bluuebunny/crossref_metadata_2025_split huggingface dataset:
The dimerization domain of the HIV‐1 capsid protein binds a capsid protein‐derived peptide: A biophysical characterization
Authors: Garzón María T. , Lidón‐Moya María C. , Barrera Francisco N. , Prieto Alicia , Gómez Javier , Mateu Mauricio G. , Neira José L. 
Published: May 2004

AbstractThe type 1 HIV presents a conical capsid formed by ∼1500 units of the capsid protein, CA. Homodimer‐ization of CA via its C‐terminal domain, CA‐C, constitutes a key step in virion assembly. CA‐C dimerization is largely mediated by reciprocal interactions between residues of its second α‐helix. Here, we show that an N‐terminal‐acetylated and C‐terminal–amidated peptide, CAC1, comprising the sequence of the CA‐C dimerization helix plus three flanking residues at each side, is able to form a complex with the entire CA‐C domain. Thermal denaturation measurements followed by circular dichroism (CD), NMR, and size‐exclusion chromatography provided evidence of the interaction between CAC1 and CA‐C. The apparent dissociation constant of the heterocomplex formed by CA‐C and CAC1 was determined by several biophysical techniques, namely, fluorescence (using an anthraniloyl‐labeled peptide), affinity chromatography, and isothermal titration calorimetry. The three techniques yielded similar values for the apparent dissociation constant, in the order of 50 μM. This apparent dissociation constant was only five times higher than was the dissociation constant of both CA‐C and the intact capsid protein homodimers (10 μM).
Modulation of the structural integrity of helix F in apomyoglobin by single amino acid replacements
Authors: Picotti Paola , Marabotti Anna , Negro Alessandro , Musi Valeria , Spolaore Barbara , Zambonin Marcello , Fontana Angelo 
Published: May 2004

AbstractThe conformational features of native and mutant forms of sperm‐whale apomyoglobin (apoMb) at neutral pH were probed by limited proteolysis experiments utilizing up to eight proteases of different substrate specificities. It was shown that all proteases selectively cleave apoMb at the level of chain segment 82–94 (HEAELKPLAQSHA), encompassing helix F in the X‐ray structure of the holo form of the native protein; for example, thermolysin cleaves the Pro 88–Leu 89 peptide bond. These results indicate that helix F is highly flexible or largely disrupted in apoMb. Because helix F contains the helix‐breaking Pro 88 residue, we propose that helix F is kept in place in the native holo protein by a variety of helix–heme stabilizing interactions. To modulate the stability of helix F, the Pro88Ala and Pro88Gly mutants were prepared by site‐directed mutagenesis, and their conformational properties investigated by both far‐UV circular dichroism spectroscopy and limited proteolysis. The helix content of the Pro88Ala mutant was somewhat enhanced with respect to that of both native and Pro88Gly mutant, as expected from the fact that Ala is the strongest helix inducer among the 20 amino acid residues. The rate of limited proteolysis of the three apoMb variants by thermolysin and proteinase K was in the order native > Pro88Gly >> Pro88Ala, in agreement with the scale of helix propensity of Ala, Gly, and Pro. The possible role of the flexible/unfolded chain segment 82–94 for the function and fate of apoMb at the cellular level is discussed.
A novel and conserved pocket of human κ‐Fab fragments: Design, synthesis, and verification of directed affinity ligands
Authors: Carredano Enrique , Baumann Herbert , Grönberg Anna , Norrman Nils , Glad Gunnar , Zou Jinyu , Ersoy Oguz , Steensma Elles , Axén Andreas 
Published: May 2004

