bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient participation groups in general practice in the National Health Service
Authors: Brown Ian 
Published: March 2003

General practice remains the organizational hub of first level health services in the United Kingdom. Patient participation groups are probably the most well known model for public participation in this setting and, although still not widespread, they have been a slowly expanding area of development for almost three decades. This paper sets out to critically asses patient participation groups in general practice by considering the context of their development and reviewing the research literature about groups. Critical issues needing more study and key methodological challenges are then discussed.Patient participation groups have been a somewhat shifting and contested phenomenon, embracing trends and changing as policy priorities have changed over the years. There is some evidence to think that they might have potential as a local element within a public participation strategy in the National Health Service. However, the field studies are very limited and more research of a better quality is needed. The state of knowledge is not adequate to be able to say with any confidence if or how such groups should be developed. A better understanding is needed of the public’s perspectives on this and other models of participation. There are many other questions to do with patient participation groups’ purpose, equitable access, and effectiveness that need to be addressed. The methodological challenges include issues of how to involve all stakeholders in the research process; and how to study less tangible aspects of general practice organization, such as culture and power, that effect the public’s participation.
Public perceptions about low back pain and its management: a gap between expectations and reality?
Authors: Moffett Jennifer A. Klaber , Newbronner Elizabeth , Waddell Gordon , Croucher Karen , Spear Steven 
Published: March 2003

ObjectiveTo compare public perceptions and patient perceptions about back pain and its management with current clinical guidelines.DesignA survey using a quota sampling technique.SettingOn‐the‐street in South Derbyshire in the UK.Subjects507 members of the general population aged between 20 and 60 years, including a representative subsample of 40% who had experienced back pain in the previous year.SurveyTo test knowledge and perceptions of back pain and its best management using statements based on The Back Book which was produced in conjunction with the Royal College of General Practitioners and based on best available evidence. In addition expectations of back pain management and outcome were investigated.ResultsForty percent of this sample had experienced back pain during the previous year, more than half of whom had consulted their GP. More than half believed the spine is one of the strongest part of the body, but nearly two thirds incorrectly believed that back pain is often due to a slipped disc or trapped nerve. Two thirds expected a GP to be able to tell them exactly what was wrong with their back, although slightly fewer among those who had consulted. Most expected to have an X‐ray, especially if they had consulted. Most recognised that the most important thing a GP can do is offer reassurance and advice. The responses were not related to age, gender or social class. Those who had consulted appeared to have slightly more misconceptions: this could be partly due to people with more severe problems or more misconceptions being more likely to consult, but also suggests either that GPs are still giving inaccurate information or at least failing to correct these misconceptions.ConclusionsThe problem of managing back pain might be reduced by closing the gap between the public’s expectations and what is recommended in the guidelines through the promotion of appropriate health education messages. Further professional education of GPs also appears to be needed to update them in the most effective approach to managing back pain.
Challenges of participatory research: reflections on a study with breast cancer self‐help groups
Authors: Gray Ross E. , Fitch Margaret , Davis Christine , Phillips Catherine 
Published: March 2003

ObjectiveTo review and discuss issues related to participatory research, as they apply within the arena of cancer control.DesignA participatory research study with breast cancer self‐help groups is referred to for description and discussion purposes. That study employed primarily individual and group interviews to assess benefits and limitations of self‐help groups.SettingsFour breast cancer self‐help groups in Ontario communities provided the core involvement in the participatory research project.ResultsThe values and practices of mainstream academic research often conflict with those of research emphasizing participation and control of communities under study, leading to a variety of challenges for the latter approaches. Practical constraints faced by many community groups have important implications for participatory research approaches.ConclusionsA balance needs to be found for participatory research within cancer control – one that ensures that the core aims of participatory research are maintained, while simultaneously acknowledging the various challenges that make a fully participatory project unrealistic. Steps can be taken to achieve a workable balance.
Consulting about consulting: challenges to effective consulting about public health research
Authors: Graham Janne , Broom Dorothy , Whittaker Andrea 
Published: March 2003

