bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enzyme replacement therapy results in substantial improvements in early clinical phenotype in a mouse model of globoid cell leukodystrophy
Authors: Lee Wing C. , Courtenay Andrew , Troendle Frederick J. , Stallings‐Mann Melody L. , Dickey Chad A. , Delucia Michael W. , Dickson Dennis W. , Eckman Christopher B. 
Published: June 2005

ABSTRACTGloboid cell leukodystrophy (GLD) or Krabbe disease is a devastating, degenerative neurological disorder caused by mutations in the galactosylceramidase (GALC) gene that severely affect enzyme activity. Currently, treatment options for this disorder are very limited. Enzyme replacement therapy (ERT) has been shown to be effective in lysosomal storage disorders with predominantly peripheral manifestations such as type I Gaucher's and Fabry's disease. Little however is known about the possible benefit of ERT in GLD, which has a substantial central nervous system component. In this study, we examined the effect of peripheral GALC injections in the twitcher mouse model of the disease. Although we were unable to block the precipitous decline that normally occurs just before death, we did observe significant early improvements in motor performance, a substantial attenuation in the initial failure to thrive, and an increase in life span. Immunohistochemical and activity analyses demonstrated GALC uptake in multiple tissues, including the brain. This was associated with a decrease in the abnormal accumulation of the GALC substrate psychosine, which is thought to play a pivotal role in disease pathology. These results indicate that peripheral ERT is likely to be beneficial in GLD.
Protein–protein interactions as a tool for site‐specific labeling of proteins
Authors: Jäger Marcus , Michalet Xavier , Weiss Shimon 
Published: June 2005

AbstractProbing structures and dynamics within biomolecules using ensemble and single‐molecule fluorescence resonance energy transfer requires the conjugation of fluorophores to proteins in a site‐specific and thermodynamically nonperturbative fashion. Using single‐molecule fluorescence‐aided molecular sorting and the chymotrypsin inhibitor 2–subtilisin BPN′ complex as an example, we demonstrate that protein–protein interactions can be exploited to afford site‐specific labeling of a recombinant double‐cysteine variant of CI2 without the need for extensive and time‐consuming chromatography. The use of protein–protein interactions for site‐specific labeling of proteins is compatible with and complementary to existing chemistries for selective labeling of N‐terminal cysteines, and could be extended to label multiple positions within a given polypeptide chain.
Oligomerization of the fifth transmembrane domain from the adenosine A2A receptor
Authors: Thévenin Damien , Lazarova Tzvetana , Roberts Matthew F. , Robinson Clifford R. 
Published: June 2005

AbstractThe human adenosine A2A receptor (A2AR) belongs to one of the largest family of membrane proteins, the G‐protein coupled receptors (GPCRs), characterized by seven transmembrane (TM) helices. Little is known about the determinants of their structures, folding, assembly, activation mechanisms, and oligomeric states. Previous studies in our group showed that peptides corresponding to all seven TM domains form stable helical structures in detergent micelles and lipid vesicles. However, the peptides behave differently; TM5 is the only peptide to have a ratio [θ]222/[θ]208 obtained by circular dichroism (CD) spectroscopy>1. This finding suggested to us that TM5 might self‐associate. In the present study, we investigate the unique properties of the TM5 domain. We performed detailed analyses of TM5 peptide behavior in membrane‐mimetic environments using CD spectroscopy, fluorescence spectroscopy and Förster resonance energy transfer, and gel electrophoresis. We find that TM5 peptide has the ability to self‐associate to form oligomeric structures in various hydrophobic milieus and that these oligomers are highly resistant to temperature and chemical denaturation. We also find that mutation of the full‐length A2AR at position M193, which is located in the fifth TM domain, noticeably alters A2AR monomer: dimer ratio as observed on SDS‐PAGE. Our results suggest that parallel association of TM5 dimers may play a role in the known adenosine A2A receptor dimerization. This study represents the first evidence of an individual GPCR transmembrane domain self‐association.
Simultaneous optimization of enzyme activity and quaternary structure by directed evolution
Authors: Vamvaca Katherina , Butz Maren , Walter Kai U. , Taylor Sean V. , Hilvert Donald 
Published: June 2005

