bluuebunny/crossref_metadata_2025 huggingface dataset:
Material properties of interstitial lamellae reflect local strain environments
Authors: Goodwin Kelly J. , Sharkey Neil A.
Published: October 2002

The objective of this study was to determine if the material properties of bone at the lamellar level are related to the predominant mode and magnitude of mechanical strain experienced in situ. The tibia and first metatarsal bones of five unpaired cadaveric lower extremities were instrumented with strain gauge rosettes and subjected to repeated loading trials in an apparatus that replicates the muscle forces and external loads experienced by the foot and shank while walking. The spatial distributions of axial strain within diaphyseal cross‐sections taken from each bone were subsequently determined. Nanoindentation measurements were then performed on the same cross‐sections to determine the compressive elastic moduli of individual lamellae located within osteonal, interstitial, and outer circumferential microstructures. Twenty percent of the variance in interstitial elastic modulus within cross‐sections of diaphyseal bone was explained by local strain magnitude. Lamellae residing in regions of compressive strain displayed significantly higher compressive elastic modulus values than those located in predominantly tensile regions (19.9 ± 1.6 GPa compared to 17.9 ± 1.7 GPa, p < 0.05). Elastic moduli of interstitial lamellae were 11% greater than those of osteonal or outer circumferential lamellae, irrespective of strain or anatomical location (p < 0.001). Differences exist in the material properties of individual bone lamellae located within different anatomical regions and different microstructures, and these differences are related to the distribution of axial strain. These findings suggest that mechanical strain, or another closely related variable, may influence the design and ultimate mechanical behavior of the extra‐cellular matrix found in lamellar bone. This tissue heterogeneity is of potential importance in bone fragility and adaptation. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Effect of mechanical compression on the vascular permeability of the dorsal root ganglion
Authors: Kobayashi Shigeru , Yoshizawa Hidezo
Published: October 2002

The dorsal root ganglion contains primary sensory neurons and is closely related to low back pain and sciatia. The present study investigated whether endoneurial edema, which is involved in the onset of pain and nerve dysfunction, was increased in the dorsal root ganglion by compression. The influence of mechanical compression on the vascular permeability of the lumbar dorsal root ganglion was determined. The dorsal root ganglion is reported to have a higher vascular permeability compared with other nerve tissues as well as lacking a blood‐nerve barrier. However, only a few studies have assessed the influence of mechanical compression on the dorsal root ganglion, especially its vascular permeability.

In dogs, laminectomy was performed at L7 and the dorsal root ganglion of the seventh lumbar spinal nerve was compressed for 1 h using four kinds of clips with various strengths. After clip removal, Evans blue albumin (EBA) or horseradish peroxidase (HRP) was administered intravenously as a tracer. After sacrifice, the EBA‐injected specimens were observed by fluorescence microscopy and the HRP‐injected specimens were observed by light and transmission electron microscopy.

After compression of the dorsal root ganglion at 15 gf or more, leakage of tracer into the endoneurial space was markedly increased compared with the sham‐operated group and severe edema was noted. Extravascular leakage of tracer was obvious around venules and capillaries. Electron microscopy showed an increase of extravascular HRP in the gap junctions and fenestrae between endothelial cells due to increased vascular permeability. However, the dorsal root ganglion was covered with a thick perineurium and HRP that leaked from the blood vessels did not enter the epineurium even after compression at 60 gf. It was proven that the increased vascular permeability occurred as well as in leakage of dye within the dorsal root ganglion after a single hour of compression of the dorsal root ganglion. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
The role of adsorbed endotoxin in particle‐induced stimulation of cytokine release
Authors: Cho David R. , Shanbhag Arun S. , Hong Chi‐Yuan , Baran George R. , Goldring Steven R.
Published: October 2002

Numerous in vitro models have demonstraed the capacity of wear particles to stimulate the release of soluble pro‐inflammatory products with the ability to induce local bone resorption. Recent observations have demonstrated that binding of lipopolysaccharide (LPS) to particulate wear deris can significantly modulate the pattern of cell response in the in vitro models. These findings raise concerns over the possible role of LPS in the athogenesis of aseptic looseing after total joint replacements, and also indicates the importance of controlling for possible confounding effects of LPS contamination in the in vitro models used to study the reactive nature of wear debris. Our studies were undertaken to rigorously analyze the effects of particle‐associated LPS on cell responses and to assess the efficacy ofdifferent treatment protocols to inactivate LPS associated with different particulate materials. Particles of cobalt‐chrome alloy, titanium‐6‐aluminum‐4‐vanadium, titanium nitride and silica were pretreated with LPS and exposed to multiple treatment protocols. When cells were treated with „as‐received”︁ particles prepared by washing in ethanol, small amounts of TNF‐α, IL‐1β, and IL‐1α were detected. In contrast, all particle species pretreated with LPS produced marked increases in TNF‐α, IL‐1α, and IL‐1β release, as well as upregulation of corresponding mRNa levels even after ethanol washing. Boiling the LPS‐pretreated particles in 1% acetic acid or autoclaving and baking the particles also markedly reduced and in some instances abolished the effect of the LPS‐pretreatment. This indicates that LPS binds to the surface of particles of diverse composition and that the bound LPS is biologically active. Treatment protocols to inactivate particle‐associated LPS demonstrated significant differences in effcacy. When the most rigorous treatments were utilized, essentially all LPS activity could be eliminated. Particles treated with these methods retained some capacity to stimulated cytokine release, but activities were markedly reduced. These results provide further evidnce indicating that LPS contamination of particulate materials can markedly enhance their biological activity. This potential confounding effect needs to be carefully monitored and controlled in the in vitro model systems systems used to evaluate wear particles. Furthermore, the presence of particle‐associated endotoxin at the bone‐implant interface in vivo could markedly enhance the adverse biological activity of particulate wear debris. © 2002 Published by Elsevier Science Ltd. On behalf of Orthopaedic Research Society.
The role of p105 protein in NFκB activation in ANA‐1 murine macrophages following stimulation with titanium particles
Authors: Soloviev Alexander , Schwarz Edward M. , Kuprash Dmitry V. , Nedospasov Sergei A. , Edward Puzas J. , Rosier Randy N. , O'Keefe Regis J.
Published: October 2002

