bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiglucocorticoid RU38486 reduces net protein catabolism in experimental acute renal failure
Authors: Mondry Adrian 
Published: February 2005

Abstract
Background
In acute renal failure, a pronounced net protein catabolism occurs that has long been associated with corticoid action. By competitively blocking the glucocorticoid receptor with the potent antiglucocorticoid RU 38486, the present study addressed the question to what extent does corticoid action specific to uremia cause the observed muscle degradation, and does inhibition of glucocorticoid action reduce the protein wasting?

Methods
RU 38486 was administered in a dose of 50 mg/kg/24 h for 48 h after operation to fasted bilaterally nephrectomized (BNX) male adult Wistar rats and sham operated (SHAM) controls. Protein turnover was evaluated by high performance liquid chromatography (HPLC) of amino acid efflux in sera from isolated perfused hindquarters of animals treated with RU 38486 versus untreated controls.

Results
Administration of RU 38486 reduces the total amino acid efflux (TAAE) by 18.6% in SHAM and 15.6% in BNX and efflux of the indicator of net protein turnover, phenylalanine (Phe) by 33.3% in SHAM and 13% in BNX animals as compared to the equally operated, but untreated animals. However, the significantly higher protein degradation observed in BNX (0.6 ± 0.2 nmol/min/g muscle) versus SHAM (0.2 ± 0.1 nmol/min/g muscle) rats, as demonstrated by the marker of myofribrillar proteolytic rate, 3-Methylhistidine (3 MH) remains unaffected by administration of RU 38486 (0.5 ± 0.1 v. 0.2 ± 0.1 nmol/min/g muscle in BNX v. SHAM).

Conclusion
RU 38486 does not act on changes of muscular protein turnover specific to uremia but reduces the effect of stress- stimulated elevated corticosterone secretion arising from surgery and fasting. A potentially beneficial effect against stress- induced catabolism in severe illness can be postulated that merits further study.
The pre-vaccination regional epidemiological landscape of measles in Italy: contact patterns, effort needed for eradication, and comparison with other regions of Europe
Authors: Manfredi Piero , Cleur Eugene M , Williams John R , Salmaso Stefania , Atti Marta Ciofi degli 
Published: February 2005

Abstract
Background
Strong regional heterogeneity and generally sub-optimal rates of measles vaccination in Italy have, to date, hampered attainment of WHO targets for measles elimination, and have generated the need for the new Italian National Measles Elimination Plan. Crucial to success of the plan is the identification of intervention priorities based upon a clear picture of the regional epidemiology of measles derived from the use of data to estimate basic parameters. Previous estimates of measles force of infection for Italy have appeared anomalously low. It has been argued elsewhere that this results from Italian selective under-reporting by age of cases and that the true measles force of infection in Italy is probably similar to that of other European countries. A deeper examination of the evidence for this conjecture is undertaken in the present paper.

Methods
Using monthly regional case notifications data from 1949 to the start of vaccination in 1976 and notifications by age from 1971–76, summary equilibrium parameters (force of infection (FOI), basic reproductive ratio (R0) and critical vaccination coverage (p
c
)) are calculated for each region and for each of 5 plausible contact patterns. An analysis of the spectra of incidence profiles is also carried out. Finally a transmission dynamics model is employed to explore the correspondence between projections using different estimates of force of infection and data on seroprevalence in Italy.

Results
FOI estimates are lower than comparable European FOIs and there is substantial regional heterogeneity in basic reproductive ratios; certain patterns of contact matrices are demonstrated to be unfeasible. Most regions show evidence of 3-year epidemic cycles or longer, and compared with England & Wales there appears to be little synchronisation between regions. Modelling results suggest that the lower FOI estimated from corrected aggregate national data matches serological data more closely than that estimated from typical European data.

