bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for the regulation of levels of plasma adhesion molecules by proinflammatory cytokines and their soluble receptors in type 1 diabetes
Authors: Mohamed‐Ali V. , Armstrong L. , Clarke D. , Bolton C. H. , Pinkney J. H. 
Published: March 2003

Abstract. Mohamed‐Ali V, Armstrong L, Clarke D, Bolton CH, Pinkney JH (University College London Medical School, Whittington Hospital, London; University Department of Medicine, Southmead Hospital, Bristol; and Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK). Evidence for the regulation of levels of plasma adhesion molecules by proinflammatory cytokines and their soluble receptors in type 1 diabetes. J Intern Med 2001; 250: 415–421. Objectives. To investigate the regulation of soluble adhesion molecules by tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6), and relationships with circulating cytokine receptors, in vivo, in type 1 diabetes. Design. Cross‐sectional study. Setting. University hospital diabetes clinic. Subjects. A total of 47 non‐nephropathic, Caucasian type 1 diabetics and 39 nondiabetic controls. Outcome measures. Plasma levels of TNF‐α, IL‐6, their soluble receptors and adhesion molecules intercellular adhesion molecule‐1 (sICAM‐1), vascular cell adhesion molecule‐1 (sVCAM‐1), sE‐selectin and von Willebrand factor (vWF), and risk factors for cardiovascular disease. Results. Plasma concentrations of IL‐6 were elevated in diabetic patients compared with controls [median (interquartiles) 1.28 (0.89–2.65) vs. 0.66 (0.45–1.73) pg mL−1: P=0.016], and in these patients IL‐6 and soluble IL‐6 receptor (sIL‐6R) levels correlated with concentrations of sICAM‐1 (r=0.41, P=0.012 and r=0.31, P=0.04, respectively). Tumour necrosis factor‐α soluble receptor‐2 (sTNFRII), but not TNF‐α or tumour necrosis factor soluble receptor‐1 (sTNFRI), was elevated in diabetic subjects (P=0.027). Plasma TNF‐α levels correlated with sVCAM‐1 (r=0.39, P=0.008), triglycerides (r=0.36, P=0.021) and diastolic blood pressure (r=0.35; P=0.024). Both sTNFRI and sTNFRII correlated with blood pressure (r=0.46, P=0.002; r=0.32, P=0.034) and triglycerides (r=0.33, P=0.033; r=0.29, P=0.05). In contrast, HDL‐cholesterol and triglyceride were related to sE‐selectin (r=−0.45 and +0.45; both P < 0.001). Neither sE‐selectin nor vWF were related to cytokine concentrations. Finally, both TNF‐α and sIL‐6R correlated sTNFRI and RII (r=0.44–0.49, P < 0.001). None of these interactions were apparent in control subjects. Conclusions. (i) IL‐6, through effects on sICAM‐1, and TNF‐α via effects on sVCAM‐1, may promote vascular adhesion; (ii) plasma levels of TNF‐α are associated with dyslipidaemia and increased blood pressure, adding to vascular disease risk; (iii) the actions of both cytokines are probably modified by altered production of soluble receptors in diabetic subjects.
The genetical history of humans and the great apes
Authors: KAESSMANN H. , PÄÄBO S. 
Published: March 2003

Abstract. Kaessmann H, Pääbo S (Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany). The genetical history of humans and the great apes. J Intern Med 2002; 251: 1–18.When and where did modern humans evolve? How did our ancestors spread over the world? Traditionally, answers to questions such as these have been sought in historical, archaeological, and fossil records. However, increasingly genetic data provide information about the evolution of our species. In this review, we focus on the comparison of the variation in the human gene pool to that of our closest evolutionary relatives, the great apes, because this provides a relevant perspective on human genetical evolution. For instance, comparisons to the great apes show that humans are unique in having little genetic variation as well as little genetic structure in their gene pool. Furthermore, genetic data indicate that humans, but not the great apes, have experienced a period of dramatic growth in their early history.
Cardiovascular disease, hypertension and renal function in primary hyperparathyroidism
Authors: Hedbäck G. M. , Odén A. S. 
Published: March 2003

