bluuebunny/crossref_metadata_2025 huggingface dataset:
Infection with Replication-deficient Adenovirus Induces Changes in the Dynamic Instability of Host Cell Microtubules
Authors: Warren James C. , Rutkowski Adam , Cassimeris Lynne
Published: June 2006

Adenovirus translocation to the nucleus occurs through a well characterized minus end-directed transport along microtubules. Here, we show that the adenovirus infection process has a significant impact on the stability and dynamic behavior of host cell microtubules. Adenovirus-infected cells had elevated levels of acetylated and detyrosinated microtubules compared with uninfected cells. The accumulation of modified microtubules within adenovirus-infected cells required active RhoA. Adenovirus-induced changes in microtubule dynamics were characterized at the centrosome and at the cell periphery in living cells. Adenovirus infection resulted in a transient enhancement of centrosomal microtubule nucleation frequency. At the periphery of adenovirus-infected cells, the dynamic instability of microtubules plus ends shifted toward net growth, compared with the nearly balanced growth and shortening observed in uninfected cells. In infected cells, microtubules spent more time in growth, less time in shortening, and underwent catastrophes less frequently compared with those in uninfected cells. Drug-induced inhibition of Rac1 prevented most of these virus-induced shifts in microtubule dynamic instability. These results demonstrate that adenovirus infection induces a significant stabilizing effect on host cell microtubule dynamics, which involve, but are not limited to, the activation of the RhoGTPases RhoA and Rac1.
Heterogeneous Nuclear Ribonucleoprotein (hnRNP) E1 Binds to hnRNP A2 and Inhibits Translation of A2 Response Element mRNAs
Authors: Kosturko Linda D. , Maggipinto Michael J. , Korza George , Lee Joo Won , Carson John H. , Barbarese Elisa
Published: June 2006

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2 is a trans-acting RNA-binding protein that mediates trafficking of RNAs containing the cis-acting A2 response element (A2RE). Previous work has shown that A2RE RNAs are transported to myelin in oligodendrocytes and to dendrites in neurons. hnRNP E1 is an RNA-binding protein that regulates translation of specific mRNAs. Here, we show by yeast two-hybrid analysis, in vivo and in vitro coimmunoprecipitation, in vitro cross-linking, and fluorescence correlation spectroscopy that hnRNP E1 binds to hnRNP A2 and is recruited to A2RE RNA in an hnRNP A2-dependent manner. hnRNP E1 is colocalized with hnRNP A2 and A2RE mRNA in granules in dendrites of oligodendrocytes. Overexpression of hnRNP E1 or microinjection of exogenous hnRNP E1 in neural cells inhibits translation of A2RE mRNA, but not of non-A2RE RNA. Excess hnRNP E1 added to an in vitro translation system reduces translation efficiency of A2RE mRNA, but not of nonA2RE RNA, in an hnRNP A2-dependent manner. These results are consistent with a model where hnRNP E1 recruited to A2RE RNA granules by binding to hnRNP A2 inhibits translation of A2RE RNA during granule transport.
Regulated Synthesis and Functions of Laminin 5 in Polarized Madin-Darby Canine Kidney Epithelial Cells
Authors: Mak Grace Z. , Kavanaugh Gina M. , Buschmann Mary M. , Stickley Shaun M. , Koch Manuel , Goss Kathleen Heppner , Waechter Holly , Zuk Anna , Matlin Karl S.
Published: June 2006

Renal tubular epithelial cells synthesize laminin (LN)5 during regeneration of the epithelium after ischemic injury. LN5 is a truncated laminin isoform of particular importance in the epidermis, but it is also constitutively expressed in a number of other epithelia. To investigate the role of LN5 in morphogenesis of a simple renal epithelium, we examined the synthesis and function of LN5 in the spreading, proliferation, wound-edge migration, and apical–basal polarization of Madin-Darby canine kidney (MDCK) cells. MDCK cells synthesize LN5 only when subconfluent, and they degrade the existing LN5 matrix when confluent. Through the use of small-interfering RNA to knockdown the LN5 α3 subunit, we were able to demonstrate that LN5 is necessary for cell proliferation and efficient wound-edge migration, but not apical–basal polarization. Surprisingly, suppression of LN5 production caused cells to spread much more extensively than normal on uncoated surfaces, and exogenous keratinocyte LN5 was unable to rescue this phenotype. MDCK cells also synthesized laminin α5, a component of LN10, that independent studies suggest may form an assembled basal lamina important for polarization. Overall, our findings indicate that LN5 is likely to play an important role in regulating cell spreading, migration, and proliferation during reconstitution of a continuous epithelium.
Ppc89 Links Multiple Proteins, Including the Septation Initiation Network, to the Core of the Fission Yeast Spindle-Pole Body
Authors: Rosenberg Joshua A. , Tomlin Gregory C. , McDonald W. Hayes , Snydsman Brian E. , Muller Eric G. , Yates John R. , Gould Kathleen L.
Published: June 2006