Objective To understand barriers to obtaining input from consumers in developing public health research. Methods Documentation of a failed attempt at consumer consultation supplies information on barriers to effective involvement and conditions that must prevail to improve consultation. Results People are keen to be heard in the formulation of health research. However, competing demands and limited resources make it difficult for community groups to allocate scarce resources to consultation. Sometimes research issues may seem ‘academic’ and thus remote from the urgent priorities of the people with whom researchers wish to consult. Consultation may require more time than researchers on limited budgets can afford. Conclusions Despite a general public health commitment to involving consumers in research development, obstacles to consultation make it difficult to incorporate it into the research agenda. Implications Researchers and funding bodies will need to allocate resources to consumer consultation if it is to become the rule rather than the exception in public health research.
The ethics of evidence‐based patient choice
Authors: Parker Michael 
Published: March 2003

In this paper I analyse the ethical implications of the concept of ‘evidence‐based patient choice’ in the light of criticism of the ‘individualism’ of patient‐centred medicine. I argue that individualism in the sense used by the critics of patient centred medicine is not an inevitable consequence of an emphasis on patient choice and that a concern with the promotion of individual choices is not incompatible with ‘communitarian’ values.Indeed, I argue that any ethical approach to decision‐making in health‐care must be capable of taking seriously both the moral status of the individual (and of his or her choices) and the moral significance of the social dimensions of such choices. The best way to ensure respect for the principle of autonomy, I suggest, is to facilitate and encourage social interactions of a particular, deliberative, kind. This is also the best way to ensure that the broader public interest is taken into account in decision‐making.
A decision aid for men with early stage prostate cancer: theoretical basis and a test by surrogate patients
Authors: Feldman‐Stewart Deb , Brundage Michael D. , Van Manen Lori 
Published: March 2003

Background We developed a decision aid for patients with curable prostate cancer based on Svenson’s DiffCon Theory of Decision Making. This study was designed to determine if surrogate patients using the aid could understand the information presented, complete all tasks, show evidence of differentiation, and arrive at a preferred treatment choice. Methods Men, at least 50 years old and never diagnosed with prostate cancer, were recruited through local advertisements. Participants were asked to imagine that they were a case‐scenario patient. Then they completed the decision aid interview, which included three components: (i) information presentation, with comprehension questions, (ii) exercises to help identify attributes important to the decision, and (iii) value‐clarification exercises. Results Sixty‐nine men volunteered. They had a mean age of 61.2 (range 50–83) years, 37% had no formal education beyond high school, and 87% were living with a partner. All participants completed all aspects of the interview. They answered an average of 10 comprehension questions each, with a mean of 94.7% correct without a prompt. Each attribute in the information presented was identified by at least one participant as important to his decision. Participants identified a median of five attributes as important (ranges 1–14) at each of three points during the interview; 75% changed at least one important attribute during the interview. Forty‐nine per cent of participants also identified attributes as important that were not included in the presented information. Participants showed a wide range of values in each of seven trade‐off exercises. Eighty‐eight per cent of participants showed evidence of differentiation; 75% had a clear treatment preference by the end of the interview. Conclusions Our decision aid appears to meet its goals for surrogate patients and illustrates the strengths of the DiffCon theory. The ability of the aid to accommodate wide variability, both in information needs and in important attributes, is a particular strength of the decision aid. It now requires testing in patients with prostate cancer.
Purification and characterization of the thyrotropin‐releasing hormone (TRH)‐degrading serum enzyme and its identification as a product of liver origin
Authors: Schmitmeier Stephanie , Thole Hubert , Bader Augustinus , Bauer Karl 
Published: March 2003