Abstract. Hedbäck GM, Odén AS (Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden). Cardiovascular disease, hypertension, and renal function in primary hyperparathyroidism. J Intern Med 2002; 251: 476–483. Objectives. Patients with primary hyperparathyroidism run an increased risk of death in cardiovascular disease. Long ago, hypertension was found to frequently occur in these patients. The aim of this study was to compare the death risk after surgery for hyperparathyroidism of hypertensive patients with that of normotensive ones, and to investigate relations between variables of cardiovascular disease and variables of hyperparathyroidism and renal function. Methods. A series of 845 patients with primary hyperparathyroidism and serum creatinine ≤160 μmol L−1 was followed‐up mean 10.2 (SD 5.7) years after surgery. Survival and correlation tests were performed. Death risk was estimated using a hazard function according to Poisson. Results. The death risk of hypertensive hyperparathyroid patients was 50% higher compared with that of the normotensive patients, but the yearly death risk decrease after surgery for the hypertensive patients was almost doubled as compared with the decrease of the normotensive patients. Cardiovascular disease was directly related to serum calcium level, adenoma weight, osteitis fibrosa, and serum creatinine, and inversely related to glomerular filtration rate and urine osmolality, but unrelated to the symptom variables. A negative relation was found between cardiovascular disease and renal stone disease. Conclusions. It can be concluded that cardiovascular disease is more a part of primary hyperparathyroidism than just associated with it, being related to both serum calcium and adenoma weight. There was also a relationship between cardiovascular disease and decreased renal function. Death risk decrease after surgery was rather more pronounced for the hypertensive patients compared with the normotensive ones.
Prevalence and significance of cardiovascular risk factors in a large cohort of patients with familial hypercholesterolaemia
Authors: De Sauvage Nolting P. R. W. , Defesche J. C. , Buirma R. J. A. , Hutten B. A. , Lansberg P. J. , Kastelein J. J. P. 
Published: March 2003

Abstract.  de Sauvage Nolting PRW, Defesche JC, Buirma RJA, Hutten BA, Lansberg PJ, Kastelein JJP (Academic Medical Center, Amsterdam; Clinical Research, Haarlem; Slotervaart Hospital, Amsterdam; the Netherlands). Prevalence and significance of cardiovascular risk factors in a large cohort of patients with familial hypercholesterolaemia. J Intern Med 2003; 253: 161–168.Objective.  Patients with familial hypercholesterolaemia (FH) vary widely in terms of onset of cardiovascular disease (CVD).Design.  The association between cardiovascular risk factors and prevalent CVD was examined in a cross‐sectional study in order to elucidate their contribution to atherogenesis.Setting and subjects.  Patients were recruited from 37 Dutch Lipid Clinics. The diagnosis of FH was based on a uniform diagnostic protocol, confirmed by DNA analysis in 62% of the cases. All patients were investigated free from any lipid‐lowering drug for at least 6 weeks.Main outcome measures.  Differences in lipids, lipoproteins and other risk factors for CVD were analysed in FH patients with and without CVD.Results.  A total of 526 patients were assessed and more than 37% had a history of CVD with a mean age of onset of 46.8 years. Mean LDL cholesterol (LDL‐C) levels were severely elevated (8.38 ± 2.13 mmol L−1). In univariate analysis, age, presence of hypertension or diabetes, body mass index, triglycerides (TG) and low HDL cholesterol (HDL‐C) were all significantly associated with CVD. Also in multivariate analysis, all these risk factors, except TG and diabetes, were significantly linked to CVD.Conclusion.  A high CVD risk in this large well‐documented characterized sample of FH patients is not only conferred by elevated LDL‐C but also by low HDL‐C.
Automatic high‐precision measurements of the location and width of Kikuchi bands in electron backscatter diffraction patterns
Authors: Krieger Lassen  
Published: March 2003

The demands for reliability and precision of crystal orientation data obtained through automatic analysis of electron backscattering patterns (EBSPs) in the SEM result in similar demands on the quality of the band position data which is provided by an image analysis procedure.This paper describes a new image processing procedure which is capable of providing accurate measurements of the location and width of typically 10–15 bands in digitized EBSPs of average quality. The new procedure is based on the Hough transform (HT) for line detection, and employs a special backmapping technique for generating two simplified HTs which separately focus on bright and dark lines in the images. A coordinated search for peaks in the two HTs leads to precise estimates of both the position and the width of bands in the patterns.A visual evaluation of the data produced by the new procedure shows that it performs significantly better than the conventional procedure with regard to both reliability and precision. Additionally, the measured band width data are fairly precise and can be used for obtaining a more robust and reliable indexing of the bands. Finally, the computational costs of the new procedure are smaller than for the conventional procedure.
The response of SiC fibres to vacuum plasma spraying and vacuum hot pressing during the fabrication of titanium matrix composites
Authors: Baker  , Grant  , Jenkins  
Published: March 2003

