bluuebunny/crossref_metadata_2025 huggingface dataset:
Prosthetic Mitral Valve Thrombosis: Can Fluoroscopy Predict the Efficacy of Thrombolytic Treatment?
Authors: Montorsi Piero , Cavoretto Dario , Alimento Marina , Muratori Manuela , Pepi Mauro
Published: September 2003

Background

Thrombolysis (T) is an effective therapy for prosthetic valve thrombosis (PVT). Debate still exists as to which clinical or noninvasive finding best predict the result of T. The aim of the study was to investigate the role of fluoroscopy (F) to predict efficacy of T in pts with mitral PVT.

Methods

We evaluated 17 consecutive pts with bileaflet mitral PVT. F criteria for PVT were: abnormal disc motion and calculated opening angle >25°. T was carried out with tissue-type plasminogen activator (tPA; 100 mg over 3 hours followed by heparin infusion for 24 hours) and was considered successful when normalization of leaflet motion and opening angle occurred. Results were evaluated according to symptom duration (<21 days, early PVT; >21 days, late PVT) and to F pattern of PVT (blocked leaflet versus hypomobile leaflet).

Results

F showed disc motion alteration in 24 of 34 leaflets: 8 leaflets were blocked, whereas 16 were hypomobile. Early (12.7±6.1 days, range 3–21) and late (113±114 days, range 28–365) PVT was present in 8 and 7 pts, respectively. Thrombolysis was successful in 20 of 24 leaflets. Blocked leaflet fully recovered only in early PVT (n=4) pts, whereas they remained blocked in late PVT (n=4). On the contrary, in all of the cases with hypomobile leaflet, disc motion normalized regardless duration of symptoms and extent of disc motion reduction. Interestingly, 4 leaflets with late PVT was diagnosed as blocked by trans-thoracic (TTE). F showed a residual disc movement in all: they fully recovered after T. Two pts with late PVT had both leaflets affected (1 blocked +1 hypomobile); although blocked leaflet did not respond to T, the normalization of hypomobile significantly improved clinical condition.

Conclusions

F can predict result of T in mitral PVT. PVT with F evidence of hypomobile leaflet always recovers regardless of symptom duration and extent of disc motion reduction, suggesting that the small amount of thrombus needed to interfere with discs motion in bileaflet prostheses remains sensitive to T even after a long time. PVT with F evidence of blocked leaflet has a favorable response to T only in case of early PVT. Late PVT with blocked leaflet does not respond to T, suggesting a larger and stratified thrombus and the coexistence of pannus and, in our series, always required surgery. However, if a hypomobile leaflet coexists, T may be used to restore normal movement of hypomobile leaflet so that to improve patient clinical and hemodynamic condition before operation.
The Sustainability of the Asian Welfare System after the Financial Crisis
Authors: Chan Raymond
Published: September 2003

From mid-1970s, Asian societies have experienced unprecedented economic growth, and have invested in the development of their own welfare regimes, which offers support to the individual even though public funding is limited. Welfare development received growing attention in Asia. The financial crisis that began in 1997 signified a drastic change in the policy context. The future of Asian economy and employment is bleak, and governments must face the risk of shrinking public resources in response to increasing social demands. The paper discussed the risks of our welfare system, and the weaknesses of public sector, community and private welfare in meeting these increasing social demands after the financial crisis, as observed in Hong Kong and other Asian societies. Although work income and occupational welfare will still be the primary protection systems of individuals and families, partly due to the dominance of neo-liberalism in the global economy and the free market system in this region. However, given the possibility of increasing vulnerability to unemployment in the future, it is also necessary to install a stronger collective system of social security and policies to pool resources together to share the risks. Of course, these initiatives will require a redefinition of the notion of citizenship and the contract that exist among individuals, and between the state and its citizens.
Globalisation and Economic Insecurity: A Need for a New Social Policy in Malaysia
Authors: Shari Ishak
Published: September 2003

The globalisation of economies offers new opportunities to both developed and developing countries in terms of promoting growth, improving income, and reducing poverty and inequality. However, it has also given rise to labour flexibility, wage depression, and eroded important elements of redistribution and weakened social protection systems. The 1997–1998 financial crisis in Southeast and Northeast Asia further exposed important limitations in the ability of such existing systems to cope with the crisis. This paper identifies new forms of economic insecurities generated by the renewed growth of labour flexibility as globalisation weakens the basis of social partnership and tripartism. It examines Malaysia's development experience, the impact of the crisis on workers' economic security, and assesses the adequacy of existing social protection programmes in its response to new types of economic insecurities generated by globalisation. It argues that these issues need to be addressed in formulating policies to ensure equitable social development in Malaysia in the future.
The "World" of the Enlightenment to Come (Exception, Calculation, Sovereignty)
Authors: Derrida Jacques
Published: September 2003

Taking as its point of departure Edmund Husserl's 1935-36 text The Crisis of European Sciences, this essay attempts to develop a new conception of reason by means of a thoroughgoing critique of some ideas often used to support and define it. Because the notion of "enlightenment" has been tied since the time of Kant to a certain coming of age of reason or rationality, the "enlightenment" to come must at once draw upon the resources of this reason and open reason to some of the aporias it has traditionally rejected. Reducible neither to a simple irrationalism nor to a mere mode of calculative thought, such reason must ultimately challenge, it is argued, not only the sovereignty and identity of the (human) subject but the very concepts of sovereignty and identity. Only such a renewed thinking of reason or of what is reasonable, the essay suggests, can help us diagnose, analyze, and help treat some of the aporias posed by a whole host of contemporary issues, from cloning to the erosion of the nation-state to globalization and terrorism. Only in this way can we at once "save the honor of reason" - to use a phrase that runs throughout the essay - and help reorient the reason of politics, of the sciences, and, indeed, of philosophy along the lines of a more fundamental and urgent ethical imperative.
Emerging Applications of the Tumor Necrosis Factor Family of Ligands and Receptors in Cancer Therapy
Authors: Younes Anas , Kadin Marshall E.
Published: September 2003

