bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitric Oxide Acts in Conjunction with Proinflammatory Cytokines to Promote Cell Death in Osteoblasts
Authors: Damoulis Petros D. , Hauschka Peter V.
Published: June 2006

Proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin-1β are known modulators of bone remodeling in vitro and in vivo. The same cytokines induce the production of nitric oxide (NO) in various cell types, including osteoblasts and osteoclasts, and NO has recently been implicated in the regulation of bone resorption. We investigated the relationship between NO levels and cell viability in MC3T3-E1, a well-characterized osteoblastic cell line. NO donors at high concentrations (≥0.5 mM) produce a significant cytotoxic effect over a 48 h period. Various combinations of the three cytokines strongly promote endogenous NO production, and high NO levels are correlated with the loss of cell viability. Although TNF-α produces NO-independent cytotoxicity, NO greatly enhances this cytotoxic effect. Human and mouse TNF-α differ in their cytotoxic effects, and human TNF-α induces lower levels of NO production. In cocultures of RAW 264.7 mouse macrophages stimulated with lipopolysaccharide and IFN-γ, and untreated MC3T3-E1 osteoblasts, addition of anti–TNF-α antibody and inhibition of NO synthesis have additive, protective effects on osteoblast viability. NO cytotoxicity involves an apoptotic mechanism. Our results underline the importance of NO and TNF-α as cytotoxic mediators in the osseous microenvironment and might explain the observed deficiency of bone formation in inflammatory sites.
Advanced Glycation Endproducts Stimulate Interleukin-6 Production by Human Bone-Derived Cells
Authors: Takagi Miki , Kasayama Soji , Yamamoto Takehisa , Motomura Takashi , Hashimoto Kunihiko , Yamamoto Hiroyasu , Sato Bunzo , Okada Shintaro , Kishimoto Tadamitsu
Published: June 2006

Advanced glycation endproducts (AGEs), which result from nonenzymatic reactions of glucose with tissue proteins, have been shown to accumulate on long-lived proteins in advanced aging and diabetes mellitus. Thus, AGEs have been implicated in some of the chronic complications associated with these disorders. In this study, we investigated the effects of the glucose-modified protein on the production of the potent bone resorption factors by cells derived from explants of human bone. AGEs stimulated the release of interleukin-6 (IL-6) in the culture supernatants from the bone-derived cells and increased the levels of IL-6 mRNA in the cells. By contrast, the levels of IL-11 in the culture supernatants were not altered by AGEs, and the other bone resorption factors IL-1α and IL-1β were undetectable (<1.0 pg/ml) either without or with the treatment of AGEs. Electrophoretic mobility-shift assays revealed that the transcription nuclear factor-κB, which is critical for the inducible expression of IL-6, was activated in the nuclear extracts from mouse osteoblastic MC3T3-E1 cells treated with AGEs. These results suggest that AGEs are involved in bone remodeling modulation by stimulating IL-6 production in human bone-derived cells.
Development and Validation of a Discriminative Quality of Life Questionnaire for Osteoporosis (The OPTQoL)
Authors: Lydick Eva , Zimmerman Sheryl Itkin , Yawn Barbara , Love Betsey , Kleerekoper Michael , Ross Philip , Martin Allison , Holmes Richard
Published: June 2006

We report the development and validation of an osteoporosis-targeted quality of life questionnaire to measure the impact of the disease in the general population. From multiple focus groups with women with osteoporosis, healthy women at risk for osteoporosis, spouses and relatives of women with osteoporosis, and health care providers, we identified over 300 potential items related to the disease. A lengthy questionnaire incorporated these items and was administered to a second large study cohort of 222 women with clinical osteoporosis (history of fracture, significant height loss, and/or kyphosis); 101 women with known low bone mineral density levels that would categorize them as osteoporotic but who had not yet shown obvious physical manifestations of the disease; and 142 women with other conditions (such as arthritis, cancer, depression) expected to also have an impact on quality of life. Final items from among the original 300 were chosen for their demonstrated relationship with osteoporosis as measured by clinical manifestations and low bone density and with quality of life measured by a standard generic questionnaire, the SF-36. The final questionnaire contains 26 scored items in three domains—physical activity, adaptations, and fears—and six nonscored questions relating to osteoporotic changes and diagnosis. This instrument is unique among osteoporosis-targeted questionnaires in that it attempts to measure the total impact of the disease on quality of life within a population at a single point in time.
Gonadal and Adrenal Androgens Are Potent Regulators of Human Bone Cell Metabolism In Vitro
Authors: Kasperk Christian H. , Wakley Glenn K. , Hierl Thomas , Ziegler Reinhard
Published: June 2006

