bluuebunny/crossref_metadata_2025 huggingface dataset:
Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/γ
c
null
immunodeficient mice
Authors: Masuda Hirotaka , Maruyama Tetsuo , Hiratsu Emi , Yamane Junichi , Iwanami Akio , Nagashima Takashi , Ono Masanori , Miyoshi Hiroyuki , Okano Hirotaka James , Ito Mamoru , Tamaoki Norikazu , Nomura Tatsuji , Okano Hideyuki , Matsuzaki Yumi , Yoshimura Yasunori
Published: February 2007

Human uterine endometrium exhibits unique properties of cyclical regeneration and remodeling throughout reproductive life and also is subject to endometriosis through ectopic implantation of retrogradely shed endometrial fragments during menstruation. Here we show that functional endometrium can be regenerated from singly dispersed human endometrial cells transplanted beneath the kidney capsule of NOD/SCID/γ
c
null
immunodeficient mice. In addition to the endometrium-like structure, hormone-dependent changes, including proliferation, differentiation, and tissue breakdown and shedding (menstruation), can be reproduced in the reconstructed endometrium, the blood to which is supplied predominantly by human vessels invading into the mouse kidney parenchyma. Furthermore, the hormone-dependent behavior of the endometrium regenerated from lentivirally engineered endometrial cells expressing a variant luciferase can be assessed noninvasively and quantitatively by
in vivo
bioluminescence imaging. These results indicate that singly dispersed endometrial cells have potential applications for tissue reconstitution, angiogenesis, and human–mouse chimeric vessel formation, providing implications for mechanisms underlying the physiological endometrial regeneration during the menstrual cycle and the establishment of endometriotic lesions. This animal system can be applied as the unique model of endometriosis or for other various types of neoplastic diseases with the capacity of noninvasive and real-time evaluation of the effect of therapeutic agents and gene targeting when the relevant cells are transplanted beneath the kidney capsule.
The optimal height of the synaptic cleft
Authors: Savtchenko Leonid P. , Rusakov Dmitri A.
Published: February 2007

Signal integration in the brain is determined by the size and kinetics of rapid synaptic responses. The latter, in turn, depends on the concentration profile of neurotransmitter in the synaptic cleft. According to a traditional view, narrower clefts should correspond to higher intracleft concentrations of neurotransmitter, and therefore to the enhanced activation of synaptic receptors. Here, we argue that narrowing the cleft also increases electrical resistance of the intracleft medium and therefore reduces local receptor currents. We employ detailed theoretical analyses and Monte Carlo simulations to propose that these two contrasting phenomena result in a relatively narrow range of cleft heights at which the synaptic receptor current reaches its maximum. Over a physiological range of synaptic parameters, the “optimum” height falls between ≈12 and 20 nm. This range is consistent with the structure of central synapses reported by electron microscopy. Therefore, our results suggest that a simple fundamental principle may underlie the synaptic cleft architecture: to maximize synaptic strength.
Relational representation in the olfactory system
Authors: Cleland Thomas A. , Johnson Brett A. , Leon Michael , Linster Christiane
Published: February 2007

The perceptual quality of odors usually is robust to variability in concentration. However, maps of neural activation across the olfactory bulb glomerular layer are not stable in this respect; rather, glomerular odor representations both broaden and intensify as odorant concentrations are increased. The relative levels of activation among glomeruli, in contrast, remain relatively stable across concentrations, suggesting that the representation of odor quality may rely on these relational activity patterns. However, the neural normalization mechanisms enabling extraction of such relational representations are unclear. Using glomerular imaging activity profiles from the rat olfactory bulb together with computational modeling, we here show that (
i
) global normalization preserves concentration-independent odor-quality information; (
ii
) perceptual similarities, as assessed behaviorally, are better predicted by normalized than by raw bulbar activity profiles; and (
iii
) a recurrent excitatory circuit recently described in the olfactory bulb is capable of performing such normalization. We show that global feed-forward normalization in a sensory system is behaviorally relevant, and that a center-surround neural architecture does not necessarily imply center-surround function.
Malaria hemozoin is immunologically inert but radically enhances innate responses by presenting malaria DNA to Toll-like receptor 9
Authors: Parroche Peggy , Lauw Fanny N. , Goutagny Nadege , Latz Eicke , Monks Brian G. , Visintin Alberto , Halmen Kristen A. , Lamphier Marc , Olivier Martin , Bartholomeu Daniella C. , Gazzinelli Ricardo T. , Golenbock Douglas T.
Published: February 2007

Hemozoin (HZ) is an insoluble crystal formed in the food vacuole of malaria parasites. HZ has been reported to induce inflammation by directly engaging Toll-like receptor (TLR) 9, an endosomal receptor. “Synthetic” HZ (β-hematin), typically generated from partially purified extracts of bovine hemin, is structurally identical to natural HZ. When HPLC-purified hemin was used to synthesize the crystal, β-hematin had no inflammatory activity. In contrast, natural HZ from
Plasmodium falciparum
cultures was a potent TLR9 inducer. Natural HZ bound recombinant TLR9 ectodomain, but not TLR2. Both TLR9 stimulation and TLR9 binding of HZ were abolished by nuclease treatment. PCR analysis demonstrated that natural HZ is coated with malarial but not human DNA. Purified malarial DNA activated TLR9 but only when DNA was targeted directly to the endosome with a transfection reagent. Stimulatory quantities of natural HZ contain <1 μg of malarial DNA; its potency in activating immune responses was even greater than transfecting malarial DNA. Thus, although the malarial genome is extremely AT-rich, its DNA is highly proinflammatory, with the potential to induce cytokinemia and fever during disease. However, its activity depends on being bound to HZ, which we propose amplifies the biological responses to malaria DNA by targeting it to a TLR9
+
intracellular compartment.
Axonal-SMN (a-SMN), a protein isoform of the survival motor neuron gene, is specifically involved in axonogenesis
Authors: Setola Veronica , Terao Mineko , Locatelli Denise , Bassanini Stefania , Garattini Enrico , Battaglia Giorgio
Published: February 2007

