bluuebunny/crossref_metadata_2025 huggingface dataset:
Germ cell mutagenesis in medaka fish after exposures to high-energy cosmic ray nuclei: A human model
Authors: Shimada Atsuko , Shima Akihiro , Nojima Kumie , Seino Yo , Setlow Richard B.
Published: April 2005

Astronauts beyond the Earth's orbit are exposed to high-energy cosmic-ray nuclei with high values of linear energy transfer (LET), resulting in much more biological damage than from x-rays or γ-rays and may result in mutations and cancer induction. The relative biological effectiveness of these nuclei depends on the LET, rising to as high as ≈50 at LET values of ≈100-200 keV/μm. An endpoint of concern is germ cell mutations passed on to offspring, arising from exposure to these nuclei. A vertebrate model for germ cell mutation is Medaka fish (
Oryzias latipes
). We exposed wild type males to doses of 1 GeV per nucleon Fe nuclei or to 290 MeV per nucleon C nuclei. They were mated to females with recessive mutations at five-color loci. The transparent embryos from >100 days of mating (representing exposed sperm, spermatids, or spermatogonia) were observed so as to detect dominant lethal mutations and total color mutations, even though the embryos might not hatch. The relative number of mutant embryos as a function of dose were compared with those induced by γ-rays. The relative biological effectiveness values for dominant lethal mutations and total color mutations for exposed sperm and spermatids were 1.3-2.1 for exposure to C nuclei and 1.5-3.0 for exposure to Fe nuclei. (The spermatogonial data were uncertain.) These low values, and the negligible number of viable mutations, compared with those for mutations in somatic cells and for neoplastic transformation, indicate that germ cell mutations arising from exposures to cosmic ray nuclei are not a significant hazard to astronauts.
Protein fibrils in nature can enhance amyloid protein A amyloidosis in mice: Cross-seeding as a disease mechanism
Authors: Lundmark Katarzyna , Westermark Gunilla T. , Olsén Arne , Westermark Per
Published: April 2005

Secondary, or amyloid protein A (AA), amyloidosis is a complication of chronic inflammatory diseases, both infectious and noninfectious. AA constitutes the insoluble fibrils, which are deposited in different organs, and is a major N-terminal part of the acute phase protein serum AA. It is not known why only some patients with chronic inflammation develop AA amyloidosis. Nucleation is a widely accepted mechanism in amyloidogenesis. Preformed amyloid-like fibrils act as nuclei in amyloid fibril formationin vitro, and AA amyloid fibrils and synthetic amyloid-like fibrils also may serve as seed for fibril formationin vivo. In addition to amyloid fibrils, there is a variety of similar nonmammalian protein fibrils with β-pleated structure in nature. We studied three such naturally occurring protein fibrils: silk fromBombyx mori, Sup35 fromSaccharomyces cerevisiae, and curli fromEscherichia coli. Our results show that these protein fibrils exert amyloid-accelerating properties in the murine experimental AA amyloidosis, suggesting that such environment factors may be important risk factors in amyloidogenesis.
Design and synthesis of a 3′-
O
-allyl photocleavable fluorescent nucleotide as a reversible terminator for DNA sequencing by synthesis
Authors: Ruparel Hameer , Bi Lanrong , Li Zengmin , Bai Xiaopeng , Kim Dae Hyun , Turro Nicholas J. , Ju Jingyue
Published: April 2005

DNA sequencing by synthesis (SBS) offers an approach for potential high-throughput sequencing applications. In this method, the ability of an incoming nucleotide to act as a reversible terminator for a DNA polymerase reaction is an important requirement to unambiguously determine the identity of the incorporated nucleotide before the next nucleotide is added. A free 3′-OH group on the terminal nucleotide of the primer is necessary for the DNA polymerase to incorporate an incoming nucleotide. Therefore, if the 3′-OH group of an incoming nucleotide is capped by a chemical moiety, it will cause the polymerase reaction to terminate after the nucleotide is incorporated into the DNA strand. If the capping group is subsequently removed to generate a free 3′-OH, the polymerase reaction will reinitialize. We report here the design and synthesis of a 3′-modified photocleavable fluorescent nucleotide, 3′-
O
-allyl-dUTP-PC-Bodipy-FL-510 (PC-Bodipy, photocleavable 4,4-difluoro-4-bora-3α,4α-diaza-
s
-indacene), as a reversible terminator for SBS. This nucleotide analogue contains an allyl moiety capping the 3′-OH group and a fluorophore Bodipy-FL-510 linked to the 5 position of the uracil through a photocleavable 2-nitrobenzyl linker. Here, we have shown that this nucleotide is a good substrate for a DNA polymerase. After the nucleotide was successfully incorporated into a growing DNA strand and the fluorophore was photocleaved, the allyl group was removed by using a Pd-catalyzed reaction to reinitiate the polymerase reaction, thereby establishing the feasibility of using such nucleotide analogues as reversible terminators for SBS.
Expression of PrPC on cellular components of sheep blood
Authors: Halliday S. , Houston F. , Hunter N.
Published: April 2005

