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51.
Apolipoprotein(a) phenotypes are reliable biomarkers for familial aggregation of coronary heart disease 总被引:2,自引:0,他引:2
Peros E Geroldi D D'Angelo A Falcone C Montagna L Carabela M Emanuele E 《International journal of molecular medicine》2004,13(2):243-247
Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic molecule formed by the covalent binding of the highly polymorphic apolipoprotein(a) [apo(a)] to apoprotein B-100 of LDL. High Lp(a) concentrations are a recognized genetic risk factor for coronary heart disease (CHD) and have been shown to be related with a familial clustering of ischemic cardiac events. Nevertheless, the association between apolipoprotein(a) isoforms and a positive familial history of CHD has received far less attention. In this report, we explored the distribution of apo(a) phenotypes in 127 CHD subjects with a family history of coronary events and in 92 CHD patients without such a history. Twenty-two apo(a) isoforms were detected by a high-resolution immunoblotting method. In univariate analysis, the percentage of subjects with at least one small sized apo(a) isoform was significantly higher in CHD patients with a positive family history than in those without (P<0.01). Multivariate analysis showed that apo(a) isoforms of low molecular weight were the best predictors of familial aggregation of cardiac ischemia. We conclude that apo(a) size polymorphism is strongly associated with a familial history of CHD and is more efficient than Lp(a) plasma concentrations in predicting the familial clustering of coronary disease. When detected by high-resolution techniques, apo(a) phenotypes are objective laboratory markers that can substitute for a knowledge of a positive family history of CHD and should be used, together with Lp(a) levels, to better assess the familial predisposition to coronary events. 相似文献
52.
Anti-HBs Cellular Immune Response in Kidney Recipients before and 4 Months after Transplantation 下载免费PDF全文
Patricia Aguilar Edith Renoult Loraine Jarrosson Marie Nathalie Kolopp-Sarda Christine Prin Mathieu Gilbert C. Faure Mich
le Kessler Marie C. Bene Chantal Kohler Anne Kennel De March 《Clinical and Vaccine Immunology : CVI》2003,10(6):1117-1122
Patients with renal failure represent a population at risk for hepatitis B, since only 50 to 60% of them develop protective humoral responses after vaccination. As this could be due to an altered regulation of cellular immune responses, the objectives of the present study were to evaluate the proliferative abilities of lymphocytes from patients with chronic renal failure after stimulation in vitro with a mitogen (pokeweed mitogen [PWM]) or HBsAg. In order to differentiate between the immunodeficiency associated with renal failure and that due to immunosuppression posttransplantation, the same subjects were tested before and 4 months after kidney transplantation. The lymphoproliferation assay used was performed by flow cytometry, which is based on sequential analysis of the cell cycle and which allows analysis of cytokine production. Serologically, the group of 36 patients tested comprised 22% nonresponders, 30% poor responders, and 48% responders. Lymphocyte growth was observed for all patients after stimulation with PWM, indicating that these cells had the capacity to proliferate in vitro. The level of lymphoproliferation in response to PWM was significantly reduced after transplantation, yet both before and after transplantation, all serologic nonresponders developed cellular responses to at least two vaccines. No correlation between humoral and cellular responses was shown. Proliferating cells were lymphocytes, which mostly secreted interleukin 4 (IL-4) and IL-10 for the three serologic groups. This study suggests that even when repeated vaccination fails to induce significant antibody levels in patients with renal failure, specific HBs cellular responses develop, and these may prove to be efficient in protecting these patients against hepatitis B. 相似文献
53.
54.
