bluuebunny/crossref_metadata_2025 huggingface dataset:
Interval exercise versus continuous exercise in patients with moderate to severe chronic obstructive pulmonary disease – study protocol for a randomised controlled trial [ISRCTN11611768]
Authors: Puhan Milo A , Büsching Gilbert , vanOort Evelien , Zaugg Christian , Schünemann Holger J , Frey Martin
Published: August 2004

Background

Physical exercise has become a cornerstone of management of chronic obstructive pulmonary disease (COPD) because it leads to clinically relevant improvements of exercise capacity and health-related quality of life (HRQL). Despite the scarcity of randomised trials directly comparing exercise protocols, current guidelines recommend high intensity continuous exercise for lower extremities as the probably most effective exercise modality. However, for patients admitted to inpatient respiratory rehabilitation programmes, it is often difficult to initiate such an exercise programme because they are severely limited by dyspnoea and leg fatigue and therefore unable to perform continuous exercise at higher intensities and for periods longer than 30 minutes. Interval exercise may be an attractive alternative for these COPD patients because it allows high intensity exercise with recovery periods. The aim of this study is to assess if interval exercise compared to high intensity continuous exercise is not of inferior effectiveness in terms of HRQL and exercise capacity improvements but associated with better exercise tolerance in patients with moderate to severe COPD at the beginning of a respiratory rehabilitation.

Methods/Design

We will assign patients with moderately severe to severe COPD to either continuous exercise or interval exercise using a stratified randomisation. Patients will follow 12–15 exercise sessions during a comprehensive inpatient respiratory rehabilitation. Primary end point for effectiveness is HRQL as measured by the Chronic Respiratory Questionnaire (CRQ) two weeks after the end of rehabilitation and secondary endpoints include additional clinical outcomes such as functional exercise capacity, other HRQL measures, patients' experience of physical exercise as well as physiological measures of the effects of physical exercise such as cardiopulmonary exercise testing. Including expected drop-outs, we will need 52 patients per group to show differences corresponding to the minimal clinically important difference of the CRQ. Outcome assessors and investigators involved in data analysis will be blinded to group assignment until analyses have been carried out.

Discussion

Clinicians and the scientific community need evidence on the benefits and tolerance of exercise protocols available in clinical practice. The proposed trial will provide important and needed data on interval and continuous exercise for decision making in clinical practice.
Rubia cordifolia, Fagonia cretica linn and Tinospora cordifolia exert neuroprotection by modulating the antioxidant system in rat hippocampal slices subjected to oxygen glucose deprivation
Authors: Rawal Avinash K , Muddeshwar Manohar G , Biswas Saibal K
Published: August 2004

Background

The major damaging factor during and after the ischemic/hypoxic insult is the generation of free radicals, which leads to apoptosis, necrosis and ultimately cell death. Rubia cordifolia (RC), Fagonia cretica linn (FC) and Tinospora cordifolia (TC) have been reported to contain a wide variety of antioxidants and have been in use in the eastern system of medicine for various disorders. However, their mechanism of action was largely unknown. We therefore selected these herbs for the present study to test their neuroprotective ability and the associated mechanism in rat hippocampal slices subjected to oxygen-glucose deprivation (OGD).

Methods

Hippocampal Slices were subjected to OGD (oxygen glucose deprivation) and divided into 3 groups: control, OGD and OGD + drug treated. Cytosolic Cu-Zn superoxide dismutase (Cu-Zn SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), nitric oxide (NO) was measured as nitrite (NO2) in the supernatant and protein assays were performed in the respective groups at various time intervals. EPR was used to establish the antioxidant effect of RC, FC and TC with respect to superoxide anion (O2.-), hydroxyl radicals (. OH), nitric oxide (NO) radical and peroxynitrite anion (ONOO) generated from pyrogallol, menadione, DETA-NO and Sin-1 respectively. RT-PCR was performed for the three groups for GCLC, iNOS, Cu-Zn SOD and GAPDH gene expression.

Results

All the three herbs were effective in elevating the GSH levels, expression of the gamma-glutamylcysteine ligase and Cu-Zn SOD genes. The herbs also exhibited strong free radical scavenging properties against reactive oxygen and nitrogen species as studied by electron paramagnetic resonance spectroscopy. In addition all the three herbs significantly diminished the expression of iNOS gene after 48 hours which plays a major role in neuronal injury during hypoxia/ischemia.

Conclusions

RC, FC and TC therefore attenuate oxidative stress mediated cell injury during OGD and exert the above effects at both the cytosolic as well as at gene expression level and may be an effective therapeutic tool against ischemic brain damage.
Atypical vessels as an early sign of intracardiac myxoma?
Authors: Dübel Hans-Peter , Knebel Fabian , Gliech Volker , Konertz Wolfgang , Rutsch Wolfgang , Baumann Gert , Borges Adrian Constantin
Published: August 2004

We report on a woman with previously unknown left atrial myxoma, who underwent percutaneous coronary intervention. 45 months after the initial coronary angiography, echocardiography demonstrated a large atrial myxoma, which was not seen echocardiographically before. The retrospective analysis of the pre-intervention coronary angiography revealed atypical vessels in the atrial septum, which are interpreted as early signs of myxoma.
A catalog of human cDNA expression clones and its application to structural genomics
Authors: Büssow Konrad , Quedenau Claudia , Sievert Volker , Tischer Janett , Scheich Christoph , Seitz Harald , Hieke Brigitte , Niesen Frank H , Götz Frank , Harttig Ulrich , Lehrach Hans
Published: August 2004

