bluuebunny/crossref_metadata_2025 huggingface dataset:
A genetic analysis of ambulatory cardiorespiratory coupling
Authors: Kupper Nina , Willemsen Gonneke , Posthuma Danielle , De Boer Dolf , Boomsma Dorret I. , De Geus Eco J.C.
Published: March 2005

This study assessed the heritability of ambulatory heart period, respiratory sinus arrhythmia (RSA), and respiration rate and tested the hypothesis that the well‐established correlation between these variables is determined by common genetic factors. In 780 healthy twins and siblings, 24‐h ambulatory recordings of ECG and thorax impedance were made. Genetic analyses showed considerable heritability for heart period (37%–48%), RSA (40%–55%), and respiration rate (27%–81%) at all daily periods. Significant genetic correlations were found throughout. Common genes explained large portions of the covariance between heart period and RSA and between respiration rate and RSA. During the afternoon and night, the covariance between respiration rate and RSA was completely determined by common genes. This overlap in genes can be exploited to increase the power of linkage studies to detect genetic variation influencing cardiovascular disease risk.
Filter properties of root mean square successive difference (RMSSD) for heart rate
Authors: Berntson Gary G. , Lozano David L. , Chen Yun‐Ju
Published: March 2005

The root mean square successive difference (RMSSD) in heart period series is a time domain measure of heart period variability. The RMSSD is sensitive to high‐frequency heart period fluctuations in the respiratory frequency range and has been used as an index of vagal cardiac control. By transfer function simulations, the RMSSD statistic is shown to represent a high‐pass filter that effectively captures respiratory sinus arrhythmia but also passes lower frequency fluctuations that can include sympathetic influences. These simulations, together with analysis of actual heart period series, reveal that the RMSSD is biased by basal heart period. Although between‐subjects levels of RMSSD covary highly with spectral estimates of high‐frequency variability, within‐subject RMSSD change scores account for only 50–60% of the variance in spectral estimates. The present findings raise caveats in the applications and interpretation of the RMSSD statistic.
The effects washing carrots in solutions of hydrogen peroxide on the microbial and carotenoid quality of juice and salads
Authors: Hajduk Ewa , Surówka Krzysztof
Published: March 2005

This study assesses the microbial and carotenoid quality of juice and salad obtained from carrots washed in water with the addition of hydrogen peroxide (H2O2) in various concentrations, and for various lengths of treatment. The carrots were dipped in 1, 5 and 10% solutions of H2O2 for 1 or 2 min, and quality assessments made on the basis of the degree of microbial contamination, by determining total bacteria count and the most probable count of coliforms. Changes in the content of caroteinoid pigments, that is, α‐carotene, β‐carotene and lutein, were determined by the HPLC method as well as retinol equivalents. From the results obtained, it was deduced that the washing of carrots in 5 and 10% solutions of H2O2 for 2 min had the strongest antimicrobial effect, because it resulted in a reduction of microbial contamination by two logarithmic cycles. The same solutions produced a limited decrease in α‐carotene and β‐carotene content and the retinol equivalent in carrot juice, but they had no effect on the level of these constituents in salads.
Acute cardiodepressant effects induced by bolus intravenous administration of amiodarone in rabbits
Authors: Lessa Marcos Adriano , Tibiriçá Eduardo
Published: March 2005

Amiodarone is a potent anti‐arrhythmic with a large pharmacological spectrum that shares the mechanisms of action of all classes of anti‐arrhythmic drugs. Originally used in the treatment of supraventricular arrhythmias, it has also been used to treat ventricular tachyarrhythmias. The recent inclusion of amiodarone in the Advanced Cardiac Life Support protocols warrants the characterization of the hemodynamic profile resulting from the rapid venous administration of the drug. Thus, the main purpose of the present study was to investigate the acute hemodynamic profile resulting from the bolus i.v. injection of amiodarone, compared with bolus i.v. administration of lidocaine. We investigated the acute hemodynamic effects of amiodarone and lidocaine, in an experimental model of open‐chest pentobarbital‐anesthetized rabbits (n = 24). Amiodarone (5 mg/kg) induced immediate reductions in mean arterial pressure (MAP) of 32 ± 5% (P < 0.001), accompanied by reductions in cardiac contractility and relaxation, as assessed by left ventricular (LV) +dP/dtmaxand −dP/dtmax(40 ± 4 and 36 ± 4% respectively) (P < 0.001), heart rate (HR) 10 ± 1% (P < 0.05), cardiac output (CO) 24 ± 5% (P < 0.001) and systemic vascular resistance (SVR) 19 ± 3.5% (P < 0.05). Lidocaine (3 mg/kg) induced reductions in: MAP of 18 ± 7% (P < 0.001), LV +dP/dtmaxand −dP/dtmax(40 ± 5 and 22 ± 7% respectively) (P < 0.001), HR 7 ± 1% (P < 0.01) and CO of 23 ± 6% (P < 0.001). SVR increased by 9 ± 1.5% (P > 0.05). It is concluded that rapid i.v. administration of both amiodarone and lidocaine induces significant cardiovascular depression mainly characterized by immediate reductions in cardiac contractility.
Treatment of behavioural symptoms and dementia in Parkinson's disease
Authors: Hanagasi Hasmet A. , Emre Murat
Published: March 2005

