bluuebunny/crossref_metadata_2025 huggingface dataset:
Nigeria's Fledgling Friendship with Japan: The Beginning of a 'Special Partnership'?
Authors: Ampiah Kweku
Published: February 2006

Since the inauguration of President Olusegun Obasanjo as President of Nigeria Japan's attitude towards the West African state seems to have been positively transformed. The relationship between the two countries kicked-off with panache after the President's first visit to Tokyo in April 1999 as President elect to renew acquaintances. The two countries are now bound together in a "Special Relationship", which provides them with a coherent framework for regular and constructive consultations. The recent developments replace a period of immobilist diplomacy between Tokyo and Abuja especially during when Nigerian domestic politics was infested with military dictatorships.Tokyo's recent initiatives toward Abuja have to be seen within the context of Japan's invigorated diplomatic initiatives toward sub-Saharan Africa as manifested through the Tokyo International Conference on African Development. The relationship is also premised on Nigeria's hegemonic position within the sub-region of West Africa. As a result, Japan has relatively increased its economic assistance to Nigeria in recent years and is seemingly showing signs of interest in the economic development of Nigeria. On his part, President Obasanjo has pledged his country's determination "to change from the way and manner business was done in Nigeria in the recent past in order to institute a new regime of accountability and transparency in conformity with internationally accepted codes of business ethics".
Aripiprazole in the treatment of acute manic or mixed episodes in patients with bipolar I disorder: a 3-week placebo-controlled study
Authors: Sachs Gary , Sanchez Raymond , Marcus Ronald , Stock Elyse , Mcquade Robert , Carson William , Abou-Gharbia Neveen , Impellizzeri Cheryl , Kaplita Stephen , Rollin Linda , Iwamoto Taro
Published: February 2006

This study compares the efficacy, safety, and tolerability of a partial dopamine agonist, aripiprazole, with placebo in the treatment of patients with bipolar I disorder experiencing an acute manic or mixed episode. In total, 272 hospitalized patients were randomized to aripiprazole 30mg/day or placebo in this 3-week, double-blind, placebo-controlled trial. Dosing could be reduced to 15mg/day for tolerability and, subsequently, increased to 30mg/day based on clinical response. Primary efficacy measure was mean change from baseline to endpoint in Young Mania Rating Scale (YMRS) total score; response was defined as 50% decrease from baseline YMRS score. Aripiprazole-treated patients demonstrated significantly greater improvement from baseline to endpoint in mean YMRS total scores compared with placebo-treated patients as early as Day 4 and sustained through Week 3. A significantly higher response rate was observed in aripiprazole-treated patients (53% vs. 32% at endpoint). Aripiprazole produced significantly greater improvements from baseline on other efficacy assessments compared with placebo, including Clinical Global Impression – Bipolar Version Severity and Improvement scores. The 30mg/day dose was maintained by 85% of aripiprazole-treated patients. Incidence of discontinuations due to adverse events was similar for aripiprazole (8.8%) and placebo (7.5%). Aripiprazole treatment resulted in no significant difference from placebo in change in mean body weight and was not associated with elevated serum prolactin or QTc prolongation. In conclusion, aripiprazole demonstrated superior efficacy to placebo in the treatment of patients with bipolar I disorder presenting with acute manic or mixed episodes, and exhibited a favourable safety and tolerability profile.
The adult psychiatrist's dilemma: psychostimulant use in attention deficit/hyperactivity disorder
Authors: Ashton Heather , Gallagher Peter , Moore Brian
Published: February 2006

Children who have taken psychostimulants long term for attention deficit/hyperactivity disorder (ADHD) are now presenting at adult psychiatry clinics at an age at which bipolar disorder and schizophrenia may first appear and at which pregnancy is a possibility. Doctors who may have little experience in the management of ADHD or use of psychostimulants are faced with decisions on whether to continue or withdraw medication. A literature search conducted to clarify these issues revealed that, although psychostimulants are generally efficacious in ADHD, the risks of withdrawal reactions and of possible long-term effects such as drug addiction, psychosis and depression, or effects in pregnancy, have not been adequately investigated. In particular, there is little information on the effects of withdrawal and no firm guidelines on methods of psychostimulant discontinuation. There is a need for further research to clarify the pharmacological issues involved in the drug treatment of ADHD and for overlapping arrangements between child and adult psychiatry clinics in the management of ADHD.
The influence of the CYP2D6 polymorphism on psychopathological and extrapyramidal symptoms in the patients on long-term antipsychotic treatment
Authors: Plesnicčar Blanka Kores , Zalar Bojan , Breskvar Katja , Dolzžan Vita
Published: February 2006

Poor response to antipsychotics treatment and extrapyramidal side effects (EPS) are the most challenging problems in the treatment of schizophrenia. Several studies were investigating the impact of polymorphic cytochrome P450 2D6 gene ( CYP2D6) on EPS but the results were conflicting. There are practically no clinical studies of long-term treatment of schizophrenia and CYP2D6 polymorphism. Our aim was to evaluate the influence of CYP2D6 genotype on psychopathological symptoms and the occurrence of EPS in Slovenian outpatients with schizophrenia or schizoaffective disorder in stable remission, receiving long-term maintenance antipsychotic treatment.

In total 131 outpatients meeting the DSM IV criteria for schizophrenia or schizoaffective disorder and receiving maintenance therapy with haloperidol, fluphenazine, zuclopethixole or risperidone were genotyped for 14 polymorphic CYP2D6alleles. Psychopathological symptoms were assessed with the Positive and Negative Symptom Scale for Schizophrenia (PANSS). EPS were assessed with the Simpson Angus Scale (SAS), the Barnes Akathisia Scale and the Abnormal Involuntary Movement Scale (AIMS).