AbstractNatural evolution has produced efficient enzymes of enormous structural diversity. We imitated this natural process in the laboratory to augment the efficiency of an engineered chorismate mutase with low activity and an unusual hexameric topology. By applying two rounds of DNA shuffling and genetic selection, we obtained a 400‐fold more efficient enzyme, containing three non‐active‐site mutations. Detailed biophysical characterization of the evolved variant suggests that it exists predominantly as a trimer in solution, but is otherwise similarly stable as the parent hexamer. The dramatic structural and functional effects achieved by a small number of seemingly innocuous substitutions highlights the utility of directed evolution for modifying protein–protein interactions to produce novel quaternary states with optimized activities.
Mutagenic analysis of the nucleation propensity of oxidized Alzheimer's β‐amyloid peptide
Authors: Christopeit Tony , Hortschansky Peter , Schroeckh Volker , Gührs Karlheinz , Zandomeneghi Giorgia , Fändrich Marcus 
Published: June 2005

AbstractThe formation of polypeptide aggregates represents a nucleated polymerization reaction in which an initial nucleation event (lag phase) is followed by the extension of newly formed nuclei into larger aggregates, including fibrils (growth phase). The efficiencies of these reactions relate to the lag time (lag phase) and to the rate of aggregation (growth phase), which can be determined from experimental aggregation curves. Here we present a mutagenic analysis in which we replace valine 18 of the Alzheimer's Aβ (1–40) peptide with 17 different amino acids and determine its effect on the lag time, and therefore, on the propensity of nucleation. Comparison with various physico‐chemical properties shows that nucleation is affected in a predictable manner depending on the β‐sheet propensity and hydrophobicity of residue 18. In addition, we observe a direct proportionality between the lag time and the rate of aggregation. These data imply that the two reactions, nucleation and polymerization, are governed by very similar physicochemical principles and that they involve the formation of the same types of noncovalent interactions.
Solution structure of thioredoxin h1 from Arabidopsis thaliana
Authors: Peterson Francis C. , Lytle Betsy L. , Sampath Sujatha , Vinarov Dmitriy , Tyler Ejan , Shahan Mark , Markley John L. , Volkman Brian F. 
Published: June 2005

AbstractPresent in virtually every species, thioredoxins catalyze disulfide/dithiol exchange with various substrate proteins. While the human genome contains a single thioredoxin gene, plant thioredoxins are a complex protein family. A total of 19 different thioredoxin genes in six subfamilies has emerged from analysis of the Arabidopsis thaliana genome. Some function specifically in mitochondrial and chloroplast redox signaling processes, but target substrates for a group of eight thioredoxin proteins comprising the h subfamily are largely uncharacterized. In the course of a structural genomics effort directed at the recently completed A. thaliana genome, we determined the structure of thioredoxin h1 (At3g51030.1) in the oxidized state. The structure, defined by 1637 NMR‐derived distance and torsion angle constraints, displays the conserved thioredoxin fold, consisting of a five‐stranded β‐sheet flanked by four helices. Redox‐dependent chemical shift perturbations mapped primarily to the conserved WCGPC active‐site sequence and other nearby residues, but distant regions of the C‐terminal helix were also affected by reduction of the active‐site disulfide. Comparisons of the oxidized A. thaliana thioredoxin h1 structure with an h‐type thioredoxin from poplar in the reduced state revealed structural differences in the C‐terminal helix but no major changes in the active site conformation.
Precursor complex structure of pseudouridine synthase TruB suggests coupling of active site perturbations to an RNA‐sequestering peripheral protein domain
Authors: Hoang Charmaine , Hamilton Christopher S. , G.Mueller Eugene , Ferré‐D'Amaré Adrian R. 
Published: June 2005

