bluuebunny/crossref_metadata_2025_split huggingface dataset:
Airways hyper‐responsiveness to bradykinin and methacholine: effects of inhaled fluticasone
Authors: Reynolds C. J. , Togias A. , Proud D. 
Published: March 2003

SummaryBackground Although inhaled corticosteroids are the most effective anti‐inflammatory agents available for the treatment of asthma, they have, at best, only modest effects on airways responsiveness to methacholine. Thus, hyper‐responsiveness to methacholine is a relatively insensitive monitor of the effectiveness of glucocorticoids in asthmatic subjects.Objective The study aimed to determine if airways hyper‐responsiveness to bradykinin provides a more sensitive index of glucocorticoid responsiveness in asthmatic subjects than does hyper‐responsiveness to methacholine.Methods A double‐blind, placebo‐controlled, parallel group study comparing the effects of inhaled fluticasone (220 µg twice daily) on responsiveness to the two stimuli in asthmatic subjects who had never previously received corticosteroid therapy. Drug (n = 13) or placebo (n = 12) were administered for 16 weeks. Responsiveness to bradykinin and methacholine was determined at baseline and at 4 week intervals.Results Placebo did not alter responsiveness to either stimulus compared to baseline. Fluticasone treatment significantly reduced responsiveness to bradykinin (P < 0.001 by Friedman anova) and methacholine (P = 0.02), but changes in responsiveness to bradykinin were significantly greater than those in methacholine responsiveness (P = 0.002). Bradykinin responsiveness was decreased at all treatment times compared to baseline, while methacholine responsiveness was not decreased until 8 weeks of therapy. When data were analyzed as changes from baseline (ΔLog PD20), ΔLog PD20 for methacholine was not different at any time‐point between the two treatment groups. By contrast, ΔLog PD20 for bradykinin was significantly greater in patients receiving fluticasone compared to those on placebo at all but the 16‐week treatment time. Ten of 13 subjects receiving fluticasone failed, on at least one post‐treatment visit, to show a 20% fall in forced expiratory volume (FEV1), even at the highest dose of bradykinin.Conclusions Airways responsiveness to bradykinin is more profoundly, and more rapidly, reduced by inhaled glucocorticoids than is responsiveness to methacholine. Airways hyper‐responsiveness to bradykinin provides a convenient and sensitive monitor of glucocorticoid responsiveness in asthma.
Analysis of association and linkage for the interleukin‐4 and interleukin‐4 receptor balpha; regions in Swedish atopic dermatitis families
Authors: Söderhäll C. , Bradley M. , Kockum I. , Luthman H. , Wahlgren C.‐F. , Nordenskjöld M. 
Published: March 2003

SummaryBackground Atopic dermatitis (AD) is caused by genetic and environmental factors that interact to determine disease susceptibility and severity. Several lines of evidence suggest that the IL‐4 gene and the IL‐4‐receptor alpha (IL‐4Rα) gene are involved in the development of atopic diseases.Objective The objective of this study was to evaluate the possible involvement of the chromosomal regions 5q31 and 16p12, which include the genes coding for the IL‐4 and the IL‐4Rα in AD.Methods We conducted linkage analysis and association studies using the microsatellite markers D16S298 and D16S403 and a single nucleotide polymorphism in the promoter region of the IL‐4 gene (− 590C/T) in 406 Swedish families with at least two siblings affected with AD, in total 1514 individuals.Results and Conclusion We report linkage (P < 0.005) to the − 590C/T polymorphism in the promoter of the IL‐4 gene for the semiquantitative trait severity score of AD. Neither linkage nor association was found to the IL‐4Rα chromosomal region.
The skin fungus‐induced Th1‐ and Th2‐related cytokine, chemokine and prostaglandin E2 production in peripheral blood mononuclear cells from patients with atopic dermatitis and psoriasis vulgaris
Authors: Kanda N. , Tani K. , Enomoto U. , Nakai K. , Watanabe S. 
Published: March 2003

