bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical study of interaction of winter flounder antifreeze protein with ice
Authors: Jorov Alexander , Zhorov Boris S. , Yang Daniel S.C.
Published: May 2004

Antifreeze proteins (AFPs) are synthesized by various organisms to enable their cells to survive subzero environment. These proteins bind to small ice crystals and inhibit their growth, which if left uncontrolled would be fatal to cells. The crystal structures of a number of AFPs have been determined; however, crystallographic analysis of AFP–ice complex is nearly impossible. Molecular modeling studies of AFPs' interaction with ice surface is therefore invaluable. Early models of AFP–ice interaction suggested H‐bond as the primary driving force behind such interaction. Recent experimental evidence, however, suggested that hydrophobic interactions could be the main contributor to AFP–ice association. All computational studies published to date were carried out to verify the H‐bond model, and no works attempting to verify the hydrophobic interaction model have been published. In this work, we Monte Carlo–minimized complexes of several AFPs with ice taking into account nonbonded interactions, H‐bonds, and the hydration potential for proteins. Parameters of the hydration potential for ice were developed with the assumption that the free energy of the water–ice association should be close to zero at equilibrium melting temperature. Our calculations demonstrate that desolvation of hydrophobic groups in the AFPs upon their binding to the grooves at the ice surface is indeed the major stabilizing contributor to the free energy of AFP–ice binding. This study is consistent with available structural and mutation data on AFPs. In particular, it explains the paradoxical finding that substitution of Thr residues with Val does not affect the potency of winter flounder AFP whereas substitution with Ser abolished its antifreeze activity.
Heterodimers of wild‐type and subunit interface mutant enzymes of glutathione S‐transferase A1–1: Interactive or independent active sites?
Authors: Vargo Melissa A. , Colman Roberta F.
Published: May 2004

Heterodimers of rat glutathione S‐transferase A1–1 were formed using one wild‐type subunit and one subunit with a mutation at the interface to evaluate whether the subunits are interactive or independent. Within the subunit interface, we are considering two regions of interactions: one region consists of a “hydrophobic ball and socket” with Phe 52 from one subunit as the ball and Phe 136 from the second subunit as one of the socket residues. The second region of interaction consists of Arg 69 and Glu 97 from both subunits. The heterodimers were formed after incubation in 1,6‐hexanediol. Because one subunit in each pair had a His‐tag, the heterodimers were purified using a nickel‐nitrilotriacetic acid column. The specific activities of the heterodimer were compared with those of the two homodimers to determine whether the less active, mutant subunit communicates with the other subunit. Two of the heterodimers, wild type/R69E‐His and wild type/E97Q‐His, displayed specific activities much lower than that expected for independent active sites; in these cases, there are new close repulsive interactions and the low activity of one subunit is communicated to the neighboring subunit. In contrast, the other two heterodimers, wild type/R69Q‐His and F136A/wild type‐His, exhibited specific activities similar to those expected for independent active sites; in these heterodimers, the closest interaction is not repulsive or occurs over a much longer distance and the subunits act independently. We conclude that whether the subunits interact or are independent depends on the nature of the interactions at the subunit interface.
Why Deliberate? The Encounter Between Deliberation and New Public Managers
Authors: Parkinson John
Published: May 2004

A number of organizations in Britain's National Health Service (NHS) have been experimenting with ‘deliberative’ techniques of citizen involvement, techniques that were designed with democratic imperatives in mind. However, political practices are moulded by their institutional settings and the goals of their proponents, so it is unlikely that they have been left ‘pure’ following their encounter with public management imperatives.

This paper offers an explanation for the interest in deliberative processes in the NHS by comparing deliberative and public management imperatives, as well as discussing more case‐specific motivations, drawing on interviews with health policy actors between May and July 2001. I then use those insights to highlight gaps between the deliberative ideal and deliberative practice, showing what has been gained and what has been lost in the encounter between deliberative democracy and new public managers.
The UK Core Executive's Use of Public Service Agreements as a Tool of Governance
Authors: James Oliver
Published: May 2004

The contemporary literature on governance notes the difficulties that core executives, central points for steering and co‐ordinating public activity, have in undertaking this strategic function. The UK core executive, particularly the Treasury, has developed a regime of Public Service Agreements (PSAs) as a novel and ambitious tool of governance, particularly for public services. The tool incorporates improved priority setting, information about performance, and incentive effects for ministers and officials through a system of performance targets. However, systems for setting priorities are fragmented and include those focused on the Prime Minister's Office and Cabinet Office. Monitoring has been improved, although measures often provide a limited, or sometimes even potentially misleading, impression of progress towards valued goals. The direct incentive effects of PSAs appear to be weak. While the link between the system and the allocation of expenditure has engaged the interest of departments in discussing priorities, ministerial and other officials’ responsibility for performance has been limited. Targets have increasingly been seen as by ministers as minimum pledges of performance rather than tools for stretching and improving performance. Various forms of blame avoidance and blame shifting have occurred and the credibility of the PSA system is in danger of being undermined by frequent changes to targets and misrepresentation of performance in some areas.
Reshaping Public Administration: The Spanish Experience Compared to the UK
Authors: Torres LourDes , Pina Vicente
Published: May 2004

This paper analyses the nature and extent of the policies of modernizing Spanish public administration. Successive Spanish governments have been involved in modernizing public administration with the stress on customer focus, improving service delivery and implementing quality awards, service charts and information technologies.