The spindle-pole body (SPB), the yeast analog of the centrosome, serves as the major microtubule (MT) organizing center in the yeast cell. In addition to this central function, the SPB organizes and concentrates proteins required for proper coordination between the nuclear-division cycle and cytokinesis. For example, the Schizosaccharomyces pombe septation-initiation network (SIN), which is responsible for initiating actomyosin ring constriction and septation, is assembled at the SPB through its two scaffolding components, Sid4 and Cdc11. In an effort to identify novel SIN interactors, we purified Cdc11 and identified by mass spectrometry a previously uncharacterized protein associated with it, Ppc89. Ppc89 localizes constitutively to the SPB and interacts directly with Sid4. A fusion between the N-terminal 300 amino acids of Sid4 and a SPB targeting domain of Ppc89 supplies the essential function of Sid4 in anchoring the SIN. ppc89Δ cells are inviable and exhibit defects in SPB integrity, and hence in spindle formation, chromosome segregation, and SIN localization. Ppc89 overproduction is lethal, resulting primarily in a G2 arrest accompanied by massive enlargement of the SPB and increased SPB MT nucleation. These results suggest a fundamental role for Ppc89 in organization of the S. pombe SPB.
Conserved Elements of the RAM Signaling Pathway Establish Cell Polarity in the BasidiomyceteCryptococcus neoformansin a Divergent Fashion from Other Fungi
Authors: Walton Felicia J. , Heitman Joseph , Idnurm Alexander
Published: June 2006

In eukaryotes the complex processes of development, differentiation, and proliferation require carefully orchestrated changes in cellular morphology. Single-celled eukaryotes provide tractable models for the elucidation of signaling pathways involved in morphogenesis. Here we describe a pathway regulating cell polarization and separation in the human pathogenic fungus Cryptococcus neoformans. An insertional mutagenesis screen identified roles for the ARF1, CAP60, NDH1, KIC1, CBK1, SOG2, and TAO3 genes in establishing normal colony morphology. ARF1 and CAP60 are also required for capsule production, a virulence factor, and ARF1 confers resistance to the antifungal fluconazole. KIC1, CBK1, SOG2, and TAO3 are homologues of genes conserved in other eukaryotes; in Saccharomyces cerevisiae they constitute components of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. A targeted deletion of a fifth component of RAM (MOB2) conferred identical phenotypes to kic1, cbk1, sog2, or tao3 mutations. Characterization of these genes in C. neoformans revealed unique features of the RAM pathway in this organism. Loss of any of these genes caused constitutive hyperpolarization instead of the loss of polarity seen in S. cerevisiae. Furthermore, sensitivity to the drugs FK506 and cyclosporin A demonstrates that the RAM pathway acts in parallel with the protein phosphatase calcineurin in C. neoformans but not in S. cerevisiae. These results indicate that conserved signaling pathways serve both similar and divergent cellular roles in morphogenesis in these divergent organisms.
Demographic effects of the introduction of steroid contraception in developed countries
Authors: Leridon Henri
Published: June 2006

The use of the contraceptive pill increased very rapidly in the 1970s in many developed countries, and fertility almost simultaneously started to decline. We discuss here the possibility of a causal link between these two major changes. We first provide evidence for a relationship between the spread of oral contraceptive use and the change in fertility in many European countries over the last three or four decades. The situation of specific countries is examined more in depth on the basis of available literature. We then review the various theories attempting to explain these trends and see how the family planning variables are treated in these approaches. At the country level, the conclusion is unambiguous: within individual countries, there is no systematic negative correlation between fertility and contraceptive pill use. The development of hormonal contraception cannot be considered as responsible for either starting or the size of the fertility decline. A more subtle chain of causality must be considered, but there is no agreement on a general theory of fertility changes. Most authors, however, agree that the diffusion of modern contraception has certainly contributed to the reduction in the number of unwanted pregnancies and has also facilitated and favoured the adoption of new (more restrictive) norms for the ideal family size.
Case Selection: Insights fromRethinking Social Inquiry
Authors: Shively W. Phillips
Published: June 2006

This book, responding to the stimulus of the volume by Gary King, Robert Keohane, and Sidney Verba, helps to carry forward King et al.'s original purpose—to bridge quantitative and qualitative perspectives and find the unity of method underlying both of them. Whether or not we accept King et al.'s own vision of the underlying unity, it is clear that their work has been a catalyst for progress in this direction.
Paraproteinemic Neuropathies
Authors: Chacko Jebin M. , Spinner Warren D.
Published: June 2006

Paraproteinemic neuropathies comprise a diverse group of disorders that includes monoclonal gammopathy of undetermined significance, primary amyloidosis, multiple myeloma, cryoglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes) syndrome, and Waldenstrom macroglobulinemia. Various factors including hepatitis C virus, vascular endothelial growth factor, and an array of cytokines are implicated in the pathogenesis of these conditions. More recently, a variety of novel antibody specificities, and vasculitis, have also been described as contributory factors in the development of these neuropathies. Therapeutic approaches for paraproteinemic neuropathies have included administration of cytotoxic agents, steroids, interferon-α, intravenous immunoglobulin, radiation, bone marrow transplantation, and more recently, drugs such as rituximab and bevacizumab. In this article, we review some of the well-known features of these diseases, and highlight some of the more recent findings from the vast literature for these diseases.
Neuromuscular Highlights—AAN 2005
Authors: Cheema Zahid , Saperstein David , Jackson Carolyn , Newman Daniel
Published: June 2006

