Total orthotopic small bowel transplantation in swine under FK 506

Previous experimental studies in rodents and in dogs have established the efficacy of FK 506 in controlling the immunologic events following small bowel or multivisceral transplantation.1–5 To complete the assessment of FK 506 in experimental small bowel transplantation, we present here our experience with the frequently used swine model

Top-down control of visual sensory processing during an ocular motor response inhibition task

The study addressed whether top-down control of visual cortex supports volitional behavioral control in a novel antisaccade task. The hypothesis was that anticipatory modulations of visual cortex activity would differentiate trials on which subjects knew an anti- versus a pro-saccade response was required. Trials consisted of flickering checkerboards in both peripheral visual fields, followed by brightening of one checkerboard (target) while both kept flickering. Neural activation related to checkerboards before target onset (bias signal) was assessed using electroencephalography. Pretarget visual cortex responses to checkerboards were strongly modulated by task demands (significantly lower on antisaccade trials), an effect that may reduce the predisposition to saccade generation instigated by visual capture. The results illustrate how top-down sensory regulation can complement motor preparation to facilitate adaptive voluntary behavioral control

Estimation of functional connectivity from electromagnetic signals and the amount of empirical data required

An increasing number of neuroimaging studies are concerned with the identification of interactions or statistical dependencies between brain areas. Dependencies between the activities of different brain regions can be quantified with functional connectivity measures such as the cross-correlation coefficient. An important factor limiting the accuracy of such measures is the amount of empirical data available. For event-related protocols, the amount of data also affects the temporal resolution of the analysis. We use analytical expressions to calculate the amount of empirical data needed to establish whether a certain level of dependency is significant when the time series are autocorrelated, as is the case for biological signals. These analytical results are then contrasted with estimates from simulations based on real data recorded with magnetoencephalography during a resting-state paradigm and during the presentation of visual stimuli. Results indicate that, for broadband signals, 50–100 s of data is required to detect a true underlying cross-correlations coefficient of 0.05. This corresponds to a resolution of a few hundred milliseconds for typical event-related recordings. The required time window increases for narrow band signals as frequency decreases. For instance, approximately 3 times as much data is necessary for signals in the alpha band. Important implications can be derived for the design and interpretation of experiments to characterize weak interactions, which are potentially important for brain processing

Identification of Protein Tyrosine Phosphatase Receptor Gamma Extracellular Domain (sPTPRG) as a Natural Soluble Protein in Plasma

BACKGROUND:PTPRG is a widely expressed protein tyrosine phosphatase present in various isoforms. Peptides from its extracellular domain have been detected in plasma by proteomic techniques. We aim at characterizing the plasmatic PTPRG (sPTPRG) form and to identify its source.METHODOLOGY/PRINCIPAL FINDINGS:The expression of sPTPRG was evaluated in human plasma and murine plasma and tissues by immunoprecipitation and Western blotting. The polypeptides identified have an apparent Mr of about 120 kDa (major band) and 90 kDa (minor band) respectively. Full length PTPRG was identified in the 100.000 7g pelleted plasma fraction, suggesting that it was present associated to cell-derived vesicles (exosomes). The release of sPTPRG by HepG2 human hepatocellular carcinoma cell line was induced by ethanol and sensitive to metalloproteinase and not to Furin inhibitors. Finally, increased levels of the plasmatic 3c120 kDa isoform were associated with the occurrence of liver damage.CONCLUSIONS:These results demonstrate that sPTPRG represent a novel candidate protein biomarker in plasma whose increased expression is associated to hepatocyte damage. This observation could open a new avenue of investigation in this challenging field

Distribution of different isoforms of receptor protein tyrosine phosphatase \u3b3 (Ptprg-RPTP \u3b3) in adult mouse brain: upregulation during neuroinflammation.

