bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human cerebrospinal fluid peptidomics
Authors: Yuan Xianglin , Desiderio Dominic M. 
Published: February 2005

AbstractCerebrospinal fluid (CSF) has frequently been extensively studied to explore several different central nervous system (CNS) disorders because it contains proteins, enzymes, hormones, neuropeptides and neurotransmitters that play critical regulatory roles in many different physiological processes. Individual neuropeptidergic systems in CSF have been studied. In theory, peptidomics offers a bird's‐eye, comprehensive and systems‐level approach to analyze all of the peptidergic systems that have been expressed in CSF at any given time. In this study, low molecular mass (Mr < 5 kDa) peptides were isolated by ultrafiltration. The isolated peptides, with or without trypsin digestion, were preferentially enriched with a solid‐phase extraction cartridge, and the peptides were separated with capillary liquid chromatography and analyzed with on‐line quadrupole time‐of‐flight mass spectrometry (MS). In this proof‐of‐principle study, the 20 representative MS‐characterized peptides were shown to be derived from 12 proteins, among which four proteins, amyloid‐like protein 1, secretogranin I, granin‐like neuroendocrine peptide precursor and neurosecretory protein VGF, have been shown elsewhere to be either associated with CNS disorders or to play a central role in the CNS. The long‐term goals of this peptidomics study are to monitor the changes (amount; modifications) of CSF peptides, clarify the aberrant processing of large intact protein precursors, elucidate the molecular mechanisms of CNS disorders and find biomarkers. This analytical method is effective for the analysis of the human lumbar CSF peptidome. Copyright © 2005 John Wiley & Sons, Ltd.
Quantification of the Aβ peptide in Alzheimer's plaques by laser dissection microscopy combined with mass spectrometry
Authors: Rüfenacht Pascal , Güntert Andreas , Bohrmann Bernd , Ducret Axel , Döbeli Heinz 
Published: February 2005

AbstractThe accumulation and aggregation of the beta‐amyloid peptide (Aβ) in the brain represents a key factor in the pathogenesis of Alzheimer's disease (AD). Many of the transgenic mouse models for AD exhibit an amyloid pathology with neuritic plaques but they typically vary by the type and abundance of plaques identified in their brains and by the onset and severity of cognitive impairment. Thus, an important consideration in the characterization of AD transgenic mouse models should be the quantitative evaluation of the amyloid load in the brain together with a detailed physico‐chemical analysis of Aβ from the deposited plaques. Here we present an analytical procedure to collect single amyloid plaques from anatomically defined brain regions by laser dissection microscopy that can be quantitatively assessed in their Aβ isoforms composition by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. Quantification was achieved by stable isotope dilution using calibrated 15N‐labeled Aβ standards that were spiked in the sample immediately after laser dissection. Using this method, we found that the amyloid loads in brain plaques isolated from the transgenic AD mouse model PS2APP or from human were similar. Total Aβ composition was estimated at ∼50–100 fmol per excised plaque disc, as confirmed by immunoblot analysis. N‐Terminal truncated Aβ isoforms were identified in both transgene and human amyloid plaques but with significantly elevated levels in human samples. Copyright © 2005 John Wiley & Sons, Ltd.
Proteomics and peptidomics in neuroscience. Experience of capabilities and limitations in a neurochemical laboratory
Authors: Paulson Linda , Persson Rita , Karlsson Gösta , Silberring Jerzy , Bierczynska‐Krzysik Anna , Ekman Rolf , Westman‐Brinkmalm Ann 
Published: February 2005

