bluuebunny/crossref_metadata_2025 huggingface dataset:
Is early intervention for psychosis a waste of valuable resources?
Authors: Pelosi Anthony J. , Birchwood Max
Published: February 2003

The concept of early intervention for psychosis has received much attention in recent years. The experience of pioneer services in the USA and Australia has convinced the UK Government to set aside millions of pounds to make dedicated early intervention teams an integral part of standard mental health services across the country. Other governments are set to follow suit. The rationale for early intervention is that there is a higher success rate if psychotic symptoms are treated early than if they are treated after they have been present for some time. It is also claimed that interventions early in the course of the illness can decrease the psychosocial impact of a psychotic illness that leads to secondary disability. But have these assertions been empirically demonstrated? Do such services simply take valuable resources, both in terms of funding and staff, from an already-overstretched mental health system, or do they change the trajectory of the disease process in a fundamental way? Dr Max Birchwood, Director of the Birmingham Early Intervention Service, and Dr Anthony Pelosi, consultant psychiatrist with a ‘generic’ community service in East Kilbride, Scotland, debate this issue.
Use of cognitive therapy for relapse prevention in chronic depression
Authors: Scott Jan , Palmer Stephen , Paykel Eugene , Teasdale John , Hayhurst Hazel
Published: February 2003

Background

There is a lack of data on the cost-effectiveness of relapse prevention in depression.

Method

A total of 158 subjects with partially remitted major depression despite adequate clinical treatment were randomly allocated to cognitive therapy in addition to antidepressants and clinical management v. antidepressants and clinical management alone. Relapse rates and health care resource utilisation were measured prospectively over 17 months.

Results

Cumulative relapse rates in the cognitive therapy group were significantly lower than in the control group (29%v.47%). The incremental cost incurred in subjects receiving cognitive therapy over 17 months (£779; 95% CI £387–£1170) was significantly lower than the overall mean costs of cognitive therapy (£1164; 95% CI £1084–£1244). The incremental cost-effectiveness ratio ranged from £4328 to £5027 per additional relapse prevented.

Conclusions

In individuals with depressive symptoms that are resistant to standard treatment, adjunctive cognitive therapy is more costly but more effective than intensive clinical treatment alone.
Disintegration of the components of language as the path to a revision of Bleuler's and Schneider's concepts of schizophrenia
Authors: Ceccherini-Nelli Alfonso , Crow Timothy J.
Published: February 2003

Background

The 20th century ended without a resolution of the debate about the supremacy of Schneider's psychopathological conceptualisation of schizophrenia (the first-rank symptoms) over Bleuler's ‘four As' (disorders of association and affect, ambivalence and autism).

Aims

To examine the relationships between linguistic deviations and symptoms in patients with acute psychosis.

Method

We assessed language disturbances and first-rank symptoms with the Clinical Language Disorder Rating Scale (CLANG) in 30 consecutive patients with acute psychosis, selected for the presence of at least one active first-rank symptom, and 15 control participants with depression but no psychotic symptoms.

Results

Strong positive correlations were found between the CLANG factor ‘poverty’ (of speech) and first-rank delusions of control and (‘delusional perceptions’) between semantic/phonemic paraphasias and verbal auditory hallucinations. Language disturbances were superior to nuclear symptoms in discriminating ICD–10 schizophrenia from other psychoses.

Conclusions

Evaluating the features of psychosis as deviations in the cerebral organisation of language paves the way to a concept of psychosis that supersedes these traditional but competing categorical concepts.
Care needs of elderly people with schizophrenia
Authors: Mcnulty Seamus V. , Duncan Laing , Semple Margaret , Jackson Graham A. , Pelosi Anthony J.
Published: February 2003

Background

Little is known of the needs of elderly patients with psychotic illnesses.

Aims

To measure the care needs of an epidemiologically based group of patients over the age of 65 years suffering from psychotic illness, using a standardised assessment.

Method

All patients aged 65 years and over with a diagnosis of schizophrenia and related disorders from a defined catchment area were identified. Their health and social care needs were investigated using the Cardinal Needs Schedule.

Results

The 1-year prevalence of schizophrenia and related disorders was 4.44 per 1000 of the population at risk. There were high levels of unmet need for many patients, including those in National Health Service (NHS) continuing-care beds.

Conclusions

Many needs were identified, all of which could be addressed using the existing skills of local health and social care professionals. The investigation raises serious concerns about standards of hospital and community care for elderly patients with schizophrenia. The findings may be unique, reflecting long-standing problems within a particularly hard-pressed part of the NHS. However, it is not known whether a similar situation exists in other parts of the UK.
Assertive community treatment across the Atlantic: comparison of model fidelity in the UK and USA
Authors: Fiander Matthew , Burns Tom , Mchugo Gregory J. , Drake Robert E.
Published: February 2003

Background

The significant reductions in hospital admission demonstrated in US assertive community treatment (ACT) studies have not been replicated in the UK. Explanations cite poor UK ‘model fidelity’ and/or better UK standard care. No international model-fidelity comparisons exist.

Aims

To compare high-fidelity US ACT teams with a UK team.

Method

The UK700's ACT team (n=97) was compared with high-fidelity US ACT teams (n=73) by using two measures: a forerunner of the Dartmouth Assertive Community Treatment schedule (to assess adherence to ACT principles) and 2-year prospective activity data.

Results

The UK and US teams had similar high-fidelity scores. Although significant differences were found in the amount and type of activity, practice differences in areas central to ACT were not great.