Androgens stimulate bone formation and play an important role in the maintenance of bone mass. Clinical observations suggest that both gonadal and adrenal androgens contribute to the positive impact of androgenic steroids on bone metabolism. We investigated the mechanism of action of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfated compound dehydroepiandrosterone sulfate (DHEAS) on human osteoblastic cells (HOCs) in vitro. The DHEA- and DHEAS-induced effects were analyzed in parallel with the actions elicited by the gonadal androgen dihydrotestosterone (DHT). There was no qualitative difference between the effects of gonadal and adrenal androgens on HOC metabolism in vitro. Both were stimulatory as regards cell proliferation and differentiated functions, but the gonadal androgen DHT was significantly more potent than DHEA. The actions of DHT and DHEA on HOC proliferation and alkaline phosphatase (ALP) production could be prevented by the androgen receptor antagonist hydroxyflutamide and inhibitory transforming growth factor β antibodies (TGF-βab), respectively, but were not affected by the presence of the 3β-hydroxysteroid dehydrogenase (3βHSD) and 5-α-reductase (5-AR) inhibitor 17β-N,N-diethylcarbamoyl-4-methyl-4aza-5α-androstan-3-one (4-MA). This indicates that DHT and DHEA (1) exert their mitogenic effects by androgen receptor–mediated mechanisms, (2) stimulate ALP production by increased TGF-β expression, (3) that the action of DHT is not affected by the presence of 4-MA, and that (4) DHEA does not need to be metabolized by 3βHSD or 5-AR first to exert its effects on HOCs in vitro.
Periprosthetic Bone Loss and Regional Bone Turnover in Uncemented Total Hip Arthroplasty: A Prospective Study Using High Resolution Single Photon Emission Tomography and Dual-Energy X-Ray Absorptiometry
Authors: Mr. Kröger Heikki , Vanninen Esko , Overmyer Margit , Miettinen Hannu , Rushton Neil , Suomalainen Olavi
Published: June 2006

Single photon emission computed tomography (SPECT) at 6 and 12 months and dual-energy X-ray absorptiometry (DXA) at 0, 6, and 12 months were performed prospectively in 15 patients who had undergone uncemented total hip arthroplasty (THA) without any complications. Periprosthetic bone mineral density (BMD) decreased significantly in all regions of interests (ROIs) during 1 year of follow-up. The greatest annual decrease was found in the lesser trochanter region (22.1%). From 6–12 months, SPECT activity in the operated side decreased significantly (10–24%) in all ROIs, with the exception of the medial cortex ROI. In contrast, increases (8–36%) were found in the contralateral side. At 12 months, the operated versus control difference was still 10% in the lesser trochanter ROI, but as much as about 70% in the greater trochanter and tip ROIs. The decrease in BMD was significantly related to an increase in SPECT activity in the lesser trochanter region (r = −0.589, p < 0.05). In conclusion, increased periprosthetic SPECT activity seems to be associated with increased bone loss. We suggest that increased SPECT activity and subsequent bone loss reflect altered stress distribution and bone remodeling in the femur after prosthesis implantation.
Identification of Apolipoprotein A-II in Cerebrospinal Fluid of Pediatric Brain Tumor Patients by Protein Expression Profiling
Authors: de Bont Judith M , den Boer Monique L , Reddingius Roel E , Jansen Jaap , Passier Monique , van Schaik Ron HN , Kros Johan M , Sillevis Smitt Peter AE , Luider Theo H , Pieters Rob
Published: June 2006

Background: Our aim was to detect differences in protein expression profiles of cerebrospinal fluid (CSF) from pediatric patients with and without brain tumors.

Methods: We used surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry and Q10 ProteinChip arrays to compare protein expression profiles of CSF from 32 pediatric brain tumor patients and 70 pediatric control patients. A protein with high discriminatory power was isolated and identified by subsequent anion-exchange and reversed-phase fractionation, gel electrophoresis, and mass spectrometry. The identity of the protein was confirmed by Western blotting and immunohistochemistry.

Results: Of the 247 detected protein peak clusters, 123 were differentially expressed between brain tumor and control patients with a false discovery rate of 1%. Double-loop classification analysis gave a mean prediction accuracy of 88% in discriminating brain tumor patients from control patients. From the 123 clusters, a highly overexpressed protein peak cluster in CSF from brain tumor patients was selected for further analysis and identified as apolipoprotein A-II. Apolipoprotein A-II expression in CSF was correlated with the CSF albumin concentration, suggesting that the overexpression of apolipoprotein A-II is related to a disrupted blood–brain barrier.

Conclusions: SELDI-TOF mass spectrometry can be successfully used to find differentially expressed proteins in CSF of pediatric brain tumor and control patients. Apolipoprotein A-II is highly overexpressed in CSF of pediatric brain tumor patients, which most likely is related to a disrupted blood–brain barrier. Ongoing studies are aimed at finding subtype specific proteins in larger groups of pediatric brain tumor patients.
Willensfreiheit und strafrechtliche Unrechtslehre
Authors: Lampe Ernst-Joachim
Published: June 2006

I.

Die ewige Wiederkehr der Diskussion über die Willensfreiheit des Menschen hat in den letzten Jahren nicht nur neue wissenschaftliche Erkenntnisse, sondern sogar ein neues „Menschenbild” hervorgebracht. Dieses Bild wird einerseits von der Selbsterfahrung idealistisch entworfen:

„Wir erfahren uns als freie und folglich als verantwortende, autonome Agenten. Esscheint uns, als gingen unsere Entscheidungen unseren Handlungen voraus und wirkten auf Prozesse im Gehirn ein, deren Konsequenz dann die Handlung ist”.
Strafrechtliche Wiedergutmachung und ihr Verhältnis zum zivilrechtlichen Schadensersatz
Authors: Freund Georg , Carrera Enara Garro
Published: June 2006