We describe here a systematic approach to the identification of human proteins and protein fragments that can be expressed as soluble proteins in Escherichia coli. A cDNA expression library of 10,825 clones was screened by small-scale expression and purification and 2,746 clones were identified. Sequence and protein-expression data were entered into a public database. A set of 163 clones was selected for structural analysis and 17 proteins were prepared for crystallization, leading to three new structures.
Glucocorticoid-induced TNF receptor family gene (GITR) knockout mice exhibit a resistance to splanchnic artery occlusion (SAO) shock
Authors: Cuzzocrea Salvatore , Nocentini Giuseppe , Di Paola Rosanna , Mazzon Emanuela , Ronchetti Simona , Genovese Tiziana , Muià Carmelo , Caputi Achille P , Riccardi Carlo
Published: August 2004

In the present study, we used glucocorticoid-induced tumor necrosis factor (TNF) receptor family gene knockout (GITR-KO) mice to evaluate a possible role of GITR on the pathogenesis of splanchnic artery occlusion (SAO) shock, which was induced in mice by clamping the superior mesenteric artery and the celiac artery for 30 min, followed thereafter by release of the clamp (reperfusion). At 60 min after reperfusion, animals were killed for histological examination and biochemical studies. There was a marked increase in the lipid peroxidation in the ileum of the SAO-shocked, GITR wild-type (WT) mice after reperfusion. The absence of GITR significantly reduced the lipid peroxidation in the intestine. SAO-shocked WT mice developed a significant increase of ileum tissue, TNF-α, and myeloperoxidase activity and marked histological injury. SAO shock was also associated with a significant mortality (5% survival at 24 h after reperfusion). Reperfused ileum tissue sections from SAO-shocked WT mice showed positive staining for P-selectin, intercellular adhesion molecule 1 (ICAM-1), and E-selectin. The intensity and degree of P-selectin, E-selectin, and ICAM-1 were markedly reduced in tissue section from SAO-shocked, GITR-KO mice. SAO-shocked, GITR-KO mice also showed a significant reduction of the TNF-α production and neutrophil infiltration into the reperfused intestine, an improved histological status of the reperfused tissues, and an improved survival. Taken together, our results clearly demonstrate that GITR plays an important role in the ischemia and reperfusion injury and put forward the hypothesis that modulation of GITR expression may represent a novel and possible strategy.
2-Arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces the migration of EoL-1 human eosinophilic leukemia cells and human peripheral blood eosinophils
Authors: Oka Saori , Ikeda Shinobu , Kishimoto Seishi , Gokoh Maiko , Yanagimoto Shin , Waku Keizo , Sugiura Takayuki
Published: August 2004

2-Arachidonoylglycerol (2-AG) is an endogenous cannabinoid receptor ligand. To date, two types of cannabinoid receptors have been identified: the CB1 receptor, abundantly expressed in the brain, and the CB2 receptor, expressed in various lymphoid tissues such as the spleen. The CB1 receptor has been assumed to play an important role in the regulation of synaptic transmission, whereas the physiological roles of the CB2 receptor remain obscure. In this study, we examined whether the CB2 receptor is present in human eosinophils and found that the CB2 receptor is expressed in human peripheral blood eosinophils. In contrast, human neutrophils do not contain a significant amount of the CB2 receptor. We then examined the effect of 2-AG on the motility of eosinophils. We found that 2-AG induces the migration of human eosinophilic leukemia EoL-1 cells. The migration evoked by 2-AG was abolished in the presence of SR144528, a CB2 receptor antagonist, or by pretreatment of the cells with pertussis toxin, suggesting that the CB2 receptor and Gi/o are involved in the 2-AG-induced migration. The migration of EoL-1 cells induced by 2-AG was suggested to be a result of chemotaxis. In contrast to 2-AG, neither anandamide nor free arachidonic acid elicited the migration. Finally, we examined the effect of 2-AG on human peripheral blood eosinophils and neutrophils and found that 2-AG induces migration of eosinophils but not neutrophils. These results suggest that the CB2 receptor and its endogenous ligand 2-AG may be closely involved in allergic inflammation accompanied by the infiltration of eosinophils.
Scavenger receptor A mediates H2O2 production and suppression of IL-12 release in murine macrophages
Authors: Józefowski Szczepan , Kobzik Lester
Published: August 2004