Conclusion
Results suggest forces of infection in Italy, though everywhere remaining below the typical European level, are historically higher in the South where currently vaccination coverage is lowest. There appears to be little evidence to support the suggestion that a higher true force of infection is masked by age bias in reporting.
Molecular strategies to inhibit HIV-1 replication
Authors: Nielsen Morten Hjuler , Pedersen Finn Skou , Kjems Jørgen 
Published: February 2005

AbstractThe human immunodeficiency virus type 1 (HIV-1) is the primary cause of the acquired immunodeficiency syndrome (AIDS), which is a slow, progressive and degenerative disease of the human immune system. The pathogenesis of HIV-1 is complex and characterized by the interplay of both viral and host factors. An intense global research effort into understanding the individual steps of the viral replication cycle and the dynamics during an infection has inspired researchers in the development of a wide spectrum of antiviral strategies. Practically every stage in the viral life cycle and every viral gene product is a potential target. In addition, several strategies are targeting host proteins that play an essential role in the viral life cycle. This review summarizes the main genetic approaches taken in such antiviral strategies.
Comparison between logistic regression and neural networks to predict death in patients with suspected sepsis in the emergency room
Authors: Jaimes Fabián , Farbiarz Jorge , Alvarez Diego , Martínez Carlos 
Published: February 2005

Abstract
Introduction
Neural networks are new methodological tools based on nonlinear models. They appear to be better at prediction and classification in biological systems than do traditional strategies such as logistic regression. This paper provides a practical example that contrasts both approaches within the setting of suspected sepsis in the emergency room.

Methods
The study population comprised patients with suspected bacterial infection as their main diagnosis for admission to the emergency room at two University-based hospitals. Mortality within the first 28 days from admission was predicted using logistic regression with the following variables: age, immunosuppressive systemic disease, general systemic disease, Shock Index, temperature, respiratory rate, Glasgow Coma Scale score, leucocyte counts, platelet counts and creatinine. Also, with the same input and output variables, a probabilistic neural network was trained with an adaptive genetic algorithm. The network had three neurone layers: 10 neurones in the input layer, 368 in the hidden layer and two in the output layer. Calibration was measured using the Hosmer-Lemeshow goodness-of-fit test and discrimination was determined using receiver operating characteristic curves.

Results
A total of 533 patients were recruited and overall 28-day mortality was 19%. The factors chosen by logistic regression (with their score in parentheses) were as follows: immunosuppressive systemic disease or general systemic disease (2), respiratory rate 24–33 breaths/min (1), respiratory rate ≥ 34 breaths/min (3), Glasgow Come Scale score ≤12 (3), Shock Index ≥ 1.5 (2) and temperature <38°C (2). The network included all variables and there were no significant differences in predictive ability between the approaches. The areas under the receiver operating characteristic curves were 0.7517 and 0.8782 for the logistic model and the neural network, respectively (P = 0.037).

Conclusion
A predictive model would be an extremely useful tool in the setting of suspected sepsis in the emergency room. It could serve both as a guideline in medical decision-making and as a simple way to select or stratify patients in clinical research. Our proposed model and the specific development method – either logistic regression or neural networks – must be evaluated and validated in an independent population.
Patterns of Resistance and Incomplete Response to Docetaxel by Gene Expression Profiling in Breast Cancer Patients
Authors: Chang Jenny C. , Wooten Eric C. , Tsimelzon Anna , Hilsenbeck Susan G. , Gutierrez M. Carolina , Tham Yee-Lu , Kalidas Mamta , Elledge Richard , Mohsin Syed , Osborne C. Kent , Chamness Gary C. , Allred D. Craig , Lewis Michael T. , Wong Helen , O'Connell Peter 
Published: February 2005