Die Wiedergutmachung des durch eine Straftat bewirkten Schadens wird – soweit ersichtlich – in allen kontinentaleuropäischen Rechtsordnungen zumindest bei der Strafzumessung berücksichtigt. Die näheren Kriterien einer spezifisch strafrechtlich relevanten Wiedergutmachung sowie die genauen Konsequenzen für das Ob und Wie strafrechtlicher Reaktion auf die begangene Straftat sind jedoch noch immer weitgehend ungeklärt und werden dementsprechend in den verschiedenen europäischen Staaten – trotz eines gewissen Grundkonsenses – sehr unterschiedlich beurteilt. Im Folgenden sollen kurz die entsprechenden gesetzlichen Regelungen in Deutschland, Österreich und Spanien unter Berücksichtigung ihres Verständnisses in Rechtsprechung und Literatur exemplarisch skizziert und in ein im Entstehen begriffenes Europäisches Strafrechtssystem eingeordnet werden. Dabei lässt die exakte Erfassung des beschränkten strafrechtlichen Stellenwerts zivilrechtlichen Schadensersatzes die weiteren – letztlich viel bedeutsameren – spezifisch strafrechtlich relevanten Aspekte klarer hervortreten. Ein Vorschlag für eine in den genannten Rechtsordnungen einheitliche klarstellende gesetzliche Regelung (in deutscher und spanischer Sprache), welche auch die in diesen Kontext gehörende Problematik des Rücktritts vom Versuch angemessen bewältigt, rundet die Überlegungen ab und soll einen Anstoß für weitere Diskussionen geben.
Rechtsstaatswidrige Verfahrensverzögerungen im Strafverfahren als Verfahrenshindernis von Verfassungs wegen
Authors: Waßmer Martin Paul
Published: June 2006

Immer wieder gibt es Strafverfahren, die von extremen rechtsstaatswidrigen Verfahrensverzögerungen geprägt sind. Im Jahre 2000 hat der BGH in einer Grundsatzentscheidung (BGHSt. 46, 159ff.) diesbezüglich die Annahme eines Verfahrenshindernisses grundsätzlich für möglich erachtet. Diese Lösung ist aber sowohl grundsätzlich als auch in den Einzelheiten umstritten, zumal die bisherige Diskussion „ohne dogmatische oder systematische Leitlinien“ sein soll. Dass Leitlinien existieren und sich die vorhandenen Differenzen weitgehend überbrücken lassen, wird nachfolgend gezeigt.
Load Profile and Fluid Composition Influence the Soak Behavior of UHMWPE Implants
Authors: Schwenke T , Schneider E , Wimmer MA
Published: June 2006

Wear of total joint replacements is determined gravimetrically in simulator studies. A mix of bovine serum, distilled water, and additives is intended to replicate the lubrication conditions in vivo. Load soak stations are used to correct for weight gain due to fluid absorption. Although the implementation of a soak station is considered only as an option for wear testing, this study indicated that fluid absorption depends on the lubricant composition as well as on the applied load profile. Two different fluid recipes were tested with three load scenarios each. Standard ultra-high molecular weight polyethylene (UHMWPE) pins acted against commercially available ceramic hip balls. Dynamic (0 to 1000 N), static (1000 N), and no load were applied for 23.1 days (or 2·106 cycles). Both lubricant recipes based on the same mix of deionized water and newborn calf serum (final protein content: 30 g/L), and differed in the chemicals admixed to the fluid to minimize bacterial growths and to prevent protein precipitation. After test completion, the group of samples tested in fluid B gained 2.4-, 3.6-, and 4.2-fold the weight of samples submersed in fluid A for the dynamically, statically, and nonloaded samples, respectively. The specimens showed a significantly higher weight gain under dynamic load than subjected to static or no load for both fluids. The results of this study suggest the implementation of a load-soak control station for every wear test when UHMWPE materials are examined.
Measuring and Modeling the Displacement of Connate Water in Chalk Core Plugs During Water Injection
Authors: Korsbech U. , Aage H. K. , Andersen B. L. , Hedegaard K. , Springer N.
Published: June 2006

The movement of connate water spiked with gamma-emitting 22Na (a radioactive sodium isotope) was studied during laboratory waterflooding of oil-saturated chalk at connate-water saturation from a North Sea reservoir. Using a 1D gamma-monitoring technique, it was observed that connate water is piled up at the front of the injection water and forms a mixed water bank with almost 100% connate water in the front, behind which a gradual transition to pure injection water occurs. This result underpins log interpretations from waterflooded chalk reservoirs. An ad hoc model was set up by use of the results, and the process was examined theoretically at a larger scale.
Artificial Intelligence Used to Evaluate 23 Single-Well Surfactant-Soak Treatments
Authors: Weiss William W. , Xie Xina , Weiss Jason , Subramanium Vishu , Taylor Archie , Edens Fred
Published: June 2006

Following a series of laboratory imbibition-cell experiments, field tests were conducted to determine the effectiveness of surfactant-soak treatments as a single-well enhanced-oil-recovery (EOR) technique. The tests were conducted in the dolomite interval of the Phosphoria formation. Artificial intelligence was applied to analyze the mixed test results. The analysis suggested that the gamma ray log can be used to predict results and that a minimum amount of surfactant is required to improve production.
Conditional Statistical Moment Equations for Dynamic Data Integration in Heterogeneous Reservoirs
Authors: Li Liyong , Tchelepi Hamdi A.
Published: June 2006

An inversion method for the integration of dynamic (pressure) data directly into statistical moment equations (SMEs) is presented. The method is demonstrated for incompressible flow in heterogeneous reservoirs. In addition to information about the mean, variance, and correlation structure of the permeability, few permeability measurements are assumed available. Moreover, few measurements of the dependent variable are available. The first two statistical moments of the dependent variable (pressure) are conditioned on all available information directly. An iterative inversion scheme is used to integrate the pressure data into the conditional statistical moment equations (CSMEs). That is, the available information is used to condition, or improve the estimates of, the first two moments of permeability, pressure, and velocity directly. This is different from Monte Carlo (MC) -based geostatistical inversion techniques, where conditioning on dynamic data is performed for one realization of the permeability field at a time. In the MC approach, estimates of the prediction uncertainty are obtained from statistical post-processing of a large number of inversions, one per realization.

