bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell Polarity and Asymmetric Cell Division within Human Hematopoietic Stem and Progenitor Cells
Authors: Giebel Bernd
Published: February 2008

Like other somatic stem cells, hematopoietic stem cells (HSC) contain the capacity to self-renew and to give rise to committed progenitor cells that are able to replenish all hematopoietic cell types. To keep a constant level of HSC, the decision whether their progeny maintain the stem cell fate or become committed to differentiation needs to be highly controlled. In this context it became evident that HSC niches fulfill important functions in keeping the level of HSC more or less constant. Before discovering such niches, it was widely assumed that HSC divide asymmetrically to give birth to a daughter cell maintaining the stem cell fate and to another one which is committed to differentiation. Here, I summarize some of the experimental data being compatible with the model of asymmetric cell division and review some of our latest findings, which demonstrate the occurrence of asymmetric cell divisions within the HSC and hematopoietic progenitor cell compartment. Since cell polarity is an essential prerequisite for asymmetrically dividing as well as for migrating cells, I will also discuss some aspects of cell polarity of primitive hematopoietic cells.
The Origins of Human Embryonic Stem Cells: A Biological Conundrum
Authors: Brink Thore C. , Sudheer Smita , Janke Doreen , Jagodzinska Justyna , Jung Marc , Adjaye James
Published: February 2008

Human inner cell mass (ICM) cells isolated from in vitro fertilized blastocysts are the progenitor cells used to establish in vitro stable human embryonic stem cells (hESCs) which are pluripotent and self-renew indefinitely. This long-term perpetuation of hESCs in the undifferentiated state is thought to be an in vitro adaptation of the ICM cells. To investigate at the molecular level how hESCs acquired their unique properties, transcriptional profiles of isolated ICM cells and undifferentiated hESCs were compared. We identified 33 genes enriched in the ICM compared to the trophectoderm and hESCs. These genes are involved in signaling cascades (SEMA7A and MAP3K10), cell proliferation (CUZD1 and MS4A7) and chromatin remodeling (H1FOO and HRMT1L4). Furthermore, primordial germ cell-specific genes (SGCA and TEX11) were detected as expressed in the ICM cells and not hESCs. We propose that the transcriptional differences observed between ICM cells and hESCs might be accounted for by adaptive reprogramming events induced by the in vitro culture conditions which are distinct from that of in vitro fertilized blastocysts. hESCs are a distinct cell type lacking in the human embryo but, nonetheless, resemble the ICM in their ability to differentiate into cells representative of the endodermal, ectodermal and mesodermal cell lineages.
The Case for a Metabolic Stem Cell Niche
Authors: Cross Michael , Alt Rüdiger , Niederwieser Dietger
Published: February 2008

Despite more than 40 years of experience with the use of haematopoietic stem cells (HSC) in the clinic and the identification of a plethora of regulatory signals of clear relevance to their function, it has proven remarkably difficult to amplify these cells efficiently in culture without a concurrent loss of potential. Based on considerations of haematopoietic environments in the embryo and the adult, on published observations of metabolic compartmentalisation between neighbouring cells in other tissues, and on considerations of the selective pressures acting on the evolution of generative and regenerative systems, we propose that the amplification of HSC may be tied obligatorily to limiting metabolic conditions provided by the niche. We suggest that this conceptually simple arrangement could combine the support of HSC with the containment of self-renewal activity within a rare and highly defined set of physiological sites, whilst avoiding the accumulation of potentially leukaemogenic mutations in the stem cell pool.
Specific GATA-Binding Elements in the GnRH Promoter Are Required for Gene Expression Pulse Activity: Role of GATA-4 and GATA-5 in This Intermittent Process
Authors: Leclerc Gilles M. , Bose Sudeep K. , Boockfor Fredric R.
Published: February 2008

Recent evidence reveals that several GATA factors act as versatile transcriptional modulators in neuroendocrine gene expression. The rat GnRH promoter is expressed in an episodic fashion that requires a portion of the promoter termed the neuron-specific enhancer (NSE) for activity. In this study, we examined whether certain GATA regulatory elements in the NSE are necessary for this intermittent activity. When injected into individual living GT1-7 cells, luciferase reporter constructs containing mutations of either GATA-A- or GATA-B-binding sites resulted in a marked reduction in gene expression pulse frequency, while mutations of both sites virtually abolished pulses. In subsequent studies, RT-PCR and western blot analysis revealed for the first time that GATA-5 and GATA-6 were expressed in GT1-7 cells, but electrophoretic mobility shift assays demonstrated further that GATA-5 bound to one of these GATA sites: GATA-A. Chromatin immunoprecipitation analysis revealed that all three factors, GATA-4, GATA-5, and GATA-6, were associated with the GnRH promoter in vivo. Interestingly though, immunoneutralization of GATA-5 or GATA-4 (reported to bind GATA-B) abolished gene expression pulses, but injection of GATA-6 antibody did not, indicating that of these factors just GATA-5 and GATA-4 are critical for intermittent activity. Finally, gel shift competition experiments revealed an interaction between proteins binding at the GATA-A site and those associating with an adjacent OCT1 site, previously shown to be necessary for pulse formation. These findings indicate that episodic GnRH gene expression pulses are mediated by GATA-5 and GATA-4, likely acting through the GATA-binding sites in the GnRH NSE region. Moreover, our observations that factors associated with GATA sites may also interact with OCT1 sites and that both are critical for pulse activity raise the intriguing possibility that GnRH pulse elaboration is a highly complex process that may require the coordinated interaction of several NSE-binding elements of the GnRH promoter.
Apoptosis of Lactotrophs Induced by D2 Receptor Activation Is Estrogen Dependent
Authors: Radl Daniela B. , Zárate Sandra , Jaita Gabriela , Ferraris Jimena , Zaldivar Verónica , Eijo Guadalupe , Seilicovich Adriana , Pisera Daniel
Published: February 2008