AbstractAntibodies of type IgG may be divided into two classes, called λor κ, depending on the type of light chain. We have identified a conserved pocket between the two domains CH1 and CL of human IgG κ‐Fab, which is not present in the λ type. This pocket was used as a target docking site with the purpose of exploring the possibilities of designing affinity ligands that could function as such even after immobilization to gel. The idea of the design arose mainly from the results of the saturated transfer difference (STD‐NMR) screening of 46 compounds identified by means of virtual docking of 60 K diverse compounds from the Available Chemicals Directory (ACD). Surface plasmon resonance (SPR) was used as an alternative method to monitor binding in solution. A total of 24 compounds belonging to a directed library were designed, synthesized, and screened in solution. They consist essentially of an amino acid condensed to a N,N′‐methylated phenyl urea. STD‐NMR results suggest that a small hydrophobic side chain in the condensed amino acid promotes binding, whereas a hydroxyl‐group–containing side chain implies absence of STD‐NMR signals. Three compounds of the directed library were immobilized and evaluated as chromatographic probes. In one case, using D‐Pro as the condensed amino acid, columns packed with ligand‐coupled Sepharose (Amersham Biosciences) retained two different monoclonal samples of κ‐Fab fragments with different variable regions, whereas a sample of monoclonal λ‐Fab fragments was not retained under similar chromatographic conditions.
The structure of Ski8p, a protein regulating mRNA degradation: Implications for WD protein structure
Authors: Madrona A. Yarrow , Wilson David K. 
Published: May 2004

AbstractSki8p is a 44‐kD protein that primarily functions in the regulation of exosome‐mediated, 3′→ 5′ degradation of damaged mRNA. It does so by forming a complex with two partner proteins, Ski2p and Ski3p, which complete a complex that is capable of recruiting and activating the exosome/Ski7p complex that functions in RNA degradation. Ski8p also functions in meiotic recombination in complex with Spo11 in yeast. It is one of the many hundreds of primarily eukaryotic proteins containing tandem copies of WD repeats (also known as WD40 or β‐transducin repeats), which are short ∼40 amino acid motifs, often terminating in a Trp–Asp dipeptide. Genomic analyses have demonstrated that WD repeats are found in 1%–2% of proteins in a typical eukaryote, but are extremely rare in prokaryotes. Almost all structurally characterized WD‐repeat proteins are composed of seven such repeats and fold into seven‐bladed β propellers. Ski8p was thought to contain five WD repeats on the basis of primary sequence analysis implying a five‐bladed propeller. The 1.9 Å crystal structure unexpectedly exhibits a seven‐bladed propeller fold with seven structurally authentic WD repeats. Structure‐based sequence alignments show additional sequence diversity in the two undetected repeats. This demonstrates that many WD repeats have not yet been identified in sequences and also raises the possibility that the seven‐bladed propeller may be the predominant fold for this family of proteins.
Cathepsin L‐deficient mice exhibit abnormal skin and bone development and show increased resistance to osteoporosis following ovariectomy
Authors: Potts Wendy , Bowyer Jonathan , Jones Huw , Tucker David , Freemont Anthony J. , Millest Andrew , Martin Colin , Vernon Wendy , Neerunjun Diane , Slynn Gillian , Harper Fiona , Maciewicz Rose 
Published: May 2004

SummaryThe role of cathepsin L in normal physiological processes was assessed using cathepsin L homozygous knockout mice (B6;129‐Ctsltm1Alpk). These mice were generated using gene targeting in embryonic stem cells. Null mice fail to express mRNA and protein to cathepsin L. They developed normally and were fertile. The distinct phenotypic change exhibited was a progressive hair loss, culminating in extensive alopecia by 9 months of age. Histological analysis of the skin from homozygous mice revealed diffuse epithelial hyperplasia, hypotrichosis, hair shaft fragmentation and utricle formation. These findings provide evidence that cathepsin L is involved in the regulation of epithelial cell proliferation and differentiation in the skin. In addition, the role of cathepsin L in bone remodelling was evaluated. Using bone histomorphometric measurements, trabecular, but not cortical, bone volume was found to be significantly decreased in the cathepsin L heterozygote and homozygote mice compared to the wild‐type mice. Following ovariectomy, it was observed that loss of trabecular bone, the most metabolically active component of bone, occurred to a lesser extent in homozygote, and heterozygote mice, than was seen in wild‐type mice. These observations suggest that cathepsin L is likely to have a role in controlling bone turnover during normal development and in pathological states.
Reduced incidence of gastroduodenal ulcers associated with lumiracoxib compared with ibuprofen in patients with rheumatoid arthritis
Authors: Kivitz A. J. , Nayiager S. , Schimansky T. , Gimona A. , Thurston H. J. , Hawkey C. 
Published: May 2004