Several examples of flow in heterogeneous domains in a quarter-five-spot setting are used to demonstrate the CSME-based method. We found that as the number of pressure measurements increases, the conditional mean pressure becomes more spatially variable, while the conditional pressure variance gets smaller. Iteration of the CSME inversion loop is necessary only when the number of pressure measurements is large. Use of the CSME simulator to assess the value of information in terms of its impact on prediction uncertainty is also presented.
The Solvency of a General Insurance Company in Terms of Emerging Costs
Authors: Daykin C. D. , Bernstein G. D. , Coutts S. M. , Devitt E. R. F. , Hey G. B. , Reynolds D. I. W. , Smith P. D.
Published: June 2006

The authors challenge the traditional balance sheet concept of the solvency of a general insurance company and put forward an emerging costs concept, which enables the true nature of the assets and liabilities to be taken into account, including their essential variability. Simulation is suggested as a powerful tool for use in examining the financial strength of a company. A simulation model is then used to explore the resilience of a company's financial position to a variety of possible outcomes and to assess the probability that the assets will prove adequate to meet the liabilities with or without an assumption of continuing new business. This suggests the need for an appropriate asset margin assessed individually for each company. The implications for the management and supervision of general insurance companies are explored. The suggestion is made that the effectiveness of supervision based on the balance sheet and a crude solvency margin requirement is limited. More responsibility should be placed on an actuary or other suitably qualified professional individual to report on the overall financial strength of the company, both to management and to the supervisory authorities.
On the Definition of Catastrophe Claims and the Calculation of their Expected Cost for the Purpose of Long Range Planning and Profit Centre Control
Authors: Ajne Björn , Wide Harry
Published: June 2006

Some reasons are given for paying special attention to the gross cost of catastrophe claims in planning and control. A method is then described of defining catastrophe claims and estimating their expected cost. The various steps in applying the method to real data and its performance for planning and control are discussed and illustrated in conjunction with an investigation carried out on a company portfolio.
Evaluation of cat and owner characteristics and their relationships to outdoor access of owned cats
Authors: Clancy Elizabeth A. , Moore Antony S. , Bertone Elizabeth R.
Published: June 2006

Objective—To examine characteristics of cats and their owners with regard to outdoor access of owned cats.

Design—Cross-sectional study.

Animals—184 owned cats admitted to a veterinary referral center for nonemergency health concerns.

Results—Cats acquired recently were less likely to be allowed outdoors than those acquired during previous years. Outdoor access was often limited during the day; few owners allowed their cats to remain outdoors at night. Cats acquired from shelters were more likely to be kept exclusively as indoor pets than those cats acquired as strays. The presence of dogs but not other cats in the household was associated with increased outdoor access. Age, health status, and onychectomy status were not significantly associated with outdoor access. Cats allowed outdoor access were more likely to have been bitten by other cats.

Conclusions and Clinical Relevance—The basis for an owner's decision to allow outdoor access appears to be multifactorial, and there may be regional differences in outdoor access of owned cats. Acquisition source is associated with outdoor access of owned cats. Availability of information regarding outdoor access of cats may influence decision making. Educational efforts targeted at specific groups of cat owners, as well as programs that acknowledge owner beliefs regarding quality of life for their cats, may help to address the health, safety, and population concerns associated with outdoor access of owned cats. (J Am Vet Med Assoc2003;222:15417–1545)
Modeling for local dynamic behaviors of phenol biodegradation in bubble columns
Authors: Feng Wei , Wen Jianping , Jia Xiaoqiang , Yuan Qing , Sun Yan , Liu Cuiyun
Published: June 2006

A coupled three‐dimensional (3‐D) model, combining hydrodynamics with biochemical reactions, was developed to simulate the local transient flow patterns and the dynamic behaviors of cell growth and phenol biodegradation by yeast Candida tropicalis in the bubble‐column bioreactor, using the computational fluid dynamic (CFD) method. In order to validate this proposed model effectively, the validation of the local hydrodynamic characteristics of the gas‐mineral salt solution (gas‐liquid) two‐phase system, with the phenol concentration of 1200 mg/L, and with the absence of cells, was performed in a square‐sectioned bubble column bioreactor using the LDA system and conductivity probe. Furthermore, the validation of phenol biodegradation behaviors by yeast Candida tropicalis at different initial concentrations of phenol and cell was also carried out in the above bubble‐column bioreactor. The results indicated that the model simulations had a satisfying agreement with the experimental data. Finally, the local instantaneous flow and phenol biodegradation features including gas holdup, gas velocity, liquid velocity, cell concentration and phenol concentration inside the bioreactor were successfully predicted in different‐scale bubble columns by the proposed model. © 2006 American Institute of Chemical Engineers AIChE J, 2006
Comparison of potential adjustment variables representing primary intellectual level in epidemiological studies on neurotoxicity
Authors: Rouch Isabelle , Chouanière Dominique , Wild Pascal , Fontana Jean‐Marc , Boillat Marcel‐André
Published: June 2006

Background

Primary intellectual abilities (PIA) are a confounder in epidemiological studies on neurotoxicity. A good measure of this confounder should be independent of age as PIA is an intrinsic ability. Furthermore, as PIA is related to health endpoints, any measure of PIA should reveal this association. This study is aimed at comparing vocabulary test, diploma and age at end of schooling properties as measures of PIA in a non‐exposed population of workers.