Conclusions

The failure of UK ACT studies to demonstrate the outcome differences of early US studies cannot be attributed entirely to the lack of ACT fidelity.
Electroconvulsive therapy in Hong Kong
Authors: Chung K.-F. , Ng Y.-K. , Yiu G.-C. , Cheung H.-K.
Published: February 2003

Aims and Method

We conducted the first systematic territory-wide survey of electroconvulsive therapy (ECT) practice and utilisation in Hong Kong. All public ECT services were evaluated with a postal questionnaire, a visit and observations of ECT administration. All private ECT practitioners were surveyed using a postal questionnaire.

Results

Most practice areas at the public ECT services in Hong Kong complied with College guidelines. However, a few private practitioners were still using outdated ECT machines. The number of ECT courses completed in 1998 was 0.34 per 10 000 population, which was much lower than the rate of ECT use in Western countries.

Clinical Implications

We obtained basic information on ECT services in Hong Kong and on areas requiring immediate attention.
Experience of thioridazine use before and after the Committee on Safety of Medicines warning
Authors: Matthews Tim , Weston Sian Nersy
Published: February 2003

Aims and Method

To describe the use of thioridazine in a population of adults with learning disabilities at the time of the warning issued by the Committee on Safety of Medicines (CSM). Also, to observe the result of discontinuation of thioridazine and to examine factors that were associated with adverse events. Retrospective case note analysis was carried out for a sample of individuals with a learning disability.

Results

Over 50% of those on regular thioridazine experienced adverse events during or following drug withdrawal. Adverse events were significantly associated with the duration of previous thioridazine prescription. Higher drug dosage and a more severe degree of learning disability may also be factors linked to poorer outcomes.

Clinical Implications

More caution may be required when reducing or withdrawing antipsychotic medication in this patient group.
A survey of liaison psychiatry services in the south-west of England
Authors: Howe Alison , Hendry Julie , Potokar John
Published: February 2003

Aims and Method

A postal survey was conducted to establish an overview of liaison psychiatry services in the south-west of England. Questionnaires were sent to all clinical directors of medicine, accident and emergency, and mental health in trusts which provide acute medical services.

Results

Thirty-six questionnaires were returned (77%), covering 17 out of 18 trusts providing acute services. Five trusts (28%) have a comprehensive dedicated liaison psychiatry service. A further six trusts (33%) have a service for deliberate self-harm only. Many respondents were critical of what they perceived to be an inadequate service. Five trusts had introduced a service in the 12 months preceding the survey.

Clinical Implications

An unmet need for liaison psychiatry services is clearly perceived across the south-west of England.
Drug misuse in pregnancy: the impact of a specialist treatment service
Authors: Day Ed , Porter Lyn , Clarke Alyson , Allen Debbie , Moselhy Hamdy , Copello Alex
Published: February 2003

Aims and Method

The use of illegal drugs is becoming increasingly common and presents particular problems in pregnancy. There is strong evidence to suggest that improvements in obstetric and neonatal outcomes can be made by attempts to treat the substance misuse problem, although this group may have limited engagement with traditional medical services. We conducted a retrospective case note review of a specialist ‘mother and baby team’ within a drug misuse treatment service to determine whether it had achieved its original service aims.

Results

There was a high level of engagement with the service, with the majority of cases staying in contact for over 20 weeks. The average dose of methadone fell during the course of the pregnancies, and at the time of delivery, only 20 of the 80 cases (25%) still in contact with the service had urine tests that were positive for heroin. A significant number of women managed to completely detoxify from all drugs by the point of delivery, in contrast with previous studies conducted with this patient population.

Clinical Implications

This study demonstrates that the specialist service for pregnant drug users has been effective in engaging those misusing drugs in treatment, leading to significant improvements in key outcome measures.
Transient behaviour of an electrically heated catalytic converter on a motorcycle engine in cold start conditions
Authors: Horng R-F , Chou H-M
Published: February 2003

An experimental investigation on the cold-start idle condition of an electrically heated catalytic converter on a four-stroke engine has been carried out. The preheated temperature of the catalytic converter and the level of CO emission of the catalyst were studied, and other measured quantities included the exhaust gas temperatures at the mid-section and at the outlet of the catalytic converter and the concentration of CO. The preheated temperatures of the catalytic converter were varied from raw temperature (non-preheating) to 100, 140 and 180 °C. The levels of CO emissions were set at 1.0, 1.5 and 2.0 per cent. The catalyst was tested with and without heat-storing material around the heater. The experimental results revealed that the catalytic converter with a preheated temperature of 180 °C triggered an early catalytic reaction. A high-level CO setting has the same effect, with the optimum value at approximately 2.0 per cent.
On-board conversion of alcohols to ethers for fumigation in compression ignition engines
Authors: Armbruster H , Stucki S , Olsson E , Gjirja S
Published: February 2003

