Diffusion Tensor Model links to Neurite Orientation Dispersion and Density Imaging at high b-value in Cerebral Cortical Gray Matter

Diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) are widely used models to infer microstructural features in the brain from diffusion-weighted MRI. Several studies have recently applied both models to increase sensitivity to biological changes, however, it remains uncertain how these measures are associated. Here we show that cortical distributions of DTI and NODDI are associated depending on the choice of b-value, a factor reflecting strength of diffusion weighting gradient. We analyzed a combination of high, intermediate and low b-value data of multi-shell diffusion-weighted MRI (dMRI) in healthy 456 subjects of the Human Connectome Project using NODDI, DTI and a mathematical conversion from DTI to NODDI. Cortical distributions of DTI and DTI-derived NODDI metrics were remarkably associated with those in NODDI, particularly when applied highly diffusion-weighted data (b-value = 3000 sec/mm^{2}). This was supported by simulation analysis, which revealed that DTI-derived parameters with lower b-value datasets suffered from errors due to heterogeneity of cerebrospinal fluid fraction and partial volume. These findings suggest that high b-value DTI redundantly parallels with NODDI-based cortical neurite measures, but the conventional low b-value DTI is hard to reasonably characterize cortical microarchitecture

Human cardiac tissue in a microperfusion chamber simulating extracorporeal circulation - ischemia and apoptosis studies

<p>Abstract</p> <p>Background</p> <p>After coronary artery bypass grafting ischemia/reperfusion injury inducing cardiomyocyte apoptosis may occur. This surgery-related inflammatory reaction appears to be of extreme complexity with regard to its molecular, cellular and tissue mechanisms and many studies have been performed on animal models. However, finding retrieved from animal studies were only partially confirmed in humans. To investigate this phenomenon and to evaluate possible therapies in vitro, adequate human cardiomyocyte models are required. We established a tissue model of human cardiomyocytes preserving the complex tissue environment. To our knowledge human cardiac tissue has not been investigated in an experimental setup mimicking extracorporeal circulation just in accordance to clinical routine, yet.</p> <p>Methods</p> <p>Cardiac biopsies were retrieved from the right auricle of patients undergoing elective coronary artery bypass grafting before cardiopulmonary bypass. The extracorporeal circulation was simulated by submitting the biopsies to varied conditions simulating cardioplegia (cp) and reperfusion (rep) in a microperfusion chamber. Cp/rep time sets were 20/7, 40/13 and 60/20 min. For analyses of the calcium homoeostasis the fluorescent calcium ion indicator FURA-2 and for apoptosis detection PARP-1 cleavage immunostaining were employed. Further the anti-apoptotic effect of carvedilol [10 μM] was investigated by adding into the perfusate.</p> <p>Results</p> <p>Viable cardiomyocytes presented an intact calcium homoeostasis under physiologic conditions. Following cardioplegia and reperfusion a time-dependent elevation of cytosolic calcium as a sign of disarrangement of the calcium homoeostasis occurred. PARP-1 cleavage also showed a time-dependence whereas reperfusion had the highest impact on apoptosis. Cardioplegia and carvedilol could reduce apoptosis significantly, lowering it between 60-70% (p < 0.05).</p> <p>Conclusions</p> <p>Our human cardiac preparation served as a reliable cellular model tool to study apoptosis in vitro. Decisively cardiac tissue from the right auricle can be easily obtained at nearly every cardiac operation avoiding biopsying of the myocardium or even experiments on animals.</p> <p>The apoptotic damage induced by the ischemia/reperfusion stimulus could be significantly reduced by the cold crystalloid cardioplegia. The additional treatment of cardiomyocytes with a non-selective β-blocker, carvedilol had even a significantly higher reduction of apoptotis.</p

In situ annealing of superconducting MgB2 films prepared by pulsed laser deposition