Although class A type I/II scavenger receptor (SR-A) is involved in numerous macrophage functions, its signaling ability remains uncertain. We used monoclonal antibodies (mAb) to specifically stimulate receptors on mouse alveolar (AMs) and peritoneal macrophages (PMs). Immobilized anti-SR-A (2F8) and anti-FcγR II/III (2.4G2) mAb stimulated hydrogen peroxide (H2O2) production in normal C3H/HeJ AMs (by 55% and 98%, respectively) and resident PMs (66% and 128%). The 2F8 mAb-stimulated H2O2 production resulted from specific stimulation of SR-A, since this response was absent in AMs from SR-A-deficient or C57BL/6 mice—the latter strain expressing an allelic form of SR-A, unrecognizable by 2F8 mAb. H2O2 production stimulated by anti-SR-A but not by anti-FcγRII/III mAb was preserved in FcγRI/III-deficient mice, ruling out involvement of FcγRs in the 2F8 mAb effect. In comparison with the FcγR-stimulated respiratory burst, the response to anti-SR-A mAb was delayed and, unlike the former, inhibited by pertussis toxin. Ligation of SR-A also inhibited lipopolysaccharide plus interferon-γ-stimulated interleukin-12 (IL-12) release, by 25% in AMs and by 68% in thioglycollate-elicited PMs, consistent with different levels of SR-A expression. Neither nitrite nor IL-6 accumulation was affected by anti-SR-A mAb. SR-A-stimulated H2O2 does not seem to mediate the inhibition of IL-12 release, since the inhibition was neither reversed by scavenging of H2O2 nor mimicked by exogenous H2O2. Our results indicate that SR-A not only mediates endocytosis but can also generate signals such as H2O2, which may affect microbicidal or proinflammatory functions.
IL-4-induced macrophage-derived IGF-I protects myofibroblasts from apoptosis following growth factor withdrawal
Authors: Wynes Murry W , Frankel Stephen K , Riches David W H
Published: August 2004

The development of idiopathic pulmonary fibrosis (IPF) is associated with myofibroblast accumulation and collagen deposition in the lung parenchyma. Recent studies have suggested that the fibroproliferative response is associated with immune deviation toward a T helper cell type 2 (Th2) cytokine profile. In addition, myofibroblast accumulation may be the result of resistance to physiologic apoptosis. If and how these events are linked remain largely unknown. Insulin-like growth factor-I (IGF-I) is a fibroblast growth and survival factor that has long been implicated in the pathogenesis of IPF. We have previously shown that interstitial macrophage-derived IGF-I correlates with disease severity in IPF, and the Th2 cytokines interleukin (IL)-4 and IL-13 stimulate the expression and secretion of IGF-I by macrophages. In the present study, we tested the hypothesis that IL-4-induced, macrophage-derived IGF-I protects myofibroblasts from apoptosis. Using a growth factor withdrawal model of apoptosis in the myofibroblast cell line, CCL39, we demonstrate that conditioned media from IL-4-stimulated macrophages protect myofibroblasts from apoptosis. The survival effect is lost when IGF-I is immunodepleted from macrophage-conditioned media with IGF-I-specific antibodies. We also show that the protection of myofibroblasts by macrophage-derived IGF-I correlates with and is dependent on the activation of the prosurvival kinases Akt and extracellular signal-regulated kinase. These findings support the view that IL-4-stimulated, macrophage-derived IGF-I may contribute to the persistence of myofibroblasts in pulmonary fibrosis in the Th2-deviated environment of the fibrotic lung.
Macrophages from lupus-prone MRL mice are characterized by abnormalities in Rho activity, cytoskeletal organization, and adhesiveness to extracellular matrix proteins
Authors: Longacre Angelika , Koh Jason S , Hsiao Kevin K-H , Gilligan Hannah , Fan Hanli , Patel Vimal A , Levine Jerrold S
Published: August 2004

Macrophages (mφ) from prediseased mice of the major murine models of lupus have an identical defect in cytokine expression that is triggered by serum and/or apoptotic cells. It is striking that cytokine expression in the absence of serum and apoptotic cells is equivalent to that of nonautoimmune mice. Here, we show that mφ from prediseased lupus-prone MRL/MpJ (MRL/+) or MRL/MpJ-Tnfrsf6lpr (MRL/lpr) mice also have reversible abnormalities in morphology, cytoskeletal organization, and adhesive properties. In the presence of serum, MRL mφ adhered in increased numbers to a variety of extracellular matrix proteins compared with mφ from two nonautoimmune strains. However, in the absence of serum, adhesion by MRL mφ was similar to that of nonautoimmune mφ. Increased adhesion by MRL mφ was also observed in the presence of apoptotic, but not necrotic, cells. The morphology and actin-staining pattern of adherent MRL mφ were consistent with reduced activity of Rho, a cytoskeletal regulator. Indeed, MRL mφ cultured in the presence of serum had markedly decreased levels of active Rho compared with nonautoimmune mφ. It is remarkable that when cultured in the absence of serum, MRL mφ displayed normal Rho activity and cytoskeletal morphology. Addition of a Rho inhibitor to normal mφ reproduced the morphologic and cytoskeletal abnormalities observed in MRL mφ. Taken together, our findings support the hypothesis that mφ from MRL and other systemic lupus erythematosus-prone mice have an apoptotic, cell-dependent, autoimmune phenotype that affects a broad range of mφ functions, including cytokine gene expression and Rho-dependent cytoskeletal regulation.
Phosphatase inhibition potentiates IL-6 production by mast cells in response to FcɛRI-mediated activation: involvement of p38 MAPK
Authors: Boudreau Robert T M , Hoskin David W , Lin Tong-Jun
Published: August 2004