Six patients (4.6%) were genotyped as poor metabolizers (PMs). PMs scored significantly higher on the negative subscale for PANSS. There were no statistically significant differences between the group of PMs and the group of patients with at least one functional CYP2D6 allele in view of patient's characteristics or any of the items of the AIMS, the SAS or the Barnes Akathisia Scale.

CYP2D6 genotype may not be the major factor that determines the susceptibility to antipsychotic-induced EPS in Slovenian patients in stable remission and on maintenance therapy with antipsychotics that are mainly CYP2D6 substrates. However, CYP2D6 genotype might be a factor contributing to the persistent negative symptoms of schizophrenia.
Temple and Dynasty: Hezekiah, the Remaking of Judah and the Rise of the Pan-Israelite Ideology
Authors: Finkelstein Israel , Silberman Neil Asher
Published: February 2006

This article deals with the momentous events that took place in Judah in the short period of time between 732 (and mainly 722) and 701 BCE. A torrent of refugees from the North, mostly from the areas bordering on Judah, dramatically changed the demographic structure in the Southern Kingdom. The population seems to have at least doubled and included significant north Israelite communities. This situation created, in fact, a pan-Israelite state. Hezekiah reacted to this challenge in two ways, both aimed at strengthening the authority of the central government. Countryside shrines were abolished and the cult was centralized in the Jerusalem Temple, probably in an attempt to prevent the new immigrants from visiting the Bethel temple in their old homeland. In the same short period of time, the story of the early days of the Davidide dynasty was first put in writing, combining southern and northern traditions in a single national narrative.
Hebrew Syntactic Inversions and their Literary Equivalence in English: Robert Alter’s Translations of Genesis and 1 and 2 Samuel
Authors: De Regt Lénart J.
Published: February 2006

This article focuses on syntactic inversions in the Hebrew of Genesis and 1 and 2 Samuel. These can be explained in terms of contrastive focus or topical referents (before the verb), and most salient information represented by the verb (when the verb occurs at the end of the sentence). Second, it analyses the extent to which Robert Alter has expressed the functions of these syntactic inversions in literary language (literary language being his translational norm). This study concludes that when the preverbal element is not under contrastive focus but represents a topical referent, this information is not newer than what is mentioned in the rest of the sentence and there are no alternatives in the context to rule out. It allows the most prominent information to come at the end of the sentence. So, when it is a topical referent (or spatial/temporal basis) that has been put in first position in the Hebrew, maintaining such syntactic inversions in an English translation wrongly suggests focus on the fronted element. The translator should render the respective ways of expressing contrastive focus and of referring to a topical referent in Hebrew into forms of the receptor language which closely correspond in function and literary effect.
‘Let my Soul Die with the Philistines’ (Judges 16.30)
Authors: Galpaz-Feller Pnina
Published: February 2006

Samson stands between the columns of the Temple of Dagon. Samson addresses God and asks for help. Samson grips the pillars of temple powerfully, then he pulls down the temple on himself and on all the Philistines, and the narrator adds proudly: ‘So the dead which he slew at his death were more than they which he slew in his life’ (Judg. 16:30). Samson’s death is accompanied by a heroic act. Samson is not the only biblical hero who is led to choose death. When one compares the deeds of Abimelech, Ahitophel, Zimri and Saul who took their own lives, and their last moments, one finds that Samson’s death is unique.
Bursting at the Seams: Phonetic Rhetoric in the Speeches of Elihu
Authors: Lynch Matthew J.
Published: February 2006

This study explores the abundant ‘phonetic rhetoric’—or, language that depicts the expression and reception of words about words—in the Elihu Speeches (Job 32-37). This phonetic rhetoric frames nearly all of Elihu’s speech, and constitutes approximately one quarter of his language. An analysis of this rhetorical feature contributes to the ongoing debates about the place of Elihu in the book of Job, and to the interpretation of his character. It suggests that the Elihu Speeches climax the painful ordeal of Job following the rounds of dialogue with his companions. Furthermore, Elihu’s phonetic rhetoric depicts his character as oblivious to his own verbosity and the impact of his words vis-àvis Job’s desire to hear from God.
‘God Will Redeem My Soul from Sheol’: The Psalms of the Sons of Korah
Authors: Mitchell David C.
Published: February 2006

After defining the Korah collection, this study shows that biblical tradition about the Korahites is marked by the theme of redemption from Sheol. This theme is discussed, particularly in regard to the resurrection of the dead. Then an examination of the Korah Psalms shows that the theme appears there also. Moreover, some of these psalms seem to feature the related idea of the righteous being caught up in the air when the earth opens. These ideas occur in later literature with proof-texts from the Korah Psalms, which would appear to be their source. Correspondences are drawn between these traits of the Korah Psalms and the author’s proposed eschatological programme in the Psalter.
Effect of Loading and Surface Modification of MWCNTs on the Fracture Behavior of Epoxy Nanocomposites
Authors: Ganguli S. , Aglan H. , Dennig P. , Irvin G.
Published: February 2006

