Altered expression of transforming growth factor-βs in chronic renal rejection

Altered expression of transforming growth factor-βs in chronic renal rejection. We examined the altered expression of transforming growth factor-βs in chronic renal rejection in humans, including transforming growth factor beta-1 (TGF-β1), TGF-β2, TGF-β3 and their receptors, transforming growth factor beta receptor type I (TβR-I) and TβR-II. Using Northern blot analysis and immunohistochemistry, 10 specimens of chronically rejected and 8 normal kidney samples were analyzed. By Northern blot analysis the expression of mRNA encoding TGF-β1, TGF-β2, TGF-β3 (P < 0.02), TβR-I and TβR-II (P < 0.02) was decreased in chronically rejected renal cortex samples, compared to normal controls. Immunohistochemical analysis of the normal renal cortex showed strong immunostaining for TGF-β1 and TGF-β3, and mild immunostaining for TGF-β2 in the proximal and distal tubulointerstitium, but no signal for any of the TGF-β isoforms in the glomeruli or in the cortical vessels. In sharp contrast, the glomeruli and the cortical vessels of the rejected kidney specimens exhibited strong immunostaining for TGF-β1 and TGF-β3, whereas the tubules revealed a decrease in immunoreactivity. TβRI and TβRII immunostaining showed similar changes as observed with TGF-β1 and TGF-β3 antibodies. There was a concomitant increase in B-cell accumulation in the glomeruli, while T-cells and macrophages were diffusely abundant in the rejected samples. Since TGF-βs are potent inducers of extracellular matrix proteins and have been shown to be involved in fibrotic disease, the increase in TGF-β1 and TGF-β3 immunoreactivity in the glomeruli suggests that there is a redistribution in TGF-β expression in chronic renal allograft rejection. Together with changes affected by B-cell mediated immunity, the above alterations might contribute to the histopathological changes that occur in this disorder, such as intimal fibrosis, arteriosclerosis and glomerular and tubular sclerosis

A global charter for the public\u27s health - The public\u27s health: the role, functions, competencies, education

Political leaders increasingly perceive health as being crucial to achieving growth, development, equity and stability throughout the world. Health is now understood as a product of complex and dynamic relations generated by numerous determinants at different levels of governance. Governments need to take into account the impact of social, environmental and behavioural health determinants, including economic constraints, living conditions, demographic changes and unhealthy lifestyles in many of the World Health Organization (WHO) Member States. This understanding and increasing globalization means it is very timely to review the role of (global) public health in this changing societal and political environment

Diagnostic accuracy of contrast-enhanced MR angiography in severe carotid stenosis: meta-analysis with metaregression of different techniques

Contrast-enhanced magnetic resonance angiography (CE-MRA) has become a well-established noninvasive imaging method for the assessment of severe carotid stenosis (70–99% by NASCET criteria). However, CE-MRA is not a standardised technique, but encompasses different concurrent techniques. This review analyses possible differences. A bivariate random effects meta-analysis of 17 primary diagnostic accuracy studies confirmed a high pooled sensitivity of 94.3% and specificity of 93.0% for carotid CE-MRA in severe carotid stenosis. Sensitivity was fairly uniform among the studies, while specificity showed significant variation (I2 = 73%). Metaregressions found significant differences for specificity with two covariates: specificity was higher when using not only maximum intensity projection (MIP) images, but also three-dimensional (3D) images (P = 0.01). Specificity was also higher with electronic images than with hardcopies (P = 0.02). The timing technique (bolus-timed, fluoroscopically triggered or time-resolved) did not result in any significant differences in diagnostic accuracy. Some nonsignificant trends were found for the percentages of severe carotid disease, acquisition time and voxel size. In conclusion, in CE-MRA of severe carotid stenosis the three major timing techniques yield comparably high diagnostic accuracy, electronic images are more specific than hardcopies, and 3D images should be used in addition to MIP images to increase the specificity

Aberrant antigenic expression in extranodal NK/T-cell lymphoma: a multi-parameter study from Thailand