Previous biochemical studies have indicated that the membrane‐bound thyrotropin‐releasing hormone (TRH)‐degrading enzyme (TRH‐DE) from brain and liver and the serum TRH‐DE are derived from the same gene. These studies also suggested that the serum enzyme is of liver origin. The present study was undertaken to verify these hypotheses. In different species, a close relationship between the activities of the serum enzyme and the particulate liver enzyme was noticed. The activity of the serum enzyme decreased when rats were treated with thioacetamide, a known hepatotoxin. With hepatocytes cultured in a sandwich configuration, release of the TRH‐DE into the culture medium could also be demonstrated.The trypsin‐solubilized particulate liver TRH‐DE and the serum TRH‐DE were purified to electrophoretic homogeneity. Both enzymes and the brain TRH‐DE were recognized by a monoclonal antibody generated with the purified brain enzyme as antigen. Lectin blot analysis indicated that the serum enzyme and the liver enzyme are glycoproteins containing a sugar structure of the complex type, whereas the brain enzyme exhibits an oligomannose/hybrid glycostructure. A molecular mass of 97 000 Da could be estimated for all three enzymes after deglycosylation and SDS/PAGE followed by Western blotting.Fragment analysis of the serum TRH‐DE revealed that the peptide sequences correspond to the cDNA deduced amino‐acid sequences of the membrane‐bound brain TRH‐DE, whereby two peptides were identified that are encoded by exon 1. These data strongly support the hypothesis that the TRH‐DEs are all derived from the same gene, whereby the serum enzyme is generated by proteolytic cleavage of the particulate liver enzyme.
Assessment of telomere length and factors that contribute to its stability
Authors: Saldanha Sabita N. , Andrews Lucy G. , Tollefsbol Trygve O. 
Published: March 2003

Short strands of tandem hexameric repeats known as telomeres cap the ends of linear chromosomes. These repeats protect chromosomes from degradation and prevent chromosomal end‐joining, a phenomenon that could occur due to the end‐replication problem. Telomeres are maintained by the activity of the enzyme telomerase. The total number of telomeric repeats at the terminal end of a chromosome determines the telomere length, which in addition to its importance in chromosomal stabilization is a useful indicator of telomerase activity in normal and malignant tissues. Telomere length stability is one of the important factors that contribute to the proliferative capacity of many cancer cell types; therefore, the detection and estimation of telomere length is extremely important. Until relatively recently, telomere lengths were analyzed primarily using the standard Southern blot technique. However, the complexities of this technique have led to the search for more simple and rapid detection methods. Improvements such as the use of fluorescent probes and the ability to sort cells have greatly enhanced the ease and sensitivity of telomere length measurements. Recent advances, and the limitations of these techniques are evaluated. Drugs that assist in telomere shortening may contribute to tumor regression. Therefore, factors that contribute to telomere stability may influence the efficiency of the drugs that have potential in cancer therapy. These factors in relation to telomere length are also examined in this analysis.
Identification and characterization of the natural electron donor ferredoxin and of FAD as a possible prosthetic group of benzoyl‐CoA reductase (dearomatizing), a key enzyme of anaerobic aromatic metabolism
Authors: Boll Matthias , Fuchs Georg 
Published: March 2003

Under anoxic conditions most aromatic compounds are metabolized via benzoyl‐CoA which becomes reduced by benzoyl‐CoA reductase (dearomatizing); this enzyme was recently described in the bacterium Thauera aromatica [Boll, M. & Fuchs, G. (1995) Eur. J. Biochem. 234, 921−933]. It catalyzes the reaction benzoyl‐CoA + 2 e− + 2 H+ + 2 MgATP + 2 H2O ← cyclohexa‐1,5‐diene‐1‐carboxyl‐CoA + 2 MgADP + 2 Pi. The iron‐sulfur protein has a native molecular mass of 160−170 kDa and consists of four different subunits. In addition a flavin may be present.The nature of the potential prosthetic group and the natural electron donor were determined. Purified benzoyl‐CoA reductase preparations contained 0.25−0.3 mol FAD/mol enzyme. Cells grown anaerobically with aromatic substrates contained a ferredoxin which represented the main, if not the only ferredoxin present. It was purified from 200 g cells with a yield of 60 mg and its N‐terminal amino acid sequence was determined. The native molecular mass was 9659 ± 2 Da as determined by electrospray mass spectrometry. The protein contained 7.6 ± 0.6 mol iron and 7.6 ± 1 mol acid‐labile sulfur/mol. The ultraviolet−visible spectrum of the protein was typical for ferredoxins with maxima at 280 nm and 390 nm (in the oxidized state). The estimated molar absorption coefficients were 63 500 M−1 cm−1 at 280 nm and 40 500 M−1 cm−1 at 390 nm. The difference spectrum between the oxidized and the reduced form had a maximum at 415 nm with Δε415 = 8200 M−1 cm−1. 1 mol ferredoxin became reduced/mol dithionite added, suggesting the presence of two [4Fe‐4S] clusters. The average midpoint potential of the iron‐sulfur clusters was −450 mV.The ferredoxin gene was cloned and sequenced. It was located in a gene cluster coding for enzymes involved in anaerobic aromatic metabolism. The amino acid sequence of the T. aromatica ferredoxin showed high similarities to several other ferredoxins containing 2[4Fe‐4S] clusters, e.g. from Clostridia and phototrophic bacteria. The reduced ferredoxin served as electron donor for benzoyl‐CoA reduction at a three times higher rate compared with the rate obtained with the artificial electron donor reduced methyl viologen. The turnover number with the natural electron donor of 5 s−1 can explain the bacterial growth rate with benzoate as substrate. Half‐maximal enzyme acitivity was obtained with 6 μM reduced ferredoxin, at an estimated cellular concentration of 70 μM ferredoxin. Both the low apparent Km value and the turnover number are consistent with the proposed role of ferredoxin in aromatic‐ring reduction.
Comparison of the kinetics of active efflux of 99mTc‐MIBI in cells with P‐glycoprotein‐mediated and multidrug‐resistance protein‐associated multidrug‐resistance phenotypes
Authors: Vergote Jackie , Moretti Jean‐Luc , De Vries Elisabeth G. E. , Garnier‐Suillerot Arlette 
Published: March 2003

