bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ageing and medicine
Authors: Grimley Evans J. 
Published: March 2003

Abstract. Grimley Evans J (University of Oxford, Oxford, UK). Ageing and medicine (Review). J Intern Med 2000; 247: 159–167.Throughout the world, populations are ageing. The response of the health services needs to be based on a knowledge of the nature of human ageing and the principles of rational health care for older people. Ageing comes about from interactions between intrinsic (genetic) and extrinsic (environment and lifestyle) factors. Health care has to be responsive to the general needs of older people, but also to recognize the heterogeneity produced by different rates and patterns of individual ageing. There are now real possibilities of improving the course of human ageing through modulation of both intrinsic and extrinsic processes. There is also a need to adapt social institutions to what is a permanent change in demography.
Carotid and femoral atherosclerosis, cardiovascular risk factors and C‐reactive protein in relation to smokeless tobacco use or smoking in 58‐year‐old men
Authors: Wallenfeldt K. , Hulthe J. , Bokemark L. , Wikstrand J. , Fagerberg B. 
Published: March 2003

Abstract. Wallenfeldt K, Hulthe J, Bokemark L, Wikstrand J, Fagerberg B (Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden). Carotid and femoral atherosclerosis, cardiovascular risk factors and C‐reactive protein in relation to smokeless tobacco use or smoking in 58‐year‐old men. J Intern Med 2001; 250: 492–501. Objectives. To examine the associations between smokeless tobacco use, smoking, cardiovascular risk factors, inflammation and ultrasound‐assessed measures of atherosclerosis in the carotid and femoral arteries. Subjects. The study was performed in a population‐based sample of clinically healthy men (n=391) all 58 years old. Exclusion criteria were cardiovascular or other clinically overt diseases or continuous medication with cardiovascular drugs. Methods. The habits of smoking and oral moist snuff use were assessed by questionnaires. C‐reactive protein (CRP) was assessed by high sensitive enzyme‐linked immunosorbent assay (ELISA). Intima‐media thickness (IMT) in the carotid bulb, the common carotid artery and the common femoral artery and plaque occurrence were measured by ultrasound. Results. The use of oral moist snuff was associated with serum triglycerides and waist–hip ratio (WHR), but not with CRP or ultrasound‐assessed measures of subclinical atherosclerosis. Smoking, on the other hand, was associated with CRP, the components in the metabolic syndrome and IMT as well as plaques in the carotid and femoral arteries. In comparison to never‐smokers the current smokers had higher values of WHR, triglycerides, C‐reactive protein and IMT in carotid bulb and femoral artery. Ex‐smokers were in general more obese and had a femoral IMT that was in‐between that of never‐smokers and current smokers. Conclusions. Tobacco smoking, but not oral moist snuff use, was associated with carotid and femoral artery IMT, and increased levels of CRP. Current smoking was also associated with abdominal obesity. Ex‐smokers though, are generally more obese. Smoking was also associated with hyperinsulinaemia, dyslipidaemia and high blood pressure, i.e. the metabolic syndrome. The inhaled smoke from the combustion of tobacco seems to be an important aetiological factor in the atherosclerotic process.
Diabetes and advanced glycation endproducts
Authors: Vlassara H. , Palace M.R. 
Published: March 2003

Abstract. Vlassara H, Palace MR (Department of Geriatrics, Division of Experimental Diabetes and Ageing, Mount Sinai School of Medicine, and Department of Medicine, Division of Endocrinology, Mount Sinai School of Medicine, NY, USA). Diabetes and Advanced Glycation Endproducts. J Intern Med 2002; 251: 87–101.Bio‐reactive advanced glycation endproducts (AGE) alter the structure and function of molecules in biological systems and increase oxidative stress. These adverse effects of both exogenous and endogenously derived AGE have been implicated in the pathogenesis of diabetic complications and changes associated with ageing including atherosclerosis, renal, eye and neurological disease. Specific AGE receptors and nonreceptor mechanisms contribute to these processes but also assist in the removal and degradation of AGE. The final disposal of AGE depends on renal clearance. Promising pharmacologic strategies to prevent AGE formation, reduce AGE toxicity, and/or inactivate AGE are under investigation.
Is there a role for microorganisms in the pathogenesis of sarcoidosis?
Authors: Du Bois R. M. , Goh N. , McGrath D. , Cullinan P. 
Published: March 2003

