modern cultivars.Key words: rice, Oryza sativa, AFLP, landraces, genetic diversity.
Genomic regions determining resistance to leaf stripe (Pyrenophora graminea) in barley
Authors: Arru L , Niks R E , Lindhout P , Valé G , Francia E , Pecchioni N
Published: November 2002

Leaf stripe is a seed-borne disease of barley (Hordeum vulgare) caused by Pyrenophora graminea. Little is known about the genetics of resistance to this pathogen. In the present work, QTL analysis was applied on two recombinant inbred line (RIL) populations derived from two- and six-rowed barley genotypes with different levels of partial resistance to barley leaf stripe. Quantitative trait loci for partial resistance were identified using the composite interval mapping (CIM) method of PLABQTL software, using the putative QTL markers as cofactors. In the L94 × 'Vada' mapping population, one QTL for resistance was detected on chromosome 2H; the same location as the leaf-stripe resistance gene Rdg1 mapped earlier in 'Alf', where it confers complete resistance to the pathogen. An additional minor-effect QTL was identified by further analyses in this segregating population on chromosome 7H. In L94 × C123, two QTLs for resistance were mapped, one each on chromosomes 7H and 2H.Key words: QTLs, leaf stripe, Pyrenophora graminea, composite interval mapping, barley.
Cloning of disease-resistance homologues in end sequences of BAC clones linked toFom-2, a gene conferring resistance toFusariumwilt in melon (Cucumis meloL.)
Authors: Wang Yi-Hong , Choi Woobong , Thomas Claude E , Dean Ralph A
Published: November 2002

Disease resistance has not yet been characterized at the molecular level in cucurbits, a group of high-value, nutritious, horticultural plants. Previously, we genetically mapped the Fom-2 gene that confers resistance to Fusarium wilt races 0 and 1 of melon. In this paper, two cosegregating codominant markers (AM, AFLP marker; FM, Fusarium marker) were used to screen a melon bacterial artificial chromosome (BAC) library. Identified clones were fingerprinted and end sequenced. Fingerprinting analysis showed that clones identified by each marker assembled into two separate contigs at high stringency. GenBank searches produced matches to leucine-rich repeats (LRRs) of resistance genes (R genes); to retroelements and to cellulose synthase in clones identified by FM; and to nucleotide-binding sites (NBSs) of R genes, retroelements, and cytochrome P-450 in clones identified by AM. A 6.5-kb fragment containing both NBS and LRR sequences was found to share high homology to TIR (Toll-interleukin-1 receptor)NBSLRR R genes, such as N, with 42% identity and 58% similarity in the TIRNBS and LRR regions. The sequence information may be useful for identifying NBSLRR class of R genes in other cucurbits.Key words: BAC end sequencing, Cucumis melo L., Fusarium wilt, R gene.
Identification of repetitive, genome-specific probes in crucifer oilseed species
Authors: Somers Daryl J , Demmon Goewin
Published: November 2002

Direct amplification of minisatellite DNA by PCR (DAMD PCR) was used to amplify and subsequently clone several fragments of DNA from crucifer species. The PCR-derived fragments of DNA were generated using known minisatellite core sequences as PCR primers. Southern hybridization of these putative minisatellite DNA fragments revealed that many were genome-specific; they hybridized with high affinity only to the genomic DNA of the species from which they were cloned. The DNA fragments were believed to be dispersed in the genome, based on smear-like hybridization signals on EcoRI-, BamHI-, and HindIII-digested genomic DNA. Genome-specific probes were specifically isolated from Brassica rapa (A genome), Brassica nigra (B genome), and Sinapis alba in addition to several other crucifer species. The sequence of a B. rapa specific probe (pBr17.1.3A) contained a minisatellite region that could be divided into three tandem repeats; each repeat contained between two and five subrepeats and each subrepeat shared a highly conserved core region of 29 bp. This minisatellite sequence also hybridized with high affinity to the A genome species B. napus and B. juncea. This research showed that dispersed, genome-specific probes can be isolated using DAMD PCR and that these probes could be used to detect and quantify alien DNA present in progeny from intergeneric or interspecific crosses.Key words: Brassica, genome specific, marker-assisted selection, minisatellite.
Mapping the SRY gene in Microtus cabrerae: a vole species with multiple SRY copies in males and females
Authors: Fernández Rosa , Barragán María José L , Bullejos Mónica , Marchal Juan Alberto , Martínez Sergio , de la Guardia Rafael Díaz , Sánchez Antonio
Published: November 2002