PrPC, a glycosylphosphatidylinositol-linked glycoprotein, plays a central role in the pathogenesis of transmissible spongiform encephalopathies (TSEs), undergoing a conformational alteration to the disease-associated isoform, commonly designated PrPSc. PrPC is expressed in many tissues other than the nervous system, although its precise function(s) remains unclear. It has previously been demonstrated that TSEs can be transmitted by blood transfusion in sheep. The aim of this work was to identify which components of blood carried the infection. As an initial step, the distribution of PrPC on cellular components of sheep blood was examined to identify potential targets for infection. Cell-surface expression of PrPC was found only on peripheral blood mononuclear cells (PBMCs); however, platelets also contained significant amounts of intracellular PrPC. The level of PrPC expressed on the cell surface of PBMCs was influenced by PrP genotype, with the highest levels found in scrapie-susceptible VRQ/VRQ sheep and the lowest levels in scrapie-resistant ARR/ARR sheep. In susceptible sheep, PrPC was expressed at varying levels on all major subsets of PBMCs, with the highest levels on the CD21+ subset of B cells, and PrP expression was upregulated dramatically on CD21+ B cells in some scrapie-infected sheep.
Differential maturation and subcellular localization of severe acute respiratory syndrome coronavirus surface proteins S, M and E
Authors: Nal Béatrice , Chan Cheman , Kien Francois , Siu Lewis , Tse Jane , Chu Kid , Kam Jason , Staropoli Isabelle , Crescenzo-Chaigne Bernadette , Escriou Nicolas , van der Werf Sylvie , Yuen Kwok-Yung , Altmeyer Ralf
Published: April 2005

Post-translational modifications and correct subcellular localization of viral structural proteins are prerequisites for assembly and budding of enveloped viruses. Coronaviruses, like the severe acute respiratory syndrome-associated virus (SARS-CoV), bud from the endoplasmic reticulum-Golgi intermediate compartment. In this study, the subcellular distribution and maturation of SARS-CoV surface proteins S, M and E were analysed by using C-terminally tagged proteins. As early as 30 min post-entry into the endoplasmic reticulum, high-mannosylated S assembles into trimers prior to acquisition of complexN-glycans in the Golgi. Like S, M acquires high-mannoseN-glycans that are subsequently modified into complexN-glycans in the Golgi. TheN-glycosylation profile and the absence ofO-glycosylation on M protein relate SARS-CoV to the previously described group 1 and 3 coronaviruses. Immunofluorescence analysis shows that S is detected in several compartments along the secretory pathway from the endoplasmic reticulum to the plasma membrane while M predominantly localizes in the Golgi, where it accumulates, and in trafficking vesicles. The E protein is not glycosylated. Pulse-chase labelling and confocal microscopy in the presence of protein translation inhibitor cycloheximide revealed that the E protein has a short half-life of 30 min. E protein is found in bright perinuclear patches colocalizing with endoplasmic reticulum markers. In conclusion, SARS-CoV surface proteins S, M and E show differential subcellular localizations when expressed alone suggesting that additional cellular or viral factors might be required for coordinated trafficking to the virus assembly site in the endoplasmic reticulum-Golgi intermediate compartment.
Generation of recombinant influenza A virus without M2 ion-channel protein by introduction of a point mutation at the 5′ end of the viral intron
Authors: Cheung T. K. W. , Guan Y. , Ng S. S. F. , Chen H. , Wong C. H. K. , Peiris J. S. M. , Poon L. L. M.
Published: April 2005

The aim of this study was to inhibit influenza virus M2 protein expression by mutating the splicing signal of the M gene. Mutations were introduced into the GU dinucleotide sequence at the 5′-proximal splicing site of the M gene (corresponding to nt 52–53 of M cRNA). Transfected cells expressing mutated M viral ribonucleoproteins failed to generate M2 mRNA. Interestingly, recombinant viruses with mutations at the dinucleotide sequence were viable, albeit attenuated, in cell culture. These recombinants failed to express M2 mRNA and M2 protein. These observations demonstrated that the GU invariant dinucleotide sequence at the 5′-proximal splicing site of M gene is essential for M2 mRNA synthesis. These results also indicated that the M2 ion-channel protein is critical, but not essential, for virus replication in cell culture. This approach may provide a new way of producing attenuated influenza A virus.
Use of influenza C virus glycoprotein HEF for generation of vesicular stomatitis virus pseudotypes
Authors: Hanika Andrea , Larisch Birthe , Steinmann Eike , Schwegmann-Weßels Christel , Herrler Georg , Zimmer Gert
Published: April 2005

Influenza C virus contains two envelope glycoproteins: CM2, a putative ion channel protein; and HEF, a unique multifunctional protein that performs receptor-binding, receptor-destroying and fusion activities. Here, it is demonstrated that expression of HEF is sufficient to pseudotype replication-incompetent vesicular stomatitis virus (VSV) that lacks the VSV glycoprotein (G) gene. The pseudotyped virus showed characteristic features of influenza C virus with respect to proteolytic activation, receptor usage and cell tropism. Chimeric glycoproteins composed of HEF ectodomain and VSV-G C-terminal domains were efficiently incorporated into VSV particles and showed receptor-binding and receptor-destroying activities but, unlike authentic HEF, did not mediate efficient infection, probably because of impaired fusion activity. HEF-pseudotyped VSV efficiently infected polarized Madin–Darby canine kidney cells via the apical plasma membrane, whereas entry of VSV-G-complemented virus was restricted to the basolateral membrane. These findings suggest that pseudotyping of viral vectors with HEF might be useful for efficient apical gene transfer into polarized epithelial cells and for targeting cells that express 9-O-acetylated sialic acids.
Rolling-circle amplification of Torque teno virus (TTV) complete genomes from human and swine sera and identification of a novel swine TTV genogroup
Authors: Niel Christian , Diniz-Mendes Leonardo , Devalle Sylvie
Published: April 2005