Fumigation of dimethyl ether (DME) is an interesting option for using methanol as a fuel in compression ignition engines. In this concept, a fraction of the methanol used as a fuel is catalytically converted on-board to DME and water, and the products of the conversion are introduced into the engine via the combustion air. With an optimized engine the performance as well as emissions are comparable with those obtained when running the engine on alcohol with polyethylene glycol as ignition improver. The methanol conversion has been tested with different catalysts under various conditions. Because of its superior thermal stability and the low costs, γ-Al2O3 has been selected as the most promising catalyst for converting methanol to DME in suffcient rates for an on-board application. The chemical kinetics and the mass transfer limitations of the γ-Al2O3 catalyst used for the methanol dehydration were evaluated. The rate-determining step of the catalytic reaction is found to be the reaction of adsorbed intermediates (the Langmuir-Hinshelwood mechanism); mass transfer is limited by Knudsen diffusivity. The kinetic data were used to design a catalytic converter for fuel processing on-board. Providing DME for fumigation in a 180 kW engine will require approximately 0.7 kg of catalyst. The compact catalyst is necessary for an effcient and fast start-up of the process. The transient behaviour (cold/warm start-up; load changes) of a fixed-bed reactor with γ-Al2O3 has been estimated using simplified models, which show that the cold start problem should be manageable in less than 1 min. With the hot gas of a methanol burner in front of the fixed bed or a bifunctional catalyst, the catalyst bed can be heated to 250 °C and the reaction of methanol to DME started within 25 s. This is an acceptable time for cold-starting an engine in heavy-duty vehicles.
Pretreatment Effects on the Catalytic Activity of Jordanian Bentonite
Authors: Mahmoud Sabri , Hammoudeh Ayman , Al-Noaimi Mousa
Published: February 2003

De-tert-butylation of 2-tert-butylphenol was carried out over thermally-treated and acid-treated Jordanian bentonite clay samples. This reaction was found to follow first-order kinetics for all clay samples with different pretreatment procedures. The apparent rate constant, k, was also determined, and found to depend on the pretreatment. Thermal pretreatment at temperatures up to 250°C has an enhancing effect on surface acid sites. The total surface acidity (Ho <4.8) and the concentration of strong acid sites peaked at 250°C. Also, as a result, the maximum catalyst activity was obtained with samples treated at this temperature. Acid pretreatment with 0.10 M HCl, 1.0 M H2SO4 or 1.0 M H3PO4, followed by thermal treatment at 250°C produced the best enhancement effect on the surface acidity and catalytic activity.
Wettability of Montmorillonite Clays in Humic Acid Solutions
Authors: de López-Durán Juan Dios García , Khaldoun Asmae , Kerkeb Mohamed Larbi , Ramos-Tejada María del Mar , González-Caballero Fernando
Published: February 2003

The effect of humic acid (HA) adsorption on the hydrophilicity of two different montmorillonite samples (Na-montmorillonite, NaMt, and a Na-fluorinated Na-montmorillonite, FNaMt, or ‘Rassoul’) was investigated. The changes in the wettability of clays were discussed in terms of the non-electrostatic free energy of interaction between the clay particles immersed in aqueous humic acid solutions (ΔG121), using the van Oss-Chaudhury-Good (vOCG) model. The surface free energy components (both non-polar or Lifshitz-van der Waals, and polar or acid-base) of clays were obtained from contact angle measurements, after adsorption of humic acid, at acid or basic pH, in 10−2 M NaCl solutions. It was found that: (1) at acid pH, a progressive decrease in the hydrophilic character of both clays was observed when the humic acid concentration was increased; (2) at basic pH, the hydrophilic character of both samples studied increased with HA concentration; (3) the effect of humic acid adsorption on the wettability of model edge surfaces of the laminar montmorillonite particles was estimated from a parallel study on silica and alumina surfaces, and only a slight decrease in the hydrophilicity was observed, whatever the pH of the liquid media. The ζ potentials of both clays in the absence and presence of humic acid were determined and the linkage between ζ potential and the electron-donor character of the materials is discussed.
Biogeochemical and Environmental Factors in Fe Biomineralization: Magnetite and Siderite Formation
Authors: Roh Y. , Zhang C.-L. , Vali H. , Lauf R. J. , Zhou J. , Phelps T. J.
Published: February 2003

The formation of siderite and magnetite by Fe(III)-reducing bacteria may play an important role in C and Fe geochemistry in subsurface and ocean sediments. The objective of this study was to identify environmental factors that control the formation of siderite (FeCO3) and magnetite (Fe3O4) by Fe(III)-reducing bacteria. Psychrotolerant (<20°C), mesophilic (20–35°C) and thermophilic (>45°C) Fe(III)-reducing bacteria were used to examine the reduction of a poorly crystalline iron oxide, akaganeite (β-FeOOH), without a soluble electron shuttle, anthraquinone disulfuonate (AQDS), in the presence of N2, N2-CO2(80:20, V:V), H2 and H2-CO2 (80:20, V:V) headspace gases as well as in
-buffered medium (30–210 mM) under a N2 atmosphere. Iron biomineralization was also examined under different growth conditions such as salinity, pH, incubation time, incubation temperature and electron donors. Magnetite formation was dominant under a N2 and a H2 atmosphere. Siderite formation was dominant under a H2-CO2 atmosphere. A mixture of magnetite and siderite was formed in the presence of a N2-CO2 headspace. Akaganeite was reduced and transformed to siderite and magnetite in a
-buffered medium (>120 mM) with lactate as an electron donor in the presence of a N2 atmosphere. Biogeochemical and environmental factors controlling the phases of the secondary mineral suite include medium pH, salinity, electron donors, atmospheric composition and incubation time. These results indicate that microbial Fe(III) reduction may play an important role in Fe and C biogeochemistry as well as C sequestration in natural environments.
Characterization and a Fast Method for Synthesis of Sub-Micron Lithiophorite
Authors: Yang Deng-Shiu , Wang Ming-Kuang
Published: February 2003