AbstractThe increasing use of proteomics has created a basis for new strategies to develop methodologies for rapid identification of protein patterns in living organisms. It has also become evident that proteomics has other potential applications than protein and peptide identification, e.g. protein characterization, with the aim of revealing their structure, function(s) and interactions of proteins. In comparative proteomics studies, the protein expression of a certain biological system is compared with another system or the same system under perturbed conditions. Global identification of proteins in neuroscience is extremely complex, owing to the limited availability of biological material and very low concentrations of the molecules. Moreover, in addition to proteins, there are number of peptides that must also be considered in global studies on the central nervous system. In this overview, we focus on and discuss problems related to the different sources of biological material and sample handling, which are part of all preparatory and analytical steps. Straightforward protocols are desirable to avoid excessive purification steps, since loss of material at each step is inevitable. We would like to merge the two worlds of proteomics/peptidomics and neuroscience, and finally we consider different practical and technical aspects, illustrated with examples from our laboratory. Copyright © 2005 John Wiley & Sons, Ltd.
Fourier transform infrared/attenuated total reflectance analysis of water diffusion in poly[styrene‐b‐isobutylene‐ b‐styrene] block copolymer membranes
Authors: Mountz David A. , Storey Robson F. , Mauritz Kenneth A. 
Published: February 2005

AbstractA Fourier transform infrared/attenuated total reflectance technique was used to study the diffusion of water through poly(styrene‐b‐isobutylene‐b‐styrene) block copolymers (BCPs), as well as sulfonated (H+) and Na+‐sulfonated ionomer versions. Diffusion data were collected and interpreted for these membranes versus polystyrene block composition, degree of sulfonation, Na+ ion content in the ionomers, and the effect of initially dry versus prehydrated conditions. An “early time” diffusion coefficient, D, decreased with increasing percent polystyrene for a series of unmodified BCPs. D decreased with increasing degree of sulfonation, and with increasing ion content for the Na+‐exchanged samples and this was interpreted in terms of diffusion limitations caused by a strong tendency for ion hydration. The method also yielded information relating to the time evolution of water structure from the standpoint of degree of intermolecular hydrogen bonding. Membrane prehydration causes profound increases in D for both the unmodified BCP and sulfonated samples, as in plasticization. The simultaneous acquisition of information relating to interactions between water molecules and interactions of water molecules with functional groups on the host polymer matrix offers more information than conventional diffusion measurement techniques that simply count transported molecules. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 764–776, 2005
The use of the triangular test with response‐adaptive treatment allocation
Authors: Coad D. Stephen , Ivanova Anastasia 
Published: February 2005

AbstractA clinical trial is considered in which two treatments with binary responses are to be compared. A popular sequential stopping rule, the triangular test, is studied when various response‐adaptive treatment allocation rules are applied, such as the recently proposed drop‐the‐loser rule, an urn randomization scheme. The paper extends previous work by Coad and Rosenberger, who combined the triangular test with the randomized play‐the‐winner rule. The purpose of the paper is to investigate to what extent the variability of an adaptive design affects the overall performance of the triangular test. The adaptive rules under consideration are described and some of their asymptotic properties are summarized. Simulation is then used to assess the performance of the triangular test when combined with the various adaptive rules. The main finding is that the drop‐the‐loser rule is the most promising of the adaptive rules considered in terms of a less variable allocation proportion and a smaller number of treatment failures. The use of this rule with the triangular test is beneficial compared with the triangular test with equal allocation, since it yields fewer treatment failures on average while providing comparable power with similar expected sample size. The results of an AIDS trial are used to illustrate the performance of the triangular test when combined with the drop‐the‐loser rule. Copyright © 2005 John Wiley & Sons, Ltd.
Statistical design and analysis of pharmacogenetic trials
Authors: Kelly Patrick J. , Stallard Nigel , Whittaker John C. 
Published: February 2005

AbstractPharmacogenetic trials investigate the effect of genotype on treatment response. When there are two or more treatment groups and two or more genetic groups, investigation of gene–treatment interactions is of key interest. However, calculation of the power to detect such interactions is complicated because this depends not only on the treatment effect size within each genetic group, but also on the number of genetic groups, the size of each genetic group, and the type of genetic effect that is both present and tested for. The scale chosen to measure the magnitude of an interaction can also be problematic, especially for the binary case.Elston et al. proposed a test for detecting the presence of gene–treatment interactions for binary responses, and gave appropriate power calculations. This paper shows how the same approach can also be used for normally distributed responses. We also propose a method for analysing and performing sample size calculations based on a generalized linear model (GLM) approach. The power of the Elston et al. and GLM approaches are compared for the binary and normal case using several illustrative examples. While more sensitive to errors in model specification than the Elston et al. approach, the GLM approach is much more flexible and in many cases more powerful. Copyright © 2005 John Wiley & Sons, Ltd.
The prognosis of impaired left ventricular systolic function and heart failure in a middle‐aged and elderly population in an urban population segment of Copenhagen
Authors: Raymond Ilan , Mehlsen Jesper , Pedersen Frants , Dimsits Jeannett , Jacobsen Jørgen , Hildebrandt Per Rossen 
Published: February 2005