Abnormalities of the tumor necrosis factor (TNF) family members have been linked to several human diseases, including cancer. Novel treatment strategies for cancer are emerging based on an understanding of the function of TNF family members. The advantage of these strategies is their potential to selectively target cancer cells, while sparing normal cells. Combining these new strategies with currently available treatments such as chemotherapy and radiation therapy is under investigation, with promising results. However, because some TNF family members are toxic to normal mammalian cells when administered systemically, only a few TNF family members have potential therapeutic value. This concise review focuses on the clinical implications of four TNF family members for cancer treatment: CD30/CD30 ligand, CD40/CD40 ligand, receptor activator of nuclear factor-κB (RANK)/RANK ligand, and TNF-related apoptosis-inducing ligand (TRAIL) Apo-2L/TRAIL receptors.
Salt Loading Affects Cortisol Metabolism in Normotensive Subjects: Relationships with Salt Sensitivity
Authors: Kerstens Michiel N. , van der Kleij Frank G. H. , Boonstra Arnold H. , Sluiter Wim J. , Koerts Jan , Navis Gerjan , Dullaart Robin P. F.
Published: September 2003

We studied cortisol metabolism together with insulin sensitivity [homeostatic model assessment (HOMA)] and renal hemodynamics in 19 salt-resistant (sr) and nine salt-sensitive (ss) normotensive subjects after a low- and high-salt diet. Results are described as high- vs. low-salt diet. Sum of urinary cortisol metabolite excretion (∑metabolites) increased in sr subjects (3.8 ± 1.6 vs. 3.1 ± 1.1 μg/min per square meter, P < 0.05) and decreased in ss subjects (2.3 ± 1.0 vs. 2.9 ± 1.1 μg/min per square meter, P < 0.05). Plasma 0830 h cortisol decreased in sr subjects but did not change significantly in ss subjects. In all subjects, the absolute blood pressure change correlated negatively with the percentage change in ∑metabolites (P < 0.05) and positively with the percentage change in renal vascular resistance (P < 0.05). ∑metabolites during high-salt diet correlated negatively with the percentage changes in plasma 0830 h cortisol (P < 0.05) and renal vascular resistance (P = 0.05). HOMA did not change in either group, but the percentage change in HOMA correlated positively with the percentage change in plasma cortisol (P = 0.001) and negatively with the percentage change in ∑metabolites (P < 0.01). Parameters of 11β-hydroxysteroid dehydrogenase activity were not different between groups and did not change. In conclusion, these data suggest that cortisol elimination is affected differently after salt loading in sr and ss subjects. Changes in circulating cortisol might contribute to individual sodium-induced alterations in insulin sensitivity.
Expression and Degradation of Androgen Receptor: Mechanism and Clinical Implication
Authors: Lee Dong Kun , Chang Chawnshang
Published: September 2003

The androgen-androgen receptor (AR) signaling pathway plays a key role in proper development and function of male reproductive organs, such as prostate and epididymis, as well as nonreproductive organs, such as muscle, hair follicles, and brain. Abnormalities in the androgen-AR signaling pathway have been linked to diseases, such as male infertility, Kennedy’s disease, and prostate cancer. Regulation of AR activity can be achieved in several different ways: modulation of AR gene expression, androgen binding to AR, AR nuclear translocation, AR protein stability, and AR trans-activation. This review covers mechanisms implicated in the control of AR protein expression and degradation, and their potential linkage to the androgen-related diseases. A better understanding of such mechanisms may help us to design more effective androgens and antiandrogens to battle androgen-related diseases.
The Decisive Role of Free Fatty Acids for Protein Conservation during Fasting in Humans with and without Growth Hormone
Authors: Nørrelund Helene , Nair K. Sreekumaran , Nielsen Steen , Frystyk Jan , Ivarsen Per , Jørgensen Jens Otto Lunde , Christiansen Jens Sandahl , Møller Niels
Published: September 2003

During fasting, a lack of GH increases protein loss by close to 50%, but the underlying mechanisms remain uncertain. The present study tests the hypothesis that the anabolic actions of GH depend on mobilization of lipids. Seven normal subjects were examined on four occasions during a 37-h fast with infusion of somatostatin, insulin, and glucagon for the final 15 h: 1) with GH replacement, 2) with GH replacement and antilipolysis with acipimox, 3) without GH and with antilipolysis, and 4) with GH replacement, antilipolysis, and infusion of intralipid. Urinary urea excretion, serum urea concentrations, and muscle protein breakdown (assessed by labeled phenylalanine) increased by almost 50% during fasting with suppression of lipolysis. Addition of GH during fasting with antilipolysis did not influence indexes of protein degradation, whereas restoration of high FFA levels regenerated proportionally low concentrations of urea and decreased whole body protein degradation (phenylalanine to tyrosine conversion) by 10–15%, but failed to affect muscle protein metabolism. Thus, the present data provide strong evidence that FFA are important protein-sparing agents during fasting. The finding that inhibition of lipolysis eliminates the ability of GH to restrict fasting protein loss indicates that stimulation of lipolysis is the principal protein-conserving mechanism of GH.
The available‐enthalpy cycle. II: Applications to idealized baroclinic waves
Authors: Marquet Pascal
Published: September 2003

The local available‐enthalpy cycle proposed in Part I of this paper is applied to document energetics of three numerical simulations, representing life cycles of idealized baroclinic waves. An improved temporal numerical scheme defined in Part I is used in this study, together with the Arpège‐IFS model using a T42 triangular truncation. A 45°N and 200 hPa dry unstable jet is constructed with the most unstable mode at zonal wave number 8. Energetic impacts of both horizontal and vertical diffusion schemes are determined separately.