J. J. Palacios J. Ferro N. Ruiz Palma S. G. Roces H. Villar J. Rodríguez P. Prendes 《European journal of clinical microbiology & infectious diseases》1998,17(11):767-772
The aim of this study was to compare the results of a commercial assay based on the ligase chain reaction [(LCR) LCx Probe System MTB; Abbott, USA] with those of culture in liquid medium (Septi-Chek AFB; Becton-Dickinson, USA) and culture on the egg-based Löwenstein-Jensen solid medium for the direct detection of Mycobacterium tuberculosis complex in nonrespiratory specimens. The results were analyzed according to the standard definition of a true-positive result. Two hundred thirty-five nonrespiratory samples routinely submitted to rule out tuberculosis were analyzed. All samples were smear-negative. Mycobacterial growth in either culture medium was detected in 18 (7.6%) specimens: Mycobacterium tuberculosis was recovered from seven (38.9%) specimens cultured on Löwenstein-Jensen medium and from 18 (100%) specimens cultured in Septi-Chek AFB. The LCR protocol was positive in 22 specimens. None of the LCR-negative controls showed positive results. All samples positive by culture on Löwenstein-Jensen medium were positive by culture in liquid medium and by the LCR assay. However, Mycobacterium tuberculosis was detected by culture in liquid medium in two specimens that were negative by the LCR assay, whereas six specimens negative by culture in liquid medium were positive by the LCR protocol; three of these were identified as true-positive results of the LCR assay. The sensitivity, specificity, and positive and negative predictive values were 33.3%, 100%, 100%, and 93.8%, respectively, for Löwenstein-Jensen medium; 85.7%, 100%, 100%, and 98.6% for the liquid medium; and 90.4%, 98.5%, 86.3%, and 99% for the LCR assay. These findings indicate that the LCR assay may be a valid method of high diagnostic yield for direct detection of Mycobacterium tuberculosis complex in nonrespiratory specimens. 相似文献
55.
DC-SIGN mediates the binding of Aspergillus fumigatus and keratinophylic fungi by human dendritic cells 总被引:2,自引:0,他引:2
Human contact with fungi does not usually lead to pathological consequences, as the immune system manages to defeat the invader pathogens. Nevertheless, under immune suppression, fungi overcome immune defenses and cause diseases that range from nonserious colonizations of keratinizated tissue (Dermatophytosis) to life threatening disseminated infections (Aspergillosis). Host defenses against fungi rely on innate and adaptative responses, with dendritic cell (DC) and macrophage surface receptors having a major role in the recognition of fungal pathogens and in the orchestration of an effective immune response. DC-SIGN is a C-type lectin involved in the recognition of bacterial, viral and parasitic pathogens, as well as in interactions between cells of the immune system. Its expression is restricted to DCs and subsets of macrophages. Here we show that DC-SIGN mediates the binding and capture of Aspergillus fumigatus and keratinophylic fungi, including Chrysosporium tropicum, by human DCs, describe the requirements of these interactions and discuss their potential involvement in the onset and persistence of pulmonary fungal infections. 相似文献
56.
Analysis of heart rate variability (HRV) is a valuable, non-invasive method for quantifying autonomic cardiac control in humans.
Frequency-domain analysis of HRV involving myocardial ischaemic episodes should take into account its non-stationary behaviour.
The wavelet transform is an alternative tool for the analysis of non-stationary signals. Fourteen patients have been analysed,
ranging from 40 to 64 years old and selected from the European Electrocardiographic ST-T Database (ESDB). These records contain
33 ST episodes, according to the notation of the ESDB, with durations of between 40s and 12min. A method for analysing HRV
signals using the wavelet transform was applied to obtain a time-scale representation for very low-frequency (VLF), low-frequency
(LF) and high-frequency (HF) bands using the orthogonal multiresolution pyramidal algorithm. The design and implementation
using fast algorithms included a specially adapted decomposition quadrature mirror filter bank for the frequency bands of
interest. Comparing a normality zone against the ischaemic episode in the same record, increases in LF (0.0112±0.0101 against
0.0175±0.0208s2Hz−1; p<0.1) and HF (0.0011±0.0008 against 0.0017±0.0020s2Hz−1; p<0.05) were obtained. The possibility of using these indexes to develop an ischaemic-episode classifier was also tested.
Results suggest that wavelet analysis provides useful information for the assessment of dynamic changes and patterns of HRV
during myocardial ischaemia. 相似文献
57.
58.