The SRY gene is a single-copy, male-specific gene, located on the Y chromosome in most mammals. However, recently we have described the presence of multiple polymorphic copies of this gene in both males and females of the vole species Microtus cabrerae. Here, we present the chromosomal localization of SRY gene copies in this species by fluorescent in situ hybridization (FISH). This technique localized these gene copies in the short arm, and hence in the euchromatic region, of the Y chromosome. Furthermore, several copies of the SRY gene are located on the X chromosome. These copies are spread along the entire heterochromatic region of the X chromosome, occupying the whole short arm, the centromeric region, and the pericentromeric region of the long arm.Key words: FISH mapping, Micotus cabrerae, SRY gene, X chromosome, Y chromosome.
Hordoindolines are associated with a major endosperm-texture QTL in Barley (Hordeum vulgare)
Authors: Beecher B , Bowman J , Martin J M , Bettge A D , Morris C F , Blake T K , Giroux M J
Published: November 2002

Endosperm texture has a tremendous impact on the end-use quality of wheat (Triticum aestivum L.). Cultivars of barley (Hordeum vulgare L.), a close relative of wheat, also vary measurably in grain hardness. However, in contrast to wheat, little is known about the genetic control of barley grain hardness. Puroindolines are endosperm-specific proteins found in wheat and its relatives. In wheat, puroindoline sequence variation controls the majority of wheat grain texture variation. Hordoindolines, the puroindoline homologs of barley, have been identified and mapped. Recently, substantial allelic variation was found for hordoindolines among commercial barley cultivars. Our objective was to determine the influence of hordoindoline allelic variation upon grain hardness and dry matter digestibility in the 'Steptoe' × 'Morex' mapping population. This population is segregating for hordoindoline allele type, which was measured by a HinA/HinB/Gsp composite marker. One-hundred and fifty lines of the 'Steptoe' × 'Morex' population were grown in a replicated field trial. Grain hardness was estimated by near-infrared reflectance (NIR) and measured using the single kernel characterization system (SKCS). Variation attributable to the HinA/HinB/Gsp locus averaged 5.7 SKCS hardness units (SKCS U). QTL analysis revealed the presence of several areas of the genome associated with grain hardness. The largest QTL mapped to the HinA/HinB/Gsp region on the short arm of chomosome 7 (5H). This QTL explains 22% of the SKCS hardness difference observed in this study. The results indicate that the Hardness locus is present in barley and implicates the hordoindolines in endosperm texture control.Key words: puroindolines, grain hardness, digestibility.
Mapping tightly linked genes controlling potyvirus infection at the Rsv1 and Rpv1 region in soybean
Authors: Gore M A , Hayes A J , Jeong S C , Yue Y G , Buss G R , Maroof MA Saghai
Published: November 2002

Soybean mosaic virus (SMV) and peanut mottle virus (PMV) are two potyviruses that cause yield losses and reduce seed quality in infested soybean (Glycine max (L.) Merr.) fields throughout the world. Rsv1 and Rpv1 are genes that provide soybean with resistance to SMV and PMV, respectively. Isolating and characterizing Rsv1 and Rpv1 are instrumental in providing insight into the molecular mechanism of potyvirus recognition in soybean. A population of 1056 F2 individuals from a cross between SMV- and PMV-resistant line PI 96983 (Rsv1 and Rpv1) and the susceptible cultivar 'Lee 68' (rsv1 and rpv1) was used in this study. Disease reaction and molecular-marker data were collected to determine the linkage relationship between Rsv1, Rpv1, and markers that target candidate disease-resistance genes. F2 lines showing a recombination between two of three Rsv1-flanking microsatellite markers were selected for fine mapping. Over 20 RFLP, RAPD, and microsatellite markers were used to map 38 loci at high-resolution to a 6.8-cM region around Rsv1 and Rpv1. This study demonstrates that Rsv1 and Rpv1 are tightly linked at a distance of 1.1 cM. In addition, resistance-gene candidate sequences were mapped to positions flanking and cosegregating with these resistance loci. Based on comparisons of genetic markers and disease reactions, it appears likely that several tightly linked genes are conditioning a resistance response to SMV. We discuss the specifics of these findings and investigate the utility of two disease resistance related probes for the screening of SMV or PMV resistance in soybean.Key words: NBS, multigene family, and disease resistance.
Sequence rearrangement in the AT-rich minisatellite of the novel rice transposable elementBasho
Authors: Inukai Tsuyoshi , Sano Yoshio
Published: November 2002