Lithiophorite is a naturally occurring phyllomanganate which has been identified in soils and ores. Studies on a synthetic version have shed light on the conditions required for the formation of lithiophorite. In this study, we successfully prepared lithiophorite under highly alkaline conditions. In addition, we found that Li+, Al3+ and hydrothermal treatment are all necessary for the formation of lithiophorite. Lithiophorite, birnessite and Li-intercalated gibbsite were examined by infrared (IR) spectroscopy. The Mn oxide sheets of lithiophorite and birnessite were found to have quite similar structural environments. On the other hand, the LiAl2(OH)6 sheets are affected more markedly by the Mn oxide sheets. After intercalation, the symmetry of the six interlayer OH groups of LiAl2(OH)6 is reduced and they are divided into two groups occupying different sites, corresponding to the IR absorption bands at 3480 and 3312 cm−1, respectively.
The effect of contextual cues on children's ability to remember an occurrence of a repeated event
Authors: Pearse Sarah L. , Powell Martine B. , Thomson Donald M.
Published: February 2003

Purpose. This study examined the usefulness of contextual cues in enhancing the accuracy of children's narrative accounts of an occurrence of a repeated event.

Method. Children aged 6 to 7 years took part in the same staged event four times whereby 16 target details varied in each occurrence (e.g. the colour of a cloak varied each time). Three days later, the children's free recall of the final occurrence was elicited. This occurrence was identified in one of two ways. Either it was identified via the temporal term ‘last’, or else the term ‘last’ was combined with a feature related to the environmental context or setting that was unique to the occurrence (i.e., the interviewer referred to a new object that was worn throughout the occurrence or a new person who carried out the event). For each condition, performance was compared to that of children who experienced the event only once.

Results. Children's memory of details specific to the target occurrence was better after the single than the repeated event. However for both event types, children who were given the contextual and temporal cue performed better than those who were given the temporal cue only. The benefit of using a contextual cue did not result in an increase in errors.

Conclusion. Contextual cues (generated by an interviewer) can facilitate children's recall of an occurrence of an event. However, further research needs to determine whether this finding would generalize to a more practical situation where the child (rather than the interviewer) generates the cues.
Effective interventions for acquisitive offenders: An investigation of cognitive skills programmes
Authors: Wilson Sally , Attrill Gill , Nugent Francis
Published: February 2003

Purpose. Previous research has suggested that cognitive skills programmes completed by offenders may be more effective in reducing reconviction with nonacquisitive than acquisitive offenders. This study investigates whether a similar pattern is present with offenders who have completed accredited cognitive skills programmes in prisons in England and Wales.

Method. Questionnaires measuring the cognitive deficits targeted by the programmes were administered to 8,303 offenders participating in cognitive skills programmes while in custody. A checklist on the individuals' behaviour was also completed for each participant. The questionnaires and the behaviour checklist were completed before, after, and at 8 weeks after the end of the course. Participants were assigned to one of three groups dependent upon the number of convictions they had received for acquisitive offences; non‐acquisitive, medium acquisitive and high acquisitive.

Results. Offenders in the high acquisitive group showed greater need in the cognitive deficits at the pre‐course stage than the other two groups, for both the self‐completion questionnaires and the behaviour checklist. A comparison of preand post‐course scores on the questionnaires and the behaviour checklist showed positive effect sizes for all three groups. Some of the variables showed a greater change from pre‐ to post‐course in the groups that had been convicted of more acquisitive offences.

Conclusion. Cognitive skills programmes appear to be as effective with offenders convicted of acquisitive crime as non‐acquisitive crime, although highly acquisitive offenders may benefit from an additional intervention. Further studies are needed to investigate whether this same result is upheld when the outcome measure is reconviction.
Variability of lichen diversity in a climatically heterogeneous area (Liguria, NW Italy)
Authors: Brunialti Giorgio , Giordani Paolo
Published: February 2003

The influence of environmental variables on epiphytic lichens in Liguria (NW Italy) was examined using two complementary approaches. Firstly, the variability of lichen vegetation in relation to environmental variables was investigated. Secondly, the variability of Lichen Biodiversity (LB) counts, used in biomonitoring studies, was analysed in relation to bioclimatic areas. Geomorphology strongly affects lichen vegetation. The coastal mountain ridge and the Tyrrhenian-Po valley watershed limit the distribution range of three different communities: a Parmelion community with a high frequency of coastal suboceanic species, a Parmelion community rich in oak wood species and the Pannelietum acetabuli association, situated beyond the Po Valley watershed. Substantial differences in the distribution of lichen communities related to a climatic gradient (from humid Mediterranean to dry sub-Mediterranean regions) are not matched by corresponding statistically significant differences in LB counts. More accurate studies are necessary to define homogeneous bioclimatic areas, in which LB values can be compared for biomonitoring purposes.
Takhtajan's floristic regions and foliicolous lichen biogeography: a compatibility analysis
Authors: Lücking Robert
Published: February 2003