The role of ageostrophic winds within the Ekman layer is investigated, leading to an explanation for large observed values for the dissipation terms and to a new formulation of the potential‐energy conversions. The magnitudes of these new conversion terms are compared with those of the usual barotropic and baroclinic conversions. A new version for the available‐enthalpy cycle is proposed. It is suitable for open systems and it includes explicitly the potential‐energy component as a transitional reservoir. Finally, some results from Intensive Observing Period 15 of the Fronts and Atlantic Storm‐Track EXperiment are compared with those from the idealized diabatic experiment. Copyright © 2003 Royal Meteorological Society
Some aspects of the effect of surface friction on flows over mountains
Authors: Peng Melinda S. , Thompson William T.
Published: September 2003

The effect of surface friction on flow over mountains in stratified fluids is investigated using a two‐dimensional version of the Naval Research Laboratory's non‐hydrostatic Coupled Ocean/Atmosphere Mesoscale Prediction System (COAMPS). Without surface friction, flow over a mountain attains a maximum speed at the surface on the lee slope. With surface friction, the flow speed vanishes at the surface and reaches a maximum near the top of the boundary layer (BL). Corresponding to this wind distribution is a shallow layer of very large vertical wind shear beneath the jet maximum and a weaker but deeper sheared layer elsewhere. This strong shear generates maximum turbulent kinetic energy (TKE) at the jet maximum region. Meanwhile, the buoyancy effect associated with the mountain gravity wave inhibits the production of the TKE above the jet maximum region. The combined effects of shear and buoyancy lead to a very shallow BL on the lee slope. In general, surface friction reduces the amplitude of mountain gravity waves. Comparison of the flow fields with the outline of the BL height indicates that flow characteristics correspond closely to the distribution of the BL height. It is hypothesized that the reduction in mountain‐wave amplitude in the presence of surface friction is due to the reduction in the slope of the BL height as compared to the terrain height. For narrower and/or higher mountains, the BL height exhibits a secondary peak on the lee side that further modifies the wave. Simulations using the BL height as a solid mountain without surface friction confirm that characteristics of flow over the mountain are associated with the distribution of BL height rather than the terrain height field. As the non‐dimensional mountain height increases, the magnitude of the effect of surface friction decreases due to decreasing BL depth on the lee side, with the result that the BL height profile becomes closer to the terrain height field.

The effect of surface friction on asymmetric mountains is also investigated. Without surface friction, the pressure drag shows distinctive reduction with a secondary peak on the downstream side, but the effect is less when the secondary peak is on the upstream side. With surface friction, all three mountains have similar pressure drag, corresponding to their similar BL height profiles. Copyright © 2003 Royal Meteorological Society
Application of a Static Reactive Power Compensator (STATCOM) and a Dynamic Braking Resistor (DBR) for the Stability Enhancement of a Large Wind Farm
Authors: Wu Xueguang , Arulampalam Atputharajah , Zhan Changjiang , Jenkins Nick
Published: September 2003

A control strategy to improve the stability of a large wind farm using a Static Reactive Power Compensator (STATCOM) and Dynamic Braking Resistor (DBR) is proposed and investigated. The STATCOM supplies the reactive power demand of the wind farm dynamically in order to maintain the network voltage. The DBR is controlled by Liapunov's stability criterion to absorb the active power of the wind farm during the network fault. The performance of the STATCOM and DBR, applied to a large wind farm (60MW), is studied in PSCAD/EMTDC. The simulation results show that effective control of the STATCOM and DBR together can enhance the stability of large wind farms.
Wind/Hybrid Power System Applications for New England Islands
Authors: Manwell James F. , McGowan Jon G. , Blanco Gabriel
Published: September 2003

This paper summarizes a feasibility study of potential wind-hybrid power systems for the islands of New England. The work included the compilation of an inventory of New England coastal islands, a categorization of the islands according to energy related criteria, and an overview of their present electricity supply. It also includes a proposal of wind-hybrid power systems for two selected islands, and an estimation of their technical performance and economic merits.
Firecrackers Noise
Authors: Tandon N.
Published: September 2003

Fireworks are used all over the world to celebrate special occasions. Noise produced by firecrackers that are used to celebrate these occasions has been highlighted. This impulse type of noise can cause hearing damage. Noise measurements of firecrackers show that they produce high sound pressure peak levels. Typical firecracker impulse noise levels are given. Noise limits and measurement methods used for the fireworks in some countries are presented.
Evaluating peer mediation outcomes in educational settings: A meta‐analytic review
Authors: Burrell Nancy A. , Zirbel Cindy S. , Allen Mike
Published: September 2003