Summary of Neuromuscular Presentations at the 57th Annual AAN 2005 meeting in Miami Florida on topics of Facioscapulohumeral muscular dystrophy (FSHD), Duchenne muscular dystrophy (DMD), Diabetic Neuropathy, Charco Marie Tooth disease (CMT), Comparison of injected steroids versus Surgery for carpal tunnel syndrome, Rituximab in Anti-MAG associated polyneuropathy, Cannabis based medicine (CBM) in the treatment of neuropathic pain, utility of skin biopsy with intraepidermal nerve fiber density (IENFD) in sensory complaints, comparing sympathetic skin responses (SSRs) and skin biopsy in diagnosing small fiber sensory neuropathy, Chronic inflammatory demyelinating polyneuropathy (CIDP) clinical and electrophysiologic predictors, affect of limb warming in mild ulnar nerve conduction study (NCS) abnormalities, Tamoxifen affect in ALS, open label study of 3,4 DAP, Pyridostigmine and Ephedrine in fast channel syndrome, Mexilitine as an antimyotonia treatment in myotonic dystrophy (DM1), frontal lobe impairment evaluation in DM1 and DM2 patients and phenotype–genotype correlation in patients with dysferlinopathy.
Fibroblast growth factor signals regulate a wave of Hedgehog activation that is essential for coronary vascular development
Authors: Lavine Kory J. , White Andrew C. , Park Changwon , Smith Craig S. , Choi Kyunghee , Long Fanxin , Hui Chi-chung , Ornitz David M.
Published: June 2006

Myocardial infarction and ischemic heart disease are the leading cause of death in the industrial world. Therapies employed for treating these diseases are aimed at promoting increased blood flow to cardiac tissue. Pharmacological induction of new coronary growth has recently been explored, however, clinical trials with known proangiogenic factors have been disappointing. To identify novel therapeutic targets, we have explored signaling pathways that govern embryonic coronary development. Using a combination of genetically engineered mice and an organ culture system, we identified novel roles for fibroblast growth factor (FGF) and Hedgehog (HH) signaling in coronary vascular development. We show that FGF signals promote coronary growth indirectly by signaling to the cardiomyoblast through redundant function of Fgfr1 and Fgfr2. Myocardial FGF signaling triggers a wave of HH activation that is essential for vascular endothelial growth factor (Vegf)-A, Vegf-B, Vegf-C, and angiopoietin-2 (Ang2) expression. We demonstrate that HH is necessary for coronary vascular development and activation of HH signaling is sufficient to promote coronary growth and to rescue coronary defects due to loss of FGF signaling. These studies implicate HH signaling as an essential regulator of coronary vascular development and as a potential therapeutic target for coronary neovascularization. Consistent with this, activation of HH signaling in the adult heart leads to an increase in coronary vessel density.
Distinct functions of homeodomain-containing and homeodomain-less isoforms encoded by homothorax
Authors: Noro Barbara , Culi Joaquim , McKay Daniel J. , Zhang Wen , Mann Richard S.
Published: June 2006

The homothorax (hth) gene of Drosophila melanogaster is required for executing Hox functions, for head development, and for forming the proximodistal (PD) axis of the appendages. We show that alternative splicing of hth generates two types of protein isoforms, one that contains a DNA-binding homeodomain (HthFL) and one that does not contain a homeodomain (HDless). Both types of Hth isoforms include the evolutionarily conserved HM domain, which mediates a direct interaction with Extradenticle (Exd), another homeodomain protein. We show that although both HthFL and HDless isoforms of Hth can induce the nuclear localization of Exd, they carry out distinct sets of functions during development. Surprisingly, we find that many of hth’s functions, including PD patterning and most Hox-related activities, can be executed by the HDless isoforms. In contrast, antennal development shows an absolute dependency on the HthFL isoform. Thus, alternative splicing of hth results in the generation of multiple transcription factors that execute unique functions in vivo. We further demonstrate that the mouse ortholog of hth, Meis1, also encodes a HDless isoform, suggesting that homeodomain-less variants of this gene family are evolutionarily ancient.
The myocardin family of transcriptional coactivators: versatile regulators of cell growth, migration, and myogenesis
Authors: Pipes G.C. Teg , Creemers Esther E. , Olson Eric N.
Published: June 2006

The association of transcriptional coactivators with sequence-specific DNA-binding proteins provides versatility and specificity to gene regulation and expands the regulatory potential of individual cis-regulatory DNA sequences. Members of the myocardin family of coactivators activate genes involved in cell proliferation, migration, and myogenesis by associating with serum response factor (SRF). The partnership of myocardin family members and SRF also controls genes encoding components of the actin cytoskeleton and confers responsiveness to extracellular growth signals and intracellular changes in the cytoskeleton, thereby creating a transcriptional–cytoskeletal regulatory circuit. These functions are reflected in defects in smooth muscle differentiation and function in mice with mutations in myocardin family members. This article reviews the functions and mechanisms of action of the myocardin family of coactivators and the physiological significance of transcriptional coactivation in the context of signal-dependent and cell-type-specific gene regulation.
Sex‐dimorphic effects of progesterone and its reduced metabolites on gene expression of myelin proteins by rat Schwann cells
Authors: Magnaghi Valerio , Veiga Sergio , Ballabio Marinella , Gonzalez Lucas C. , Garcia‐Segura Luis M. , Melcangi Roberto C.
Published: June 2006