Takhtajan's floristic regions of the world, based on vascular plant distribution, were used for a comparative analysis of foliicolous lichen biogeography. Of the 35 regions distinguished by that author, 23 feature foliicolous lichens. The South-East African, Fijian, Polynesian and Hawaiian regions lack sufficient information and were excluded from further analysis. Using multi-dimensional scaling and cluster and cladistic analyses, the remaining 19 regions were grouped into six lichenogeographical regions: (1) Neotropics, (2) African Paleotropics (including Madagascar, Réunion and Seychelles), (3) Eastern Paleotropics (including North-East Australia and New Caledonia), (4) Valdivian region (temperate rainforest in southern South America), (5) Tethyan region (subtropical areas of Macaronesia, Mediterranean, and Western Irano-Turanian) and (6) Neozealandic-Tasmanian region (temperate rainforests of New Zealand and Tasmania). Affinities between these six large scale regions, with 57–77% shared species, are still stronger than those between the 35 smaller scale regions denned by Takhtajan [(20−)40–60(−75)% shared species]. Based on presence/absence within each of the six regions, 22 potential distribution patterns were defined for foliicolous lichens. Many species are widely distributed; 21% are cosmopolitan or pantropical, while 19% are disjunct on at least two continents, and only 60% are restricted to one of the three major tropical areas (nearly 100% in vascular plants). Most of the latter are found in the Neotropics, while the African Paleotropics are poor in endemics. Most genera deviate significantly from overall distribution patterns; for example, Strigula and Calopadia have higher proportions of widely distributed species, while Porina displays a concentration of Eastern Paleotropical endemics. Species diversity and composition of the six regions indicate that the three extra-tropical foliicolous lichen biotas (Valdivian, Tethyan, Neozealandic-Tasmanian) are the result of partly separate evolutionary histories. On the other hand, there is a strong affinity between the Neotropics and the African Paleotropics, suggesting a shared Western Gondwanan element in the foliicolous lichen biotas of these two regions.
The spontaneous polymerization of plasminogen activator inhibitor type‐2 and Z‐antitrypsin are due to different molecular aberrations
Authors: Wilczynska Malgorzata , Lobov Sergei , Ny Tor
Published: February 2003

The wild‐type form of plasminogen activator inhibitor type‐2 (PAI‐2) and the pathogenic Z‐mutant of α1‐antitrypsin (α1AT) are serpins that spontaneously polymerize by the loop–sheet mechanism. Compared to the consensus serpin sequence, both PAI‐2 and Z‐α1AT have deviations in the so‐called breach region located at the top of the A β‐sheet. In the case of Z‐α1AT, conformational perturbations caused by a single amino acid substitution result in polymerization in vivo and predisposes to disease. To test whether the polymerization of PAI‐2 is due to aberrations in the breach region, we constructed substitution mutants of PAI‐2 with conserved residues in this region. Analysis of the mutants revealed that deviations in the breach region modulate but are not the major cause of PAI‐2 polymerization. Rather, PAI‐2 exists in a highly polymerogenic conformation and does not require conformational rearrangements before polymerization can take place.
Binding and retention of polycationic peptides and dendrimers in the vascular wall
Authors: Sakharov D.V. , Jie A.F.H. , Filippov D.V. , Bekkers M.E.A. , van Boom J.H. , Rijken D.C.
Published: February 2003

Extracellular matrix (ECM) of tissues, vascular tissue in particular, contains a high concentration of negatively charged glycosaminoglycans (GAGs), which are involved in the regulation of cell motility, cell proliferation and the regulation of enzyme activities. Previously, we have shown that the vascular ECM is capable of binding an extremely high concentration of positively charged molecules, such as polylysine. Vascular ECM can be used therefore as a substrate for binding and retention of drugs delivered intravascularly, if these drugs are endowed with an ability to bind to the vascular ECM. In this study, we evaluated a number of positively charged molecules as potential affinity vehicles for delivery of drugs to the vascular ECM. We labelled the molecules of interest with fluorescence and compared them ex vivo in terms of binding and retention in the de‐endothelialised rat carotid artery after intravascular delivery under pressure. High molecular weight polylysine (84 kDa) and polyamidoamine (PAMAM) dendrimers accumulated in the wall of the artery up to a concentration of 10 mg/ml and were not washed away significantly after 4 h of perfusion of the artery. A 24‐mer peptide containing a consensus sequence for binding to GAGs (ARRRAARA)3, 2.7 kDa, was comparable to high molecular weight polylysine and dendrimers in terms of binding and retention. A 14‐mer GAG‐binding peptide from vitronectin and low molecular weight polylysine, 3 kDa, accumulated in the vascular wall up to about 3 mg/ml and was washed away after 30 min of perfusion. A 10‐mer consensus GAG‐binding peptide did not bind significantly to the vascular tissue. We conclude that the consensus 24‐mer GAG‐binding peptide is by far superior to polylysine of a similar molecular weight in terms of binding to vascular tissue, and can provide high accumulation and long‐term retention of a low molecular weight compound (fluorescein, as a model molecule) in the vascular wall. Rationally designed GAG‐binding peptides can be useful as affinity vehicles for targeting drugs to the vascular ECM.
Trans‐acting factors may cause dystrophin splicing misregulation in BMD skeletal muscles
Authors: Sironi M. , Cagliani R. , Comi G.P. , Pozzoli U. , Bardoni A. , Giorda R. , Bresolin N.
Published: February 2003

We analyzed dystrophin alternative splicing events in a large number of Becker muscular dystrophy (BMD) affected individuals presenting major hot‐spot deletions. Evidence is shown that altered splicing patterns in these patients do not directly result from the gene defect but probably derive from modifications in trans‐ rather than cis‐acting factors. Several potential CUG‐binding protein 2 (CUG‐BP2) binding sites were found to be located in the dystrophin gene region encompassing exons 43–60 and CUG‐BP2 transcript analysis indicated that not only expression levels are increased in dystrophic muscles but also that different CUG‐BP2 isoforms are expressed. The possibility that CUG‐BP2 might have a role in dystrophin splicing regulation is discussed.
Bsp1p/Ypr171p is an adapter that directly links some synaptojanin family members to the cortical actin cytoskeleton in yeast
Authors: Wicky Sidonie , Frischmuth Sabine , Singer-Krüger Birgit
Published: February 2003