Behavioural symptoms such as anxiety, depression and psychosis are common in Parkinson's disease (PD), and dementia occurs in about 90% of the patients. These symptoms can be more disabling than the motor dysfunction and they negatively impact quality of life, increase caregiver distress and are more frequently associated with nursing home placement. Depression can be treated with counselling and pharmacotherapy. Tricyclic antidepressants or selective serotonin reuptake inhibitors are widely used, but there is still need for controlled clinical trials. Management of psychosis in PD is complex and includes elimination of identifiable risk factors, reduction of polypharmacy and administration of atypical neuroleptics, which can alleviate psychotic symptoms without worsening motor functions. Clozapine is the best documented atypical neuroleptic shown to be effective against psychosis in PD patients. Cholinesterase inhibitors may prove additional benefit in psychotic PD patients. Recent evidence from small double‐blind and open‐label trials suggests that cholinesterase inhibitors may be effective in the treatment of dementia associated with PD.
Metropolitan Open‐Space Protection with Uncertain Site Availability
Authors: HAIGHT ROBERT G. , SNYDER STEPHANIE A. , REVELLE CHARLES S.
Published: March 2005

Abstract: Urban planners acquire open space to protect natural areas and provide public access to recreation opportunities. Because of limited budgets and dynamic land markets, acquisitions take place sequentially depending on available funds and sites. To address these planning features, we formulated a two‐period site selection model with two objectives: maximize the expected number of species represented in protected sites and maximize the expected number of people with access to protected sites. These objectives were both maximized subject to an upper bound on area protected over two periods. The trade‐off between species representation and public access was generated by the weighting method of multiobjective programming. Uncertainty was represented with a set of probabilistic scenarios of site availability in a linear‐integer formulation. We used data for 27 rare species in 31 candidate sites in western Lake County, near the city of Chicago, to illustrate the model. Each trade‐off curve had a concave shape in which species representation dropped at an increasing rate as public accessibility increased, with the trade‐off being smaller at higher levels of the area budget. Several sites were included in optimal solutions regardless of objective function weights, and these core sites had high species richness and public access per unit area. The area protected in period one depended on current site availability and on the probabilities of sites being undeveloped and available in the second period. Although the numerical results are specific for our study, the methodology is general and applicable elsewhere.
Pleistocene Reindeer and Global Warming
Authors: GRAYSON DONALD K. , DELPECH FRANÇOISE
Published: March 2005

Abstract: Current concerns for the future of reindeer and caribou (Rangifer tarandus) in the far north under conditions of global warming focus on the increased energetic and predation costs associated with warmer winters and on vegetation change and increased insect harassment caused by warmer summers. At the Grotte XVI archaeological site (Dordogne, southwestern France), episodes of summer warming between about 36,000 and 12,000 radiocarbon years ago appear to be associated with lowered relative abundances of reindeer. As the Pleistocene ended and summer temperatures climbed higher, reindeer were extirpated from southern France. A similar phenomenon appears to have occurred here during the prior Eemian interglacial. These records suggest that increased summer temperatures under conditions of global warming may have a direct negative effect on reindeer and caribou populations, including a northward displacement of their southern distributional boundary.
Metapopulation Extinction Risk under Spatially Autocorrelated Disturbance
Authors: KALLIMANIS A. S. , KUNIN W. E. , HALLEY J. M. , SGARDELIS S. P.
Published: March 2005

Abstract: Recent extinction models generally show that spatial aggregation of habitat reduces overall extinction risk because sites emptied by local extinction are more rapidly recolonized. We extended such an investigation to include spatial structure in the disturbance regime. A spatially explicit metapopulation model was developed with a wide range of dispersal distances. The degree of aggregation of both habitat and disturbance pattern could be varied from a random distribution, through the intermediate case of a fractal distribution, all the way to complete aggregation (single block). Increasing spatial aggregation of disturbance generally increased extinction risk. The relative risk faced by populations in different landscapes varied greatly, depending on the disturbance regime. With random disturbance, the spatial aggregation of habitat reduced extinction risk, as in earlier studies. Where disturbance was spatially autocorrelated, however, this advantage was eliminated or reversed because populations in aggregated habitats are at risk of mass extinction from coarse‐scale disturbance events. The effects of spatial patterns on extinction risk tended to be reduced by long‐distance dispersal. Given the high levels of spatial correlation in natural and anthropogenic disturbance processes, population vulnerability may be greatly underestimated both by classical (nonspatial) models and by those that consider spatial structure in habitat alone.
Adaptive Units for Conservation: Population Distinction and Historic Extinctions in the Island Scrub‐Jay
Authors: DELANEY KATHLEEN S. , WAYNE ROBERT K.
Published: March 2005

Abstract:  The Island Scrub‐Jay (Aphelocoma insularis) is found on Santa Cruz Island, California, and is the only insular bird species in the continental United States. We typed seven microsatellite loci and sequenced a portion of the mitochondrial DNA control region of Island Scrub‐Jays and their closest mainland relative, the Western Scrub‐Jay (Aphelocoma californica), to assess levels of variability and effective population size and to examine the evolutionary relationship between the two species. The estimated female effective population size, Nef, of the Island Scrub‐Jay was 1603 (90% confidence interval: 1481–1738) and was about 7.5% of the size of the mainland species. Island and Western Scrub‐Jays have highly divergent control‐region sequences, and the value of 3.14 ± 0.09% sequence divergence between the two species suggests a divergence time of approximately 151,000 years ago. Because the four northern Channel Islands were joined as one large island as recently as 11,000 years ago, extinctions must have occurred on the three other northern Channel islands, Santa Rosa, San Miguel, and Anacapa, highlighting the vulnerability of the remaining population. We assessed the evolutionary significance of four island endemics, including the Island Scrub‐Jay, based on both genetic and adaptive divergence. Our results show that the Island Scrub‐Jay is a distinct species of high conservation value whose history and adaptive potential is not well predicted by study of other island vertebrates.
A Freshwater Classification Approach for Biodiversity Conservation Planning
Authors: HIGGINS JONATHAN V. , BRYER MARK T. , KHOURY MARY L. , FITZHUGH THOMAS W.
Published: March 2005