AbstractAims:To determine the prognosis, total mortality and cardiac morbidity, of patients with left ventricular systolic dysfunction and heart failure (HF) in a general population sample.Methods and results:A total of 764 subjects, 432 females and 332 males, median age (range) 66 years (50–89), participated in this cross sectional survey. The study population was recruited from randomly selected general practitioners and stratified to include a minimum of 150 persons in each age decade stratum. Each participant filled in a heart failure questionnaire and ECG, blood tests and echocardiography were performed. Median (range) follow‐up was 1145 (51–1197) days. Subjects with LVEF≤0.40 had a significantly higher all‐cause mortality (27.8% vs. 5.6%, P<0.0001), admission rate for HF (25.0% vs. 1.9%, P<0.0001) and for other cardiac causes (25.0% vs. 6.3%, P<0.0001) than in subjects with LVEF>0.40. The age and gender adjusted 2‐year relative risk of death was 4.6 (95% C.I.=1.6–13.2). No significant difference in mortality was found between subjects with or without heart failure symptoms.Conclusion:Significantly higher mortality as well as cardiac morbidity was found in subjects with symptomatic and asymptomatic LV systolic dysfunction compared to those with normal systolic function. These conditions were among the strongest predictors of all‐cause mortality and cardiac morbidity.
Pilot assessment of the response of several pulmonary hemodynamic variables to sublingual sildenafil in candidates for heart transplantation
Authors: Gómez‐Sánchez Miguel Angel , de la Calzada Carlos Saenz , Subías Pilar Escribano , Jiménez Juan Francisco Delgado , Salvador María Lázaro , González Agustín Albarrán , Calvo Luis Cea 
Published: February 2005

AbstractObjective:To determine the acute vasodilator effect of sublingual sildenafil in heart transplant candidates with severe pulmonary hypertension due to severe left ventricular dysfunction (LVD).Background:Pulmonary hypertension confers an increased risk of early graft failure.Patients and methods:Seven patients, (mean age of 53±8) with severe LVD (mean EF: 19±1.7%, functional class III–IV) due to coronary artery disease, dilated cardiomyopathy and valvulopathy were evaluated for heart transplant. All patients presented a mean transpulmonary gradient >12 mmHg and pulmonary vascular resistances >2.5 W.U., despite full treatment for advanced heart failure. The following hemodynamic data were obtained at basal state and then 15, 30 and 45 min after administration of 100 mg of sublingual sildenafil: right atrial, mean pulmonary artery pressure (mPAP), mean pulmonary capillary wedge pressures, mean transpulmonary gradient (mTPG), blood pressure, cardiac output, pulmonary vascular resistances (PVR) and systemic vascular resistances. Sublingual sildenafil was given without changing the previous treatment of heart failure.Results:After 30 min of sublingual sildenafil, mPAP decreased from 37 (28–61) to 30 (16–42) mmHg and PVR decreased from 5.2 (1.9–13.8) to 2.5 (1.4–3.9) W.U. after 45 min. Mean TPG decreased from 19 (16–33) to 12 (8–14) mmHg at 45 min. Mean pulmonary capillary wedge pressure, cardiac output, systemic vascular resistances and mean blood pressure were unchanged. Sublingual sildenafil was well tolerated, with only transient facial flushing in 4 patients and mild headache in 2.Conclusions:Based on this initial study, sublingual sildenafil may be a useful alternative drug to perform acute vasodilator test in heart transplant candidates with significant pulmonary hypertension due to severe LVD. Nevertheless, further studies are warranted to confirm our results.
An 8‐year follow‐up study of acute admissions with heart failure in a multiethnic population
Authors: Sosin Michael D. , Bhatia Gurbir S. , Zarifis John , Davis Russell C. , Lip Gregory Y.H. 
Published: February 2005