Purpose Chemotherapy for operable breast cancer decreases the risk of death. Docetaxel is one of the most active agents in breast cancer, but resistance or incomplete response is frequent. Patients and Methods Core biopsies from 24 patients were obtained before treatment with neoadjuvant docetaxel (four cycles, 100 mg/m2 every 3 weeks), and response was assessed after chemotherapy. After 3 months of neoadjuvant chemotherapy, surgical specimens (n = 13) were obtained, and laser capture microdissection (LCM; n = 8) was performed to enrich for tumor cells. From each core, surgical, and LCM specimen, sufficient total RNA (3 to 6 μg) was extracted for cDNA array analysis using the Affymetrix HgU95-Av2 GeneChip (Affymetrix, Santa Clara, CA). Results From the initial core biopsies, differential patterns of expression of 92 genes correlated with docetaxel response (P = .001). However, the molecular patterns of the residual cancers after 3 months of docetaxel treatment were strikingly similar, independent of initial sensitivity or resistance. This relative genetic homogeneity after treatment was observed in both LCM and non-LCM surgical specimens. The residual tumor after treatment in tumors that were initially sensitive indicates selection of a residual and resistant subpopulation of cells. The gene expression pattern was populated by genes involved in cell cycle arrest at G2M (eg, mitotic cyclins and cdc2) and survival pathways involving the mammalian target of rapamycin. Conclusion A specific and consistent gene expression pattern was found in residual tumors after docetaxel treatment. These profiles provide therapeutic targets that could lead to improved treatment.
Communicating With Realism and Hope: Incurable Cancer Patients' Views on the Disclosure of Prognosis
Authors: Hagerty Rebecca G. , Butow Phyllis N. , Ellis Peter M. , Lobb Elizabeth A. , Pendlebury Susan C. , Leighl Natasha , Mac Leod Craig , Tattersall Martin H.N. 
Published: February 2005

Purpose To identify preferences for the process of prognostic discussion among patients with incurable metastatic cancer and variables associated with those preferences. Patients and Methods One hundred twenty-six (58%) of 218 patients invited onto the study participated. Eligible patients were the consecutive metastatic cancer patients of 30 oncologists, who were diagnosed within 6 weeks to 6 months before recruitment, over 18 years of age, and without known mental illness. Patients completed a postal survey measuring patient preferences for the manner of delivery of prognostic information, including how doctors might instill hope. Results Ninety-eight percent of patients wanted their doctor to be realistic, provide an opportunity to ask questions, and acknowledge them as an individual when discussing prognosis. Doctor behaviors rated the most hope giving included offering the most up to date treatment (90%), appearing to know all there is to know about the patient's cancer (87%), and saying that pain will be controlled (87%). The majority of patients indicated that the doctor appearing to be nervous or uncomfortable (91%), giving the prognosis to the family first (87%), or using euphemisms (82%) would not facilitate hope. Factor analysis revealed six general styles and three hope factors; the most strongly endorsed styles were realism and individualized care and the expert/positive/collaborative approach. A range of demographic, psychological, and disease factors were associated with preferred general and hope-giving styles, including anxiety, information-seeking behavior, expected survival, and age. Conclusion The majority of patients preferred a realistic and individualized approach from the cancer specialist and detailed information when discussing prognosis.
Calcium-Sensing Receptor Expression in Human Adipocytes
Authors: Cifuentes Mariana , Albala Cecilia , Rojas Cecilia 
Published: February 2005

AbstractThe presence of the extracellular calcium-sensing receptor (CaSR) has been demonstrated in numerous cells that are key in the control of serum calcium concentrations, underscoring its relevance in systemic calcium homeostasis. The more recent evidence of its presence in tissues not involved in this function has broadened the spectrum of interest in this protein, now known to regulate diverse cell functions such as proliferation, differentiation, and apoptosis. This study shows the expression of CaSR in human omental adipose tissue, isolated adipocytes, and adipocyte progenitor cells as assessed by RT-PCR and immunoblotting. This is the first report of CaSR being expressed in human adipocytes and adipocyte progenitor cells, opening the possibility to investigate the physiological implications and thus contributing a novel component for adipose tissue biology research.
The Remarkable Conservation of Corticotropin-Releasing Hormone (CRH)-Binding Protein in the Honeybee (Apis mellifera) Dates the CRH System to a Common Ancestor of Insects and Vertebrates
Authors: Huising Mark O. , Flik Gert 
Published: February 2005