Background/Aims: Dopamine (DA) inhibits prolactin release and reduces lactotroph proliferation by activating D2 receptors. DA and its metabolite, 6-hydroxydopamine (6-OHDA), induce apoptosis in different cell types. DA receptors and DA transporter (DAT) were implicated in this action. Considering that estradiol sensitizes anterior pituitary cells to proapoptotic stimuli, we investigated the effect of estradiol on the apoptotic action of DA and 6-OHDA in anterior pituitary cells, and the involvement of the D2 receptor and DAT in the proapoptotic effect of DA. Methods: Viability of cultured anterior pituitary cells from ovariectomized rats was determined by MTS assay. Apoptosis was evaluated by Annexin-V/flow cytometry and TUNEL. Lactotrophs were identified by immunocytochemistry. Results: DA induced apoptosis of lactotrophs in an estrogen-dependent manner. In contrast, estradiol was not required to trigger the apoptotic action of 6-OHDA. Cabergoline, a D2 receptor agonist, induced lactotroph apoptosis, while sulpiride, a D2 receptor antagonist, blocked DA-induced cell death. The blockade of DAT by GBR12909 did not affect the apoptotic action of DA, but inhibited 6-OHDA-induced apoptosis. Conclusion: These data show that DA, through D2 receptor activation, induces apoptosis of estrogen-sensitized anterior pituitary cells, and suggest that DA contributes to the control of lactotroph number not only by inhibiting proliferation but also by inducing apoptosis.
Theory of Input Spike Auto- and Cross-Correlations and Their Effect on the Response of Spiking Neurons
Authors: Moreno-Bote Rubén , Renart Alfonso , Parga Néstor
Published: February 2008

Spike correlations between neurons are ubiquitous in the cortex, but their role is not understood. Here we describe the firing response of a leaky integrate-and-fire neuron (LIF) when it receives a temporarily correlated input generated by presynaptic correlated neuronal populations. Input correlations are characterized in terms of the firing rates, Fano factors, correlation coefficients, and correlation timescale of the neurons driving the target neuron. We show that the sum of the presynaptic spike trains cannot be well described by a Poisson process. In fact, the total input current has a nontrivial two-point correlation function described by two main parameters: the correlation timescale (how precise the input correlations are in time) and the correlation magnitude (how strong they are). Therefore, the total current generated by the input spike trains is not well described by a white noise gaussian process. Instead, we model the total current as a colored gaussian process with the same mean and two-point correlation function, leading to the formulation of the problem in terms of a Fokker-Planck equation. Solutions of the output firing rate are found in the limit of short and long correlation timescales. The solutions described here expand and improve on our previous results (Moreno, de la Rocha, Renart, & Parga, 2002) by presenting new analytical expressions for the output firing rate for general IF neurons, extending the validity of the results for arbitrarily large correlation magnitude, and by describing the differential effect of correlations on the mean-driven or noise-dominated firing regimes. Also the details of this novel formalism are given here for the first time. We employ numerical simulations to confirm the analytical solutions and study the firing response to sudden changes in the input correlations. We expect this formalism to be useful for the study of correlations in neuronal networks and their role in neural processing and information transmission.
Fast Recursive Filters for Simulating Nonlinear Dynamic Systems
Authors: Hateren J. H. van
Published: February 2008

A fast and accurate computational scheme for simulating nonlinear dynamic systems is presented. The scheme assumes that the system can be represented by a combination of components of only two different types: first-order low-pass filters and static nonlinearities. The parameters of these filters and nonlinearities may depend on system variables, and the topology of the system may be complex, including feedback. Several examples taken from neuroscience are given: phototransduction, photopigment bleaching, and spike generation according to the Hodgkin-Huxley equations. The scheme uses two slightly different forms of autoregressive filters, with an implicit delay of zero for feedforward control and an implicit delay of half a sample distance for feedback control. On a fairly complex model of the macaque retinal horizontal cell, it computes, for a given level of accuracy, one to two orders of magnitude faster than the fourth-order Runge-Kutta. The computational scheme has minimal memory requirements and is also suited for computation on a stream processor, such as a graphical processing unit.
Nanoparticle Self-Lighting Photodynamic Therapy for Cancer Treatment
Authors: Chen Wei
Published: February 2008

Photodynamic therapy (PDT) has been designated as a "promising new modality in the treatment of cancer" since the early 1980s. Light must be delivered in order to activate photodynamic therapy. Most photosensitizers have strong absorption in the ultraviolet (UV)-blue range, therefore,
UV-blue light is needed for their activation. Unfortunately, UV-blue light has minimal penetration into tissue and its application for in vivo activation is a problem. To solve the problem and enhance the PDT treatment for deep cancers, we introduce new PDT systems in which the light
is generated by afterglow nanoparticles with attached photosensitizers. When the nanoparticle-photosensitizer conjugates are targeted to tumor, the light from afterglow nanoparticles will activate the photosensitizers for photodynamic therapy. Therefore, no external light is required for treatment.
More importantly, it can be used to treat deep tumor such as breast cancer because the light source is attached to the photosensitizers and are delivered to the tumor cells all together. This new modality is refereed as Nanoparticle Self-Lighting Photodynamic Therapy (NSLPDT).
Development of Receptor Targeted Magnetic Iron Oxide Nanoparticles for Efficient Drug Delivery and Tumor Imaging
Authors: Yang Lily , Cao Zehong , Sajja Hari Krishna , Mao Hui , Wang Liya , Geng Huaying , Xu Hengyi , Jiang Tieshan , Wood William C. , Nie Shuming , Wang Y. Andrew
Published: February 2008

