bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerated Bone Turnover in Pregnant Women with McCune-Albright Syndrome
Authors: Osada Hisao , Sakamoto Rie , Seki Katsuyoshi , Sekiya Souei
Published: April 2005

Bone turnover in pregnant women with McCune-Albright syndrome may be affected by both the syndrome and pregnancy. This study evaluated changes in biochemical bone turnover markers in pregnant women with the syndrome. Serum calcium, phosphorus, 1,25-dihydroxyvitamin D (1,25-(OH)2D), intact osteocalcin (I-OC) and alkaline phosphatase (ALP), and urinary pyridinoline (Pyr), deoxypyridinoline (D-Pyr) and hydroxyproline (HPR) were measured during pregnancy and postpartum in 2 women with McCune-Albright syndrome. Serum calcitonin (CT), and plasma intact parathyroid hormone (I-PTH) and parathyroid hormone-related protein (PTHrP) were also measured in 1 patient. Serum corrected Ca levels were normal or low-normal; phosphorus levels were normal, and 1,25-(OH)2D levels increased toward term and decreased thereafter, similar to normal pregnant women. Urinary Pyr, D-Pyr and HPR were elevated during pregnancy compared to normal pregnant women, peaked just after delivery, and decreased thereafter. Serum I-OC and ALP levels were high during pregnancy and postpartum. Intact PTH levels were increased during pregnancy and postpartum compared to normal pregnant women, whereas serum CT and PTHrP levels were not elevated. Both bone formation and absorption appear to be more enhanced during pregnancy and postpartum in women with McCune-Albright syndrome than in normal pregnant women. Additional or amplified cyclic AMP synthesis in bone cells through activation of the α subunit of G protein, independent of hormonal control, may explain the high local bone turnover.
Physical Training Decreases Total Plasma Homocysteine and Cysteine in Middle-Aged Subjects
Authors: Gaume V. , Mougin F. , Figard H. , Simon-Rigaud M.L. , N’Guyen U.N. , Callier J. , Kantelip J.P. , Berthelot A.
Published: April 2005

Aims: The aim of this study was to evaluate whether endurance exercise in middle-aged men induces changes in plasma total homocysteine (tHcy) and total cysteine (tCys), and whether these changes depend on the diet especially on vitamin B6, folic acid and vitamin B12 intakes. Methods: Twelve trained subjects (52.33 ± 2.4 years) and twelve untrained subjects (56.23 ± 0.9 years) volunteered for the present study. tHcy and tCys were measured with high-pressure liquid chromatography at rest in both groups and during an incremental exercise performed on a cycle ergometer until exhaustion in the trained subjects. Results: At baseline homocysteinemia and cysteinemia were lower in trained subjects (7.48 ± 0.4 and 183.45 ± 13.6 µmol/l) compared with untrained subjects (9.79 ± 0.4 µmol/l, p < 0.001; 229.01 ±14.7 µmol/l, p < 0.05, respectively). Incremental exercise also induced a decrease in tHcy and tCys concentrations. Moreover, tHcy concentration was negatively related to the folic acid and B12 intakes in untrained (r = –0.589, p < 0.05; r = –0.580, p < 0.05, respectively) as well as in trained groups (r = –0.709, p < 0.01; r = –0.731, p < 0.01, respectively) whereas no correlation between tCys and vitamin in the diet was observed. Conclusion: This study demonstrates that the combined effects of a chronic physical exercise and a high folate and vitamin B12 intake could be responsible for the reduction of plasma tHcy and tCys concentrations that might be a key for the prevention of many diseases.
Effect of Hyperprotidic Diet Associated or Not with Hypercalcic Diet on Calcium Oxalate Stone Formation in Rat
Authors: Sakly R. , Bardaoui M. , Neffati F. , Moussa A. , Zakhama A. , Najjar M.F. , Hammami M.
Published: April 2005

The aim of this study was to determine whether protein, administered alone or simultaneously with a hypercalcic diet, was able to aggravate calcium oxalate stone formation in rats. Thirty-two male Wistar rats were randomly divided into four groups of 8 rats each and assigned a calcium oxalate lithogenic diet added to their drinking water for 3 weeks. One group, used as reference, received a standard diet prepared in our laboratory. The second was assigned the same diet but supplemented with 7.5 g animal proteins/100 g diet. The third received a diet containing 500 mg calcium more than the standard group. The diet given to the last group was supplemented with calcium and protein at the same doses indicated previously. One day before the end of treatment, each animal was placed in a metabolic cage to collect 24-hour urine samples and determine urinary creatinine, urea, calcium, magnesium, phosphate, uric acid, citric acid and oxalate levels. Immediately thereafter, aortic blood was collected to determine the same parameters as in urine. The kidneys were also removed to determine calcium oxalate deposits. Our results showed an increased 24-hour urinary excretion of calcium, oxalate and uric acid and decreased urinary citric acid excretion only in groups that received protein supplementation. At the same time, calcium oxalate deposits were found significantly higher in hyperprotidic diets than reference or calcium-supplemented groups. According to these findings, glomerular filtration, fractional excretion of urea and reabsorption of water, calcium and magnesium were found significantly lower in hyperprotidic diets compared to other groups. These results demonstrate that proteins could seriously aggravate calcium oxalate stones and cause renal disturbances.
Mitochondrial DNA Variants in a Portuguese Population of Patients with Alzheimer’s Disease
Authors: Grazina Manuela , Silva Filipe , Santana Isabel , Pratas João , Santiago Beatriz , Oliveira Miguel , Carreira Isabel , Cunha Luís , Oliveira Catarina
Published: April 2005