Vacuum plasma spraying (VPS) and vacuum hot pressing (VHP) have been used to fabricate Ti‐6Al‐4V matrix composite material reinforced longitudinally with DERA Sigma C coated SiC 1140+ fibres. VPS of Ti‐6Al‐4V onto Sigma 1140+ SiC fibres caused no fibre/matrix interfacial reaction. During VHP a fibre/matrix reaction occurred, producing a mixture of fine (< 50 nm) TiCx(x ≤ 1) adjacent to the fibre coating and coarse‐grained (0.3–0.5 μm) equiaxed TiCxadjacent to the Ti matrix. A decrease in C concentration with increasing distance from the C coating is proposed, and is consistent with the evidence presented. A similar thickness and morphology of reaction product arose from conventional foil–fibre foil processing, but the matrix coated fibre/hot isostatic pressing process led to a slightly thicker reaction layer. The TiCxreaction product acted as a diffusion barrier, inhibiting further reaction more effectively than in experiments on earlier SiC fibres having a C coating.Surface damage was shown to be a factor in lowering 1140+ SiC fibre failure stress. Surface damage to 1140+ fibres resulted from both VPS and VHP, the former causing a slight reduction in mean ultimate tensile strength (UTS), and a large reduction in the bend strain to failure Weibull modulus. This damage was caused by both fibre winding and by deposition of metal during VPS, giving rise to coating flaws, and is not in itself considered to be a major problem. Surface damage increased after VHP, reducing the mean UTS and tensile Weibull modulus, and the mean bend strain to failure. This damage arose from bending and flattening of the rough monotapes, and from the fibre/matrix reaction caused by thermal exposure. The level of damage to 1140+ SiC fibre from VHP was reduced by modification of the process path. Increasing the VHP temperature and lowering the pressure ramp rate reduced fibre damage sufficiently to enable a macroscopic composite UTS of 95% of the theoretical maximum to be achieved.
Imaging damage evolution in a small particle metal matrix composite
Authors: Evans  , Phaneuf  , Boyd  
Published: March 2003

It is difficult to study effectively microstructural damage in metal matrix composites (MMCs) due to artefacts arising from traditional metallographic sample preparation techniques. The sectioning and imaging capabilities of the focused ion beam (FIB) microscope provide an excellent method for studying damage accumulation in MMCs.The capabilities of the FIB system have been used to carry out a study of damage evolution in a powder‐processed/hot‐extruded Al2080/SiCp MMC. Microvoid damage is found to be preserved accurately during FIB sectioning, allowing measurements of the fraction of decohered particles and the void area fraction. These microscopic damage measurements are correlated with the macroscopic damage parameter, D, as determined by density measurements.Using transmission electron microscopy, the evolution of dislocation structures at the SiC–matrix interfaces has been examined. A previously unreported decohesion mechanism has been observed.
Improved estimation of the pair correlation function of random sets
Authors: Mattfeldt T. , Stoyan D. 
Published: March 2003

The texture of binary spatial structures can be characterized by second‐order methods of spatial statistics. The pair correlation function, which describes the structure in terms of spatial correlation as a function of distance, is of central importance in this context. Conventionally, the pair correlation function of stationary and isotropic random sets is estimated as the ratio of the covariance to the square of volume fraction of the phase of interest. In the present paper, an improved estimator of the pair correlation function is presented, where the covariance is divided by the square of a distance‐adapted estimator of volume fraction. The new estimator is explained mathematically and applied to simulated images of the Boolean model and to microscopic images from neoplastic and non‐neoplastic human glandular tissues. It leads to a considerable reduction of bias and variance of estimated pair correlation functions, in particular for large distances.
Tapping‐mode tuning‐fork near‐field scanning optical microscopy of low power semiconductor lasers
Authors: Lu N. H. , Lin W. C. , Tsai D. P. 
Published: March 2003