Nanocomposites consisting of multiwalled carbon nanotubes (MWCNTs) and a bifunctional epoxy resin are manufactured by a unique dispersion technique. The effect of loading and surface modification of the MWCNTs on the mechanical properties and fracture behavior of the nanocomposites is studied. Both a scanning electron microscope (SEM) and an atomic force microscope (AFM) are used to identify the mechanisms by which the nanocomposites acquired their fracture resistance. At 0.1 wt% loading, both ball-milled and acid-treated MWCNT composites perform better than the neat resin. An increase of 40% in the fracture toughness has been achieved at 0.15 wt% loading with ball-milled MWCNTs. An increase of 80% in the fracture toughness has been achieved at 0.15 wt% loading in the acid-treated MWCNT nanocomposites. The AFM images of the MWCNT nanocomposites reveal that the MWCNTs are well dispersed in both the systems. A better dispersion of MWCNTs has been achieved with acid treatment than with ball milling. The SEM images of the fractured surfaces reveal a tremendous increase in the number of fracture surface features associated with the acid-treated MWCNT nanocomposites, in comparison with the ball-milled MWCNT nanocomposites and the neat resin.
Synthesis and Characterization of Salicylic Acid-Based Poly(Anhydride-Ester) Copolymers
Authors: Schmeltzer Robert C. , Uhrich Kathryn E.
Published: February 2006

A series of poly(anhydride-esters) based on poly(1,10-bis( o-carboxyphenoxy)decanoate) (CPD) and poly(1,6-bis( p-carboxyphenoxy)hexane) ( p-CPH) were synthesized by melt-condensation polymerization. Poly-(anhydride-esters) that contain CPD hydrolytically degraded into salicylic acid, however, these homopolymers have mechanical and thermal characteristics that limit their use in clinical applications. The synthesis and characterization of copolymers of CPD with p-CPH, a monomer known to generate mechanically stable homopolymers, was investigated. By changing the CPD to p-CPH monomer ratios, the salicylic acid loading and thermal/mechanical properties of the copolymers was a controlling factor; increasing the CPD concentration increased the salicylate loading but decreased the polymer stability; whereas increasing the p-CPH concentration increased the thermal and mechanical stability of the copolymers. Specifically, decreasing the CPD: p-CPH ratio resulted in lower salicylate loading and increased thermal decomposition temperatures. The glass transition temperatures (°C) varied from 27 to 38°C, a desirable range for elastomeric biomedical implants.
An Oral Delivery System for Insulin
Authors: Mahkam M. , Allahverdipoor M. , Mohammadi R. , Ranaei-Siadat S. O. , Rashidi M. R. , Davaran S. , Barshan M. , Ranaei-Siadat S. E.
Published: February 2006

Crosslinked 2-hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA) copolymer hydrogels were studied as drug delivery systems. Terephthalic acid was covalently linked with 2-hydroxyethyl methacrylate (HEMA), abbreviated as cross-linking agent (CA). Free radical copolymerization of HEMA and MAA with terephthetalic acid (CA) (2, 4, and 6%) as crosslinking agent were carried out at 70°C. The structure of the CA was confirmed by FT-IR, 1H-NMR and 13C-NMR spectroscopy. The composition of the crosslinked three-dimensional polymers were determined by FTIR spectroscopy. Glass transition temperature (Tg) of the network polymers was determined calorimetrically. The effect of copolymer composition on the swelling behavior and hydrolytic degradation was studied in simulated gastric fluid (SGF, pH 1) and simulated intestinal fluid (SIF, pH 7.4). The swelling and hydrolytic behavior of the copolymers depended on the content of MAA which caused a decrease in gel swelling in SGF or an increase in gel swelling in SIF. It was observed that in acidic media hydrogen bonds formed due to the protonation of the carboxylic acid groups of the MAA while in more basic or neutral conditions electrostatic repulsion occurred between the ionized carboxylic acid groups. This complex behavior affected the macroscopic swelling properties of the resultant hydrogels. The amount of drug release depended on the degree of hydrogel swelling and crosslinking.
Economic Crisis and the Construction of a Neo-Liberal Regulatory Regime in Korea
Authors: Pirie Iain
Published: February 2006

A consistent theme of the literature on the ontology of the 1997 South Korean crisis is the key role played by regulatory failures and the growing weakness of the state. This paper seeks to briefly highlight both the insights and the limitations of this approach to understanding the crisis. Having done so, we shall set out the argument that the crisis created an opportunity for reformist Korean élites to advance their longstanding, but previously frustrated, project to create a comprehensive unambiguously neo-liberal regulatory regime. This paper will also seek to highlight the implications of our reading of the development of the Korean political economy for broader debates on economic liberalisation, crisis and the future of the developmental state.
Long-term results and competing risk analysis of the H89 trial in patients with advanced-stage Hodgkin lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte (GELA)
Authors: Fermé Christophe , Mounier Nicolas , Casasnovas Olivier , Brice Pauline , Divine Marine , Sonet Anne , Bouafia Fahdela , Bastard-Stamatoullas Aspasia , Bordessoule Dominique , Voillat Laurent , Reman Oumedaly , Blanc Michel , Gisselbrecht Christian ,   for the Groupe d'Etude des Lymphomes de l'Adulte
Published: February 2006