Abstract. du Bois RM, Goh N, McGrath D, Cullinan P (Royal Brompton Hospital and Imperial College, London, UK). Is there a role for microorganisms in the pathogenesis of sarcoidosis (Minisymposium)?J Intern Med2003;253:4–17.Sarcoidosis is a granulomatous disease that has the immunopathological features of being antigen‐driven. It is a complex disease that appears to arise from the interaction of one or more triggers with an immunologically predisposed host. Previous reports of familial clustering and varying prevalence of sarcoidosis in different populations could reflect differences in ethnic predisposition or differences in local environmental exposures. This review focuses specifically on these areas that have been the subjects of intensive investigation recently. Specific focus is provided on the issue of an infective trigger and highlights popular candidates. It is concluded that microbes are a likely trigger (but not as an infection) in a genetically predisposed individual and that this initial event culminates in the sarcoidosis granulomatous response.
Using GaAsP photodiodes to characterize ultrashort pulses under high numerical aperture focusing in microscopy
Authors: MILLARD A. C. , FITTINGHOFF D. N. , SQUIER J. A. , MÜLLER M. , GAETA A. L. 
Published: March 2003

SummaryWe demonstrate for the first time that the two‐photon response of GaAsP photodiodes can be used to conveniently characterize the spatial and temporal profiles of ultrashort pulses at the focus of a high numerical aperture system.
Three‐dimensional spectral precision distance microscopy of chromatin nanostructures after triple‐colour DNA labelling: a study of the BCR region on chromosome 22 and the Philadelphia chromosome
Authors: Esa A. , Edelmann P. , Kreth G. , Trakhtenbrot L. , Amariglio N. , Rechavi G. , Hausmann M. , Cremer C. 
Published: March 2003

Topological analysis of the three‐dimensional (3D) chromatin nanostructure and its function in intact cell nuclei implies the use of high resolution far field light microscopy, e.g. confocal laser scanning microscopy (CLSM). However, experimental evidence indicates that, in practice, under biologically relevant conditions, the spatial resolution of CLSM is limited to about 300 nm in the lateral direction and about 700 nm in the axial direction. To overcome this shortcoming, the use of a recently developed light microscopical approach, spectral precision distance microscopy (SPDM) is established. This approach is based on the precise localization of small labelling sites of a given target in spectrally differential images. By means of quantitative image analysis, the bary centres (intensity weighted centroid analogous to the centre of mass) of these independently registered labelling sites can be used as point markers for distance and angle measurements after appropriate calibration of optical aberrations (here, polychromatic shifts). In combination with specific labelling of very small chromatin target sites with dyes of different spectral signatures by fluorescence in situ hybridization (FISH), SPDM presently allows us to analyse the nuclear topology in three‐dimensionally conserved nuclei with a ‘resolution equivalent’, many times smaller than the conventional optical resolution.Chronic myelogeneous leukaemia (CML) is genetically characterized by the fusion of parts of the BCR and ABL genes on chromosomes 22 and 9, respectively. In most cases, the fusion leads to a translocation t(9; 22) producing the Philadelphia chromosome. SPDM was applied to analyse the 3D chromatin structure of the BCR region on the intact chromosome 22 and the BCR‐ABL fusion gene on the Philadelphia chromosome (Ph) by using a new triple‐colour FISH protocol: two different DNA probes were used to detect the BCR region and the third DNA probe was used to identify the location of the ABL gene. Consistent 3D distance measurements down to values considerably smaller than 100 nm were performed. The angle distributions between the three labelled sites on the Philadelphia chromosome territory were compared to two state‐of‐the‐art computer models of nuclear chromatin structure. Significant differences between measured and simulated angle distributions were obtained, indicating a complex and non‐random angle distribution.
Femtosecond near‐field scanning optical microscopy study of molecular thin films
Authors: Kawashima H. , Furuki M. , Tatsuura S. , Tian M. , Sato Y. , Pu L. S. , Tani T. 
Published: March 2003

A near‐field scanning optical microscope has been combined with a two‐colour time‐resolved pump‐probe measurement system. It has a noise‐equivalent transmittance change of 5.0 × 10−5 for a probe pulse with an intensity of 30 nW. The system has been used for evaluating molecular thin films that have a domain structure, particularly for observing a gate action of the single domains. The results include key features to understand an origin of the domains and suggest that the film composition is uniform over a distance of several micrometres.
Centrifuge polarizing microscope. II. Sample biological applications
Authors: Inoué S. , Goda M. , Knudson R. A. 
Published: March 2003