<p>Abstract</p> <p>Background</p> <p>Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is not common worldwide, but it is the most common T- and NK-cell lymphomas in many Asian countries. Immunophenotypic profiles were studied based on limited series. The authors, therefore, studied on ENKTL according to characterize immunophenotypic profiles as well as the distribution of EBV subtype and LMP-1 gene deletion.</p> <p>Methods</p> <p>By using tissue microarray (TMA), immunohistochemical study and EBV encoded RNA (EBER) in situ hybridization were performed. T-cell receptor (TCR) gene rearrangement, EBV subtyping, and LMP-1 gene deletion were studied on the available cases.</p> <p>Results</p> <p>There were 22 cases eligible for TMA. ENKTL were positive for CD3 (91%), CD5 (9%), CD7 (32%), CD4 (14%), CD56 (82%), TIA-1 (100%), granzyme B (95%), perforin (86%), CD45 (83%), CD30 (75%), Oct2 (25%), and IRF4/MUM1 (33%). None of them was positive for βF1, CD8, or CD57. TCR gene rearrangement was negative in all 18 tested cases. EBV was subtype A in all 15 tested cases, with 87% deleted LMP-1 gene. Cases lacking perforin expression demonstrated a significantly poorer survival outcome (p = 0.008).</p> <p>Conclusions</p> <p>The present study demonstrated TIA-1 and EBER as the two most sensitive markers. There were a few CD3 and/or CD56 negative cases noted. Interestingly, losses of CD45 and/or CD7 were not uncommon while Oct2 and IRF4/MUM1 could be positive in a subset of cases. Based on the present study in conjunction with the literature review, determination of PCR-based TCR gene rearrangement analysis might not be a useful technique for making diagnosis of ENKTL.</p

Der EBNA2-codierende Bereich im viralen Genom Epstein-Barr Virus (EBV)-positiver Falle von Morbus Hodgkin. [The EBNA2 coding region in the viral genome of Epstein-Barr virus (EBV)-positive cases of Hodgkin's disease]

Epstein-Barr virus (EBV)-genome containing cases of Hodgkin's disease (HD) are known to express latent membrane protein (LMP) of EBV but no EBV nuclear antigen 2 (EBNA2). We investigated 35 cases of HD for the presence of EBV genome sequences to know whether EBNA2 coding region is deleted in HD. 27 cases had general EBV sequences, none had evidence of a deletion of EBNA2. 26 cases turned out to harbour EBV type 1, one case had EBV type 2. The absence of EBNA2 protein expression in HD can not be explained by a deletion of EBNA2 coding region. EBV type 1 is the prevalent subtype of EBV in our series of HD

In vitro evaluation of stent patency and in-stent stenoses in 10 metallic stents using MR angiography

In vitro study to investigate the suitability of contrast enhanced magnetic resonance angiography (CEMRA) for determination of stent patency and grading of in-stent stenoses in 10 metallic stents. The Acculink carotid, DynaLink, Easy Wallstent, JostentSelfX XF, Luminexx, Omnilink, sinus-SuperFlex, SMART, Symphony and ZA stent were separately placed in a vascular phantom. Dedicated stenoses inside the stents generated a concentric lumen narrowing of 50%. CEMRA was performed for each stent. Signal loss inside the stents and artificial lumen narrowing were assessed objectively using the evaluation software of the MR imager. Moreover, three blinded observers determined visibility of stent patency and in-stent stenoses subjectively on a 3-point scale and graded in-stent stenoses. Loss of signal intensity within the stent lumen ranged between 90% (Wallstent) and 5% (ZA), artificial lumen narrowing between 56% (Symphony) and 22% (ZA). For the Symphony and Wallstent, visibility of patency and in-stent stenoses was impaired and the observers' grading exaggerated the degree of stenoses (by 23% and 33%, respectively). For the remainder of stents, patency and stenoses were visible and stenoses were graded accurately (less than 10% discrepancy from reference standard). In this in vitro study, eight of 10 stents presented with MRI characteristics which enabled determination of stent patency and accurate grading of clinically relevant in-stent stenoses