From 1989 to 1996, 533 eligible patients with stage IIIB/IV Hodgkin lymphoma (HL) were randomly assigned to receive 6 cycles of hybrid MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone/Adriamycin [doxorubicin], bleomycin, vinblastine; n = 266) or ABVPP (doxorubicin, bleomycin, vinblastine, procarbazine, prednisone; n = 267). Patients in complete remission (CR) or partial response of at least 75% after 6 cycles received 2 cycles of consolidation chemotherapy (CT) (n = 208) or subtotal nodal irradiation (RT) (n = 210). A better survival probability was observed after ABVPP alone: the 10-year overall survival (OS) estimates were 90% for ABVPP×8, 78% for MOPP/ABV×8, 82% for MOPP/ABV with RT, and 77% for ABVPP×6 with RT (P = .03); and the 10-year disease-free survival (DFS) estimates were 70%, 76%, 79%, and 76%, respectively (P = .09). The 10-year DFS estimates for patients treated with consolidation CT or RT were 73% and 78% (P = .07), and OS estimates were 84% and 79%, respectively (P = .29). These results showed that RT was not superior to consolidation CT after a doxorubicin-induced CR in patients with advanced HL. An analysis of competing risks identified age more than 45 years as a significant risk factor for death, relapse, and second cancers. Prospective evaluation of late adverse events may improve the management of patients with HL.
Expression of Jak2V617F causes a polycythemia vera–like disease with associated myelofibrosis in a murine bone marrow transplant model
Authors: Wernig Gerlinde , Mercher Thomas , Okabe Rachel , Levine Ross L. , Lee Benjamin H. , Gilliland D. Gary
Published: February 2006

An acquired somatic mutation, Jak2V617F, was recently discovered in most patients with polycythemia vera (PV), chronic idiopathic myelofibrosis (CIMF), and essential thrombocythemia (ET). To investigate the role of this mutation in vivo, we transplanted bone marrow (BM) transduced with a retrovirus expressing either Jak2 wild-type (wt) or Jak2V617F into lethally irradiated syngeneic recipient mice. Expression of Jak2V617F, but not Jak2wt, resulted in clinicopathologic features that closely resembled PV in humans. These included striking elevation in hemoglobin level/hematocrit, leukocytosis, megakaryocyte hyperplasia, extramedullary hematopoiesis resulting in splenomegaly, and reticulin fibrosis in the bone marrow. Histopathologic and flow cytometric analyses showed an increase in maturing myeloid lineage progenitors, although megakaryocytes showed decreased polyploidization and staining for acetylcholinesterase. In vitro analysis of primary cells showed constitutive activation of Stat5 and cytokine-independent growth of erythroid colony-forming unit (CFU-E) and erythropoietin hypersensitivity, and Southern blot analysis for retroviral integration indicated that the disease was oligoclonal. Furthermore, we observed strain-specific differences in phenotype, with Balb/c mice demonstrating markedly elevated leukocyte counts, splenomegaly, and reticulin fibrosis compared with C57Bl/6 mice. We conclude that Jak2V617F expression in bone marrow progenitors results in a PV-like syndrome with myelofibrosis and that there are strain-specific modifiers that may in part explain phenotypic pleiotropy of Jak2V617F-associated myeloproliferative disease in humans.
Conditional up-regulation of IL-2 production by p38 MAPK inactivation is mediated by increased Erk1/2 activity
Authors: Kogkopoulou Olga , Tzakos Evaggelos , Mavrothalassitis George , Baldari Cosima T , Paliogianni Fotini , Young Howard A , Thyphronitis George
Published: February 2006

The p38 mitogen-activated protein kinase regulates many cellular processes in almost all eukaryotic cell types. In T cells, p38 was shown to regulate thymic development and cytokine production. Here, the role of p38 on interleukin-2 (IL-2) production by human peripheral blood CD4+ T cells was examined. When T cells were stimulated under weak stimulation conditions, pharmaceutical and molecular p38 inhibitors induced a dramatic increase of IL-2 production. In contrast, IL-2 levels were not affected significantly when strong stimulation was provided to T cells. The increase in IL-2 production, following p38 inhibition, was associated with a strong up-regulation of extracellular signal-regulated kinase (Erk)1/2 activity. Furthermore the Erk inhibitor U0126 was able to counteract the effect of p38 inhibition on IL-2 production, supporting the conclusion that p38 mediates its effect through Erk. These results suggest that the p38 kinase, through its ability to control Erk activation levels, acts as a gatekeeper, which prevents inappropriate IL-2 production. Also, the finding that p38 acts in a strength-of-stimulation-dependent way provides an explanation for previously reported, contradictory results regarding the role of this kinase in IL-2 expression.
The long pentraxin PTX3 as a link among innate immunity, inflammation, and female fertility
Authors: Bottazzi Barbara , Bastone Antonio , Doni Andrea , Garlanda Cecilia , Valentino Sonia , Deban Livija , Maina Virginia , Cotena Alessia , Moalli Federica , Vago Luca , Salustri Antonietta , Romani Luigina , Mantovani Alberto
Published: February 2006

The long pentraxin 3 (PTX3) is member of a complex superfamily of multifunctional proteins characterized by a cyclic multimeric structure. PTX3 is highly conserved in evolution and is produced by innate-immunity cells in response to proinflammatory signals and Toll-like receptor engagement. PTX3 plays complex, nonredundant functions in vivo, acting as a predecessor of antibodies, recognizing microbes, activating complement, facilitating pathogen recognition by phagocytes, and hence, playing a nonredundant role in resistance against selected pathogens. In addition, PTX3 is essential in female fertility by acting as a nodal point for the assembly of the cumulus oophorus hyaluronan-rich extracellular matrix. Thus, the prototypic long pentraxin PTX3 is a multifunctional, soluble pattern recognition receptor acting as a nonredundant component of the humoral arm of innate immunity and involved in matrix deposition and female fertility.
Religion, place and space: a framework for investigating historical geographies of religious identities and communities
Authors: Brace Catherine , Bailey Adrian R. , Harvey David C.
Published: February 2006

