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1.
Different mechanisms by which anti-DNA MoAbs bind to human endothelial cells and glomerular mesangial cells. 下载免费PDF全文
T M Chan G Frampton N A Staines P Hobby G J Perry J S Cameron 《Clinical and experimental immunology》1992,88(1):68-74
The mechanisms by which anti-DNA MoAbs derived from MRL-lpr/lpr mice, bind to human umbilical vein endothelial cells (HUVEC) and glomerular mesangial cells were studied using a cellular ELISA. DNAse-treatment of either the MoAb or HUVEC followed by reconstitution with DNA and/or histones was performed to determine whether DNA and histones mediated such binding. It was found that MoAb410 bound to HUVEC and mesangial cells in the form of preformed DNA/anti-DNA immune complex, and such binding was facilitated by histones. In contrast, MoAb 152 bound directly to cell membrane-associated DNA, and adding DNA to MoAb 152 reduced its cellular binding. DNA binds endothelial cell surface and histones enhance the binding of both MoAb 410 and MoAb 152 to HUVEC by increasing cell membrane-associated DNA. Finally, the degree of MoAb binding to HUVEC is critically influenced by the relative concentrations of antibody, DNA, and histones. 相似文献
2.
3.
Incidence of childhood diabetes mellitus in Yorkshire, northern England, is associated with nitrate in drinking water: an ecological analysis 总被引:7,自引:1,他引:6
R. C. Parslow P. A. McKinney G. R. Law A. Staines R. Williams H. J. Bodansky 《Diabetologia》1997,40(5):550-556
Summary The relationship between the incidence of childhood-onset insulin-dependent diabetes mellitus and levels of nitrate in drinking
water in the former Yorkshire Regional Health Authority was investigated by means of an ecological analysis. A population-based
register contributed 1797 0–16-year-olds diagnosed with diabetes between 1978 and 1994. Nitrate data were based on 9330 samples
of drinking water tested between 1990 and 1995 in 148 water supply zones, for which 1991 census small area statistics were
taken on population density, ethnicity and socio-economic status. Diabetes incidence was positively associated with raised
mean nitrate levels with a standardised incidence ratio of 115 in zones with greater than 14.85 mg · l–1 (χ2 = 26.81, 1 df, p < 0.001). Significant negative trends were found between standardised incidence ratios and proportion of non-whites in the
population (χ2 = 33.57, 1 df, p < 0.001), childhood population density (χ2 = 30.81, 1 df, p < 0.001) and the Townsend deprivation score (χ2 = 33.89, 1 df, p < 0.001). Poisson regression modelling, adjusting for the other factors, showed a significant increase in relative incidence
rate ratio from a baseline of 1 at nitrate levels below 3.22 mg · l–1 to 1.27 (95 % confidence interval 1.09,1.48) for mean nitrate levels above 14.85 mg · l–1. An association between higher nitrate levels in domestic drinking water and incidence of childhood diabetes has been demonstrated.
This was not explained by the ethnic composition of the population, population density or socioeconomic status. Nitrate in
drinking water may be a precursor of chemicals which are toxic to the pancreas. [Diabetologia (1997) 40: 550–556]
Received: 24 October 1996 and in revised form: 20 December 1996 相似文献
4.
We hypothesized that sensory input from the moving leg induces presynaptic inhibition of the soleus H reflex pathway in the contralateral stationary leg. The results showed a crossed inhibition during passive pedalling movement of the leg, which was not removed by low levels of tonic contraction of soleus in the stationary leg. The inhibition was correlated exponentially to the rate of the movement (R2=0.934, P<0.05) and was not dependent on the quadrants through which the moving leg was passing. Static flexion of the stationary leg caused ipsilateral inhibition of the reflexes (t=5.590, P<0.05), independent of the orientations of the other leg. We concluded that sensory inflow from the moving leg induces presynaptic inhibition in the stationary leg, that a complex transformation of the sensory input in the spinal cord or brain underlies the tonic crossed inhibition and phasic ipsilateral inhibition, and that descending motor commands exert a powerful control over these sensorimotor modulatory mechanisms. 相似文献
5.