The rationale, design and general performance of the CPM (centrifuge polarizing microscope) were described in Part I of this study (Inouéet al. J. Microsc. 201 (2001) 341–356. In this second part, we describe observations on several biological samples that we have explored over the past two years using the CPM.As described in the first part of the study, although the CPM was basically designed as a high‐extinction centrifuge polarizing microscope, it also allows observations of the specimen exposed to high centrifugal fields up to 10 500 × g (earth's gravitational acceleration) in fluorescence (532‐nm excitation) and in DIC (differential interference or Nomarski contrast).
A new surface characterization technique: RIMAPS (Rotated Image with Maximum Average Power Spectrum)
Authors: Fuentes N. O. , Favret E. A. 
Published: March 2003

SummaryThis work introduces a new imaging technique, Rotated Image with Maximum Average Power Spectrum (RIMAPS), for use in determining orientation and characteristics of surface topography. It consists of computing the maximum value of the averaged power spectrum, given by one step of the two‐dimensional Fourier transform, for each angle of rotation of a digitized image. The basic measurement science of this technique is described and different cases are studied. The characterization of simple geometrical figures explains the meaning of peaks and their angular positions given by RIMAPS analysis. A known surface pattern made on a sample of pure copper, mechanically ground, is used to study reproducibility, dependence on image quality and topography scale relative to pixel size and magnification. Samples of pure zinc, mechanically ground and chemically etched, were used to show the main features of RIMAPS analysis when characterizing a more complicated pattern on a real surface. All the studies performed under different conditions for observation and acquisition of images give strong evidence of the stability and robustness of RIMAPS as a technique for the characterization of topography.
Efficient embedding technique for preparing small specimens for stereological volume estimation: zebrafish larvae
Authors: Hill A. J. , Howard C. V. , Cossins A. R. 
Published: March 2003

SummaryStereological sampling regimes, in particular volume and number estimation, often require systematic uniformly random sections throughout a specimen. A method has been developed to increase the efficiency of preparing fish larvae for sectioning prior to histological or stereological analysis. Embedding a group of larvae in a resin block using this technique greatly reduces the quantity of sections produced and allows easy assessment of sample groups. Saving time in this way therefore makes stereology a more viable research tool.
Simultaneously identifying S‐phase labelled cells and immunogold‐labelling of vinculin in focal adhesions
Authors: Owen G. RH. , Meredith D. O. , Gwynn I. Ap , Richards R. G. 
Published: March 2003

SummaryA new combination of autoradiography and immunolabelling techniques is presented that allows the simultaneous identification of both S‐phase cells and their focal adhesions using scanning electron microscopy. The technique allows both labels to be discerned visually by their unique shapes and location within and on the cell. S‐phase cells were radio‐labelled with a pulse of tritiated thymidine, selectively incorporated into synthesizing DNA. The cells were then immunogold‐labelled for the focal adhesion protein, vinculin, prepared for autoradiography, and embedded in resin. The resin was then polymerized before removing the substrate, to expose the embedded cell undersurface. Electron‐energy ‘sectioning’ of the sample by varying the accelerating voltage of the electron beam allowed separate S‐phase cell identification in one electron‐energy ‘section’ and visualization of immunogold label in another ‘section’, within the same cell. As a result of applying this technique it was possible to positively identify S‐phase cells and immunogold‐labelled focal adhesions on the same cell simultaneously, which could be used to quantify focal adhesion sites on different substrates.
On the orientational analysis of planar fibre systems from digital images
Authors: Kärkkäinen S. , Jensen E. B. V. , Jeulin D. 
Published: March 2003

SummaryThe orientational characteristics of fibres in digital images are studied. The fibres are modelled by a planar Boolean model whose typical grain is a thick (coloured) fibre. The aim is to make stereological inference on the rose of directions of the unobservable central fibres from observations made on a digital image of the thick fibres. For central fibres, the relation between the rose of directions and the point intensity, observed on a sampling line, is known. We derive, under regularity conditions, the relation between the unobservable point intensity and the scaled variogram observed on the line in a binary and a greyscale image. Using such a relation, it is possible to draw inference about the rose of directions from the scaled variogram, which is easy and quick to determine in a digital image.
Photoperiod Affects the Ability of Testosterone to Alter Proopiomelanocortin mRNA, but not Luteinizing Hormone‐Releasing Hormone mRNA, Levels in Male Sheep
Authors: Hileman Stanley M. , Kuehl David E. , Jackson Gary L. 
Published: March 2003