Macrophage activation by particulate debris from orthopaedic implants triggers an inflammatory response that ultimately leads to periprosthetic bone resorption and implant failure. TNFα‐has been identified as a critical cytokine involved in the response to debris particles but the mechanisms involved in activation of TNFα synthesis are unclear. The current study demonstrates rapid induction of TNFα following stimulation with titanium particles in the murine macrophage cell line, ANA‐1. Electrophoretic mobility shift assays demonstrated NFκB DNA binding activity within 15 min of exposure to titanium particles, and experiments with an NFκB luciferase promoter confirmed the induction of NFκkB mediated transcription by titanium particles. Furthermore, titanium particles induced a 2‐fold induction in TNFα promoter activity, and mutation of the kB2a site, one of the four NFκkB‐binding sites in the TNFα promoter, resulted in decreased activation. Since NFκkB is a critical regulator of inflammation and is involved in activation of the TNFα promoter, additional experiments were performed to determine the mechanism of NFκkB activation by particles. NFκkB activation was found to be dependent upon proteasome activity, since administration of MG 132, a proteasome inhibitor, blocked NFκkB activation. However, IkBα is only slightly decreased following Ti treatment, in contrast to marked degradation following stimulation with LPS. Recently, another proteasome‐dependent pathway of NFκkB activation has been described involving degradation of p105, a precursor of p50 that binds to p65. p105 degradation occurred following titanium stimulation, suggesting that this recently described mechanism for NFκkB activation is operant in ANA‐1 cells following exposure to titanium particles. These findings demonstrate that activation of the NFκkB signaling pathway is rapidly induced by titanium particles in ANA‐1 cells and is associated with p105 degradation. TNFα induction appears to be mediated, at least in part, through NFκkB binding to the kB2a site of the TNFα promoter. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Cerebral GABA release and GAD activity in protein‐ and tryptophan‐restricted rats during development
Authors: Del Angel‐Meza A.R. , Ramı́rez‐Cortes L. , Adame‐González I.G. , González Burgos I. , Beas‐Zárate C.
Published: October 2002

To evaluate the effects on the GABAergic system, Wistar rats were raised on a chronically protein‐ and tryptophan‐restricted diet with 8% protein, based on either Purina chow or corn. There was a significant decrease in both body and cerebral weight in the restricted animals compared with the control group fed with a 23% protein diet. In animals fed mainly corn, glutamic acid decarboxylase (GAD) activity increased significantly at the ages studied (14, 30, and 60 days) in the cerebral cortex and hippocampus. In the same way, γ‐aminobutyric acid (GABA) release decreased significantly in early life in both brain regions, then increased in 30–60‐day‐old animals corn‐fed predominantly in the cerebral cortex.

The reduction in GABA release may be attributable to a decrease in GABAergic cell density, which could induce an over‐activation of 5‐hydroxytryptamine (5‐HTergic) receptors, leading in turn to the observed enhancement of GAD activity. Taken together, these results may represent a plastic response by GABAergic neurons to (5‐HTergic under‐stimulation in mainly corn‐fed animals.
Regionalism and the nationalization of the legislative vote in post-communist Russian politics
Authors: Ishiyama John T.
Published: October 2002

This study examines the extent to which the nationalization of the vote has occurred in Russia since 1993. To what extent is the Russian party vote “nationalized”, or in other words, to what extent are there differences between the national party vote and the party vote in the various regions of the country? What explains why such variations exist? To answer these questions, I examine a number of factors (the strength of the local executive, the degree to which local parties are entrenched, etc.) that explain why party politics in certain regions in Russia are characterized by a more “nationalized” vote than others.
Neurohormonal activation in heart failure after acute myocardial infarction treated with beta‐receptor antagonists
Authors: Persson Hans , Andréasson Karin , Kahan Thomas , Eriksson Sven V. , Tidgren Bo , Hjemdahl Paul , Hall Christian , Erhardt Leif
Published: October 2002

Background:

Few studies have described how neurohormonal activation is influenced by treatment with beta‐receptor antagonists in patients with heart failure after acute myocardial infarction. The aims were to describe neurohormonal activity in relation to other variables and to investigate treatment effects of a beta1 receptor‐antagonist compared to a partial beta1 receptor‐agonist.

Methods:

Double‐blind, randomized comparison of metoprolol 50–100 mg b.i.d. (n‐74), and xamoterol 100–200 mg b.i.d (n‐67). Catecholamines, neuropeptide Y‐like immunoreactivity (NPY‐LI), renin activity, and N‐terminal pro‐atrial natriuretic factor (N‐ANF) were measured in venous plasma before discharge and after 3 months. Clinical and echocardiographic variables were assessed.

