762 research outputs found
Endoscopic access closure for direct implantation of valved stents
OBJECTIVES: The off-pump trans left ventricular approach provides an alternative option for insertion of stented aortic valves of any size for endovascular replacement. One of the key steps in this procedure is the repair of the ventricle after catheter withdrawal. This study evaluates the reliability of a new device for sutureless and quick repair of the left ventricle access. METHODS: The Amplatz-nitinol occluder consists of two square heads that squeeze the ventricle wall between them thus sealing the ventricular defect. In four adult pigs weighing 55 kg, left thoracoscopy was performed to open the pericardium and visualise the cardiac apex. Following a heparin injection (100 U/kg) under ICUS and fluoroscopic control, we inserted a 30 F sheath into the epigastric area through the cardiac apex up into the left ventricle thus simulating the approach for an off-pump aortic valve replacement. The sheath was then removed and the ventricle closed with the occluder. Animals were followed-up for three hours; the haemodynamics and pericardial bleeding were recorded. The animals were then sacrificed and the gross anatomy of the heart was examined. RESULTS: The device was successfully deployed in four animals in less than one minute. ACT was above 200 seconds in all cases. All animals survived the procedure with a mean arterial pressure of 50 +/- 15 mm Hg. Bleeding during deployment was 80 +/- 20 ml and over a 3 hour period was 800 +/- 20 ml. Examination of the gross anatomy examination demonstrated the correct positioning of the device. CONCLUSIONS: The occluder is easy to use and the procedure is feasible and reproducible. However, the occluder design requires technical improvements in order to reduce bleeding before it can be used clinically
Altering crystal growth and annealing in ice-templated scaffolds.
The potential applications of ice-templating porous materials are constantly expanding, especially as scaffolds for tissue engineering. Ice-templating, a process utilizing ice nucleation and growth within an aqueous solution, consists of a cooling stage (before ice nucleation) and a freezing stage (during ice formation). While heat release during cooling can change scaffold isotropy, the freezing stage, where ice crystals grow and anneal, determines the final size of scaffold features. To investigate the path of heat flow within collagen slurries during solidification, a series of ice-templating molds were designed with varying the contact area with the heat sink, in the form of the freeze drier shelf. Contact with the heat sink was found to be critical in determining the efficiency of the release of latent heat within the perspex molds. Isotropic collagen scaffolds were produced with pores which ranged from 90 μm up to 180 μm as the contact area decreased. In addition, low-temperature ice annealing was observed within the structures. After 20 h at -30 °C, conditions which mimic storage prior to lyophilization, scaffold architecture was observed to coarsen significantly. In future, ice-templating molds should consider not only heat conduction during the cooling phase of solidification, but the effects of heat flow during ice growth and annealing.The authors gratefully acknowledge the financial support of the Gates Cambridge Trust, the Newton Trust, and ERC Advanced Grant 320598 3D-E. A.H. held a Daphne Jackson Fellowship funded by the University of Cambridge.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10853-015-9343-
16th IHIW: Immunogenetics of Aging
Ageing is a process characterised by progressive loss of
function in multiple different organ systems, such as
the nervous, endocrine and immune systems. Current
data showing that ageing processes may be associated
with alterations in the immune system suggest that
some of the genetic determinants of senescence might
be polymorphic genes that regulate immune responses.
The ‘Immunogenetics of Aging’ programme was a
component introduced in the 14th International HLA
and Immunogenetics Workshop (IHIWS) and developed
further within the 15th and 16th. The aim of this
component was to determine the contribution of
immune genes to successful ageing and an increased
capacity to reach the extreme limits of lifespan. Within
the 16th IHIWS, new populations were included, and
the number of samples analysed was increased. Analysis
was focused on innate immunity genes (KIR and
MBL2) and their correlation with CMV serostatus.