Abstract  Data obtained in our and other laboratories have indicated that progesterone (P) and its derivatives, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), stimulate the expression of two myelin proteins of the peripheral nervous system (PNS) [i.e., glycoprotein zero (P0) and peripheral myelin protein 22 (PMP22)]. We have now considered the effects of P and its derivatives on these and other myelin proteins [i.e., myelin‐associated glycoprotein (MAG) and myelin and lymphocyte protein (MAL)] in sex‐specific cultures of rat Schwann cells. Gene expression of myelin proteins was assessed by RNase protection assay. Treatment with P or DHP induced a stimulatory effect on P0 mRNA levels in male but not in female Schwann cells. In contrast, treatment with THP increased gene expression of P0 exclusively in female Schwann cells. A similar sex‐difference was also evident for other myelin proteins. Indeed, PMP22 expression was stimulated by treatment with P in male cultures, whereas THP induced an increase of mRNA levels in female cultures. Moreover, MAG was stimulated by THP treatment in male cultures only, whereas MAL expression was unaffected by neuroactive steroid treatment in both male and female cultures. In conclusion, the present observations indicate that the effects of neuroactive steroids on myelin proteins are sexually dimorphic. This finding might represent an important background for sex‐specific therapies of acquired and inherited peripheral neuropathies.
Collateral sprouting of human epidermal nerve fibers following intracutaneous axotomy
Authors: Hahn Katrin , Sirdofsky Michael , Brown Anna , Ebenezer Gigi , Hauer Peter , Miller Clint , Polydefkis Michael
Published: June 2006

Abstract Despite the clinical need, there are no therapeutic compounds available to promote peripheral nerve regeneration. In part, this may be due to a lack of sensitive measures of nerve growth. Here, we describe a novel approach of measuring collateral sprouting of epidermal nerve fibers (ENF) in human subjects and describe the effect of the neuroimmunophilin ligand timcodar dimesylate on collateral nerve sprouting. The objective of this study was to describe a model of intracutaneous axotomy and evaluate the ability of timcodar dimesylate to accelerate human cutaneous nerve regeneration through collateral sprouting. Subjects were randomized to receive placebo, 12.5 or 50 mg/day timcodar dimesylate in a prospective, two‐center, double‐blind, placebo‐controlled trial. A 3‐mm distal thigh punch skin biopsy was performed at baseline, and a 4‐mm overlapping concentric biopsy was taken after 56 days of treatment. Biopsies were processed to visualize ENF, and the collateral sprouting distance (CSD) was measured. Sixty‐two subjects completed the trial, and the CSD was measurable in 52. The CSD (mean ± SEM) was 474.5 µm ± 38.3, 473.4 µm ± 28.4, and 450.8 µm ± 26.5 for the placebo, low and high dose groups, respectively (p = 0.84). The baseline ENF density was associated with the CSD (p = 0.02). Collateral sprouting was efficiently measured using an intracutaneous axotomy model and suggests a collateral sprouting rate of 8.5 µm/day in healthy subjects. The model was consistent across treatment groups and had a low coefficient of variation. Timcodar dimesylate treatment was safe over an 8‐week period but did not improve collateral sprouting among healthy subjects.
SIMPLE mutation analysis in dominant demyelinating Charcot‐Marie‐Tooth disease: three novel mutations
Authors: Latour Philippe , Gonnaud Pierre‐Marie , Ollagnon Elisabeth , Chan Victor , Perelman Serge , Stojkovic Tanya , Stoll Claude , Vial Christophe , Ziegler François , Vandenberghe Antoon , Maire Irène
Published: June 2006

Abstract  Charcot‐Marie‐Tooth disease type 1C (CMT1C) is caused by mutations in the small integral membrane protein of the lysosome/late endosome (SIMPLE). We analyzed the coding sequence of SIMPLE in DNA of 53 unrelated cases of dominant demyelinating CMT disease with no mutations in PMP22, GJB1, MPZ, EGR2, and NEFL genes. Four different missense mutations were observed in six families. The mutation Gly112Ser was found in two families confirming its frequent occurrence in SIMPLE mutations. Three novel mutations were also identified: Ala111Gly (two families), Pro135Ser, and Pro135Thr. Familial studies revealed that all carriers of mutations (n = 38), aged from 1 to 78 years, were symptomatic, notably children under 10 years (n = 8). Motor conduction velocities in the median nerve ranked from 16.4 to 32.8 m/s (n = 20). In our series of 968 unrelated dominant demyelinating CMT cases (1992–2005), the percentage of SIMPLE mutations was 0.6 (6/968).
Galanin receptor expression in cultured human keratinocytes and in normal human skin
Authors: Dallos Attila , Kiss Mária , Polyánka Hilda , Dobozy Attila , Kemény Lajos , Husz Sándor
Published: June 2006