The development of multifunctional nanoparticles that have dual capabilities of tumor imaging and delivering therapeutic agents into tumor cells holds great promises for novel approaches for tumor imaging and therapy. We have engineered urokinase plasminogen activator receptor (uPAR)
targeted biodegradable nanoparticles using a size uniform and amphiphilic polymer-coated magnetic iron oxide (IO) nanoparticle conjugated with the amino-terminal fragment (ATF) of urokinase plasminogen activator (uPA), which is a high affinity natural ligand for uPAR. We further developed
methods to encapsulate hydrophobic chemotherapeutic drugs into the polymer layer on the IO nanoparticles, making these targeted magnetic resonance imaging (MRI) sensitive nanoparticles drug delivery vehicles. Using a fluorescent drug doxorubicin (Dox) as a model system, we showed that this
hydrophobic drug can be efficiently encapsulated into the uPAR-targeted IO nanoparticles. This class of Dox-loaded nanoparticles has a compact size and is stable in pH 7.4 buffer. However, encapsulated Dox can be released from the nanoparticles at pH 4.0 to 5.0 within 2 hrs. In comparison
with the effect of equivalent dosage of free drug or non-targeted IO-Dox nanoparticles, uPAR-targeted IO-Dox nanoparticles deliver higher levels of Dox into breast cancer cells and produce a stronger inhibitory effect on tumor cell growth. Importantly, Dox-loaded IO nanoparticles maintain
their T2 MRI contrast effect after being internalized into the tumor cells due to their significant susceptibility effect in the cells, indicating that this drug delivery nanoparticle has the potential to be used as targeted therapeutic imaging probes for monitoring the drug delivery
using MRI.
An Essay on Searching for Curriculum and Pedagogy for African American Students
Authors: Grant Carl A.
Published: February 2008

What should be the nature of the curriculum and instructional pedagogy for African American students has a long history of debate. Currently, Afrocentric curriculum/ pedagogy and multicultural curriculum/pedagogy are the main focus of the debate. This essay discusses the nature and purpose of both curricula and critiques their strengths and weaknesses. An argument is present as to which of these curricular concepts best suits the current needs of African American students. Finally, implications are listed for using both Afrocentric and multicultural curricula and pedagogies.
Customer (In)Justice and Emotional Labor: The Role of Perspective Taking, Anger, and Emotional Regulation†
Authors: Rupp Deborah E. , Silke McCance A. , Spencer Sharmin , Sonntag Karlheinz
Published: February 2008

This study investigates the impact of customer interpersonal and informational injustice on service workers' emotional labor (surface acting). Results from a study conducted on 152 bank tellers in Germany showed that customers are evaluated by employees as a potential source of unfairness. Perceptions of customer justice were found to interact with individual differences in perspective taking in the prediction of surface acting such that the negative effect of customer injustice on surface acting was stronger for those low in perspective taking (compared to those high in perspective taking). Although anger was expected to mediate this moderated effect, this hypothesis was not confirmed. Considering the results post hoc, a revised theoretical model is proposed based on Cropanzano, Weiss, Suckow, and Grandey's model of justice and emotional regulation. Future research is needed to test this model and determine what leads employees to deploy emotional regulation strategies when faced with unfair customers.
Impact of coherent versus multiple identities on knowledge integration
Authors: Willem Annick , Scarbrough Harry , Buelens Marc
Published: February 2008

This paper addresses the influence of two competing views of social identity on knowledge integration. One view sees social identity primarily as a coherent characteristic of organizations, which can leverage knowledge integration by unconditional cooperative behaviour, shared values, mindsets, trust, and loyalty. The opposing view considers social identity as multiple and fragmented. This fragmented view emphasizes the problematic nature of social identity for knowledge integration and states that social identity is an additional barrier to knowledge integration in organizations. The aim of this paper is to examine these competing accounts and to develop insight into the underlying mechanisms that lead to the different effects of social identity on knowledge integration. Two polar case studies illustrate the different effects of a coherent versus multiple identity on knowledge integration and the need for a coherent company-wide social identity, instead of a multiple community or group based social identity, to leverage knowledge integration in organizations.
“Heroin Baby”
Authors: Ash Susan
Published: February 2008

This article investigates the iconic/indexical relations between photograph and referent in 19th- and 20th-century fund-raising campaigns by the children's charity Barnardo's. Dr. Barnardo's strategies to secure donations evolved out of the 18th-century practices to display charity children in public spectacles. Such benevolent entreaties function as speech acts, deploying the challenge “I dare you to help,” backed up with “Shame on you for not responding.” The article argues that public images (i.e., the 1999 campaign image of an infant preparing to inject heroin) may instigate the shame affect as theorized by S. Tomkins and E. K. Sedgwick. Indeed, this nexus of critical theory can help us to understand the resistance to benevolence as within the parameters of the shame-humiliation-anger response. The objective is to investigate how photographs have a determining influence in shaping how we view human crises and ultimately how we evaluate these conflicts.
Utilizing Qualitative Data Analysis Software
Authors: Hwang Sungsoo
Published: February 2008