Results:

N‐ANF showed the closest correlations to clinical and echocardiographic measures of heart failure severity, e.g. NYHA functional class, furosemide dose, exercise tolerance, systolic and diastolic function. Plasma norepinephrine, dopamine and renin activity decreased after 3 months on both treatments, in contrast to a small increase in NPY‐LI which was greater (by 3.9 pmol/l, 95% CI 1.2–6.6) in the metoprolol group. N‐ANF increased on metoprolol, and decreased on xamoterol (difference: 408 pmol/l, 95% CI 209–607). Increase above median of NPY‐LI (>25.2 pmol/l, odds ratio 2.8, P‐0.0050) and N‐ANF (>1043 pmol/l, odds ratio 2.8, P‐0.0055) were related to long term (mean follow‐up 6.8 years) cardiovascular mortality.

Conclusions:

Decreased neurohormonal activity, reflecting both the sympathetic nervous system and the renin–angiotensin system, was found 3 months after an acute myocardial infarction with heart failure treated with beta‐receptor antagonists. The small increase in NPY‐LI may suggest increased sympathetic activity or reduced clearance from plasma. The observed changes of N‐ANF may be explained by changes in cardiac preload, renal function, and differences in beta‐receptor mediated inhibition of atrial release of N‐ANF. NPY‐LI, and N‐ANF at discharge were related to long term cardiovascular mortality.
Therapeutic options and heart failure survival score predictability in an academic heart failure center: an analysis of 120 consecutive patients during a 1‐year period
Authors: Gradaus Rainer , Kerber Sebastian , Böcker Dirk , Scheld Hans H. , Breithardt Günter , Deng Mario C.
Published: October 2002

Background:

the incidence and prevalence of patients with advanced heart failure is increasing worldwide and the number of cardiac transplantations remains limited.

Aims:

it was the aim of the study to describe our experience with the increasing number of available medical, interventional and cardiac surgery options, and to assess heart failure survival score predictability in an academic heart failure center within a 1‐year follow‐up.

Methods and Results:

in all patients who were referred for cardiac transplant evaluation within a 12‐month period between April 1998 and March 1999 at our Interdisciplinary Heart Failure and Transplant Program, our team assessed all medical interventions as well as interventional and surgical treatment options that were available, based on the clinical profile on initial presentation. In 92% of the 120 patients referred for cardiac transplantation evaluation, drug therapy could be optimized. A considerable number of patients could be subjected to an organ‐preserving intervention or surgery, either PTCA (n ‐ 11), CABG (n ‐ 4), valve repair (n ‐ 7), multisite pacing (n ‐ 7), or partial ventricular resection (n ‐ 5). Only a small group of patients with the worst heart failure survival score were listed for heart transplantation (n ‐ 17) or received a ventricular assist device (n ‐ 3).

Conclusions:

within a contemporary cohort of advanced heart failure patients, only a small number of patients will undergo cardiac transplantation, which is predictable by the heart failure survival score. Most patients will undergo optimized medical therapy and a considerable number will be subjected to interventional or surgical treatment options.
Effect of dofetilide on QT dispersion and the prognostic implications of changes in QT dispersion for patients with congestive heart failure
Authors: Brendorp Bente , Elming Hanne , Jun Li , Køber Lars , Torp‐Pedersen Christian ,   for the DIAMOND Study Group
Published: October 2002

Aims:

Drug‐induced changes in QT dispersion may be a way of detecting harmful repolarisation abnormalities for patients receiving antiarrhythmic drugs affecting ventricular repolarisation.

Methods and results:

In 463 congestive heart failure (CHF) patients enrolled in the Danish Investigations Of Arrhythmia and Mortality On Dofetilide‐CHF (DIAMOND‐CHF) study, both pre‐treatment and on‐treatment day 2–6 QT dispersion was available from standard 12‐lead ECGs. Patients were randomised in a double‐blind manner to receive either placebo or dofetilide, a new class III antiarrhythmic drug. During a median follow‐up of 19 months (minimum 1 year), 179 patients (39%) died (135 patients from cardiac causes). Changes in QT dispersion did not predict all‐cause or cardiac mortality for patients treated with dofetilide in multivariate survival analysis (Risk ratio: 1.02, 95% confidence interval: 0.97–1.08, P>0.4). This finding was independent of pre‐treatment QT dispersion. Dofetilide caused a small QT dispersion increment of 8 ms, not different from the changes seen in the placebo group (3 ms).

Conclusion:

For patients with CHF and reduced left ventricular systolic function, changes in QT dispersion following treatment with dofetilide do not predict all‐cause or cardiac mortality. The dofetilide‐induced QT dispersion changes are small and comparable to those seen in placebo treated patients.
Detecting early clinical deterioration in chronic heart failure patients post‐acute hospitalisation—a critical component of multidisciplinary, home‐based intervention?
Authors: Stewart Simon , Horowitz John D.
Published: October 2002

Aims:

To firstly describe the prevalence, characteristics and consequences of early clinical deterioration (ECD) in chronic heart failure (CHF) patients discharged from acute hospital care and, secondly, to examine the potential benefits of a multidisciplinary, home‐based intervention (HBI) in limiting the common sequelae of such deterioration.