AbstractCRH-binding protein (CRH-BP) is a key factor in the regulation of CRH signaling; it modulates the bioactivity and bioavailability of CRH and its related peptides. The conservation of CRH-BP throughout vertebrates was only recently demonstrated. Here we report the presence of CRH-BP in the honeybee (Apis mellifera) and other insects. Honeybee CRH-BP resembles previously characterized vertebrate CRH-BP sequences with respect to conserved cysteine residues, gene organization, and overall sequence identity. Phylogenetic analyses confirm the unambiguous orthology of insect and vertebrate CRH-BP sequences. Soon after their discovery, it was noted that insect diuretic hormone-I (DH-I) and its receptor share similarities with the vertebrate CRH family and their receptors. Despite these similarities, demonstration of common ancestry of DH-I and the vertebrate CRH family is still speculative: the mature neuropeptides are short, and their genes differ substantially with regard to the number of coding exons. Moreover, DH and CRH receptors belong to the much larger family of G protein-coupled receptors. In contrast, the unique and conspicuous features of CRH-BP greatly facilitate the establishment of orthology over much larger evolutionary distances. The identification of CRH-BP in insects clearly indicates that this gene predates vertebrates by at least several hundred million years. Moreover, our findings imply that a CRH system is shared by insects and vertebrates alike and, consequently, that it has been present at least since the common ancestor to both phylogenetic lines of proto- and deuterostomians.
Identification of the Salmon Somatolactin Receptor, a New Member of the Cytokine Receptor Family
Authors: Fukada Haruhisa , Ozaki Yuichi , Pierce Andrew L. , Adachi Shinji , Yamauchi Kohei , Hara Akihiko , Swanson Penny , Dickhoff Walton W. 
Published: February 2005

AbstractSomatolactin (SL) is a pituitary hormone of the GH/prolactin (PRL) family that so far has been found only in fish. Compared with GH and PRL, the primary structure of SL is highly conserved among divergent fish species, suggesting it has an important function and a discriminating receptor that constrains structural change. However, SL functions are poorly understood, and receptors for SL have not yet been identified. During cloning of GH receptor cDNA from salmon, we found a variant with relatively high (38–58%) sequence identity to vertebrate GH receptors and low (28–33%) identity to PRL receptors; however, the recombinant protein encoding the extracellular domain showed only weak binding of GH. Ligand binding of the recombinant extracellular domain for this receptor confirmed that the cDNA encoded a specific receptor for SL. The SL receptor (SLR) has common features of a GH receptor including FGEFS motif, six cysteine residues in the extracellular domain, a single transmembrane region, and Box 1 and 2 regions in the intracellular domain. These structural characteristics place the SLR in the cytokine receptor type I homodimeric group, which includes receptors for GH, PRL, erythropoietin, thrombopoietin, granulocyte-colony stimulating factor, and leptin. Transcripts for SLR were found in 11 tissues with highest levels in liver and fat, supporting the notion that a major function of SL is regulation of lipid metabolism. Cloning SLR cDNA opens the way for discovery of new SL functions and target tissues in fish, and perhaps novel members of this receptor family in other vertebrates.
Single Assay for Amino-Terminal Fragments of Cardiac A- and B-Type Natriuretic Peptides
Authors: Ala-Kopsala Minna , Ruskoaho Heikki , Leppäluoto Juhani , Seres Leila , Skoumal Reka , Toth Miklos , Horkay Ferenc , Vuolteenaho Olli 
Published: February 2005

Abstract
Background: High circulating concentrations of N-terminal fragments of A- and B-type natriuretic peptides (NT-proANP and NT-proBNP) identify patients with impaired cardiac function. ProANP-derived peptides are particularly sensitive to increased preload of the heart and proBNP-derived peptides to increased afterload; therefore, combining the information from the ANP and BNP systems into a single analyte could produce an assay with increased diagnostic and prognostic power.
Methods: We prepared a hybrid peptide containing peptide sequences from both NT-proBNP and NT-proANP (referred to as NT-proXNP) by recombinant techniques and used it to develop a RIA combining weighed concentrations of NT-proANP and NT-proBNP into a new virtual analyte, NT-proXNP. We used the novel method to measure the circulating concentrations in healthy persons and in patients with cardiac disorders. We also characterized the assay by HPLC analysis of the immunoreactive molecular forms in human plasma and serum.
Results: The results from the novel assay correlated well with independent home-made NT-proANP and NT-proBNP assays (r2 = 0.75–0.85) as well with the arithmetic sum of NT-proANP and NT-proBNP (r2 = 0.92). Patients with valvular heart disease (VHD) and coronary artery disease (CAD) had significantly increased NT-proXNP concentrations. The areas under the curve (AUC) of the NT-proXNP assay in detecting VHD and CAD (0.961 and 0.924, respectively) were significantly larger than the AUC of either NT-proANP (0.947 and 0.872) or NT-proBNP (0.913 and 0.782) assays. HPLC analysis showed that the novel NT-proXNP assay detects two major classes of circulating immunoreactivity corresponding to peptides derived from NT-proANP and NT-proBNP.
Conclusions: Our novel immunoassay mimics the physiologic signaling system working in the body by converging the information obtained from the activation of ANP and BNP into a single virtual analyte, NT-proXNP. It appears to have a diagnostic efficiency equal to or slightly better than that of individual NT-proANP or NT-proBNP assays.
Use of an In Vivo Biotinylated Single-Chain Antibody as Capture Reagent in an Immunometric Assay to Decrease the Incidence of Interference from Heterophilic Antibodies
Authors: Warren David J , Bjerner Johan , Paus Elisabeth , Børmer Ole P , Nustad Kjell 
Published: February 2005

