Plasma C-reactive protein as a marker of cardiac allograft vasculopathy in heart transplant recipients

OBJECTIVES: This study was initiated to determine whether heart transplant recipients (HTRs) with cardiac allograft vasculopathy (CAV) have increased levels of high-sensitivity C-reactive protein (hsCRP) and to examine whether an increase in hsCRP after heart transplantation predicts the development of CAV. Furthermore, the effect of pravastatin on plasma levels of hsCRP in HTRs was investigated. BACKGROUND: The relationship between CAV and hsCRP, as well as the effect of statins on hsCRP in HTRs, has not been well established. METHODS: On referral for their annual angiographic control study, 150 consecutive HTRs (mean 6.5 years since transplantation) were included. Plasma levels of hsCRP were measured before angiography and compared with patients with (n = 52) and without (n = 98) CAV. In 49 of these patients, we additionally analyzed hsCRP in blood samples stored from their six-month visit after the transplantation procedure. Furthermore, in a randomized, crossover study, hsCRP was analyzed in 17 male HTRs before and after six weeks of treatment with 20 mg pravastatin. RESULTS: Median levels of CRP were elevated among patients with CAV compared with those with normal angiograms [3.86 (1.78 to 7.00) vs. 1.08 (0.72 to 2.13) mg/l, p < 0.001]. Prospectively evaluated hsCRP levels from six months to follow-up were significantly higher among those who developed CAV compared with those with normal angiograms [+2.76 (1.56 to 5.00) vs. +0.07 (-0.57 to 0.41) mg/l, p < 0.001]. On multivariate analysis, the increase in hsCRP was the only significant predictor of CAV. Six weeks of treatment with pravastatin significantly reduced hsCRP levels by 25%, without any relation to changes in lipid values. CONCLUSIONS: Elevated plasma levels of CRP are associated with angiographic evidence of CAV, and the increase in hsCRP is a strong predictor of development of CAV. Statin treatment reduces levels of hsCRP and should be used in HTRs, regardless of their lipid levels.     

Effects of castration, sex steroids, LHRH and glucocorticoids on LHRH binding in the anterior pituitary of male rats

In the present study we have examined the effects of gonadotrophin releasing hormone (LHRH), sex steroids and glucocorticoids on the binding of LHRH to receptors in the pituitary of male intact and castrated rats. In intact rats, LHRH (10 μg/day) treatment for 11 days caused a significant increase in LHRH binding, whereas testosterone (500 μg/day) or oestradiol (50 μg/day) were inhibitory. 17-hydroxyprogesterone and dexamethasone were without effects. In castrated rats, LHRH caused a marginal decrease in LHRH binding. Much greater inhibition was observed with testosterone and oestradiol. 17-hydroxyprogesterone reduced binding to that of intact controls, whereas dexamethasone was ineffective. When different doses of sex steroids were tested, both oestradiol, testosterone and 5α-dihydrotestosterone inhibited LHRH in a dose-dependent manner. The lowest doses of steroids causing significant inhibition of LHRH binding in castrated animals were 0.5, 50 and 500 μg/day for oestradiol, 5α-dihydrotestosterone and testosterone, respectively. The present study shows that pituitary receptors for LHRH are regulated both by sex steroids and LHRH itself.     

Calprotectin (S100A8/S100A9) and Myeloperoxidase: Co-Regulators of Formation of Reactive Oxygen Species

Inflammatory mediators trigger polymorphonuclear neutrophils (PMN) to produce reactive oxygen species (ROS: O₂^-, H₂O₂, ∙OH). Mediated by myeloperoxidase in PMN, HOCl is formed, detectable in a chemiluminescence (CL) assay. We have shown that the abundant cytosolic PMN protein calprotectin (S100A8/A9) similarly elicits CL in response to H₂O₂ in a cell-free system. Myeloperoxidase and calprotectin worked synergistically. Calprotectin-induced CL increased, whereas myeloperoxidase-triggered CL decreased with pH > 7.5. Myeloperoxidase needed NaCl for CL, calprotectin did not. 4-hydroxybenzoic acid, binding ∙OH, almost abrogated calprotectin CL, but moderately increased myeloperoxidase activity. The combination of native calprotectin, or recombinant S100A8/A9 proteins, with NaOCl markedly enhanced CL. NaOCl may be the synergistic link between myeloperoxidase and calprotectin. Surprisingly- and unexplained- at higher concentration of S100A9 the stimulation vanished, suggesting a switch from pro-oxidant to anti-oxidant function. We propose that the ∙OH is predominant in ROS production by calprotectin, a function not described before.     