Spinal muscular atrophy (SMA) is an autosomal recessive disease of childhood due to loss of the telomeric survival motor neuron gene,
SMN1
. The general functions of the main
SMN1
protein product, full-length SMN (FL-SMN), do not explain the selective motoneuronal loss of SMA. We identified axonal-SMN (a-SMN), an alternatively spliced
SMN
form, preferentially encoded by the
SMN1
gene in humans. The a-SMN transcript and protein are down-regulated during early development in different tissues. In the spinal cord, the a-SMN protein is selectively expressed in motor neurons and mainly localized in axons. Forced expression of a-SMN stimulates motor neuron axonogenesis in a time-dependent fashion and induces axonal-like growth in non-neuronal cells. Exons 2b and 3 are essential for the axonogenic effects. This discovery indicates an unexpected complexity of the
SMN
gene system and may help in understanding the pathogenesis of SMA.
Substance P mediates antiapoptotic responses in human colonocytes by Akt activation
Authors: Koon Hon-Wai , Zhao Dezheng , Zhan Yanai , Moyer Mary P. , Pothoulakis Charalabos
Published: February 2007

We examined the hypothesis that substance P (SP) and the neurokinin-1 receptor (NK-1R), both
in vitro
and
in vivo
, promote mucosal healing during recovery from colitis by stimulating antiapoptotic pathways in human colonic epithelial cells. For the
in vitro
experiments, human nontransformed NCM460 colonocytes stably transfected with NK-1R (NCM460-NK-1R cells) were exposed to SP, and cell viability assays, TUNEL assays, and Western blot analyses were used to detect apoptotic and antiapoptotic pathways. SP exposure of NCM460-NK-1R colonocytes stimulated phosphorylation of the antiapoptotic molecule Akt and inhibited tamoxifen-induced cell death and apoptosis evaluated by the cell viability assay and poly(ADP-ribose) polymerase cleavage, respectively. SP-induced phosphorylation of Akt and cleavage of poly(ADP-ribose) polymerase were inhibited by blockade of integrin αVβ3, Jak2, and activation of phosphatidylinositol 3-kinase. For the
in vivo
experiments, C57BL/6 mice, administered 5% dextran sulfate (DSS) dissolved in tap water for 5 days followed by a 5-day recovery period, were treated with the NK-1R antagonist CJ-12,255 or vehicle. Vehicle-treated mice showed increased colonic Akt phosphorylation and apoptosis compared with mice that received no DSS. In contrast, daily i.p. administration of CJ-12,255 for 5 days post-DSS suppressed Akt activation, exacerbated colitis, and enhanced apoptosis, and pharmacologic inhibition of Akt, either alone or together with CJ-12,255, produced a similar effect. Thus, SP, through NK-1R, possesses antiapoptotic effects in the colonic mucosa by activating Akt, which prevents apoptosis and mediates tissue recovery during colitis.
Nucleus- and cell-specific gene expression in monkey thalamus
Authors: Murray Karl D. , Choudary Prabhakara V. , Jones Edward G.
Published: February 2007

Nuclei of the mammalian thalamus are aggregations of neurons with unique architectures and input–output connections, yet the molecular determinants of their organizational specificity remain unknown. By comparing expression profiles of thalamus and cerebral cortex in adult rhesus monkeys, we identified transcripts that are unique to dorsal thalamus or to individual nuclei within it. Real-time quantitative PCR and
in situ
hybridization analyses confirmed the findings. Expression profiling of individual nuclei microdissected from the dorsal thalamus revealed additional subsets of nucleus-specific genes. Functional annotation using Gene Ontology (GO) vocabulary and Ingenuity Pathways Analysis revealed overrepresentation of GO categories related to development, morphogenesis, cell–cell interactions, and extracellular matrix within the thalamus- and nucleus-specific genes, many involved in the Wnt signaling pathway. Examples included the transcription factor
TCF7L2
, localized exclusively to excitatory neurons; a calmodulin-binding protein
PCP4
; the bone extracellular matrix molecules
SPP1
and
SPARC
; and other genes involved in axon outgrowth and cell matrix interactions. Other nucleus-specific genes such as
CBLN1
are involved in synaptogenesis. The genes identified likely underlie nuclear specification, cell phenotype, and connectivity during development and their maintenance in the adult thalamus.
Crystal structure of the N-terminal domain of the human protooncogene Nup214/CAN
Authors: Napetschnig Johanna , Blobel Günter , Hoelz André
Published: February 2007