As a basis for assessing the reforms, we compare Spanish New Public Management (NPM) developments with the initiatives undertaken in the UK. The paper evaluates the usage of NPM concepts in the Spanish and UK experiences and cultural differences based on public and common law traditions respectively, locating these reforms in a comparative context. We focus on why similar concepts and initiatives could provide such different results in each country and how the cultural and institutional features produce differences in the way that NPM postulates are defined, implemented, monitored and evaluated. The answer is probably rooted in the context in which the initiatives have been developing.
The Impact of New Public Management Reforms on Public Servants’ Ethics: Towards a Theory
Authors: Maesschalck Jeroen
Published: May 2004

Recent years have witnessed an increasing concern about the impact of New Public Management (NPM) reforms on public servants’ ethics. The academic literature about this topic is still characterized by considerable confusion and the article proposes a falsifiable theory as a way out of this. Specifically, it demonstrates that, when all the claims in the literature are translated into the proposed conceptual framework, they amount to an integrated set of propositions (that is, a theory) about the causal relationship between organizational processes (as changed by NPM‐reforms) and public servants’ ethics. Such an integrated theory is possible because, although the normative positions taken by the authors are clearly rival ones, their empirical claims are complementary. With the diverse claims thus integrated into one theory, the article provides a basis for empirical research and for the NPM‐ethics debate to proceed in a more explicit and systematic way.
Chlorhexidine anaphylaxis: case report and review of the literature
Authors: Krautheim A. B. , Jermann T. H. M. , Bircher A. J.
Published: May 2004

Chlorhexidine is a widely used antiseptic and disinfectant. Compared to its ubiquitous use in medical and non‐medical environments, the sensitization rate seems to be low. Multivarious hypersensitivity reactions to the agent have been reported, including delayed hypersensitivity reactions such as contact dermatitis, fixed drug eruptions and photosensitivity reactions. An increasing number of immediate‐type allergies such as contact urticaria, occupational asthma and anaphylactic shock have been reported. In the case report, we describe anaphylaxis due to topical skin application of chlorhexidine, confirmed by skin testing and sulfidoleukotriene stimulation test (CAST®: cellular antigen stimulation test). The potential risk of anaphylactic reactions due to the application of chlorhexidine is well known, especially that application to mucous membranes can cause anaphylactic reactions and was therefore discouraged. The use of chlorhexidine at a 0.05% concentration on wounds and intact skin was so far thought to be safe. Besides our patient, only one other case of severe anaphylactic reaction due to application of chlorhexidine on skin has been reported. Hypersensitivity to chlorhexidine is rare, but its potential to cause anaphylactic shock is probably underestimated. This review should remind all clinicians of an important potential risk of this widely used antiseptic.
Rarefaction method for assessing plant species diversity on a regional scale
Authors: Koellner Thomas , Hersperger Anna M. , Wohlgemuth Thomas
Published: May 2004

In national conservation plans, it is necessary to comparatively assess species pools of different regions and monitor their changes over time. Two specific problems arise: i) species diversity must be standardized per area, because regions differ in size, and ii) the diversity measure should take into account how common or rare the species are on the regional scale. We used the rarefaction method combined with a fitting procedure to calculate the expected number of species E(S). The method takes into account the nonlinearity of species and area, as well as how common or rare each species is and allows analysis of species groups’ contribution to total species diversity. The slope parameter of the fitted power function is used as an indicator of species turnover, and thus, of β‐diversity. For the analysis, Switzerland was divided into seven biogeographic regions (256–10 642 km2). The diversity of the total species pool and of six ecological species groups was investigated for each region. In every biogeographic region, we find the lowest species turnover in the fertilized meadow group, and the highest species turnover in the pioneer/weedy species and the mountain species groups pioneer/weedy. The results show that among Swiss regions, differences in E(S) are mainly due to the presence or absence of mountain species. Other species groups show a rather constant contribution to the regional species pools. We found the rarefaction method to be a very useful tool for assessing Swiss plant species diversity on a regional scale.
Early reduction of post‐fire recruitment of Pinus nigra by post‐dispersal seed predation in different time‐since‐fire habitats
Authors: Ordóñez José Luis , Retana Javier
Published: May 2004

This study analyses the effects of post‐dispersal predation of Pinus nigra seeds on the initial recruitment of this species in areas burned by large wildfires, where P. nigra shows very low regeneration. In three different habitats obtained in a gradient of time since fire in Catalonia (NE Spain), we have evaluated the effects of seed predators (ants, rodents and birds) on post‐dispersal seed removal and early seedling establishment of P. nigra by using selective exclosures limiting their access to seeds. Ants were the most efficient seed predator group, followed by rodents and birds. The contribution of each group to overall predation showed large seasonal variations. The first seeds dispersed in winter were mainly predated by rodents, which also registered their highest abundance in this season of the year. In spring, at the end of the natural dissemination period of P. nigra seeds, ants became the major predators, this fact coinciding with their increased abundance. Birds showed the lowest predation values. In the seedling establishment experiment, only in the exclusion treatment of the three predator groups was there initial establishment in all habitats, especially in the recently burned area, where there was seedling establishment in all exclusion treatments. The post‐dispersal seed predation by different animal groups and low seedling emergence in the different habitats obtained in this study, together with the low seed availability of P. nigra seeds in burned areas, do not predict a favourable outlook for the natural post‐fire recolonization of this species, which might even affect its overall distribution area in the region.
Cholecystokinin blockade alters the systemic immune response in rats with acute pancreatitis
Authors: De La Mano Ana Maria , Sevillano Sara , Manso Manuel Antonio , Pérez Martin , Dios Isabel de
Published: May 2004