SummaryBackground It is suggested that skin fungi may be involved in the development of atopic dermatitis (AD) and psoriasis vulgaris (PV).Objective We studied skin fungus‐induced Th1‐ or Th2‐related cytokine, chemokine and prostaglandin E2 (PGE2) secretion in peripheral blood mononuclear cells (PBMC) from patients with AD and PV and normal subjects.Methods PBMC were cultured with the extracts of Malassezia furfur (MF), Candida albicans (CA) and Trichophyton rubrum (TR). The cytokine, chemokine and PGE2 amounts in the supernatants were measured by enzyme‐linked immunosorbent assays.Results MF induced IL‐4 and macrophage‐derived chemokine (MDC) secretion in AD patients, while induced IFN‐γ and interferon‐inducible protein of 10 kDa (IP‐10) secretion in PV patients, however, did not induce either secretion in normal subjects. CA induced IL‐4, MDC, IFN‐γ and IP‐10 secretion in AD and PV patients and normal subjects. In AD patients, the magnitude of IL‐4 and MDC responses to CA was higher than that to MF. Compared with PV patients and normal subjects, the magnitude of IL‐4 and MDC responses to CA was higher while that of IFN‐γ and IP‐10 responses to CA was lower in AD patients. TR induced moderate IL‐4 and MDC secretion only in AD patients. The three fungi induced higher levels of PGE2 secretion in AD patients than in PV patients and normal subjects. Cyclooxygenase‐2 inhibitor NS‐398 suppressed PGE2 responses to MF, CA and TR, and partially suppressed IL‐4 and MDC responses to MF, CA and TR, while enhanced IFN‐γ and IP‐10 responses to CA in AD patients, and these effects of NS‐398 were reversed by cyclic AMP analogue.Conclusion AD patients manifest Th2‐skewed responses to MF, CA and TR, which may be partially attributable to the enhanced PGE2 responses to these fungi. PV patients manifest Th1‐skewed responses to MF.
A survey of women's preferences regarding alternative surgical treatments for menorrhagia
Authors: Sculpher Mark J , Dwyer Nuala , Browning James , Horsley Sue , Cullimore John 
Published: March 2003

BackgroundMenorrhagia represents a major health burden to a large number of women in the UK. A range of medical and surgical treatments is now available for the condition, but each has its own advantages and limitations.MethodsA postal survey was undertaken of women with apparently uncomplicated menorrhagia referred to one of two NHS hospitals. The aim was to elicit women's preferences for the characteristics of surgical treatment and, specifically, to assess how they traded‐off the characteristics of hysterectomy and minimal access surgery.ResultsA total of 221 women returned their questionnaire and were included in the study (59% of those sent out). The characteristics most frequently rated as `very important' were getting back to usual activities as soon as possible (57%), experiencing the least pain and discomfort (46%), spending a short time in hospital (46%) and stopping periods for good (43%). The single characteristic most frequently rated as the most important by women was stopping periods for good (28%). Similar proportions of women preferred abdominal hysterectomy (43%) and endometrial resection (41%) when these were described to them. When asked to think about specific treatments of which they were aware, strong positive (43%) and negative (42%) preferences were indicated. Women's main information source was their general practitioner (70%), but only 44% considered themselves well‐informed about menorrhagia and its treatment.ConclusionsMany women referred to hospital with menorrhagia have conflicting objectives for treatment, feel under‐informed about therapies and have not formed treatment preferences. It is important to develop well‐structured and accessible sources of information for women and methods to elicit their treatment preferences, and to evaluate the impact of such tools on treatment selection and outcomes.
Attitudes to randomized clinical trials amongst out‐patients attending a medical oncology clinic
Authors: Ellis Peter M. , Dowsett Sharon M. , Butow Phyllis N. , Tattersall Martin H.N. 
Published: March 2003