In this study we identified a novel protein, Bsp1p, that interacts directly with two yeast synaptojanins, Sjl2p and Sjl3p, but not with Sjl1p. The interaction takes place via the Sac1/polyphosphoinositide phosphatase domain, whose conserved C‐terminal region is important for binding. Subcellular localization and genetic interactions revealed a function of Bsp1p in the cortical actin cytoskeleton. A fraction of Bsp1p was found to be membrane‐associated. Studies with mutants of phosphatidylinositol 4‐kinase, PIK1, suggested that the interaction with membranes is facilitated by phosphoinositides. We propose that Bsp1p is an adapter that links Sjl2p and Sjl3p to the cortical actin cytoskeleton.
Reconstitution of water channel function of an aquaporin overexpressed and purified from Pichia pastoris
Authors: Karlsson Maria , Fotiadis Dimitrios , Sjövall Sara , Johansson Ingela , Hedfalk Kristina , Engel Andreas , Kjellbom Per
Published: February 2003

The aquaporin PM28A is one of the major integral proteins in spinach leaf plasma membranes. Phosphorylation/dephosphorylation of Ser274 at the C‐terminus and of Ser115 in the first cytoplasmic loop has been shown to regulate the water channel activity of PM28A when expressed in Xenopus oocytes. To understand the mechanisms of the phosphorylation‐mediated gating of the channel the structure of PM28A is required. In a first step we have used the methylotrophic yeast Pichia pastoris for expression of the pm28a gene. The expressed protein has a molecular mass of 32462 Da as determined by matrix‐assisted laser desorption ionization‐mass spectrometry, forms tetramers as revealed by electron microscopy and is functionally active when reconstituted in proteoliposomes. PM28A was efficiently solubilized from urea‐ and alkali‐stripped Pichia membranes by octyl‐β‐D‐thioglucopyranoside resulting in a final yield of 25 mg of purified protein per liter of cell culture.
CD36‐mediated endocytic uptake of advanced glycation end products (AGE) in mouse 3T3‐L1 and human subcutaneous adipocytes
Authors: Kuniyasu Akihiko , Ohgami Nobutaka , Hayashi Shigeki , Miyazaki Akira , Horiuchi Seikoh , Nakayama Hitoshi
Published: February 2003

Interaction of advanced glycation end products (AGE) with AGE receptors induces several cellular phenomena potentially relating to diabetic complications. We here show that AGE‐modified bovine serum albumin (BSA) is endocytosed by adipocytes via CD36. Upon differentiation, 3T3‐L1 and human subcutaneous adipose cells showed marked increases in endocytic uptake and subsequent degradation of [125I]AGE‐BSA, which were inhibited effectively by the anti‐CD36 antibody. Ligand specificity of CD36 for modified BSAs was compared with that of LOX‐1 and scavenger receptor class A. Effect of fucoidan on [125I]AGE‐BSA binding showed a sharp contrast to that on [125I]‐oxidized low density lipoprotein. These results implicate that CD36‐mediated interaction of AGE‐modified proteins with adipocytes might play a pathological role in obesity or insulin‐resistance.
Myeloperoxidase/nitrite‐mediated lipid peroxidation of low‐density lipoprotein as modulated by flavonoids
Authors: Kostyuk Vladimir A. , Kraemer Tilo , Sies Helmut , Schewe Tankred
Published: February 2003

In the presence of a H2O2‐generating system, myeloperoxidase (MPO) caused conjugated diene formation in low‐density lipoprotein (LDL), indicating lipid peroxidation which was dependent on nitrite but not on chloride. The oxidation of LDL was inhibited by micromolar concentrations of flavonoids such as (−)‐epicatechin, quercetin, rutin, taxifolin and luteolin, presumably via scavenging of the MPO‐derived NO2 radical. The flavonoids served as substrates of MPO leading to products with distinct absorbance spectra. The MPO‐catalyzed oxidation of flavonoids was accelerated in the presence of nitrite.
Photoreduction of the quinone pool in the bacterial photosynthetic membrane: identification of infrared marker bands for quinol formation
Authors: Mezzetti Alberto , Leibl Winfried , Breton Jacques , Nabedryk Eliane
Published: February 2003

The photoreduction of the quinone (Q) pool in the photosynthetic membrane of the purple bacterium Rhodobacter sphaeroides was investigated by steady‐state and time‐resolved Fourier transform infrared difference spectroscopy. The results are consistent with the existence of a homogeneous Q pool inside the chromatophore membrane, with a size of around 20 Q molecules per reaction center. IR marker bands for the quinone/quinol (Q/QH2) redox couple were recognized. QH2 bands are identified at 1491, 1470, 1433 and 1388–1375 cm−1. The 1491 cm−1 band, which is sensitive to 1H/2H exchange, is assigned to a C–C ring mode coupled to a C–OH mode. A feature at ∼1743/1720 cm−1 is tentatively related to a perturbation of the carbonyl modes of phospholipid head groups induced by QH2 formation. Complex conformational changes of the protein in the amide I and II spectral ranges are also apparent during reduction and reoxidation of the Q pool.
Chloroplast precursor protein translocon
Authors: May Timo , Soll Jürgen
Published: February 2003