Acute pancreatitis (AP) is characterized by initial pancreatic injury resulting from the activation of digestive enzymes and, later, widespread inflammation to distant organs. The aim of this study was to study whether the time‐course of inflammatory events during AP induced by bile‐pancreatic duct obstruction (BPDO) varies after lowering the acinar enzyme content by L364,718 (0.1 mg/kg/day) administration over 7 days before inducing AP. Flow cytometric immunophenotyping was used to analyse the following at different AP stages: distribution of major circulating leucocyte subsets, activation state of circulating neutrophils and monocytes as reflected by CD11b expression and tumour necrosis factor‐α (TNF‐α) production and the contribution of T‐cell‐derived pro‐(TNF‐α) and anti‐(IL‐10) inflammatory mediators. TNF‐α plasma levels and neutrophil infiltration in pancreas and lung were also measured. At early BPDO times, L364,718 treatment partially inhibited leukocytosis and increase in peripheral blood neutrophils and monocytes as well as TNF‐α expression by monocytes. However, from 6 h onwards after BPDO, L364,718 treatment was unable to prevent either pancreatic and lung neutrophil infiltration or the release of TNF‐α from activated monocytes. By its action on circulating lymphocytes, L364,718 treatment enhanced the severity of the inflammatory response induced by BPDO. Peripheral blood lymphocytes were recruited from earlier BPDO times, and 12 h after BPDO, T cells displayed a significantly higher reserve of TNF‐α able to be released under stimulation but lower functional reserve of interleukin‐10 (IL‐10) than observed in untreated rats. It is concluded that lowering the acinar enzyme content through L364,718 treatment prevents earlier systemic immune events in BPDO‐induced AP. However, at the point of maximal injury, the inflammatory response became pronounced, largely due to the role played by activated T lymphocytes.
Reduced progression of atherosclerosis in apolipoprotein E‐deficient mice treated with lacidipine is associated with a decreased susceptibility of low‐density lipoprotein to oxidation
Authors: Cristofori Patrizia , Crivellente Federica , Campagnola Mario , Pasini Anna Fratta , Garbin Ulisse , Rigoni Anna , Tosetti Maria , Turton John , Faustinelli Ivo , Cominacini Luciano
Published: May 2004

A study has been carried out in the apolipoprotein (apo) E‐deficient mouse to investigate the activity of lacidipine (a calcium antagonist with antioxidant properties) in inhibiting the development of atherosclerotic lesions; of particular interest were changes in the susceptibility of low‐density lipoproteins (LDL) to oxidation. Mice receiving a Western‐type diet to accelerate the development of atherosclerosis were treated orally with vehicle or lacidipine at 3 or 10 mg/kg/day for 8 weeks. Lacidipine treatment (at 3 or 10 mg/kg) had no effect on the plasma lipid profile. However, a significant (P < 0.01) dose‐related reduction of 43 and 50% of the aortic lesion area in respect to vehicle‐treated mice was observed. Moreover, the resistance of mouse plasma LDL to undergo lipid peroxidation was significantly (P < 0.01) increased in apo E‐deficient mice treated with lacidipine. The native LDL‐like particle, derived from apo E‐deficient mice treated with lacidipine, contained significantly lower concentrations of malonyldialdehyde than the vehicle‐treated control group (P < 0.01). After exposure to human umbilical vein endothelial cells, LDL‐like particle vitamin E levels (expressed as area under the curve; AUC), were significantly higher (P < 0.01) in both the 3 and 10 mg/kg lacidipine‐treated groups, in comparison with the vehicle‐treated control animals. We conclude that lacidipine reduced the extent of the atherosclerotic area in hypercholesterolaemic apo E‐deficient mice, and that this reduction may be associated with the capacity of the drug to decrease the susceptibility of LDL to oxidation.
A novel option for dosing of proton pump inhibitors: dispersion of lansoprazole orally disintegrating tablet in water via oral syringe
Authors: Gremse D. A. , Donnelly J. R. , Kukulka M. J. , Lloyd E. , Lee C.
Published: May 2004

Background : A new formulation of lansoprazole, the lansoprazole orally disintegrating tablet, rapidly disintegrates in water eliminating the need for swallowing whole pills.

Aim : To assess the effect that dispersing the lansoprazole orally disintegrating tablet in water would have on lansoprazole pharmacokinetics.