Methods:

This phenomenon was studied in 90 CHF patients assigned to the intervention arm of a randomised study of HBI. ECD was defined as death, unplanned re‐admission or clinical instability (detected at a home visit) within 14 days of hospital discharge. Multivariate analysis was used to determine the independent correlates of ECD. Using these data, a 1:1 case–control ratio of patients assigned to the usual care arm of the study was selected to match those patients exhibiting non‐fatal ECD and subject to HBI. Subsequent morbidity and mortality rates were then compared on the basis of the presence or absence of non‐fatal ECD and/or HBI.

Results:

Of the 90 patients assigned to HBI, two died suddenly, five required an unplanned re‐admission to hospital and 28 were found to be clinically unstable at a planned home visit, within 14 days of discharge from the index admission. The combined prevalence of ECD this cohort was therefore 39% (35 of 90 patients) and was independently correlated with greater age (OR‐1.1 per yearly increment; P<0.001) and comorbidity (OR‐2.0 per incremental Charlson index of comorbidity score; P<0.001). Patients who exhibited clinical instability at the home visit were significantly more likely to be non‐adherent to prescribed treatment (10 of 28 vs. 9 of 55; P<0.05). Compared to the remainder of the cohort also subject to HBI, despite remedial intervention, patients who exhibited non‐fatal ECD had reduced event‐free survival (11 of 33 vs. 38 of 55; P<0.001), more frequent unplanned re‐admission (0.2 vs. 0.1 admissions/patient/month; P<0.01), and more prolonged hospital stay (1.6 vs. 0.5 days/patient/month; P<0.001) in the subsequent 6‐month period. However, compared to case–controls, these patients (n‐33 in both groups) had fewer days of hospitalisation (1.6 vs. 3.6 days/patient/month; P‐0.05) and, most significantly, were more likely to survive to 6 months (6 vs. 13 died; P<0.05).

Conclusion:

ECD is a common phenomenon in older CHF patients discharged from acute hospital care and is associated with poorer health outcomes in the longer‐term. Post‐discharge HBI is an important means for identifying and addressing ECD. Although HBI conveys benefits incremental to usual care, these data also provide a sound basis for increasing its effectiveness by applying earlier home visits in selected ‘high‐risk’ patients.
The incomplete Bucindolol Evaluation in Acute myocardial infarction Trial (BEAT)
Authors: Torp‐Pedersen Christian , Køber Lars , Ball Stephen , Hall Alistair , Brendorp Bente , Ottesen Michael Mundt , Berning Jens , Jensen Gorm , Hampton John , Zilles Peter , Eberle Siegfried , Carlsen Jan
Published: October 2002

The aim of this study was to evaluate the efficacy of adding the beta‐blocker bucindolol to standard therapy shortly after a myocardial infarction in a high‐risk population with reduced left ventricular function.

Methods

The study was planned to include 2000 patients with an enzyme confirmed myocardial infarction and severely reduced left ventricular function determined by echocardiography (corresponding to ejection fraction ≤0.35). The primary endpoint was all cause mortality and the secondary endpoints were time to first event of death, progression of heart failure or reinfarction—and the components. The study was closed early due to discontinuation of development of bucindolol by the manufacturer. Therefore, 170 patients were randomised to receive bucindolol and 173 to receive placebo.

Results

There were 27 deaths in the bucindolol group and 30 in the placebo group, hazard ratio of bucindolol 0.88 (95% confidence limits 0.5–1.5; P‐0.6). There were 9/4 (bucindolol/placebo, P‐0.16) heart failure events and 5/17 (P‐0.01) reinfarctions in the bucindolol/placebo groups.

Conclusion

Due to early closure it is unknown whether bucindolol changes mortality in high‐risk post myocardial infarct patients when added to best medical therapy. The frequency of reinfarction was significantly reduced.
Cajal bodies and coilin—moving towards function
Authors: Ogg Stephen C. , Lamond Angus I.
Published: October 2002

Many nuclear factors are concentrated within nonmembrane-bound subnuclear bodies. The Cajal body is an example of a conserved nuclear compartment that has been linked to molecular disease. Recent studies have shown Cajal bodies to be surprisingly mobile and offer clues about their function in the cell.
The influence of print advertisement organization on odd‐ending price image effects
Authors: Coulter Keith S.
Published: October 2002

Although findings have been inconsistent, there is some evidence from both experimental studies and field research that prices set just below the nearest round figure produce higher than expected demand at that level. Other research has demonstrated that the organization of verbal and/or pictorial elements of a print advertisement can influence the persuasive impact of that ad. The author combines these two streams of research in examining preference for brands associated with 0‐ versus 9‐ending prices that are displayed in different advertising layouts. Results indicate that the higher than expected demand associated with 9‐ending prices is more likely when prices are placed to the left of attended verbal information contained in an ad, due to the more positive evaluations of price that occur with more efficient subconscious processing.
Selective transport and accumulation of alkanes by Rhodococcus erythropolis S+14He
Authors: Kim In Seon , Foght Julia M. , Gray Murray R.
Published: October 2002