Chloroplasts are believed to have originated from a photosynthetic, prokaryotic ancestor. As the result of endosymbiotic evolution, most of the genes of the endocytobiont were displaced to the host nucleus. Today's chloroplasts must import most of their proteins from the cytosol as precursors. Oligomeric protein complexes in the chloroplast outer and inner envelope membranes are responsible for the specific recognition and membrane translocation of precursor proteins. The translocon at the outer membrane of chloroplasts and the inner membrane of chloroplasts act jointly during the import process. Several translocon subunits have been partially characterized in their molecular structure and function. Initial evidence indicates the prokaryotic origin of some chloroplast translocon components.
Cytoskeleton cross‐talk during cell motility
Authors: Small J.Victor , Kaverina Irina , Krylyshkina Olga , Rottner Klemens
Published: February 2003

Cell crawling entails the co‐ordinated creation and turnover of substrate contact sites that interface with the actin cytoskeleton. The initiation and maturation of contact sites involves signalling via the Rho family of small G proteins, whereas their turnover is under the additional influence of the microtubule cytoskeleton. By exerting relaxing effects on substrate contact assemblies in a site‐ and dose‐specific manner, microtubules can promote both protrusion at the front and retraction at the rear, and thereby control cell polarity.
Nuclear transport and transcriptional regulation
Authors: Turpin Pierre , Ossareh-Nazari Batool , Dargemont Catherine
Published: February 2003

Studies over the past 10 years have provided major insights into the molecular mechanisms responsible for active transport of macromolecules in and out of the nucleus. Nucleocytoplasmic transport pathways correspond to active and signal‐mediated processes that involve substrates, adaptors and receptors. Regulation of both nuclear import and nuclear export is mainly exerted at the level of transport complex formation and has emerged as one of the most efficient mechanisms to adapt gene expression to the cell environment by restricting the access of transcriptional regulators to their target genes.
Structural information for explaining the molecular mechanism of protein biosynthesis
Authors: Clark Brian F.C , Thirup Søren , Kjeldgaard Morten , Nyborg Jens
Published: February 2003

Protein biosynthesis is controlled by a number of proteins external to the ribosome. Of these, extensive structural investigations have been performed on elongation factor‐Tu and elongation factor‐G. This now gives a rather complete structural picture of the functional cycle of elongation factor‐Tu and especially of the elongation phase of protein biosynthesis. The discovery that three domains of elongation factor‐G are structurally mimicking the amino‐acylated tRNA in the ternary complex of elongation factor‐Tu has been the basis of much discussion of the functional similarities and functional differences of elongation factor‐Tu and elongation factor‐G in their interactions with the ribosome. Elongation factor‐G:GDP is now thought to leave the ribosome in a state ready for checking the codon‐anticodon interaction of the aminoacyl‐tRNA contained in the ternary complex of elongation factor‐Tu. Elongation factor‐G does this by mimicking the shape of the ternary complex. Other translation factors such as the initiation factor‐2 and the release factor 1 or 2 are also thought to mimic tRNA. These observations raise questions concerning the possible evolution of G‐proteins involved in protein biosynthesis.
Obligate intracellular parasites: Rickettsia prowazekii and Chlamydia trachomatis
Authors: Zomorodipour Alireza , Andersson Siv G.E
Published: February 2003

Transitions to obligate intracellular parasitism have occurred at numerous times in the evolutionary past. The genome sequences of two obligate intracellular parasites, Rickettsia prowazekii and Chlamydia trachomatis, were published last year. A comparative analysis of these two genomes has revealed examples of reductive convergent evolution, such as a massive loss of genes involved in biosynthetic functions. In addition, both genomes were found to encode transport systems for ATP and ADP, not otherwise found in bacteria. Here, we discuss adaptations to intracellular habitats by comparing the information obtained from the recently published genome sequences of R. prowazekii and C. trachomatis.
Prognostic factors relating to survival in uterine endometrioid carcinoma
Authors: Hirai M. , Hirono M. , Oosaki T. , Hayashi Y. , Yoshihara T. , Matsuzaki O.
Published: February 2003

Objective: Epidemiologic and clinicohistopathologic prognostic factors of uterine endometrioid carcinomas were analyzed. The association of estrogen related factors, focused on adenomyosis in the prognosis of endometrioid carcinomas was also examined. Methods: Risk factors of surgically treated 286 patients with endometrioid carcinoma (Stage I–III) were statistically analyzed. Results: Overall a recurrence‐free 5‐year survival rate was 81% (Stage I, 94%, Stage II, 71% and Stage III, 40%). Significant prognostic factors were lymph node metastases (P=0.0035) and serosal/parametrial invasion (P=0.014) by multivariate analysis. Endometrioid carcinomas with co‐existing adenomyosis tend to be associated with endometrial hyperplasia (P=0.04, Fisher's exact test), diagnosed in less invasive status (myometrial invasion, P=0.004 and serosal/parametrial invasion, P=0.006) and therefore have a favorable prognosis (P=0.01, log rank test). Conclusions: A favorable prognosis of endometrioid carcinomas with co‐existing estrogen related factors (adenomyosis and endometrial hyperplasia) was suggested.
Childhood adversities in patients with fibromyalgia and somatoform pain disorder
Authors: Imbierowicz Katrin , Egle Ulrich T.
Published: February 2003