Atlas.ti is qualitative data analysis (QDA) software, and its recent version 5.2.12 is now more user friendly as a Windows-based application. Atlas.ti provides some very useful tools in academic research, particularly for social science disciplines. This review offers a case study of utilizing a QDA software package, with two examples of research presented to show how to utilize Atlas.ti. This will serve as a practical guide for qualitative researchers who are beginning to use the QDA software Atlas.ti.
Improved RNA quality and TaqMan®Pre-amplification method (PreAmp) to enhance expression analysis from formalin fixed paraffin embedded (FFPE) materials
Authors: Li Jinghuan , Smyth Paul , Cahill Susanne , Denning Karen , Flavin Richard , Aherne Sinead , Pirotta Marco , Guenther Simone M , O'Leary John J , Sheils Orla
Published: February 2008

Background

Archival formalin-fixed paraffin-embedded (FFPE) tissues represent an abundant source of clinical specimens; however their use is limited in applications involving analysis of gene expression due to RNA degradation and modification during fixation and processing. This study improved the quality of RNA extracted from FFPE by introducing a heating step into the selected extraction protocols. Further, it evaluated a novel pre-amplification system (PreAmp) designed to enhance expression analysis from tissue samples using assays with a range of amplicon size (62–164 bp).

Results

Results from the Bioanalyzer and TaqMan® data showed improvement of RNA quality extracted using the modified protocols from FFPE. Incubation at 70°C for 20 minutes was determined to be the best condition of those tested to disrupt cross-links while not compromising RNA integrity. TaqMan® detection was influenced by master mix, amplicon size and the incorporation of a pre-amplification step. TaqMan® PreAmp consistently achieved decreased CT values in both snap frozen and FFPE aliquots compared with no pre-amplification.

Conclusion

Modification to extraction protocols has facilitated procurement of RNA that may be successfully amplified using QRT-PCR. TaqMan® PreAmp system is a robust and practical solution to limited quantities of RNA from FFPE extracts.
Rutoside decreases human macrophage-derived inflammatory mediators and improves clinical signs in adjuvant-induced arthritis
Authors: Kauss Tina , Moynet Daniel , Rambert Jérôme , Al-Kharrat Abir , Brajot Stephane , Thiolat Denis , Ennemany Rachid , Fawaz Fawaz , Mossalayi M Djavad
Published: February 2008

Background

Dietary flavonols may play an important role in the adjunct therapy of chronic inflammation. The availability of therapeutic formulations of pentahydroxyflavone glycoside, rutoside (RU), led us to investigate the ability of this molecule to modulate the release of various proinflammatory mediators from human activated macrophages in vitro and to ameliorate arthritic markers in a rat model.

Methods

RU was added simultaneously to human macrophages during their activation. Cells were then analyzed for inflammation-related gene expression using a specific array, and cell supernatants were collected to measure inflammatory mediators. RU was also injected into adjuvant-induced arthritic rats, and disease progression and body weight were evaluated until 50 days after injection. Sera and peritoneal macrophages were also collected to quantify the RU effect on various inflammatory markers.

Results

RU inhibited inflammation-related gene expression in activated human macrophages and the release of nitric oxide, tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6 from these cells. In a rat model, RU inhibited clinical signs of chronic arthritis, correlating with decreased levels of inflammatory cytokines detected in rat sera and macrophage supernatants.

Conclusion

Thus, RU may have clinical value in reducing inflammatory manifestations in human arthritis and other inflammatory diseases.
The Association between the FTO Gene and Fat Mass in Humans Develops by the Postnatal Age of Two Weeks
Authors: López-Bermejo Abel , Petry Clive J. , Díaz Marta , Sebastiani Giorgia , de Zegher Francis , Dunger David B. , Ibáñez Lourdes
Published: February 2008

Objective: Little is known about the genetic determinants of fat mass around birth. We hypothesized that the common rs9939609 single-nucleotide polymorphism (SNP) in FTO is associated with fat mass and metabolic parameters in neonates.

Design: We conducted a cross-sectional, hospital-based study.

Patients: Patients included 234 full-term, healthy newborns [122 girls and 112 boys; gestational age (mean, range), 39.0 (37.0–42.0) wk; birth weight, 3.2 (1.9–4.2) kg].

Methods: Cord-blood insulin, IGF-I, IGF-binding protein-1, adiponectin, and visfatin were measured by specific immunoassays. Body composition was assessed by dual-energy x-ray absorptiometry at about 13 d (range, 9–20 d). Genotyping of rs9939609 was achieved by restriction fragment length polymorphism analysis.

Results: The rs9939609 SNP in FTO was not associated with birth weight; however, it was associated with serum visfatin (P < 0.001), with weight and ponderal index at age 2 wk (P < 0.05), and with total, truncal, and abdominal fat (P < 0.05 to P = 0.01), so that AA homozygotes had 37% higher plasma visfatin concentration and 17, 20, and 17% higher total, truncal, and abdominal fat mass, respectively, than T-carrier neonates.