Alzheimer’s disease (AD) is the most common neurodegenerative disorder associated with dementia in late adulthood. Mitochondrial respiratory chain impairment has been detected in the brain, muscle, fibroblasts and platelets of AD patients, indicating a possible involvement of mitochondrial DNA (mtDNA) in the etiology of the disease. Several reports have identified mtDNA mutations in AD patients, but there is no consensual opinion regarding the cause of the impairment. We have studied mtDNA NADH dehydrogenase subunit 1 nucleotides 3337–3340, searching for mutations. Our study group included 129 AD patients and 125 healthy age-matched controls. We have found alterations in two AD patients: one had two already known mtDNA modifications (3197 T-C and 3338 T-C) and the other a novel transition (3199 T-C) which, to our knowledge, has not been described before.
Identification of Novel Mutations of the DAX-1 Gene in Patients with X-Linked Adrenal Hypoplasia Congenita
Authors: Choi Jin-Ho , Shin Young-Lim , Kim Gu-Hwan , Kim Youngho , Park Sangwook , Park Jung-Young , Oh Changkyu , Yoo Han-Wook
Published: April 2005

Objective: X-linked adrenal hypoplasia congenita (AHC) is a condition clinically featuring adrenal insufficiency and hypogonadotropic hypogonadism caused by mutations of DAX-1. This study was undertaken to characterize the molecular defects of DAX-1 in 3 unrelated Korean patients with AHC. Patients and Methods: Patient 1 is a 6-year-old boy who presented with a salt-losing adrenal crisis in the neonatal period. Patient 2 is a 3-year-old boy who manifested aspiration pneumonia and adrenal insufficiency at the age of 1 month. Patient 3 is a 7-year-old boy who developed an adrenal crisis at the age of 3 days. In each of these patients, DAX-1 was analyzed by direct DNA sequencing after polymerase chain reaction amplification of the entire coding region. Results: Direct sequencing of DAX-1 revealed two novel mutations, 1156_1157delCT in patient 1 and another novel nonsense mutation W105X in patient 2. Patient 3 had complete deletion of DAX-1. In patient 3, serum transaminases and creatine kinase levels were elevated while the glycerol kinase activity of leukocytes was decreased. Markedly elevated glycerol excretion was detected by urine organic acid analysis. Patient 3 was diagnosed as Xp21 contiguous gene syndrome associated with deletions of the entire IL1RAPL, GK genes and the C-terminal region of DMD gene. Conclusions: Two novel mutations of DAX-1 were detected in 2 unrelated patients with AHC, and complete deletion of DAX-1 in a patient with Xp21 contiguous gene syndrome who also presented with glycerol kinase deficiency, Duchenne muscular dystrophy, and AHC.
Rac1 Regulation of Surface Expression of Protease-Activated Receptor-1 and Responsiveness to Thrombin in Vascular Smooth Muscle Cells
Authors: Yufu Tatsuya , Hirano Katsuya , Bi Dan , Hirano Mayumi , Nishimura Junji , Iwamoto Yukihide , Kanaide Hideo
Published: April 2005

Objective—

Protease-activated receptor-1 (PAR1) mediates the thrombin-induced proliferation and hypertrophy of vascular smooth muscle cells. A role of Rac1 in the regulation of PAR1 expression was investigated.

Methods and Results—

Treatment with simvastatin, a hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, for 24 hours attenuated the transient [Ca
2+
]
i
elevation induced by thrombin. Immunofluorescence staining revealed that simvastatin decreased the surface expression of PAR1 in a manner dependent on protein geranylgeranylation. Introduction of a Rac1/Cdc42 inhibitory fragment but not a RhoA inhibitory fragment using a cell-penetrating peptide also attenuated the response to thrombin and decreased the surface expression of PAR1. Finally, downregulation of Rac1, but not RhoA, using an RNA interference technique attenuated the thrombin-induced [Ca
2+
]
i
elevation. However, the level of PAR1 mRNA and the total amount of PAR1 protein remained unchanged.

Conclusions—

Here, we provide for the first time 3 lines of evidence that Rac1 plays a critical role in maintaining the surface expression of PAR1 and the responsiveness to thrombin in vascular smooth muscle cells. Rac1 is suggested to regulate the constitutive trafficking of PAR1 and thereby regulate the surface expression of PAR1.
Binding and Internalization of C-Reactive Protein by Fcgamma Receptors on Human Aortic Endothelial Cells Mediates Biological Effects
Authors: Devaraj Sridevi , Du Clos Terry W. , Jialal Ishwarlal
Published: April 2005

Objective—In addition to being a cardiovascular risk marker, recent studies support a role for CRP in atherothrombosis. Several investigators have reported that CRP binds to Fcgamma receptors on leukocytes. The aim of the study is to determine the processing of CRP by human aortic endothelial cells (HAECs).