Methods : Forty healthy adult men and women (18–43 years) received two single 15 mg lansoprazole orally disintegrating tablet doses separated by 3 days (one administered directly onto the tongue without water and one dispersed in water and administered orally via syringe) in a randomized, crossover fashion. Serial plasma samples were determined from 0 to 12 h for each dose. Ratios of central values for peak plasma exposure (Cmax) and mean overall extent of exposure (area under the plasma concentration) were used to compare the bioavailability.

Results : The two dosing regimens were bioequivalent, with the point estimate for area under the plasma concentration equalling 1.080 (confidence interval 1.012–1.152) and the point estimate for Cmax equalling 1.082 (confidence interval 0.961–1.218).

Conclusions : Dispersing the 15 mg lansoprazole orally disintegrating tablet in water and administering the dose orally via syringe is bioequivalent to the 15 mg intact lansoprazole orally disintegrating tablet with respect to lansoprazole area under the plasma concentration and Cmax. This dosing route provides an additional, convenient dosing option for lansoprazole.
Randomized controlled azathioprine withdrawal after more than two years treatment in Crohn's disease: increased relapse rate the following year
Authors: Vilien M. , Dahlerup J. F. , Munck L. K. , Nørregaard P. , Grønbæk K. , Fallingborg J.
Published: May 2004

Introduction : Azathioprine is effective for maintenance of remission in Crohn's disease, however, duration of efficacy and the dose response relationship has not been fully evaluated.

Aims : To investigate whether patients kept in remission by azathioprine treatment for >2 years benefit from further treatment, and to explore dose–response relationship.

Patients and methods : In an open 12‐month trial, patients with inactive Crohn's disease after >2 years (median 37 months) of azathioprine treatment were randomized to azathioprine withdrawal or continued treatment. Primary end point was relapse defined as: (i) Crohn's disease activity index rise ≥ 75, and Crohn's disease activity index >150 or (ii) disease activity requiring intervention.

Results : Of 29 patients, 28 completed the observation period or relapsed. Eleven of 13 patients (85%) continuing azathioprine remained in remission compared with seven of 15 (47%) observed without azathioprine (P = 0.043). In patients who had been treated with azathioprine >1.60 mg/kg/day the difference was even more pronounced, eight of nine (89%) vs. four of 12 (33%) respectively (P = 0.017).

Conclusions : Patients with Crohn's disease in remission after >2 years of continuous azathioprine treatment will benefit from further continued treatment. Further controlled studies with azathioprine doses <2.0 mg/kg/day are needed.
Long‐term effect of Helicobacter pylori eradication on the reversibility of acid secretion in profound hypochlorhydria
Authors: Iijima K. , Sekine H. , Koike T. , Imatani A. , Ohara S. , Shimosegawa T.
Published: May 2004

Background : Although profound hypochlorhydria is considered to be an important risk factor for development of gastric cancer, long‐term effect of Helicobacter pylori eradication on its reversibility remains uncertain.

Aim : To clarify the change in acid secretion after eradication in a long‐term follow‐up over 5 years in patients with profound hypochlorhydria.

Methods : Twenty‐three H. pylori‐positive patients with hypochlorhydria (<0.6 mmol/10 min) were enrolled prospectively. Assessment of gastrin‐stimulated acid output and histologic evaluation of biopsy specimens were performed prior to, and 1, 7 months after eradication. Subsequently, gastric acid secretion was assessed for long‐term period over 5 years after eradication in 12 patients.

Results : Gastric acid secretion was reversed to normal range in nine of 23 patients (39%) at 7 months after eradication. In the long‐term follow‐up, gradual and significant recovery in gastric acid secretion was observed up to 2 years post‐therapy. However, there was no additional increase during the last 3 years of 5‐year follow‐up period, leaving the acid secretory levels subnormal in the majority of the patients.

Conclusions : This long‐term follow‐up study suggests that the pathologic process has already progressed to an irreversible stage in the majority of H. pylori‐positive patients with marked body atrophy and profound hypochlorhydria.
Outcome of emergency ERCP for acute cholangitis in patients 90 years of age and older
Authors: Hui C.‐K. , Liu C.‐L. , Lai K.‐C. , Chan S.‐C. , Hu W. H. C. , Wong W.‐M. , Cheung W. W. , Ng M. , Yuen M.‐F. , Chan A. O. , Lo C. M. , Fan S.‐T. , Wong B. C. Y.
Published: May 2004

Background : An increasing proportion of the general population across the Western World now survives to an advanced age. However, there is limited data on the outcome of therapeutic endoscopic retrograde cholangiopancreatography in patients above 90 years of age with severe acute cholangitis.

Aim : To determine the relative frequency of postendoscopic retrograde cholangiopancreatography complication in this group of patients.

Methods : The postendoscopic retrograde cholangiopancreatography complications related outcome of 64 patients aged 90 years and above (Group 1) with severe acute cholangitis were retrospectively compared with 165 patients under the age of 90 years (Group 2).

Results : The postendoscopic retrograde cholangiopancreatography complication rate was 4.7% (three patients) in Group 1 and 7.3% (12 patients) in Group 2. There was no significant difference in the postendoscopic retrograde cholangiopancreatography complication rate between the two groups (P = 0.567). The relative frequency of 30‐day mortality was 7.8% (five patients) in Group 1 and 4.2% (seven patients) in Group 2 (P = 0.227).