Conclusion: Our findings support a role of the common rs9939609 SNP in FTO gene in the early stages of fat accretion in humans and disclose novel associations between this SNP and both serum visfatin and abdominal fat mass in neonates.
Androgen Receptor Gene CAG Repeat Polymorphism and X-Chromosome Inactivation in Children with Premature Adrenarche
Authors: Lappalainen Saila , Utriainen Pauliina , Kuulasmaa Tiina , Voutilainen Raimo , Jääskeläinen Jarmo
Published: February 2008

Context: There is variation in the adrenal androgen levels and clinical findings of children with premature adrenarche (PA).

Objectives: We hypothesized that androgen sensitivity, indicated by the length of CAG repeat in the X-chromosomal androgen receptor (AR) gene has a role in the polygenic pathogenesis of PA.

Design and Patients: We performed a cross-sectional association study among 73 Finnish Caucasian children with PA (10 boys and 63 girls) and 97 age- and gender-matched healthy controls (18 boys and 79 girls).

Main Outcome Measures: AR gene methylation-weighted CAGn(mwCAGn) via CAGn length and X-chromosome inactivation analysis and clinical phenotype were determined.

Setting: The study took place at a university hospital.

Results: PA subjects had significantly shorter mwCAGn than controls [mean difference (95% confidence interval); 0.76 (0.14–1.38); P = 0.017]. AR gene mwCAGn did not correlate with androgen or SHBG levels in either group. In children with PA, mwCAGn correlated positively with body mass index (BMI) (τ = 0.19; P = 0.02). The mean of mwCAGn was significantly shorter in PA children with lower BMI compared with PA children with higher BMI [BMI sd score < 0.79, n = 35, vs. BMI sd score > 0.79, n = 36; 1.13 (0.38–1.87), P = 0.004] and in PA children with lower BMI compared with healthy children with same BMI (P = 0.004).

Conclusions: The AR gene CAGn polymorphism may have a significant role in the pathogenesis of PA, especially in lean children.
Nerve repair by denatured muscle autografts promotes sustained sensory recovery in leprosy
Authors: Pereira J. H. , Palande D. D. , Narayanakumar T. S. , Subramanian A. S. , Gschmeissner S. , Wilkinson M.
Published: February 2008

A total of 38 patients with leprosy and localised nerve damage (11 median at the wrist and 37 posterior tibial at the ankle) were treated by 48 freeze-thawed skeletal muscle autografts ranging between 2.5 cm and 14 cm in length. Sensory recovery was noted in 34 patients (89%) and was maintained during a mean period of follow-up of 12.6 years (4 to 14). After grafting the median nerve all patients remained free of ulcers and blisters, ten demonstrated perception of texture and eight recognised weighted pins. In the posterior tibial nerve group, 24 of 30 repairs (80%) resulted in improved healing of the ulcers and 26 (87%) demonstrated discrimination of texture. Quality of life and hand and foot questionnaires showed improvement; the activities of daily living scores improved in six of seven after operations on the hand, and in 14 of 22 after procedures on the foot. Another benefit was subjective improvement in the opposite limb, probably because of the protective effect of better function in the operated side. This study demonstrates that nerve/muscle interposition grafting in leprosy results in consistent sensory recovery and high levels of patient satisfaction. Ten of 11 patients with hand operations and 22 of 25 with procedures to the foot showed sensory recovery in at least one modality.
Bicondylar osteochondritis dissecans in the knee
Authors: Hanna S. A. , Aston W. J. S. , Gikas P. D. , Briggs T. W. R.
Published: February 2008

We describe two cases of osteochondritis dissecans (OCD) affecting both femoral condyles in the same knee. The patients presented with recurrent episodes of pain and swelling, but these were initially thought to be ‘growing pains’. Eventually, a delayed diagnosis of bicondylar OCD was established and both patients were referred for further management. After assessing the extent of the disease on MRI, matrix-induced autologous chondrocyte implantation was performed to treat the defects of the lateral condyle in each case, with a plan to address the medial defects at a later stage. Proposed theories on the aetiology of the condition and available methods of treatment are discussed. A diagnosis of OCD should be considered in young patients with persistent knee pain and effusions, and MRI is the investigation of choice for early detection.
Radiological landmarks for placement of the tunnels in single-bundle reconstruction of the anterior cruciate ligament
Authors: Pinczewski L. A. , Salmon L. J. , Jackson W. F. M. , von Bormann R. B. P. , Haslam P. G. , Tashiro S.
Published: February 2008

There is little evidence examining the relationship between anatomical landmarks, radiological placement of the tunnels and long-term clinical outcomes following anterior cruciate ligament (ACL) reconstruction. The aim of this study was to investigate the reproducibility of intra-operative landmarks for placement of the tunnels in single-bundle reconstruction of the ACL using four-strand hamstring tendon autografts.

Isolated reconstruction of the ACL was performed in 200 patients, who were followed prospectively for seven years with use of the International Knee Documentation Committee forms and radiographs. Taking 0% as the anterior and 100% as the posterior extent, the femoral tunnel was a mean of 86% (sd 5) along Blumensaat’s line and the tibial tunnel was 48% (sd 5) along the tibial plateau. Taking 0% as the medial and 100% as the lateral extent, the tibial tunnel was 46% (sd 3) across the tibial plateau and the mean inclination of the graft in the coronal plane was 19° (sd 5.5).