The overexpression of two membrane glycoproteins, P‐glycoprotein and multidrug‐resistance protein (MRP1) is a major cause of resistance to chemotherapeutic agents in the treatment of human cancers. Both proteins confer a similar multidrug‐resistant (MDR) phenotype. 99mTc‐MIBI, a myocardial imaging agent, which is also useful for the detection of a variety of tumours, has been shown to be a substrate for P‐glycoprotein and MRP1. It thus may provide additional information about the P‐glycoprotein and MRP1 status of tumour cells.In order to obtain information on the substrate specificity of these proteins, we have studied the transport kinetics of Tc‐MIBI in two cell lines, K562/ADR and GLC4/ADR, which overexpress P‐glycoprotein and MRP1, respectively. The mean active efflux coefficient ka, which is proportional to the ratio of maximal efflux rate VM to the apparent Michaelis‐Menten constant Km, used to characterise the efficiency of the active efflux, was very similar being 1.9 ± 0.6×10−11 s−1 cells ml and 1.3 ± 0.5×10−11 s−1 cells ml for drug‐resistant K562 and GLC4, respectively. These values are 50−100‐times lower than for daunorubicin and other anthracycline derivatives, strongly suggesting that the efficiency of both transporters to pump Tc‐MIBI is by far less than that to efflux anthracyclines.Our data show that (a) P‐glycoprotein and MRP transporter efficiencies to wash out Tc‐MIBI are similar, in spite of a different suspected mechanism of its transport and (b) that both transporters are less efficient to pump Tc‐MIBI than to pump anthracyclines (the ka parameter is about 100‐times lower for TC‐MIBI than for anthracycline).
Evidence of noncovalent dimerization of calmodulin
Authors: Lafitte Daniel , Heck Albert J. R. , Hill Tessa J. , Jumel Kornelia , Harding Stephen E. , Derrick Peter J. 
Published: March 2003