AbstractBackground: Heterophilic antibodies are a common source of interference in immunometric assays. We tested the hypothesis that the incidence of such interference could be decreased by use of a recombinant in vivo-biotinylated single-chain antibody (scFv) as the capture reagent.Methods: We established three assays for carcinoembryonic antigen (CEA) with the capture antibody either chemically biotinylated whole monoclonal T84.66 immunoglobulin, a corresponding F(ab′)2 fragment, or a site-specifically biotinylated T84.66-derived single-chain antibody (scFv). Antibodies were attached to streptavidin-coated microplates. A common europium-labeled anti-CEA tracer monoclonal antibody was used. The F(ab′)2 assay used a buffer that contained bovine immunoglobulin and aggregated irrelevant monoclonal antibody MAK33 as blocking agents. The whole T84.66 immunoglobulin and scFv assays were performed without addition of blocking agents. From a previous study of 11 261 sera, we tested 390 samples that had displayed heterophilic antibody interference and 179 samples that had not.Results: After correction for bias and analytical variation [2.56 × SD (from the precision profile)], 383 samples displayed significantly different values (&gt;1 μg/L) in the whole T84.66-based assay and the F(ab′)2 assay. In contrast, only nine samples showed falsely high CEA concentrations in the scFv assay. After blocking agents were added to the assay buffer, eight of the nine samples displayed results equivalent to those of the F(ab′)2 assay, and sample dilution produced equivalent results for the remaining sample.Conclusion: Their ability to be site-specifically biotinylated and their relative resistance to heterophilic antibody interference indicate that single-chain antibodies may be useful solid-phase reagents in immunometric assays.
Material Properties for Use in FEA Modeling: Sealant Behavior with Ambient Laboratory Climate Aging
Authors: Wolf AT , Cleland-Host HL 
Published: February 2005

Abstract
Stress relaxation uniaxial testing is used to define the behavior of elastomeric materials in their functional range. The stress-strain data obtained by this method are used in finite element analysis (FEA) to model the behavior of the material in a given application. The objective of this study is to determine the effect of aging on the uniaxial stress-strain properties of silicone sealants. This paper examines the material behavior changes that occur as these sealants continue to cure at ambient laboratory conditions. The study is intended as a first step toward developing simple working models that account for the effects of sealant aging in FEA modeling. Uniaxial stress relaxation testing was conducted on six commercially available silicone structural glazing, insulating glazing, and weatherproofing sealants in tension and in compression at temperatures of −20°C, 22°C, and 80°C. Testing was carried out immediately after cure, i.e., after three days for two-part and after 30 days for one-part sealants, and after an additional one-year storage period at ambient laboratory conditions. The test specimens were pre-loaded prior to testing in order to eliminate the Mullins effect. Testing was carried out over a strain range of −45–90%. The specimen was loaded to the desired strain level and then allowed to relax. The load at the end of the relaxation period was used to calculate the engineering stress. Coefficient of variance (CoV) was used to determine the significance of material property changes with continued sealant cure. No significant changes in engineering properties were observed for two sealants. For two further sealants, half or more of the test results were within CoV, and no clear trends in property drift could be derived. The changes in material properties of the final two sealants were well outside the CoV limit, and moderate to strong stiffening was observed.