The in situ annealing conditions of pulsed laser deposited MgB2 films were studied. The precursor films were deposited at 250 C from a stoichiometric MgB2 target in a 120mTorr Ar atmosphere. The films were then in situ annealed at a temperature from 450 C to 800 C and an annealing time from 1 minute to 10 minutes. We found that the superconducting properties depend in a crucial way on the annealing conditions: temperature, heating rate and time. The best film with a thickness of ~600nm was obtained under the following annealing conditions: Tanneal=680-690 C, tanneal=1 min, heating rate= 38 C/min. The Tc onset of the film is 28K with a transition width of ~10K. The hysteresis loop of magnetic moment of the film indicates weak field dependence in high fields. Magneto-optical imaging of the film showed quite homogeneous magnetic flux penetration, indicating structural homogeneity. The films without annealing showed no superconductivity.Comment: 12 pages, 6 figure

GalNAc glycoprotein expression by breast cell lines, primary breast cancer and normal breast epithelial membrane

Over-expression of N-acetylgalactosamine glycoproteins as detected by binding of the lectin from Helix pomatia (HPA), is associated with metastatic competence and poor patient prognosis in a range of human adenocarcinomas. These glycoproteins remain poorly characterised, and their functional role has yet to be elucidated. This study describes characterisation of a range of human breast/breast cancer cell lines for the expression of the N-acetylgalactosaminylated glycoproteins of interest, and their comparison with normal breast epithelium and a range of clinical breast carcinoma samples. Confocal and light microscopy studies revealed cytochemical HPA-binding patterns consistent with a fundamental disruption in normal glycobiosynthetic pathways attending increasing metastatic potential. We report the most complete comparative analysis of HPA-binding ligands from cultured breast cells, clinical breast carcinoma samples and normal breast epithelium to date. Lectin blotting identified 11 major HPA-binding glycoprotein bands common to both clinical tumour samples and breast cell lines and 6 of these bands were also expressed by samples of normal breast epithelium, albeit at much lower levels. Moreover, very marked quantitative but not qualitative differences in levels of expression consistent with metastatic capability were noted. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

The challenge to verify ceramide's role of apoptosis induction in human cardiomyocytes - a pilot study

<p>Abstract</p> <p>Background</p> <p>Cardioplegia and reperfusion of the myocardium may be associated with cardiomyocyte apoptosis and subsequent myocardial injury. In order to establish a pharmacological strategy for the prevention of these events, this study aimed to verify the reliability of our human cardiac model and to evaluate the pro-apoptotic properties of the sphingolipid second messenger ceramide and the anti-apoptotic properties of the acid sphingomyelinase inhibitor amitryptiline during simulated cardioplegia and reperfusion ex vivo.</p> <p>Methods</p> <p>Cardiac biopsies were retrieved from the right auricle of patients undergoing elective CABG before induction of cardiopulmonary bypass. Biopsies were exposed to <it>ex vivo </it>conditions of varying periods of cp/rep (30/10, 60/20, 120/40 min). Groups: I (untreated control, n = 10), II (treated control cp/rep, n = 10), III (cp/rep + ceramide, n = 10), IV (cp/rep + amitryptiline, n = 10) and V (cp/rep + ceramide + amitryptiline, n = 10). For detection of apoptosis anti-activated-caspase-3 and PARP-1 cleavage immunostaining were employed.</p> <p>Results</p> <p>In group I the percentage of apoptotic cardiomyocytes was significantly (p < 0.05) low if compared to group II revealing a time-dependent increase. In group III ceramid increased and in group IV amitryptiline inhibited apoptosis significantly (p < 0.05). In contrast in group V, under the influence of ceramide and amitryptiline the induction of apoptosis was partially suppressed.</p> <p>Conclusion</p> <p>Ceramid induces and amitryptiline suppresses apoptosis significantly in our ex vivo setting. This finding warrants further studies aiming to evaluate potential beneficial effects of selective inhibition of apoptosis inducing mediators on the suppression of ischemia/reperfusion injury in clinical settings.</p