The newly developed inverted tapping‐mode tuning‐fork near‐field scanning optical microscopy (TMTF‐NSOM) is used to study the local near‐field optical properties of strained AlGaInP/Ga0.4In0.6P low power visible multiquantum‐well laser diodes. In contrast to shear‐force mode NSOM, TMTF‐NSOM provides the function to acquire the evanescent wave intensity ratio |I(2ω)|/|I(ω)| image, from which the evanescent wave decay coefficient q can be evaluated for a known tapping amplitude. Moreover, we probe the near‐field stimulated emission spectrum, which gives the free‐space laser light wavelength λo and the index of refraction nr of the laser diode resonant cavity. Once q, λo, and nr are all measured, we can determine the angle of incidence θo of the dominant totally internally reflected waves incident on the front mirror facet of the resonator. Determination of such an angle is very important in modelling the stability of the laser diode resonator.
Dynamic experimentation on the confocal laser scanning microscope: application to soft‐solid, composite food materials
Authors: Plucknett K. P. , Pomfret S. J. , Normand V. , Ferdinando D. , Veerman C. , Frith W. J. , Norton I. T. 
Published: March 2003

Confocal laser scanning microscopy (CLSM) is used to follow the dynamic structural evolution of several phase‐separated mixed biopolymer gel composites. Two protein/polysaccharide mixed gel systems were examined: gelatin/maltodextrin and gelatin/agarose. These materials exhibit ‘emulsion‐like’ structures, with included spherical particles of one phase (i.e. polymer A) within a continuous matrix of the second (i.e. polymer B). Compositional control of these materials allows the phase order to be inverted (i.e. polymer B included and polymer A continuous), giving four basic variants for the present composites. Tension and compression mechanical tests were conducted dynamically on the CLSM, with crack/microstructure interactions investigated using a notched compact tension geometry. Gelatin/maltodextrin composites exhibit a ‘pseudo‐yielding’ stress/strain response in both tension and compression, when the gelatin‐rich phase is continuous, which was attributed to debonding of the particle/matrix interface. This behaviour is significantly less apparent for both the gelatin/agarose composites, and the maltodextrin continuous gelatin/maltodextrin composites, with these materials responding in a nominally linear elastic manner.Values of the interfacial fracture energy for selected compositions of the two biopolymer systems were determined by 90° peel testing, where a gelatin layer was peeled from either a maltodextrin or agarose substrate. For biopolymer layers ‘cast’ together, a value of 0.2 ± 0.2 J m−2 was obtained for the fracture energy of a gelatin/maltodextrin interface, while a significantly higher value of 6.5 ± 0.2 J m−2 was determined for a gelatin/agarose interface.The interfacial fracture energy of the two mixed systems was also determined following an indirect elastomer composite debonding model. An interfacial fracture energy of ∼0.25 J m−2 was determined using this approach for the gelatin continuous gelatin/maltodextrin composite, which compares favourably with the value calculated directly by peel testing (i.e. ∼0.2 J m−2). A somewhat higher value was estimated for the gelatin continuous gelatin/agarose system (1.0–2.0 J m−2), using this model, although there are severe limitations to this approach for this mixed gel system. In the present case, it is believed that the differing mechanical response of the two mixed biopolymer systems, when the gelatin phase is continuous, arises from the order of magnitude difference in interfacial fracture energy. It is postulated that polymer interdiffusion may occur across the interface for the gelatin/agarose system, to a significantly greater extent than for interfaces between gelatin and maltodextrin, resulting in a higher interfacial fracture energy.
Tracing DiO‐labelled tumour cells in liver sections by confocal laser scanning microscopy
Authors: Timmers M. , Vermijlen D. , Vekemans K. , Zanger R. DE , Wisse E. , Braet F. 
Published: March 2003

SummaryInvestigating rare cellular events is facilitated by studying thick sections with confocal laser scanning microscopy (CLSM). Localization of cells in tissue sections can be done by immunolabelling or by fluorescent labelling of cells prior to intravenous administration. Immunolabelling is technically complicated because of the preservation of antigens during fixation and the problems associated with the penetration of the antibodies. In this study, an alternative and simple approach for the labelling of cells in vitro with the fluorescent probe DiO and its subsequent application in vivo will be outlined. The method was applied to trace DiO‐labelled colon carcinoma cells (CC531s) in 100 µm thick liver sections. In vitro and in vivo experiments revealed that DiO‐labelling of CC531s cells had no cytotoxic or antiproliferative effect and the cells preserved their susceptibility towards hepatic NK cells or Kupffer cells. In addition, DiO remained stable for at least 72 h in the living cell. DiO‐labelled CC531s cells could be traced all over the tissue depth and anti‐metastatic events such as phagocytosis of tumour cells by Kupffer cells could be easily observed. In situ staining with propidium iodide (nucleic acids) or rhodamine‐phalloidin (filamentous actin) resulted in additional tissue information. The data presented improved the understanding of the possible effects of the vital fluorescent probe DiO on cell function and provided a limit of confidence for CLSM imaging of DiO‐labelled cells in tissue sections.
Automatic fluorescent tag detection in 3D with super‐resolution: application to the analysis of chromosome movement
Authors: Thomann D. , Rines D. R. , Sorger P. K. , Danuser G. 
Published: March 2003