This investigation summarizes existing research on peer mediation outcomes in school‐based settings. The meta‐analytic review
examines the outcomes associated with incorporating a mediation program to manage school conflict. Results indicate a 93 percent agreement rate and
that 88 percent of the participants were satisfied with the agreements reached. The review answers critics and demonstrates the value of
school‐based mediation programs.
Behavior analysis for approaching the desired trajectory in every trial of learning control
Authors: Takahashi Tohru
Published: September 2003

Much research has been carried out on learning control in which the desired trajectory is completed during repetition of the same operation. Many application classes from linear systems to certain classes of nonlinear systems have been investigated, along with the conditions of their learning stability. However, there seems to be no discussion of the manner of approach of the real trajectory to the desired trajectory in each trial. The reason for investigating this behavior in each trial is that the approach to the desired trajectory may be limited to certain directions, depending on the procedure to which the learning control is applied. In general, as a first step to considering the problem of learning control of the approach of a system with multiple degrees of freedom from a restricted region to the desired target in each trial, a linear time‐invariant learning control system with one input and one output is characterized. In this system, the real trajectory approaches the desired trajectory, given as a function of time, from one of the regions sandwiching the desired target. The obtained results are confirmed by simulation. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(1): 61–71, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10021
Inelastic earthquake response of single‐story asymmetric buildings: an assessment of simplified shear‐beam models
Authors: Stathopoulos K. G. , Anagnostopoulos S. A.
Published: September 2003

The inelastic seismic torsional response of simple structures is examined by means of shear‐beam type models as well as with plastic hinge idealization of one‐story buildings. Using mean values of ductility factors, obtained for groups of ten earthquake motions, as the basic index of post‐elastic response, the following topics are examined with the shear‐beam type model: mass eccentric versus stiffness eccentric systems, effects of different types of motions and effects of double eccentricities. Subsequently, comparisons are made with results obtained using a more realistic, plastic hinge type model of single‐story reinforced concrete frame buildings designed according to a modern Code. The consequences of designing for different levels of accidental eccentricity are also examined for the aforementioned frame buildings. Copyright © 2003 John Wiley & Sons, Ltd.
A response‐spectrum‐based envelope for Mohr's circle
Authors: Menun Charles
Published: September 2003

Mohr's circle is commonly used to determine the combinations of normal and shear stresses that act in any direction at a location of interest within a structure. During an earthquake, the radius and center of Mohr's circle naturally fluctuate with time. In such cases, an envelope that bounds the time‐varying realizations of Mohr's circle at a given location is desirable to facilitate the identification of critical combinations of normal and shear stresses at that location. In this paper, a response‐spectrum‐based procedure for predicting the envelope that bounds Mohr's circle in a linear‐elastic structure subjected to seismic loads is developed. The accuracy of the proposed envelope is evaluated by comparing it to the results of time‐history analyses performed on a concrete gravity dam using simulated and recorded ground motions. It is found that the proposed envelope has a level of accuracy that is commensurate with its response spectrum bases. The largest observed difference between the simulated and predicted envelopes is less than 10%. Copyright © 2003 John Wiley & Sons, Ltd.
Intracerebroventricular passive immunization with anti‐Aβ antibody in Tg2576
Authors: Chauhan Neelima B. , Siegel George J.
Published: September 2003

Current Alzheimer's disease (AD) research has established the fact that excessive genesis of Aβ derived from amyloidogenic processing of β‐amyloid (Aβ) precursor protein is fundamental to AD pathogenesis. There has been considerable interest in using immunization strategies for clearing excessive Aβ. Studies in animal models of AD have shown that active immunizations or systemic passive immunizations reduced cerebral plaque load and improved behavioral deficits. However, clinical translation of an active immunization strategy was interrupted because of evidence for meningoencephalitis produced in some patients who received Aβ vaccine. Studies in animal models have shown perimicrovascular hemorrhages and inflammation after sustained systemic immunizations in animals with vascular amyloid. In this light, our data showing the effects of a single intracerebroventricular (ICV) injection of anti‐Aβ in the Alzheimer's Swedish mutant model Tg2576 are intriguing. We have previously demonstrated that a single ICV injection of anti‐Aβ into the third ventricle of 10‐month‐old Tg2576 mice reduced cerebral plaques, reversed Aβ‐induced depletion of presynaptic SNAP‐25, and abolished astroglial activation as seen 1 month post‐injection (Chauhan and Siegel [2002] J. Neurosci. Res. 69:10–23). The present report demonstrates that a single ICV injection of 10 μg anti‐Aβ in 10‐month‐old Tg2576 mice reduced cerebral plaques, with decreased inflammation at this stage as evidenced by a reduced number of interleukin‐1β‐positive microglia surrounding Congophilic plaques. Moreover, at this particular age, no microhemorrhage was discernible, as evidenced by the absence of hemosiderin deposition after a single ICV injection of anti‐Aβ. This is the first report demonstrating absence of microhemorrhage and reduced inflammation after the ICV introduction of anti‐Aβ in Tg2576 mice at 10 months of age. These facts indicate that, although invasive, ICV injection of anti‐Aβ may be a safer method of vaccination in AD, possibly through reducing the vascular exposure to antibody. Further studies are warranted to determine the lasting effects of a single ICV anti‐Aβ injection in animals with and without abundant plaque burden and at older ages. © 2003 Wiley‐Liss, Inc.
Expression of antisense bcl‐2 cDNA abolishes tumorigenicity and enhances chemosensitivity of human malignant glioma cells
Authors: Zhu Cong Ju , Li Yong Biao , Wong Meng Cheong
Published: September 2003