SummaryBackground : Lumiracoxib (Prexige; Novartis Pharma AG, Basel, Switzerland) is a cyclooxygenase‐2 selective inhibitor associated with improved gastrointestinal safety compared with nonsteroidal anti‐inflammatory drugs, in patients with osteoarthritis.Aim : To compare the gastroduodenal safety of lumiracoxib with ibuprofen and celecoxib in patients with rheumatoid arthritis.Methods : A total of 893 patients with rheumatoid arthritis were randomized to lumiracoxib 400 mg once daily, lumiracoxib 800 mg once daily, ibuprofen 800 mg three times daily or celecoxib 200 mg twice daily for 13 weeks, in a double‐blind randomised controlled clinical trial. The primary endpoint was the cumulative incidence of gastroduodenal ulcers over 13 weeks.Results : The incidence of gastroduodenal ulcers ≥3 mm with lumiracoxib 400 mg once daily (2.8%) or lumiracoxib 800 mg once daily (4.3%) was significantly lower than with ibuprofen (13.6%, all P < 0.01) and not different from celecoxib (1.9%). The incidence of adverse events was similar for lumiracoxib 400, 800 mg and celecoxib (78, 75 and 77%, respectively) and higher with ibuprofen (86%). Discontinuation for adverse events was highest for ibuprofen (12.5% vs. 7.9–8.8% for the other groups).Conclusions : Lumiracoxib demonstrated gastroduodenal safety superior to ibuprofen and similar to celecoxib in patients with rheumatoid arthritis.
Postoperative complications in the first 24 hours: a general surgery audit
Authors: Zeitz Kathryn , McCutcheon Helen , Albrecht Annette 
Published: May 2004

Background.  Traditionally, the purpose of routine postoperative surveillance has been to detect postoperative complications. The literature reports well‐documented, procedure‐specific postoperative complication rates. However, there are no reports detailing the prevalence of postoperative complications in general surgical ward settings, where nurses care for patients following a variety of surgical procedures.Aims.  This paper reports an audit of the frequency and type of postoperative complications in a general surgical population occurring in the first 24 hours postoperatively.Method.  A patient record audit was undertaken for all postoperative patients who returned to two general surgical wards. This was conducted sequentially, involving a 4 week data collection phase in each participating ward during 2001.Results.  The audit sample comprised 144 patient records with an average patient age of 54 years. Statistically significant results included the rate of postoperative nausea and vomiting of 37·5% (n = 54), and 17% (n = 25) of patients experiencing another ‘clinical event’.Limitations.  The findings reflect only those complications recorded/documented in postoperative patients’ records, and cannot be generalized beyond the sample and setting.Conclusions.  Postoperative patients cared for on general surgical wards experienced a high level of nausea and vomiting, while the occurrence of life‐threatening complications was small.
Women's experience of endometriosis
Authors: Denny Elaine 
Published: May 2004

Background.  Endometriosis is a chronic disease affecting between 5% and 15% of women of reproductive age. Diagnosis can be delayed for many years, despite the existence of severe pain, and women often find that their experiences are not taken seriously by health professionals. Little research has been conducted into how endometriosis affects their lives.Aim.  The aim of this paper is to report a study exploring women's experience of living with endometriosis.Method.  A qualitative approach was used, in which women were asked to relate their stories starting from the first experience of symptoms that they associated with endometriosis. Key areas to be followed‐up during interviews were identified by women with endometriosis who were not participants. Fifteen semi‐focused interviews were conducted, and thematic and content analysis were carried out using the identified key areas, and themes elicited from initial analysis of the interview transcripts. From these two processes the final themes of delay in diagnosis, pain, dyspareunia, treatment, work and social relationships, the workplace, and the future emerged.Findings.  Despite the existence of severe pain, often described as ‘intense’ or ‘overwhelming’, women experienced delay in receiving a diagnosis of endometriosis, and their symptoms were frequently trivialized or normalized. This, and the limited effectiveness of treatments, affected relationships with partners and family, work, and sexual relations, although individual experiences in each area were diverse.Conclusion.  The experience of endometriosis pervades all aspects of a woman's life. This experience is compounded by the side effects of many treatments. Women with this disease need to be taken seriously, and not have their pain trivialized or normalized. Nurses are often well‐placed to assist patients in receiving sensitive and appropriate care.
Sensitivity and specificity of serology in determining recent acute Campylobacter infection
Authors: Taylor B. V. , Williamson J. , Luck J. , Coleman D. , Jones D. , McGregor A. 
Published: May 2004