The use of intra-operative landmarks resulted in reproducible placement of the tunnels and an excellent clinical outcome seven years after operation. Vertical inclination was associated with increased rotational instability and degenerative radiological changes, while rupture of the graft was associated with posterior placement of the tibial tunnel. If the osseous tunnels are correctly placed, single-bundle reconstruction of the ACL adequately controls both anteroposterior and rotational instability.
Ezetimibe-Associated Immune Thrombocytopenia
Authors: Pattis Peter , Wiedermann Christian J
Published: February 2008

Objective:

To describe a case of immune thrombocytopenia associated with treatment with ezetimibe, a cholesterol absorption inhibitor.

Case Summary:

A 72-year-old man presented with severe thrombocytopenia (platelets 3 × 103/μL) and “wet purpura” 4 weeks after being started on daily therapy using a combination of ezetimibe 10 mg/simvastatin 20 mg. Platelet counts normalized after administration of ezetimibe/ simvastatin was stopped. Nine months later, the patient was restarted on simvastatin because of uncorrected dyslipidemia. Platelet counts remained within the normal range following that rechallenge.

Discussion:

Registry data revealed the possibility of ezetimibe-induced thrombocytopenia, but, as of December 3, 2007, no other case reports on this interaction had been published. This case illustrates the probable occurrence of ezetimibe-induced thrombocytopenia. Platelet counts dropped significantly when ezetimibe therapy was initiated, then resolved upon discontinuation of therapy. Other causes of thrombocytopenia were ruled out, and rechallenge with simvastatin further supports the presence of a causal relationship between thrombocytopenia and ezetimibe. Use of the Naranjo probability scale indicated a probable relationship between thrombocytopenia and ezetimibe therapy. An adverse reaction scale specific for evaluation of drug-induced thrombocytopenia also indicated the probable likelihood of ezetimibe-induced thrombocytopenia. This patient was not rechallenged with ezetimibe due to the highly suggestive timeline present and unnecessary risk for him.

Conclusions:

Ezetimibe-associated thrombocytopenia cannot be ruled out in the patient reported here. Clinicians should be aware of this adverse event.
Isoflavones regulate secretion of leukemia inhibitory factor and transforming growth factor β and expression of glycodelin in human endometrial epithelial cells
Authors: Xu Jin-Wen , Yasui Naomi , Ikeda Katsumi , Pan Wei-Jun , Watanabe June , Shiotani Masahide , Yanaihara Atsushi , Miki Tomohiro , Yamori Yukio
Published: February 2008

Isoflavones have attracted much attention due to their association with health benefits; however, comprehensive understanding of the beneficial impacts of isoflavones on uterine biology at the molecular level remains unexplored. In the present study, our data showed that isoflavones aglycones AglyMax, genistein, and equol, but not daidzein, within the range of plasma concentration, displayed bioavailability in regulating the secretion of leukemia inhibitory factor (LIF) and transforming growth factor β (TGF-β) in Ishikawa cells, which was blocked by an estrogen receptor antagonist ICI 182 780, mitogen-activated protein kinase kinase (MEK)1/2 inhibitor PD98059, and p38 mitogen-activated protein kinase inhibitor SB203580. We also found that AglyMax and genistein increased in cyclic AMP release and the expression of glycodelin protein in Ishikawa cells assayed using western blot and immunochemical staining. The MEK1/2 inhibitor PD98059 and the protein kinase A inhibitor H89, but not SB203580, attenuated this glycoprotein expression. Moreover, isoflavone aglycones AglyMax stimulated LIF, and TGF-β secretion, and glycodelin expression in separate primary endometrial epithelial cells in the follicular phase or luteal phase from healthy subject donors. Overall, our findings suggest that isoflavones may alter the uterine expression of estrogen-responsive genes.
Stress-induced regulation of steroidogenic acute regulatory protein expression in head kidney of Gilthead seabream (Sparus aurata)
Authors: Castillo Juan , Castellana Barbara , Acerete Laura , Planas Josep V , Goetz Frederick W , Mackenzie Simon , Tort Lluis
Published: February 2008

Steroidogenic acute regulatory protein (StAR) transfers cholesterol over the inner mitochondrial membrane. In mammals, StAR controls this rate-limiting step of steroidogenesis, but its expression and regulation has not been well explored in fish. The present work investigates StAR mRNA expression in the head kidney of the gilthead seabream (Sparus aurata) under different stressors. We have cloned the StAR cDNA (1461 bp) in seabream (accession number EF640987), which has an open reading frame of 861 nucleotides encoding a polypeptide of 286 aa, and displays high sequence identity with StAR of other fish and mammalian counterparts. Seabream StAR transcripts were found to be expressed exclusively in head kidneys and gonads. In fish under acute stress (chased with a net), plasma cortisol levels peaked within 1 h, were still high after 6 h, and decreased after 16 h, although no increases in head kidney StAR expression were observed at any time post-stressor. Fish under chronic high-density stress showed cortisol levels 90-fold higher than controls and StAR mRNA levels increased threefold. Lipopolysaccharide (LPS) injection increased head kidney StAR mRNA levels after 6 h, reached a maximum at 12 h, and decreased until 72 h. When the head kidney cells were incubated in vitro and treated with ACTH or LPS, ACTH induced an increase in StAR expression as expected, but LPS induced a reduction in StAR expression. In conclusion, StAR expression in seabream head kidneys is highly regulated by different stressors.
Pathophysiological basis for thyrotoxicosis as an aggravating factor in post-ischemic brain injury in rats
Authors: Rastogi Leena , Gupta Sushil , Godbole Madan M
Published: February 2008