AbstractThe pseudouridine synthase TruB is responsible for the universally conserved post‐transcriptional modification of residue 55 of elongator tRNAs. In addition to the active site, the “thumb,” a peripheral domain unique to the TruB family of enzymes, makes extensive interactions with the substrate. To coordinate RNA binding and release with catalysis, the thumb may be able to sense progress of the reaction in the active site. To establish whether there is a structural correlate of communication between the active site and the RNA‐sequestering thumb, we have solved the structure of a catalytically inactive point mutant of TruB in complex with a substrate RNA, and compared it to the previously determined structure of an active TruB bound to a reaction product. Superposition of the two structures shows that they are extremely similar, except in the active site and, intriguingly, in the relative position of the thumb. Because the two structures were solved using isomorphous crystals, and because the thumb is very well ordered in both structures, the displacement of the thumb we observe likely reflects preferential propagation of active site perturbations to this RNA‐binding domain. One of the interactions between the active site and the thumb involves an active site residue whose hydrogen‐bonding status changes during the reaction. This may allow the peripheral RNA‐binding domain to monitor progress of the pseudouridylation reaction.
Treatment outcomes for adolescent ectodermal dysplasia patients treated with dental implants
Authors: SWEENEY I. P. , FERGUSON J. W. , HEGGIE A. A. , LUCAS J. O. 
Published: June 2005

Summary.To evaluate dental implant survival in patients with ectodermal dysplasia (ED). To assess patterns of hypodontia in this patient group.Methods.  A retrospective analysis of the use of dental implants in ED patients treated at the Royal Children's Hospital, Melbourne.Results.  Sixty‐one implants were placed into 14 patients (nine male and five female). The mean age of patients receiving maxillary implants was 18 years 6 months (range 17 years 9 months−20 years 0 months) and mandibular implants was 17 years 5 months (range 12 years 2 months−21 years 11 months). The mean follow‐up period was 3 years 4 months (range 1 year 18 months−5 years 1 month). Forty‐three implants were placed in the anterior mandible, three in the posterior mandible and the remaining 15 in the anterior maxilla. Of the 61 implants placed, 54 [88·5%] successfully integrated and were able to be restored. Three of the 15 implants placed into the anterior maxilla [20%] failed, while four of the 46 in the anterior mandible failed [8·7%]. Five of the 14 patients [35·7%] had at least one implant fail prior to abutment connection. At the 12‐month review appointments, 41 of the integrated 54 implants [76%] were reviewed and classed as successful, giving an overall success at follow up of 67·2%. Thirteen implants [21·3%] were unable to be reviewed owing to geographical reasons. Teeth most likely to be present in the maxilla were the central incisors [71%], first molars [54%] and canines [43%], whereas in the mandible they were the canines [53%] and the first premolars and first molars [40%].Conclusions.  Dental implants can be placed, restored and loaded in ED patients. Maxillary teeth most likely to be present are the central incisors, canines and first molars, whereas in the mandible the canines, first premolars and molars are most likely to be present. Prior to cessation of growth, implant placement in the symphyseal region of the anterior mandible may be performed with caution. Despite the limited numbers and with due consideration to jaw development, the results support the continual use of endosseous dental implants in this group of patients for optimal clinical outcomes.
Restoration of severely decayed primary incisors using indirect composite resin restoration technique
Authors: MOTISUKI C. , SANTOS‐PINTO L. , GIRO E. M. A. 
Published: June 2005

Summary.Caries of primary incisors is a common problem in paediatric dentistry in some countries. The restoration of primary incisors which have been severely damaged by early childhood caries or trauma is also a difficult challenge for clinicians. This case report describes an indirect technique for the restoration of primary anterior teeth using composite resin reinforced with a fibreglass post. Over a one‐year period, the crowns have demonstrated good retention and aesthetic results. The restorations were provided in two short chair‐side sections, with satisfactory patient cooperation.
Pain: a review of three commonly used pain rating scales
Authors: Williamson Amelia , Hoggart Barbara 
Published: June 2005