Despite a well-established interest in the relationship between space and identity, geographers still know little about how communal identities in specific places are built around a sense of religious belonging. This paper explores both the theoretical and practical terrain around which such an investigation can proceed. The paper makes space for the exploration of a specific set of religious groups and practices, which reflected the activities of Methodists in Cornwall during the period 1830-1930. The paper is concerned to move analysis beyond the `officially sacred' and to explore the everyday, informal, and often banal, practices of Methodists, thereby providing a blueprint for how work in the geography of religion may move forward.
Demands for Religious Care in the Taiwanese Health System
Authors: Tzeng Huey-Ming , Yin Chang-Yi
Published: February 2006

In order to care ethically nurses need to care holistically; holistic care includes religious/spiritual care. This research attempted to answer the question: Do nurses have the resources to offer religious care? This article discusses only one aspect - the provision of religious care within the Taiwanese health care system. It is assumed that, if hospitals do not provide enough religious services, nurses working in these hospitals cannot be fully ethical beings or cannot respect patients’ religious needs. The relevant literature was reviewed, followed by a survey study on the provision of religious facilities and services. Aspects considered are: the religions influences in and on Taiwanese society; the religious needs of patients and their families; strategies that patients use to enable them to cope with their health care problems; professional motives for attuning to patients’ religious needs; and hospital provision for meeting the religious and spiritual needs of patients. A survey of nursing executives showed differences between religious service provision in hospitals with and without a hospice ward. The practical implications for hospital management and nursing practice are discussed.
Developing the Concept of Moral Sensitivity in Health Care Practice
Authors: Lützén Kim , Dahlqvist Vera , Eriksson Sture , Norberg Astrid
Published: February 2006

The aim of this Swedish study was to develop the concept of moral sensitivity in health care practice. This process began with an overview of relevant theories and perspectives on ethics with a focus on moral sensitivity and related concepts, in order to generate a theoretical framework. The second step was to construct a questionnaire based on this framework by generating a list of items from the theoretical framework. Nine items were finally selected as most appropriate and consistent with the research team’s understanding of the concept of moral sensitivity. The items were worded as assumptions related to patient care. The questionnaire was distributed to two groups of health care personnel on two separate occasions and a total of 278 completed questionnaires were returned. A factor analysis identified three factors: sense of moral burden, moral strength and moral responsibility. These seem to be conceptually interrelated yet indicate that moral sensitivity may involve more dimensions than simply a cognitive capacity, particularly, feelings, sentiments, moral knowledge and skills.
Views on Dignity of Elderly Nursing Home Residents
Authors: Franklin Lise-Lotte , Ternestedt Britt-Marie , Nordenfelt Lennart
Published: February 2006

Discussion about a dignified death has almost exclusively been applied to palliative care and people dying of cancer. As populations are getting older in the western world and living with chronic illnesses affecting their everyday lives, it is relevant to broaden the definition of palliative care to include other groups of people. The aim of the study was to explore the views on dignity at the end of life of 12 elderly people living in two nursing homes in Sweden. A hermeneutic approach was used to interpret the material, which was gathered during semi-structured interviews. A total of 39 interviews were transcribed. The analysis revealed three themes: (1) the unrecognizable body; (2) fragility and dependency; and (3) inner strength and a sense of coherence.
Nurses’ and Physicians’ Opinions on Aggressiveness of Treatment for General Ward Patients
Authors: Svantesson Mia , Sjökvist Peter , Thorsén Håkan , Ahlström Gerd
Published: February 2006

The aim of this study was to evaluate agreement between nurses’ and physicians’ opinions regarding aggressiveness of treatment and to investigate and compare the rationales on which their opinions were based. Structured interviews regarding 714 patients were performed on seven general wards of a university hospital. The data gathered were then subjected to qualitative and quantitative analyses. There was 86% agreement between nurses’ and physicians’ opinions regarding full or limited treatment when the answers given as ‘uncertain’ were excluded. Agreement was less (77%) for patients with a life expectancy of less than one year. Disagreements were not associated with professional status because the physicians considered limiting life-sustaining treatment as often as the nurses. A broad spectrum of rationales was given but the results focus mostly on those for full treatment. The nurses and the physicians had similar bases for their opinions. For the majority of the patients, medical rationales were used, but age and quality of life were also expressed as important determinants. When considering full treatment, nurses used quality-of-life rationales for significantly more patients than the physicians. Respect for patients’ wishes had a minor influence.
Naming of Rickettsiae and Rickettsial Diseases
Authors: RAOULT DIDIER , FOURNIER PIERRE‐EDOUARD , EREMEEVA MARINA , GRAVES STEPHEN , KELLY PATRICK J. , OTEO JOSÉ A. , SEKEYOVA ZUZANA , TAMURA AKIRA , TARASEVICH IRINA , ZHANG LIJUAN
Published: February 2006

Abstract: Over the last 20 years, advances in molecular techniques have greatly facilitated the identification of the members of the Rickettsiales, and numerous new species and diseases have been described. In this paper, we review taxonomic rules and appropriate approaches to valid naming of rickettsial species and the diseases they cause.
Progress in Rickettsial Genome Analysis from Pioneering of Rickettsia prowazekii to the Recent Rickettsia typhi
Authors: WALKER DAVID H. , YU XUE‐JIE
Published: February 2006