Selective transport and accumulation of n‐alkanes by Rhodococcus erythropolis S+14He was studied by growing cells on n‐hexadecane, n‐octadecane or the branched alkane pristane, and on mixtures of hydrocarbons. Ultrastructural analysis by transmission electron microscopy (TEM) revealed hydrocarbon inclusion bodies present in cells grown on the three alkanes, but not in cells grown on soluble media or exposed to nonmetabolized 2,2,4,4,6,8,8‐heptamethylnonane (HMN). n‐Hexadecane had the highest rates of accumulation within the cells and higher overall consumption rates relative to the other alkanes. These rates decreased when the molar concentration of n‐hexadecane was decreased in hydrocarbon mixtures, but at the same time the accumulation of n‐hexadecane in intracellular inclusions became increasingly selective. Sodium azide significantly inhibited the accumulation of n‐hexadecane, consistent with an active transport mechanism for accumulation. These results indicate that R. erythropolis S+14He is able to selectively discriminate and preferentially transport n‐hexadecane from mixtures of structurally similar alkanes into intracellular inclusions by an energy‐driven transport system. This selective membrane transport of hydrocarbon isomers has potential application for separations, bioprocessing, and the development of novel biosensors. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 650–659, 2002.
HPLC determination of phenylpropanolamine in pharmaceutical OTC preparations
Authors: Nakashima Kenichiro , Kanehara Saori , Kaddoumi Amal
Published: October 2002

A convenient HPLC method to determine phenylpropanolamine (PPA) in addition to phenylephrine (PE) and chlorpheniramine (CPA) in commercially available over‐the‐counter (OTC) preparations has been developed. Sample solutions were prepared by dilution with water or methanol followed by filtration and direct injection into the HPLC system. The mobile phase was a mixture of methanol–acetonitrile–acetic acid (0.1 M)–triethylamine (20:20:60:0.6, v/v/v/v) containing sodium heptanesulfonate (0.5 mM) as an ion pair. The separation was achieved on a reversed‐phase ODS column with detection wavelength set at 254 nm. The compounds showed good linearity in the range 2.5–1000 µM with detection limits ranged from 0.13 to 0.48 µM. PE, caffeine and CPA were well separated when present together with PPA. The method was applied to the determination of PPA in pharmaceutical preparations including hard and soft capsules. Copyright © 2002 John Wiley & Sons, Ltd.
Detection of inhaled clenbuterol in horse urine by GC/MS2
Authors: Van Eenoo P. , Delbeke F. T. , Deprez P.
Published: October 2002

Clenbuterol, a β‐adrenergic agonist, is used in the treatment of recurrent airway obstruction in horses. It is prohibited by horse racing authorities, because of its stimulating and growth‐promoting properties. However, information on detection times of clenbuterol after administration by nebulization is lacking. In this study, a fast, sensitive quantitative GC‐MS2method for the detection of clenbuterol in urine was developed. Alkaline liquid–liquid extraction was followed by derivatization to a cyclic methyl boronate derivative and analysis on a Finnigan MAT GCQ instrument. Method validation showed good linearity in the range 0.1–2.0 ng/mL, excellent repeatability and specificity. The limit of quantitative detection of the method was 0.1 ng/ml. Different instrumental parameters of the ion trap mass spectrometer were changed to increase the number of diagnostic ions for the cyclic methyl boronate derivative of clenbuterol. The influence of these changes and their applicability within the requirements and the criteria for mass spectrometry set by the responsible regulatory bodies are discussed. Clenbuterol was administered via nebulization to five standardbred mares (0.4 µg/kg body weight). Analysis of the urine samples resulted in the detection of clenbuterol, as early as 2 h post administration and for up to 36 h post treatment. Generally, maximum urinary concentrations of 1.2 ng/mL were reached after ­6–9 h. Copyright © 2002 John Wiley & Sons, Ltd.
A batch‐type time‐true ATM‐network simulator—design for parallel processing
Authors: Logothetis Michael , Liotopoulos Fotios
Published: October 2002

This paper presents a new type of network simulator for simulating the call‐level operations of telecom networks and especially ATM networks. The simulator is a pure time‐true type as opposed to a call‐by‐call type simulator. It is also characterized as a batch‐type simulator. The entire simulation duration is divided into short time intervals of equal duration,t. Duringt, a batch processing of call origination or termination events is executed and the time‐points of these events are sorted. The number of sorting executions is drastically reduced compared to a call‐by‐call simulator, resulting in considerable timesaving. The proposed data structures of the simulator can be implemented by a general‐purpose programming language and are well fitted to parallel processing techniques for implementation on parallel computers, for further savings of execution time. We have first implemented the simulator in a sequential computer and then we have applied parallelization techniques to achieve its implementation on a parallel computer. In order to simplify the parallelization procedure, we dissociate the core simulation from the built‐in call‐level functions (e.g. bandwidth control or dynamic routing) of the network. The key point for a parallel implementation is to organize data by virtual paths (VPs) and distribute them among processors, which all execute the same set of instructions on this data. The performance of the proposed batch‐type, time‐true, ATM‐network simulator is compared with that of a call‐by‐call simulator to reveal its superiority in terms of sequential execution time (when both simulators run on conventional computers). Finally, a measure of the accuracy of the simulation results is given. Copyright © 2002 John Wiley & Sons, Ltd.
Association between first trimester absence of fetal nasal bone on ultrasound and Down syndrome
Authors: Otaño L. , Aiello H. , Igarzábal L. , Matayoshi T. , Gadow E.C.
Published: October 2002

Objectives

To evaluate the association between absence of nasal bone on ultrasound and Down syndrome in fetuses at 11–14 weeks of pregnancy.

Methods

One hundred and ninety‐four consecutive fetuses from singleton pregnancies undergoing chorionic villi sampling (CVS) were evaluated by transabdominal ultrasound. A sagittal view of the fetal face was obtained and the absence or presence of nasal bone was recorded and correlated with the fetal karyotype.