Conclusion : Urgent biliary decompression with endoscopic retrograde cholangiopancreatography in patients 90 years of age and older with severe acute cholangitis is a safe and effective procedure in the hands of highly skilled endoscopists and is not associated with increased morbidity or mortality even in this group of high risk patients.
Reflection in preregistration nursing curricula
Authors: Nicholl Honor , Higgins Agnes
Published: May 2004

Background.  The concepts of reflection and reflective practice are increasingly popular themes in the nursing literature. Reflective practice has been advocated as a method for overcoming the divergence between nursing theory and practice, and as a means of articulating and developing knowledge embedded in practice. However, these claims are based more on theoretical debate than research evidence. In common with other regulatory bodies, the Irish regulatory nursing body advocates the need for reflective nurses, and curricula are being adapted to reflect this. These changes are taking place when there is still little guidance on the teaching or assessment of reflective practice. Given the lack of research on the topic and the need for evidence on which to base the teaching of reflective practice, a descriptive exploratory study was undertaken.

Aim.  The aim of this paper is to report how a group of nurse teachers perceived and interpreted reflective practice in preregistration nursing curricula in schools of nursing in The Republic of Ireland.

Methods.  Data were collected using a postal questionnaire distributed to all schools of nursing involved in the preregistration diploma in nursing (n = 40).

Results.  The results indicate variation between institutions in the number of hours allocated to the subject and where reflective practice was included in the curriculum. Emphasis was placed on theoretical models of reflection as opposed to the process or the skills required to become a reflective practitioner. Lecture and group discussion were the dominant teaching methods. Additionally, a number of teachers expressed dissatisfaction with the preparation they had received to teach the subject, and identified some of the challenges they experience when teaching reflective practice.

Conclusions.  The results provide a focus for further debate amongst nurse educators involved in implementing reflective practice in the curriculum. The results are limited by a response rate of 50% and by the geographic setting. Further research is needed to substantiate the findings of the study. However, there results do suggest that there is a need to clarify curricular content in relation to reflective practice and prepare nurse tutors for their role in teaching this subject more effectively.
Smoking habits and predictors of continued smoking in patients with acute coronary syndromes
Authors: Attebring Mona From , Hartford Marianne , Hjalmarson Agneta , Caidahl Kenneth , Karlsson Thomas , Herlitz Johan
Published: May 2004

Background.  Most patients with acute coronary syndrome quit smoking when hospitalized, although several have been found to relapse and resume smoking within 3 months.

Aim.  This paper reports a study to identify factors that can predict who will resume smoking after hospitalization for an acute coronary syndrome.

Methods.  Patients (n = 1320) below the age of 75 years, admitted to a Swedish university hospital coronary care unit with acute coronary syndromes, between September 1995 and September 1999, were consecutively included. Data were collected from hospital medical records and included information on previous clinical history, former illnesses and smoking. During their hospitalization, an experienced nurse interviewed the patients by using a structured questionnaire to obtain additional information. Patients were followed up 3 months after the discharge. Those who continued to smoke (non‐quitters) were compared with those who had stopped (quitters) with regard to age, sex, medical history, clinical course, and intention to quit. To identify factors independently related to continued smoking, a logistical regression in a formal forward stepwise mode was used.

Results.  Of the patients admitted, 33% were current smokers. Three months after discharge, 51% of these patients were still smoking. There were no significant differences in age, gender or marital status between non‐quitters and quitters. In a multivariate analysis, independent predictors of continued smoking were: non‐participation in the heart rehabilitation programme (P = 0·0008); use of sedatives/antidepressants at time of admission (P = 0·001); history of cerebral vascular disease (P = 0·002), history of previous cardiac event (P = 0·01); history of smoking‐related pulmonary disease (P = 0·03) and cigarette consumption at index (P = 0·03).

Conclusions.  Smoking patients who do not participate in a heart rehabilitation programme may need extra help with smoking cessation. The findings may provide means of identifying patients in need of special intervention.
Spiritual perspectives, needs and nursing interventions of Christian African–Americans
Authors: Conner Norma E. , Eller Lucille Sanzero
Published: May 2004

Background. Although the amount of literature on spiritual needs and care has increased, in practice there has been little change in how nurses assess spiritual need. This suggests that not all spiritual needs of patients are being addressed. Based on the assumption that spiritual needs vary by culture, this study focused on one subgroup, namely Christian African–Americans.

Aims. The aim of this paper is to report a study examining spiritual perspectives, spiritual needs and desired nursing interventions during hospitalization identified by Christian African–Americans.

Methods. A descriptive correlational design was employed. A convenience sample (n = 44) was recruited from three African–American churches. Descriptive statistics were calculated, and one‐wayanovas used to examine spiritual perspectives and spiritual values. Content analysis was used to analyse and summarize qualitative data. Instruments included the Spiritual Perspective Scale (SPS) and two open‐ended questions.

Results. The mean age of participants was 56 years (range 19–84). The majority was female (86%); 71% of respondents strongly agreed that they had spiritual needs to be met during hospitalization. Mean score for the SPS was 5·7 (sd = 0·36). Respondents used a total of 103 phrases to describe spiritual needs, based on three dimensions of connectedness: connectedness to God (50 phrases), connectedness to others (37 phrases) and connectedness to self (16 phrases). Desired nursing interventions included: participating in spiritual activities (n = 41); demonstrating caring qualities (n = 27); providing comforting measures (n = 13); providing reassurance (n = 9); recognizing the spiritual caregiver role (n = 7); and incorporating diversity in care (n = 3).