Abstract  Galanin (GAL) is a biologically active neuropeptide that is widely distributed in the nervous system. GAL exerts diverse action via the GAL receptors (GALR1, GALR2, and GALR3), which belong in the superfamily of G‐protein‐coupled transmembrane receptors. In human skin, GAL‐like immunoreactivity has been reported in free nerve endings and fibers of the dermis. The extraneuronal expression of GAL has also been demonstrated. Although the GALRs are essential for biological functions, the expressions of different GALR subtypes in cultured human keratinocytes have not yet been investigated. The aim of our study was to investigate the mRNA and protein expressions of the different GALRs in the HaCaT immortalized keratinocyte cell line and in cultured human keratinocytes. When reverse transcription (RT)‐polymerase chain reaction (PCR) was used with different GALR‐specific primers, only GALR2 mRNA was identified in cultured HaCaT cells and keratinocytes. Sequencing of the PCR products proved the presence of GALR2 mRNA in the keratinocytes. The presence of GALR2 protein was next investigated, using a polyclonal antibody against human GALR2. Both the HaCaT cells and the cultured keratinocytes displayed specific immunohistochemical staining, with higher intensity on the surface of the keratinocytes. Immunohistochemical investigations of normal human skin specimens revealed that GALR2 was expressed with high intensity in the basal layer of the epidermis and also around the hair follicles in the dermis. GAL treatment of the keratinocytes resulted in an increase in cytosolic Ca2+ concentration, suggesting that GALR2 is a functional receptor. Further studies are necessary to clarify the biological effects of GAL in the skin.
Child consent and the law: an insight and discussion into the law relating to consent and competence
Authors: Parekh S. A.
Published: June 2006

Background  The law governing consent for children is not very clear. A child can consent to treatment but usually in practice is unable to refuse it. Even if both the child and parents refuse treatment, courts are reluctant to accept this, particularly if it is in the best interest of the child.

Discussion  In order to consent to treatment, a child must be competent enough to do so, and this competence is judged usually by a doctor. Children can even consent to contraceptives and abortion if ‘competent’ to do so. This concept perfectly lacks moral, ethical and emotional competence, and judgement of competence is carried out usually purely scientifically by pure science‐orientated objective professionals like doctors. A broad discussion about the issues of children refusing treatment is conducted from the legal, ethical and philosophical point of view. Life‐saving treatment and various other cases are also discussed.

Conclusion  There is no right answer to the question. A more holistic approach is needed, and not only doctors but also sociologists, care specialists and even clergymen should be asked to judge competence in a multidisciplinary environment, particularly for contraceptives and abortion. This multidisciplinary working can be extended to other areas in medical law as well particularly in light of changes in medicine. Experience in life should be valued in a decision‐making environment for judging competence. The law in relation to child consent is unclear and requires changes in order to clarify what is perceived as the child’s best interest.
Parental beliefs about the nature of ADHD behaviours and their relationship to referral intentions in preschool children
Authors: Maniadaki K. , Sonuga‐Barke E. , Kakouros E. , Karaba R.
Published: June 2006

Background  Parental beliefs about child problem behaviour have emerged as closely related to referral intentions to mental health services.

Methods  This study compared beliefs of severity, impact and advice seeking for attention deficit/hyperactivity disorder (ADHD) behaviours of parents whose preschool children present ADHD behaviours with those of parents whose children do not display such behaviours. Both parents of 295 preschoolers, aged 4–6 years, enrolled in kindergartens in Athens, filled in: (i) a questionnaire composed by a vignette describing a hypothetical 5‐year‐old child presenting ADHD symptoms followed by rating scales assessing dimensions of severity, impact and referral intention, and (ii) the ‘Strengths and Difficulties Questionnaire’ for screening ADHD behaviours in their own child.

Results  Results showed that almost half of the parents who reported ADHD behaviours in their own child replied that they had never met a child exhibiting such behaviours. These parents also perceived such behaviours as being less severe and with less negative family impact than parents who did not report such behaviours in their own child.

Conclusions  Parents whose preschool child displays ADHD behaviours tend to perceive them as normal developmental patterns and may suspend the referral of the child. Implications of these findings for early identification of ADHD are discussed.
Unmet health, welfare and educational needs of disabled children in an impoverished South African peri‐urban township
Authors: Saloojee G. , Phohole M. , Saloojee H. , IJsselmuiden C.
Published: June 2006

Background  Childhood disability in South Africa has failed to receive adequate attention from governmental agencies, such as the health, education and social welfare departments, despite there being more than 1 million disabled children in the country. This study sought to assess the unmet rehabilitation, education and welfare needs of disabled children living in a peri‐urban township.

Methods  As no register of disabled children existed, snowball sampling was used to recruit a convenience sample of 156 disabled children living in Orange Farm township near Soweto, South Africa. Children’s impairments, their health and educational needs, and the availability and utilization of services were assessed using a structured interview.

Results  Few disabled children attended pre‐school (35%) or school (44%). Only a quarter (26%) of children in need of rehabilitation received such services. Children with motor impairments were more likely to receive rehabilitation than those with intellectual impairment (44% vs. 8%, P < 0.0001). Of the 233 assistive devices required, only 64 (28%) had been issued. Less than half (45%) of the children entitled to a social assistance grant were receiving it. Lack of money, limited awareness about available services, and bureaucratic obstacles were the main reasons offered by caregivers for the low utilization of available services and resources.