Multiply primed rolling-circle amplification is a novel technology that uses bacteriophage phi29 DNA polymerase to amplify circular DNA molecules, without the need for prior knowledge of their sequences. In an attempt to detectTorque teno virus(TTV), rolling-circle amplification was used to amplify DNA extracted from eight human and four pig serum samples. All samples gave high molecular weight (>30 kb) amplification products. By restriction endonuclease digestion, these products generated DNA fragments whose sizes were consistent with those of human TTV (3·8 kb) and swine TTV (Sd-TTV; 2·9 kb) genomes. Two TTV isolates derived from a single AIDS patient, as well as two Sd-TTV isolates derived from a single pig, were characterized by complete nucleotide sequencing. One of the Sd-TTV isolates showed very low (43–45 %) nucleotide sequence similarity to the other Sd-TTV isolate and to the prototype isolate Sd-TTV31, and could be considered the prototype of a novel genogroup.
A double-stranded RNA from a Phytophthora species is related to the plant endornaviruses and contains a putative UDP glycosyltransferase gene
Authors: Hacker Caroline V. , Brasier Clive M. , Buck Kenneth W.
Published: April 2005

A new dsRNA was isolated from a Phytophthora isolate from Douglas fir. Sequence analysis showed the dsRNA to consist of 13 883 bp and to contain a single open reading frame with the potential to encode a polyprotein of 4548 aa. This polyprotein contained amino acid sequence motifs characteristic of virus RNA-dependent RNA polymerases (RdRps) in its C-terminal region and motifs characteristic of RNA helicases in its N-terminal region. These sequence motifs were related to corresponding motifs in plant viruses in the genus Endornavirus. In phylogenetic trees constructed from the RdRp and helicase motifs of a range of ssRNA and dsRNA viruses, the Phytophthora RdRp and helicase sequences clustered with those of the plant endornaviruses with good bootstrap support. The properties of the Phytophthora dsRNA are consistent with its being classified as the first non-plant member of the genus Endornavirus, for which we propose the name phytophthora endornavirus 1 (PEV1). A region between the RdRp and helicase domains of the PEV1 protein had significant amino acid sequence similarity to UDP glycosyltransferases (UGTs). Two sequence motifs were identified, one characteristic of all UGTs and the other characteristic of sterol UGTs. The PEV1 UGT would be the first for an RNA virus, although ecdysteroid UGT genes have been found in many baculoviruses. The PEV1 UGT was only distantly related to baculovirus ecdysteroid UGTs, which belong to a family distinct from the sterol UGTs.
A single immunization with a rhabdovirus-based vector expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels of SARS-CoV-neutralizing antibodies
Authors: Faber Milosz , Lamirande Elaine W. , Roberts Anjeanette , Rice Amy B. , Koprowski Hilary , Dietzschold Bernhard , Schnell Matthias J.
Published: April 2005

Foreign viral proteins expressed by rabies virus (RV) have been shown to induce potent humoral and cellular immune responses in immunized animals. In addition, highly attenuated and, therefore, very safe RV-based vectors have been constructed. Here, an RV-based vaccine vehicle was utilized as a novel vaccine against severe acute respiratory syndrome coronavirus (SARS-CoV). For this approach, the SARS-CoV nucleocapsid protein (N) or envelope spike protein (S) genes were cloned between the RV glycoprotein G and polymerase L genes. Recombinant vectors expressing SARS-CoV N or S protein were recovered and their immunogenicity was studied in mice. A single inoculation with the RV-based vaccine expressing SARS-CoV S protein induced a strong SARS-CoV-neutralizing antibody response. The ability of the RV-SARS-CoV S vector to confer immunity after a single inoculation makes this live vaccine a promising candidate for eradication of SARS-CoV in animal reservoirs, thereby reducing the risk of transmitting the infection to humans.
A novel envelope protein involved in White spot syndrome virus infection
Authors: Huang Ru , Xie Yunli , Zhang Jianhong , Shi Zhengli
Published: April 2005

One open reading frame (designated vp76) from the White spot syndrome virus (WSSV) genome has the motif of a cytokine I receptor and has been identified as a structural protein. In this paper, vp76 was expressed in Escherichia coli and used to prepare a specific antibody to determine the location of the corresponding protein in the intact virion, the nucleocapsids and the envelope of WSSV. Western blotting with the VP76 antiserum confirmed that VP76 was an envelope protein of WSSV. To investigate the function of the VP76, WSSV was neutralized with the VP76-specific antiserum at different concentrations and injected intramuscularly into crayfish. The mortality curves showed that the VP76 antiserum could partially attenuate infection with WSSV, suggesting that VP76 is an envelope protein involved in WSSV infection.
Arabidopsis Tic110 Is Essential for the Assembly and Function of the Protein Import Machinery of Plastids
Authors: Inaba Takehito , Alvarez-Huerta Mayte , Li Ming , Bauer Jörg , Ewers Carolin , Kessler Felix , Schnell Danny J.
Published: April 2005