Methods

The design was a cross‐sectional study of 413 non‐exposed workers (203 women and 210 men) selected from a health check‐up center. The effect of age on the vocabulary score was assessed using an analysis of covariance adjusted for diploma. Relationships between neuropsychological performances and vocabulary score, diploma and end of schooling age were, respectively, assessed using multiple linear regressions adjusted for age and gender.

Results

Vocabulary score increased significantly with age, both for men and women. The increase was 0.14 word per year for women, and 0.18 word per year for men. The explained variance of the models evaluating the relationships between age at end of schooling, diploma, vocabulary test, and neuropsychological performances was quite similar for the three measures of PIA.

Conclusions

Vocabulary score was found to be age‐related, even after adjustment for diploma. No difference was found between these three variables in terms of their relationship to neuropsychological endpoints. Moreover, the literature shows that vocabulary test performances are influenced by exposure to neurotoxic agents. These results suggest that vocabulary score could be of interest for participants of similar ages and similar diplomas. Otherwise, the other two variables would be better PIA measures in neurotoxicology studies. Am. J. Ind. Med. 2006. © 2006 Wiley‐Liss, Inc.
Telemedicine in sub‐Saharan Africa: The case of teleophthalmology and eye care in Ethiopia
Authors: Kifle Mengistu , Mbarika Victor W.A. , Datta Pratim
Published: June 2006

Department of Information Systems, Washington State University, Pullman, WA. E‐mail: pdatta@wsu.edu The authors examine the need and adoption of teleophthalmology in sub‐Saharan Africa. Ethiopia, like most sub‐Saharan African countries, is faced with limited specialists and health care services. These services are often concentrated in the urban areas, leaving most of the rural population (about 70% of the country) without adequate and timely health care delivery. In Ethiopia, the ratio of ophthalmologists to the population is 1:1,200,000, resulting in inadequate delivery of ophthalmology‐related health care services. Using both primary and secondary data collection approaches, the authors report the need for telemedicine as well as the adoption and application of teleophthalmology in Ethiopia. Further, they present Ethiopia's teleophthalmology network, integrated teleconsultation, and teleeducation services. The authors conclude by presenting this research as a starting point to investigate further teleophthalmology and other telemedicine services for Ethiopia and by extension, other developing countries. Therefore, they bring a much‐underresearched region (sub‐Saharan Africa) and a much‐underresearched technology (telemedicine) to the forefront of information systems (IS) research. It is the authors' hope that colleagues in the field will be motivated to investigate this “forgotten” region of the world that is yet to reap the full potentials of information and communications technologies (ICTs).
Prenatal developmental toxicity evaluation of 2′,3′‐dideoxyinosine (ddI) and 2′,3′‐didehydro‐3′‐deoxythymidine (d4T) co‐administered to Swiss Albino (CD‐1) mice
Authors: Price Catherine J. , George Julia D. , Marr Melissa C. , Myers Christina B. , Bieler Gayle S. , Williams Rick L. , Jahnke Gloria D.
Published: June 2006

BACKGROUND:In pregnant women, antiretroviral drugs improve maternal health and reduce vertical transmission of human immunodeficiency virus to the infant. However, few nonclinical studies have examined the potential for adverse drug interactions.METHODS:On gestational days (GD) 6–16, mice were dosed with vehicle, ddI (360, 1440, or 2880 mg/kg/day, p.o.), d4T (60, 240, or 480), or ddI/d4T combinations (360/60, 1440/240, or 2880/480). Daily doses were divided into two equal parts that were administered ≥6‐hr apart. Body weight, clinical signs, and feed consumption were monitored. Pregnancies (22–24/group) were confirmed at necropsy. Maternal liver and gravid uterine weights (GUW), uterine implants (resorption, live or dead fetus), fetal body weight, gender, and morphologic anomalies (external, visceral, skeletal) were recorded.RESULTS:Maternal body weight, clinical signs, and GUW were unaffected. Maternal weight change corrected for GUW was greater than controls at 60 and 480 d4T. Relative feed consumption during treatment was increased relative to controls at 1440 and 2880 ddI and 2880/480 ddI/d4T. Relative maternal liver weight was elevated above controls at 240 and 480 d4T and 2880/480 ddI/d4T, and above the constituent dose of ddI at 1440/240 and 2880/480 ddI/d4T. Liver weight was not affected by ddI and there was no significant drug interaction. Prenatal mortality and morphologic anomalies were not increased. Fetal body weight showed only a decreasing trend for ddI/d4T, no effect for ddI or d4T, and no statistically significant drug interaction.CONCLUSIONS:In pregnant mice, ddI/d4T combinations were not associated with well‐defined developmental toxicity or adverse drug interactions.Birth Defects Research (Part B) 77:207–215, 2006. © 2006 Wiley‐Liss, Inc.
Chiral interaction in Gly‐capped N‐terminal motif of 310‐helix and domino‐type induction in helix sense
Authors: Ousaka Naoki , Inai Yoshihito , Okabe Takahiro
Published: June 2006