The intense immunohistochemical reaction for the enzyme adenosine deaminase displayed by neurons in the tuberomammillary nucleus in the rat was used to study the distribution and morphology of cells comprising this nucleus, their fiber fields within the posterior hypothalamus and their projection pathways from the hypothalamus. Neurons immunoreactive for adenosine deaminase were found along ventricular and basal aspects of the hypothalamus from the level of the dorsomedial nucleus to the caudal pole of the mammillary body. Approximately 4500 neurons were seen on each side of the brain. Positive neurons showed a complex distribution, largely avoiding nuclear boundaries within the posterior basal hypothalamus and mammillary body. This distribution is mapped in detail and a nomenclature based on topography is introduced so that different regions of the cell distribution may be discussed more easily. Reactive neurons showed a Golgi-like staining which allowed careful study of their morphology. In general, neurons were large, with major axes of from 22 to 30 micron, and bipolar in shape. A second, smaller cell type, 14-16 micron in diameter was also seen and, although often less intensely stained, it was considered a constituent of tuberomammillary nucleus of the hypothalamus as well. Stained dendritic arbours extended considerable distances from the parent cell bodies and branched regularly. Dendrites showed very sparse spines and had an apparently scalloped surface. Features suggestive of varicose segments of dendrites were also noted. The long, smooth dendrites of positive neurons were often seen to aggregate into bundles which avoided nuclear boundaries and tended to collect adjacent to basal and ventricular surfaces of the posterior hypothalamus. Varicose fibers immunoreactive for adenosine deaminase formed a dense network within the hypothalamus. These fibers were considered to derive from the positive neurons in the tuberomammillary nucleus and were similar to adenosine deaminase-immunoreactive fibers seen throughout much of the rest of the brain. The density of this type of positive fiber was, however, much greater within the hypothalamus. The region of the posterior basal hypothalamus also contained relatively sparse populations of adenosine deaminase-positive fibers, apparently distinct from this network. These consisted of a field of fine fibers in the median division of the medial mammillary nucleus and a few large varicosities in the dorsolateral part of the median eminence.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
6.
Fine specificity of autoantibodies to calreticulin: epitope mapping and characterization 总被引:2,自引:0,他引:2 下载免费PDF全文
Eggleton P Ward FJ Johnson S Khamashta MA Hughes GR Hajela VA Michalak M Corbett EF Staines NA Reid KB 《Clinical and experimental immunology》2000,120(2):384-391
Extracellular calreticulin (CRT) as well as anti‐CRT antibodies have been reported in patients with various autoimmune disorders and CRT has been implicated in ‘epitope spreading’ to other autoantigens such as the Ro/SS‐A complex. In addition, antibodies against parasite forms of the endoplasmic reticulum chaperone, CRT, have been found in patients suffering from onchocerciasis and schistosomiasis. In this study, we screened sera for anti‐CRT antibodies from patients with active and inactive systemic lupus ertythematosus (SLE) and primary or secondary Sjögren’s syndrome. Approximately 40% of all SLE patients were positive for anti‐CRT antibodies. The antigenic regions of CRT were determined using full length CRT and fragments of CRT prepared in yeast and Escherichia coli, respectively. Synthetic 15mer peptides corresponding to the major autoantigenic region of CRT (amino acids 1–289), each one overlapping by 12 amino acids, were used to map the B cell epitopes on the CRT protein recognized by autoimmune sera. Major antigenic epitopes were found to be associated with the N‐terminal half of the protein in 69% of the SLE sera from active disease patients, while the C‐domain was not antigenic. Major epitopes were found to be reactive with antibodies in sera from SLE patients with both active and inactive disease, spanning different regions of the N and P‐domains. Sera from both healthy and disease controls and primary Sjögren’s syndrome patients were non‐reactive to these sequences. Limited proteolysis of CRT with two major leucocyte serine proteases, elastase and cathepsin G, demonstrated that an N‐terminal region of CRT is resistant to digestion. Interestingly, some of the epitopes with the highest reactivity belong to the fragments of the protein which bind to C1q and inhibit complement activation. Whether C1q association with CRT is a pathological or protective interaction between these two proteins is currently under investigation. 相似文献
7.
Danielle K. Bourque Inara Chacon Fonseca Andrea Staines Ronni Teitelbaum Michelle M. Axford Rebekah Jobling David Chiasson David Chitayat 《American journal of medical genetics. Part A》2019,179(7):1325-1329
Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) is a rare, autosomal dominant disorder of interstitial lung development, leading to pulmonary hypertension, and death in infancy. Associated features include malformations of the heart, gastrointestinal tract, and genitourinary system. ACDMPV is caused by heterozygous variants in the FOXF1 gene or microdeletions involving FOXF1. We present a male infant with ACDMPV, hypoplastic left heart sequence (HLHS), duodenal atresia, and imperforate anus due to a de novo, in frame deletion in FOXF1: c.209_214del (p.Thr70_Leu71del). Previous reports have suggested that microdeletions involving FOXF1 are associated with ACDMPV with congenital heart defects, including HLHS, gastrointestinal atresias, and other anomalies; whereas likely pathogenic variants within FOXF1 have not been reported with ACDMPV and HLHS. This is the first patient reported with ACDMPV, HLHS, imperforate anus, and duodenal atresia associated with a likely pathogenic variant in the FOXF1 gene. 相似文献
8.