The translocon at the inner envelope membrane of chloroplasts (Tic) plays a central role in plastid biogenesis by coordinating the sorting of nucleus-encoded preproteins across the inner membrane and coordinating the interactions of preproteins with the processing and folding machineries of the stroma. Despite these activities, the precise roles of known Tic proteins in translocation, sorting, and preprotein maturation have not been defined. In this report, we examine the in vivo function of a major Tic component, Tic110. We demonstrate that Arabidopsis thaliana Tic110 (atTic110) is essential for plastid biogenesis and plant viability. The downregulation of atTic110 expression results in the reduced accumulation of a wide variety of plastid proteins. The expression of dominant negative mutants of atTic110 disrupts assembly of Tic complexes and the translocation of preproteins across the inner envelope membrane. Together, these data suggest that Tic110 plays a general role in the import of nuclear-encoded preproteins as a common component of Tic complexes.
MicroRNA-Directed Regulation of ArabidopsisAUXIN RESPONSE FACTOR17Is Essential for Proper Development and Modulates Expression of Early Auxin Response Genes
Authors: Mallory Allison C. , Bartel David P. , Bartel Bonnie
Published: April 2005

The phytohormone auxin plays critical roles during plant growth, many of which are mediated by the auxin response transcription factor (ARF) family. MicroRNAs (miRNAs), endogenous 21-nucleotide riboregulators, target several mRNAs implicated in auxin responses. miR160 targets ARF10, ARF16, and ARF17, three of the 23 Arabidopsis thaliana  ARF genes. Here, we describe roles of miR160-directed ARF17 posttranscriptional regulation. Plants expressing a miRNA-resistant version of ARF17 have increased ARF17 mRNA levels and altered accumulation of auxin-inducible GH3-like mRNAs, YDK1/GH3.2, GH3.3, GH3.5, and DFL1/GH3.6, which encode auxin-conjugating proteins. These expression changes correlate with dramatic developmental defects, including embryo and emerging leaf symmetry anomalies, leaf shape defects, premature inflorescence development, altered phyllotaxy along the stem, reduced petal size, abnormal stamens, sterility, and root growth defects. These defects demonstrate the importance of miR160-directed ARF17 regulation and implicate ARF17 as a regulator of GH3-like early auxin response genes. Many of these defects resemble phenotypes previously observed in plants expressing viral suppressors of RNA silencing and plants with mutations in genes important for miRNA biogenesis or function, providing a molecular rationale for phenotypes previously associated with more general disruptions of miRNA function.
The effect of ZD1839 (IressaTM), an epidermal growth factor receptor tyrosine kinase inhibitor, in combination with cisplatin, on apoptosis in SCC‐15 cells
Authors: Al‐Hazzaa A. , Bowen I. D. , Randerson P. , Birchall M. A.
Published: April 2005

Abstract.  The aim of this study was to determine the effect of ZD1839 on growth and apoptosis in SCC‐15 (a human head and neck cancer cell line) alone, or in combination with cisplatin. High expression of the epidermal growth factor receptor has been implicated in the development of squamous cell carcinomas of head and neck. ZD1839 (‘Iressa’) is an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor that blocks signal transduction pathways implicated in proliferation and survival of cancer cells, and other host‐dependent processes promoting cancer growth. Here, growth arrest was observed with 3.64 µm ZD1839. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (sMTT) viability assay revealed a significant decrease (P < 0.001) in the percentage of surviving cells upon treatment with ZD1839 and cisplatin compared with cisplatin or ZD1839 on their own. Combined therapy of 3.64 µm ZD1839 for 24 h, prior to administration of 100 µm cisplatin, significantly (P < 0.001) and additively increased the cytotoxicity effect of cisplatin. p53‐independent apoptosis was seen with cisplatin treatment, a novel finding. These data support the use of ZD1839 in anti‐cancer therapy, and particularly in combination therapy. Cisplatin may induce p53‐independent apoptosis. Over‐expression of Bcl‐2 in head and neck squamous cell carcinoma tumour cell lines is unlikely to be a general mechanism to protect these cells from apoptosis.
Depth determination from a non‐stationary magnetic profile for scaling geology
Authors: Bansal A.R. , Dimri V.P.
Published: April 2005

The conventional spectral analysis method for interpretation of magnetic data assumes stationary spatial series and a white‐noise source distribution. However, long magnetic profiles may not be stationary in nature and source distributions are not white. Long non‐stationary magnetic profiles can be divided into stationary subprofiles following Wiener filter theory. A least‐squares inverse method is used to calculate the scaling exponents and depth values of magnetic interfaces from the power spectrum. The applicability of this approach is demonstrated on non‐stationary synthetic and field magnetic data collected along the Nagaur–Jhalawar transect, western India. The stationarity of the whole profile and the subprofiles of the synthetic and field data is tested. The variation of the mean and standard deviations of the subprofiles is significantly reduced compared with the whole profile. The depth values found from the synthetic model are in close agreement with the assumed depth values, whereas for the field data these are in close agreement with estimates from seismic, magnetotelluric and gravity data.
On the electrical reflectivity tensor in d.c. electric field modelling
Authors: Sun J.
Published: April 2005