The mammalian nuclear pore complex (NPC) is an ≈120-MDa proteinaceous assembly consisting of ≈30 proteins and is the sole gate in the nuclear envelope. The human protooncogene
Nup214
was first identified as a target for chromosomal translocation involved in leukemogenesis. Nup214 is located on the cytoplasmic face of the NPC and is implicated in anchoring the cytoplasmic filaments of the NPC and recruiting the RNA helicase Ddx19. Here, we present the crystal structure of the human Nup214 N-terminal domain at 1.65-Å resolution. The structure reveals a seven-bladed β-propeller followed by a 30-residue C-terminal extended peptide segment, which folds back onto the β-propeller and binds to its bottom face. The β-propeller repeats lack any recognizable sequence motif and are distinguished by extensive insertions between the canonical β-strands. We propose a mechanism by which the C-terminal peptide extension is involved in NPC assembly.
A plant porphyria related to defects in plastid import of protochlorophyllide oxidoreductase A
Authors: Pollmann Stephan , Springer Armin , Buhr Frank , Lahroussi Abder , Samol Iga , Bonneville Jean-Marc , Tichtinsky Gabrielle , von Wettstein Diter , Reinbothe Christiane , Reinbothe Steffen
Published: February 2007

The plastid envelope of higher plant chloroplasts is a focal point of plant metabolism. It is involved in numerous pathways, including tetrapyrrole biosynthesis and protein translocation. Chloroplasts need to import a large number of proteins from the cytosol because most are encoded in the nucleus. Here we report that a loss-of-function mutation in the
outer plastid envelope 16-kDa protein
(
oep16
) gene causes a conditional seedling lethal phenotype related to defects in import and assembly of NADPH:protochlorophyllide (Pchlide) oxidoreductase A. In the isolated knockout mutant of
Arabidopsis thaliana
, excess Pchlide accumulated in the dark operated as photosensitizer and provoked cell death during greening. Our results highlight the essential role of the substrate-dependent plastid import pathway of precursor Pchlide oxidoreductase A for seedling survival and the avoidance of developmentally programmed porphyria in higher plants.
Pericentric heterochromatin reprogramming by new histone variants during mouse spermiogenesis
Authors: Govin Jérôme , Escoffier Emmanuelle , Rousseaux Sophie , Kuhn Lauriane , Ferro Myriam , Thévenon Julien , Catena Raffaella , Davidson Irwin , Garin Jérôme , Khochbin Saadi , Caron Cécile
Published: February 2007

During male germ cell postmeiotic maturation, dramatic chromatin reorganization occurs, which is driven by completely unknown mechanisms. For the first time, we describe a specific reprogramming of mouse pericentric heterochromatin. Initiated when histones undergo global acetylation in early elongating spermatids, this process leads to the establishment of new DNA packaging structures organizing the pericentric regions in condensing spermatids. Five new histone variants were discovered, which are expressed in late spermiogenic cells. Two of them, which we named H2AL1 and H2AL2, specifically mark the pericentric regions in condensing spermatids and participate in the formation of new nucleoprotein structures. Moreover, our investigations also suggest that TH2B, an already identified testis-specific H2B variant of unknown function, could provide a platform for the structural transitions accompanying the incorporation of these new histone variants.
Antigen-specific precursor frequency impacts T cell proliferation, differentiation, and requirement for costimulation
Authors: Ford Mandy L. , Koehn Brent H. , Wagener Maylene E. , Jiang Wanhong , Gangappa Shivaprakash , Pearson Thomas C. , Larsen Christian P.
Published: February 2007

After a brief period of antigenic stimulation, T cells become committed to a program of autonomous expansion and differentiation. We investigated the role of antigen-specific T cell precursor frequency as a possible cell-extrinsic factor impacting T cell programming in a model of allogeneic tissue transplantation. Using an adoptive transfer system to incrementally raise the precursor frequency of antigen-specific CD8+ T cells, we found that donor-reactive T cells primed at low frequency exhibited increased cellular division, decreased development of multifunctional effector activity, and an increased requirement for CD28- and CD154-mediated costimulation relative to those primed at high frequency. The results demonstrated that recipients with low CD4+ and CD8+ donor-reactive T cell frequencies exhibited long-term skin graft survival upon CD28/CD154 blockade, whereas simultaneously raising the frequency of CD4+ T cells to ∼0.5% and CD8+ T cells to ∼5% precipitated graft rejection despite CD28/CD154 blockade. Antigenic rechallenge of equal numbers of cells stimulated at high or low frequency revealed that cells retained an imprint of the frequency at which they were primed. These results demonstrate a critical role for initial precursor frequency in determining the CD8+ T cell requirement for CD28- and CD154-mediated costimulatory signals during graft rejection.
Gating and Inward Rectifying Properties of the MthK K+ Channel with and without the Gating Ring
Authors: Li Yang , Berke Ian , Chen Liping , Jiang Youxing
Published: February 2007