Results

A successful view of the fetal profile was possible in 183 of 194 (94%) fetuses. The nasal bone was absent in three of five fetuses with Down syndrome, and in one of 175 (0.6%) chromosomally normal fetuses.

Conclusion

Absence of nasal bone by first trimester ultrasound was significantly associated with Down syndrome. When a proper view of the fetal face was obtained, the nasal bone was visible in more than 99% of karyotypically normal fetuses. Copyright © 2002 John Wiley & Sons, Ltd.
Agreement between predicted risk and prevalence of Down syndrome in first trimester nuchal translucency screening
Authors: Prefumo Federico , Thilaganathan Basky
Published: October 2002

The agreement between predicted risks of Down syndrome and observed prevalence was investigated in a population of 11 847 singleton pregnancies screened by first trimester nuchal translucency at a single institution. Twenty‐seven cases of Down syndrome were observed; 20 were detected prenatally by nuchal translucency and maternal age screening, three by other means and four postnatally. The screened women were grouped according to their predicted risk of having an affected pregnancy, and this was compared with the observed prevalence. A significant correlation between predicted and observed prevalences was noted, thus demonstrating that risk estimates for Down syndrome based on first trimester nuchal translucency screening are accurate. Copyright © 2002 John Wiley & Sons, Ltd.
Role of the CdS buffer layer as an active optical element in Cu(In,Ga)Se2thin‐film solar cells
Authors: Orgassa Kay , Rau Uwe , Nguyen Quang , Werner Schock Hans , Werner Jürgen H.
Published: October 2002

ZnO/CdS/Cu(In,Ga)Se2(CIGS) thin‐film heterojunction solar cells with CdS buffer layers of thicknesses between 0 and 85 nm are characterized by current–voltage, quantum efficiency, and optical reflection measurements. We investigate the correlation between the short‐circuit current density and the CdS layer thickness, focusing on the counteracting effects of light absorption and reduced optical reflection induced by the CdS layer. Both effects almost compensate each other for CdS layer thicknesses between 0 and 40 nm. Thus, an optimization of the short‐circuit current density is not achieved by omitting the CdS layer, but rather by replacing the CdS buffer with an alternative buffer material with higher bandgap energy and optical constants similar to those of CdS. Copyright © 2002 John Wiley & Sons, Ltd.
Composite beams and floor systems fully integrated with building services
Authors: Chung K F
Published: October 2002

This paper reviews the latest design developments in composite beams and floor systems fully integrated with building services. A number of composite floor systems developed specifically for integration of building services in commercial buildings are presented, namely, fabricated beams with tapered webs, haunched beams, trusses, stub girders, parallel beam grillage systems and slim floor systems.

Furthermore, the design and construction of steel and composite beams with large web openings is also discussed. Recent design developments for steel beams with web openings of various shapes and composite beams with large web openings to Eurocode 4 are also reported.
Genetic Screening for MEN1 Mutations in Families Presenting with Familial Primary Hyperparathyroidism
Authors: Perrier Nancy D. , Villablanca Andrea , Larsson Catharina , Wong Mariwil , Ituarte Philip , Teh Bin Tean , Clark Orlo H.
Published: October 2002

A large number of families with familial isolated hyperparathyroidism (FIHP) have been reported. We wanted to determine if some of these families represent early manifestations of full‐blown syndromes such as multiple endocrine neoplasia type 1
(MEN‐1), as early identification may alter surgical and medical management. Four small families with a family history of hyperparathyroidism without clear‐cut MEN‐1 features were screened for a MEN1 mutation. The 10 exons of the MEN1 gene were amplified and analyzed by single‐strand conformation analysis
(SSCA). Abnormal SSCA shifts were then sequenced using an automated sequencer. Two germline mutations were found: R527X and P277H. The former was detected in three members of a family consisting of two children and a mother. At the time of testing the youngest son was normocalcemic and clinically normal but subsequently developed hyperparathyroidism (HPT). Since the initial testing, the family has been confirmed to be a MEN‐1 family as the mother has developed abdominal pain and an elevated serum pancreatic polypeptide and the younger brother an anterior pituitary tumor and recurrent HPT. The latter P277H mutation was identified in two of three members tested from another family. Manifestations of MEN‐1 syndrome have also developed. The father now has developed diarrhea and elevated serum gastrin; and the daughter has developed recurrent HPT. Genetic screening of families who clinically have FIHP is important and may influence the type of medical and surgical treatment and follow‐up, as some have MEN‐1 syndrome. Long‐term screening for MEN syndromes should be included in this set of patients. Positive screening may predict disease and allow early detection and appropriate treatment before initiation of symptoms.
Temporal Bone Pathology in Fetuses Exposed to Isotretinoin
Authors: Moerike Shelley , Pantzar J. Tapio , de Sa Derek
Published: October 2002