Collaborative studies suggested that both activating
and inhibitory KIR and functionally relevant MBL2
haplotypes are important factors for control of CMV
infection in the elderly and therefore for chronic
low-grade inflammation. Results showed that these
genes might be predictive biomarkers in ageing and longevity. Prevalence of MBL2 haplotypes determining
absence of the protein (LYPB, LYQC and HYPD) was
observed in elderly people with a higher CMV antibody
titre. The high CMV titre was also associated
with a decreased frequency of the activatory KIR2DS5
and A1B10 haplotypes in elderly. Due to the role of
KIR and low or deficient MBL haplotypes in viral
infections, these genetic markers could be considered
as indicators of a need for CMV prophylaxis at younger
age and therefore increased probability of longer
lifespan
Closure of left ventricle perforation with the use of muscular VSD occluder
Growing experience in interventional cardiology leads to the use of large diameter of vascular equipment. In some instances, the so-called hybrid procedures are performed. After performing the interventional procedure, the opening in ventricular wall is closed surgically. Our intention was to check if the MVSDO can be used to close the perforation in the heart after the interventional cardiology procedure performed through the left ventricular (LV) free wall. In three pigs under general anesthesia, the heart was exposed through a small substernal incision. The LV was punctured and an 18F sheath was introduced into the LV. A 14 mm MVSDO was inserted through the 10F Delivery System. Using both the echocardiographic and angiographic guidance, the MVSDO was placed on the LV wall to close the opening in the LV. Time and volume of bleeding was recorded. In all cases the occluder was successfully placed closing the opening, bleeding observed after deployment of occluder lasted for approximately 2 min. We think MVSD occluder can be used to close the LV free wall perforation after hybrid interventional cardiac procedure. Early bleeding through MVSDO might be resolved by the manufacturing of new occluder with better sealing properties
PTSD is associated with an increase in aged T cell phenotypes in adults living in Detroit
Psychosocial stress is thought to play a key role in the acceleration of immunological aging. This study investigated the relationship between lifetime and past-year history of post-traumatic stress disorder (PTSD) and the distribution of T cell phenotypes thought to be characteristic of immunological aging
Pitfalls in the characterization of circulating and tissue-resident human γδ T cells
Dissection of the role and function of human γδ T cells and their heterogeneous subsets in cancer, inflammation, and auto-immune diseases is a growing and dynamic research field of increasing interest to the scientific community. Therefore, harmonization and standardization of techniques for the characterization of peripheral and tissue-resident γδ T cells is crucial to facilitate comparability between published and emerging research. The application of commercially available reagents to classify γδ T cells, in particular the combination of multiple Abs, is not always trouble-free, posing major demands on researchers entering this field. Occasionally, even entire γδ T cell subsets may remain undetected when certain Abs are combined in flow cytometric analysis with multicolor Ab panels, or might be lost during cell isolation procedures. Here, based on the recent literature and our own experience, we provide an overview of methods commonly employed for the phenotypic and functional characterization of human γδ T cells including advanced polychromatic flow cytometry, mass cytometry, immunohistochemistry, and magnetic cell isolation. We highlight potential pitfalls and discuss how to circumvent these obstacles
Peripheral blood T-cell signatures from high-resolution immune phenotyping of γδ and αβ T-cells in younger and older subjects in the Berlin Aging Study II
Background Aging and latent infection with Cytomegalovirus (CMV) are thought
to be major factors driving the immune system towards immunosenescence,
primarily characterized by reduced amounts of naïve T-cells and increased
memory T-cells, potentially associated with higher morbidity and mortality.
The composition of both major compartments, γδ as well as αβ T-cells, is
altered by age and CMV, but detailed knowledge of changes to the γδ subset is
currently limited. Results Here, we have surveyed a population of 73 younger
(23–35 years) and 144 older (62–85 years) individuals drawn from the Berlin
Aging Study II, investigating the distribution of detailed differentiation
phenotypes of both γδ and αβ T-cells. Correlation of frequencies and absolute
counts of the identified phenotypes with age and the presence of CMV revealed
a lower abundance of Vδ2-positive and a higher amount of Vδ1-positive cells.
We found higher frequencies of late-differentiated and lower frequencies of
early-differentiated cells in the Vδ1+ and Vδ1-Vδ2-, but not in the Vδ2+
populations in elderly CMV-seropositive individuals confirming the association
of these Vδ2-negative cells with CMV-immunosurveillance. We identified the
highest Vδ1:Vδ2 ratios in the CMV-seropositive elderly. The observed increased
CD4:CD8 ratios in the elderly were significantly lower in CMV-seropositive
individuals, who also possessed a lower naïve and a larger late-differentiated
compartment of CD8+ αβ T-cells, reflecting the consensus in the literature.
Conclusions Our findings illustrate in detail the strong influence of CMV on
the abundance and differentiation pattern of γδ T-cells as well as αβ T-cells
in older and younger people. Mechanisms responsible for the phenotypic
alterations in the γδ T-cell compartment, associated both with the presence of
CMV and with age require further clarification
Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance.
BACKGROUND: Colorectal cancer (CRC) progression is associated with suppression of host cell-mediated immunity and local immune escape mechanisms. Our aim was to assess the immune function in terms of expression of TNF, IFNG and FOXP3 in CRC.
METHODS: Sixty patients with CRC and 15 matched controls were recruited. TaqMan quantitative PCR and methylation-specific PCR was performed for expression and DNA methylation analysis of TNF, IFNG and FOXP3. Survival analysis was performed over a median follow-up of 48 months.
RESULTS: TNF was suppressed in tumour and IFNG was suppressed in peripheral blood mononuclear cells (PBMCs) of patients with CRC. Tumours showed enhanced expression of FOXP3 and was significantly higher when tumour size was >38 mm (median tumour size; P=0.006, Mann-Whitney U-test). Peripheral blood mononuclear cell IFNG was suppressed in recurrent CRC (P=0.01). Methylated TNFpromoter (P=0.003) and TNFexon1 (P=0.001) were associated with significant suppression of TNF in tumours. Methylated FOXP3cpg was associated with significant suppression of FOXP3 in both PBMC (P=0.018) and tumours (P=0.010). Reduced PBMC FOXP3 expression was associated with significantly worse overall survival (HR=8.319, P=0.019).
CONCLUSIONS: We have detected changes in the expression of immunomodulatory genes that could act as biomarkers for prognosis and future immunotherapeutic strategies
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