In MthK, a Ca2+-gated K+ channel from Methanobacterium thermoautotrophicum, eight cytoplasmic RCK domains form an octameric gating ring that controls the intracellular gate of the ion conduction pore. The binding of Ca2+ ions to the RCK domains alters the conformation of the gating ring, thereby opening the gate. In the present study, we examined the Ca2+- and pH-regulated gating and the rectifying conduction properties of MthK at the single-channel level. The open probability (Po) of MthK exhibits a sigmoidal relationship with intracellular [Ca2+], and a Hill coefficient >1 is required to describe the dependence of Po on [Ca2+], suggesting cooperative Ca2+ activation of the channel. Additionally, intracellular Ca2+ also blocks the MthK pore in a voltage-dependent manner, rendering an apparently inwardly rectifying I-V relation. Intracellular pH has a dual effect on MthK gating. Below pH 7.5, the channel becomes insensitive to Ca2+. This occurs because the gating ring is structurally unstable at this pH and tends to disassemble (Ye, S., Y. Li, L. Chen, and Y. Jiang. 2006. Cell. 126:1161–1173). In contrast, above pH 7.5, a further increase in pH shifts the Po-[Ca2+] relation towards a lower Ca2+ concentration, augments Po at saturating [Ca2+], and activates the channel even in the absence of Ca2+. Channel activity is marked by bursts of rapid openings and closings separated by relatively longer interburst closings. The duration of interburst closing and the burst length are highly Ca2+ and pH dependent, whereas the kinetics of intraburst events is Ca2+ and pH independent. The rapid intraburst openings and closings are also observed with the isolated MthK pore lacking the attached intracellular gating ring. The fast kinetic events, independent of both Ca2+ and pH, therefore appear to be determined by processes occurring within the ion conduction pore, whereas the slow events reflect the gating process controlled by Ca2+ and pH through the gating ring.
Gain-of-Function Mutations in the MEC-4 DEG/ENaC Sensory Mechanotransduction Channel Alter Gating and Drug Blockade
Authors: Brown Austin L. , Fernandez-Illescas Silvia M. , Liao Zhiwen , Goodman Miriam B.
Published: February 2007

MEC-4 and MEC-10 are the pore-forming subunits of the sensory mechanotransduction complex that mediates touch sensation in Caenorhabditis elegans (O'Hagan, R., M. Chalfie, and M.B. Goodman. 2005. Nat. Neurosci. 8:43–50). They are members of a large family of ion channel proteins, collectively termed DEG/ENaCs, which are expressed in epithelial cells and neurons. In Xenopus oocytes, MEC-4 can assemble into homomeric channels and coassemble with MEC-10 into heteromeric channels (Goodman, M.B., G.G. Ernstrom, D.S. Chelur, R. O'Hagan, C.A. Yao, and M. Chalfie. 2002. Nature. 415:1039–1042). To gain insight into the structure–function principles that govern gating and drug block, we analyzed the effect of gain-of-function mutations using a combination of two-electrode voltage clamp, single-channel recording, and outside-out macropatches. We found that mutation of A713, the d or degeneration position, to residues larger than cysteine increased macroscopic current, open probability, and open times in homomeric channels, suggesting that bulky residues at this position stabilize open states. Wild-type MEC-10 partially suppressed the effect of such mutations on macroscopic current, suggesting that subunit–subunit interactions regulate open probability. Additional support for this idea is derived from an analysis of macroscopic currents carried by single-mutant and double-mutant heteromeric channels. We also examined blockade by the diuretic amiloride and two related compounds. We found that mutation of A713 to threonine, glycine, or aspartate decreased the affinity of homomeric channels for amiloride. Unlike the increase in open probability, this effect was not related to size of the amino acid side chain, indicating that mutation at this site alters antagonist binding by an independent mechanism. Finally, we present evidence that amiloride block is diffusion limited in DEG/ENaC channels, suggesting that variations in amiloride affinity result from variations in binding energy as opposed to accessibility. We conclude that the d position is part of a key region in the channel functionally and structurally, possibly representing the beginning of a pore-forming domain.
Bruton's tyrosine kinase (BTK) is a binding partner for hypoxia induced mitogenic factor (HIMF/FIZZ1) and mediates myeloid cell chemotaxis
Authors: Su Qingning , Zhou Yifu , Johns Roger A.
Published: February 2007

Hypoxia induced mitogenic factor (HIMF) is a member of the FIZZ/resistin/RELM family of proteins that we have shown to have potent mitogenic, angiogenic, and vasoconstrictive effects in the lung vasculature. In the current report, we identified Bruton's tyrosine kinase (BTK) as a functional HIMF binding partner through glutathione S‐transferase (GST)‐HIMF pull‐down studies and mass spectrometry. Using primary cultured HIMF‐stimulated murine bone marrow cells, we demonstrated that HIMF causes redistribution of BTK to the leading edge of the cells. HIMF stimulation induced BTK autophosphorylation, which peaked at 2.5 min. A transwell migration assay showed that treatment with recombinant murine HIMF induced migration of primary cultured bone marrow cells that was completely blocked by the BTK inhibitor, LFM‐A13. Our results demonstrate BTK as the first known functional binding partner of the HIMF/FIZZ family of proteins and that HIMF acts as a chemotatic molecule in stimulating the migration of myeloid cells through activation of the BTK pathway.—Su, Q., Zhou, Y., and Johns, R. A. Bruton's tyrosine kinase (BTK) is a binding partner for hypoxia induced mitogenic factor (HIMF/ FIZZ1) and mediates myeloid cell chemotaxis. FASEB J. 21, 1377–1383 (2007)
VEGF‐induced heme oxygenase‐1 confers cytoprotection from lethal hyperoxia in vivo
Authors: Siner Jonathan M. , Jiang Ge , Cohen Zaza I. , Shan Peiying , Zhang Xuchen , Lee Chun Geun , Elias Jack A. , Lee Patty J.
Published: February 2007