Bcl‐2 is a key antiapoptotic protein, and it confers survival advantages on many types of tumors by inhibiting apoptotic cell death. Malignant gliomas are the most common primary central nervous system tumors, but the role of bcl‐2 in these tumors has not been defined. We investigated the impact of bcl‐2 on malignant gliomas by suppressing its expression. Antisense human bcl‐2 cDNA was transfected into human malignant glioma cells. The effects of bcl‐2 protein down‐regulation on glioma cell morphology, in vitro tumor growth, and tumorigenicity in nude mice, as well as chemosensitivity to cisplatin, were studied. Expression of antisense bcl‐2 cDNA decreased bcl‐2 protein by more than sixfold. Antisense bcl‐2 stable transfectants (AS‐bcl‐2) showed profound morphological change and markedly retarded cell growth in vitro. Transplantation of AS‐bcl‐2 cells resulted in no tumor formation, whereas backbone plasmid transfectant control formed tumors in each mouse transplanted. Expression of antisense bcl‐2 in glioma cells resulted in significantly increased cytotoxicity of cisplatin. In conclusion, antisense bcl‐2 expression can effectively reduce glioma survival, including retarding in vitro growth, complete loss of tumorigenicity, and significantly enhanced cisplatin cytotoxicity. These results suggest that bcl‐2 plays an important role in glioma malignancy and chemoresistance. Development of strategies targeted at bcl‐2 has the potential to advance treatment for malignant gliomas. © 2003 Wiley‐Liss, Inc.
Suppressive effects of BmK IT2 on nociceptive behavior and c‐Fos expression in spinal cord induced by formalin
Authors: Zhang Xu‐Ying , Bai Zhan‐Tao , Chai Zhi‐Fang , Zhang Jian‐Wei , Liu Ying , Ji Yong‐Hua
Published: September 2003

In this study, the suppressive effects of BmK IT2, a kind of Na+ channel‐specific modulator from the venom of the scorpion Buthus martensi Karsch, on biphasic nociceptive behavior in rats and c‐Fos expression in rat spinal cord induced by formalin were investigated. Fifty microliters of 2.5% formalin were subcutaneously injected into the rat hind paw; 0.1 and 1 μg doses of BmK IT2 were subcutaneously administered into the rat ipsilateral hind paw 1 min before or 10 min after formalin injection individually, and the number of flinches per 5 min was counted. The detection of c‐Fos expression induced by formalin in either the absence or the presence of BmK IT2 was carried out with the ABC method. Biphasic nociceptive behavior in rats was significantly suppressed by pretreatment with BmK IT2. No. of flinches/5 min in the second phase was also decreased by posttreatment with BmK IT2. In addition, c‐Fos expression induced by formalin was significantly inhibited in all laminae of L4–5 spinal cord by pre‐ or posttreatment with BmK IT2. The suppression of BmK IT2 in the first‐ and second‐phase behaviors may be attributed to the anesthesia of the toxin toward nociceptors and primary afferents and its selective modulation of tetrodotoxin‐resistant Na+ currents of dorsal root ganglion neurons, respectively. In addition, the nonparallel suppression of BmK IT2 on flinch behavior and c‐Fos expression induced by formalin may be ascribed to the different activity patterns of afferent fibers and central neurons. © 2003 Wiley‐Liss, Inc.
Uptake of serotonin by adult rat corpus callosum is partially reduced by common antidepressants
Authors: Reyes‐Haro Daniel , García‐Alcocer Guadalupe , Miledi Ricardo , García‐Colunga Jesús
Published: September 2003

The corpus callosum (CC) is the main white matter tract involved in interhemispheric brain communication. We establish that uptake of [3H]5‐hydroxytryptamine (5‐HT) in CC is partially inhibited by some antidepressants. Slices of the adult rat CC had a high‐affinity uptake of 5‐HT. About 80% of this uptake was Na+ dependent, with a Michaelis‐Menten constant, Km, of 420 ± 80 nM and a rate of 5‐HT uptake, Vmax, of 9.5 ± 0.8 pmol/mg protein/min. The 5‐HT uptake was reduced ∼60% at pH 5 compared with that at pH 7. Fluoxetine (Prozac) inhibited only 43% of 5‐HT uptake in a concentration‐dependent manner, with an affinity constant, Ki, of 44.7 ± 10.0 nM. We also studied the effects of other monoamine uptake inhibitors, all at 10 μM, and found that zimelidine, imipramine, and clomipramine inhibited 5‐HT uptake in the CC by ∼30–40%. The fluoxetine‐insensitive 5‐HT uptake was not altered by high concentrations of dopamine plus norepinephrine. The present data show that Na+‐dependent 5‐HT uptake occurs in the CC and optic nerve and that this uptake is partially sensitive to antidepressants and probably mediated by the serotonin transporter, which may be relevant during depression. © 2003 Wiley‐Liss, Inc.
Overexpression of amyloid precursor protein is associated with degeneration, decreased viability, and increased damage caused by neurotoxins (prostaglandins A1 and E2, hydrogen peroxide, and nitric oxide) in differentiated neuroblastoma cells
Authors: Hanson Amy J. , Prasad Judith E. , Nahreini Piruz , Andreatta Cynthia , Kumar Bipin , Yan Xiang‐Dong , Prasad Kedar N.
Published: September 2003