Isotretinoin can be teratogenic, affecting many tissues, including the ear. However, there are only two histopathologic studies of the temporal bone in affected humans, and neither describes the findings in early gestation. We had the opportunity to study both temporal bones in each of two fetuses (22 and 24 weeks) exposed to isotretinoin in early gestation. One of the fetuses had a dilated IVth ventricle and a hypoplastic cerebellar vermis, while no dysmorphic features were seen in the other. In both infants the external ears were not noticeably abnormal. Histologically, anomalies of the middle ear included medial deviation of the malleus, forward displacement of the incus, and a small tympanic cavity (4/4); unilateral absence of the stapes (1/4); single “columella” crus and hypoplastic footplate (3/4); and unilateral dehiscence of the facial canal in one infant. Autolysis limited the examination of the labyrinth, but there was reduction in the number of cochlear spirals, and dilatation of the saccule in both infants. Anomalies of the middle and inner ear can be present without anomalies of the external ear or the central nervous system, and may be found even after relatively short exposures. These anomalies are similar to those detected in experimental exposure to isotretinoin, and are consistent with altered expression of the goosecoid gene.
Enteric Nervous System: Development and Developmental Disturbances—Part 2
Authors: Newgreen Donald , Young Heather M.
Published: October 2002

This review, which is presented in two parts, summarizes and synthesizes current views on the genetic, molecular, and cell biological underpinnings of the early embryonic phases of enteric nervous system (ENS) formation and its defects. Accurate descriptions of the phenotype of ENS dysplasias, and knowledge of genes which, when mutated, give rise to the disorders (see Part 1 in the previous issue of this journal), are not sufficient to give a real understanding of how these abnormalities arise. The often indirect link between genotype and phenotype must be sought in the early embryonic development of the ENS. Therefore, in this, the second part, we provide a description of the development of the ENS, concentrating mainly on the origin of the ENS precursor cells and on the cell migration by which they become distributed throughout the gastrointestinal tract. This section also includes experimental evidence on the controls of ENS formation derived from classic embryological, cell culture, and molecular genetic approaches. In addition, for reasons of completeness, we also briefly describe the origins of the interstitial cells of Cajal, a cell population closely related anatomically and functionally to the ENS. Finally, a brief sketch is presented of current notions on the developmental processes between the genes and the morphogenesis of the ENS, and of the means by which the known genetic abnormalities might result in the ENS phenotype observed in Hirschsprung's disease.
Different types of microsomal enzymes catalyze ortho‐ or para‐hydroxylation in the biosynthesis of carnation phytoalexins
Authors: Reinhard Klaus , Matern Ulrich
Published: October 2002

Cell suspension cultures of carnation (Dianthus caryophyllus L.) accumulate, upon challenge with crude fungal elicitor, various dianthramide phytoalexins, all of which derive from N‐benzoylanthranilate. In vitro, microsomes from the elicited carnation cells hydroxylated N‐benzoylanthranilate in the 4‐ and/or 2′‐positions to yield the hydroxyanthranilate and/or salicyloyl derivatives. 2′‐Hydroxylation was shown to precede 4‐hydroxylation in the formation of N‐salicyloyl‐4‐hydroxyanthranilate, and both these activities depended strictly on NADPH and molecular oxygen. 4‐Hydroxylation was shown to be catalyzed by cytochrome P‐450‐dependent monooxygenase(s), whereas the 2′‐hydroxylating activity appeared to be due to a novel class of enzymes, also responding synergistically to NADH in combination with NADPH and showing apparent inhibition by cytochrome c but not by carbon monoxide. The difference in type of 4‐ and 2′‐hydroxylases was corroborated by the exclusive inhibition of either activity in imidazole vs. MOPS buffers as well as their differential heat sensitivities. In the course of these studies, low concentrations of N‐salicyloylanthranilate turned out to inhibit the cytochrome P‐450‐dependent 4‐hydroxylation more strongly than any of the commercial inhibitor chemicals tested, while neither the substrate, N‐benzoylanthranilate, nor the final product, N‐salicyloyl‐4‐hydroxyanthranilate, exhibited such significant inhibition. In addition, 2′‐hydroxylation activity was affected much less by N‐benzoylanthranilate, N‐salicyloylanthranilate or by inhibitor chemicals. The results demonstrate the requirement of two different classes of hydroxylase activities that appear to introduce the antimycotic quality to the dianthramides for phytoalexin defense.
Succinate:quinone oxidoreductases – what can we learn from Wolinella succinogenes quinol:fumarate reductase?
Authors: Lancaster C.Roy D
Published: October 2002

The structure of Wolinella succinogenes quinol:fumarate reductase by X‐ray crystallography has been determined at 2.2‐Å resolution [Lancaster et al. (1999), Nature 402, 377–385]. Based on the structure of the three protein subunits A, B, and C and the arrangement of the six prosthetic groups (a covalently bound FAD, three iron–sulphur clusters, and two haem b groups) a pathway of electron transfer from the quinol‐oxidising dihaem cytochrome b in the membrane to the site of fumarate reduction in the hydrophilic subunit A has been proposed. By combining the results from site‐directed mutagenesis, functional and electrochemical characterisation, and X‐ray crystallography, a residue was identified which is essential for menaquinol oxidation. [Lancaster et al. (2000), Proc. Natl. Acad. Sci. USA 97, 13051–13056]. The location of this residue in the structure suggests that the coupling of the oxidation of menaquinol to the reduction of fumarate in dihaem‐containing succinate:quinone oxidoreductases could be associated with the generation of a transmembrane electrochemical potential. Based on crystallographic analysis of three different crystal forms of the enzyme and the results from site‐directed mutagenesis, we have derived a mechanism of fumarate reduction and succinate oxidation [Lancaster et al. (2001) Eur. J. Biochem. 268, 1820–1827], which should be generally relevant throughout the superfamily of succinate:quinone oxidoreductases.
mik1+ G1–S transcription regulates mitotic entry in fission yeast
Authors: Ng Szu Shien , Anderson Mark , White Stewart , McInerny Christopher J
Published: October 2002