Conclusion  Children with disabilities living in Orange Farm are not enjoying the rights and services to which they are entitled. Innovative, co‐ordinated service delivery strategies, and better‐informed caregivers combined with community recognition of, and support for, the needs of disabled children are required to address these unmet needs.
Critical appraisal of rigour in interpretive phenomenological nursing research
Authors: De Witt Lorna , Ploeg Jenny
Published: June 2006

Aim.  This paper reports a critical review of published nursing research for expressions of rigour in interpretive phenomenology, and a new framework of rigour specific to this methodology is proposed.

Background.  The rigour of interpretive phenomenology is an important nursing research methods issue that has direct implications for the legitimacy of nursing science. The use of a generic set of qualitative criteria of rigour for interpretive phenomenological studies is problematic because it is philosophically inconsistent with the methodology and creates obstacles to full expression of rigour in such studies.

Methods.  A critical review was conducted of the published theoretical interpretive phenomenological nursing literature from 1994 to 2004 and the expressions of rigour in this literature identified. We used three sources to inform the derivation of a proposed framework of expressions of rigour for interpretive phenomenology: the phenomenological scholar van Manen, the theoretical interpretive phenomenological nursing literature, and Madison's criteria of rigour for hermeneutic phenomenology.

Findings.  The nursing literature reveals a broad range of criteria for judging the rigour of interpretive phenomenological research. The proposed framework for evaluating rigour in this kind of research contains the following five expressions: balanced integration, openness, concreteness, resonance, and actualization. Balanced integration refers to the intertwining of philosophical concepts in the study methods and findings and a balance between the voices of study participants and the philosophical explanation. Openness is related to a systematic, explicit process of accounting for the multiple decisions made throughout the study process. Concreteness relates to usefulness for practice of study findings. Resonance encompasses the experiential or felt effect of reading study findings upon the reader. Finally, actualization refers to the future realization of the resonance of study findings.

Conclusion.  Adoption of this or similar frameworks of expressions of rigour could help to preserve the integrity and legitimacy of interpretive phenomenological nursing research.
Adopting a personal digital assistant system: application of Lewin's change theory
Authors: Lee Ting‐Ting
Published: June 2006

Aim.  This paper reports a study exploring nurses’ perceptions of adopting an information system using handheld computers (personal digital assistants) in their daily practice.

Background.  Handheld computers have recently been used in nursing information systems for patient care, but few studies have explored their impact on users. By understanding clinicians’ experiences of using this technology, strategies can be implemented to smooth the change process in adopting their use, thus achieving optimal patient outcomes.

Method.  A descriptive, exploratory approach was used to study nurses’ perceptions of using personal digital assistants as part of a hospital information system. A purposive sample of 15 nurses participated in one‐to‐one, in‐depth interviews from February to March 2004. Nurses’ perceptions of the adoption process were analysed using Lewin's force field theory of change as a framework.

Findings.  Nurses initially resisted using the personal digital assistant system (unfreezing stage), then came around to using it (moving stage), and finally adopted the system in their daily practice (re‐freezing stage). However, an anticipatory stage also occurred and this could serve as a feedback mechanism to improve the system for current and future use.

Conclusion.  Educational programmes should be provided and strategic planning should be done in the early stage of implementing a policy to adopt new technology. In addition, the adoption process and learning period could be shortened by improving the system's content design. During this transition stage, dual charting should be used as a backup only for a limited time to avoid adding extra work to nurses’ already heavy workload. Finally, the concept of confidentiality should be reinforced and stressed early in the educational programme to protect patient data, which can easily be accessed in computerized systems.
Using narrative pedagogy: learning and practising interpretive thinking
Authors: Ironside Pamela M.
Published: June 2006

Aim.  This paper reports a hermeneutic study undertaken to explicate students’ experiences in educational courses in which teachers enact Narrative Pedagogy.

Background.  International interest in developing and implementing discipline‐specific pedagogies is becoming commonplace as teachers respond to the challenges of preparing students for contemporary practice. Lifeworld Pedagogy, developed in Scandinavia, and Narrative Pedagogy, developed in the United States of America, Canada and New Zealand, are two approaches developed from nursing research for nursing education that provide teachers with research‐based alternatives to conventional pedagogy. Further research is needed, however, that addresses how new pedagogies are experienced in schools of nursing.

Method.  Teachers and students from 22 schools of nursing in the United States of America were interviewed over a 4‐year period between 2002 and 2005. Using interpretive phenomenology as the philosophical background and Heideggerian hermeneutics as the method, accounts from 52 participants were analysed by a research team.

Findings.  The theme Learning and Practising Interpretive Thinking reveals how reform is occurring in schools of nursing that use Narrative Pedagogy. It documents how Narrative Pedagogy helps students challenge their assumptions and think through and interpret situations they encounter from multiple perspectives. Findings suggest that by focusing teachers’ and students’ attention on thinking and interpreting as communal experiences, interpretive pedagogies such as Narrative Pedagogy engage teachers and students in pooling their wisdom, challenging their preconceptions, envisioning new possibilities for providing care and engaging with others to ensure patient‐centred care and safety.

