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1.
Segregation analysis indicates a major gene in the control of interleukine-5 production in humans infected with Schistosoma mansoni. 总被引:2,自引:1,他引:1 下载免费PDF全文
V. Rodrigues Jr L. Abel K. Piper A. J. Dessein 《American journal of human genetics》1996,59(2):453-461
The interleukine-5 (IL-5) is a hormone of the immune system that is the main regulator of eosinopoiesis, eosinophil maturation and activation, and immunoglobulin A production. Thus, IL-5 contributes in several ways to human immune defenses against various pathogens, including helminths and infectious agents of the digestive and respiratory tracts. On the other hand, the increase in eosinophil number and the activation of these cells, which both have been related to elevated IL-5 production, are the cause of severe pathological disorders, as in asthma or hypereosinophilic syndromes. Although the immunological pathways leading to IL-5 synthesis have been identified, the reasons for the large variability observed in IL-5 production among subjects exposed to comparable antigenic stimulation are unknown. To investigate the role of genetic factors in this variability, we conducted a segregation analysis in a Brazilian population infected by the helminth parasite Schistosoma mansoni. The analysis was performed on IL-5 levels produced by blood mononuclear cells of these subjects after in vitro restimulation with either parasite extracts (IL-5/schistosomula sonicates [SS] phenotype) or a T-lymphocyte mitogen (IL-5/phytohemagglutin [PHA]). The results provide clear evidence for the segregation of a codominant major gene controlling IL-5/SS and IL-5/PHA production and accounting for 70% and 73% of the phenotypic variance, respectively; the frequency of the allele predisposing to low IL-5 production was approximately .22 for both phenotypes. No significant relationship was found between these genes and the gene controlling infection intensities by S. mansoni detected in a previous study. Linkage studies are ongoing to locate those genes that would help to characterize the genetic factors involved in pathological conditions such as severe helminth infections and allergic diseases. 相似文献
2.
Adipo(cyto)kines are mostly produced by adipose tissue and orchestrate the adverse
impact of excess adiposity on cardiovascular risk. Adipokines also contribute
importantly to the pathophysiology of rheumatoid arthritis. Congruent with data
reported in previous investigations, Kang and colleagues report in this issue of
Arthritis Research & Therapy that adipokine concentrations are
further associated with metabolic risk and inflammation and that the
leptin–adiponectin ratio associates with the carotid artery resistive index in
rheumatoid arthritis. Guided by evidence reported thus far on cardiovascular risk, we
discuss six reasons why careful elucidation of adipokine–cardiovascular risk
relations is needed in rheumatoid arthritis.In this issue of Arthritis Research & Therapy, Kang and colleagues
investigate whether adipokines could link inflammation, metabolic risk factors and
cardiovascular disease in rheumatoid arthritis (RA) [1]. Evidence in support of this paradigm was reported previously [2-6]. Patients with RA experience a markedly increased cardiovascular risk that is
driven by metabolic risk factors and by high-grade inflammation [7]. Kang and colleagues measured adiponectin, leptin, resistin, tumor necrosis
factor alpha and interleukin-6 concentrations and assessed the common carotid artery
intima-media thickness, resistive index (RI) and plaque presence by high-resolution
ultrasonography [1]. Concentrations of some of the adipokines related to inflammatory markers
including C-reactive protein levels and the erythrocyte sedimentation rate, and to
metabolic syndrome features.In a previous study by our group, leptin and adiponectin concentrations were not
associated with carotid intima-media thickness and plaque [3]. In addition, the leptin–adiponectin ratio and carotid RI as markers of
cardiovascular risk have not been reported in RA. For these reasons, besides the
abovementioned analyses, Kang and colleagues assessed (only) the relationship of the
leptin–adiponectin ratio with carotid RI. In univariate analysis, the
leptin–adiponectin ratio as well as age, homeostasis model assessment for insulin
resistance, waist circumference and body mass index were associated with the carotid RI.