Prolonged exposure to hyperoxia results in hyperoxic acute lung injury (HALI). Vascular endothelial growth factor (VEGF) has been shown to have cytoprotective effects and prolong survival in an in vivo model of HALI. Heme oxygenase‐1 (HO‐1) has protective effects in hyperoxia; therefore, we hypothesized that induction of HO‐1 would be an important contributor to VEGF‐induced cytoprotection. Using inducible, lung‐specific VEGF overexpressing transgenic mice, we demonstrated that VEGF is a potent inducer of HO‐1 mRNA and protein in mouse lung. To evaluate the effect of inhibition of HO‐1 on injury, VEGF transgenic mice were treated with HO‐1 short interfering RNA (HO‐1 siRNA) and exposed to hyperoxia. Total lung lavage protein concentration, TUNEL staining, lipid peroxidation, and wet‐to‐dry ratio were all increased, consistent with increased injury. These findings were corroborated by survival studies in which inhibition of HO‐1 function using tin‐protoporphryin or silencing of HO‐1 with lentiviral HO‐1 short hairpin RNA (ShRNA) significantly decreased survival in hyperoxia. We conclude from these data that VEGF‐induced HO‐1 is an important contributor to cytoprotection in this in vivo model of acute lung injury and that alterations in VEGF function in the lung are likely to be important determinants of the outcome of acute lung injury.—Siner, J. M., Jiang, G., Cohen, Z. I., Shan, P., Zhang, X., Lee, C. G., Elias, J. A., Lee, P. J. VEGF‐induced heme oxygenase‐1 confers cytoprotection from lethal hyper‐oxia in vivo. FASEB J. 21, 1422–1432 (2007)
Selective gene activation by spatial segregation of insulin receptor B signaling
Authors: Uhles Sabine , Moede Tilo , Leibiger Barbara , Berggren Per-Olof , Leibiger Ingo B
Published: February 2007

Insulin exerts pleiotropic effects at the cellular level. Signaling via the two isoforms of the insulin receptor (IR) may explain the activation of different signaling cascades, while it remains to be explored how selectivity is achieved when utilizing the same IR isoform. We now demonstrate that insulin‐stimulated transcription of c‐fos and glucokinase genes is activated simultaneously in the insulin‐producing β‐cell via IR‐B localized in different cellular compartments. Insulin activates the glucokinase gene from plasma membrane‐standing IR‐B, while c‐fos gene activation is dependent on clathrin‐mediated IR‐B‐endocytosis and signaling from early endosomes. Moreover, glucokinase gene up‐regulation requires the integrity of the jux‐tamembrane IR‐B NPEY‐motif and signaling via PI3K‐C2α‐like/PDK1/PKB, while c‐fos gene activation requires the intact C‐terminal YTHM‐motif and signaling via PI3K Ia/Shc/MEK1/ERK. By using IR‐B as an example it is thus possible to demonstrate how spatial segregation allows simultaneous and selective signaling via the same receptor isoform in the same cell.—Uhles S., Moede T., Leibiger B., Berggren P.‐O., and Leibiger I. B. Selective gene activation by spatial segregation of insulin receptor B signaling. FASEB J. 21, 1609–1621 (2007)
Community Service Experiences and Commitment to Volunteering1
Authors: Taylor Trevor P. , Mark Pancer S.
Published: February 2007

University students who were involved in a community service field placement completed the Inventory of Service Experience (ISE), a measure that was designed to assess the extent to which they felt supported by family, friends, and the organizations with which they worked; and the extent to which they experienced positive outcomes (e.g., enhanced skills, a feeling of “having made a difference”) in their community service setting. Students who had a more supportive and positive experience, as assessed by the ISE, were more likely to have continued to work as volunteers in the setting 2 months after they had completed their course requirements. The implications of these results for community service programs are discussed.
The Effects of Social Motivational Training Following Perceived and Actual Interpersonal Offenses at Work1
Authors: Dupuis Réjeanne , Struthers C. Ward
Published: February 2007

This research was designed to examine the effects of social motivational training (SMT) on coworker interactions following perceived and actual workplace transgressions. Study 1 participants were assigned to an SMT condition or a control condition (Job Satisfaction Training; JST). Their responses to a scenario‐based transgression were measured before and immediately after training. Study 2 examined the effects of multiple exposure of SMT 1 week after initial training. In Study 3, workers recounted a negative event at work, received SMT or JST, and an actual behavior was assessed. Study 4 involved face‐to‐face intervention. After recounting the negative event, participants were given one‐on‐one SMT or JST. Results indicate that SMT facilitated a prosocial motivational profile immediately after and 1 week following training.
Considerations in the Treatment of Dyslipidemia Associated With Chronic Kidney Failure and Renal Transplantation
Authors: Davidson Michael
Published: February 2007

In comparison to the general population, individuals with chronic kidney failure experience an increased risk for atherosclerotic cardiovascular disease attributed predominantly to pronounced abnormalities in lipid metabolism. The emerging consensus is that patients with chronic kidney failure should be treated aggressively for dyslipidemia. Statins reduce the risk of cardiovascular disease in a range of at‐risk patients; this class of lipid‐lowering drugs should be considered first‐line treatment of dyslipidemia observed in renal disease patients. Although the statins share a common lipid‐lowering effect, there are differences within this class of drugs. The statins differ in their pharmacokinetic effects, drug interaction profiles, and risk of myotoxicity. This article characterizes the dyslipidemia observed in the renal failure setting and reviews the therapeutic considerations involved in selecting among the statins. Lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, and rosuvastatin are the available statins in the United States.
Safety and Efficacy of Resistance Training in Patients With Chronic Heart Failure: Research‐Based Evidence
Authors: Benton Melissa J.
Published: February 2007