This study tested the hypothesis that photoperiod affects the ability of testosterone to reduce proopiomelanocortin (POMC) mRNA levels in the arcuate nucleus and luteinizing hormone‐releasing hormone (LHRH) mRNA levels in both the preoptic area (POA) or medial basal hypothalamus (MBH). Twenty castrated male sheep were assigned to one of four treatment groups (i): short days (SD;n=5) (ii), short days with testosterone (SD+T; n=5) (iii), long days (LD; n=5), or (iii) long days with testosterone (LD+T; n=5). Blood samples were collected twice weekly for the last 3 weeks of photoperiod treatment and assessed for LH to validate the response to photoperiod. After evaluating LH levels, one animal each from the LD+T and SD+T groups was excluded from the analyses. Mean concentrations of LH were lower (P<0.01) in the LD+T group than in the other treatment groups, which did not differ (P>0.10) from each other. Neither POA nor MBH LHRH mRNA levels were affected (P>0.10) by treatment. Conversely, POMC mRNA levels were suppressed (P<0.01) in the LD+T males compared with the other treatment groups which did not differ (P>0.10) from each other. These observations suggest that photoperiod specific, testosterone‐induced alterations in LHRH mRNA levels are not a mechanism whereby testosterone suppresses LHRH release, and that increased beta‐endorphin synthesis and release do not mediate testosterone‐induced seasonal suppression of LHRH release.
Corticosteroid Effects on Serotonin Responses in Granule Cells of the Rat Dentate Gyrus
Authors: Karten Y. J. G. , Stienstra C. M. , Joëls M. 
Published: March 2003

AbstractGranule cells in the rat dentate gyrus contain mineralocorticoid and glucocorticoid receptors to which the adrenal hormone corticosterone binds with differential affinity. These cells also express various receptor‐subtypes for serotonin (5‐HT), including the 5‐HT1A receptor which mediates a membrane hyperpolarization accompanied by a decrease in membrane resistance. Earlier studies have shown that removal of corticosterone by adrenalectomy, particularly in the dentate gyrus, results in enhanced expression of the 5‐HT1A receptor mRNA and increased 5‐HT1A receptor binding capacity. This was normalized by activation of mineralocorticoid receptors or concurrent activation of both receptor types. In the present, intracellular recording study in vitro, we examined if the altered levels of 5‐HT1A receptor mRNA and protein are associated with changes in the response to 5‐HT. We found that the hyperpolarization and resistance decrease induced in granule cells by a submaximal (10 µM) dose of 5‐HT were unaltered 2–4 days after adrenalectomy, indicating a dissociation between corticosteroid actions on 5‐HT1A receptor mRNA/protein levels and functional responses to 5‐HT. Subsequent occupation of mineralocorticoid receptors in vitro significantly suppressed the 5‐HT induced change in resistance, 1–4 h after steroid application. Compared to this, concurrent activation of glucocorticoid receptors led to large responses to 5‐HT. This modulation by steroids was not observed with a higher dose of 5‐HT (30 µM). The data suggest that with moderate amounts of 5‐HT, corticosteroids affect the information flow through the dentate gyrus such that excitatory transmission is promoted with predominant mineralocorticoid receptor activation and attenuated with additional glucocorticoid receptor occupation.
The Differential Regulation of CART Gene Expression in a Pituitary Cell Line and Primary Cell Cultures of Ovine Pars Tuberalis Cells
Authors: Barrett P. , Morris M. A. , Moar K. M. , Mercer J. G. , Davidson J. A. , Findlay P. A. , Adam C. L. , Morgan P. J. 
Published: March 2003