Importantly, in multivariate analysis, only age and the leptin–adiponectin ratio
remained significantly related to the carotid RI. The leptin–adiponectin ratio may
thus provide information about the presence of subclinical cardiovascular disease beyond
that on insulin resistance as assessed by the homeostasis model of insulin resistance,
as well as adiposity extent as represented by body mass index and waist circumference in
RA.Adipo(cyto)kines comprise a vast range of disparate soluble bioactive proteins that are
mostly secreted by adipose tissue [8]. These molecules participate in biological processes that include
inflammatory responses and thereby orchestrate the adverse impact of excess adiposity on
cardiovascular risk and incident type 2 diabetes [8]. Adipokines represent both adiposity extent and biological activity. RA is a
prototypic inflammatory disease. In this context, ~200 recently reported investigations
substantiate an important involvement of adipokines in RA activity and severity [9]. By contrast, despite the contribution of adipokines to altered
cardiovascular risk in non-RA subjects and the enhanced cardiovascular risk in RA, there
is a striking paucity of reported studies on the potential role of adipokines in
atherogenesis in RA.A myriad of pertinent reasons exist why the role of adipokines in cardiovascular risk
amongst patients with RA requires thorough elucidation. First, RA can modify adipokine
production [3,9].Second, and presumably more important, the presence of autoimmunity can alter the
effects of adipokines on cardiovascular risk [3,4]. In non-RA subjects, adiponectin production decreases with increasing
adiposity and this adipokine has anti-inflammatory properties [8]. However, in RA adiponectin has marked proinflammatory properties [9]. In fact, in Kang and colleagues’ study the adiponectin concentrations
were paradoxically positively associated with the erythrocyte sedimentation rate [1]. Whereas in non-RA subjects adiponectin improves metabolic risk and also
directly inhibits atherogenesis, we reported recently that in RA, upon using
comprehensive potential confounder-adjusted analysis, adiponectin concentrations
associated paradoxically with high blood pressure [3,4] and in white but not black Africans with enhanced endothelial activation [4]. Endothelial activation mediates the very initial stages of atherosclerosis [3-6]. Whether such paradoxical relations represent altered effects mediated by RA
or a compensatory increase in adiponectin production in the presence of heightened
cardiovascular risk and in an attempt to reduce this risk needs further investigation [4].Third, conventional risk factors and disease characteristics can impact on
adipokine–atherogenesis relationships in RA [5]. Resistin concentrations thus associate independently with endothelial
activation in RA, but this relation is present only in those with, and not in those
without, traditional risk factors, abdominal obesity, joint damage as reflected by the
presence of deformed joints or prolonged disease duration [5]. This observation further supports the need for sensitivity analysis in the
present context. By contrast, interleukin-6 concentrations are more consistently
associated with endothelial activation in RA [6].Fourth, the effects of adipokines on cardiovascular risk require examination prior to
targeting the respective molecules in an attempt to reduce disease activity and severity
in RA [3]. Indeed, should the protective effect of adiponectin on cardiovascular risk
be preserved amongst patients with RA, then its blockade would be expected to further
enhance cardiovascular risk [3].Fifth, RA influences adiposity and its distribution, which also associates with
atherosclerosis in this disease [7,10].Finally, as illustrated by the disparity in adiponectin–endothelial activation
relations amongst Africans previously alluded to, population origin impacts on
adipokine–cardiovascular risk relations in RA [4].A caveat of Kang and colleagues’ study is that potential confounders were not
systematically identified. For example, gender, cardiovascular drug use, antirheumatic
agent use and the glomerular filtration rate can all influence both the concentrations
and effects of adipokines [3-6]. Nevertheless, this investigation reinforces previously reported evidence
that strongly suggests an intriguing and important involvement of adipokines in RA
atherogenesis. 相似文献
3.
Quantitative data play an important role in palynological research. With the advent of digital imaging in light and electron microscopy, palynologists now have the opportunity to perform measurements faster and more precisely than ever before. Several image analysis software packages already exist for these tasks, but they are often expensive, difficult to use or not adapted to the specific needs of palynologists. After studying the daily workflow of a palynologist, we designed CARNOY, an image analysis application written from the ground up for use in palynology and morphology. CARNOY offers an easy-to-use interface and several features to make measuring easier and faster. The program can export measurements to almost every other software package for further analysis and is available for free on the Internet. 相似文献
4.
Caroline Michot Asmaa Mamoune Joseph Vamecq Mai Thao Viou Lu-Sheng Hsieh Eric Testet Jeanne Lainé Laurence Hubert Anne-Frédérique Dessein Monique Fontaine Chris Ottolenghi Laetitia Fouillen Karim Nadra Etienne Blanc Jean Bastin Sophie Candon Mario Pende Arnold Munnich Pascale de Lonlay 《生物化学与生物物理学报:疾病的分子基础》2013,1832(12):2103-2114
5.
6.
7.
Patrick H. Dessein Hon-Chun Hsu Linda Tsang Aletta M. E. Millen Angela J. Woodiwiss Gavin R. Norton Ahmed Solomon Miguel A. Gonzalez-Gay 《PloS one》2015,10(3)
Objective
To determine whether kidney function independently relates to endothelial activation and ultrasound determined carotid atherosclerosis in black and white Africans with rheumatoid arthritis (RA).Methods
We calculated the Jelliffe, 5 Cockcroft-Gault equations, Salazar-Corcoran, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (EGFR) equations in 233 (112 black) RA patients.Results
The CKD-EPI eGFR was <90 ml/min/1.73m2 in 49.1% and 30.6% of black and white patients, respectively (odds ratio (95% confidence interval) = 2.19 (1.28–3.75), p = 0.004). EGFRs were overall consistently associated with monocyte chemoattractant protein-1 and angiopoietin 2 concentrations in white patients, and with carotid intima-media thickness and plaque in black participants. Amongst black patients, plaque prevalence was 36.7% and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was not associated with plaque presence for the MDRD equation (p = 0.3), whereas the respective relationship was significant or borderline significant (p = 0.003 to 0.08) and of similar extent (p>0.1 for comparisons of AUC (SE)) for the other 8 equations. Based on optimal eGFR cutoff values with sensitivities and specificities ranging from 42 to 60% and 70 to 91% respectively, as determined in ROC curve analysis, a low eGFR increased the odds ratio for plaque 2.2 to 4.0 fold.Conclusion
Reduced kidney function is independently associated with atherosclerosis and endothelial activation in black and white Africans with RA, respectively. CKD is highly prevalent in black Africans with RA. Apart from the MDRD, eGFR equations are useful in predicting carotid plaque presence, a coronary heart disease equivalent, amongst black African RA patients. 相似文献8.