Objective To assess the understanding of and attitudes towards randomized clinical trials amongst patients attending oncology out‐patient clinics. Design Cross‐sectional survey. Subjects Patients attending medical oncology out‐patient clinics at a Sydney teaching hospital. Main outcome Patients' willingness to participate in a randomized clinical trial. Results Sixty consecutive patients were surveyed. The mean age was 55.2 (SD 14) years. Eighty‐eight per cent of respondents thought that patients should be asked to participate in trials testing new treatments, however, only a third would consider participating in a randomized trial themselves. If a trial was endorsed by an independent cancer information service such as the NSW Cancer Council, 72% of respondents would be more likely to participate. Knowledge about randomized trials was not high. Respondents scored a median of 3 out of 7 (interquartile range, 2–4) correct answers to a series of questions about randomized trials. Patients willing to participate in a randomized trial were more likely to perceive the doctor favourably (P = 0.05), less likely to perceive trials as experimental (P = 0.05) and less likely to perceive trials as representing an inconvenience or loss of control (P = 0.09). Conclusions Understanding amongst patients of the need for and mechanisms of randomized clinical trials is not good. This may contribute to the difficulties investigators face in seeking consent for clinical trials. Evaluation of new strategies to educate the public and patients about randomized trials is needed. Involvement of consumers in the design and conduct of clinical trials and evaluation of strategies to improve doctors' communication of clinical trial information is also required.
Pilot study of an information aid for women with a family history of breast cancer
Authors: Warner Ellen , Goel Vivek , Ondrusek Nancy , Thiel Elaine C. , Lavina  , Lickley  , Chart Pamela L. , Meschino Wendy S. , Doan Brian D. , Carroll June C. , Taylor Kathryn M. 
Published: March 2003

ObjectiveTo develop and pilot study an information aid for women with a family history of breast cancer.Design, setting and participantsThe information aid, consisting of a booklet and audiotape, was developed by a multi‐disciplinary team of health care professionals, breast cancer survivors and their relatives. Women with no personal history of breast cancer, on the waiting list for a familial breast cancer clinic at either of two centres, who could read English, were eligible for the pilot study which consisted of three sets of mailed questionnaires.Main outcome measuresThe baseline questionnaires included: demographic information: the Breast Cancer and Heredity Knowledge Scale (BCHK); psychological measures (the State‐Trait Anxiety Inventory [STAI], Centre for Epidemiologic Studies Depression Scale [CES‐D] and an item about breast cancer worry), and an item about breast cancer risk perception. Immediately after reviewing the information aid, participants completed a satisfaction survey, the risk perception and cancer worry items and a checklist about their personal family history. The third set of questionnaires, completed 2–4 weeks after reviewing the aid, was identical to the first. Patients then attended their scheduled clinic visit and an objective hereditary breast cancer risk assessment was made by the genetic counselling team.Results and conclusionsOf 97 eligible women who were contacted, 67 completed all three sets of questionnaires. Overall, women were very satisfied with the aid and 96% would recommend it to other women. There was a highly significant improvement in their knowledge scores after they reviewed the aid. Anxiety and depression did not change and there was a decline in breast cancer worry. Risk perception did not change significantly. Ninety per cent of women completed their personal family history checklist accurately. Several important improvements have been made in the information aid and it will now be evaluated in the community.
Using focus groups to seek the views of patients dying from cancer about the care they receive
Authors: Raynes Norma V. , Leach Jack M. , Rawlings Barbara , Bryson Rebecca J. 
Published: March 2003

PurposeThe prime purpose of the study was to investigate whether focus groups were a practical way of seeking the views of dying people and whether the information collected added to that collected by more established methods.DesignA sample frame of Macmillan nurse patients was collated from which three cluster samples were randomly selected to participate in focus groups. The focus groups were structured with an experienced facilitator and recorder to answer three key questions.Setting and participantsPatients of Macmillan nurses in three NHS Trusts in West Yorkshire who were living at home with incurable cancer. They were aware of their condition and were willing to participate.Main variables studiedThe three key questions were; what kind of help are you currently receiving? What sort of help do you want? Of the kind of help you are receiving what kind is most important to you?Results17 patients participated in three focus groups. Participants were generally fairly able and living with spouses or relatives. They were of varying age with different types and duration of cancer. They were receiving a range of health and social services of varying importance to them. More help was particularly wanted with support for daily living, support from specialist cancer nurses, help getting out and with housework. Macmillan nurses and general practice services were highly rated in some but not all three trust areas.ConclusionsWe propose that focus groups are a practical way of collecting information about dying patients that can complement other sources of information in planning and auditing the provision of care.
Improving communication between health professionals and women in maternity care: a structured review
Authors: Rowe Rachel E. , Garcia Jo , Macfarlane Alison J. , Davidson Leslie L. 
Published: March 2003