Methods and Results—Binding studies were performed by incubation of HAECs with biotinylated CRP (B-CRP, 25 to 200 μg/mL) for 30 to 180 minutes at 4°C. B-CRP binding was quantitated using streptavidin-fluorescein isothiocyanate followed by flow cytometry. Saturable binding of CRP was obtained at 60 minutes with a CRP concentration between 100 to 150 μg/mL and Kd of 88 nM. CRP binding was inhibited by 10× cold CRP (58%). CRP (100 μg/mL) significantly upregulated surface expression of Fcgamma receptors, CD32, as well as CD64 on HAECs (P<0.01). Also, preincubation with anti-CD32 and CD64 antibodies significantly inhibited maximal binding of CRP to HAECs 64% and 30%, respectively, whereas antibodies to CD16 had no effect. Internalization of CRP, as determined by loss of surface expression, was 50%. Also, binding and internalization of biotinylated CRP was confirmed by confocal microscopy and CRP colocalized with CD32 and CD64. Most importantly, the increase in interleukin-8, intercellular adhesion molecule 1, and vascular cell adhesion molecule-1 and the decrease in eNOS and prostacyclin induced by CRP was abrogated with antibodies to CD32 and CD64.

Conclusions—We demonstrate that CRP mediates its biological effects on HAECs via binding and internalization through Fcgamma receptors, CD32 and CD64.
Rule-Based Category Learning is Impaired in Patients with Parkinson's Disease but not in Patients with Cerebellar Disorders
Authors: Maddox W. Todd , Aparicio Paul , Marchant Natalie L. , Ivry Richard B.
Published: April 2005

The basal ganglia and cerebellum have both been implicated in motor skill acquisition. Recent hypotheses concerning cognitive functions of the basal ganglia and cerebellum have emphasized that these subcortical structures may also contribute to nonmotor learning. To explore this issue, patients with Parkinson's disease (PD) and patients with cerebellar lesions (CB) were tested on two category-learning tasks. Identical stimulus displays were used for the two tasks, consisting of a reference line and target line. In the length task, the two categories were defined based on the length of the target line. In the distance task, the two categories were defined by the distance between the target and reference lines. Thus, both categories could be defined by a simple rule in which attention must be restricted to a single relevant dimension. Consistent with previous results, the patients with PD were impaired on both tasks compared with neurologically healthy controls. In contrast, the CB patients performed similar to the control participants. Model-based analyses indicate that the patients with PD were able to select the appropriate categorization rule, but that they adopted suboptimal category boundaries in both conditions and were more variable in the application of the selected rule. These results provide an important neuropsychological dissociation on a non-motor-learning task between the effects of basal ganglia and cerebellar lesions. Moreover, the modeling work suggests that at least part of the Parkinson patients' impairment on these tasks reflect a tendency to exhibit strong response biases.
An Electrophysiological Investigation of Factors Facilitating Strategic Recollection
Authors: Herron J. E. , Wilding E. L.
Published: April 2005

Episodic memory is thought to be mediated by executive processes that facilitate the retrieval of task-relevant information at the expense of irrelevant information. The exclusion task [A process dissociation framework: Separating automatic from intentional uses of memory.Journal of Memory and Language, 30, 513-541, 1991] can be used to explore these processes. In this task, studied items from one source (“targets”) are endorsed on one response key, whereas new and studied items from another source (“nontargets”) are rejected on another key. Herron and Rugg [Strategic influences on recollection in the exclusion task: Electrophysiological evidence.Psychonomic Bulletin and Review, 10, 703-710, 2003] reported that nontargets elicited the ERP correlate of recollection (the “left parietal old/new effect”) when target accuracy was low, but not when it was high. Their explanation for this was that participants only focused exclusively on the recollection of target information when the likelihood of target recollection was high, as under these conditions this strategy is one that that will give rise to accurate task performance. The fact, however, that targets were encoded in different tasks in the high-and low-accuracy groups means that the results can also be explained in terms of the encoding operations performed at study rather than in terms of target accuracy. This study was designed to distinguish between these competing accounts. All targets were encoded elaboratively. Target accuracy was reduced in one condition with a 40-min study-test interval. Nontargets elicited no left parietal effect in either condition, suggesting that target-specific strategic retrieval is facilitated by certain classes of encoding operations rather than simply high target accuracy per se.
Relating Eulerian and Lagrangian Statistics for the Turbulent Dispersion in the Atmospheric Convective Boundary Layer
Authors: Dosio Alessandro , Guerau de Arellano Jordi Vilá , Holtslag Albert A. M. , Builtjes Peter J. H.
Published: April 2005

Eulerian and Lagrangian statistics in the atmospheric convective boundary layer (CBL) are studied by means of large eddy simulation (LES). Spectra analysis is performed in both the Eulerian and Lagrangian frameworks, autocorrelations are calculated, and the integral length and time scales are derived. Eulerian statistics are calculated by means of spatial and temporal analysis in order to derive characteristic length and time scales. Taylor’s hypothesis of frozen turbulence is investigated, and it is found to be satisfied in the simulated flow.

Lagrangian statistics are derived by tracking the trajectories of numerous particles released at different heights in the turbulent flow. The relationship between Lagrangian properties (autocorrelation functions) and dispersion characteristics (particles’ displacement) is studied through Taylor’s diffusion relationship, with special emphasis on the difference between horizontal and vertical motion. Results show that for the horizontal motion, Taylor’s relationship is satisfied. The vertical motion, however, is influenced by the inhomogeneity of the flow and limited by the ground and the capping inversion at the top of the CBL. The Lagrangian autocorrelation function, therefore, does not have an exponential shape, and consequently, the integral time scale is zero. If distinction is made between free and bounded motion, a better agreement between Taylor’s relationship and the particles’ vertical displacement is found.