Inflammatory reactions are considered one of the important etiologic factors in the pathogenesis of Alzheimer's disease (AD). Prostaglandins such as PGE2 and PGA1 and free radicals are some of the agents released during inflammatory reactions, and they are neurotoxic. The mechanisms of their action are not well understood. Increased levels of β‐amyloid fragments (Aβ40 and Aβ42), generated through cleavage of amyloid precursor protein (APP), oxidative stress, and proteasome inhibition, are also associated with neurodegeneration in AD brains. Therefore, we investigated the effect of PGs and oxidative stress on the degeneration and viability of cyclic AMP‐induced differentiated NB cells overexpressing wild‐type APP (NBP2‐PN46) under the control of the CMV promotor in comparison with differentiated vector (NBP2‐PN1) or parent (NBP2) control cells. Results showed that differentiated NBP2‐PN46 cells exhibited enhanced spontaneous degeneration and decreased viability in comparison with differentiated control cells, without changing the level of Aβ40 and Aβ42. PGA1 or PGE2 treatment of differentiated cells caused increased degeneration and reduced viability in all three cell lines. These effects of PGs are not due to alterations in the levels of vector‐derived APP mRNA or human APP holoprotein, secreted levels of Aβ40 and Aβ42, or proteasome activity. H2O2 or SIN‐1 (an NO donor) treatment did not change vector‐derived APP mRNA levels, but H2O2 reduced the level of human APP protein more than SIN‐1. Furthermore, SIN‐1 increased the secreted level of Aβ40, but not of Aβ42, whereas H2O2 had no effect on the level of secreted Aβ fragments. Both H2O2 and SIN‐1 inhibited proteasome activity in the intact cells. The failure of neurotoxins to alter APP mRNA levels could be due to the fact that they do not affect CMV promoter activity. These results suggest that the mechanisms of action of PGs on neurodegeneration are different from those of H2O2 and SIN‐1 and that the mechanisms of neurotoxicity of H2O2 and SIN‐1 are, at least in part, different from each other. © 2003 Wiley‐Liss, Inc.
Expression of CD137 and its ligand in human neurons, astrocytes, and microglia: Modulation by FGF‐2
Authors: Reali Camilla , Curto Monica , Sogos Valeria , Scintu Franca , Pauly Susanne , Schwarz Herbert , Gremo Fulvia
Published: September 2003

CD137 (ILA, 4‐1BB), a member of the tumor necrosis factor receptor family, and its ligand CD137‐L were assayed by RT‐PCR and immunocytochemistry in cultured human brain cells. Results demonstrated that both neurons and astrocytes expressed specific RNA for CD137 and its protein, which was found both on the plasma membrane and in the cytoplasm. Surprisingly, microglia, which also expressed CD137 mRNA, showed negative immunostaining. CD137‐L‐specific RNA was detected only in astrocytes and neurons. When brain cells were treated with fibroblast growth factor‐2 (FGF‐2), upregulation of CD137 but not of its ligand was observed in neurons and astrocytes. Protein localization was also affected. In microglia, an inhibition of RNA expression was induced by treatment, whereas CD137‐L remained negative. Our data are the first demonstration that human brain cells express a protein found thus far in activated immunocompetent cells and epithelia. Moreover, they suggest not only that CD137 and CD137‐L might play a role in interaction among human brain cells, but also that FGF‐2 might have an immunoregulatory function in brain, modulating interaction of the central nervous system with peripheral immunocompetent cells. © 2003 Wiley‐Liss, Inc.
Protein kinase A and calcium/calmodulin‐dependent protein kinase II regulate D‐[3H]aspartate release in auditory brain stem nuclei
Authors: Zhang J. , Suneja S.K. , Potashner S.J.
Published: September 2003

We noted previously that after unilateral cochlear ablation (UCA) in young adult guinea pigs, plastic changes in glutamatergic transmitter release in several brain stem auditory nuclei depended on protein kinase C. In this study, we assessed whether such changes depended on protein kinase A (PKA) and calcium/calmodulin‐dependent protein kinase II (CaMKII). The electrically‐evoked release of D‐[3H]aspartate (D‐[3H]Asp) was quantified in vitro as an index of glutamatergic transmitter release in the major subdivisions of the cochlear nucleus (CN) and the main nuclei of the superior olivary complex (SOC). In tissues from intact animals, dibutyryl‐cyclic adenosine monophosphate (DBcAMP), a PKA activator, elevated D‐[3H]Asp release by 1.9–3.7‐fold. The PKA inhibitor, H‐89 (2 μM), did not alter the evoked release but blocked the stimulatory effects of DBcAMP. These findings suggested that PKA could positively regulate glutamatergic transmitter release. Seven days after the ablation of one cochlea and its cochlear nerve, the stimulatory effect of DBcAMP remained evident. After 145 postablation days, H‐89 blocked the plastic elevations of D‐[3H]Asp release in the ipsilateral CN and lateral (LSO) and medial (MSO) superior olive. A CaMKII inhibitor, KN‐93, produced similar blocks, suggesting that the postablation plasticities in these nuclei depended on PKA or CaMKII. Both H‐89 and KN‐93 elevated release in the medial nucleus of the trapezoid body (MNTB) and the contralateral MSO, suggesting that either kinase could be used by endogenous mechanisms in these nuclei to downregulate glutamatergic release. © 2003 Wiley‐Liss, Inc.
Influence of motor unit firing patterns on evaluation of muscle activities by Karhunen–Loève expansion
Authors: Nakamura Yukihiro , Kaneko Hidekazu , Kiryu Tohru , Suzuki Shinya S. , Saitoh Yoshiaki
Published: September 2003