Although a rich body of research exists regarding the safety and efficacy of resistance training, health care providers continue to caution patients with heart failure not to engage in this type of exercise. Research studies utilizing resistance training demonstrate improvements in muscular strength and endurance, New York Heart Association functional class, and quality of life. Despite the hemodynamic changes which occur during resistance exercise, no negative outcomes have been reported. The purpose of this paper is to review the most current research regarding the use of resistance training with heart failure patients to provide assistance to clinicians and enable them to provide education and appropriate recommendations to their patients.
Applying Five Key Success Factors to Optimize the Quality of Care for Patients Hospitalized With Coronary Artery Disease
Authors: Parkosewich Janet , Funk Marjorie , Bradley Elizabeth H.
Published: February 2007

Quality improvement (QI) efforts aimed at optimizing adherence to coronary artery disease quality indicators are helping to bridge the serious gaps in the quality of care for this population. Motivation for these initiatives is prompted by a number of sources, including the public reporting of hospitals' adherence to these indicators found on the Center for Medicare and Medicaid Services Web site. Although complex barriers challenge QI efforts, results of recent studies demonstrate that the use of five key success factors reduces these barriers and accelerates improvement. Integral components of this model include administrative support that cultivates a blameless culture that strives for perfection; committed and respected champions; goals that are shared within the organization; the use of timely, credible data at the organizational and individual levels; and implementation of a QI initiative tailored to the complexity of the project. In this review article, the authors discuss how quality of care is measured, provide examples of successful QI programs, and describe how the use of a QI model composed of five key success factors can accelerate QI efforts and optimize the care of patients hospitalized with coronary artery disease.
Thrombocytopenia Following Heparin Flush
Authors: McNulty Iris , Katz Eliezer , Kim Karissa Y.
Published: February 2007

A total of 23 patients who developed heparin‐induced thrombocytopenia following exposure to heparin solely due to intravascular catheter or filter flush were the subjects of prospective studies of argatroban therapy. Heparin doses were 10–13,000 U, with a mean exposure of 8±4 days. Following heparin‐induced thrombocytopenia diagnosis and heparin cessation, 13 patients received argatroban (mean dose of 1.8±1.1μg/kg/min for 5.5±3.9 days), achieving activated partial thromboplastin times of 63±23 seconds, and 10 historical control patients received no direct thrombin inhibitors. Platelet count recovered to a mean of 207±153×109/L (n=12) after 5.5±3.9 days of argatroban therapy and to a mean of 127±63×109/L (n=8) 5 days after baseline in the control group. A composite end point of death, amputation, or new thrombosis within 37 days occurred in five (38.5%) argatroban‐treated patients and four (40%) controls. Death was the most common untoward outcome (approximately 30% of each group). No argatroban‐treated patient and two (20%) control patients experienced new thrombosis. Major bleeding was comparable between groups. Heparin‐induced thrombocytopenia can occur following minimal heparin exposure, including heparin flushes; in these patients, argatroban provides effective alternative anticoagulation as compared with historical controls.
Nesiritide for Pulmonary Arterial Hypertension With Decompensated Cor Pulmonale
Authors: Kingman Martha S. , Thompson Brenda S. , Newkirk Trixie , Torres Fernando
Published: February 2007

Pulmonary arterial hypertension complicated by decompensated cor pulmonale is a challenging clinical problem with few effective therapeutic options. B‐type natriuretic peptide is a pluripotent hormone that promotes diuresis and natriuresis, vasodilates systemic and pulmonary vessels, and reduces circulating levels of endothelin and aldosterone. It may represent a possible therapeutic strategy for decompensated cor pulmonale in the same manner that it is used to treat decompensated left heart failure. The authors report their experience with B‐type natriuretic peptide as adjunctive therapy for pulmonary arterial hypertension complicated by decompensated cor pulmonale. A detailed case report is presented followed by the evaluation of a series of 11 cases occurring in eight patients from December 2002 through April 2004.
Gender Differences in Implantable Cardioverter‐Defibrillator Patients at the Time of Insertion
Authors: Smith Genevieve , Dunbar Sandra B. , Valderrama Amy L. , Viswanathan Bindu
Published: February 2007

Gender differences in physical and psychological health and responses in persons receiving implantable cardioverter‐defibrillators (ICDs) have been reported but are not well delineated. This study examined symptoms of pain and sleep difficulties, functional status, and psychological responses in 180 (75%) men and 60 (25%) women before and immediately following their first ICD implantation. Women were significantly younger, less likely to be married, and had less history of coronary artery disease than men. Forty‐eight percent of women were New York Heart Association class III–IV vs. 27% of men (p<0.05). Women had lower functional status and were more likely to report symptoms of increased pain severity and sleep difficulties. Differences in functional status and pain were reduced after adjusting for New York Heart Association class and age, respectively. There were no differences in depressive symptoms or anxiety. Clinical implications of gender‐related responses include the need to address symptoms of heart failure as well as increased pain and sleep difficulties in women at the time surrounding ICD implantation. Longitudinal studies and gender‐focused nursing interventions should be developed to promote better understanding of responses and to improve recovery outcomes for ICD patients.
Consequences and Predictors of Depression in Patients With Chronic Heart Failure: Implications for Nursing Care and Future Research
Authors: Johansson Peter , Dahlström Ulf , Broström Anders
Published: February 2007