The cross-sectional epidemiological studies investigating hyperthyroidism as a risk factor for hypertension and stroke are not conclusive. Several case studies, however, indicate that persistent thyrotoxicosis aggravates neurological damage subsequent to a stroke. To test the hypothesis, we measured physiological and biochemical parameters in a model of transient focal ischemia in rats with prior induction of thyrotoxicosis to investigate its effects. Age- and weight-matched rats were made hyperthyroid prior to middle cerebral artery (MCA) occlusion and killed after 3 days of reperfusion. We then estimated neurological deficit scores, body temperature, circulating total and free thyroxine (fT4) levels, lipid peroxide and thiol levels, and lactate dehydrogenase activity. While the standard 2-h occlusion of MCA resulted in very high mortality in hyperthyroid animals, the 30-min MCA occlusion resulted in a significant increase in neurological deficits compared with sham-operated animals. We observed a twofold or more increase in circulating fT4 levels in rats receiving thyroxine. The increase in infarct size directly correlated with the increased dose of thyroxine. A significant thyroxine dose-dependent increase in lipid peroxide (malondialdehyde levels, P<0.05), lactate dehydrogenase activity (P<0.01), and a significant decrease in protective thiol levels (P<0.05) were observed. The data support our hypothesis that thyrotoxicosis is an independent risk factor which contributes to the aggravation of post-stroke injury and death. The study results indicate a need to control thyrotoxicosis in elderly populations to reduce the risk.
Passivity‐based sliding mode control for nonlinear systems
Authors: Koshkouei Ali J.
Published: February 2008

Passivity with sliding mode control for a class of nonlinear systems with and without unknown parameters is considered in this paper. In fact, a method for deriving a nonlinear system with external disturbances to a passive system is considered. Then a passive sliding mode control is designed corresponding to a given storage function. The passivity property guarantees the system stability while sliding mode control techniques assures the robustness of the proposed controller. When the system includes unknown parameters, an appropriate updated law is obtained so that the new transformed system is passive. The passivation property of linear systems with sliding mode is also analysed. The linear and nonlinear theories are applied to a simple pendulum model and the gravity‐flow/pipeline system, respectively. Copyright © 2008 John Wiley & Sons, Ltd.
Fine‐mapping subtelomeric deletions and duplications by comparative genomic hybridization in 42 individuals
Authors: DeScipio Cheryl , Spinner Nancy B. , Kaur Maninder , Yaeger Dinah , Conlin Laura K. , Ambrosini Anthony , Hu Sufen , Shan Simei , Krantz Ian D. , Riethman Harold
Published: February 2008

Human subtelomere regions contain numerous gene‐rich segments and are susceptible to germline rearrangements. The availability of diagnostic test kits to detect subtelomeric rearrangements has resulted in the diagnosis of numerous abnormalities with clinical implications including congenital heart abnormalities and mental retardation. Several of these have been described as clinically recognizable syndromes (e.g., deletion of 1p, 3p, 5q, 6p, 9q, and 22q). Given this, fine‐mapping of subtelomeric breakpoints is of increasing importance to the assessment of genotype–phenotype correlations in these recognized syndromes as well as to the identification of additional syndromes. We developed a BAC and cosmid‐based DNA array (TEL array) with high‐resolution coverage of 10 Mb‐sized subtelomeric regions, and used it to analyze 42 samples from unrelated patients with subtelomeric rearrangements whose breakpoints were previously either unmapped or mapped at a lower resolution than that achievable with the TEL array. Six apparently recurrent subtelomeric breakpoint loci were localized to genomic regions containing segmental duplication, copy number variation, and sequence gaps. Small (1 Mb or less) candidate gene regions for clinical phenotypes in separate patients were identified for 3p, 6q, 9q, and 10p deletions as well as for a 19q duplication. In addition to fine‐mapping nearly all of the expected breakpoints, several previously unidentified rearrangements were detected. © 2008 Wiley‐Liss, Inc.
Population demography and social structure changes in Eulemur fulvus rufus from 1988 to 2003
Authors: Erhart Elizabeth M. , Overdorff Deborah J.
Published: February 2008

Eulemur fulvus rufus has been described as having stable multi‐male/multi‐female groups, a male‐biased sex ratio, and female philopatry. However, in a 16‐year study of this subspecies we documented a great deal of demographic change as several groups permanently fissioned, some groups disappeared, and new groups formed. We split the dataset into two periods, 1988 to 1993 and 1994 to 2003, which coincided with the first disappearance of a study group (in August 1994) and the first permanent group fission (in December 1994). The average group size decreased by nearly half between the study periods (10.5–5.6), while the frequency of group membership changes increased (2.0–8.3 times/year), and the birth rate decreased (0.56–0.38). Females, as well as males, immigrated into study groups and transferred between groups, something that has been rarely seen in this subspecies. We also found a significant decline in the amount of fruit from the earliest part of the study to the latter part of the study. Study groups did not switch to other types of foods during periods of fruit shortage, but traveled outside of their home range areas more often over the study period. Finally, the density E. f. rufus decreased in the study area while the densities of their main food competitors, Varecia variegata and Eulemur rubriventer, increased. Although few primate populations are numerically stable over time, we suggest that female behavioral responses to decreases in fruit availability may have influenced some of the demographic changes we witnessed in this study. Am J Phys Anthropol, 2008. © 2008 Wiley‐Liss, Inc.
Determination of acetylsalicylic acid and its major metabolite, salicylic acid, in human plasma using liquid chromatography–tandem mass spectrometry: application to pharmacokinetic study of Astrix® in Korean healthy volunteers
Authors: Bae Soo Kyung , Seo Kyung Ah , Jung Eun Ji , Kim Ho‐Sook , Yeo Chang‐Woo , Shon Ji‐Hong , Park Kyung‐Mi , Liu Kwang‐Hyeon , Shin Jae‐Gook
Published: February 2008