SummaryIn this paper, we describe an algorithmic framework for the automatic detection of diffraction‐limited fluorescent spots in 3D optical images at a separation below the Rayleigh limit, i.e. with super‐resolution. We demonstrate the potential of super‐resolution detection by tracking fluorescently tagged chromosomes during mitosis in budding yeast. Our biological objective is to identify and analyse the proteins responsible for the generation of tensile force during chromosome segregation. Dynamic measurements in living cells are made possible by green fluroescent protein (GFP)‐tagging chromosomes and spindle pole bodies to generate cells carrying four fluorescent spots, and observe the motion of the spots over time using 3D‐fluorescence microscopy. The central problem in spot detection arises with the partial or complete overlap of spots when tagged objects are separated by distances below the resolution of the optics. To detect multiple spots under these conditions, a set of candidate mixture models is built, and the best candidate is selected from the set based on χ2‐statistics of the residuals in least‐square fits of the models to the image data.Even with images having a signal‐to‐noise ratio (SNR) as low as 5–10, we are able to increase the resolution two‐fold below the Rayleigh limit. In images with a SNR of 5–10, the accuracy with which isolated tags can be localized is less than 5 nm. For two tags separated by less than the Rayleigh limit, the localization accuracy is found to be between 10 and 20 nm, depending on the effective point‐to‐point distance. This indicates the intimate relationship between resolution and localization accuracy.
Attenuation of Hypothalamic‐Pituitary‐Adrenal Axis Stress Responses in Late Pregnancy: Changes in Feedforward and Feedback Mechanisms
Authors: Johnstone H. A. , Wigger A. , Douglas A. J. , Neumann I. D. , Landgraf R. , Seckl J. R. , Russell J. A. 
Published: March 2003

AbstractThe hypothalamic‐pituitary‐adrenal axis is hyporesponsive to stress in late pregnancy, exemplified as reduced adrenocorticotropic hormone (ACTH) and corticosterone responses to restraint, but the mechanisms are unknown. We investigated forward drive and negative feedback upon the hypothalamic‐pituitary‐adrenal axis in pregnant rats. Corticotropin‐releasing hormone (CRH) and vasopressin mRNA expression in the parvocellular paraventricular nucleus and mineralocorticoid and glucocorticoid receptor expression in the paraventricular nucleus and hippocampus were quantified with in situ hybridization. Because it can enhance the corticosterone negative feedback signal, 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) bioactivity in these brain regions and anterior pituitary was measured in vitro, and ACTH and corticosterone stress responses were measured after intracerebroventricular glycyrrhetinic acid, an 11β‐HSD inhibitor. Changes in corticosterone feedback on ACTH secretion were examined after pharmacological adrenalectomy by metyrapone and aminoglutethimide. Parvocellular paraventricular nucleus CRH mRNA content was reduced on day 21 and the CRH mRNA : vasopressin mRNA ratio was unaltered, indicating decreased production of both CRH and vasopressin. An increase in glucocorticoid receptor mRNA expression in the dentate gyrus (mineralocorticoid receptor mRNA expression was unaltered) and increased 11β‐HSD1 activity in the paraventricular nucleus and anterior pituitary suggest an increase in slow negative feedback mechanisms in pregnancy, but glycyrrhetinic acid did not modify the stress response. After metyrapone/aminoglutethimide treatment, corticosterone decreased ACTH secretion more slowly in pregnancy, indicating a decrease in rapid feedback sensitivity. Thus, reduced forward drive rather than increased effectiveness of glucocorticoid negative feedback may underlie stress hyporesponsiveness of the hypothalamic‐pituitary‐adrenal axis in pregnancy.