Depression is common among patients with chronic heart failure (HF) and leads to more symptoms of HF, decreased quality of life, and an increased risk for premature death. Depressed HF patients also use more health care resources, which increases the economic burden on the health care system. The assessment of risk factors of depression such as age younger than 60–65 years, poor physical functioning, previous depression, poor self‐efficacy, living alone, and distressful relationships, in combination with the use of depression instruments, can be helpful in detecting depression in HF patients. Unfortunately, interventions on how to relieve depression in patients with HF have not been investigated thoroughly; however, depression agents as well as HF education, social support, exercise therapy, stress management, and relaxation have been shown to be useful interventions. Because of poor outcomes, studies that examine the effectiveness and/or side effects of pharmacologic as well as nonpharmacologic interventions on depressed patients with HF are needed.
Satisfaction With Heart Transplantation
Authors: Jalowiec Anne , Grady Kathleen L. , White‐Williams Connie
Published: February 2007

This research investigated patient satisfaction with heart transplantation (HT) 6 months after surgery. The authors explored whether HT patients would make the decision to have HT again and examined medical, psychosocial, and demographic factors associated with satisfaction or dissatisfaction in 257 HT recipients. Nonparametric statistics were used. Satisfaction with HT could be rated from 1 (not satisfied) to 10 (very satisfied). Eighty‐seven percent of the patients were highly satisfied with HT 6 months after surgery (ratings of 8–10); 1% rated their satisfaction as low (1–3), and 12% rated it as moderate (4–7). Factors associated with less satisfaction with HT were: more symptom distress, greater disability, more stress, poor coping ability, feeling that the interventions of the HT team were not very helpful, less life satisfaction, and lower quality of life. Ninety‐three percent indicated that they either definitely or probably would decide to have HT again; 7% responded “probably not” or “not sure.” Factors associated with a negative perception of having another HT were: poor coping ability, less life satisfaction, lower quality of life, being male, and being married.
Systems for Care of Hypertension in the United States
Authors: Krakoff Lawrence R.
Published: February 2007

Control of hypertension in recent clinical trials varies from 48% to 65%. However, in community care of hypertension in the United States, estimates of control of hypertension are far lower. The United States has no single system of care; however, several care systems can be identified for comparison, such as the Department of Veterans Affairs, managed care organizations, and the Indian Health Service. This review compares control of hypertension in certain centers in these systems with that achieved in clinical trials and in the community at large. Certain components of care systems are assessed for their contribution to the control of hypertension. The author concludes that for community control of hypertension to approach that achieved in clinical trials, the use of physician extenders, together with reduced or minimal cost of medication, improved education of providers with feedback, and computerization of management systems will be needed. In addition, specific interventions targeted to medically underserved groups will be required.
Translocation of heparanase into nucleus results in cell differentiation
Authors: Nobuhisa Tetsuji , Naomoto Yoshio , Okawa Takaomi , Takaoka Munenori , Gunduz Mehmet , Motoki Takayuki , Nagatsuka Hitoshi , Tsujigiwa Hidetsugu , Shirakawa Yasuhiro , Yamatsuji Tomoki , Haisa Minoru , Matsuoka Junji , Kurebayashi Junichi , Nakajima Motowo , Taniguchi Shun’ichiro , Sagara Junji , Dong Jian , Tanaka Noriaki
Published: February 2007

We recently reported that heparanase, one of the extracellular matrix‐degrading enzymes, which plays a critical role in cancer progression, is located not only in the cytoplasm but also in the nucleus. Here we identified nuclear translocation of heparanase as a key step in cell differentiation. We applied an in vitro differentiation model of HL‐60 cells with 12–0‐tetradecanoylphorbol‐13‐acetate (TPA), in which nuclear translocation of heparanase was observed using immunohistochemical analysis. In this system, nuclear translocation of heparanase was abolished by inhibitors of heat shock protein 90 (HSP90), suggesting the involvement of HSP90 in translocation of heparanase. We further confirmed that overexpression of active form of heparanase induced differentiation of HL‐60 cells, although the catalytic negative form of heparanase did not. Therefore we speculate that nuclear translocation of enzymatically active heparanase may be involved in cellular differentiation. Our results suggest that a novel function of heparanase upon cell differentiation would raise a potential new strategy for cancer therapy of promyeloid leukemia and other types of cancer. (Cancer Sci 2007; 98: 535–540)
Brucellosis‐induced immune thrombocytopenia mimicking ITP: a report of seven cases
Authors: YıLMAZ M. , TIRYAKI O. , NAMıDURU M. , OKAN V. , OGUZ A. , BUYUKHATIPOGLU H. , KARAOGLAN I. , YıLMAZ B.
Published: February 2007

Brucellosis continues to be an important cause of fever in underdeveloped countries and in rural areas of developed world. It is a multisystemic disease, associated with wide variety of symptoms. A wide variety of symptoms, including haematological abnormalities, such as anaemia, thrombocytopenia, pancytopenia, dissemine intravascular coagulation and leucopoenia could be seen, all of which are more common than usually thought. In this short study, we present a relatively uncommon haematological manifestation that of isolated thrombocytopenia mimicking idiopathic thrombocytopenic purpura, which we observed in seven of 114 patients who were diagnosed with brucellosis in our hospital over a 2‐year period. Having given brucellosis treatment with rifampicin and doxycycline, complete remission was achieved and thrombocyte count returned to normal in all cases.
Burnout and ‘stress of conscience’ among healthcare personnel
Authors: Glasberg A. L. , Eriksson S. , Norberg A.
Published: February 2007

Title. Burnout and ‘stress of conscience’ among healthcare personnel

Aim.  This paper reports a study examining factors that may contribute to burnout among healthcare personnel.