Aims and objectives.  This review aims to explore the research available relating to three commonly used pain rating scales, the Visual Analogue Scale, the Verbal Rating Scale and the Numerical Rating Scale. The review provides information needed to understand the main properties of the scales.Background.  Data generated from pain‐rating scales can be easily misunderstood. This review can help clinicians to understand the main features of these tools and thus use them effectively.Method.  A MedLine review via PubMed was carried out with no restriction of age of papers retrieved. Papers were examined for methodological soundness before being included. The search terms initially included pain rating scales, pain measurement, Visual Analogue Scale, VAS, Verbal Rating Scale, VRS, Numerical/numeric Rating Scale, NRS. The reference lists of retrieved articles were used to generate more papers and search terms. Only English Language papers were examined.Conclusions.  All three pain‐rating scales are valid, reliable and appropriate for use in clinical practice, although the Visual Analogue Scale has more practical difficulties than the Verbal Rating Scale or the Numerical Rating Scale. For general purposes the Numerical Rating Scale has good sensitivity and generates data that can be statistically analysed for audit purposes. Patients who seek a sensitive pain‐rating scale would probably choose this one. For simplicity patients prefer the Verbal Rating Scale, but it lacks sensitivity and the data it produces can be misunderstood.Relevance to clinical practice.  In order to use pain‐rating scales well clinicians need to appreciate the potential for error within the tools, and the potential they have to provide the required information. Interpretation of the data from a pain‐rating scale is not as straightforward as it might first appear.
Risk management of extravasation of cytostatic drugs at the Adult Chemotherapy Outpatient Clinic of a university hospital
Authors: Adami Nilce Piva , De Gutiérrez Maria Gaby Rivero , Da Fonseca Selma Montosa , De Almeida Elizabeth Pinto Magalhães 
Published: June 2005

Aims and objectives.  To verify the incidence of extravasation of cytostatic drugs in patients treated on an outpatient basis at a university hospital in the city of São Paulo, Brazil, during the period from 1998 to 2002, and to assess the quality of care provided by the nursing team using a protocol adopted for the treatment of this adverse event as a parameter.Background.  The movement for quality in healthcare services has been a recent event in Brazil, mainly as the result of the Brazilian Program of Hospital Accreditation instituted in 1998. Considering the emphasis on risk management, it is important to mention the monitoring of the occurrence of extravasations of cytostatic drugs in order to improve the quality of nursing care provided to cancer patients.Design and methods.  An evaluative study with a descriptive, prospective and longitudinal design was conducted, based on the documentary analysis of the notification of 216 extravasations of vesicant and irritant drugs that occurred between 1998 and 2002 and the corresponding prescriptions of cold or hot compresses.Results.  The mean incidence of extravasations ranged from 0·2 to 1·4% over the five years of the study. Incorrect prescription of the type of compress was observed for three patients. Undesired effects were ulcers caused by the extravasation of vinblastine and dacarbazine in two cases.Conclusions.  The low incidence of both extravasation and tissue damage demonstrates the adequate quality of nursing care provided to cancer patients at the outpatient clinic studied. However, the identification of the lack of 12 records of thermal treatment and of three erroneous prescriptions requires the implementation of educational measures to prevent these types of incident.Relevance to clinical practice.  The relevance of this study to clinical practice is to increase the awareness and involvement of the nursing team in the maintenance of a continuous surveillance system of the process and results of chemotherapy administration in order to increase the quality of care and the safety of the patient.
Obesity: translation and testing of a survey instrument for use in Taiwan
Authors: Hsieh Pei‐Lin , Cholowski Krystyna , FitzGerald Mary 
Published: June 2005