Abstract:  Freshwater biodiversity is highly endangered and faces increasing threats worldwide. To be complete, regional plans that identify critical areas for conservation must capture representative components of freshwater biodiversity as well as rare and endangered species. We present a spatially hierarchical approach to classify freshwater systems to create a coarse filter to capture representative freshwater biodiversity in regional conservation plans. The classification framework has four levels that we described using abiotic factors within a zoogeographic context and mapped in a geographic information system. Methods to classify and map units are flexible and can be automated where high‐quality spatial data exist, or can be manually developed where such data are not available. Products include a spatially comprehensive inventory of mapped and classified units that can be used remotely to characterize regional patterns of aquatic ecosystems. We provide examples of classification procedures in data‐rich and data‐poor regions from the Columbia River Basin in the Pacific Northwest of North America and the upper Paraguay River in central South America. The approach, which has been applied in North, Central, and South America, provides a relatively rapid and pragmatic way to account for representative freshwater biodiversity at scales appropriate to regional assessments.
Monitoring and Evaluation in Conservation: a Review of Trends and Approaches
Authors: STEM CAROLINE , MARGOLUIS RICHARD , SALAFSKY NICK , BROWN MARCIA
Published: March 2005

Abstract:  There is growing recognition among conservation practitioners and scholars that good project management is integrally linked to well‐designed monitoring and evaluation systems. Most conservation organizations have attempted to develop and implement monitoring and evaluation systems, often with mixed results. One problem seems to be that organizations are trying to build their systems from scratch, overlooking lessons learned from the many efforts to develop useful and practical monitoring and evaluation approaches. Thus, we undertook a review of monitoring and evaluation approaches in conservation and other fields including international development, public health, family planning, education, social services, and business. Here, we present our results for the field of conservation. We categorized the considerable variety of monitoring and evaluation approaches into four broad purposes: basic research; accounting and certification; status assessment; and effectiveness measurement. We focus here on status assessment and effectiveness measurement. Specific lessons that emerged follow: different monitoring and evaluation needs require different approaches; conceptual similarities are widespread among prevailing approaches; inconsistent language impedes communication; confusion among monitoring and evaluation components hinders practitioner ability to choose the appropriate component; and monitoring only quantitative biological variables is insufficient. We suggest that the conservation community continue support of collaborative initiatives to improve monitoring and evaluation, establish clear definitions of commonly used terms, clarify monitoring and evaluation system components, apply available approaches appropriately, and include qualitative and social variables in monitoring efforts.
Armageddon Versus Extinction
Authors: ORR DAVID W.
Published: March 2005

Note from the Editor: Some readers may feel that topics such as politics and religion are inappropriate for a scientific journal. Our “Conservation in Context” column, however, is intended to cover the entire spectrum of the context within which the science of conservation biology must operate. Thus, we freely and openly explore topics in this column that ordinarily are not addressed in scientific journals, to better understand the real‐world constraints and opportunities that define how conservation science is applied in a complex world.
Role of phosphorylation in p53 acetylation and PAb421 epitope recognition in baculoviral and mammalian expressed proteins
Authors: Warnock Lorna J. , Raines Sally A. , Mee Trevor R. , Milner Jo
Published: March 2005

Post‐translational modifications, such as phosphorylation and acetylation of the tumour suppressor protein p53, elicit important effects on the function and the stability of the resultant protein. However, as phosphorylation and acetylation are dynamic events subject to complex controls, elucidating the relationships between phosphorylation and acetylation is difficult. In the present study we sought to address this problem by comparing full‐length wild‐type p53 with full‐length p53 proteins mutated at specific phosphorylation targets. Recombinant murine p53 proteins were expressed in insect cells (using the baculoviral expression vector system) and in a mammalian in vitro transcription/translation reticulocyte lysate system. In p53 proteins derived from baculoviral expression vectors, S37A (but not S37D) was found to abrogate phosphorylation at S15. Lysine 382 (K382) is constitutively acetylated and was shown to form part of the epitope recognized by PAb421. Lysine 373 (K373) was only acetylated following substitutions at S315 (S315A or S315D) or at S378 (S378A). Importantly, in baculoviral expressed proteins, PAb421 reactivity was independent of K373 acetylation status, indicating that acetylation at K382 specifically determines the PAb421 epitope.
Novel aggregate formation of a frame‐shift mutant protein of tissue‐nonspecific alkaline phosphatase is ascribed to three cysteine residues in the C‐terminal extension
Authors: Komaru Keiichi , Ishida Yoko , Amaya Yoshihiro , Goseki‐Sone Masae , Orimo Hideo , Oda Kimimitsu
Published: March 2005