AbstractIn 1994, we reported a cross‐sectional survey of acute heart failure admissions to a city centre hospital serving a multiethnic population and found ethnic differences in aetiological factors and short‐term (in‐patient) mortality. We analysed long‐term mortality data for this original survey cohort after 8 years’ follow‐up. At 8 years’ follow‐up, the total mortality was 90.5% amongst Europeans and 87.0% amongst non‐Europeans (log rank test, P=0.0705). The non‐European patients had significantly better survival at all time points until 6 years, after which the survival curves start to converge. In univariate analysis, age <75.6 years (that is, the median age of the whole cohort), use of beta‐blockers, use of ACE inhibitors, and absence of atrial fibrillation were significantly associated with increased survival. In addition, patients who had had an echocardiographic examination had significantly prolonged survival when compared to those who did not. Using a Cox multiple regression analysis, age, renal impairment, atrial fibrillation, absence of echocardiography, absence of beta‐blockers or ACE inhibitor use (and not ethnicity) remained significant predictors of mortality at 8 years. While this follow‐up study has suggested that survival following admission for acutely decompensated heart failure is not different between different ethnic groups when corrected for age, it is clear from the younger age of heart failure patients from ethnic minority groups and the relatively high prevalence, that the burden of heart failure is greater in these populations. Future observational and therapeutic trials in heart failure should include sufficient numbers of participants from ethnic minority groups to ensure that the results can be applied to the population at risk.
Geological relationships and40Ar/39Ar age constraints on gold mineralisation at Tarcoola, central Gawler gold province, South Australia
Authors: BUDD A. R. , FRASER G. L. 
Published: February 2005

The Tarcoola Goldfield is one of several districts included in the recently proposed central Gawler gold province. Understanding of the genesis of the deposits in this metallogenic province is in its infancy, and dating the age of alteration, mineralisation and microdiorite dyke intrusions has been carried out at Tarcoola as a first step towards developing mineral‐systems models for the province. At Tarcoola, four samples of sericite from alteration as well as one sample of hornblende from a microdiorite dyke yield40Ar/39Ar ages ofca 1580 Ma. Geological and petrological relationships suggest that this age represents the time of fracture‐controlled Au mineralisation. These data provide evidence for coeval Au mineralisation, microdiorite dyke intrusion and local deformation. This mineralisation age is indistinguishable from U–Pb ages for the regional Gawler Range – Hiltaba volcano‐plutonic complex, and is more than 100 million years younger than the Paxton Granite, which is part‐host to the mineralisation. Possible temporal and genetic relationships with other deposits in the central Gawler gold province remain to be tested.
Late Oligocene Kangaroo Well Local Fauna from the Ulta Limestone (new name), and climate of the Miocene oscillation across central Australia
Authors: MEGIRIAN D. , MURRAY P. , SCHWARTZ L. , VON DER BORCH C. 
Published: February 2005

The Late Oligocene Kangaroo Well Local Fauna from the Ulta Limestone (new name), northwestern Lake Eyre Basin correlates best with vertebrate assemblages from the Etadunna, Namba and Wipajiri Formations of the central Lake Eyre Basin, and from the Carl Creek Limestone (Karumba Basin) of northwestern Queensland. The biochronologically informative marsupials, Neohelos tirarensis (Diprotodontidae, Zygomaturinae), Marlu sp. cf. M. kutjamarpensis and Pildra sp. cf. P. magnus (Pseudocheiridae), and Ektopodon ulta sp. nov. (Ektopodontidae), indicate that the Kangaroo Well Local Fauna may be slightly older than the Kutjamarpu Local Fauna (Wipajiri Formation) and slightly younger than the Ngama Local Fauna (zone D of the Etadunna Formation) of Late Oligocene age. A new species of primitive ?Wynyardiidae, Ayekaye jaredi sp. nov., is described, and the nomenclature of two extinct gastropods, Glyptophysa rodingae (McMichael) and Cupedora lloydi (McMichael) (new combinations), the type localities of which are in the Ulta Limestone, is revised in line with current taxonomy. The Ulta Limestone, an alluvial calclithite composed primarily of caliche fabrics, and its correlatives were deposited during the Miocene oscillation climatic event. Palaeoclimatic modelling using sedimentological data, crocodilians and extant analogs of fossil terrestrial gastropods indicates that the average annual temperature at Kangaroo Well during the Late Oligocene was probably between 14 and 20°C, while mean annual rainfall was probably <600 mm. Similar associations from central parts of the Lake Eyre Basin, from Riversleigh, northwestern Queensland, and from Bullock Creek, north‐central Northern Territory, indicate that such conditions were widespread during depositional phases of the Miocene oscillation. Palaeoclimatic indicators do not support the presence of widespread closed forests in northwestern Queensland and across the inland of the Northern Territory and South Australia during the Miocene oscillation.
Geomorphology and surficial sediments of the southeast Australian continental margin
Authors: BOYD R. , RUMING K. , ROBERTS J. J. 
Published: February 2005