The receptor protein tyrosine phosphatase \u3b3 (Ptprg-RPTP\u3b3) is a receptor protein widely expressed in many tissues, including the central nervous system (CNS). Several RPTP\u3b3 isoforms are expressed in the brain during development and in adulthood, but their distribution and role are unknown. In this study, we investigated the distribution of some RPTP\u3b3 isoforms in the adult brain using antibodies against the epitopes localized in the C- and in the N-terminal domains of the full length isoform of RPTP\u3b3. We found a predominant and widespread neuronal positivity throughout the neocortex, hippocampus, striatum and in many nuclei of the brainstem and cerebellum. At least 2 distinct isoforms that can co-exist in various compartments in the same cell are detectable in different neuron types. Immunopositivity for epitopes located in both the N- and C-terminus domains were found in the neuropil of cortical and hippocampal neurons, whereas the N-terminal domain positivity was found in the soma, often without colocalization with its C-terminal counterpart. Among glial cells, some protoplasmic and perivascular astrocytes and the cerebellar Bergmann glia, express RPTP\u3b3. The astrocytic expression of RPTP\u3b3 and putative processing isoforms of 120 and 80 kDa increases during neuroinflammation, in particular 24 h after LPS treatment. Activated astrocytes were found to be strongly positive for RPTP\u3b3 also in a mice model of Alzheimer's disease. Our results confirm previous findings and enrich the current knowledge of RPTP\u3b3 distribution in the CNS, highlighting a role of RPTP\u3b3 during neuroinflammation processes

Quantum diffusion with disorder, noise and interaction

Disorder, noise and interaction play a crucial role in the transport properties of real systems, but they are typically hard to control and study both theoretically and experimentally, especially in the quantum case. Here we explore a paradigmatic problem, the diffusion of a wavepacket, by employing ultra-cold atoms in a disordered lattice with controlled noise and tunable interaction. The presence of disorder leads to Anderson localization, while both interaction and noise tend to suppress localization and restore transport, although with completely different mechanisms. When only noise or interaction are present we observe a diffusion dynamics that can be explained by existing microscopic models. When noise and interaction are combined, we observe instead a complex anomalous diffusion. By combining experimental measurements with numerical simulations, we show that such anomalous behavior can be modeled with a generalized diffusion equation, in which the noise- and interaction-induced diffusions enter in an additive manner. Our study reveals also a more complex interplay between the two diffusion mechanisms in regimes of strong interaction or narrowband noise.Comment: 11 pages, 10 figure

In‐Depth Immunological Typization of Children with Sickle Cell Disease: A Preliminary Insight into Its Plausible Correlation with Clinical Course and Hydroxyurea Therapy

Sickle cell disease (SCD) is a condition of functional hypo‐/a‐splenism in which predisposition to bacterial infections is only a facet of a wide spectrum of immune‐dysregulation disorders forming the clinical expression of a peculiar immunophenotype. The objective of this study was to perform an in‐depth immunophenotypical characterization of SCD pediatric patients, looking for plausible correlations between immunological biomarkers, the impact of hydroxyurea (HU) treatment and clinical course. This was an observational case–control study including 43 patients. The cohort was divided into two main groups, SCD subjects (19/43) and controls (24/43), differing in the presence/absence of an SCD diagnosis. The SCD group was split up into HU+ (12/19) and HU− (7/19) subgroups, respectively receiving or not a concomitant HU treatment. The principal outcomes measured were differences in the immunophenotyping between SCD patients and controls through chi‐squared tests, t‐tests, and Pearson’s correlation analysis between clinical and immunological parameters. Leukocyte and neutrophil increase, T‐cell depletion with prevalence of memory T‐cell compartment, NK and B‐naïve subset elevation with memory and CD21low B subset reduction, and IgG expansion, significantly distinguished the SCD HU− subgroup from controls, with naïve T cells, switched‐memory B cells and IgG maintaining differences between the SCD HU+ group and controls (p‐value of <0.05). The mean CD4+ central‐memory T‐cell% count was the single independent variable showing a positive correlation with vaso‐occlusive crisis score in the SCD group (Pearson’s R = 0.039). We report preliminary data assessing plausible clinical implications of baseline and HU‐related SCD immunophenotypical alterations, which need to be validated in larger samples, but potentially affecting hypo‐/a‐splenism immuno‐chemoprophylactic recommendations

Rapid recognition of drug-resistance/sensitivity in leukemic cells by Fourier transform infrared microspectroscopy and unsupervised hierarchical cluster analysis.