C Morland J Michael D Adu T Kizaki A J Howie A Morgan N A Staines 《Clinical and experimental immunology》1991,83(1):126-132
The effect of the administration of a xenogeneic anti-idiotype antibody (anti-Id33) to a cross-reactive idiotype (Id33) present on anti-dsDNA antibody was examined in 6-week-old (NZB/NZW) F1 (BWF1) female mice. The administration of anti-Id33 led to a transient reduction in immunoglobulins expressing Id33, followed by a rise at 30 and 34 weeks that was significantly higher than in untreated mice (P less than 0.05). Likewise, anti-dsDNA antibody levels were significantly higher at 10 and 18 weeks than in untreated mice (P less than 0.01). No differences were seen in survival to 40 weeks, proteinuria or the severity of glomerulonephritis. Concurrent administration of cyclosporin A (CyA) with anti-Id33 markedly ameliorated glomerular injury and proteinuria and improved survival. By contrast, glomerular injury, proteinuria and survival were worse in mice treated with cyclophosphamide plus anti-Id33, compared with untreated mice. Neither CyA nor cyclophosphamide treatment, when given with anti-Id33 altered serum levels of anti-dsDNA, anti-ssDNA or Id33+ immunoglobin, compared with untreated mice. The different effects of CyA and cyclophosphamide on T lymphocytes and their discrepant effects on glomerular injury when given with anti-Id33 in this model lead us to postulate a role for T lymphocytes in the glomerular injury of BWF1 lupus. 相似文献
9.
Glomerulonephritis induced by pre-formed immune complexes containing monoclonal antibodies of defined affinity and isotype. 下载免费PDF全文
The work presented here represents the first report of the induction of experimental immune complex (IC) disease in mice using monoclonal antibodies (MoAb) derived from somatic cell hybridization. IC were formed using two antigens of either high (DNP19BSA) or low (DNP4BSA) epitope density and five MoAb (four IgGl with varying affinities for the dinitrophenol hapten and one IgM with a similar affinity to that of the lowest affinity IgGl). Circulating levels and sizes of IC were dependent on the affinity of the antibody component of the complex. When antigen of high epitope density was used, the glomerular localization of injected IC was diffuse mesangial for the IgM antibody, focal mesangial for the highest affinity IgG and diffuse, and predominantly capillary for the low affinity IgG antibodies. Subepithelial electron dense deposits were observed only with IC made with the low affinity IgG antibodies. When IC containing antigen of a lower epitope density were injected, localization was only observed with IC made near equivalence. Deposition of these IC was less prominent than that found when IC containing antigen of higher epitope density were injected. The relevance of these findings to the pathogenesis of glomerulonephritis is discussed. 相似文献
10.
Modulation of Whole-Cell Currents in Plasmodium Falciparum-Infected Human Red Blood Cells by Holding Potential and Serum 总被引:3,自引:0,他引:3
Henry M. Staines Trevor Powell J. Clive Ellory Stéphane Egée Franck Lapaix Gaëtan Decherf Serge L. Y. Thomas Christophe Duranton† Florian Lang† Stephan M. Huber† 《The Journal of physiology》2003,552(1):177-183
Recent electrophysiological studies have identified novel ion channel activity in the host plasma membrane of Plasmodium falciparum -infected human red blood cells (RBCs). However, conflicting data have been published with regard to the characteristics of induced channel activity measured in the whole-cell configuration of the patch-clamp technique. In an effort to establish the reasons for these discrepancies, we demonstrate here two factors that have been found to modulate whole-cell recordings in malaria-infected RBCs. Firstly, negative holding potentials reduced inward currents (i.e. at negative potentials), although this result was highly complex. Secondly, the addition of human serum increased outward currents (i.e. at positive potentials) by approximately 4-fold and inward currents by approximately 2-fold. These two effects may help to resolve the conflicting data in the literature, although further investigation is required to understand the underlying mechanisms and their physiological relevance in detail. 相似文献