Mast cells are crucial effector cells in the immune response through mediator secretion and release of cytokines. A coordinated balance between protein kinases and phosphatases plays an essential role in the regulation of mast cell mediator secretion. We have previously shown that treatment of mast cells with okadaic acid (OA), a protein phosphatase 2A (PP2A) inhibitor, results in a dose-dependent increase in interleukin (IL)-6 production. We show here for the first time a synergism between OA and immunoglobulin E (IgE)-mediated IL-6 secretion by murine bone marrow-derived mast cells (BMMC). Selective p38 mitogen-activated protein kinase (p38 MAPK) inhibition reduces OA and IgE-mediated IL-6 production. Regulation of p38 MAPK by PP2A was demonstrated, as OA treatment caused a dose-dependent increase in p38 MAPK phosphorylation. Antigen-mediated activation of murine mast cells also resulted in an increase in p38 MAPK phosphorylation, which was potentiated by cotreatment of the cells with OA. Lastly, in two mast cell lines (human mast cell-1 5C6 and murine MC/9) and primary-cultured murine BMMC, we show by coimmunoprecipitation an interaction between p38 MAPK and PP2A. These data support a role for PP2A through interaction with p38 MAPK in the regulation of IgE-dependent mast cell activation.
Contribution of CD30/CD153 but not of CD27/CD70, CD134/OX40L, or CD137/4-1BBL to the optimal induction of protective immunity toMycobacterium avium
Authors: Flórido Manuela , Borges Margarida , Yagita Hideo , Appelberg Rui
Published: August 2004

A panel of monoclonal antibodies specific for CD27 ligand (CD70), CD30 ligand (CD153), CD134 ligand (OX40L), and CD137 ligand (4-1BBL) were screened in vivo for their ability to affect the control of Mycobacterium avium infection in C57Bl/6 mice. Only the blocking of CD153 led to increased mycobacterial burdens. We then used CD30-deficient mice and found an increase in the proliferation of two strains of M. avium in these mice as compared with control animals. The increased mycobacterial growth was associated with decreased T cell expansion and reduced interferon-γ (IFN-γ) responses as a result of reduced polarization of the antigen-specific, IFN-γ-producing T cells. At late times but not early in infection, the lymphoid cuff surrounding granulomas was depleted in the CD30-deficient animals. This report expands our knowledge about tumor necrosis factor superfamily members involved in the immune responses to mycobacterial infection by identifying CD30–CD153 interactions as required for optimal immune control of M. avium infection.
The bi-directional translocation of MARCKS between membrane and cytosol regulates integrin-mediated muscle cell spreading
Authors: Disatnik Marie-Hélène , Boutet Stéphane C. , Pacio Wilfred , Chan Annie Y. , Ross Lindsey B. , Lee Christine H. , Rando Thomas A.
Published: August 2004

The regulation of the cytoskeleton is critical to normal cell function during tissue morphogenesis. Cell-matrix interactions mediated by integrins regulate cytoskeletal dynamics, but the signaling cascades that control these processes remain largely unknown. Here we show that myristoylated alanine-rich C-kinase substrate (MARCKS) a specific substrate of protein kinase C (PKC), is regulated by α5β1 integrin-mediated activation of PKC and is critical to the regulation of actin stress fiber formation during muscle cell spreading. Using MARCKS mutants that are defective in membrane association or responsiveness to PKC-dependent phosphorylation, we demonstrate that the translocation of MARCKS from the membrane to the cytosol in a PKC-dependent manner permits the initial phases of cell adhesion. The dephosphorylation of MARCKS and its translocation back to the membrane permits the later stages of cell spreading during the polymerization and cross-linking of actin and the maturation of the cytoskeleton. All of these processes are directly dependent on the binding of α5β1 integrin to its extracellular matrix receptor, fibronectin. These results demonstrate a direct biochemical pathway linking α5β1 integrin signaling to cytoskeletal dynamics and involving bi-directional translocation of MARCKS during the dramatic changes in cellular morphology that occur during cell migration and tissue morphogenesis.
Globular domains 4/5 of the laminin α3 chain mediate deposition of precursor laminin 5
Authors: Sigle Randy O. , Gil Susana G. , Bhattacharya Mallar , Ryan Maureen C. , Yang Tai-Mei , Brown Tod A. , Boutaud Ariel , Miyashita Yuko , Olerud John , Carter William G.
Published: August 2004

In epidermal wounds, precursor laminin 5 (α3β3γ2) is deposited in the provisional basement membrane (PBM) before other BM components. Precursor laminin 5 contains G4/5 globular domains at the carboxyl terminus of the α3 chain. Here, the function of G4/5 was evaluated in deposition of laminin 5. Soluble laminin 5, secreted by keratinocytes in culture, is cleaved by an endogenous protease releasing G4/5. Thrombin, a serum protease, cleaves G4/5 indistinguishably from endogenous protease. Soluble human precursor laminin 5, but not cleaved laminin 5, was bound and deposited by mouse keratinocytes null for mouse α3 chain (α3–/– MKs). The deposition rescued adhesion and spreading and survival. In a model for PBM assembly, precursor laminin 5 was deposited along fibronectin fibrils at the junction between co-cultures of keratinocytes and fibroblasts. In both models, the deposition of precursor laminin 5 was inhibited by removal of G4/5 with thrombin. To confirm that G4/5 participates in deposition, the human LAMA3A gene was modified to produce α3 chains either without or with G4/5 that cannot be cleaved. Both precleaved and noncleavable α3 isoforms were expressed in α3–/– MKs, where they deposited sufficiently to rescue adhesion via integrins α3β1 and α6β4. Despite this similarity, noncleavable laminin 5 was at least threefold more efficiently deposited than precleaved isoform. We conclude that the G4/5 domain in the α3 chain facilitates deposition of precursor laminin 5 into the PBM in epidermal wounds.
Myosin Va is required for normal photoreceptor synaptic activity
Authors: Libby Richard T. , Lillo Concepcion , Kitamoto Junko , Williams David S. , Steel Karen P.
Published: August 2004