Primary fibromyalgia is regarded as disorder with a complex symptomatology, and no morphological alterations. Findings increasingly point to a dysfunction of the central nervous pain processing. The study aims to discuss vulnerability for fibromyalgia from a developmental psychopathological perspective. We investigated the presence of psychosocial adversities affecting the childhood of adult fibromyalgia patients (FM) and compared them to those of patients with somatoform pain disorders (SOM) and a control group (CG) with medically explained chronic pain. Using the structured biographical interview for pain patients (SBI‐P), 38 FM patients, 71 SOM patients, and 44 CG patients were compared on the basis of 14 childhood adversities verified as relevant regarding longterm effects for adult health by prospective studies. The FM patients show the highest score of childhood adversities. In addition to sexual and physical maltreatment, the FM patients more frequently reported a poor emotional relationship with both parents, a lack of physical affection, experiences of the parents’ physical quarrels, as well as alcohol or other problems of addiction in the mother, separation, and a poor financial situation before the age of 7. These experiences were found to a similar extent in the SOM patients, but distinctly less frequently in the CG. The results point to early psychosocial adversities as holding a similar etiological meaning in fibromyalgia as well as in somatoform pain disorders. The potential role of these factors as increasing the vulnerability for fibromyalgia is discussed.
Experimental muscle pain and tenderness following infusion of endogenous substances in humans
Authors: Mørk Hanne , Ashina Messoud , Bendtsen Lars , Olesen Jes , Jensen Rigmor
Published: February 2003

Several human models of myofascial pain exist, but none are similar to clinical pain. The aim of the present study was to develop a clinically relevant model of prolonged human myofascial pain using infusion of the naturally occurring endogenous substances. Initially, bradykinin (Bk), serotonin (5‐hydroxytryptamine (5‐HT)), histamine (His), prostaglandin E2 (PGE2), adenosine‐tri‐phosphate (ATP), and their combinations were infused into the trapezius muscle of 36 healthy subjects in a total of 67 sessions to identify substances, which could induce a moderate muscle pain. PGE2, ATP, and a combination of Bk, 5‐HT, His, and PGE2 produced the intended moderate pain. These substances were further examined in a randomised, blinded, placebo‐controlled dose‐finding design in 15 healthy subjects in 68 sessions. PGE2 (3, 6, and 12 nmol/ml) induced mild pain and tenderness not different from placebo. ATP (9000, 18,000, and 36,000 nmol/ml) induced pain of moderate to strong intensity (P=0.04) and the dose of 18,000 nmol/ml furthermore produced moderate local tenderness (P=0.04). Because of unacceptable side effects in subsequent examinations, further studies of ATP in humans were suspended. Infusion of the combination of Bk (92 nmol), 5‐HT (156 nmol), His (140 nmol), and PGE2 (1.95 nmol) produced a moderate pain intensity (P=0.04) and mild tenderness (P=0.04) without inducing unacceptable side effects. Intramuscular infusion of a combination of Bk, 5‐HT, His, and PGE2 induced a prolonged moderate pain and tenderness in healthy humans, and this model may be a valuable tool in future studies of the pathophysiological mechanisms of myofascial pain.
Validation of the arthritis self‐efficacy short‐form scale in German fibromyalgia patients
Authors: Mueller Annette , Hartmann Mechthild , Mueller Knut , Eich Wolfgang
Published: February 2003

Self‐efficacy is assumed to account for significant variance in the treatment outcome of chronic pain patients. The aim of this study was to provide a German version of an approved measure of disease‐related self‐efficacy in fibromyalgia (FM) patients which assesses treatment outcomes and specific differences compared to other pain patients. The 8‐item short‐form of the arthritis self‐efficacy scale was translated into German (ASES‐D) and administered to 148 FM patients and 53 patients with rheumatoid arthritis (RA). In addition, similar cognitive constructs (locus of control, optimism/pessimism, and general self‐efficacy) and disease‐related variables (pain, functioning, depression, and coping) were assessed. The instrument was further applied to 43 FM patients who underwent interdisciplinary group therapy. Validation methods consisted of correlation, principal component analysis and difference testing between the disease groups. The instrument met good psychometric properties. Evidence for construct validity was provided. Self‐efficacy was sensitive to changes and could be used in predicting the treatment outcome in FM patients. The German short‐form ASES‐D is a further step toward an internationally comparable assessment of disease‐related self‐efficacy in FM.
Non‐reciprocal regulation of the redox state of the glutathione–glutaredoxin and thioredoxin systems
Authors: Trotter Eleanor W , Grant Chris M
Published: February 2003

Our studies in yeast show that there is an essential requirement for either an active thioredoxin or an active glutathione (GSH)–glutaredoxin system for cell viability. Glutathione reductase (Glr1) and thioredoxin reductase (Trr1) are key regulatory enzymes that determine the redox state of the GSH–glutaredoxin and thioredoxin systems, respectively. Here we show that Trr1 is required during normal cell growth, whereas there is no apparent requirement for Glr1. Analysis of the redox state of thioredoxins and glutaredoxins in glr1 and trr1 mutants reveals that thioredoxins are maintained independently of the glutathione system. In contrast, there is a strong correlation between the redox state of glutaredoxins and the oxidation state of the GSSG/2GSH redox couple. We suggest that independent redox regulation of thioredoxins enables cells to survive in conditions under which the GSH–glutaredoxin system is oxidized.