Objective To review trials of the effectiveness of interventions aimed at improving communication between health professionals and women in maternity care. Search strategy  The electronic databases Medline, PsycLit, The Cochrane Library, BIDS Science and Social Science Indexes, Cinahl and Embase were searched. Final searches were carried out in April 2000. Inclusion criteria Controlled trials of interventions explicitly aimed at improving communication between health professionals and women in maternity care were included. Other trials were included where two reviewers agreed that this was at least part of the aim. Data extraction and synthesis 95 potentially eligible papers were identified, read by one reviewer and checked against the inclusion criteria. The 11 included trials were read, assessed for quality and summarized in a structured tabular form. Results The included trials evaluated interventions to improve the presentation of information about antenatal testing, to promote informed choice in maternity care, woman‐held maternity records and computer‐based history taking. Four trials in which women were provided with extra information about antenatal testing in a variety of formats suggested that this was valued by women and may reduce anxiety. Communication skills training for midwives and doctors improved their information giving about antenatal tests. The three trials of woman‐held maternity records suggested that these increase women's involvement in and control over their care. Conclusions The trials identified by this review addressed limited aspects of communication and focused solely on antenatal care. Further research is required in several areas, including trials of communication skills training for health professionals in maternity care and other interventions to improve communication during labour and in the postnatal period.
Identification of the 19S regulatory particle subunits from the rice 26S proteasome
Authors: Shibahara Tadashi , Kawasaki Hiroshi , Hirano Hisashi 
Published: March 2003

The 26S proteasome, a protein complex consisting of a 20S proteasome and a pair of 19S regulatory particles (RP), is␣involved in ATP‐dependent proteolysis in eukaryotes. In␣yeast, the RP contains six different ATPase subunits and, at least, 11 non‐ATPase subunits. In this study, we identified the rice homologs of yeast RP subunit genes from the rice expressed sequence tag (EST) library. The complete nucleotide sequences of the homologs for five ATPase subunits, OsRpt1, OsRpt2, OsRpt4, OsRpt5 and OsRpt6, and five non‐ATPase subunits, OsRpn7, OsRpn8, OsRpn10, OsRpn11 and OsRpn12, and the partial sequences of one ATPase subunit, OsRpt3, and six non‐ATPase subunits, OsRpn1, OsRpn2, OsRpn3, OsRpn5, OsRpn6 and OsRpn9, were determined. Gene homologs of four ATPase subunits, OsRpt1, OsRpt2, OsRpt4 and OsRpt5, and three non‐	ATPase subunits, OsRpn1, OsRpn2 and OsRpn9, were found to be encoded by duplicated genes. The rice RP was purified by immunoaffinity chromatography with a Protein A column immobilized antibody against rice 20S proteasome, and the subunit composition was determined. The homologs obtained from the rice EST library were identified as genes encoding subunits of RP purified from rice, including the both products of duplicated genes by using electrospray ionization quadrupole time‐of‐flight mass spectrometry. Post‐translational modifications and processing in rice RP subunits were also identified. Various types of RP complex with different subunit compositions are present in rice cells, suggesting the multiple functions of rice proteasome.
Role of conserved residues within helices IV and VIII of the oxaloacetate decarboxylase β subunit in the energy coupling mechanism of the Na+ pump
Authors: Schmid Markus , Vorburger Thomas , Pos Klaas Martinus , Dimroth Peter 
Published: March 2003