Chiral interaction of helical peptide with chiral molecule, and concomitant induction in its helix sense have been demonstrated in optically inactive nonapeptide (1) possessing Gly at its N‐terminus: H–Gly–(ΔZPhe–Aib)4–OCH3(1: ΔZPhe = Z‐dehydrophenylalanine; Aib = α‐aminoisobutyric acid). Spectroscopic measurements [mainly nuclear magnetic resonance (NMR) and circular diochroism (CD)] as well as theoretical simulation have been carried out for that purpose. Peptide1in the 310‐helix tends to adopt preferentially a right‐handed screw sense by chiral Boc‐L‐amino acid (Boc:t‐butoxycarbonyl). Induction in the helix sense through the noncovalent chiral domino effect should be derived primarily from the complex supported by the three‐point coordination on the N‐terminal sequence. Thus the 310‐helical terminus consisting of only α‐amino acid residues enables chiral recognition of the Boc‐amino acid molecule, leading to modulation of the original chain asymmetry. Dynamics in the helix‐sense induction also have been discussed on the basis of a low‐temperature NMR study. Furthermore, the inversion of induced helix sense has been achieved through solvent effects. © 2006 Wiley Periodicals, Inc. Biopolymers 83:337–351, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
A novel approach to chronic total occlusions: The crosser system
Authors: Melzi Gloria , Cosgrave John , Biondi‐Zoccai Giuseppe L. , Airoldi Flavio , Michev Iassen , Chieffo Alaide , Sangiorgi Giuseppe M. , Montorfano Matteo , Carlino Mauro , Colombo Antonio
Published: June 2006

Objectives: To evaluate safety and efficacy of the CROSSER CTO Recanalization System (CROSSER). Background: The CROSSER, a novel device dedicated to recanalization of chronic total occlusions (CTO), relies on a monorail catheter delivering vibrational energy to facilitate the crossing of occluded coronary arteries. Methods: We included de novo or restenotic occlusions in native coronary arteries with typically unfavorable characteristics and a prior failed guidewire attempt either performed in a previous procedure or just before the usage of the CROSSER. The end points analyzed were technical success (ability to cross or facilitate a guidewire crossing into the true lumen), angiographic success (<20% residual stenosis and TIMI flow grade 3), and clinical success (angiographic success and freedom from major adverse cardiac events at 30 days). Results: Twenty‐eight patients (30 lesions) were included. The morphology was blunt in 83.3% and the length of the occlusion was >20 mm in 76.6%. The median age of the CTO was 9 months (range 3–60 months). Technical success was obtained in 19 (63%) occlusions and angiographic success in 16 (53%): 26.3% in lesions with prior procedural failure and 73.7% when CROSSER was attempted after initial guidewire failure. Complications were: one guidewire perforation without consequences and one peri‐procedural myocardial infarction (MI). No events occurred within 30‐day follow‐up after discharge. Conclusions: In our experience, the CROSSER System is safe and increases the success of opening CTO refractory to guidewires. This novel device may represent an useful adjunct to the armamentarium of the interventional cardiologist. © 2006 Wiley‐Liss, Inc.
Surface‐climate attributes at Injisuthi Outpost, Drakensberg, and possible ramifications for weathering
Authors: Sumner Paul D. , Nel Werner
Published: June 2006

Aerial and sub‐aerial climatic data were collected from a station at 1920 m a.s.l. in the Injisuthi region of the South African Drakensberg. Sensors monitored air temperature, soil surface and rock surface temperature, for two rock types, over the summer and winter of 2001/2002. Rainfall was measured from the summer of 2001 to January 2004. These are the first rock and soil surface‐climate data to be collected for an exposed site at this altitude in the area. Rainfall over the two calendar years 2002 and 2003 was found to be below estimates for the region, but patterns imply numerous rock wetting and drying cycles in summer. At the site, air, rock and soil temperatures differ considerably on a diurnal basis with respect to both absolute temperature and daily ranges. Mean rock daily ranges, as conducive to possible thermal fatigue, are found to be similar in the summer and winter periods. Of the two rock types monitored, the darker coloured basalt attained higher maximum and marginally lower minimum temperatures than the sandstone. Soil frost did not occur at 2·5 cm depth, but rock did reach below −6 °C in winter. Both rock types maintain relatively high rock temperatures in winter (exceeding 25 °C), thus chemical weathering is probably only moisture restricted during this dry period. Findings highlight the importance of directly monitoring rock temperature when attempting to discern the rock weathering environment. Copyright © 2006 John Wiley & Sons, Ltd.
Neural correlates of consolidation in working memory
Authors: Mainy Nelly , Kahane Philippe , Minotti Lorella , Hoffmann Dominique , Bertrand Olivier , Lachaux Jean‐Philippe
Published: June 2006