Conclusions. The findings provide information for nurses to facilitate development of culturally appropriate spiritual nursing interventions.
Towards a Chinese definition of nursing
Authors: Pang Samantha M.C. , Wong Thomas K.S. , Wang Chun Sheng , Zhang Zhi Jun , Chan Helen Y.L. , Lam Cynthia W.Y. , Chan Kay Lok
Published: May 2004

Background.  A theory of nursing derived from nurses’ experience can reflect indigenous practice values, which in turn can act as a fertile source of ideas and inventiveness in developing a relevant knowledge base to inform practice. However, systematic study of how Chinese nurses articulate nursing in their everyday practice is lacking.

Aim.  The aim of this paper is to describe how Chinese nurses conceptualize the practice of nursing; and to arrive at a definition of nursing based on this common understanding.

Method.  A systematic inquiry using a modified version of Van Kaam's controlled explication was designed. In the prescientific phase, 254 written accounts of nurses’ views on nursing as lived in their everyday practice were collected in eight Chinese cities. In the scientific phase, concept analysis based on Aristotle's notion of four causes was adopted to capture the richness of the phrases that explain the multi‐dimensionality of Chinese nurses’ concepts of nursing. This was followed by a survey of 1782 nurses to verify the findings. The most commonly held views were summarized and a Chinese definition of nursing was drafted.

Findings.  Nursing in the Chinese sense means to understand the dynamic health status of a person, to verify health concerns dialectically, and to consider interventions with the goal of assisting the person to master the appropriate health knowledge and skills for the attainment of optimal well‐being. The survey findings show that nursing has developed into a professional caring practice in China today. The definition has some similarities with those of Western nurses, but the underpinning epistemic concerns are grounded in the philosophy of traditional Chinese medicine and Eastern ideologies.

Conclusion.  The findings provide Chinese nurses with a definition of nursing articulated in their own language. The identification of qing, li, zhi, and xin as its epistemic concerns, and the articulation of the process of nursing as ‘dialectical verification’, provides a perspective for understanding nursing based on Eastern philosophies. The findings can enhance nurses’ engagement in a cross‐cultural dialogue to promote better understanding of nursing as it is practised in different parts of the world.
Structural model for an AxxxG‐mediated dimer of surfactant‐associated protein C
Authors: Kairys Visvaldas , Gilson Michael K. , Luy Burkhard
Published: May 2004

The pulmonary surfactant prevents alveolar collapse and is required for normal pulmonary function. One of the important components of the surfactant besides phospholipids is surfactant‐associated protein C (SP‐C). SP‐C shows complex oligomerization behavior and a transition to β‐amyloid‐like fibril structures, which are not yet fully understood. Besides this nonspecific oligomerization, MS and chemical cross‐linking data combined with CD spectra provide evidence of a specific, mainly α‐helical, dimer at low to neutral pH. Furthermore, resistance to CNBr cleavage and dual NMR resonances of porcine and human recombinant SP‐C with Met32 replaced by isoleucine point to a dimerization site located at the C‐terminus of the hydrophobic α‐helix of SP‐C, where a strictly conserved heptapeptide sequence is found. Computational docking of two SP‐C helices, described here, reveals a dimer with a helix–helix interface that strikingly resembles that of glycophorin A and is mediated by an AxxxG motif similar to the experimentally determined GxxxG pattern of glycophorin A. It is highly likely that mature SP‐C adopts such a dimeric structure in the lamellar bilayer systems found in the surfactant. Dimerization has been shown in previous studies to have a role in sorting and trafficking of SP‐C and may also be important to the surfactant function of this protein.
Identifying determinants of NADPH specificity in Baeyer–Villiger monooxygenases
Authors: Kamerbeek Nanne M. , Fraaije Marco W. , Janssen Dick B.
Published: May 2004

The Baeyer–Villiger monooxygenase (BVMO), 4‐hydroxyacetophenone monooxygenase (HAPMO), uses NADPH and O2 to oxidize a variety of aromatic ketones and sulfides. The FAD‐containing enzyme has a 700‐fold preference for NADPH over NADH. Sequence alignment with other BVMOs, which are all known to be selective for NADPH, revealed three conserved basic residues, which could account for the observed coenzyme specificity. The corresponding residues in HAPMO (Arg339, Lys439 and Arg440) were mutated and the properties of the purified mutant enzymes were studied. For Arg440 no involvement in coenzyme recognition could be shown as mutant R440A was totally inactive. Although this mutant could still be fully reduced by NADPH, no oxygenation occurred, indicating that this residue is crucial for completing the catalytic cycle of HAPMO. Characterization of several Arg339 and Lys439 mutants revealed that these residues are indeed both involved in coenzyme recognition. Mutant R339A showed a largely decreased affinity for NADPH, as judged from kinetic analysis and binding experiments. Replacing Arg339 also resulted in a decreased catalytic efficiency with NADH. Mutant K439A displayed a 100‐fold decrease in catalytic efficiency with NADPH, mainly caused by an increased Km. However, the efficiency with NADH increased fourfold. Saturation mutagenesis at position 439 showed that the presence of an asparagine or a phenylalanine improves the catalytic efficiency with NADH by a factor of 6 to 7. All Lys439 mutants displayed a lower affinity for AADP+, confirming a role of the lysine in recognizing the 2′‐phosphate of NADPH. The results obtained could be extrapolated to the sequence‐related cyclohexanone monooxygenase. Replacing Lys326 in this BVMO, which is analogous to Lys439 in HAPMO, again changed the coenzyme specificity towards NADH. These results indicate that the strict NADPH dependency of this class of monooxygenases is based upon recognition of the coenzyme by several basic residues.
A Kazal prolyl endopeptidase inhibitor isolated from the skin of Phyllomedusa sauvagii
Authors: Gebhard Leopoldo G. , Carrizo Federico U. , Stern Ana L. , Burgardt Noelia I. , Faivovich Julián , Lavilla Esteban , Ermácora Mario R.
Published: May 2004