Chronic cyclosporin A nephrotoxicity, P-glycoprotein overexpression, and relationships with intrarenal angiotensin II deposits. 下载免费PDF全文
R. G. del Moral M. Andujar C. Ramírez M. Gmez-Morales M. Masseroli M. Aguilar A. Olmo F. Arrebola M. Guilln M. J. García-Chicano F. F. Nogales F. O'Valle 《The American journal of pathology》1997,151(6):1705-1714
P-glycoprotein (P-gp) expels hydrophobic substances from the cell, including chemotherapeutic agents and immunosuppressants such as cyclosporin A (CsA) and FK506. Exposure of cultured renal tubular cells to CsA induces P-gp overexpression in cell membranes. Angiotensin II has recently been implicated as the principal factor responsible for progression of interstitial fibrosis induced by CsA. To investigate the in vivo relationships between histological lesions, P-gp overexpression, and intrarenal angiotensin II deposits, we developed a model of chronic CsA toxicity in Sprague-Dawley rats treated with 25 mg/kg/day CsA for 28 and 56 days and fed either a standard maintenance diet or a low-salt diet. Immunohistochemical methods were used to study the expression of P-gp in renal tubular cells and the appearance of intrarenal angiotensin II deposits. Rats treated with CsA developed chronic nephrotoxicity lesions that were more evident in the group fed the low-salt diet. Treatment with CsA induced overexpression of P-gp in tubular cells of the kidney that increased with time. We found that immunohistochemical expression of P-gp was slightly more severe in rats fed a low-salt diet. Intrarenal deposits of angiotensin II were more evident in rats treated with CsA; these deposits also increased with time. This finding was also more relevant in rats given the low-salt diet. The up-regulation of P-gp was inversely related to the incidence of hyaline arteriopathy (r = -0.65; P < 0.05), periglomerular (r = -0.58; P < 0.05) and peritubular fibrosis (r = -0.63; P < 0.05), and intrarenal angiotensin H deposits in animals with severe signs of nephrotoxicity (r = -0.65; P < 0.05). These results support the hypothesis that the role of P-gp as a detoxicant in renal cells may be related to mechanisms that control the cytoplasmic removal of both toxic metabolites from CsA and those originating from the catabolism of signal transduction proteins (methylcysteine esters), which are produced as a result of ras activation in presence of angiotensin II. 相似文献
59.
Diego A. Gomez Philip A. May Barbara G. Tabachnick Julie M. Hasken Elizabeth R. Lyden Wendy O. Kalberg H. Eugene Hoyme Melanie A. Manning Margaret P. Adam Luther K. Robinson Kenneth Lyons Jones David Buckley Omar A. Abdul‐Rahman 《American journal of medical genetics. Part A》2020,182(10):2243-2252
Fetal alcohol spectrum disorders (FASD) describe a range of physical, behavioral, and neurologic deficits in individuals exposed to alcohol prenatally. Reduced palpebral fissure length is one of the cardinal facial features of FASD. However, other ocular measurements have not been studied extensively in FASD. Using the Fetal Alcohol Syndrome Epidemiologic Research (FASER) database, we investigated how inner canthal distance (ICD), interpupillary distance (IPD), and outer canthal distance (OCD) centiles differed between FASD and non‐FASD individuals. We compared ocular measurement centiles in children with FASD to non‐FASD individuals and observed reductions in all three centiles for ICD, IPD, and OCD. However, when our non‐FASD children who had various forms of growth deficiency (microcephaly, short‐stature, or underweight) were compared to controls, we did not observe a similar reduction in ocular measurements. This suggests that reductions in ocular measurements are a direct effect of alcohol on ocular development independent of its effect on growth parameters, which is consistent with animal models showing a negative effect of alcohol on developing neural crest cells. Interpupillary distance centile appeared to be the most significantly reduced ocular measure we evaluated, suggesting it may be a useful measure to be considered in the diagnosis of FASD. 相似文献
60.
Diego A. Gomez Lynne M. Bird Nicole Fleischer Omar A. Abdul‐Rahman 《American journal of medical genetics. Part A》2020,182(9):2021-2026
Angelman syndrome (AS) is caused by several genetic mechanisms that impair the expression of maternally‐inherited UBE3A through deletions, paternal uniparental disomy (UPD), UBE3A pathogenic variants, or imprinting defects. Current methods of differentiating the etiology require molecular testing, which is sometimes difficult to obtain. Recently, computer‐based facial analysis systems have been used to assist in identifying genetic conditions based on facial phenotypes. We sought to understand if the facial‐recognition system DeepGestalt could find differences in phenotype between molecular subtypes of AS. Images and molecular data on 261 individuals with AS ranging from 10 months through 32 years were analyzed by DeepGestalt in a cross‐validation model with receiver operating characteristic (ROC) curves generated. The area under the curve (AUC) of the ROC for each molecular subtype was compared and ranked from least to greatest differentiable phenotype. We determined that DeepGestalt demonstrated a high degree of discrimination between the deletion subtype and UPD or imprinting defects, and a lower degree of discrimination with the UBE3A pathogenic variants subtype. Our findings suggest that DeepGestalt can recognize subclinical differences in phenotype based on etiology and may provide decision support for testing. 相似文献