AbstractThe cocaine‐amphetamine regulated transcript (CART) encodes for a protein which has an important role in the regulation of appetite and body weight. To date, no details of the molecular events and signal transduction pathways which regulate this gene are available. We report the identification of CART gene expression in the GH3 pituitary cell line. We have used activators of the cAMP or protein kinase C (PKC) signal transduction pathways to show that, in GH3 cells, CART is transcriptionally up‐regulated by activators of the cAMP signal transduction pathway. We also identify CART gene expression in ovine pars tuberalis (PT) tissue and primary cell cultures. In PT cells in contrast to GH3 cells, CART gene expression is upregulated by activators of the PKC signal transduction pathway. Cultured cells have provided a valuable resource for the detailed analysis of specific regulatory mechanisms underlying transcriptional or translational regulation of genes, signal transduction events and many other cellular processes. GH3 and PT cells may therefore provide a resource for the further detailed molecular analysis of the events regulating CART gene expression and processing.
Repeated Antenatal Glucocorticoid Treatment Decreases Hypothalamic Corticotropin Releasing Hormone mRNA but not Corticosteroid Receptor mRNA Expression in the Fetal Guinea‐Pig Brain
Authors: McCabe L. , Marash D. , Li A. , Matthews S. G. 
Published: March 2003

AbstractApproximately 10% of pregnant women are treated with synthetic glucocorticoids in late gestation, to promote fetal lung maturation. The effectiveness of this treatment has led to the use of repeated dose regimens, with little knowledge of the impact on neuroendocrine development. Animal studies have recently shown that repeated fetal glucocorticoid exposure can lead to permanent changes in hypothalamic‐pituitary‐adrenal (HPA) function in offspring. In this study, we hypothesized that such treatment modifies corticotropin releasing hormone (CRH), glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) systems in the developing limbic system and hypothalamus. Pregnant guinea‐pigs were treated with dexamethasone, betamethasone or vehicle on days 40,41,50,51,60 and 61 of gestation (birth = 68 days). On day 62, guinea‐pigs were killed and the fetuses rapidly removed. Glucocorticoid treatment resulted in a dose‐dependent reduction in plasma cortisol concentrations in both male and female fetuses. There was also a significant reduction in CRH mRNA expression in the hypothalamic paraventricular nucleus. In contrast, exposure to glucocorticoid increased MR mRNA expression in the hippocampus (CA1/2 and CA3) and dentate gyrus of female fetuses. There was a small but significant increase in GR mRNA expression in limbic structures in male fetuses following treatment with 1 mg/kg dexamethasone. However, there was no significant effect of glucocorticoid exposure on hippocampal GR mRNA expression in female fetuses, or hypothalamic GR mRNA in either males or females. In conclusion, repeated maternal glucocorticoid treatment inhibits fetal HPA function. The fact that CRH mRNA levels were reduced indicates that synthetic glucocorticoids enter the fetal brain. By contrast, fetal glucocorticoid exposure does not downregulate GR mRNA, and increases MR mRNA expression. The latter likely reflects removal of circulating endogenous ligand (cortisol). These alterations may form the basis for permanently modified HPA activity in later life.
Identification of Efferent Neural Pathways from the Lamina Terminalis Activated by Blood‐Borne Relaxin
Authors: Sunn N. , McKinley M. J. , Oldfield B. J. 
Published: March 2003

AbstractThe ovarian hormone relaxin, in addition to its role in pregnancy, exerts an action on the brain to influence oxytocin and vasopressin secretion, water drinking, and cardiovascular function. Intravenous (i.v.) infusion of relaxin causes an acute water drinking response, confirming its role as a dipsogenic hormone. The aim of this study was to determine whether neurones in the lamina terminalis, which project to the hypothalamic paraventricular and supraoptic nuclei, are activated by elevated levels of circulating relaxin in conscious rats. Immunocytochemistry combined with retrograde neuronal tracing with cholera toxin B subunit conjugated to cholera toxin B (CTB‐gold) was used to identify populations of neurones responding with elevated cells of Fos protein to i.v. relaxin administration and which project to these specific hypothalamic sites. Neurones exhibiting Fos were present in the outer parts of the subfornical organ (SFO), the dorsal part of the organum vasculosum (OVLT), the supraoptic nucleus and the paraventricular nucleus. These did not occur in control rats with i.v. infusions of isotonic saline. Approximately 90% of neurones concentrated in the outer parts of the SFO and in the dorsal OVLT showed both retrogradely transported CTB‐gold and Fos in response to i.v. infusion of relaxin. These data support a role for relaxin acting on the brain to regulate body fluid and electrolyte homeostasis by activating neural pathways subserving water drinking, vasopressin and oxytocin secretion.