Myosin Va is an actin-based motor molecule, one of a large family of unconventional myosins. In humans, mutations in MYO5A cause Griscelli syndrome type 1 and Elejalde syndrome, diseases characterized by pigmentation defects and the prepubescent onset of severe neurological deficits that ultimately lead to a shortened lifespan. Mutations in the Myo5a gene in mouse cause the dilute series of mouse mutants, demonstrating that myosin Va is involved in pigmentation and neural function. Although the reason for the pigmentation abnormalities is well understood, the role of myosin Va in neural function is not. Myosin Va has been found in synaptic terminals in the retina and brain. We report here new physiological evidence for a role of myosin Va in synaptic function. Photoreceptor synapses in neurologically affected myosin Va mutant mice have both anatomical and physiological abnormalities. Thus, myosin Va is required for normal photoreceptor signalling, suggesting that it might function in central nervous system synapses in general, with aberrant synaptic activity potentially underlying the neurological defects observed in dilute lethal mice and patients with Griscelli syndrome type 1 and Elejalde syndrome.
Basolateral localisation of KCNQ1 potassium channels in MDCK cells: molecular identification of an N-terminal targeting motif
Authors: Jespersen Thomas , Rasmussen Hanne B. , Grunnet Morten , Jensen Henrik S. , Angelo Kamilla , Dupuis Delphine S. , Vogel Lotte K. , Jorgensen Nanna K. , Klaerke Dan A. , Olesen Søren-Peter
Published: August 2004

KCNQ1 potassium channels are expressed in many epithelial tissues as well as in the heart. In epithelia KCNQ1 channels play an important role in salt and water transport and the channel has been reported to be located apically in some cell types and basolaterally in others. Here we show that KCNQ1 channels are located basolaterally when expressed in polarised MDCK cells. The basolateral localisation of KCNQ1 is not affected by co-expression of any of the five KCNE β-subunits. We characterise two independent basolateral sorting signals present in the N-terminal tail of KCNQ1. Mutation of the tyrosine residue at position 51 resulted in a non-polarized steady-state distribution of the channel. The importance of tyrosine 51 in basolateral localisation was emphasized by the fact that a short peptide comprising this tyrosine was able to redirect the p75 neurotrophin receptor, an otherwise apically located protein, to the basolateral plasma membrane. Furthermore, a di-leucine-like motif at residues 38-40 (LEL) was found to affect the basolateral localisation of KCNQ1. Mutation of these two leucines resulted in a primarily intracellular localisation of the channel.
Distribution and functions of kinectin isoforms
Authors: Santama Niovi , Er Connie P. N. , Ong Lee-Lee , Yu Hanry
Published: August 2004

Kinectin is an integral transmembrane protein on the endoplasmic reticulum, binding to kinesin, interacting with Rho GTPase and anchoring the translation elongation factor-1 complex. There has been debate on the specific role(s) of kinectin in different species and cell types. Here we identified 15 novel kinectin isoforms in the mouse nervous system, constituting a family of alternatively spliced carboxyl-terminal variants. Isoform expression is subject to cell type- and developmental stage-specific regulation. We raised specific antibodies to the kinectin variants to characterise their differential intracellular localisation and discovered that certain kinectin isoforms are found in axons where kinectin was previously believed to be absent. We also demonstrated in vivo by overexpression and RNA interference assay that kinectin is selectively involved in the transport of specific types of organelles. A 160 kDa kinectin species is mainly concentrated in the endoplasmic reticulum, anchored via its transmembrane domain and is essential for endoplasmic reticulum membrane extension. A 120 kDa kinectin species is specifically associated with mitochondria, and its interaction with kinesin was found to influence mitochondrial dynamics. These findings contribute to a more unified view of kinectin function. They suggest that different cellular processes use specific kinectin isoforms to mediate intracellular motility and targeting by transient interaction with different motor proteins or other binding partners.
Dynamic alterations of specific histone modifications during early murine development
Authors: Sarmento Olga F. , Digilio Laura C. , Wang Yanming , Perlin Julie , Herr John C. , Allis C. David , Coonrod Scott A.
Published: August 2004

In order to investigate whether covalent histone modifications may be involved in early embryonic reprogramming events, changes in global levels of a series of histone tail modifications were studied during oocyte maturation and pre-implantation mouse development using indirect immunofluorescence and scanning confocal microscopy. Results showed that histone modifications could be classified into two strikingly distinct categories. The first contains stable `epigenetic' marks such as histone H3 lysine 9 methylation [Me(Lys9)H3], histone H3 lysine 4 methylation [Me(Lys4)H3] and histone H4/H2A serine 1 phosphorylation [Ph(Ser1)H4/H2A]. The second group contains dynamic and reversible marks and includes hyperacetylated histone H4, histone H3 arginine 17 methylation [Me(Arg17)H3] and histone H4 arginine 3 methylation [Me(Arg3)H4]). Our results also showed that removal of these marks in eggs and early embryos occurs during metaphase suggesting that the enzymes responsible for the loss of these modifications are probably cytoplasmic in nature. Finally, we provide data demonstrating that treatment of cellular histones with peptidylarginine deiminase (PAD) results in loss of staining for the histone H4 arginine 3 methyl mark, suggesting that PADs can reverse histone arginine methyl modifications.
Patterns of flanking sequence conservation and a characteristic upstream motif for microRNA gene identification
Authors: OHLER UWE , YEKTA SORAYA , LIM LEE P. , BARTEL DAVID P. , BURGE CHRISTOPHER B.
Published: August 2004