In fields such as rehabilitation and sports science, it is important to evaluate the state of muscle fatigue exactly in order to realize the maximum training effect while avoiding damage due to overtraining. Since the surface EMG is noninvasive and measurement is easy, the EMG evaluation parameters calculated from EMG are widely used for evaluation. It should be noted, however, that the behavior of the evaluation parameters is similar in true muscle fatigue and in cases where muscle fatigue is simulated by intentionally decreasing the muscle tension. This makes discrimination of the two cases difficult. To recognize the difference between the states of muscle activity, the authors proposed a method in which the time series of the EMG evaluation parameters is represented by a Karhunen–Loève (KL) expansion, but the physiological condition which is expressed by the result of KL expansion analysis has not been sufficiently investigated. This study uses a surface EMG simulation model in which the firing pattern of the motor units (MU) can be varied flexibly, and attempts to clarify how the MU firing pattern affects the results of analysis by KL expansion. It is found that the same analytical results as for the state of muscle fatigue can be obtained by considering the fluctuation of the firing probability in multiple MU and the accompanying intermittent MU recruitment. © 2003 Wiley Periodicals, Inc. Syst Comp Jpn, 34(12): 45–55, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10326
Chaos and complexity theory in management: an exploration from a critical systems thinking perspective
Authors: Ortegón‐Monroy Maria Carolina
Published: September 2003

This paper presents the theoretical and practical findings emerging from an exploratory study of Chaos and Complexity Theory (C&CT) as an alternative approach to propitiate new understandings about the nature of management in organizations. They show that C&CT is not theoretically coherent enough to be applied in practice. Copyright © 2003 John Wiley & Sons, Ltd.
Differential expression of ATPAF1 and ATPAF2 genes encoding F1‐ATPase assembly proteins in mouse tissues
Authors: Pı́cková Andrea , Paul Jan , Petruzzella Vittoria , Houštěk Josef
Published: September 2003

Atp11p (Atpaf1p; F1‐ATPase assembly factor 1) and Atp12p (Atpaf2p; F1‐ATPase assembly factor 2) are proteins required for the assembly of β (F1‐β) and α (F1‐α) subunits into the mitochondrial ATPase. Here we report about 100 times lower levels of ATPAF1 and ATPAF2 transcripts in relation to the mRNA levels of F1
‐α and F1
‐β in a range of mouse tissues. Quantitative reverse‐transcription polymerase chain reaction revealed nearly constant ATPAF1 expression in all tissues in both adult and 5‐day‐old mice (up to two‐fold differences), indicating that ATPAF1 rather behaves like a maintenance gene. In contrast, ATPAF2 expression differed up to 30‐fold in the tissues analysed. ATPAF2 tissue‐specific expression was also found to correlate well with mRNA levels of both F1
‐α and F1
‐β (BAT≫kidney, liver>heart, brain>skeletal muscle), showing the highest mRNA level in the thermogenic, ATPase‐poor brown adipose tissue, which is characterised by a 10‐fold decrease in ATPase/respiratory chain stoichiometry relative to the other tissues.
Changes in Hsp90 expression determine the effects of cyclosporine A on the NO pathway in rat myocardium
Authors: Rezzani Rita , Rodella Luigi , Dessy Chantal , Daneau Géraldine , Bianchi Rossella , Feron Olivier
Published: September 2003

Cyclosporine A (CsA) is associated with the development of cardiovascular toxicity in transplant patients but can exert myocardial protection against ischemia/reperfusion damages. We examined in a rat model of chronic CsA administration whether subtle variations in the NO pathway could account for these opposite effects. CsA treatment rapidly led to an increase in myocardial Hsp90 expression promoting the recruitment of Akt and calcineurin, thereby promoting eNOS activation through Ser1177 phosphorylation and Thr495 dephosphorylation, respectively. This was associated with an increase in myocardial VEGF expression and led to anti‐apoptotic effects in isolated cardiac myocytes. Upon longer CsA exposure, cardiac toxicity developed, as documented by the infiltration of connective tissue and the increase in iNOS expression. These later effects were associated with a dramatic decrease in the abundance and scaffold function of Hsp90, thereby unraveling the key role of Hsp90 in governing CsA effects.
Regulated secretion of macrophage migration inhibitory factor is mediated by a non‐classical pathway involving an ABC transporter
Authors: Flieger Oliver , Engling André , Bucala Richard , Lue Hongqi , Nickel Walter , Bernhagen Jürgen
Published: September 2003

The cytokine macrophage migration inhibitory factor (MIF) is inducibly secreted by immune cells and certain other cell types to critically participate in the regulation of the host immune response. However, MIF does not contain a N‐terminal signal sequence and the mechanism of MIF secretion is unknown. Here we show in a model of endotoxin‐stimulated THP‐1 monocytes that MIF does not enter the endoplasmatic reticulum and that MIF secretion is not inhibited by monensin or brefeldin A, demonstrating that MIF secretion occurs via a non‐classical export route. Glyburide and probenicide but not other typical inhibitors of non‐classical protein export strongly block MIF secretion, indicating that the export pathway of MIF involves an ABCA1 transporter.
Occurrence and neuroendocrine role of D‐aspartic acid and N‐methyl‐D‐aspartic acid in Ciona intestinalis
Authors: D'Aniello Antimo , Spinelli Patrizia , De Simone Antonietta , D'Aniello Salvatore , Branno Margherita , Aniello Francesco , Fisher George H , Di Fiore Maria M , Rastogi Rakesh K
Published: September 2003