In the majority of hypophosphatasia patients, reductions in the serum levels of alkaline phosphatase activity are caused by various missense mutations in the tissue‐nonspecific alkaline phosphatase (TNSALP) gene. A unique frame‐shift mutation due to a deletion of T at cDNA number 1559 [TNSALP (1559delT)] has been reported only in Japanese patients with high allele frequency. In this study, we examined the molecular phenotype of TNSALP (1559delT) using in vitro translation/translocation system and COS‐1 cells transiently expressing this mutant protein. We showed that the mutant protein not only has a larger molecular size than the wild type enzyme by ≈ 12 kDa, reflecting an 80 amino acid‐long extension at its C‐terminus, but that it also lacks a glycosylphosphatidylinositol anchor. In support of this, alkaline phosphatase activity of the cells expressing TNSALP (1559delT) was localized at the juxtanucleus position, but not on the cell surface. However, only a limited amount of the newly synthesized protein was released into the medium and the rest was polyubiquitinated, followed by degradation in the proteasome. SDS/PAGE and analysis by sucrose‐density‐gradient analysis indicated that TNSALP (1559delT) forms a disulfide‐bonded high‐molecular‐mass aggregate. Interestingly, the aggregate form of TNSALP (1559delT) exhibited a significant enzyme activity. When all three cysteines at positions of 506, 521 and 577 of TNSALP (1559delT) were replaced with serines, the aggregation disappeared and instead this modified mutant protein formed a noncovalently associated dimer, strongly indicating that these cysteine residues in the C‐terminal region are solely responsible for aggregate formation by cross‐linking the catalytically active dimers. Thus, complete absence of TNSALP on cell surfaces provides a plausible explanation for a severe lethal phenotype of a homozygote hypophosphatasia patient carrying TNSALP (1559delT).
Structural Modeling of Profiled Edge Laminae (PEL) Tools
Authors: Walczyk Daniel F. , Im Yong-Tai
Published: March 2005

Profiled Edge Laminae (PEL) tooling is a thick-layer Rapid Tooling (RT) method that involves assembling an array of laminae—each having a uniquely profiled and beveled top edge—together in a precise and repeatable manner by registering each lamina’s bottom edge and an adjacent side edge to a fixture that has precisely machined edges. The processed laminae are then clamped or bonded into a rigid tool for use in manufacturing (e.g., as a thermoforming mold). Because a PEL tool is inherently more compliant than a solid tool, manufacturing personnel who are considering its use are understandably concerned about excessive tool deflection, which may lead to unacceptable changes in tool shape, decreased tool life due to high stresses and increased wear, and part dimensional errors. The ability to predict deflection (i.e., shape changes) in a laminated construction, either clamped or bonded, is extremely important to promote widespread acceptance of the PEL method. This paper develops basic analytical structural models for both clamped and adhesively bonded PEL tools, which will allow tooling designers and engineers to predict how changing various design parameters (e.g., the number of laminations, tool material, unclamped length of laminations, bonding adhesive, adhesive thickness) affect a tool’s stiffness. Deflection results from these models are shown to agree very well with experimental results. The usefulness of these analytical models is then shown by a design example. Finally, FEM modeling of PEL tools is demonstrated and shown to provide results that agree reasonably well with experimental results. FEM modeling may allow for prediction of shape changes to a PEL tool characterized by a complex three-dimensional surface and subject to arbitrary structural loads.
Adhesive Joining Process and Joint Property With Low Melting Point Filler
Authors: Yasuda Kiyokazu , Kim Jong-Min , Fujimoto Kozo
Published: March 2005

In order to conquer the limitation of conventional solders and adhesives used in electronics packaging, a novel self-organized joining process using conductive adhesive with low melting point alloy was proposed. As a basic characteristic of the adhesive paste, the differential scanning calorimetry analysis was carried out. Joint morphology, the formation of conduction path, and the self-organized characteristics were examined. Melting fillers were preserved their initial spherelike form for nonreductive adhesive, although enlargement of the alloy colony occurred in the case of the reductive polymer. The formation of a conduction path can be controlled significantly by varying the resin performance and the process parameters such as the joint height and the volume fraction of filler. The self-organized characteristic was observed on the copper line patterned glass-epoxy substrate. The matched pair of substrates could be interconnected with excellent self-organized joint.
Experiment and Numerical Analysis of the Residual Stresses in Underfill Resins for Flip Chip Package Applications
Authors: Sham Man-Lung , Kim Jang-Kyo
Published: March 2005

Polymeric encapsulant is widely used to protect the integrated circuit chips and thus to enhance the reliability of electronic packages. Residual stresses are introduced in the plastic package when the polymer is cooled from the curing temperature to ambient, from which many reliability issues arise, including warpage of the package, premature interfacial failure, and degraded interconnections. Bimaterial strip bending experiment has been employed successfully to monitor the evolution of the residual stresses in underfrill resins for flip chip applications. A numerical analysis is developed to predict the residual stresses, which agree well with the experimental measurements. The changes of material properties, such as flexural modulus and coefficient of thermal expansion, of the resins with temperature are taken into account in the finite element analysis.
Numerical Procedure for the Laminar Developed Flow in a Helical Square Duct
Authors: Sakalis V. D. , Hatzikonstantinou P. M. , Papadopoulos P. K.
Published: March 2005