MicroRNAs are ~22-nucleotide (nt) RNAs processed from foldback segments of endogenous transcripts. Some are known to play important gene regulatory roles during animal and plant development by pairing to the messages of protein-coding genes to direct the post-transcriptional repression of these messages. Previously, we developed a computational method called MiRscan, which scores features related to the foldbacks, and used this algorithm to identify new miRNA genes in the nematode Caenorhabditis elegans. In the present study, to identify sequences that might be involved in processing or transcriptional regulation of miRNAs, we aligned sequences upstream and downstream of orthologous nematode miRNA foldbacks. These alignments showed a pronounced peak in sequence conservation about 200 bp upstream of the miRNA foldback and revealed a highly significant sequence motif, with consensus CTCCGCCC, that is present upstream of almost all independently transcribed nematode miRNA genes. Scoring the pattern of upstream/downstream conservation, the occurrence of this sequence motif, and orthology of host genes for intronic miRNA candidates, yielded substantial improvements in the accuracy of MiRscan. Nine new C. elegans miRNA gene candidates were validated using a PCR-sequencing protocol. As previously seen for bacterial RNA genes, sequence features outside of the RNA secondary structure can therefore be very useful for the computational identification of eukaryotic noncoding RNA genes. The total number of confidently identified nematode miRNAs now approaches 100. The improved analysis supports our previous assertion that miRNA gene identification is nearing completion in C. elegans with apparently no more than 20 miRNA genes now remaining to be identified.
Crystal structure of archaeal ribonuclease P protein Ph1771p from Pyrococcus horikoshii OT3: An archaeal homolog of eukaryotic ribonuclease P protein Rpp29
Authors: NUMATA TOMOYUKI , ISHIMATSU IKUKO , KAKUTA YOSHIMITSU , TANAKA ISAO , KIMURA MAKOTO
Published: August 2004

Ribonuclease P (RNase P) is the endonuclease responsible for the removal of 5′ leader sequences from tRNA precursors. The crystal structure of an archaeal RNase P protein, Ph1771p (residues 36–127) from hyperthermophilic archaeon Pyrococcus horikoshii OT3 was determined at 2.0 Å resolution by X-ray crystallography. The structure is composed of four helices (α1–α4) and a six-stranded antiparallel β-sheet (β1–β6) with a protruding β-strand (β7) at the C-terminal region. The strand β7 forms an antiparallel β-sheet by interacting with strand β4 in a symmetry-related molecule, suggesting that strands β4 and β7 could be involved in protein-protein interactions with other RNase P proteins. Structural comparison showed that the β-barrel structure of Ph1771p has a topological resemblance to those of Staphylococcus aureus translational regulator Hfq and Haloarcula marismortui ribosomal protein L21E, suggesting that these RNA binding proteins have a common ancestor and then diverged to specifically bind to their cognate RNAs. The structure analysis as well as structural comparison suggested two possible RNA binding sites in Ph1771p, one being a concave surface formed by terminal α-helices (α1–α4) and β-strand β6, where positively charged residues are clustered. A second possible RNA binding site is at a loop region connecting strands β2 and β3, where conserved hydrophilic residues are exposed to the solvent and interact specifically with sulfate ion. These two potential sites for RNA binding are located in close proximity. The crystal structure of Ph1771p provides insight into the structure and function relationships of archaeal and eukaryotic RNase P.
5-HT3 Receptor Antagonists for Prevention of Late Acute-Onset Emesis
Authors: Constenla Manuel
Published: August 2004

OBJECTIVE

To review the currently available literature on the efficacy of the 5–HT3 receptor antagonists in the prevention of late acute-onset chemotherapy-induced nausea and vomiting (12–24 h after cytotoxic treatment).

DATA SOURCES

Primary articles were identified by PubMed search (performed in March 2004) and through secondary sources. Search terms included granisetron, ondansetron, tropisetron, dolasetron, acute, chemotherapy, nausea, and vomiting (a further search was performed for palonosetron in March 2004).

STUDY SELECTION AND DATA EXTRACTION

All studies that performed regular assessments (every 2–6 h) of antiemetic control over the first 24 hours with 5–HT3 receptor antagonists were evaluated.

DATA SYNTHESIS

Current guidelines recommend the use of 5–HT3 receptor antagonists for the control of chemotherapy-induced nausea and vomiting but do not differentiate between the available agents. However, there is variability in the pharmacokinetic and pharmacodynamic profiles of these agents, and this has implications for dosing regimen, safety, efficacy, and potential drug—drug interactions. Cytotoxic agents vary in the time profile of their emetic effect; this must be considered when choosing an appropriate 5–HT3 receptor antagonist. The optimal agent should be simple to administer and provide safe and effective antiemetic protection over the whole 24–hour period.

CONCLUSIONS

The differences between the 5-HT3 receptor antagonists have important consequences for their dosing and efficacy in the control of late acute-onset chemotherapy-induced nausea and vomiting.
Treatment of Migraine Headaches with Sumatriptan in Pregnancy
Authors: Hilaire Michelle L , Cross L Brian , Eichner Samantha F
Published: August 2004

OBJECTIVE

To review the literature for treatment of migraine headaches with sumatriptan during pregnancy.