Calcium‐binding proteins, such as S‐100, dimerize readily, and this phenomenon plays an important role in their regulation of target enzymes [Krebs, J., Quadroni, M. & Van Eldik, L.J. (1995) Nat. Struct. Biol.2, 711–714; Kilby, P.M., Van Eldik, L.J. & Roberts, G.C. (1996) Structure4, 1041–1052]. We have investigated by Fourier‐transform ion cyclotron resonance (FTICR) MS the conformational states of the calcium‐binding protein calmodulin, and present clear evidence for a calmodulin dimer formed as a result of noncovalent interactions between folded monomers. Ultra‐high‐resolution electrospray ionization (ESI) mass spectra for calmodulin, obtained with a 9.4 T FTICR mass spectrometer, are presented. With the use of denaturing solutions (1 : 1 acetonitrile/water + 1% formic acid), relatively high charge states (20 < z < 10) of monomeric calmodulin ions were detected, whereas when calmodulin was electrosprayed from buffer, monomers ions with only 5–10 charges were detected. CD measurements for calmodulin in buffered solution revealed that its α‐helical content was significantly higher than that for calmodulin in acetonitrile/water solutions, consistent with a proposition that changes in charge state distributions observed in the MS experiments reflect differing states of calmodulin folding. Under buffered conditions, noncovalently bound calmodulin dimers were observed by ESI FTICR MS. Analytical ultracentrifugation experiments carried out in the same solution conditions as those used in the MS experiments were consistent with the proposed calmodulin dimer–monomer equilibrium. The ultra‐high mass resolution achieved with the 9.4 T FTICR mass spectrometer allowed unequivocal identification of the noncovalent, as opposed to covalent, character of the calmodulin dimer.
NMR studies of the C‐terminal secretion signal of the haem‐binding protein, HasA
Authors: Izadi‐Pruneyre Nadia , Wolff Nicolas , Redeker Virginie , Wandersman Cécile , Delepierre Muriel , Lecroisey Anne 
Published: March 2003

HasA is a haem‐binding protein which is secreted under iron‐deficiency conditions by the gram‐negative bacterium Serratia marcescens. It is a monomer of 19 kDa (187 residues) able to bind free haem as well as to capture it from haemoglobin. HasA delivers haem to a specific outer‐membrane receptor HasR and allows the bacteria to grow in the absence of any other source of iron. It is secreted by a signal peptide‐independent pathway which involves a C‐terminal secretion signal and an ABC (ATP‐binding cassette) transporter. The C‐terminal region of the secretion signal containing the essential secretion motif is cleaved during or after the secretion process by proteases secreted by the bacteria. In this work, we study by 1H NMR the conformation of the C‐terminal extremity of HasA in the whole protein and that of the isolated secretion signal peptide in a zwitterionic micelle complex that mimicks the membrane environment. We identify a helical region followed by a random‐coil C‐terminus in the peptide–micelle complex and we show that in both the whole protein and the complex, the last 15 residues containing the motif essential for secretion are highly flexible and unstructured. This flexibility may be a prerequisite to the recognition of HasA by its ABC transporter. We determine the cleavage site of the C‐terminal extremity of the protein and analyse the effect of the cleavage on the haem acquisition process.
Determinants of substrate specificity of a second non‐neuronal secreted acetylcholinesterase from the parasitic nematode Nippostrongylus brasiliensis
Authors: Hussein Ayman S. , Smith Angela M. , Chacón Matilde R. , Selkirk Murray E. 
Published: March 2003

We recently reported on a non‐neuronal secreted acetylcholinesterase (AChE B) from the nematode parasite Nippostrongylus brasiliensis. Here we describe the primary structure and enzymatic properties of a second secreted variant, termed AChE C after the designation of native AChE isoforms from this parasite. As for the former enzyme, AChE C is truncated at the carboxyl terminus in comparison with the Torpedo AChE, and three of the 14 aromatic residues that line the active site gorge are substituted by nonaromatic residues, corresponding to Tyr70 (Ser), Trp279 (Asn) and Phe288 (Met).A recombinant form of AChE C was highly expressed by Pichia pastoris. The enzyme was monomeric and hydrophilic, and displayed a marked preference for acetylthiocholine as substrate. A double mutation (W302F/W345F, corresponding to positions 290 and 331 in Torpedo) rendered the enzyme 10‐fold less sensitive to excess substrate inhibition and two times less susceptible to the bis quaternary inhibitor BW284C51, but did not radically affect substrate specificity or sensitivity to the ‘peripheral site’ inhibitor propidium iodide. In contrast, a triple mutant (M300G/W302F/W345F) efficiently hydrolysed propionylthiocholine and butyrylthiocholine in addition to acetylthiocholine, while remaining insensitive to the butyrylcholinesterase‐specific inhibitor iso‐OMPA and displaying a similar profile of excess substrate inhibition as the double mutant. These data highlight a conserved pattern of active site architecture for nematode secreted AChEs characterized to date, and provide an explanation for the substrate specificity that might otherwise appear inconsistent with the primary structure in comparison to other invertebrate AChEs.