Abstract: Three rickettsial genomes have been sequenced and annotated. Rickettsia prowazekii and R. typhi have similar gene order and content. The few differences between R. prowazekii and R. typhi include a 12‐kb insertion in R. prowazekii, a large inversion close to the origin of replication in R. typhi, and loss of the complete cytochrome c oxidase system by R. typhi. R. prowazekii, R. typhi, and R. conorii have 13, 24, and 560 unique genes, respectively, and share 775 genes, most likely their essential genes. The small genomes contain many pseudogenes and much noncoding DNA, reflecting the process of genome decay. R. typhi contains the largest number of pseudogenes (41), and R. conorii the fewest, in accordance with its larger number of genes and smaller proportion of noncoding DNA. Conversely, typhus rickettsiae contain fewer repetitive sequences. These genomes portray the key themes of rickettsial intracellular survival: lack of enzymes for sugar metabolism, lipid biosynthesis, nucleotide synthesis, and amino acid metabolism, suggesting that rickettsiae depend on the host for nutrition and building blocks; enzymes for the complete TCA cycle and several copies of ATP/ADP translocase genes, suggesting independent synthesis of ATP and acquisition of host ATP; and type IV secretion system. All rickettsiae share two outer membrane proteins (OmpB and Sca 4) and LPS biosynthesis machinery. RickA, unique to spotted fever rickettsiae, plays a role in induction of actin polymerization in R. conorii, but not in R. prowazekii or R. typhi. The genome of R. typhi contains four potentially membranolytic genes (tlyA, tlyC, pldA, and pat‐1) and five autotransporter genes, sca 1, sca 2, sca 3, ompA, and ompB. The presence of six 50‐amino acid repeat units in Sca 2 suggests function as an adhesin. The high laboratory passage of the sequenced strains raises the issue of the occurrence of laboratory mutations in genes not required for growth in cell culture or eggs. Resequencing revealed that eight annotated pseudogenes of E strain are actually intact genes. Comparative genomics of virulent and avirulent strains of rickettsial species may reveal their virulence factors.
Dissecting theRickettsia prowazekiiGenome: Genetic and Proteomic Approaches
Authors: TUCKER AIMEE M. , PANNELL LEWIS K. , WOOD DAVID O.
Published: February 2006

Abstract:The obligate nature ofRickettsia prowazekiiintracellular growth places severe restrictions on the analysis of rickettsial gene function and gene expression. Fortunately, this situation is improving as methods for the genetic manipulation and proteomic analysis of this fascinating human pathogen become available. In this paper, we review the current status of rickettsial genetics and the isolation of rickettsial mutants using a genetic approach. In addition, the examination of rickettsial gene expression through characterization of the rickettsial proteome will be described. This will include a description of a high‐throughput, accurate mass approach that has identified 596 rickettsial proteins in a complex rickettsial protein sample.
Preliminary Transcriptional Analysis of spoT Gene Family and of Membrane Proteins in Rickettsia conorii and Rickettsia felis
Authors: ROVERY C , LA M V , ROBINEAU S , MATSUMOTO K , RENESTO P , RAOULT D
Published: February 2006

Abstract: Rickettsiae survival implicates adaptation to different environmental conditions. We hypothesized that multiple copies of genes in bacteria with reduced genomes might account for such a process. Transcription of spoT and sca paralogs was thus analyzed in R. conorii and R. felis.
Proteomic Analysis of Rickettsia prowazekii
Authors: CHAO C C , CHELIUS D , ZHANG T , MUTUMANJE E , CHING W M
Published: February 2006

Abstract: Rickettsia prowazekii is an obligate intracellular gram‐negative bacterium. Comparative proteomics study of a virulent strain (Breinl) versus an avirulent strain (Madrid E) was performed using an integrated liquid chromatography and mass spectrometer. About 30% of predicted proteins were detected and identified. Among the detected proteins, more than 30 proteins were of unknown function in both strains. Although several proteins were detected in only one strain, the overall distribution of detected proteins in different COGs (clusters of orthologs groups) was very similar between the two strains. Functional analysis of differentially expressed proteins, either qualitatively or quantitatively, may lead to the discovery of pathogenesis‐related factors.
Molecular Characterization of a Group of Proteins Containing Ankyrin Repeats in Orientia tsutsugamushi
Authors: CHO NAM‐HYUK , KIM JO‐MIN , KWON EUN‐KYUNG , KIM SE‐YOON , HAN SEUNG‐HOON , CHU HYUK , LEE JUNG‐HEE , CHOI MYUNG‐SIK , KIM IK‐SANG
Published: February 2006

Abstract: Orientia tsutsugamushi, an obligate intracellular bacterium, is the causative agent of scrub typhus. The sequencing and analysis of full genomic DNA of O. tsutsugamushi has revealed at least 19 genes thus far encoding proteins with different numbers of ankyrin repeat domains. We have cloned several genes containing ankyrin repeats from the genome and produced fusion proteins to characterize their functions in host cells. It is likely that the proteins with ankyrin repeat domains expressed in O. tsutsugamushi‐infected cells may control the synthesis or stability of host proteins to modulate the various cellular functions after infection. The exploitation of host factors by ankyrin repeat proteins of O. tsutsugamushi may also play a critical role in its pathogenesis.
Ehrlichia ruminantium: A Promiscuous Genome
Authors: ALLSOPP MARIA , STEYN HELENA , ZWEYGARTH ERICH , ALLSOPP BASIL
Published: February 2006

Abstract: The intracellular bacterium, Ehrlichia ruminantium, is the causative agent of heartwater, a tick‐borne disease of livestock. Because vaccines need to incorporate components from several virulent isolates, it is essential to have information on the extent of genetic variation among isolates. We therefore amplified and sequenced a panel of seven core function genes.
Coxiella burnetiiInfection
Authors: KAZAR JAN
Published: February 2006