In the fission yeast Schizosaccharomyces pombe Mik1p, in combination with Wee1p, is an important inhibitor of mitosis through direct phosphorylation of Cdc2p. Here we present the observation that mik1
+ is transcribed during G1‐ and S‐phase in normally dividing cells. mik1
+ transcription is regulated by the MCB–DSC1 system, which controls expression of other genes at the G1–S interval. mik1
+ is shown to be an important target of MCB–DSC1 as it is epistatic for the mitotic delay phenotype displayed in cdc10‐C4 cells, which are mutated in a component of DSC1. The mitotic delay in cdc10‐C4 cells is bypassed by cdc2‐1w, suggesting that mik1
+ acts directly on cdc2
+, with no checkpoint function involved. Thus, mik1
+ represents a new type of MCB–DSC1 regulated gene in fission yeast, whose gene product is exclusively expressed during G1‐ and S‐phase to prevent premature mitosis during this cell cycle stage.
Neurophilin‐1 is a downstream target of transcription factor Ets‐1 in human umbilical vein endothelial cells
Authors: Teruyama Kazuhide , Abe Mayumi , Nakano Toru , Takahashi Shoki , Yamada Shogo , Sato Yasufumi
Published: October 2002

Transcription factor Ets‐1 expressed in endothelial cells promotes angiogenesis. Here, we transiently overexpressed Ets‐1 in human umbilical vein endothelial cells (HUVECs) and comprehensively searched for potential downstream targets of Ets‐1 by cDNA microarray analysis. The expression of several angiogenesis‐related genes including neuropilin‐1 was augmented by the overexpression of Ets‐1. Quantitative real‐time RT‐PCR and Western blotting confirmed the increase in the levels of neuropilin‐1 mRNA and protein. In contrast, dominant negative ets‐1 decreased the levels of neuropilin‐1 mRNA and protein. These results indicate that neuropilin‐1 is a downstream target of Ets‐1 in HUVECs.
Bruton's tyrosine kinase is a substrate of calpain in human platelets
Authors: Mukhopadhyay Saikat , Ramars Amanchy S.S. , Ochs Hans D. , Dash Debabrata
Published: October 2002

Platelet‐associated Bruton's tyrosine kinase (Btk) was completely cleaved if treated with calcium ionophore A23187 with appearance of a proteolytic product of 27 kDa size. Aggregation with thrombin also induced about 10% degradation of Btk after 30 min. Calpain inhibitors prevented Btk degradation in both. The proteolytic products of the Wiskott–Aldrich syndrome protein (WASP), a calpain and Btk substrate, and the 27 kDa degradation product of Btk did not redistribute to the Triton‐insoluble cytoskeleton in thrombin‐aggregated platelets, in contrast to the uncleaved proteins. The degradation of Btk and WASP was independent of their tyrosine phosphorylation status. These results indicate that Btk is an endogenous substrate for calpain, the cleavage of which may have functional consequences in long‐term post‐aggregation events in platelets.
Organization of cytoplasmic domains of sarcoplasmic reticulum Ca2+‐ATPase in E1P and E1ATP states: a limited proteolysis study
Authors: Danko Stefania , Yamasaki Kazuo , Daiho Takashi , Suzuki Hiroshi , Toyoshima Chikashi
Published: October 2002

In order to characterize the domain organization of sarcoplasmic reticulum Ca2+‐ATPase in different physiological states, limited proteolysis using three proteases (proteinase K (prtK), V8 and trypsin) was conducted systematically and quantitatively. The differences between E2 and E2P were examined in our previous study and E2P was characterized by the complete resistance to all three proteases (except for trypsin attack at the very top of the molecule (T1 site)). The same strategies were employed in this study for E1ATP, E1PADP and E1P states. Because of the transient nature of these states, they were either stabilized by non‐hydrolyzable analogues or made predominant by adjusting buffer conditions. Aluminum fluoride (without ADP) was found to stabilize E1P. All these states were characterized by strong (E1ATP) to complete (E1PADP and E1P) resistance to prtK and to V8 but only weak resistance to trypsin at the T2 site. Because prtK and V8 primarily attack the loops connecting the A domain to the transmembrane helices whereas the trypsin T2 site (Arg198) is located on the outermost loop in the A domain, these results lead us to propose that the A domain undergoes a large amount of rotation between E1P and E2P. Combined with previous results, we demonstrated that four states can be clearly distinguished by the susceptibility to three proteases, which will be very useful for establishing the conditions for structural studies.
Activation of mouse phosphodiesterase 3B gene promoter by adipocyte differentiation in 3T3‐L1 cells
Authors: Niiya Toshiyuki , Osawa Haruhiko , Onuma Hiroshi , Suzuki Yoshifumi , Taira Masato , Yamada Kazuya , Makino Hideichi
Published: October 2002

Activation of phosphodiesterase (PDE) 3B reduces free fatty acid output from adipocytes. Induction of PDE3B gene expression by adipocyte differentiation could improve insulin resistance. To examine whether the PDE3B promoter is activated by this differentiation, the 5′ flanking sequence of the mouse PDE3B gene was isolated. The transcription initiation site was determined to be located 195 bp upstream of the translation start site. No putative binding site for peroxisome proliferator‐activated receptor γ was found within 2 kb upstream of the transcription initiation site. This region had promoter activity, which was further activated on adipocyte differentiation in 3T3‐L1 cells.