Conclusion.  By documenting students’ experiences in courses in which Narrative Pedagogy is used, this study provides teachers with research‐based evidence to guide their pedagogical decisions. It extends international efforts to develop discipline‐specific pedagogies and offers a practical, student‐centred approach teachers can use to enhance students’ thinking.
Spirituality at the beginning of life
Authors: Hall Jennifer
Published: June 2006

Aim.  The aim of this paper was to explore the issues surrounding the spirit of the unborn child.

Background.  Pregnancy and birth have been recognised to have a spiritual nature by women and health professionals caring for them. Midwives and nurses are expected to have a holistic approach to care. I suggest that for care to be truly holistic exploration is required of the spiritual nature of the unborn fetus.

Methods.  Historical, philosophical and religious views of the spirit of the fetus, are explored as well as those of women. Investigation was made of views of the timing of ‘ensoulment’.

Results.  The review demonstrates the value women place on the sacredness of pregnancy and birth, and that the spiritual nature of the unborn should be recognised.

Conclusion.  This paper shows that the views and values women have of pregnancy and birth and the powerful, spiritual relationship they have with the unborn, indicates that further discussion and research needs to be carried out in this area.

Relevance to clinical practice.  It is recommended that all who work with women who are pregnant should recognise the spiritual nature of the unborn when carrying out care.
Every person matters: enabling spirituality education for nurses
Authors: Stern Julian , James Sarah
Published: June 2006

Aims and objectives.  This paper aims to identify how the statutory requirements relating to spirituality in nurse education can be supported in preservice and in‐service education, in the context of inter‐professional working implied by every child matters (Department for Education and Skills (DfES) Every Child Matters: Change for Children. DfES, Nottingham DfES 2004a; Every Child Matters: Change for Children in Health Services. Department of Health, London 2004).

Background.  The basis for this paper is an exploration of the current requirements relating to spirituality in nursing and the consequent requirements for training and education clarified in part through a consideration of parallel policies on spirituality in school education. Inter‐professional work, for example, across health, social care and education professions, has a long history in nursing and the changes brought about by the every child matters policy initiative have given such inter‐professional work a considerable boost. That policy change has encouraged consideration, in this article, of some common issues arising in nursing and school education professions.

Method.  This paper consists of a critical review of current and in‐coming statutory requirements related to spirituality, nursing and nurse education, and a synthetic review of definitions of and approaches to meeting spiritual needs.

Conclusion.  The emergent relational framework for considering spirituality in nurse education acknowledges the ambiguity of spirituality and treats that ambiguity as in some ways enabling rather than constraining.

Relevance to clinical practice.  It is not simply that nurse practice will be likely to change with respect to children. Every person will, in the terminology of the policy, ‘matter’: there is significant urgency to consideration of effective education and training provision.
Bystander mouth‐to‐mouth ventilation and regurgitation during cardiopulmonary resuscitation
Authors: VIRKKUNEN I. , KUJALA S. , RYYNÄNEN S. , VUORI A. , PETTILÄ V. , YLI‐HANKALA A. , SILFVAST T.
Published: June 2006

Objectives.  To determine whether there is an association between bystander mouth‐to‐mouth ventilation and regurgitation in prehospital cardiac arrest patients.

Design.  Prospectively conducted observational study.

Setting.  Data were collected from patients treated by the emergency medical service (EMS) systems in three middle‐sized or large Finnish urban communities, the Tampere District EMS and the physician‐staffed Helicopter EMSs in the Helsinki and Turku areas in southern Finland.

Subjects.  The study population consisted of 529 consecutive prehospital cardiac arrest patients with attempted resuscitation. Exclusion criteria were cardiac arrest due to trauma or drug overdose.

Main outcome measures.  Regurgitation in prehospital cardiac arrest patients documented by EMS personnel on the scene.

Results.  Regurgitation occurred in a fourth of patients. Bystander cardiopulmonary resuscitation (CPR) with mouth‐to‐mouth ventilation was associated with a significantly increased risk of regurgitation compared with no CPR (P < 0.013) and CPR without ventilations (P < 0.01).

Conclusions.  The mode and role of bystander CPR in cardiac arrest needs to be further evaluated.
A journey of hope: lessons learned from studies on rare diseases and orphan drugs
Authors: WÄSTFELT M. , FADEEL B. , HENTER J.‐I.
Published: June 2006

Rare diseases are frequently life‐threatening or chronically debilitating and the impact on the quality of life of affected patients and their family members is thus significant. However, drug development for these conditions has been limited by a lack of understanding of the underlying mechanisms of disease and the relative unavailability of subjects for clinical trials, as well as the prohibitive cost of investing in a novel pharmaceutical agent with poor market potential. Nevertheless, the introduction of Orphan Drug legislations has provided important incentives for the development of orphan drugs (i.e. drugs that have been abandoned or ‘orphaned’ by major drug companies). Moreover, recent studies on rare diseases, including inherited immunodeficiencies and metabolic disorders, have served not only to alleviate the plight of patients with rare diseases, but also yielded valuable information on biological processes of relevance for other, more common conditions. These lessons, along with the crucial importance of cooperation between academic institutions, pharmaceutical companies, patient advocacy groups and society in the elucidation of rare diseases, are highlighted in the present review.
Binding of the low‐density lipoprotein by streptococcal collagen‐like protein Scl1 of Streptococcus pyogenes
Authors: Han Runlin , Caswell Clayton C. , Lukomska Ewa , Keene Douglas R. , Pawlowski Marcin , Bujnicki Janusz M. , Kim Jiyeun K. , Lukomski Slawomir
Published: June 2006