We use the integral equation for a d.c. electric field, published in the literature, to introduce the concept of the electrical reflectivity tensor into d.c. electric field modelling. It is shown that in d.c. electric field modelling, the electric reflectivity tensor can be obtained in exactly the same way as in electromagnetic modelling. As a result, for a d.c. electric field, the quasi‐linear and the quasi‐analytical approximations, as well as the quasi‐analytical series, can be constructed in exactly the same way as in electromagnetic modelling. If the primary field is uniform, and if the anomalous body is a uniform circular cylinder or a uniform sphere, the reflectivity tensor is zero order (constant), relating to the free surface charge density. Thus, for some homogeneous bodies that have simple shapes and are embedded in a uniform primary field, the electrical reflectivity tensor is not only a mathematical mechanism for obtaining approximate solutions, but also a physical reality. Indeed, the free surface charge density is defined as the change of the electric displacement vector across the boundary surface under consideration. If the primary field is caused by a point source, and if the anomalous body is a uniform sphere, the reflectivity tensor is second order, varying slowly within the sphere. The relationship to the free surface charge density can be established only when both the reflectivity tensor and the free surface charge density are approximated by the first terms of their series solutions. If the point source is far from the centre of the sphere, the corresponding reflectivity tensor reduces to zero order, and is independent of the observation position within the sphere, i.e. it is a constant. Therefore, the basic idea of the quasi‐analytical approximation, i.e. taking the reflectivity tensor outside the integral operator, is justified in the case considered here.
The Fragmentation of a Railway: A Study of Organizational Change
Authors: Tyrrall David , Parker David
Published: April 2005

abstract This paper considers pathways of organizational change within British Rail (BR) during its long period of commercialization culminating in privatization. TheLaughlin (1991) andParker (1995a) frameworks are used to demonstrate how a new interpretative scheme supplanted the previous interpretative scheme within BR between the 1970s and privatization in the mid‐1990s, leading to a fragmented organization. BR did not survive and privatization of Britain's railways remains controversial. The study demonstrates that without the earlier changes in interpretive scheme from ‘social railway’ to ‘business railway’ to ‘profitable business’, and the associated changes in design archetypes and sub‐systems, privatization would have been both less tempting and less feasible. It is intended that the approach developed here to analyse organizational change in BR should be applicable to the study of other privatizations and to other forms of organizational change in both the public and private sectors.
Determinants of capacious memory: A process‐dissociation and experiential approach
Authors: DUBUC SÉVERINE , KARLSSON THOMAS , LALONDE ROBERT
Published: April 2005

The aim of this study is to delineate some important circumstances where exceptionally good memory performance, or capacious memory occurs. A further aim is to study memory processes involved in this memory phenomenon. In a first experiment, participants looked through two series of pictures differing in number and were evaluated in two‐alternative forced‐choice and yes‐no recognition memory tasks combined in a process‐dissociation procedure. Moreover, participants were asked to provide remember and know responses to tap recollective experience. The results as to forced‐choice recognition task accuracy and according to process‐dissociation procedure estimates were replicated in a second experiment with a more intrinsic contextual manipulation, and in a third, forgetting experiment. In addition to replicating previous findings, the results show (a) that capacious memory is associated with strong feelings of recollection; and (b) that familiarity (in terms of the process‐dissociation framework) contributes to this phenomenon.
Antecedent reactivation by surface and deep anaphora in Norwegian
Authors: HESTVIK ARILD , NORDBY HELGE , KARLSEN GEIR
Published: April 2005

Anaphora are expressions in language that depend on other linguistic entities for their full meaning. They can furthermore be divided into two types according to the level of representation where they find their antecedents: Surface anaphora, which resolve their reference at the sentence representation level, and deep anaphora, which resolve their reference at the non‐grammatical level of discourse representation. The linguistic theory of these two anaphor types, and recent findings about processing differences at these two levels, combine to predict that surface anaphora should show fast and immediate reactivation of their antecedents, whereas deep anaphora should have a slower time course of antecedent reaccess. These predictions were confirmed with two lexical decision task experiments with Norwegian stimuli.
An empirical look at the Defense Mechanism Test (DMT): Reliability and construct validity
Authors: EKEHAMMAR BO , ZUBER IRENA , KONSTENIUS MARJA‐LIISA
Published: April 2005

Although the Defense Mechanism Test (DMT) has been in use for almost half a century, there are still quite contradictory views about whether it is a reliable instrument, and if so, what it really measures. Thus, based on data from 39 female students, we first examined DMT inter‐coder reliability by analyzing the agreement among trained judges in their coding of the same DMT protocols. Second, we constructed a “parallel” photographic picture that retained all structural characteristic of the original and analyzed DMT parallel‐test reliability. Third, we examined the construct validity of the DMT by (a) employing three self‐report defense‐mechanism inventories and analyzing the intercorrelations between DMT defense scores and corresponding defenses in these instruments, (b) studying the relationships between DMT responses and scores on trait and state anxiety, and (c) relating DMT‐defense scores to measures of self‐esteem. The main results showed that the DMT can be coded with high reliability by trained coders, that the parallel‐test reliability is unsatisfactory compared to traditional psychometric standards, that there is a certain generalizability in the number of perceptual distortions that people display from one picture to another, and that the construct validations provided meager empirical evidence for the conclusion that the DMT measures what it purports to measure, that is, psychological defense mechanisms.
A randomised controlled trial of biopsy forceps and cannula aspiration for transcervical chorionic villus sampling
Authors: Von Dadelszen Peter , Sermer Mathew , Hillier Joan , Allen Lynn C. , Fernandes Bernie J.J. , Johnson Jo‐Ann M. , Shime Jerry , Winsor Elizabeth J.T. , Ryan Greg
Published: April 2005

Objective  This trial compared two instruments for transcervical chorionic villus sampling (CVS).