The incompressible fully developed laminar flow in a helically duct of square cross section is studied expressing the governing equations in terms of an orthogonal coordinate system. Numerical results are obtained with the described continuity, vorticity, and pressure (CVP) numerical method using a colocation grid for all variables. Since there are not approximations, the interaction effects of curvature, torsion and axial pressure gradient on the velocity components and the friction factor are presented. The results show that the torsion deforms substantially the symmetry of the two centrifugal vortices of the secondary flow, which for large values of torsion combined with small curvature tend to one vortex covering the whole cross section. The friction factor decreases for torsion in the range 0 to 0.1 and increases as the torsion increases further, a behavior which is more profound as the Dean number increases. Our results are stable for the calculated Dean numbers.
RESULTS OF ENDOSCOPIC MANAGEMENT OF PRIMARY VERSUS RECURRENT CARPAL TUNNEL SYNDROME IN LONG-TERM HAEMODIALYSIS PATIENTS
Authors: Yoshida Aya , Okutsu Ichiro , Hamanaka Ikki , Motomura Tomohide
Published: March 2005

In long-term haemodialysis patients, carpal tunnel syndrome (CTS) frequently occurs as a result of amyloid deposition, originating from beta-2 microglobulin, to the flexor retinaculum, paratenons and tendons themselves, which leads to an increase in carpal canal pressure and compression of the median nerve. Surgical procedures can rectify the condition, but continuing maintenance haemodialysis sometimes causes recurrence.

We endoscopically operated 1848 hands primarily, 104 recurrent post-endoscopic procedure hands and 130 recurrent post-open procedure hands using the Universal Subcutaneous Endoscope (USE) system, then analysed clinical symptoms and electrophysiological recovery for more than six months post-operatively. The patients were satisfied with the clinical results. Optimal electrophysiological improvements were reported. There were no statistical differences between three groups, except in recovery of touch sensation, which was better in the post-endoscopic group than in the post-open group. There were no complications in this series.

Our minimally invasive endoscopic procedure, using the USE system, is safe and effective for primary and recurrent CTS in haemodialysis patients.
DORSAL PLATING FOR COMMINUTED INTRA-ARTICULAR FRACTURES OF THE DISTAL END OF THE RADIUS
Authors: Osada D. , Tamai K. , Iwamoto A. , Fujita S. , Saotome K.
Published: March 2005

Forty-one dorsally displaced intra-articular fractures of the distal radius were treated by open reduction and internal fixation with the dorsal Symmetry® plates. The average age at the time of the injury was 49 years. An average follow-up period was 15 months. The final radial length averaged 11 mm, radial inclination 23°, volar tilt 7°, ulnar variance 1.5 mm, and articular incongruity 0.3 mm. According to the Gartland and Werly scales, 36 fractures were excellent and five were good. However, ulnar variance increased more than 3 mm during follow-up in eight patients, and volar tilt increased more than 5° during follow-up in ten patients. Use of dorsal Symmetry® plate is effective for unstable comminuted intra-articular distal radius fractures, but severely comminuted fractures may possibly undergo re-displacement post-operatively.
SUPERFICIAL BRANCH OF THE RADIAL NERVE PIERCING THE BRACHIORADIALIS TENDON TO BECOME SUBCUTANEOUS: AN ANATOMICAL VARIATION WITH CLINICAL RELEVANCE
Authors: Tryfonidis M. , Jass G. K. , Charalambous C. P. , Jacob S.
Published: March 2005

We dissected 20 preserved Caucasian cadaveric upper limbs looking at the relation of the superficial branch of the radial nerve (SBRN) to the brachioradialis tendon. SBRN emerged from deep to superficial position by piercing the brachioradialis tendon near its dorsal border in four limbs. The resulting dorsal tendinous band compressed the nerve and prevented longitudinal gliding movement during ulnar flexion. This is likely to increase the risk of chronic compression neuropathy (Wartenberg's syndrome). In two of these four limbs, there was a communication between the SBRN and lateral cutaneous nerve of the forearm. No such communication was found in the remaining 16 forearms. This communication could contribute to the minimal area of sensory loss observed in Wartenberg's syndrome. We recommend that this anatomical anomaly is looked for and if present dealt with during surgical treatment of Wartenberg's syndrome, as it is likely to predispose to chronic compression neuropathy.
A biomimetic tissue from cultured normal human urothelial cells: analysis of physiological function
Authors: Cross W. R. , Eardley I. , Leese H. J. , Southgate J.
Published: March 2005

The urinary bladder and associated tract is lined by the urothelium. Once considered as just an impermeable epithelium, it is becoming evident that the urothelium not only functions as a volume-accommodating urinary barrier but has additional roles, including sensory signaling. Lack of access to normal human urothelium has hampered physiological investigation, and although cell culture systems have been developed, there has been a failure to demonstrate that normal human urothelial (NHU) cells grown in vitro retain the capacity to form a functional differentiated urothelium. The aim of this study was to develop a biomimetic human urothelium from NHU cell cultures. Urothelial cells isolated from normal human urothelium and serially propagated as monolayers in serum-free culture were homogeneous and adopted a proliferative, nondifferentiated phenotype. In the presence of serum and physiological concentrations of calcium, these cells could be reproducibly induced to form stratified urothelia consisting of basal, intermediate, and superficial cells, with differential expression of cytokeratins and superficial tight junctions. Functionally, the neotissues showed characteristics of native urothelium, including high transepithelial electrical resistance of >3,000 Ω·cm2, apical membrane-restricted amiloride-sensitive sodium ion channels, basal expression of Na+-K+-ATPase, and low diffusive permeability to urea, water, and dextran. This model represents major progress in developing a biomimetic human urothelial culture model to explore molecular and functional relationships in normal and dysfunctional bladder physiology.
Development of Hepatocellular Carcinoma after Interferon Therapy in Chronic Hepatitis C
Authors: Izumi Namiki , Yasuhiro Asahina , Kurosaki Masayuki , Onuki Yuko , Nishimura Yuki , Inoue Kazunari , Ueda Ken , Tsuchiya Kaoru , Nakanishi Hiroyuki , Uchihara Masakatsu , Miyake Shozo
Published: March 2005