Background & Aims
The brain dopaminergic (DA) system is involved in fine tuning many behaviors and several human diseases are associated with pathological alterations of the DA system such as Parkinson’s disease (PD) and drug addiction. Because of its complex network integration, detailed analyses of physiological and pathophysiological conditions are only possible in a whole organism with a sophisticated tool box for visualization and functional modification.Methods & Results
Here, we have generated transgenic mice expressing the tetracycline-regulated transactivator (tTA) or the reverse tetracycline-regulated transactivator (rtTA) under control of the tyrosine hydroxylase (TH) promoter, TH-tTA (tet-OFF) and TH-rtTA (tet-ON) mice, to visualize and genetically modify DA neurons. We show their tight regulation and efficient use to overexpress proteins under the control of tet-responsive elements or to delete genes of interest with tet-responsive Cre. In combination with mice encoding tet-responsive luciferase, we visualized the DA system in living mice progressively over time.Conclusion
These experiments establish TH-tTA and TH-rtTA mice as a powerful tool to generate and monitor mouse models for DA system diseases. 相似文献9.
Helia B. Schonthaler Tamara A. Franz-Odendaal Corinne Hodel Ines Gehring Robert Geisler Heinz Schwarz Stephan C.F. Neuhauss Ralf Dahm 《Mechanisms of development》2010,127(3-4):203-219
The development of the eye lens is one of the classical paradigms of induction during embryonic development in vertebrates. But while there have been numerous studies aimed at discovering the genetic networks controlling early lens development, comparatively little is known about later stages, including the differentiation of secondary lens fibre cells. The analysis of mutant zebrafish isolated in forward genetic screens is an important way to investigate the roles of genes in embryogenesis. In this study we describe the zebrafish mutant bumper (bum), which shows a transient, tumour-like hyperproliferation of the lens epithelium as well as a progressively stronger defect in secondary fibre cell differentiation, which results in a significantly reduced lens size and ectopic location of the lens within the neural retina. Interestingly, the initial hyperproliferation of the lens epithelium in bum spontaneously regresses, suggesting this mutant as a valuable model to study the molecular control of tumour progression/suppression. Behavioural analyses demonstrate that, despite a morphologically normal retina, larval and adult bum?/? zebrafish are functionally blind. We further show that these fish have defects in their craniofacial skeleton with normal but delayed formation of the scleral ossicles within the eye, several reduced craniofacial bones resulting in an abnormal skull shape, and asymmetric ectopic bone formation within the mandible. Genetic mapping located the mutation in bum to a 4 cM interval on chromosome 7 with the closest markers located at 0.2 and 0 cM, respectively. 相似文献
10.
BACKGROUND AND AIMS: Members of Rubiaceae are generally characterized by an inferior ovary. However, Mitrasacmopsis is cited in the literature as having a semi-inferior to superior ovary. It has previously been hypothesized that the gynoecial development of Rubiaceae with semi-inferior to superior ovaries takes place in the same way as in Gaertnera, one of the most commonly cited rubiaceous genera with a superior ovary. To test this hypothesis, a floral ontogenetic study of Mitrasacmopsis was carried out with special attention paid to the gynoecial development. METHODS: Floral ontogeny and anatomy of Mitrasacmopsis were examined using scanning electron and light microscopy. KEY RESULTS: At an early developmental stage, a concavity becomes visible in the centre of the floral apex simultaneously with the perianth initiation. A ring primordium surrounding this concavity expands vertically forming the corolla tube (early sympetaly). Stamen primordia develop inside the corolla. From the bicarpellate gynoecium only two carpel tips are visible because the ovary is formed by a gynoecial hypanthium. In the basal part of each carpel, a placenta primordium is initiated. Two septa divide the ovary into two locules. In each locule, the placenta becomes mushroom shaped and distinctly stalked. Eventually, the inferior ovary of Mitrasacmopsis develops into a beaked capsule. Only very late in the fruiting stage, the continuously expanding ovary is raised above the insertion point of the persistent calyx, changing the ovary position of Mitrasacmopsis from basically inferior to secondarily semi-inferior. CONCLUSIONS: Mitrasacmopsis follows an epigynous pattern of floral development. However, the presence of a prominent beak in the fruiting stage gives the whole ovary a semi-inferior appearance. This kind of secondarily semi-inferior ovary is shown to be different from the secondarily superior ovary observed in Gaertnera. 相似文献