Many of our daily activities rely on a brain system called working memory, which implements our ability to encode information for short‐term maintenance, possible manipulation, and retrieval. A recent intracranial study of patients performing a paradigmatic working memory task revealed that the maintenance of information involves a distributed network of oscillations in the gamma band (>40 Hz). Using a similar task, we focused on the encoding stage and targeted a process referred to as short‐term consolidation, which corresponds to the encoding of novel items in working memory. The paradigm was designed to manipulate the subjects' intention to encode: series of 10 letters were presented, among which only five had to be remembered, as indicated by visual cues preceding or following each letter. During this task we recorded the intracerebral EEG of nine epileptic patients implanted in mesiotemporal structures, perisylvian regions, and prefrontal areas and used time–frequency analysis to search for neural activities simultaneous with the encoding of the letters into working memory. We found such activities in the form of increases of gamma band activity in a set of regions associated with the phonological loop, including the Broca area and the auditory cortex, and in the prefrontal cortex, the pre‐ and postcentral gyri, the hippocampus, and the fusiform gyrus. Hum Brain Mapp, 2007. © 2006 Wiley‐Liss, Inc.
Dissociating stimulus‐driven semantic and phonological effect during reading and naming
Authors: Mechelli Andrea , Josephs Oliver , Lambon Ralph Matthew A. , McClelland James L. , Price Cathy J.
Published: June 2006

The aim of the present study was to dissociate the neural correlates of semantic and phonological processes during word reading and picture naming. Previous studies have addressed this issue by contrasting tasks involving semantic and phonological decisions. However, these tasks engage verbal short‐term memory and executive functions that are not required for reading and naming. Here, 20 subjects were instructed to overtly name written words and pictures of objects while their neuronal responses were measured using functional magnetic resonance imaging (fMRI). Each trial consisted of a pair of successive stimuli that were either semantically related (e.g., “ROBIN‐nest”), phonologically related (e.g., “BELL‐belt”), unrelated (e.g., “KITE‐lobster”), or semantically and phonologically identical (e.g., “FRIDGE‐fridge”). In addition, a pair of stimuli could be presented in either the same modality (word‐word or picture‐picture) or a different modality (word‐picture or picture‐word). We report that semantically related pairs modulate neuronal responses in a left‐lateralized network, including the pars orbitalis of the inferior frontal gyrus, the middle temporal gyrus, the angular gyrus, and the superior frontal gyrus. We propose that these areas are involved in stimulus‐driven semantic processes. In contrast, phonologically related pairs modulate neuronal responses in bilateral insula. This region is therefore implicated in the discrimination of similar, competing phonological and articulatory codes. The above effects were detected with both words and pictures and did not differ between the two modalities even with a less conservative statistical threshold. In conclusion, this study dissociates the effects of semantic and phonological relatedness between successive items during reading and naming aloud. Hum Brain Mapp, 2007. © 2006 Wiley‐Liss, Inc.
Novel porous gelatin scaffolds by overrun/particle leaching process for tissue engineering applications
Authors: Kang Hyun Goo , Kim So Yeon , Lee Young Moo
Published: June 2006

Porous gelatin scaffolds were prepared using a modified overrun process, which is a novel method for preparing a porous matrix by injecting air and mixing polymer solution at low temperature. The pores in the scaffolds formed by the overrun process exhibited a dual‐pore structure due to the injection of air bubbles and ice recrystallization. However, the morphology of the overrun‐processed gelatin scaffolds had closed pore structures. The closed pore structure was reformed into a uniformly distributed and interconnected open structure by the combination of the overrun process and a particle‐leaching technique (NaCl and sucrose). The mechanical strength and biodegradation rate of gelatin scaffolds were controlled by the matrix porosity and concentration of gelatin solution. Despite higher porosity, overrun processed gelatin scaffolds showed similar mechanical strength to freeze‐dried scaffolds. After 1 week of in vitro culturing, the fibroblasts in overrun‐processed scaffolds were widely distributed on the surface of the scaffold pores, whereas cells seeded in freeze‐dried scaffolds were mainly placed on the top and bottom of the scaffolds. Therefore, the overrun process combined with a particle‐leaching technique can be applied to fabricate porous scaffolds with a desirable cellular structure for tissue engineering applications. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Chitosan scaffolds for in vitro buffalo embryonic stem‐like cell culture: An approach to tissue engineering
Authors: Thein‐Han Wah W. , Kitiyanant Yindee
Published: June 2006

Three‐dimensional (3D) porous chitosan scaffolds are attractive candidates for tissue engineering applications. Chitosan scaffolds of 70, 88, and 95% degree of deacetylation (% DD) with the same molecular weight were developed and their properties with buffalo embryonic stem‐like (ES‐like) cells were investigated in vitro. Scaffolds were fabricated by freezing and lyophilization. They showed open pore structure with interconnecting pores under scanning electron microscopy (SEM). Higher % DD chitosan scaffolds had greater mechanical strength, slower degradation rate, lower water uptake ability, but similar water retention ability, when compared to lower % DD chitosan. As a strategy to tissue engineering, buffalo ES‐like cells were cultured on scaffolds for 28 days. It appeared that chitosan was cytocompatible and cells proliferated well on 88 and 95% DD scaffolds. In addition, the buffalo ES‐like cells maintained their pluripotency during the culture period. Furthermore, the SEM and histological study showed that the polygonal buffalo ES‐like cells proliferated well and attached to the pores. This study proved that 3D biodegradable highly deacetylated chitosan scaffolds are promising candidates for ES‐like cell based tissue engineering and this chitosan scaffold and ES cell based system can be used as in vitro model for subsequent clinical applications. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007
Fabrication and mechanical and tissue ingrowth properties of unidirectionally porous hydroxyapatite/collagen composite
Authors: Yunoki Shunji , Ikoma Toshiyuki , Tsuchiya Akio , Monkawa Akira , Ohta Kazushi , Sotome Shinichi , Shinomiya Kenichi , Tanaka Junzo
Published: June 2006