Probes for the occurrence of endogenous D‐aspartic acid (D‐Asp) and N‐methyl‐D‐aspartic acid (NMDA) in the neural complex and gonads of a protochordate, the ascidian Ciona intestinalis, have confirmed the presence of these two excitatory amino acids and their involvement in hormonal activity. A hormonal pathway similar to that which occurs in vertebrates has been discovered. In the cerebral ganglion D‐Asp is synthesized from L‐Asp by an aspartate racemase. Then, D‐Asp is transferred through the blood stream into the neural gland where it gives rise to NMDA by means of an NMDA synthase. NMDA, in turn, passes from the neuronal gland into the gonads where it induces the synthesis and release of a gonadotropin‐releasing hormone (GnRH). The GnRH in turn modulates the release and synthesis of testosterone and progesterone in the gonads, which are implicated in reproduction.
High‐throughput screening of structural proteomics targets using NMR
Authors: Galvão-Botton Leonor M.P , Katsuyama Ângela M , Guzzo Cristiane R , Almeida Fábio C.L , Farah Chuck S , Valente Ana Paula
Published: September 2003

We applied a high‐throughput strategy for the screening of targets for structural proteomics of Xanthomonas axonopodis pv citri. This strategy is based on the rapid 1H–15N HSQC NMR analysis of bacterial lysates containing selectively 15N‐labelled heterologous proteins. Our analysis permitted us to classify the 19 soluble candidates in terms of ‘foldedness’, that is, the extent to which they present a well‐folded solution structure, as reflected by the quality of their NMR spectra. This classification allowed us to define a priority list to be used as a guide to select protein candidates for further structural studies.
Acetic‐acid guided visual inspection vs. cytology‐based screening for cervical cancer in the Philippines
Authors: Ngelangel C.A , Limson G.M , Cordero C.P , Abelardo A.D , Avila J.M , Festin M.R ,   UP‐DOH CCSHOSG
Published: September 2003

Objectives: To compare the validity and acceptability of acetic‐acid visualization (VIA), magnified acetic‐acid visualization (VIAM), spatula+cotton swab–Papanicolaou (Pap) smear (SS), and cervical brush–Pap smear (CB) in the detection of precursor/early cervical cancer lesions. Methods: A total of 12 992 women aged between 25 and 65 years from 14 Philippine centers were randomly allocated to the four tests. The gold standard was colposcopy with biopsy for positive/suspicious cases. Results: Sensitivity rates [95% confidence intervals (CIs)] were 37 (CI, 26.8–48.5), 34.1 (CI, 24.8–44.8), 14.3 (CI, 6.4–27.8), and 19.1 (CI, 9.2–34.6) for VIA, VIAM, SS, and CB, respectively. Specificity rates were 90.7 (CI, 89.6–91.7), 90.7 (CI, 89–91.1), 97.5 (CI, 96.8–98), and 97.9 (CI, 97.3–98.4), respectively. Kappa for the Pap smear (PS) within centers ranged from −0.154 to 0.783, and between centers from −0.028 to 0.364. Screeners preferred CB; screened‐women preferred VIA. Conclusions: The acetic‐acid visualization and VIAM methods are recommended for initial cervical cancer screening in the Philippines.
Manual vacuum aspiration for second‐trimester pregnancy termination
Authors: Todd C.S. , Soler M.E. , Castleman L. , Rogers M.K. , Blumenthal P.D.
Published: September 2003

Objectives: To compare manual and electric vacuum aspiration for surgical abortions between 14 and 18 weeks of pregnancy. Methods: A consecutive case series of pregnant women presenting to Johns Hopkins Bayview Medical Center for abortion. There were 73 women in the manual vacuum aspiration group and 37 women in the electric vacuum aspiration group. Dilatation and evacuation was performed using manual or electric vacuum aspiration according to protocol. Procedure time was assessed with the t‐test. Results: In all cases, abortion was performed with initial vacuum. Group sizes were sufficient to detect a 20% difference in mean procedure time with 80% power (calculated with two separate S.D.s for procedure time). There was no significant difference in procedure time between the two groups. Conclusions: Manual vacuum aspiration can be safely and effectively used in second‐trimester abortion procedures and should be more widely investigated for this purpose.
Biological effects after prenatal irradiation (embryo and fetus)
Authors: Valentin J.
Published: September 2003

In its 1990 recommendations, the ICRP considered the radiation risks after exposure during prenatal development. This report is a critical review of new experimental animal data on biological effects and evaluations of human studies after prenatal radiation published since the 1990 recommendations.

Thus, the report discusses the effects after radiation exposure during pre-implantation, organogenesis, and fetogenesis. The aetiology of long-term effects on brain development is discussed, as well as evidence from studies in man on the effects of in-utero radiation exposure on neurological and mental processes. Animal studies of carcinogenic risk from in-utero radiation and the epidemiology of childhood cancer are discussed, and the carcinogenic risk to man from in-utero radiation is assessed. Open questions and needs for future research are elaborated.

The report reiterates that the mammalian embryo and fetus are highly radiosensitive. The nature and sensitivity of induced biological effects depend upon dose and developmental stage at irradiation. The various effects, as studied in experimental systems and in man, are discussed in detail. It is concluded that the findings in the report strengthen and supplement the 1990 recommendations of the ICRP.