In the process of characterizing a rice wx deletion mutant, an AT-rich minisatellite sequence that consisted of units of ~80 bp was detected about 2.3 kb downstream of the wx gene. This AT-rich minisatellite was a multiple-copy element (1 × 103to 2 × 103copies per haploid genome) and interspersed in the rice genome. By BLAST homology search it was indicated that not only the tandem repeat but also both flanking sequences were conserved among copies. According to the characteristics of the termini (5'-CHH ...CTAG-3') and a target site preference for T, this AT-rich minisatellite accompanying the flanking sequences was classified into a novel transposon, Basho. The results of direct amplification of Basho showed that relatively large variation in size existed in the Basho family. We estimate the variation to be generated by not only alteration of the number of units in the minisatellite but also by duplications of larger blocks including the conserved flanking sequences caused by single-strand mispairing (SSM) at noncontiguous repeats. Because the AT-rich minisatellite contained in Basho possessed several motifs of the matrix attachment region (MAR) in its repeat unit, the functional role as MAR in the rice genome was discussed.Key words: Oryza sativa, minisatellite, Basho, single strand mispairing (SSM).
An expanded genetic linkage map ofPrunusbased on an interspecific cross between almond and peach
Authors: Bliss F A , Arulsekar S , Foolad M R , Becerra V , Gillen A M , Warburton M L , Dandekar A M , Kocsisne G M , Mydin K K
Published: November 2002

The genetic linkage map of Prunus constructed earlier and based on an interspecific F2population resulting from a cross between almond (Prunus dulcis D.A. Webb) and peach (Prunus persica L. Batsch) was extended to include 8 isozyme loci, 102 peach mesocarp cDNAs, 11 plum genomic clones, 19 almond genomic clones, 7 resistance gene analogs (RGAs), 1 RGA-related sequence marker, 4 morphological trait loci, 3 genes with known function, 4 simple sequence repeat (SSR) loci, 1 RAPD, and 1 cleaved amplified polymorphic sequence (CAP) marker. This map contains 161 markers placed in eight linkage groups that correspond to the basic chromosome number of the genus (x = n = 8) with a map distance of 1144 centimorgans (cM) and an average marker density of 6.8 cM. Four more trait loci (Y, Pcp, D, and SK) and one isozyme locus (Mdh1) were assigned to linkage groups based on known associations with linked markers. The linkage group identification numbers correspond to those for maps published by the Arús group in Spain and the Dirlewanger group in France. Forty-five percent of the loci showed segregation distortion most likely owing to the interspecific nature of the cross and mating system differences between almond (obligate outcrosser) and peach (selfer). The Cat1 locus, known to be linked to the D locus controlling fruit acidity, was mapped to linkage group 5. A gene or genes controlling polycarpel fruit development was placed on linkage group 3, and control of senesced leaf color (in late fall season) (LFCLR) was mapped to linkage group 1 at a putative location similar to where the Y locus has also been placed.Key words: Prunus, molecular markers, RFLPs, resistance gene analogs (RGAs), polycarpel fruit, stone fruits.
Genetic diversity ofCarica papayaas revealed by AFLP markers
Authors: Kim M S , Moore P H , Zee F , Fitch M MM , Steiger D L , Manshardt R M , Paull R E , Drew R A , Sekioka T , Ming R
Published: November 2002

Genetic relationships among Carica papaya cultivars, breeding lines, unimproved germplasm, and related species were established using amplified fragment length polymorphism (AFLP) markers. Seventy-one papaya accessions and related species were analyzed with nine EcoRIMseI primer combinations. A total of 186 informative AFLP markers was generated and analyzed. Cluster analysis suggested limited genetic variation in papaya, with an average genetic similarity among 63 papaya accessions of 0.880. Genetic diversity among cultivars derived from the same or similar gene pools was smaller, such as Hawaiian Solo hermaphrodite cultivars and Australian dioecious cultivars with genetic similarity at 0.921 and 0.912, respectively. The results indicated that self-pollinated hermaphrodite cultivars were as variable as open-pollinated dioecious cultivars. Genetic diversity between C. papaya and six other Carica species was also evaluated. Carica papaya shared the least genetic similarity with these species, with an average genetic similarity of 0.432; the average genetic similarity among the six other species was 0.729. The results from AFLP markers provided detailed estimates of the genetic variation within and among papaya cultivars, and supported the notion that C. papaya diverged from the rest of Carica species early in the evolution of this genus.Key words: DNA fingerprinting, germplasm, genetic relationship, molecular phylogeny, polymorphism.