Objectives: Although the incidence of hepatocellular carcinoma (HCC) has been shown to be reduced after interferon (IFN) monotherapy in chronic hepatitis C, the risk factors for the development of HCC have not been fully understood. The aim of this study is to investigate the risk factors for the development of HCC after IFN in chronic hepatitis C as well as whether the incidence of HCC will be reduced by ribavirin and IFN combination therapy or not. Methods: 495 patients with chronic hepatitis C and which received IFN monotherapy were followed and the incidence and risk factors for the development of HCC were examined. On the other hand, in the patients which received ribavirin and IFN combination therapy, the sustained response rate was assessed and the reduction rate of HCC development was predicted. Results: Multivariate analysis by the Cox proportional hazard model revealed that the risk factors for HCC development were age, male gender, severe fibrosis and outcome of IFN therapy. On ribavirin and IFN combination therapy, the sustained response rate reached 17.3% in genotype 1b and 74% in genotypes 2a and 2b infection, thus reducing 20% of the estimated incidence of HCC. Conclusion: To reduce the incidence of HCC in chronic hepatitis C, improvement of the sustained response rate is an essential issue, and ribavirin and IFN combination therapy shows to be promising.
Prevalence and Genotypes of Hepatitis G Virus among Hemodialysis Patients in Eastern Anatolia, Turkey
Authors: Ozdarendeli Aykut , Toroman Zulal A. , Kalkan Ahmet , Kilic Süleyman S. , Ozden Mehmet , Doymaz Mehmet Z.
Published: March 2005

Objectives: To study the prevalence and genotype distribution of hepatitis G virus (HGV) in hemodialysis patients in East Anatolia, Turkey. Subjects and Materials: Eighty-nine hemodialysis patients and 30 healthy individuals were analyzed by using reverse-transcriptase nested polymerase chain reaction with primers specific for 5′ untranslated region. HGV genotyping was performed by PCR and three randomly selected HGV-positive samples were sequenced. Results: Of the 89 hemodialysis patients, HGV RNA was detected in 9 (10.2%). All of our isolates were assigned to genotype 2. Conclusion: Our results showed that hemodialysis patients carry the risk for HGV infection in East Anatolia, Turkey.
Prevalence, Resource Utilization and Costs of Vascular Dementia Compared to Alzheimer’s Dementia in a Population Setting
Authors: Sicras A. , Rejas J. , Arco S. , Flores E. , Ortega G. , Esparcia A. , Suárez A. , Gordillo M.J.
Published: March 2005

Objectives: To determine the prevalence of dementia and to measure the monetary impact and health resources utilization of vascular dementia (VD) compared to Alzheimer’s dementia (AD) in persons aged over 64 years in a population setting. Methods: Retrospective, cross-sectional study. In the initial phase, information was obtained on specific clinical characteristics from the subjects with an active diagnosis of dementia. The second phase consisted of a clinical evaluation and validation of the cases. Mini-Mental State Examination was used to assess cognitive impairment. Dementia and its subtypes were determined using established diagnostic criteria. Information was obtained on the use of health care resources (direct costs) and the number of hours devoted by the primary caregiver (indirect costs) for patients with a documented diagnosis of AD or VD within the last 6 months prior to the interview. A multiple logistic regression analysis was performed to correct the model. Results: A total of 6,004 subjects were analyzed, 258 with diagnosis of dementia (overall prevalence: 4.3%). An evaluation was made of 224 patients, and gross prevalence of AD and VD was 2.4 and 1.0%, respectively. Cost per patient per semester was EUR 8,086 for AD and EUR 11,039 for VD (p = 0.016). 85.5% of the cost was attributable to primary caregiver time in AD and 84.4% in VD. Conclusions: The prevalence of AD and VD increases with age. No sociodemographic differences were seen between AD and VD. Costs associated with health care resource and primary caregiver utilization were high, being higher in VD than in AD.
Diagnostic Accuracy of Mini-Mental Status Examination and Revised Hasegawa Dementia Scale for Alzheimer’s Disease
Authors: Kim K.W. , Lee D.Y. , Jhoo J.H. , Youn J.C. , Suh Y.J. , Jun Y.H. , Seo E.H. , Woo J.I.
Published: March 2005

To compare the diagnostic accuracies of the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental Status Examination (MMSE) for Alzheimer’s diseases (AD), we administered them simultaneously to 82 AD patients and 82 age- and sex-matched nondemented control subjects. The area under the receiver operator curve (AUC) for AD of the HDS-R (AUCHDS-R) and MMSE (AUCMMSE) were bigger than 0.90 indicating that both tests are useful for detecting AD. However, AUCHDS-R (0.952) was significantly larger than that of the AUCMMSE (0.902) regardless of the educational level of the subjects, indicating that the HDS-R is more accurate than MMSE in diagnosing AD. Moreover, the superiority of the HDS-R (AUCHDS-R = 0.894) to the MMSE (AUCMMSE = 0.704) remained significant in mild AD patients alone, who are the focus of screening. In conclusion, the HDS-R is better than the MMSE as a screening instrument for AD.
Cholinesterase Inhibitor Affects the Amyloid Precursor Protein Isoforms in Patients with Alzheimer’s Disease
Authors: Liu H.C. , Chi C.W. , Ko S.Y. , Wang H.C. , Hong C.J. , Lin K.N. , Wang P.N. , Liu T.Y.
Published: March 2005