Several bacterial genera express proteins that contain collagen‐like regions, which are associated with variable (V) non‐collagenous regions. The streptococcal collagen‐like proteins, Scl1 and Scl2, of group A Streptococcus (GAS) are members of this ‘prokaryotic collagen’ family, and they too contain an amino‐terminal non‐collagenous V region of unknown function. Here, we use recombinant rScl constructs, derived from several Scl1 and Scl2 variants, and affinity chromatography to identify Scl ligands present in human plasma. First, we show that Scl1, but not Scl2, proteins from different GAS serotypes bind the same ligand identified as apolipoprotein B (ApoB100), which is a major component of the low‐density lipoprotein (LDL). Scl1 binding to purified ApoB100 and LDL is specific and concentration‐dependent. Furthermore, the non‐collagenous V region of the Scl1 protein is responsible for LDL/ApoB100 binding because only those rScls, constructed by domain swapping, which contain the V region from Scl1 proteins, were able to bind to ApoB100 and LDL ligands, and this binding was inhibited by antibodies directed against the Scl1‐V region. Electron microscopy images of Scl1–LDL complexes showed that the globular V domain of Scl1 interacted with spherical particles of LDL. Importantly, live M28‐type GAS cells absorbed plasma LDL on the cell surface and this binding depended on the surface expression of the Scl1.28, but not Scl2.28, protein. Phylogenetic analysis showed that the non‐collagenous globular domains of Scl1 and Scl2 evolved independently to form separate lineages, which differ in amino acid sequence, and these differences may account for the variations in binding patterns of Scl1 and Scl2 proteins. Present studies provide insight into the structure‐function relationship of the Scl proteins and also underline the importance of lipoprotein binding by GAS.
Ornithine lipid is required for optimal steady‐state amounts of c‐type cytochromes in Rhodobacter capsulatus
Authors: Aygun‐Sunar Semra , Mandaci Sevnur , Koch Hans‐George , Murray Ian V. J. , Goldfine Howard , Daldal Fevzi
Published: June 2006

The c‐type cytochromes are haemoproteins that are subunits or physiological partners of electron transport chain components, like the cytochrome bc1 complex or the cbb3‐type cytochrome c oxidase. Their haem moieties are covalently attached to the corresponding apocytochromes via a complex post‐translational maturation process. During our studies of cytochrome biogenesis, we uncovered a novel class of mutants that are unable to produce ornithine lipid and that lack several c‐type cytochromes. Molecular analyses of these mutants led us to the ornithine lipid biosynthesis genes of Rhodobacter capsulatus. Herein, we have characterized these mutants, and established the chemical structure of this non‐phosphorus membrane lipid from R. capsulatus. Ornithine lipids are known to induce potent host immune responses, including B‐lymphocyte mitogenicity, adjuvanticity and macrophage activation. Yet, despite their widespread occurrence in Eubacteria, and the diverse biological effects they elicit in mammals, their physiological role in bacterial cells remained hitherto poorly defined. Our findings now indicate that under certain bacterial growth conditions ornithine lipids are crucial for optimal steady‐state amounts of some extracytoplasmic proteins, including several c‐type cytochromes, and attribute them a novel and important biological function.
Unique conjugation mechanism in mycelial streptomycetes: a DNA‐binding ATPase translocates unprocessed plasmid DNA at the hyphal tip
Authors: Reuther Jens , Gekeler Cordula , Tiffert Yvonne , Wohlleben Wolfgang , Muth Günther
Published: June 2006

A single plasmid‐encoded protein, the septal DNA translocator TraB, is sufficient to promote conjugal plasmid transfer in mycelial streptomycetes. To analyse the molecular mechanism of conjugation the closely related TraB proteins from plasmids pSG5 of Streptomyces ghanaensis and pSVH1 of Streptomyces venezuelae were characterized. TraB of pSG5 was expressed as a fusion protein with eGFP and found to be localized at the hyphal tips of Streptomyces lividans by fluorescence microscopy, which strongly indicates that conjugation takes place at the tips of the mating mycelium. The TraB protein of pSVH1 was heterologously expressed in S. lividans with an N‐terminal strep‐tagII and purified as a soluble protein to near homogeneity. The purified protein was shown to hydrolyse ATP and to bind to a 50 bp non‐coding pSVH1 sequence containing a 14 bp direct repeat. The protein–DNA complex was too large to enter an agarose gel, indicating that multimers of TraB were bound to the DNA. Denaturation of the protein–DNA complex released unprocessed plasmid DNA demonstrating that the TraB protein does not possess nicking activity. Our experimental data provide evidence that conjugal DNA transfer in streptomycetes is mediated by the septal DNA translocator TraB, an plasmid‐encoded ATPase that interacts non‐covalently with DNA and translocates an unprocessed double‐stranded DNA molecule at the hyphal tip into the recipient.