Design  Randomised controlled trial.

Setting  Regional university prenatal diagnosis and treatment centre.

Population  Two hundred women were randomised at 10+0–12+6 weeks of gestation to transcervical CVS using cannula aspiration (CA) or biopsy forceps (BF).

Methods  Women undergoing indicated CVS signed informed consent. Randomisation after decision to perform transcervical CVS.

Main outcome measures  Primary outcome: the rise in maternal serum α‐fetoprotein (α‐FP). Secondary outcomes: (i) placental trauma (fetomaternal haemorrhage [FMH]); (ii) laboratory, procedure, and cytogenetic results and pregnancy outcomes; (iii) patient and operator satisfaction; and (iv) economic analyses. Analyses were performed by intention to treat.

Results  The ‐FP rise did not differ between groups; there was no other evidence of placental trauma. BF were better tolerated by women, provided culturable tissue, after fewer instrument passes, with greater ease and in less time. BF were associated with cost savings.

Conclusions  Unlike ‐FP, other markers of FMH were unaltered, questioning the reliability of α‐FP as an indicator of FMH. Compared with CA, transcervical BF caused comparable placental trauma, appeared to be similarly effective and safe and were preferred by operators and patients.
Female genital appearance: ‘normality’ unfolds
Authors: Lloyd Jillian , Crouch Naomi S. , Minto Catherine L. , Liao Lih‐Mei , Creighton Sarah M.
Published: April 2005

Objective  To describe variations in genital dimensions of normal women.

Design  Observational cross‐sectional study.

Setting  Elizabeth Garrett Anderson Hospital, University College Hospital NHS Trust, London, UK.

Population  Fifty premenopausal women having gynaecological procedures not involving the external genitalia under general anaesthetic.

Methods  A cross sectional study using digital photography and measurements of the external genitalia.

Main outcome measures  Clitoral size, labial length and width, colour and rugosity, vaginal length, distance from clitoris to urethral orifice, distance from posterior fourchette to anterior anal margin.

Results  A wide range of values were noted for each measurement. There was no statistically significant association with age, parity, ethnicity, hormonal use or history of sexual activity.

Conclusion  Women vary widely in genital dimensions. This information should be made available to women when considering surgical procedures on the genitals, decisions for which must be carefully considered between surgeon and woman.
Prostaglandin E2 vaginal gel to treat dystocia in spontaneous labour: a multicentre randomised placebo‐controlled trial
Authors: Oppenheimer Lawrence W. , Labrecque Michel , Wells George , Bland Elaine S. , Fraser William D. , Eason Erica , Brisson‐Carroll Gisele , Yetisir Elizabeth ,   Dylate Study Group
Published: April 2005

Objective  To test the safety and efficacy of prostaglandin E2 (PgE2) as a treatment for dystocia in spontaneous labour.

Design  Randomised, double‐blind, placebo‐controlled trial.

Setting  Multicentre study in nine university‐affiliated hospitals in Canada.

Population  Three hundred and thiry‐two nulliparous women with spontaneous labour at term.

Methods  Women who had progressed <2 cm of cervical dilation in the 4 hours following the diagnosis of labour were randomly assigned to receive a single dose of either 1 mg (n= 112) or 2 mg (n= 111) PgE2 vaginal gel or placebo gel (n= 109).

Main outcome measures  The primary outcome was resolution of dystocia, defined as a change in cervical dilatation of >0.5 cm per hour in the 6 hours following gel administration. Secondary outcomes were progress of labour, uterine hyperstimulation (more than five contractions in 10 minutes or a contraction lasting more than 2 minutes), use of oxytocin, method of delivery, maternal and neonatal morbidity.

Results  Dystocia resolved more often after PgE2 1 mg (49%), RR 1.53 (95% CI 1.1, 2.1) and PgE2 2 mg (49%), RR 1.5 (CI 1.1, 2.1), compared with placebo (32%). Hyperstimulation was increased after PgE2 2 mg treatment (15%), RR 5.6 (95% CI 1.7, 18), but not after PgE2 1 mg (5.4%), RR 1.9 (CI 0.50, 7.6) when compared with placebo (2.8%). There was an increase in caesarean sections performed in the second stage of labour in the PgE2 groups versus placebo. There were no differences in measures of maternal or neonatal morbidity.

Conclusion  A single 1‐mg dose of PgE2 vaginal gel is more effective than placebo in resolving dystocia, without increasing uterine hyperstimulation, but may be associated with an increase in the incidence of second stage caesarean section.
How much variation in CS rates can be explained by case mix differences?
Authors: Paranjothy S. , Frost C. , Thomas J.
Published: April 2005

Objective  To quantify the amount of variation in caesarean section (CS) rates between maternity units explained by case mix differences.