DATA SOURCES

Studies and reports were located in International Pharmaceutical Abstracts (1970-September 2003) and MEDLINE (1966-week 3 September 2003).

DATA SYNTHESIS

Research has been performed to evaluate the risk of teratogenesis after sumatriptan exposure in pregnant patients. Data have been collected in areas including placental transmission of sumatriptan, prospective pregnancy registries, open-labeled and controlled prospective studies, and a retrospective prescription-linked study. As of August 6, 2004, no randomized controlled trials have been conducted with exposure to sumatriptan during pregnancy.

CONCLUSIONS

Teratogenesis occurs in approximately 150 000 births per year which represents an incidence of 3–5%. Available literature to date indicates that exposure to sumatriptan during pregnancy has no additional risk of birth defects compared with the incidence in the general population.
Seeing things differently: The viewing time alternative to penile plethysmography
Authors: Laws D. Richard , Gress Carmen L.Z.
Published: August 2004

This paper describes the use of viewing time (VT), how long a subject looks at a probable sexual stimulus, as an alternative to penile plethysmography (PPG). We then trace the history of VT to assess sexual interest from 1942 to the present. The first computer‐generated stimulus set for PPG was developed by Canadian researchers. This set was tested using VT by the second author and found valid. The unavailability of the set for further use resulted in the authors developing a new, computermodified set with an alternate form version. This required the modification and compositing of images of real people. The proposed research using this set is described. To avoid using real photographic imagery in the future we propose use of specialized computer software that permits development of images from scratch. VT is a limited technology and we close with descriptions of new ways to assess sexual interest and behaviour using virtual reality and virtual environments.
Motivating offenders to change in therapy: An organizing framework
Authors: McMurran Mary , Ward Tony
Published: August 2004

Objectives. Motivating offenders to change in therapy is an important aspect of effective offender treatment, yet despite this, offenders' motivation to change has received little close attention in the academic and professional literature. This situation is a result of an over‐emphasis on the risk management model of rehabilitation, and a consequent failure to construe motivation within an overarching theory of offender rehabilitation.

Method. We present a social cognitive model of offender motivation — the Good Lives Model (GLM) — that provides a framework for incorporating factors that have been shown to be of importance in enhancing offender motivation. This is based upon the notion that all humans strive to achieve primary goods that are intrinsically rewarding and essential to well‐being. Where offenders are concerned, criminogenic problems relate, not to the goods offenders seek, but to the way they seek them. Any treatment approach should take this into account and focus positively on equipping people with the skills required to achieve goals rather than simply look to manage risk. The motivational construct that we use here is that of goals. In the GLM, goals are the less abstract depictions of primary human goods and it is with these that people are typically engaged in their day‐to‐day activities and lives. Looking at therapeutic goal‐setting, methods and styles of therapy, and therapist approaches, we derive theoretically‐based key issues in motivating offenders to change in therapy.

Conclusion. In conclusion, we present a summary of 12 strategies and techniques that will not only help practitioners enhance their therapeutic effectiveness, but hopefully also act as a catalyst in the development of research on offenders' motivation to change.
The use of the Psychological Inventory of Criminal Thinking Styles with English young offenders
Authors: Palmer Emma J. , Hollin Clive R.
Published: August 2004

Objectives. This study examines the psychometric properties of the Psychological Inventory of Criminal Thinking Styles (PICTS) with a sample of imprisoned English young offenders.

Method. The reliability and validity of the PICTS scales were investigated, and changes in scores on the PICTS scales over a 6‐month period were analysed.

Results. The findings suggested that from a psychometric perspective the PICTS scales were not performing as well with young offenders as with adult prisoner samples. The indices of reliability and validity were of a moderate level. Test‐retest scores calculated over the 6 months showed little change on the PICTS scores.

Conclusion. The use of the PICTS scales with young offenders is discussed with reference to previous research with adult offenders in England and North America.
Do court‐ and self‐referred domestic violence offenders share the same characteristics? A preliminary comparison of motivation to change, locus of control and anger
Authors: Bowen Erica , Gilchrist Elizabeth
Published: August 2004

Objectives. The purpose of this research was to assess whether court‐ and self‐referred domestic violence offenders differ on levels of motivation to change, personal control and anger, and hence whether these two offender groups are distinct.

Method. Thirty‐eight court‐referred and 14 self‐referred male domestic violence offenders completed three scales: URICA‐DV, Levenson Locus of Control and Novaco Anger Scale.

Results. It was found that self‐referred men exhibited significantly higher levels of motivation to change, internal locus of control and anger in response to anger‐provoking situations than did court‐referred men.

Conclusions. The results indicate that there may be fundamental differences between these two offender groups and question the suitability of combining these groups in offender treatment. Results are discussed in the context of treatment efficacy and outcome.
Minimizing extraneous, interviewer‐based interrogative suggestibility
Authors: Boon Julian C.W. , Baxter James S.
Published: August 2004

Objectives. Previous work has established that interviewer demeanour can distort interviewee performance on the Gudjonsson Suggestibility Scales (GSS). The present study assesses the effect of reducing interpersonal interaction in the GSS procedure. Interviewees' interrogative suggestibility (IS) scores obtained under four conditions were compared with established norms for the scales to identify the method most likely to reduce the effects of interpersonal factors when using the scales.