The southeast Australian continental margin stretches 1500 km north from Bass Strait to the Great Barrier Reef. This part of the Australian margin represents a distinct oceanographic, climatic and geological province. Recent initiatives by the Australian Hydrographic Office, Geoscience Australia and the Environmental Geoscience Group at the University of Newcastle have provided a new digital database of bathymetric soundings and surface‐sediment distribution for the southeast Australian margin. This database is used here to provide the first detailed digital 3‐D representations of the southeast Australian margin, leading to new morphological classifications and integrated sedimentation models. As a result of its tectonic history of asymmetric passive margin rifting, the continental margin as a whole is narrow, steep and sediment deficient. The shelf can be divided into an inner zone with bedrock cropping out or close to the surface, and an outer zone that represents the top of a Cenozoic sediment wedge. The continental shelf and slope can be classified into a variety of morphological units based on detailed analysis of geometry and slope. These units include a succession of shore‐normal zones (shoreface, inner plain, inner and mid‐slope, outer plain and continental slope) and a number of local regions (mounds, lobes, tongues, depressions, deltas and bedrock). Sediments are generally siliciclastic in composition on the inner margin and carbonate‐rich on the outer margin, reflecting carbonate production at low sea‐levels on the outer shelf/continental slope and terrestrial sediment input to the inner shelf. Fine‐grained sediments are rare on the shelf north from Port Stephens, and occur draped across the inner and mid‐slope further south. Outer shelf carbonate sediments are coarse grained with a patchy distribution related to winnowing by the East Australian Current. The East Australian Current also produces erosional depressions and southward prograding sediment tongues and lobes where it separates from the shelf off Port Stephens. The margin character varies markedly from south to north in terms of fine‐sediment distribution, depth to the shelf break and width of the outer shelf. These outer shelf features reflect an inherited palaeotopography from underlying Cenozoic sediment wedges that are better developed on the southern margin.
Gefitinib in advanced non‐small cell lung cancer
Authors: Sharma R. , Boyer M. , Clarke S. , Millward M. 
Published: February 2005

AbstractBackground:  Gefitinib is an oral, selective epidermal growth factor receptor (EGFR) inhibitor that has activity in non‐small cell lung cancer (NSCLC).Aim:  To evaluate the tolerability, safety‐profile and response of single agent gefitinib in patients with advanced stage NSCLC.Methods:  Twenty‐seven patients of good performance status with stage IIIB or IV NSCLC were entered on the study at the Sydney Cancer Centre. Gefitinib was prescribed at an oral dose of 250 mg daily, as a continuous dose. Radiological evaluation of indicator lesions occurred at baseline and were repeated every 2–3 months until disease progression. Toxicity was graded using standard measures at baseline and at every month.Results:  The response rate was 17% in the patients eligible for evaluation. Symptom improvement was observed in 75% of patients. No patients withdrew because of adverse events. Toxicity was observed in 15 patients and consisted mainly of rash (59%), which was usually mild in severity.Conclusion:  Gefitinib is active in NSCLC. It is well tolerated with minimal side‐effects. Symptomatic improvement was found in the majority of patients treated with gefitinib. There may be a role for gefitinib in the palliation of symptoms in patients with advanced NSCLC. (Intern Med J 2005; 35: 77–82)