Relationships between Eulerian and Lagrangian frameworks are analyzed by calculating the ratio β between Lagrangian and Eulerian time scales. Results show that the integral time scales are mainly constant with height for z/zi < 0.7. In the upper part of the CBL, the capping inversion transforms vertical motion into horizontal motion. As a result, the horizontal time scale increases with height, whereas the vertical one is reduced. Current parameterizations for the ratio between the Eulerian and Lagrangian time scales have been tested against the LES results showing satisfactory agreement at heights z/zi < 0.7.
Mechanisms for the Development of Locally Low-Dimensional Atmospheric Dynamics
Authors: Oczkowski Michael , Szunyogh Istvan , Patil D. J.
Published: April 2005

The complexity of atmospheric instabilities is investigated by a combination of numerical experiments and diagnostic tools that do not require the assumption of linear error dynamics. These tools include the well-established analysis of the local energetics of the atmospheric flow and the recently introduced ensemble dimension (E dimension). The E dimension is a local measure that varies in both space and time and quantifies the distribution of the variance between phase space directions for an ensemble of nonlinear model solutions over a geographically localized region. The E dimension is maximal, that is, equal to the number of ensemble members (k), when the variance is equally distributed between k phase space directions. The more unevenly distributed the variance, the lower the E dimension.

Numerical experiments with the state-of-the-art operational Global Forecast System (GFS) of the National Centers for Environmental Prediction (NCEP) at a reduced resolution are carried out to investigate the spatiotemporal evolution of the E dimension. This evolution is characterized by an initial transient phase in which coherent regions of low dimensionality develop through a rapid local decay of the E dimension. The typical duration of the transient is between 12 and 48 h depending on the flow; after the initial transient, the E dimension gradually increases with time.

The main goal of this study is to identify processes that contribute to transient local low-dimensional behavior. Case studies are presented to show that local baroclinic and barotropic instabilities, downstream development of upper-tropospheric wave packets, phase shifts of finite amplitude waves, anticyclonic wave breaking, and some combinations of these processes can all play crucial roles in lowering the E dimension.

The practical implication of the results is that a wide range of synoptic-scale weather events may exist whose prediction can be significantly improved in the short and early medium range by enhancing the prediction of only a few local phase space directions. This potential is demonstrated by a reexamination of the targeted weather observations missions from the 2000 Winter Storm Reconnaissance (WSR00) program.
Tropical Climate Regimes and Global Climate Sensitivity in a Simple Setting
Authors: Barsugli Joseph , Shin Sang-Ik , Sardeshmukh Prashant D.
Published: April 2005

Multiple tropical climate regimes are found in an atmospheric general circulation model (AGCM) coupled to a global slab ocean when the model is forced by different values of globally uniform insolation. Even in this simple setting, convection organizes into an intertropical convergence zone (ITCZ) solely due to the effect of planetary rotation, as was found in Kirtman and Schneider, for a single value of insolation. Here the response to a range of insolation values is explored, and surprisingly, multiple climate regimes characterized by radically different ITCZ structures are found. In order from the coldest to warmest climates, these are a symmetric double ITCZ, a near-symmetric equatorial ITCZ, a transient asymmetric ITCZ, and a stable, strongly asymmetric ITCZ.

The model exhibits hysteresis in the transition from the near-symmetric to the strongly asymmetric ITCZ regimes when insolation is increased and then decreased. The initial transition away from symmetry can occur in the absence of air–sea coupling; however, the coupling is essential for the establishment and maintenance of the strongly asymmetric ITCZ. Wind–evaporation–SST feedback as well as the longwave radiative effects of clouds and water vapor on SSTs appear to be important in maintaining the asymmetric regime. The existence of multiple regimes in a single AGCM, and the dependence of these regimes on SST feedbacks, may have a bearing on the ITCZ simulation errors of current coupled climate models.

The sensitivity of the global mean surface temperature generally decreases with increasing insolation, a consequence primarily of increasingly negative shortwave cloud forcing. Climate sensitivity measured across a regime transition can be much larger than the sensitivity within a single regime.
Modeling Diurnal and Intraseasonal Variability of the Ocean Mixed Layer
Authors: Bernie D. J. , Woolnough S. J. , Slingo J. M. , Guilyardi E.
Published: April 2005

The intraseasonal variability of SST associated with the passage of the Madden–Julian oscillation (MJO) is well documented; yet coupled model integrations generally underpredict the magnitude of this SST variability. Observations from the Improved Meteorological Instrument (IMET) mooring in the western Pacific during the intensive observing period (IOP) of the Tropical Ocean Global Atmosphere Coupled Ocean–Atmosphere Response Experiment (TOGA COARE) showed a large diurnal signal in SST that is modulated by the passage of the MJO. In this study, observations from the IOP of the TOGA COARE and a one-dimensional (1D) ocean mixed layer model incorporating the K-Profile Parameterization (KPP) vertical mixing scheme have been used to investigate the rectification of the intraseasonal variability of SST by the diurnal cycle and the implied impact of the absence of a representation of this process on the modeled intraseasonal variability in coupled GCMs. Analysis of the SST observations has shown that the increase of the daily mean SST by the diurnal cycle of SST accounts for about one-third of the magnitude of intraseasonal variability of SST associated with the Madden–Julian oscillation in the western Pacific warm pool.