This study investigated the effects of the three‐dimensional (3‐D) pore structure of a porous hydroxyapatite/collagen (HAp/Col) composite on their mechanical properties and in vivo tissue ingrowth. The unique 3‐D pore structure, comprising unidirectionally interconnected pores, was fabricated by the unidirectional growth of ice crystals by using a cooling stage and a subsequent freeze‐drying process. The unidirectional pores had a spindle‐shaped cross section, and their size gradually increased from the bottom to the upper face. The porous composite showed an elastic property and anisotropic compressive strength for the pore directions. While the strength and modulus parallel to the pore axis were 1.3‐ and twofold higher than those of the porous composite with spherical pores formed randomly, the strength and modulus perpendicular to the pore axis showed the lowest values. The subcutaneous implantations revealed that when compared with the random pores, the unidirectional pores promote the ingrowth of the surrounding tissues into the pores. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007
Spin states in polynuclear clusters: The [Fe2O2] core of the methane monooxygenase active site
Authors: Herrmann Carmen , Yu Lian , Reiher Markus
Published: June 2006

The ability to provide a correct description of different spin states of mono‐ and polynuclear transition metal complexes is essential for a detailed investigation of reactions that are catalyzed by such complexes. We study the energetics of different total and local spin states of a dinuclear oxygen‐bridged iron(IV) model for the intermediate Q of the hydroxylase component of methane monooxygenase by means of spin‐unrestricted Kohn–Sham density functional theory. Because it is known that the spin state total energies depend systematically on the density functional, and that this dependence is intimately connected to the exact exchange admixture of present‐day hybdrid functionals, we compare total energies, local and total spin values, and Heisenberg coupling constants calculated with the established functionals BP86 and B3LYP as well as with a modified B3LYP version with an exact exchange admixture ranging from 0 to 24%. It is found that exact exchange enhances local spin polarization. As the exact exchange admixture increases, the high‐spin state is energetically favored, although the Broken‐Symmetry state always is the ground state. Instead of the strict linear variation of the energy splittings observed for mononuclear complexes, a slightly nonlinear dependence is found. The Heisenberg coupling constants JFe1Fe2—evaluated according to three different proposals from the literature—are found to vary from −129 to −494cm−1 accordingly. The experimental finding that intermediate Q has an antiferromagnetic ground state is thus confirmed. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1223–1239, 2006
Real‐time monitoring of radiofrequency ablation of rabbit liver by respiratory‐gated quantitative temperature MRI
Authors: Lepetit‐Coiffé Matthieu , Quesson Bruno , Seror Olivier , Dumont Erik , Le Bail Brigitte , Moonen Chrit T. W. , Trillaud Hervé
Published: June 2006

Purpose

To evaluate the feasibility and precision of magnetic resonance imaging (MRI) thermometry for monitoring radiofrequency (RF) liver ablation in vivo and predicting the size of the ablation zone.

Materials and Methods

At 1.5T, respiratory‐triggered real‐time MR temperature mapping (the proton resonance frequency (PRF) method) was used to monitor RF ablation in rabbit liver (N = 6) under free breathing. The size of the ablation zones, as assessed by histological analyses, was compared with that predicted from MR thermal dose (TD) maps or derived from conventional T1‐weighted (T1w), T2‐weighted (T2w), and T1w gadolinium (Gd)‐enhanced (T1w‐Gd) images acquired immediately after the ablation, and on days 4 and 8 postprocedure.

Results

MR temperature uncertainty remained under 1–2°C even during RF deposition. The TD maps were shown to be more predictive and precise than the other MR images, with an average predictive precision for the final ablation zone size of about 1 mm as compared to the histologically proven lesion on day 8.

Conclusion

Quantitative temperature MRI during RF ablation is feasible and offered a precise indication of the ablation zone size in this preclinical study based on the lethal dose threshold. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Background suppression in time‐resolved MR angiography without mask acquisition or operator intervention
Authors: Arunachalam Arjun , Thornton Frank J. , Block Walter. F.
Published: June 2006

Purpose

To suppress static and background tissue in time‐resolved MRA studies of the full thorax or abdomen without the need of a mask image or operator intervention.

Materials and Methods

The time course of each voxel is projected onto the orthogonal complement space of a matrix that spans static and linearly enhancing signal vectors. The norm of the solution, or the projection length, acts as a confidence measure for segmenting vascular and nonvascular tissue. Voxels whose confidence measures fall below an automatically detected threshold value are considered nonvascular. These voxels undergo an increasing level of suppression as the distance of the confidence measure from the threshold grows.

Results

MIPs of processed volunteer studies were compared to the original unaltered studies to assess the improvement in clarity of vascular structures. Qualitative and quantitative comparisons of full body MIPs verify excellent suppression of nonvascular tissue in time‐resolved three‐dimensional image volumes.

Conclusion

Contrast increased by an average factor of 13 in five volunteer studies, quantitatively emphasizing the improvement in MIP processing achieved by this method. Improvement in the clarity of vascular structures in subvolume MIPs is also demonstrated to emphasize the significant increase in ease with which regions of interest can be identified. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.