Neoadjuvant cisplatinum based combination chemotherapy in patients with invasive bladder cancer: a combined analysis of two Nordic studies

OBJECTIVES: A Nordic collaborative group assessed the effectiveness of cisplatinum based combination chemotherapy prior to cystectomy in two consecutive trials. We analyzed overall survival in all patients and in prespecified subgroups defined by preoperative T-stage, gender and age. METHODS: The studies included in 1985-1997 620 patients with clinically T1G3, T2-T4aNXM0 urothelial bladder cancer and WHO performance 相似文献   

Human papillomavirus and cervical intraepithelial neoplasia grade II-III: A population-based case-control study

The association between certain human papillomaviruses (HPV) and cervical intraepithelial neoplasia (CIN) is well documented, but there is uncertainty about the strength of association and the role of co-factors is unclear. This population-based case-control study in Norwegian women 20–44 years of age included 103 cases with histologically confirmed CIN II–III and 234 age-matched and randomly selected controls. Cytological specimens from the cervix were analyzed using the polymerase chain reaction (PCR). In all, 91% of the cases and 15% of the controls were HPV DNA positive, giving a crude odds ratio (OR) of 67.2 (95% confidence interval: 28.6–157.5). The association between HPV 16 and CIN II–III was even stronger (crude OR = 123.9; 46.7 - 328.5). In logistic regression analysis, additional to HPV, only a high number of sexual partners and a low educational level contributed independently to the risk. The adjusted OR for the association between HPV and CIN II–III was 72.8 (95% Cl: 27.6–191.9). The association between HPV and CIN remains very strong even after adjustment for proposed confounding factors. The results therefore support the role of HPV as a causative agent in the development of CIN. © 1995 Wiley-Liss, Inc.     

Restoration of Cognitive Performance in Mice Carrying a Deficient Allele of 8-Oxoguanine DNA Glycosylase by X-ray Irradiation

Environmental stressors inducing oxidative stress such as ionizing radiation may influence cognitive function and neuronal plasticity. Recent studies have shown that transgenic mice deficient of DNA glycosylases display unexpected cognitive deficiencies related to changes in gene expression in the hippocampus. The main objectives of the present study were to determine learning and memory performance in C57BL/6NTac 8-oxoguanine DNA glycosylase 1 (Ogg1)^+/? (heterozygote) and Ogg1^+/+ (wild type, WT) mice, to study whether a single acute X-ray challenge (0.5 Gy, dose rate 0.457 Gy/min) influenced the cognitive performance in the Barnes maze, and if such differences were related to changes in gene expression levels in the hippocampus. We found that the Ogg1^+/? mice exhibited poorer early-phase learning performance compared to the WT mice. Surprisingly, X-ray exposure of the Ogg1^+/? animals improved their early-phase learning performance. No persistent effects on memory in the late-phase (6 weeks after irradiation) were observed. Our results further suggest that expression of 3 (Adrb1, Il1b, Prdx6) out of in total 35 genes investigated in the Ogg1^+/? hippocampus is correlated to spatial learning in the Barnes maze.     

In situ hybridization of chromosome 6 on fine-needle aspirates from breast carcinomas: Comparison of numerical abnormalities and ER/PgR status and staining pattern

The estrogen receptor (ER) gene is located on chromosome 6. The aim of our study was to investigate whether numerical chromosomal aberrations were reflected in estrogen/progesterone receptor (PgR) status and staining pattern. Fine-needle aspirates from 51 breast carcinomas were investigated immunocytochemically for ER/PgR and by in situ hybridization technique using digoxigenin-labeled α-satellite probe for chromosome 6. Cases with ≥70% two-signal nuclei were regarded as disome; the remaining tumors showed aneusomy with a variable number of signals. Aneusomy was found in 32 tumors (63%), whereas 19 (37%) had a normal number of chromosome 6. Chromosomal gain occurred in all aneusome cases except one. ER- and/or PgR-positive tumors had an equal distribution of disomy and aneusmy. Variable ER staining pattern or ER and/or PgR negativity was associated with numerical aberrations in chromosome 6 in 76% of the tumors. Cancers with uniform ER staining pattern all had normal chromosome number. Diagn. Cytopathol. 16:420–424, 1997. © 1997 Wiley-Liss, Inc.     

Shape-Adaptive DCT for Denoising of 3D Scalar and Tensor Valued Images

During the last ten years or so, diffusion tensor imaging has been used in both research and clinical medical applications. To construct the diffusion tensor images, a large set of direction sensitive magnetic resonance image (MRI) acquisitions are required. These acquisitions in general have a lower signal-to-noise ratio than conventional MRI acquisitions. In this paper, we discuss computationally effective algorithms for noise removal for diffusion tensor magnetic resonance imaging (DTI) using the framework of 3-dimensional shape-adaptive discrete cosine transform. We use local polynomial approximations for the selection of homogeneous regions in the DTI data. These regions are transformed to the frequency domain by a modified discrete cosine transform. In the frequency domain, the noise is removed by thresholding. We perform numerical experiments on 3D synthetical MRI and DTI data and real 3D DTI brain data from a healthy volunteer. The experiments indicate good performance compared to current state-of-the-art methods. The proposed method is well suited for parallelization and could thus dramatically improve the computation speed of denoising schemes for large scale 3D MRI and DTI.