Abstract Background : The measurement of serum antibodies to Campylobacter spp. has been used to investigate links between prior Campylobacter infections and the development of Guillain−Barre syndrome and its variants. Little is known of the serum antibody response to acute infections in the short‐ or long‐term.Aims : The aims of the present study were to investigate the normal serum response to an acute Campylobacter infection and the sensitivity and specificity of anti‐Campylobacter antibodies in determining recent Campylo­bacter infection.Methods : An enzyme‐linked immunosorbent assay (ELISA) method was used to measure serum anti‐Campylobacter immunoglobulin G (IgG), IgA and IgM antibodies. Controls consisted of 420 blood donors without recent gastroenteritis, 25 patients with other gastrointestinal infections, 24 patients with neurological conditions not affecting the peripheral nerves and 19 patients with autoimmune disorders. Three patient groups were assessed: 99 patients with acute Campy­lo­bacter infections, all of whom were tested 3 weeks post‐infection; 69 of these patients tested 3−6 months later; and 74 additional patients tested>20 months post‐­infection. Western blot analysis was performed on controls and patients with high titre anti‐Campylobacter anti­bodies to assess for cross‐reactivity and specificity.Results : Following acute infections, all antibody classes rose in the majority of but not in all patients, followed by decreasing titres that did not return to baseline levels. Sixteen per cent of enteritis cases did not demonstrate a rise in titres and 9% of cases had significant levels of antibodies>20 months post‐infection. The ELISA used was shown to be highly specific for the detection of Campylobacter antibodies.Conclusion : The use of Campylobacter‐specific antibody levels as the sole marker of prior infection is an unreli­able method of determining the association between Campylobacter infection and neurological disease. (Intern Med J 2004; 34: 250−258)
Can patients with dementia be assessed at a distance? The use of Telehealth and standardised assessments
Authors: Loh P.K. , Ramesh P. , Maher S. , Saligari J. , Flicker L. , Goldswain P. 
Published: May 2004

Abstract Background : Telehealth could be a medium for the provision of cognitive assessments to distant sites.Aims : The aims of the present study were to determine the interrater reliability of the Standardized Mini Mental State Exam (SMMSE) and the Geriatric Depression Scale (GDS) through Telehealth as compared to face‐to‐face administration.Methods : Duplicate interviews of subjects with cross‐over of interview modality were carried out. Twenty patients were interviewed between two sites 11 km apart. Subjects were persons older than 65 years (mean age 82 years) who consented to Telehealth assessments. The outcome measures were the differences in assessment scores between the two media.Results : The average SMMSE score by remote assessment was 24.0 (range 11.0−30.0) and by direct assessment was 24.3 (range 9.0−30.0). The correlation between direct and remote SMMSE scores was 0.90. The mean difference between direct and remote SMMSE scores was −0.3 (95% confidence interval (CI): −4.6 to 4.0). In 8 of 20 participants (40%) the difference between Telehealth and direct assessments was two points or more on the SMMSE. The average GDS by remote assessment was 6.1 (range 1.0−14.0) and by direct assessment was 5.8 (range 2.0−13.0). The correl­ation between direct and remote GDS scores was 0.78. The mean difference between direct and remote GDS assessment was 0.3 (95% CI: −3.8 to 4.4).Conclusion : Remote assessments with SMMSE and GDS using Telehealth methods yielded similar results to direct assessments. However, there was a moderate ­difference between face‐to‐face and Telehealth assessments in some subjects, which could influence clinical ­decision‐making. (Intern Med J 2004; 34: 239−242)
New concepts in breast cancer therapy
Authors: Snyder R. D. 
Published: May 2004