Design  Cross‐sectional study.

Setting  All 216 maternity units in England and Wales.

Population  Women giving birth at these maternity units between May and July 2000.

Methods  Logistic regression models were developed to investigate the relationship between case mix characteristics, and odds of (i) CS before labour, (ii) CS in labour. Using these results, overall CS rates standardised for case mix were calculated for each maternity unit. Random‐effects meta‐analysis was used to examine heterogeneity between maternity units.

Main outcome measures  CS before labour and CS during labour.

Results  Adjustment for case mix differences between maternity units explained 34% of the variance in CS rates. Odds of CS (before and in labour) increased with maternal age. Women from ethnic minority groups had lower odds of CS before labour, and increased odds of CS in labour. Women with a previous vaginal delivery had lower odds of CS, although the magnitude of this for CS before and in labour is markedly different.

Conclusions  Case mix adjustment is important to enable understanding of the factors that influence the CS rate. These include organisational and staffing levels as well as women's preferences for childbirth and clinician's attitudes. An understanding of how these factors influence the CS rate is essential for evaluation of quality and appropriateness of obstetric care provided to women.
SCINTIGRAPHIC EVALUATION OF THE DISTAL TARSAL REGION IN HORSES WITH DISTAL TARSAL PAIN
Authors: Murray Rachel C. , Dyson Sue J. , Weekes Jo S. , Short Carly , Branch Marion V.
Published: April 2005

Distal tarsal pain is a common reason for hind limb lameness, but diagnosis cannot always be made on radiographic examination. Scintigraphy may allow detection of subtle changes undetected by other diagnostic methods. We hypothesized that (1) distal tarsal pain would be associated with a loss of the expected pattern of radiopharmaceutical uptake (RU) detected in normal horses, (2) distal tarsal RU would be greater in limbs with tarsal pain than without pain, (3) RU in painful tarsi with radiographic evidence of osteoarthritis (OA) would be greater than in distal tarsal pain with no radiographic evidence of OA. The study aimed to describe radiopharmaceutical distribution in the distal tarsal region of horses with distal tarsal pain, and to compare this with the contralateral limb and results from horses without tarsal pain. Retrospective evaluation of scintigraphic images of the distal tarsal region was performed for 52 horses with distal tarsal pain: 15 with no radiographic evidence of OA (Group 1) and 37 with radiographic evidence (Group 2). The images were assessed using vertical and horizontal profile analysis across the distal tarsal region and regions of interest comparisons between the distal tarsal region and tibia within each horse (RU ratio). Painful limbs in unilaterally lame horses from Groups 1 and 2 had a significantly greater RU ratio than the respective contralateral limbs, and were significantly greater than the RU ratio in normal horses. On plantar images, mean region of interest counts were greater in the lame than the contralateral limb in Group 2 but not in Group 1. Although there was a positive correlation between lame and contralateral limb RU ratio in group 1, this was lost in group 2 horses. In lame limbs, the normal vertical activity profile was lost in 85% of group 1 and all of group 2, and the normal horizontal activity profile was lost in all of group 1 and 96% of group 2. There was a significant effect of lameness, but not of group on sites of peak activity on all profiles. The results of this study indicate that distal tarsal pain is associated with loss of the expected pattern of RU detected in normal horses. The findings also suggest that distal tarsal RU in lame limbs is greater than in limbs without pain, and that painful limbs with radiographic evidence of OA have a greater RU than painful limbs without radiographic evidence of OA.
PLAY‐DOH® AND WATER‐SOAKED GAUZE SPONGES AS ALTERNATIVE BOLUS MATERIAL FOR COBALT‐60 TELETHERAPY
Authors: Walker Michael , Cohen Noah , Menchaca Daniel
Published: April 2005

A study was performed to determine if carefully made boluses of either Play‐Doh®, or water‐soaked cotton gauze sponges differed from the commercial bolus material, Superflab, in producing maximum radiation dose when irradiated with cobalt‐60 photons. The radiation doses were measured with thermoluminescent dosimeters calibrated to be accurate for cobalt‐60 photon energies at doses less than 10.0 cGy. The resulting radiation doses were similar when using Play‐Doh®, water‐soaked sponges, or Superflab. Doses resulting from Play‐Doh® boluses more consistently approximated those of Superflab. The results of this study suggest that either Play‐Doh® or water‐soaked cotton gauze sponges can suffice as material for carefully made bolus for cobalt‐60 teletherapy.
Fragmentation and Flow Regulation of the World's Large River Systems
Authors: Nilsson Christer , Reidy Catherine A. , Dynesius Mats , Revenga Carmen
Published: April 2005

A global overview of dam-based impacts on large river systems shows that over half (172 out of 292) are affected by dams, including the eight most biogeographically diverse. Dam-impacted catchments experience higher irrigation pressure and about 25 times more economic activity per unit of water than do unaffected catchments. In view of projected changes in climate and water resource use, these findings can be used to identify ecological risks associated with further impacts on large river systems.
Clostridium difficileToxins: Mechanism of Action and Role in Disease
Authors: Voth Daniel E. , Ballard Jimmy D.
Published: April 2005