An altered platelet ratio of amyloid precursor protein (APP) isoforms might be a diagnostic, predictive, or therapeutic marker for Alzheimer’s disease (AD). Our purpose was to test the hypothesis that this ratio might serve as a therapeutic marker for AD patients treated with the cholinesterase inhibitor, galantamine. Thirty-nine patients (mean age 76.6 ± 9.4 years) with AD were treated with galantamine for 12 weeks. Patients were evaluated at baseline, 4 and 12 weeks by cognitive testing along with a determination of their platelet APP isoform ratio. Western blotting was performed to calculate the APP isoform ratio. At the end of the treatment, cognitive scores significantly improved, and the ratio of the high-molecular-weight (130 kDa) isoform to the low-molecular-weight (110–106 kDa) isoforms increased. These results suggest that cholinesterase inhibition might be involved in APP processing.
A Comparison of the Two β-Blockers Carvedilol and Atenolol on Left Ventricular Ejection Fraction and Clinical Endpoints after Myocardial Infarction
Authors: Jonsson Gisli , Abdelnoor Michael , Müller Carl , Kjeldsen Sverre Erik , Os Ingrid , Westheim Arne
Published: March 2005

Background: β-Blockers have been found to reduce mortality and morbidity in postmyocardial infarction patients. However, it is not fully understood whether all β-blockers have similar favourable cardiovascular effects. The aim of this study was to compare the effects of carvedilol and atenolol on global and regional left ventricular ejection fraction (LVEF) and on predefined cardiovascular endpoints. Methods: In a single-centre, randomized, open, endpoint-blinded, parallel group study, 232 patients with acute myocardial infarction were randomized to treatment with carvedilol or atenolol. LVEF was measured by gated blood pool scintigraphy during the first week and after 12 months. The treatment was given orally within 24 h. The mean dose was 36.2 and 72.1 mg in the carvedilol and atenolol groups, respectively. Results: No significant difference was found between the two study groups in the mean global and regional LVEF. There tended to be fewer first serious cardiovascular events in the carvedilol compared with the atenolol group (RR = 0.83, 95% CI 0.56–1.23, p = 0.39). Cold hands and feet were observed less frequently in the carvedilol group (20 vs. 33%, p = 0.025). Conclusion: In patients following an acute myocardial infarction, no difference in either global or regional LVEF was observed between baseline and 12 months when treatment with carvedilol was compared with atenolol.
Association of Ankle-Brachial Index with Severity of Angiographic Coronary Artery Disease in Patients with Peripheral Arterial Disease and Coronary Artery Disease
Authors: Sukhija Rishi , Aronow Wilbert S. , Yalamanchili Kiran , Peterson Stephen J. , Frishman William H. , Babu Sateesh
Published: March 2005

The ankle-brachial index (ABI) was correlated with the severity of coronary artery disease (CAD) in 273 patients, mean age 71 years, with peripheral arterial disease and angiographically obstructive CAD (>50% occlusion). Of 155 patients with an ABI <0.40, 130 (84%) had 3- or 4-vessel CAD, 17 (11%) had 2-vessel CAD and 8 (5%) had 1-vessel CAD. Of 80 patients with an ABI of 0.40–0.69, 37 (46%) had 3- or 4-vessel CAD, 33 (41%) had 2-vessel CAD and 10 (13%) had 1-vessel CAD. Of 38 patients with an ABI of 0.70–0.89, 10 (26%) had 3- or 4-vessel CAD, 16 (42%) had 2-vessel CAD and 12 (32%) had 1-vessel CAD. The lower the ABI, the higher the prevalence of 3- or 4-vessel CAD and the lower the prevalence of 1-vessel CAD.
Heart Failure in Diabetes mellitus: Clinical Features and Prognostic Implications
Authors: Gorelik Oleg , Almoznino-Sarafian Dorit , Alon Irena , Shteinshnaider Miriam , Chachashvily Shulamit , Tzur Irma , Modai David , Cohen Natan
Published: March 2005

We defined the prevalence and impact on survival of clinical bedside variables in 385 patients with symptomatic congestive heart failure (CHF), of whom there were 176 with and 209 without diabetes mellitus. Patients were consecutively hospitalized and admitted for various acute conditions. Following discharge all-cause mortality was recorded. Prevalence and association of various variables with mortality were statistically analyzed. Prevailing in the diabetics versus nondiabetics were younger age (p < 0.05), pulmonary edema on admission (p = 0.002), using furosemide >80 mg/day (p < 0.01) for >1 year (p < 0.01) and hyponatremia (p = 0.01). Less prevalent were chronic lung disease (p < 0.01) and cardiac arrhythmias (p = 0.001). On follow-up extending up to 60 months, diabetic patients, especially those with fasting blood glucose levels on admission ≧180 mg/dl, survived for a shorter period of time than nondiabetics (p = 0.02). Associated with increased mortality in the diabetic group were female gender (p = 0.04), furosemide ≧80 mg/day (p < 0.001) and renal dysfunction (RD; p = 0.04). The respective variables in the nondiabetics were advanced age (p < 0.001) and RD (p = 0.002). Although they were younger, diabetic patients presented more severe CHF. It is recommended that special attention should be given to diabetic females, those using higher furosemide dosages and those suffering from RD.
Body Temperature – A Marker of Infarct Size in the Era of Early Reperfusion
Authors: Ben-Dor Itsik , Haim Moti , Rechavia Eldad , Murininkas Daniel , Nahon Merav , Harell Daniella , Porter Avital , Iakobishvili Zaza , Scapa Erez , Battler Alexander , Hasdai David
Published: March 2005