Experiments from the 1D model forced with fluxes at a range of temporal resolutions and with differing vertical resolution of the model have shown that to capture 90% of the diurnal variability of SST, and hence 95% of the intraseasonal variability of SST, requires a 3-h or better temporal resolution of the fluxes and a vertical grid with an upper-layer thickness of the order of 1 m. In addition to the impact of the representation of the diurnal cycle on the intraseasonal variability of SST, the strength of the mixing across the thermocline was found to be enhanced by the proper representation of the nighttime deep mixing in the ocean, implying a possible impact of the diurnal cycle onto the mean climate of the tropical ocean.
Changes toward Earlier Streamflow Timing across Western North America
Authors: Stewart Iris T. , Cayan Daniel R. , Dettinger Michael D.
Published: April 2005

The highly variable timing of streamflow in snowmelt-dominated basins across western North America is an important consequence, and indicator, of climate fluctuations. Changes in the timing of snowmelt-derived streamflow from 1948 to 2002 were investigated in a network of 302 western North America gauges by examining the center of mass for flow, spring pulse onset dates, and seasonal fractional flows through trend and principal component analyses. Statistical analysis of the streamflow timing measures with Pacific climate indicators identified local and key large-scale processes that govern the regionally coherent parts of the changes and their relative importance.

Widespread and regionally coherent trends toward earlier onsets of springtime snowmelt and streamflow have taken place across most of western North America, affecting an area that is much larger than previously recognized. These timing changes have resulted in increasing fractions of annual flow occurring earlier in the water year by 1–4 weeks. The immediate (or proximal) forcings for the spatially coherent parts of the year-to-year fluctuations and longer-term trends of streamflow timing have been higher winter and spring temperatures. Although these temperature changes are partly controlled by the decadal-scale Pacific climate mode [Pacific decadal oscillation (PDO)], a separate and significant part of the variance is associated with a springtime warming trend that spans the PDO phases.
Should Social Science Be Critical?
Authors: Hammersley Martyn
Published: April 2005

The word critical has become an honorific title used by researchers to commend their work, or the particular approach they adopt. Conversely, the work of others is often dismissed on the grounds that it is “uncritical”. However, there are important questions about what the term critical means, about what we should be critical of, and about the form that criticism ought to take. These questions are addressed here in relation to both the role of the social researcher itself and that of researchers operating as public intellectuals. It is argued that the distinction between these roles is an important one, and has implications for what can legitimately be criticised, on what grounds, and in what way. In each case, there are proper limits to criticism, albeit different ones. Like anything else, criticism is not always a good thing.
Increasing the Degrees of Freedom in Future Group Randomized Trials
Authors: Blitstein Jonathan L. , Murray David M. , Hannan Peter J. , Shadish William R.
Published: April 2005

This article builds on the previous article by Blitstein et al. (2005), which showed how external estimates of intraclass correlation can be used to improve the precision for the analysis of an existing group randomized trial. The authors extend that work to sample size estimation and power analysis for future group-randomized trials. Often this approach will allow a smaller study than would otherwise be possible without sacrificing statistical power. Such studies are needed, for example, as pilot studies to help plan for a full-scale efficacy trial, as replication studies, or in situations in which resource constraints prohibit a larger trial. The authors discuss the circumstances under which this strategy will be most helpful and the risks associated with conducting smaller studies.
Monetary Incentives in Support of Academic Achievement
Authors: Spencer Margaret Beale , Noll Elizabeth , Cassidy Elaine
Published: April 2005

Significant resources have been directed at understanding and alleviating the achievement gap in education. Most programs focused on this aim rely on a top-down approach, including funding for infrastructure improvement, curriculum development, class size, and teacher salaries. This article presents findings from a randomized field trial that evaluates a bottom-up approach in which high-achieving students of diverse racial and ethnic backgrounds from poor families are given monetary incentives to maintain their academic standing. The evaluation was designed to explore the role of monetary incentives as a mechanism for promoting resiliency in the face of poverty-related challenge. Discussion of what motivates students to learn is framed as a function of normal cognitive and socioemotional development in challenging environments. Evaluation findings indicate that monetary incentives are effective in promoting academic success to different degrees and for different reasons depending on students’ perception of the meaning of the incentive in relation to their emergent identity.
Supervisory Perceptions of the Impact of Public Sector Personnel Practices on the Achievement of Multiple Goals
Authors: Daley Dennis M. , Vasu Michael L.
Published: April 2005

Strategic human resource management enhances productivity and the effectiveness of organizations. Research shows that when organizations employ such personnel practices as internal career ladders, formal training systems, results-oriented performance appraisal, employment security, employee voice and participation, broadly defined jobs, and performance-based compensation, they are more able to achieve their goals and objectives. Using ordinal regression analyses of data from a survey of North Carolina county social service directors and supervisors, this study examines the extent to which strategic human resource management is perceived to affect outcome assessments (or performance measurements) for welfare reform. Although strategic human resource management practices are perceived to be present, with training and employment security having notable impacts, they clearly are not a predominant feature in North Carolina counties.
Are we All Touching the Same Camel?
Authors: Franklin Aimee L. , Ebdon Carol
Published: April 2005