The membrane‐bound β subunit of the oxaloacetate decarboxylase Na+ pump of Klebsiella pneumoniae catalyzes the decarboxylation of enzyme‐bound biotin. This event is coupled to the transport of 2 Na+ ions into the periplasm and consumes a periplasmically derived proton. The connecting fragment IIIa and transmembrane helices IV and VIII of the β subunit are highly conserved, harboring residues D203, Y229, N373, G377, S382, and R389 that play a profound role in catalysis. We report here detailed kinetic analyses of the wild‐type enzyme and the β subunit mutants N373D, N373L, S382A, S382D, S382T, R389A, and R389D.In these studies, pH profiles, Na+ binding affinities, Hill coefficients, Vmax values and inhibition by Na+ was determined. A prominent result is the complete lack of oxaloacetate decarboxylase activity of the S382A mutant at Na+ concentrations up to 20 mm and recovery of significant activities at elevated Na+ concentrations (KNa ≈ 400 mm at pH 6.0), where the wild‐type enzyme is almost completely inhibited. These results indicate impaired Na+ binding to the S382 including site in the S382A mutant. Oxaloacetate decarboxylation by the S382A mutant at high Na+ concentrations is uncoupled from the vectorial events of Na+ or H+ translocation across the membrane. Based on all data with the mutant enzymes we propose a coupling mechanism, which includes Na+ binding to center I contributed by D203 (region IIIa) and N373 (helix VIII) and center II contributed by Y229 (helix IV) and S382 (helix VIII). These centers are exposed to the cytoplasmic surface in the carboxybiotin‐bound state of the β subunit and become exposed to the periplasmic surface after decarboxylation of this compound. During the countertransport of 2 Na+ and 1 H+ Y229 of center II switches between the protonated and deprotonated Na+‐bound state.
The folding of dimeric cytoplasmic malate dehydrogenase
Authors: Sanyal Suparna C. , Bhattacharyya Debasish , Das Gupta Chanchal 
Published: March 2003

Porcine heart cytoplasmic malate dehydrogenase (s‐MDH) is a dimeric protein (2 × 35 kDa). We have studied equilibrium unfolding and refolding of s‐MDH using activity assay, fluorescence, far‐UV and near‐UV circular dichroism (CD) spectroscopy, hydrophobic probe‐1‐anilino‐8‐napthalene sulfonic acid binding, dynamic lightscattering, and chromatographic (HPLC) techniques. The unfolding and refolding transitions are reversible andshow the presence of two equilibrium intermediate states. The first one is a compact monomer (MC) formed immediately after subunit dissociation and the second oneis an expanded monomer (ME), which is little less compact than the native monomer and has most of thecharacteristic features of a ‘molten globule’ state. Theequilibrium transition is fitted in the model: 2U⇆2ME⇆2MC⇆D.The time course of kinetics of self‐ refolding of s‐MDH revealed two parallel folding pathways [Rudolph, R., Fuchs, I. & Jaenicke, R. (1986)Biochemistry25, 1662–1669]. The major pathway (70%) is 2U→2M*→2M→D, the rate limiting step being the isomerization of the monomers (K1 = 1.7 × 10−3 s−1). The minor pathway (30%) involves an association step leading to the incorrectly folding dimers, prior to the very slow D*→D folding step.In this study, we have characterized the folding‐assembly pathway of dimeric s‐MDH. Our kinetic and equilibrium experiments indicate that the folding of s‐MDH involves the formation of two folding intermediates. However, whether the equilibrium intermediates are equivalent to the kinetic ones is beyond the scope of this study.
Structural studies of the O‐antigen isolated from the phenol‐soluble lipopolysaccharide of Acinetobacter baumannii (DNA group 2) strain 9
Authors: Haseley Simon R. , Holst Otto , Brade Helmut 
Published: March 2003

A polysaccharide containing D‐GalNAc,
D‐Glc and 4‐acetamido‐4,6‐dideoxy‐
D‐glucose (Qui4NAc) was isolated from the phenol‐soluble lipopolysaccharide originating from Acinetobacter baumannii strain 9. The structure of the repeating unit was shown by means of monosaccharide analyses, Smith‐degradation, partial acid hydrolysis, mass spectrometry, and NMR spectroscopy to be a branched pentasaccharide, in which the tetrasaccharide backbone is built from amino sugars only.α‐ D‐Glcp
1
∣
6
←3)‐β‐
D‐Quip4NAc‐(1←3)‐α‐
D‐GalpNAc‐(1←4)‐α‐
D‐GalpNAc‐(1←3)‐α‐
D‐GalpNAc‐(1←The polysaccharide was identified by serological and western blot analyses as the O‐antigen of the lipopolysaccharide.