Abstract:Coxiella burnetiiis an obligate intracellular bacterium that causes a worldwide zoonosis, Q fever, and can be misused as a biological warfare agent. Infection in animals (coxiellosis) is mostly persistent. Infection in humans is often asymptomatic, but it can manifest as an acute disease (usually a self‐limited flu‐like illness, pneumonia, or hepatitis) or as a chronic form (mainly endocarditis, but also hepatitis and chronic fatigue syndrome).C. burnetiiinfection in pregnant women may result in abortions, premature deliveries, and stillbirths. Infection in nature is maintained and transmitted by ticks as the principal vector and reservoir. Cattle, sheep, and goats are the most important source of human infections. Humans contractC. burnetiiinfection mostly by aerosol in contact with contaminated environs, wind playing an important factor in spreading the infection. The wide distribution ofC. burnetiicontributes to a high resistance of its extracellular small cell variant to environmental conditions. Its intracellular large cell variant, adapted to survive under harsh conditions of phagolysosomes, enables long‐term survival and persistence ofC. burnetii, namely in monocytes/macrophages. Host factors such as underlying disease and cell‐mediated immunity play a decisive role in the clinical expression ofC. burnetiiinfection. Complete genome analysis ofC. burnetiiwill certainly contribute to better understanding of the pathogenesis ofC. burnetiiinfection and will improve Q fever diagnosis and immunoprophylaxis.
Coxiella burnetiiWhole Cell Lysate Protein Identification by Mass Spectrometry and Tandem Mass Spectrometry
Authors: SKULTETY LUDOVIT , HERNYCHOVA LENKA , TOMAN RUDOLF , HUBALEK MARTIN , SLABA KATARINA , ZECHOVSKA JANA , STOFANIKOVA VERONIKA , LENCO JURAJ , STULIK JIRI , MACELA ALES
Published: February 2006

Abstract:The whole cell lysate ofCoxiella burnetiistrain RSA 493 was separated by two‐dimensional electrophoresis and more than 500 protein spots were found on silver‐stained reference map. Spots from the gels were subjected to identification based on peptide mass fingerprinting (PMF). In order to identify additional proteins, tandem mass spectrometry (MS/MS) using electrospray and matrix‐assisted laser desorption/ionization techniques was applied. The three independent approaches resulted in the identification of 197 open reading frames (ORFs). Fifty‐two proteins were identified by PMF and at least with one of the MS/MS methods, 37 proteins with both MS/MS instruments, and 19 proteins with all three techniques applied. All predictedC. burnetiiORFs were compared with the Clusters of Orthologous Groups database. The data related to identified proteins were stored and indexed in a file that can be read and searched using Microsoft Access.
Replication of Coxiella burnetii Is Inhibited in CHO K‐1 Cells Treated with Inhibitors of Cholesterol Metabolism
Authors: HOWE DALE , HEINZEN ROBERT A.
Published: February 2006

Abstract: Coxiella burnetii directs the synthesis of a large parasitophorous vacuole (PV) that is required for its replication. While some lysosomal characteristics of the PV have been described, the origin and composition of the PV membrane remain largely undefined. Cholesterol is an essential component of mammalian membranes where it lends mechanical stability and serves as a platform for signaling proteins. Using infected Chinese hamster ovary cells as a model, we examined whether cholesterol is trafficked to the C. burnetii PV membrane and the effects of inhibitors of cholesterol metabolism on C. burnetii replication. When infected cells were stained with filipin, a fluorescent polyene antifungal agent that binds cholesterol, obvious staining of PV was observed indicating the PV membrane is cholesterol‐rich. Furthermore, replication of C. burnetii was significantly inhibited in cells treated with the cholesterol metabolism inhibitors lovastatin, ketoconazole, imipramine, progesterone, and U18666A. These data suggest that cholesterol is an important component of the C. burnetii PV membrane and that normal cellular cholesterol metabolism is required for optimal C. burnetii replication.
Balb/c Mouse Model and Real‐Time Quantitative Polymerase Chain Reaction for Evaluation of the Immunoprotectivity against Q Fever
Authors: ZHANG JINGBO , WEN BOHAI , CHEN MEILING , ZHANG JUN , NIU DONGSHENG
Published: February 2006

Abstract: The Balb/c mice were infected with Coxiella burnetii and samples of blood and major organs from the infected mice were collected on days 1 to 14 after infection. The DNAs extracted from the samples were detected by a developed real‐time quantitative PCR specific for C. burnetii and high loads of C. burnetii were found in spleens, livers, and lungs, particularly in spleens. The Balb/c mice were immunized with whole cell antigen (WCA) of C. burnetii and coxiella loads in spleens of mice were assessed by the real‐time quantitative PCR on day 7 after challenge with C. burnetii. The analysis suggested that phase I whole cells were excellent immunogen that elicited complete protection against coxiella infection by two‐booster but not one‐booster immunization. The results suggest that the combination of Balb/c model and the real‐time quantitative PCR assay is a reliable and sensitive way to evaluate the efficiency of vaccines against Q fever.
Similarities and Differences in Host Cell Signaling following Infection with Different Rickettsia Species
Authors: RYDKINA ELENA , SILVERMAN DAVID J. , SAHNI SANJEEV K.
Published: February 2006