Theory offers a vast quantity of normative prescriptions concerning citizen participation in budget decisions. Yet cities struggle with this activity and report unsatisfactory outcomes. Why does this occur? It may be because, similar to the parable of the blind men describing the different parts of the camel, the extant literature suggests so many variables but does not integrate what we know to see the whole picture, nor does it eliminate variables having little explanatory value and there has been limited systematic testing of hypotheses in this area. To manage the complexity caused by a multiplicity of variables, the authors test a causal model with four different factors (structure, participants, process, and mechanisms) thought to influence effective citizen participation outcomes on cases of two midwestern cities. In this limited application, the model shows promise for predictive validity.
Capitalizing on Student Workers
Authors: Watson Douglas J. , Hassett Wendy L.
Published: April 2005

For more than a decade, the City of Auburn, Alabama, has employed university students as part-time firefighters, police aides, and 911 communicators. The most fully developed program allows students to be trained and work as state-certified firefighters. Newly constructed fire stations have separate dormitory-style rooms for the students. Tuition is paid by the city as long as the students earn at least a 2.5 grade point average. This program has been cost effective for the city and the source of tuition assistance for hundreds of college students. Furthermore, it has created a talented pool of candidates for regular city employment.
The Status of U.S. Public Pension Plans
Authors: Schneider Marguerite
Published: April 2005

The pension plans of U.S. state, county, and municipal employees play a large role in capital markets and corporate governance debates. Recent studies have investigated the governance, management, and performance of these plans, as well as their role in corporate governance. Informed by the findings of its integrative literature review, the article outlines several key considerations regarding the plans, including ones regarding the bearing of investment risk, public and private plan differentials, the presence and responsibilities of boards of trustees, and investment policy. The outlined considerations favor an appropriate balance between political and economic controls of the plans and recognize that the activism of public pension plans as institutional investors might improve the corporate governance system for all investors.
Too Much of a Good Thing
Authors: Schneider Benjamin , Paul Michelle C. , White Susan S.
Published: April 2005

The authors discuss the dangers for organizations of focusing too much on a single organizational goal or constituent, including the potential for service organizations to overemphasize a focus on end user consumer service quality. Several examples of "too much of a good thing" are presented, including examples of too much emphasis on service quality. A multiple-constituency perspective for organizational effectiveness is then introduced. This is followed by a proposal to use employees as sensors of the climates that exist in organizations for the achievement of various goals and the gratification of various constituents. Evidence is presented for the validity of employee perceptions. The authors conclude that it is dangerous for long-term organizational health to over focus on one goal or one constituency and that asking employees about the various climates to which they are responding is a useful way to know which goals the organization is attempting to achieve.
Nurselike cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1α
Authors: Nishio Mitsufumi , Endo Tomoyuki , Tsukada Nobuhiro , Ohata Junko , Kitada Shinichi , Reed John C. , Zvaifler Nathan J. , Kipps Thomas J.
Published: April 2005

We examined expression of B cell–activating factor of the tumor necrosis factor (TNF) family (BAFF) and a proliferation-inducing ligand (APRIL) on chronic lymphocytic leukemia (CLL) B cells and nurselike cells (NLCs), which differentiate from CD14+ cells when cultured with CLL B cells. NLCs expressed significantly higher levels of APRIL than monocytes and significantly higher levels of BAFF and APRIL than CLL B cells. Also, the viability of CLL B cells cultured with NLCs was significantly reduced when CLL B cells were cultured with decoy receptor of B-cell maturation antigen (BCMA), which can bind both BAFF and APRIL, but not with BAFF receptor:Fc (BAFF-R:Fc), which binds only to BAFF. The effect(s) of BAFF or APRIL on leukemia cell survival appeared additive and distinct from that of stromal cell–derived factor-1α (SDF-1α), which in contrast to BAFF or APRIL induced leukemia cell phosphorylation of p44/42 mitogen-activated protein kinase (extracellular signal-regulated kinase-1/2 [ERK1/2]) and AKT. Conversely, BAFF and APRIL, but not SDF-1α, induced CLL-cell activation of the nuclear factor–κB1 (NF-κB1) and enhanced CLL-cell expression of the antiapoptotic protein Mcl-1. However, BAFF, but not APRIL, also induced CLL-cell activation of NF-κB2. We conclude that BAFF and APRIL from NLCs can function in a paracrine manner to support leukemia cell survival via mechanisms that are distinct from those of SDF-1α, indicating that NLCs use multiple distinct pathways to support CLL-cell survival.
Resistance to farnesyltransferase inhibitors in Bcr/Abl-positive lymphoblastic leukemia by increased expression of a novel ABC transporter homolog ATP11a
Authors: Zhang Bin , Groffen John , Heisterkamp Nora
Published: April 2005

Resistance to cytotoxic drugs frequently emerges during treatment of leukemia with conventional chemotherapy. New classes of anticancer drugs, such as the farnesyltransferase inhibitors (FTIs), show therapeutic promise, but whether cells will easily develop resistance against them is not known. Here, we grew breakpoint cluster region/Abelson murine leukemia (Bcr/Abl) P190 lymphoblasts on stroma and made them resistant to the FTI SCH66336/lonafarnib to model emerging drug resistance in a patient. These cells exhibited greatly increased (> 100-fold) expression levels of a novel ATP (adenosine triphosphate)-binding cassette (ABC) transporter-homologous gene, ATP11A. We showed that overexpression of this gene provided protection against the effects of SCH66336, whereas knockdown of endogenous ATP11a using small interfering RNA (siRNA) made cells more sensitive to this drug. The lymphoblasts that were resistant to this FTI were also more resistant to FTI-276 and to GGTI-298, 2 other structurally similar inhibitors. Surprisingly, the cells were also able to survive higher concentrations of imatinib mesylate, the Bcr/Abl tyrosine kinase inhibitor. However, the cells remained sensitive to vincristine. Our results show that elevated levels of ATP11a can protect malignant lymphoblastic leukemia cells against several novel small molecule signal transduction inhibitors. A determination of the expression levels of this gene may have prognostic value when treatment with such classes of drugs is contemplated. (Blood. 2005;106: 1355-1361)
Transcriptional induction of cyclooxygenase-2 in osteoclast precursors is involved in RANKL-induced osteoclastogenesis
Authors: Han Song Yi , Lee Na Kyung , Kim Kyung Hee , Jang In Whan , Yim Mijung , Kim Jae Hong , Lee Won Jae , Lee Soo Young
Published: April 2005