As the leading cause of hospital-acquired diarrhea,Clostridium difficilecolonizes the large bowel of patients undergoing antibiotic therapy and produces two toxins, which cause notable disease pathologies. These two toxins, TcdA and TcdB, are encoded on a pathogenicity locus along with negative and positive regulators of their expression. Following expression and release from the bacterium, TcdA and TcdB translocate to the cytosol of target cells and inactivate small GTP-binding proteins, which include Rho, Rac, and Cdc42. Inactivation of these substrates occurs through monoglucosylation of a single reactive threonine, which lies within the effector-binding loop and coordinates a divalent cation critical to binding GTP. By glucosylating small GTPases, TcdA and TcdB cause actin condensation and cell rounding, which is followed by death of the cell. TcdA elicits effects primarily within the intestinal epithelium, while TcdB has a broader cell tropism. Important advances in the study of these toxins have been made in the past 15 years, and these are detailed in this review. The domains, subdomains, and residues of these toxins important for receptor binding and enzymatic activity have been elegantly studied and are highlighted herein. Furthermore, there have been major advances in defining the role of these toxins in modulating the inflammatory events involving the disruption of cell junctions, neuronal activation, cytokine production, and infiltration by polymorphonuclear cells. Collectively, the present review provides a comprehensive update on TcdA and TcdB's mechanism of action as well as the role of these toxins in disease.
Subversion Mechanisms by WhichLeishmaniaParasites Can Escape the Host Immune Response: a Signaling Point of View
Authors: Olivier Martin , Gregory David J. , Forget Geneviève
Published: April 2005

The obligate intracellular parasiteLeishmaniamust survive the antimicrobial activities of its host cell, the macrophage, and prevent activation of an effective immune response. In order to do this, it has developed numerous highly successful strategies for manipulating activities, including antigen presentation, nitric oxide and oxygen radical generation, and cytokine production. This is generally the result of interactions betweenLeishmaniacell surface molecules, particularly gp63 and LPG, and less well identified macrophage surface receptors, causing the distortion of specific intracellular signaling cascades. We describe some of the signaling pathways and intermediates that are repressed in infected cells, including JAK/STAT, Ca2+-dependent protein kinase C (PKC) isoforms, and mitogen-activated protein kinases (especially ERK1/2), and proteasome-mediated transcription factor degradation. We also discuss protein tyrosine phosphatases (particularly SHP-1), intracellular Ca2+, Ca2+-independent PKC, ceramide, and the suppressors of cytokine signaling family of repressors, which are all reported to be activated following infection, and the role of parasite-secreted cysteine proteases.
Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due toBordetella pertussisand OtherBordetellaSubspecies
Authors: Mattoo Seema , Cherry James D.
Published: April 2005

Bordetellarespiratory infections are common in people (B. pertussis) and in animals (B. bronchiseptica). During the last two decades, much has been learned about the virulence determinants, pathogenesis, and immunity ofBordetella. Clinically, the full spectrum of disease due toB. pertussisinfection is now understood, and infections in adolescents and adults are recognized as the reservoir for cyclic outbreaks of disease. DTaP vaccines, which are less reactogenic than DTP vaccines, are now in general use in many developed countries, and it is expected that the expansion of their use to adolescents and adults will have a significant impact on reducing pertussis and perhaps decrease the circulation ofB. pertussis. Future studies should seek to determine the cause of the unique cough which is associated withBordetellarespiratory infections. It is also hoped that data gathered from molecularBordetellaresearch will lead to a new generation of DTaP vaccines which provide greater efficacy than is provided by today's vaccines.
Melioidosis: Epidemiology, Pathophysiology, and Management
Authors: Cheng Allen C. , Currie Bart J.
Published: April 2005

Melioidosis, caused by the gram-negative saprophyteBurkholderia pseudomallei, is a disease of public health importance in southeast Asia and northern Australia that is associated with high case-fatality rates in animals and humans. It has the potential for epidemic spread to areas where it is not endemic, and sporadic case reports elsewhere in the world suggest that as-yet-unrecognized foci of infection may exist. Environmental determinants of this infection, apart from a close association with rainfall, are yet to be elucidated. The sequencing of the genome of a strain ofB. pseudomalleihas recently been completed and will help in the further identification of virulence factors. The presence of specific risk factors for infection, such as diabetes, suggests that functional neutrophil defects are important in the pathogenesis of melioidosis; other studies have defined virulence factors (including a type III secretion system) that allow evasion of killing mechanisms by phagocytes. There is a possible role for cell-mediated immunity, but repeated environmental exposure does not elicit protective humoral or cellular immunity. A vaccine is under development, but economic constraints may make vaccination an unrealistic option for many regions of endemicity. Disease manifestations are protean, and no inexpensive, practical, and accurate rapid diagnostic tests are commercially available; diagnosis relies on culture of the organism. Despite the introduction of ceftazidime- and carbapenem-based intravenous treatments, melioidosis is still associated with a significant mortality attributable to severe sepsis and its complications. A long course of oral eradication therapy is required to prevent relapse. Studies exploring the role of preventative measures, earlier clinical identification, and better management of severe sepsis are required to reduce the burden of this disease.