Method. Participants were allocated at random to one of four conditions: (1) standard procedure but with questions in writing (Written Questions), (2) condition 1 procedure plus written answer (Written Questions: Written Answers), (3) condition 1 procedure but with written negative feedback (Written Questions: Written Feedback), and finally (4) condition 2 procedure but with written negative feedback (Written Questions: Written Answers: Written Feedback).

Results. A key finding was that the procedure used in condition 4, in which verbal contact between interviewer and interviewee was least, produced GSS scores most closely approximating established norms for the GSS. GSS scores were higher in the other groups, although the differences between the GSS scores of conditions 4 and 2 were not significant.

Conclusion. The findings suggest ways in which the effects of interviewer demeanour on IS may be reduced. The potential usefulness of adopting new procedures for administering the GSSs is discussed, as is the potential for developing a computerized format for the GSSs.
An Interdependency Model for Police Executive Relationships
Authors: Pitman Grant
Published: August 2004

The history of Australian policing is replete with conflicts between police ministers and police commissioners. These conflicts, it is argued, can be attributed to two diametrically opposed relationship models — ‘dependency’ and ‘independency’. This paper contrasts a ‘dependency’ model that gives the minister overall control of policing, with a model of ‘independency’ that reflects the operational independence of the commissioner. Interwoven aspects of these two notions often become part of the general machinery of government. This article argues that the inherent conflict between ministers and commissioners can be overcome by the application of an ‘interdependency’ relationship model which clarifies positional roles, acknowledges the complexities of the policing mandate, and facilitates agreement between the parties on how to achieve balance between law enforcement and the maintenance of public order.
What Do We Think? Investigating the Attitudes and Life Goals of Young Offenders
Authors: Shears Gemma
Published: August 2004

This study investigates whether life goals and attitudes differ between young offenders, those deemed at risk of turning to offending behaviour, and non-offenders. The article questions (as Matza does in his delinquency and drift theory (Brown, 1998, p. 24)) the notion that the delinquent can meaningfully be distinguished from the non-delinquent. By seeking to understand the various life goals and attitudes held by young offenders, particularly with regard to crime and delinquency, this study sought to investigate ‘the effect[s] of offending behaviour programmes in influencing those attitudes' (Youth Justice Board Review, 2000/01, p. 4).

Findings from the present study mirrored those of Carroll, Hattie, Durkin, and Houghton (1997) in which differences between the three groups were noted in terms of the life goals to which the members ascribed. Particular support is lent to Carroll et al.'s findings that delinquent young people attach more importance to delinquency and freedom autonomy goals, goals associated with achieving a social image, whilst non-offenders attach more importance to educational and interpersonal goals, goals associated with achieving an academic image (Carroll, Houghton, & Baglioni, 2000; Carroll, Baglioni, Houghton, & Bramston, 1999; Carroll et al., 1997).

Findings from the second stage of the study were limited as acknowledgement was made of the difficulties of relating any attitudinal and life goal changes to the specific programmes alone. In the view of this author future studies would benefit from the adoption of a longitudinal approach, including the use of life histories to provide a continual in-depth analysis of the life goals ascribed to by young offenders.
Predicting Burglar Characteristics from Crime Scene Behaviour
Authors: Santtila Pekka , Ritvanen Antti , Mokros Andreas
Published: August 2004

The aim of the present study was to predict offender characteristics on the basis of crime scene behaviour in urban burglaries. The police files of 633 burglaries in the Finnish Metropolitan Area between 1990 and 2001 were content analysed using a predetermined list of variables. The crime scene behaviour variables were subjected to a principal component analysis. Fourteen factors indicative of different types of burglaries were identified and used to predict the characteristics of the 244 offenders using regression models. Statistically significant predictors of almost all offender characteristics were identified. From a practical point of view, the predictive models could be used in police investigations to narrow down the number of suspects.
Gender Discrimination and Regulatory Behaviour: An Exploratory Study in Policing
Authors: Prenzler Tim
Published: August 2004

This paper examines the relationship between police departments and equity agencies in Australia. Previous research has shown marked differences in the performance of police in fulfilling the requirements of equity legislation. Responsibility for ensuring compliance with antidiscrimination and affirmative action legislation rests with equity agencies — which ‘police the police’. The paper reports the results from a survey of these agencies to obtain their accounts of factors facilitating or hindering police compliance. These factors are framed in terms of agency powers, resources, regulatory strategies and police responses. The study found that regulatory agencies were highly detached from police departments and that differences in compliance were largely the result of factors independent of regulatory action. A ‘culture of under-enforcement’ remained as the most likely explanation for regulatory failure. The paper concludes by emphasising the need for more active monitoring and a more confrontational approach to under-achieving departments.
Police Recording of Theft in a Prefecture in Greece: A Research Note
Authors: Antonopoulos Georgios A.
Published: August 2004

The ‘dark figure’ of crime is a key aspect in understanding crime rates, as it constitutes an obstacle in validating the quantification of criminality. Theft, although it is significant in terms of perceived personal victimisation, may be trivial in terms of financial cost in many instances, and it is thought to have a big ‘dark figure’. The purpose of this research note is to provide some information about the police recording of theft, one of the factors that influence the construction of its ‘dark figure’, in a prefecture in Greece.