Searching for bioactive peptides, we analyzed acidic extracts of Phyllomedusa sauvagii skin and found two new proteins, PSKP‐1 and PSKP‐2, of 6.7 and 6.6 kDa, respectively, which, by sequence homology, belong to the Kazal family of serine protease inhibitors. PSKP‐1 and PSKP‐2 exhibit the unprecedented feature of having proline at P1 and P2 positions. A gene encoding PSKP‐1 was synthesized and expressed in Escherichia coli. Recombinant PSKP‐1 was purified from inclusion bodies, oxidatively refolded to the native state, and characterized by chemical, hydrodynamic and optical studies. PSKP‐1 shows inhibitory activity against a serum prolyl endopeptidase, but is unable to inhibit trypsin, chymotrypsin, V8 protease, or proteinase K. In addition, PSKP‐1 can be rendered active against trypsin by active‐site site‐specific mutagenesis, has bactericidal activity, and induces agglutination of red cells at micromolar concentrations. PSKP‐1 might protect P. sauvagii teguments from microbial invasion, by acting as an inhibitor of an as‐yet unidentified prolyl endopeptidase or directly as a microbicidal compound.
Fibroblast growth‐stimulating activity of S100A9 (MRP‐14)
Authors: Shibata Futoshi , Miyama Katsuyoshi , Shinoda Fumie , Mizumoto Jun , Takano Katsuhiko , Nakagawa Hideo
Published: May 2004

Fibroblasts play a critical role in chronic inflammation and wound healing. In this study, a fibroblast growth‐stimulating factor was purified from the exudate of carrageenan‐induced inflammation in rats. The purified protein was a disulfide‐linked homodimer. Amino acid sequence analysis of the peptides generated by cleavage with cyanogen bromide and proteinase V8 resulted in identification of the protein as S100A9. Recombinant S100A9 as well as its disulfide‐linked homodimer stimulated the proliferation of fibroblasts at a similar concentration of the purified protein. The concentration of S100A9 in the exudate was determined by immunoblot analysis. The total protein concentration in the exudate reached a maximum 4 days after carrageenan injection and then slightly decreased, whereas the concentration of S100A9 reached a maximum at day 3 and then decreased rapidly. These studies show that S100A9 is present at a high concentration in the exudate of carrageenan‐induced inflammation in rats, and that S100A9 stimulates proliferation of fibroblasts, suggesting that it plays a role in chronic inflammation.
Tet repressor residues indirectly recognizing anhydrotetracycline
Authors: Schubert Peter , Pfleiderer Klaus , Hillen Wolfgang
Published: May 2004

Two tetracycline repressor (TetR) sequence variants sharing 63% identical amino acids were investigated in terms of their recognition specificity for tetracycline and anhydrotetracycline. Thermodynamic complex stabilities determined by urea‐dependent unfolding reveal that tetracycline stabilizes both variants to a similar extent but that anhydrotetracycline discriminates between them significantly. Isofunctional TetR hybrid proteins of these sequence variants were constructed and their denaturation profiles identified residues 57 and 61 as the complex stability determinant. Association kinetics reveal different recognition of these TetR variants by anhydrotetracycline, but the binding constants indicate similar stabilization. The identified residues connect to an internal water network, which suggests that the discrepancy in the observed thermodynamics may be caused by an entropy effect. Exchange of these interacting residues between the two TetR variants appears to influence the flexibility of this water organization, demonstrating the importance of buried, structural water molecules for ligand recognition and protein function. Therefore, this structural module seems to be a key requisite for the plasticity of the multiple ligand binding protein TetR.
Oxidative neuronal injury
Authors: Chu Charleen T. , Levinthal David J. , Kulich Scott M. , Chalovich Elisabeth M. , DeFranco Donald B.
Published: May 2004