Aim and objectives.  The purpose of this paper is to describe a cross‐cultural translation and validation methodology recommended by Vallerand. The translation technique has seven steps and ensures the instrument provides data that are valid and reliable.Background.  Translation of data collection instruments is a challenge increasingly being faced by overseas students studying in the West as they choose to research contextual issues of relevance to their home culture.Methods.  Six of Vallerand's seven steps are used and modified as the methodical translation of a survey from English to Mandarin.Results.  The results revealed there was no significant difference between the original English questionnaire and Mandarin questionnaire. The validation study indicated good internal consistency. The construct validity of the Mandarin version was determined except one item which failed the test. The validation demonstrates only minor effects of language translation.Conclusion.  The Mandarin version thus is a valid tool for investigating from the perspective of school nurses, their role and potential contribution to health promotion in relation to the prevention of obesity among school children in Taiwan.Relevance to clinical practice.  The results of the study will enable school nurses and their managers to reflect critically on their contribution to the prevention of obesity among Taiwanese school children. The translation technique has enabled the researcher to minimize errors that may have occurred in translation. It adds to the quality of the instrument and offers opportunities in the future to undertake cross‐cultural comparison in an issue of great concern globally.
Lucidity in a woman with severe dementia related to conversation. A case study
Authors: Normann Hans Ketil , Henriksen Nils , Norberg Astrid , Asplund Kenneth 
Published: June 2005

Aims and objectives.  The aim of this study was to explore the presence of lucidity in a woman with severe dementia during conversations and whether it occurred when conversational partners or the woman with severe dementia initiated the conversation topics about the present, past or future time and whether she was presented with support or demands during the conversation.Background.  Communication problems as well as episodes of lucidity in people with dementia are reported in the literature.Design.  A researcher held 20 hours of conversation with a woman with severe dementia. A daughter participated for about three and a half hours. The conversation was tape‐recorded and transcribed verbatim.Methods.  The text was divided into units of analysis. Each unit of analysis was then assessed separately and discussed among the authors. Chi‐square tests and logistic regression analysis were performed. An ethics committee approved the study.Results.  The woman as initiator of the conversation topic and support to the women during conversation from the conversation partner were found to be the most significant factors explaining lucidity, while conversation about the present or past time showed no connection with lucidity. Very few topics (n = 7) concerned future time and they were not used in the statistical analysis. The researcher initiated 41%, the woman 43% and the daughter 16% of the topics. Support was registered in 49%, demands in 15% and both support and demands in 16% of the units of analysis. There were 58% topics about present and 40% about the past time.Conclusions.  The presented study is a case study and the results cannot be generalized. For the woman with severe dementia, lucidity was promoted by the conversational parties carefully focusing on conversation topics initiated by the woman while supporting her during conversation.Relevance to clinical practice.  To share the same perception of reality, focusing on the topics initiated by the patient with severe dementia and a supporting attitude to what the patient tells, will hopefully give more episodes of lucidity in the patient. This approach in caring for patients with severe dementia might give more meaning and well‐being to the conversational partners in daily care.
The nature of nursing care and rehabilitation of female stroke survivors: the perspective of hospital nurses
Authors: Kvigne Kari , Kirkevold Marit , Gjengedal Eva 
Published: June 2005

Aims and objectives.  The aim of this study was to explore the nature of nursing care and rehabilitation of female stroke survivors, as described by hospital nurses. The objectives were to uncover how the nurses perceived the care of female stroke survivors and to explore whether, and in what way, the nurses paid attention to the fact that the patients were women.Background.  Nursing care is an important aspect of the rehabilitation of stroke survivors. Little attention has been paid to gender differences in the health care system in general and in the nursing profession in particular, although it is reasonable to think that gender issues may have important implications in the rehabilitation process following a stroke.Design.  Design was phenomenological with feminist perspective.Methods.  The nurses were interviewed in‐depth. In the data analysing process we were inspired by Giorgi's phenomenological method.Results.  The nurses were focusing primarily on functional and practical aspects of the women's situation. They perceived the rehabilitation process predominately from a professional rather than the patient point of view, and from a non‐conscious and primarily gender‐neutral perspective.Conclusions.  The results indicate that the nurses perceived nursing care primarily in terms of practical actions to promote the body's functional and practical abilities. Little attention was directed to the stroke survivors’ experiences of their life body, nor to the fact that the patients were women.Relevance to clinical practice.  In order to promote care from the perspective of the female stroke survivors, we believe it is necessary to attend to the life experiences of the patient, which also mandates paying attention to how gender has an impact on their diseased bodies, every day life, values and preferences in the situation.