Abstract: Signaling interactions between vascular endothelium and invading rickettsiae provide a unique way of coordinating appropriate physiologic responses, which are important determinants of the ensuing pathogenesis mechanisms such as host defense and inflammation. Two major subgroups of pathogenic Rickettsia species, namely the typhus group (TG) and the spotted fever group (SFG), exhibit marked differences in their intracytoplasmic behavior. Using in vitro infection of cultured human endothelial cells with R. rickettsii, the causative agent of Rocky Mountain SF, we previously identified activation of NF‐κB and p38 MAP kinase as essential components of intracellular signaling events responsible for Rickettsia‐induced transcriptional activation. Our data also suggest that p38 activity does not contribute to NF‐κB response, implicating involvement of independent upstream signaling pathways. Since divergent cytopathologies suggest potentially different interactions with host cells, the aim of this study was to compare these responses after endothelial cell infection with R. conorii, the agent of Mediterranean SF, and a TG representative R. typhi, the agent of endemic typhus.
Genome Comparison Analysis of Molecular Mechanisms of Resistance to Antibiotics in the Rickettsia Genus
Authors: ROLAIN J M , RAOULT D
Published: February 2006

Abstract: In this study we describe molecular mechanisms of resistance to several classes of antibiotics within drug targets by in silico genome comparisons for bacteria of the genus Rickettsia. Apart from the mutations in the rpoB gene in naturally rifampin‐resistant Rickettsia species previously reported by our team, we found that typhus group (TG) rickettsiae had a triple amino acid difference in the highly conserved region of the L22 ribosomal protein as compared to the spotted fever group rickettsiae (SFG), which could explain the natural resistance of SFG rickettsia to erythromycin. We found also that the genome of R. conorii contains an aminoglycoside 3′‐phosphotransferase. Finally, either folA gene (encoding dihydrofolate reductase) and/or folP gene (encoding dihydropteroate synthase) was missing in the genome of rickettsial strains explaining the natural resistance to cotrimoxazole. Finally, multiple genes encoding for pump efflux were found especially in the genome of R. conorii that could be involved in resistance to antibiotics. Five specific ORFs related to antibiotic resistance have been identified in the genome of R. felis including a streptomycin resistance protein homologue, a class C beta‐lactamase, a class D beta‐lactamase, a penicillin acylase homologue, and an ABC‐type multidrug transporter system. For the first time, using this approach, an experimental beta‐lactamase activity has been shown for this bacterium. We believe that whole genome sequence analysis may help to predict several phenotypic characters, in particular resistance to antibiotics for obligate intracellular bacteria.
Nitric Oxide as a Mediator of Increased Microvascular Permeability during Acute Rickettsioses
Authors: WOODS MICHAEL E. , WEN GARY , OLANO JUAN P.
Published: February 2006

Abstract: Rickettsiae primarily infect the microvascular endothelium, leading to changes in microvascular permeability that result in potentially severe pulmonary and cerebral edema. The mechanisms responsible for these changes are not well understood. One potential mechanism of increased vascular permeability is the anti‐rickettsial nitric oxide response described by Walker and colleagues. We hypothesized that anti‐rickettsial levels of nitric oxide adversely affects microvascular permeability in vitro. To this end we sought to describe the effects of exogenous nitric oxide on the proliferation of intracellular rickettsiae while monitoring the transendothelial electrical resistance as a measure of endothelial barrier integrity. It was determined that the addition of the NO‐donor DETA NONOate at certain levels results in a dose‐dependent change in electrical resistance across the monolayer while effectively limiting the number of intracellular rickettsiae in human microvascular endothelial cells. The data presented support the idea that nitric oxide produced by infected endothelial cells may be contributing to the changes in vascular permeability that occur during acute rickettsioses. Future experiments aim to elaborate on these results in a model that more clearly depicts the in vivo response as well as to describe the changes that occur with respect to interendothelial junctions.
Cloning and Expression of 51‐kDa Antigenic Protein of Neorickettsia risticii NR‐JA1
Authors: PARK MYEONG‐KYU , KIM EUN‐HA , CHO MAE‐RIM , YI YING‐HUA , LEE MI‐JIN , SHAH DEVENDRA H. , PARK JIN‐HO , PARK BAE‐KEUN , EO SEONG‐KUG , LEE JOHN‐HWA , CHAE JOON‐SEOK
Published: February 2006

Abstract: Neorickettsia (Ehrlichia) risticii is a causative agent of acute diarrheal syndrome in horses, commonly known as Potomac horse fever. Korean isolate of N. risticii NR‐JA1 was cultivated in mouse macrophage cell line P388D1. A complete ORF of p51 antigenic protein gene was amplified and cloned into pQE32 and pcDNA3.1 vectors and the resultant clones were named as pQE32/Nr‐51 and pcDNA3.1/Nr‐51, respectively. Recombinant p51 (rp51) protein antigen was expressed in E. coli (pQE32/Nr‐51) and cos‐7 cell line (pcDNA3.1/Nr‐51). The rp51 protein showed immunoreactivity with anti‐ mouse p51 antibodies. BALB/c mice were inoculated with recombinant plasmid DNA (pcDNA3.1/Nr‐51). The serum samples collected from these BALB/c mice showed IgG ELISA titers of 1:128. In a Western immunoblot assay, these serum samples showed a strong reactivity to rp51 expressed in cos‐7 cell line transfected with pcDNA3.1/Nr‐51. The results of this preliminary indicate that N. risticii p51 protein is an immmuno‐dominant antigen and may be a good target for the development of serological or a molecular diagnostic test and possibly an improved recombinant DNA based vaccine against Potomac horse fever.