The extracellular signal regulated protein kinases (ERK1/2) are essential for normal development and functional plasticity of the central nervous system. However, a growing number of recent studies in models of cerebral ischemia, brain trauma and neurodegenerative diseases implicate a detrimental role for ERK1/2 signaling during oxidative neuronal injury. Neurons undergoing oxidative stress‐related injuries typically display a biphasic or sustained pattern of ERK1/2 activation. A variety of potential targets of reactive oxygen species and reactive nitrogen species could contribute to ERK1/2 activation. These include cell surface receptors, G proteins, upstream kinases, protein phosphatases and proteasome components, each of which could be direct or indirect targets of reactive oxygen or nitrogen species, thereby modulating the duration and magnitude of ERK1/2 activation. Neuronal oxidative stress also appears to influence the subcellular trafficking and/or localization of activated ERK1/2. Differences in compartmentalization of phosphorylated ERK1/2 have been observed in diseased or injured human neurons and in their respective animal and cell culture model systems. We propose that differential accessibility of ERK1/2 to downstream targets, which is dictated by the persistent activation of ERK1/2 within distinct subcellular compartments, underlies the neurotoxic responses that are driven by this kinase.
Structure and function of plant aspartic proteinases
Authors: Simões Isaura , Faro Carlos
Published: May 2004

Aspartic proteinases of the A1 family are widely distributed among plant species and have been purified from a variety of tissues. They are most active at acidic pH, are specifically inhibited by pepstatin A and contain two aspartic residues indispensible for catalytic activity. The three‐dimensional structure of two plant aspartic proteinases has been determined, sharing significant structural similarity with other known structures of mammalian aspartic proteinases. With a few exceptions, the majority of plant aspartic proteinases identified so far are synthesized with a prepro‐domain and subsequently converted to mature two‐chain enzymes. A characteristic feature of the majority of plant aspartic proteinase precursors is the presence of an extra protein domain of about 100 amino acids known as the plant‐specific insert, which is highly similar both in sequence and structure to saposin‐like proteins. This insert is usually removed during processing and is absent from the mature form of the enzyme. Its functions are still unclear but a role in the vacuolar targeting of the precursors has been proposed. The biological role of plant aspartic proteinases is also not completely established. Nevertheless, their involvement in protein processing or degradation under different conditions and in different stages of plant development suggests some functional specialization. Based on the recent findings on the diversity of A1 family members in Arabidopsis thaliana, new questions concerning novel structure–function relationships among plant aspartic proteinases are now starting to be addressed.
Glycosphingolipids in Plasmodium falciparum
Authors: Couto Alicia S. , Caffaro Carolina , Uhrig M. Laura , Kimura Emilia , Peres Valnice J. , Merino Emilio F. , Katzin Alejandro M. , Nishioka Masae , Nonami Hiroshi , Erra‐Balsells Rosa
Published: May 2004

Malaria remains a major health problem especially in tropical and subtropical regions of the world, and therefore developing new antimalarial drugs constitutes an urgent challenge. Lipid metabolism has been attracting a lot of attention as an application for malarial chemotherapeutic purposes in recent years. However, little is known about glycosphingolipid biosynthesis in Plasmodium falciparum. In this report we describe for the first time the presence of an active glucosylceramide synthase in the intraerythrocytic stages of the parasite. Two different experiments, using UDP‐[14C]glucose as donor with ceramides as acceptors, or UDP‐glucose as donor and fluorescent ceramides as acceptors, were performed. In both cases, we found that the parasitic enzyme was able to glycosylate only dihydroceramide. The enzyme activity could be inhibited in vitro with low concentrations of d,l‐threo‐phenyl‐2‐palmitoylamino‐3‐morpholino‐1‐propanol (PPMP). In addition, de novo biosynthesis of glycosphingolipids was shown by metabolic incorporation of [14C]palmitic acid and [14C]glucose in the three intraerythrocytic stages of the parasite. The structure of the ceramide, monohexosylceramide, trihexosylceramide and tetrahexosylceramide fractions was analysed by UV‐MALDI‐TOF mass spectrometry.

When PPMP was added to parasite cultures, a correlation between arrest of parasite growth and inhibition of glycosphingolipid biosynthesis was observed. The particular substrate specificity of the malarial glucosylceramide synthase must be added to the already known unique and amazing features of P. falciparum lipid metabolism; therefore this enzyme might represent a new attractive target for malarial chemotherapy.
Subunit composition of the glycyl radical enzyme p‐hydroxyphenylacetate decarboxylase
Authors: Andrei Paula I. , Pierik Antonio J. , Zauner Stefan , Andrei‐Selmer Luminita C. , Selmer Thorsten
Published: May 2004

p‐Hydroxyphenylacetate decarboxylase from Clostridium difficile catalyses the decarboxylation of p‐hydroxyphenylacetate to yield the cytotoxic compound p‐cresol. The three genes encoding two subunits of the glycyl‐radical enzyme and the activating enzyme have been cloned and expressed in Escherichia coli. The recombinant enzymes were used to reconstitute a catalytically functional system in vitro. In contrast with the decarboxylase purified from C. difficile, which was an almost inactive homo‐dimeric protein (β2), the recombinant enzyme was a hetero‐octameric (β4γ4), catalytically competent complex, which was activated using endogenous activating enzyme from C. difficile or recombinant activating enzyme to a specific activity of 7 U·mg−1. Preliminary results suggest that phosphorylation of the small subunit is responsible for the change of the oligomeric state. These data point to an essential function of the small subunit of the decarboxylase and may indicate unique regulatory properties of the system.