The first liquid chromatography–tandem mass spectrometry (LC/MS/MS) method for determination of acetylsalicylic acid (aspirin, ASA) and one of its major metabolites, salicylic acid (SA), in human plasma using simvastatin as an internal standard has been developed and validated. For ASA analysis, a plasma sample containing potassium fluoride was extracted using a mixture of ethyl acetate and diethyl ether in the presence of 0.5% formic acid. SA, a major metabolite of ASA, was extracted from plasma using protein precipitation with acetonitrile. The compounds were separated on a reversed‐phase column with an isocratic mobile phase consisting of acetonitrile and water containing 0.1% formic acid (8:2, v/v). The ion transitions recorded in multiple reaction monitoring mode were m/z 179 → 137, 137 → 93 and 435 → 319 for ASA, SA and IS, respectively. The coefficient of variation of the assay precision was less than 9.3%, and the accuracy exceeded 86.5%. The lower limits of quantification for ASA and SA were 5 and 50 ng/mL, respectively. The developed assay method was successfully applied for the evaluation of pharmacokinetics of ASA and SA after single oral administration of Astrix® (entero‐coated pellet, 100 mg of aspirin) to 10 Korean healthy male volunteers. Copyright © 2008 John Wiley & Sons, Ltd.
Chemische Produktion gemäß Koran und Thora. Chemie und Religion
Authors: Roth Klaus
Published: February 2008

Die Herstellung von Produkten im Einklang mit den Gesetzen des islamischen oder jüdischen Glaubens stellt sowohl für die chemische Industrie als auch für die religiösen Autoritäten eine erhebliche Herausforderung dar, die nur in vertrauensvoller Zusammenarbeit gemeistert werden kann. Ein koscher‐ oder halal‐Zertifikat bedeutet nicht, dass das Produkt aus chemischer Sicht besonders rein ist. Vielmehr wird garantiert, dass alle Rohstoffe koscher oder halal waren und der gesamte Verarbeitungsprozess im Einklang mit den religiösen Gesetzen erfolgt ist. Für die chemische Industrie öffnen sich neue Märkte und der gläubige Verbraucher kann sicher sein, dass eine zweite vertrauenswürdige Autorität den gesamten Herstellungsprozess überwacht hat.
The Impact of Computer‐assisted Auscultation on Physician Referrals of Asymptomatic Patients with Heart Murmurs
Authors: Watrous Raymond L. , Thompson W. Reid , Ackerman Stacey J.
Published: February 2008

Background

As many as 50–70% of asymptomatic children referred for specialist evaluation or echocardiography because of a murmur have no heart disease.

Hypothesis

Computer‐assisted auscultation (CAA) can improve the sensitivity and specificity of referrals for evaluation of heart murmurs.

Methods

Seven board‐certified primary care physicians were evaluated both without and with use of a computer‐based decision‐support system using 100 prerecorded patient heart sounds (55 innocent murmurs, 30 pathological murmurs, 15 without murmur). The sensitivity and specificity of their murmur referral decisions relative to American College of Cardiology/American Heart Association (ACC/AHA) guidelines, and sensitivity and specificity of murmur detection and characterization (innocent versus pathological) were measured.

Results

Sensitivity for detection of murmurs significantly increased with use of CAA from 76.6 to 89.1% (p <0.001), while specificity remained unaffected (80.0 versus 81.0%). Computer‐assisted auscultation improved sensitivity of correctly identifying pathological murmur cases from 82.4 to 90.0%, and specificity of correctly identifying benign cases (with innocent or no murmurs) from 74.9 to 88.8%. (p <0.001). Referral sensitivity increased from 86.7 to 92.9%, while specificity increased from 63.5 to 78.6% using CAA (p <0.001).

Conclusions

Computer‐assisted auscultation appears to be a promising new technology for informing the referral decisions of primary care physicians. Copyright © 2008 Wiley Periodicals, Inc.
The voice and you: development and psychometric evaluation of a measure of relationships with voices
Authors: Hayward Mark , Denney Joanna , Vaughan Sam , Fowler David
Published: February 2008

The experience of hearing voices has recently been conceptualized within a relational framework. Birtchnell's Relating Theory offers a framework capable of exploring the power and intimacy within the relationship between the hearer and the voice. However, measures of relationships with voices derived from the theory, such as the Hearer to Voice (HTV) and Voice to Hearer (VTH) by Vaughan and Fowler, have lacked robust psychometric properties. Data were available from 71 participants who completed the HTV and VTH, and analysis of these data generated a new 29‐item measure, the Voice and You (VAY), capable of assessing the ‘interrelating’ between the hearer and the voice. The VAY was completed by a further 30 participants and was found to be internally consistent, stable over time and associated with other measures of the voice‐hearing experience. The VAY offers a psychometrically stable measure of the relationship between the hearer and the voice. It may be used as an adjunct to the clinical interview and/or a measure of outcome. Copyright © 2008 John Wiley & Sons, Ltd.