Abstract Breast cancer is a common disease in the community. Its incidence is increasing but its mortality is falling. New therapeutic approaches based on a biological understanding of the disease are being investigated to improve the outcome. These include the areas of chemo­prevention and therapy in the adjuvant and advanced settings, and some derive from a better understanding of the biology of breast cancer. New prognostic indicators are being studied to enable adjuvant chemotherapy to be directed towards those most likely to benefit. Trastuzumab was the first of the new targeted therapies to be introduced into routine practice. Several other agents targeting a variety of receptors and cell pathways, such as the epidermal growth factor receptor, the vascular epithelial growth factors and various intracellular tyrosine kinase mediated pathways, are under investigation. Increasing attention is being placed on evidence‐based supportive care, both for control of symptoms such as hot flushes and for psychosocial problems such as anxiety and depression. (Intern Med J 2004; 34: 266−269)
Kennedy's disease: pathogenesis and clinical approaches
Authors: Greenland K. J. , Zajac J. D. 
Published: May 2004

Abstract Kennedy's disease, also known as spinal and bulbar muscular atrophy, is a progressive degenerative con­dition affecting lower motor neurons. It is one of nine neurodegenerative disorders caused by a polyglutamine repeat expansion. Affecting only men, Kennedy's disease is the only one of these conditions that follows an X‐linked mode of inheritance. The causative protein in Kennedy's disease, with a polyglutamine expansion residing in the first N‐terminal domain, is the androgen receptor. Research in this field has made significant advances in recent years, and with the increased understanding of pathogenic mechanisms, feasible approaches to treatments are being investigated. In Kennedy's disease research, the most significant issue to emerge recently is the role of androgens in exacerbating the disease process. On the basis of animal experiments, a viable hypothesis is that higher circulating levels of androgens in men could trigger the degeneration of motor neurons causing this disease, and that lower levels in heterozygous and homozygous women are protective. This is a major issue, as treatment of individuals affected by Kennedy's disease with testosterone has been con­sidered a reasonable therapy by some neurologists. The rationale behind this approach relates to the fact that Kennedy's disease is accompanied by mild androgen insensitivity. It was therefore believed that treatment with high doses of testosterone might compensate for this loss of androgen action, with the added benefit of preventing muscle wasting. The current review provides an overview of recent advances in the field of Kennedy's disease research, including approaches to treatment. (Intern Med J 2004; 34: 279−286)
Assessment and management of inpatients with acute diabetes‐related foot complications: room for improvement
Authors: Lawrence S. M. , Wraight P. R. , Campbell D. A. , Colman P. G. 
Published: May 2004

Abstract Background:  Australian data are currently lacking regarding management guidance, resource usage and outcomes of patients with diabetes requiring hospitali­zation for management of acute foot complications.Aims:  The aims of the present study were to review hospital admissions for diabetes‐related foot complications and current assessment and management of these complications, and to formulate recommendations for future models of care.Methods:  A retrospective review of patient records from 1 July 1999 to 30 June 2000 was carried out. Recorded assessment, investigations, management, amputation rates, referral rates and length of hospital stay were reviewed.Results:  There were 69 admission episodes in 12 months (total patients n = 50). The mean age was 64 years, with 44 male patients (64%) and 25 female patients (36%). The mean diabetes duration was 11 years (range <1−47 years). The majority of patients had type 2 dia­betes. Assessment for known risk factors for ulceration and amputation was variable with history of previous ulcer/amputation recorded for 24 (35%) admissions, results of neurological assessment recorded for 11 (16%) and assessment of pedal pulses documented for 51 (74%). Glycated haemoglobin was performed during 35 (51%) admissions. Patients were admitted under one of 11 different inpatient units and the average interdepartmental referral rate was one referral per patient per admission. The average length of stay was 17 days, with total bed days occupied 1163 days. Minor amputation was performed in 25 (36%) cases and major amputation in 8 (11%).Conclusions:  Clinical assessment, investigation and management of this population are highly variable. This has a significant impact on the final clinical outcome, and changes to current processes are required to overcome the substantial burden of diabetic foot disease. (Intern Med J 2004; 34: 229−233)