We measured body temperature in 40 consecutive patients treated for a first ST elevation acute myocardial infarction (AMI) with primary percutaneous coronary interventions. Left ventricular function was assessed by echocardiography, and blood samples were drawn for highly sensitive C-reactive protein (hs-CRP), white blood cell (WBC) count, fibrinogen, creatine kinase (CK), and cardiac troponin I levels (cTnI). The median (25th, 75th quartiles) peak 24-hour temperature was 37.4°C (36.9°C, 37.6°C). Variables significantly associated with peak 24-hour temperature were CK (p = 0.01, r = 0.42), wall motion index (p = 0.01, r = 0.41), hs-CRP (p = 0.01, r = 0.41), and cTnI (p = 0.03, r = 0.35). There was no significant correlation between peak 24-hour temperature and WBC count (p = 0.39, r = 0.14) and fibrinogen (p = 0.12, r = 0.21). Thus, peak 24-hour body temperature after ST elevation AMI probably reflects infarct size rather than a nonspecific inflammatory response.
Dilution Method to Refold Bacterially Expressed Recombinant Der f 2 and Der p 2 to Exhibit the Secondary Structure and Histamine-Releasing Activity of Natural Allergens
Authors: Takai Toshiro , Takaoka Masatoshi , Yasueda Hiroshi , Okumura Ko , Ogawa Hideoki
Published: March 2005

Background: Structurally refolded recombinant forms of major house dust mite group 2 allergens, Der f 2 and Der p 2, expressed in Escherichia coli, were prepared by solubilizing the insoluble products with urea and subsequently dialyzing against buffer. In this study, we determined conditions for refolding the urea-denatured recombinant Der f 2 and Der p 2 by one-step dilution as an alternative to dialysis, which requires several steps of handling and much time and cost. Methods: The insoluble bacterial product containing recombinant Der f 2 was solubilized with a buffer containing 8 M urea, and the solution was diluted to various urea concentrations. The refolding efficiency in each dilution was estimated from the height of the peak corresponding to the folded recombinant Der f 2 and that containing the aggregated form on anion exchange chromatography. The structure and allergenicity of the purified recombinant Der f 2 and Der p 2 refolded using the dilution method were analyzed based on circular dichroism and a basophil histamine-releasing assay, respectively. Results: Although the refolding efficiency decreased as the urea concentration in the dilution increased, experimental conditions whereby the protein and urea concentrations in the dilution were less than 0.5 mg/ml and 0.8 M, respectively, achieved maximum refolding efficiency. The recombinant allergens prepared by the dilution method exhibited the secondary structure and histamine-releasing activity of natural allergens purified from mite culture. Conclusions: The dilution method established in this study is more convenient in terms of handling, time, and cost than the dialysis method and will be useful for large-scale production and for the preparation of numbers of mutants to analyze IgE epitopes.
Airway Closure after Antigen Challenge in Cynomolgus Monkeys: Effect of the Histamine H1 Receptor Antagonist, Chlorpheniramine Maleate
Authors: Skeans Susan , Lamca James E. , House Aileen , Celly Chander S. , Hey John A. , Chapman Richard W.
Published: March 2005

Background: Airway closure is frequently observed in human asthma. However, limited information exists on the factors that cause this condition. In this study, an allergic cynomolgus monkey model was used to characterize the condition of airway closure and assess the contribution of histamine H1 receptors to this response. Methods: Oscillatory lung mechanics, arterial blood gases during ventilation on 100% O2 and functional residual capacity (FRC) assessed by helium dilution were measured before and then 10 min and 24 h after Ascaris aerosol challenge in 12 male Ascaris-sensitive cynomolgus monkeys. The monkeys were pretreated with intravenous saline or chlorpheniramine maleate (0.3 mg/kg) in a randomized crossover design. Results: Ascaris challenge produced a large increase in airway resistance, an increase in lung tissue damping (G) that measures ventilation inhomogeneity in the lung, a reduction in arterial oxygen tension (PaO2) during ventilation on 100% O2 and a reduction in FRC. These effects were seen 10 min after the Ascaris challenge, but by 24 h, these parameters had returned close to the baseline values. Chlorpheniramine maleate (0.3 mg/kg, i.v.) produced a 12-fold shift in the histamine bronchoconstrictor dose-response curve. Pretreatment of monkeys with chlorpheniramine maleate (0.3 mg/kg, i.v.) attenuated the increase in airway resistance induced by Ascaris challenge, but had only a small effect on the increase in G and the reductions in PaO2 and FRC after antigen. Conclusions: These results demonstrate that airway closure occurs immediately after the antigen challenge in allergic cynomolgus monkeys and that histamine H1 receptors contribute very minimally to this response.