Regulation of osteoclast differentiation is key to understanding the pathogenesis and to developing treatments for bone diseases such as osteoporosis. To gain insight into the mechanism of the receptor activator of nuclear factor (NF)–κB ligand (RANKL)–specific induction of the osteoclast differentiation program, we took a suppression-subtractive hybridization screening approach to identify genes specifically induced via the RANKL-Rac1 signaling pathway. Among identified targets, we show that RANKL selectively induces cyclooxygenase (COX) 2 expression via Rac1 that results in turn in production of prostaglandin E2 (PGE2) in RAW 264.7 cells. By using transient transfection assays, we found that the –233/–206 region of the COX-2 promoter gene was critical for RANKL-induced promoter activity. This RANKL-responsive region contained an NF-κB site that, when mutated, completely abolished the induction of NF-κB DNA-binding activity by RANKL. Blockade of COX-2 by celecoxib inhibits differentiation of bone marrow-derived monocyte/macrophage precursor cells (BMMs) into tartrate-resistant acid phosphatase-positive (TRAP+) osteoclastic cells. This inhibition can be rescued by the addition of exogenous PGE2, suggesting that COX-2–dependent PGE2 induction by RANKL in osteoclast precursors is required for osteoclast differentiation.
Differential requirements for the activation domain and FOG-interaction surface of GATA-1 in megakaryocyte gene expression and development
Authors: Muntean Andrew G. , Crispino John D.
Published: April 2005

GATA1 is mutated in patients with 2 different disorders. First, individuals with a GATA1 mutation that blocks the interaction between GATA-1 and its cofactor Friend of GATA-1 (FOG-1) suffer from dyserythropoietic anemia and thrombocytopenia. Second, children with Down syndrome who develop acute megakaryoblastic leukemia harbor mutations in GATA1 that lead to the exclusive expression of a shorter isoform named GATA-1s. To determine the effect of these patient-specific mutations on GATA-1 function, we first compared the gene expression profile between wild-type and GATA-1–deficient megakaryocytes. Next, we introduced either GATA-1s or a FOG-binding mutant (V205G) into GATA-1–deficient megakaryocytes and assessed the effect on differentiation and gene expression. Whereas GATA-1–deficient megakaryocytes failed to undergo terminal differentiation and proliferated excessively in vitro, GATA-1s–expressing cells displayed proplatelet formation and other features of terminal maturation, but continued to proliferate aberrantly. In contrast, megakaryocytes that expressed V205G GATA-1 exhibited reduced proliferation, but failed to undergo maturation. Examination of the expression of megakaryocyte-specific genes in the various rescued cells correlated with the observed phenotypic differences. These studies show that GATA-1 is required for both normal regulation of proliferation and terminal maturation of megakaryocytes, and further, that these functions can be uncoupled by mutations in GATA1.
The Shwachman-Diamond SBDS protein localizes to the nucleolus
Authors: Austin Karyn M. , Leary Rebecca J. , Shimamura Akiko
Published: April 2005

Shwachman-Diamond syndrome (SDS) is an autosomal recessively inherited disorder characterized by exocrine pancreatic insufficiency and bone marrow failure. The gene for this syndrome, SBDS, encodes a highly conserved novel protein. We characterized Shwachman-Bodian-Diamond syndrome (SBDS) protein expression and intracellular localization in 7 patients with SDS and healthy controls. As predicted by gene mutation, 4 patients with SDS exhibited no detectable full-length SBDS protein. Patient DF277, who was homozygous for the IVS2 + 2 T>C splice donor mutation, expressed scant levels of SBDS protein. Patient SD101 expressed low levels of SBDS protein harboring an R169C missense mutation. Patient DF269, who carried no detectable gene mutations, expressed wild-type levels of SBDS protein to add further support to the growing body of evidence for additional gene(s) that might contribute to the pathogenesis of the disease phenotype. The SBDS protein was detected in both the nucleus and the cytoplasm of normal control fibroblasts, but was particularly concentrated within the nucleolus. SBDS localization was cell-cycle dependent, with nucleolar localization during G1 and G2 and diffuse nuclear localization during S phase. SBDS nucleolar localization was intact in SD101 and DF269. The intranucleolar localization of SBDS provides further supportive evidence for its postulated role in rRNA processing.
The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both “atypical” myeloproliferative disorders and myelodysplastic syndromes
Authors: Steensma David P. , Dewald Gordon W. , Lasho Terra L. , Powell Heather L. , McClure Rebecca F. , Levine Ross L. , Gilliland D. Gary , Tefferi Ayalew
Published: April 2005