Background.  The impact on burnout of factors such as workload and interpersonal conflicts is well‐documented. However, although health care is a moral endeavour, little is known about the impact of moral strain. Interviews reveal that healthcare personnel experience a troubled conscience when they feel that they cannot provide the good care that they wish – and believe it is their duty – to give.

Methods.  In this cross‐sectional study, conducted in 2003, a sample of 423 healthcare personnel in Sweden completed a battery of questionnaires comprising the Maslach Burnout Inventory, Perception of Conscience Questionnaire, Stress of Conscience Questionnaire, Social Interactions Scale, Resilience Scale and a personal/work demographic form.

Results.  Regression analysis resulted in a model that explained approximately 59% of the total variation in emotional exhaustion. Factors associated with emotional exhaustion were ‘having to deaden one's conscience’, and ‘stress of conscience’ from lacking the time to provide the care needed, work being so demanding that it influences one's home life, and not being able to live up to others’ expectations. Several additional variables were associated with emotional exhaustion. Factors contributing to depersonalization were ‘having to deaden one's conscience’, ‘stress of conscience’ from not being able to live up to others’ expectations and from having to lower one's aspirations to provide good care, deficient social support from co‐workers, and being a physician; however, the percentage of variation explained was smaller (30%).

Conclusion.  Being attentive to our own and others’ feelings of troubled conscience is important in preventing burnout in health care, and staff need opportunities to reflect on their troubled conscience. Further research is needed into how a troubled conscience can be eased, particularly focusing on the working environment.
Cytokine Profile of T lymphocytes from Peripheral Blood and Bronchoalveolar Lavage Fluid in Patients with Active Pulmonary Tuberculosis
Authors: Boras Z. , Juretić A. , Gagro A. , Pavelić Lj
Published: February 2007

The possible immunological relationship between the pattern of Th1/Th2 cytokine production and tuberculin reactivity was assessed in patients with active Mycobacterium tuberculosis infection. The production of the intracellular cytokines interferon (IFN)‐γ and interleukin‐4 (IL‐4) was measured in CD4+ and CD8+ T cells obtained from peripheral blood and bronchoalveolar lavage fluid (BALF) of 20 tuberculin skin‐positive patients and compared with the findings recorded in nine tuberculin skin‐negative patients with active pulmonary tuberculosis. Upon stimulation with phorbol 12‐myristate acetate/ionomycin for 6 h, tuberculin‐negative patients had a significantly higher proportion of IFN‐γ‐producing CD4+ T lymphocytes in BALF than in peripheral blood, while both CD4+ and CD8+ T‐lymphocyte subsets in BALF of tuberculin‐positive patients secreted more IFN‐γ than their peripheral blood counterparts. Tuberculin‐negative patients had a significantly higher proportion of IFN‐γ‐producing CD4+ T lymphocytes in peripheral blood than tuberculin‐positive patients. There was no significant difference in the production of IFN‐γ by BALF CD4+ T lymphocytes, or by either peripheral blood or BALF CD8+ T lymphocytes. In two tuberculin‐negative patients, peripheral blood CD4+ T lymphocytes produced IL‐4. Study results suggested a higher immune activity in the blood of tuberculin‐negative patients, with an increased lymphocyte activity in BALF versus peripheral blood in both patient groups.
Dual infection with polyomavirus BK and acyclovir‐resistant herpes simplex virus successfully treated with cidofovir in a bone marrow transplant recipient
Authors: Andrei G. , Fiten P. , Goubau P. , Van Landuyt H. , Gordts B. , Selleslag D. , De Clercq E. , Opdenakker G. , Snoeck R.
Published: February 2007

Abstract: A hematopoietic stem cell transplant recipient developed a mucosal herpes simplex virus‐1 (HSV‐1) infection while under acyclovir (ACV) treatment (HSV was later shown to be resistant to ACV). Concomitantly, the patient presented a hemorrhagic cystitis (HC) due to polyomavirus BK, for which intravenous cidofovir (CDV) was prescribed. The patient benefited from the broad‐spectrum anti‐DNA virus activity of CDV, and not only the HC resolved without signs of nephrotoxicity but also the HSV‐1 lesions disappeared. This is the first report describing the effect of CDV on 2 simultaneous and unrelated DNA viral infections in an immunosuppressed transplant recipient. In addition, we describe here that this HSV‐1 isolate possesses a unique phenotype and genotype.
Treatment of Candida albicans pericarditis in a heart transplant patient
Authors: Puius Y.A. , Scully B.
Published: February 2007

Abstract: Pericarditis due to Candida species is a rare clinical entity, associated with thoracic surgery and immunosuppression. We report here the second case of pericarditis due to Candida albicans in a heart transplant patient, which presented as tamponade approximately 3 weeks post transplant, in the absence of evidence of sternal osteomyelitis. The patient was treated with pericardiocentesis and a combination of caspofungin and fluconazole, but the patient ultimately required the explantation of retained epicardial leads and the creation of a pericardial window. This case illustrates that Candida species must be considered in the differential diagnosis in post‐transplant pericarditis, and that foreign body removal is, as always, key in helping to resolve such infections. This case also demonstrates the first use of caspofungin with fluconazole to treat Candida pericarditis. We discuss the conflicting data regarding the use of caspofungin, alone or in combination therapy, in treating infections involving biofilms, such as the infected pericardium.