We tested the ability of Fourier Transform (FT) InfraRed (IR) microspectroscopy (microFTIR) in combination with unsupervised Hierarchical Cluster Analysis (HCA) in identifying drug-resistance/sensitivity in leukemic cells exposed to tyrosine kinase inhibitors (TKIs). Experiments were carried out in a well-established mouse model of human Chronic Myelogenous Leukemia (CML). Mouse-derived pro-B Ba/F3 cells transfected with and stably expressing the human p210(BCR-ABL) drug-sensitive wild-type BCR-ABL or the V299L or T315I p210(BCR-ABL) drug-resistant BCR-ABL mutants were exposed to imatinib-mesylate (IMA) or dasatinib (DAS). MicroFTIR was carried out at the Diamond IR beamline MIRIAM where the mid-IR absorbance spectra of individual Ba/F3 cells were acquired using the high brilliance IR synchrotron radiation (SR) via aperture of 15 7 15 \u3bcm(2) in sizes. A conventional IR source (globar) was used to compare average spectra over 15 cells or more. IR signatures of drug actions were identified by supervised analyses in the spectra of TKI-sensitive cells. Unsupervised HCA applied to selected intervals of wavenumber allowed us to classify the IR patterns of viable (drug-resistant) and apoptotic (drug-sensitive) cells with an accuracy of >95%. The results from microFTIR + HCA analysis were cross-validated with those obtained via immunochemical methods, i.e. immunoblotting and flow cytometry (FC) that resulted directly and significantly correlated. We conclude that this combined microFTIR + HCA method potentially represents a rapid, convenient and robust screening approach to study the impact of drugs in leukemic cells as well as in peripheral blasts from patients in clinical trials with new anti-leukemic drugs

Inapplicability of advance directives in a paternalistic setting: the case of a post-communist health system

<p>Abstract</p> <p>Background</p> <p>The Albanian medical system and Albanian health legislation have adopted a paternalistic position with regard to individual decision making. This reflects the practices of a not-so-remote past when state-run facilities and a totalitarian philosophy of medical care were politically imposed. Because of this history, advance directives concerning treatment refusal and do-not-resuscitate decisions are still extremely uncommon in Albania. Medical teams cannot abstain from intervening even when the patient explicitly and repeatedly solicits therapeutic abstinence. The Albanian law on health care has no provisions regarding limits or withdrawal of treatment. This restricts the individual's healthcare choices.</p> <p>Discussion</p> <p>The question of <it>'medically futile' </it>interventions and pointless life-prolonging treatment has been discussed by several authors. Dutch physicians call such interventions '<it>medisch zinloos</it>' (<it>senseless</it>), and the Netherlands, as one of the first states to legislate on end-of-life situations, actually regulates such issues through appropriate laws. In contrast, leaving an 'advance directive' is not a viable option for Albanian ailing individuals of advanced age. Verbal requests are provided during periods of mental competence, but unfortunately such instructions are rarely taken seriously, and none of them has ever been upheld in a legal or other official forum.</p> <p>Summary</p> <p>End-of-life decisions, treatment refusal and do-not-resuscitate policies are hazardous options in Albania, from the legal point of view. Complying with them involves significant risk on the part of the physician. Culturally, the application of such instructions is influenced from a mixture of religious beliefs, death coping-behaviors and an immense confusion concerning the role of proxies as decision-makers. Nevertheless, Albanian tradition is familiar with the notion of '<it>amanet</it>', a sort of living will that mainly deals the property and inheritance issues. Such living wills, verbally transmitted, may in certain cases include advance directives regarding end-of-life decisions of the patient including refusal or termination of futile medical treatments. Since these living wills are never formally and legally validated, their application is impossible and treatment refusal remains still non practicable. Tricks to avoid institutional treatment under desperate conditions are used, aiming to provide legal coverage for medical teams and relatives that in extreme situations comply with the advice of withholding senseless treatment.</p