A somatic mutation in the JH2 autoinhibitory domain of the Janus kinase 2 (JAK2) tyrosine kinase was recently described in polycythemia vera, essential thrombocythemia, and myelofibrosis with myeloid metaplasia. The prevalence of this mutation in either “atypical” myeloproliferative disorders (MPDs) or the myelodysplastic syndromes (MDSs) is unknown. Bone marrow–derived genomic DNA from 245 patients—119 with chronic myelomonocytic leukemia (CMML), 101 with MDS, 11 with hypereosinophilic syndrome (HES), 8 with systemic mastocytosis (SM), and 6 with chronic neutrophilic leukemia (CNL)—was screened for the JAK2 V617F mutation. A mutant allele was detected in 11 patients: 3 with CMML (3%), 5 with MDS (5%), 2 with SM, and 1 with CNL. Interestingly, one of the patients with SM and the patient with CNL with JAK2 V617F had a history of lymphoma, and this patient with SM also had associated myelofibrosis and CMML. The current observation strengthens the specific association between JAK2 V617F and classic MPD, but also suggests an infrequent occurrence in other myeloid disorders.
Severity of obstructive airway disease and risk of osteoporotic fracture
Authors: de Vries F. , van Staa T. P. , Bracke M. S. G. M. , Cooper C. , Leufkens H. G. M. , Lammers J-W. J.
Published: April 2005

The use of inhaled corticosteroids has been associated with a dose-related increased risk of fracture. This may be related to systemic absorption. However, several studies have found that patients with more severe reductions in pulmonary function had reduced bone mineral density, independent of inhaled corticosteroids. The objective of this study was to evaluate the relationship between disease severity and fracture risk.

A large case–control study (108,754 cases) was conducted using data from the UK General Practice Research Database. It was found that higher doses of inhaled corticosteroids were associated with greater risks of fracture. The crude odds ratio of fracture among patients exposed to >1,600 μg beclomethasone equivalents per day was 1.95 (95% confidence interval (CI) 1.68–2.27). When adjustments were made for disease severity and use of bronchodilators, the initial dose–response relationship between inhaled corticosteroids and fracture risk disappeared (adjusted odds ratio of 1.19 (95% CI 1.01–1.41)).

In conclusion, patients with severe obstructive airway disease are at risk of fracture. However, adequate adjustment for disease severity is essential when the association between the use of inhaled corticosteroids and risk of osteoporotic fracture is studied in observational research.
C-reactive protein as a marker of ventilator-associated pneumonia resolution: a pilot study
Authors: Póvoa P. , Coelho L. , Almeida E. , Fernandes A. , Mealha R. , Moreira P. , Sabino H.
Published: April 2005

The aim of this study was to evaluate C-reactive protein (CRP) levels, body temperature and white cell count (WCC) after prescription of antibiotics in order to describe the clinical resolution of ventilator-associated pneumonia (VAP).

A cohort of 47 VAP patients with microbiological confirmation of disease was assessed. CRP levels, body temperature and WCC were monitored daily.

On day 4 of the antibiotic therapy, the CRP level of survivors was 0.62 times the initial value, whereas, in nonsurvivors, it was 0.98. Body temperature and WCC remained almost unchanged. By day 4, a CRP of >0.6 times the initial level was a marker of poor outcome (sensitivity 0.92; specificity 0.59). Patients were divided according to their CRP patterns of response to antibiotics: fast response, slow response, nonresponse, and biphasic response. All patients with fast and slow response patterns survived, whereas those showing nonresponse and a biphasic response pattern exhibited a mortality of 78 and 75%, respectively. The adequacy of the initial antibiotic therapy had a marked influence on the rate of CRP decrease, as well as on mortality.

In conclusion, daily C-reactive protein measurements after antibiotic prescription were useful in the identification, as early as day 4, of ventilator-associated pneumonia patients with poor outcome. The identification of the pattern of C-reactive protein response to antibiotics was useful in the recognition of individual clinical course, improving or worsening, as well as of the rate of improvement.
Pulmonary hypertension in advanced sarcoidosis: epidemiology and clinical characteristics: Table. 1—
Authors: Shorr A. F. , Helman D. L. , Davies D. B. , Nathan S. D.
Published: April 2005

Pulmonary hypertension (PH) is a predictor of poor outcome in sarcoidosis. Little is known about the epidemiology of PH in sarcoidosis.

The current authors reviewed the records of patients with sarcoidosis listed for lung transplantation in the USA between January 1995 and December 2002. PH was defined as a mean pulmonary artery pressure of >25 mmHg and severe PH as a mean pulmonary artery pressure of ≥40 mmHg.

The cohort included 363 patients of whom 73.8% had PH. Neither spirometric testing nor the need for corticosteroids was associated with PH. Subjects with PH required more supplemental oxygen (2.7±1.8 L·min−1versus1.6±1.4 L·min−1). The cardiac index was lower in individuals with PH, whereas the pulmonary capillary wedge pressure was higher. In multivariate analysis, supplemental oxygen remained an independent predictor of PH, whereas the relationship between cardiac index and PH was no longer significant. As a screening test, the need for oxygen had a sensitivity and specificity of 91.8% and 32.6%, respectively.

Pulmonary hypertension is common in advanced sarcoidosis. The need for oxygen correlates with pulmonary hypertension. Since pulmonary hypertension is associated with poor outcomes and because simple clinical criteria fail to identify patients with sarcoidosis and pulmonary hypertension, more aggressive screening for this should be considered.