46 research outputs found
Low temperature magnetic properties of iron bearing sulfides and their contribution to magnetism of cometary bodies
Peer reviewe
Effect of induction therapy on the expression of molecular markers associated with rejection and tolerance
Background Induction therapy can improve kidney transplantation (KTx)
outcomes, but little is known about the mechanisms underlying its effects.
Methods The mRNA levels of T cell-related genes associated with tolerance or
rejection (CD247, GZMB, PRF1, FOXP3, MAN1A1, TCAIM, and TLR5) and lymphocyte
subpopulations were monitored prospectively in the peripheral blood of 60
kidney transplant recipients before and 7, 14, 21, 28, 60, 90 days, 6 months,
and 12 months after KTx. Patients were treated with calcineurin inhibitor-
based triple immunosuppression and induction with rabbit anti-thymocyte
globulin (rATG, n = 24), basiliximab (n = 17), or without induction (no-
induction, n = 19). A generalized linear mixed model with gamma distribution
for repeated measures, adjusted for rejection, recipient/donor age and delayed
graft function, was used for statistical analysis. Results rATG treatment
caused an intense reduction in all T cell type population and natural killer
(NK) cells within 7 days, then a slow increase and repopulation was observed.
This was also noticed in the expression levels of CD247, FOXP3, GZMB, and
PRF1. The basiliximab group exhibited higher CD247, GZMB, FOXP3 and TCAIM mRNA
levels and regulatory T cell (Treg) counts than the no-induction group. The
levels of MAN1A1 and TLR5 mRNA expressions were increased, whereas TCAIM
decreased in the rATG group as compared with those in the no-induction group.
Conclusion The rATG induction therapy was associated with decreased T and NK
cell-related transcript levels and with upregulation of two rejection-
associated transcripts (MAN1A1 and TLR5) shortly after KTx. Basiliximab
treatment was associated with increased absolute number of Treg cells, and
increased level of FOXP3 and TCAIM expression
From a Biomarker to Targeting in a Proof-Of-Concept Trial
Background There is high medical need for safe long-term immunosuppression
monotherapy in kidney transplantation. Selective targeting of post-transplant
alloantigen-(re)activated effector-T cells by anti-TNF antibodies after global
T cell depletion may allow safe drug minimization, however, it is unsolved
what might be the best maintenance monotherapy. Methods In this open,
prospective observational single-centre trial, 20 primary deceased donor
kidney transplant recipients received 2x20 mg Alemtuzumab (d0/d1) followed by
5 mg/kg Infliximab (d2). For 14 days all patients received only tacrolimus,
then they were allocated to either receive tacrolimus (TAC, n = 13) or
sirolimus (SIR, n = 7) monotherapy, respectively. Protocol biopsies and
extensive immune monitoring were performed and patients were followed-up for
60 months. Results TAC-monotherapy resulted in excellent graft survival (5yr
92%, 95%CI: 56.6–98.9) and function, normal histology, and no proteinuria.
Immune monitoring revealed low intragraft inflammation (urinary IP-10) and
hints for the development of operational tolerance signature in the TAC- but
not SIR-group. Remarkably, the TAC-monotherapy was successful in all five
presensitized (ELISPOT+) patients. However, recruitment into SIR-arm was
stopped (after n = 7) because of high incidence of proteinuria and
acute/chronic rejection in biopsies. No opportunistic infections occurred
during follow-up. Conclusions In conclusion, our novel fast-track TAC-
monotherapy protocol is likely to be safe and preliminary results indicated an
excellent 5-year outcome, however, a full–scale study will be needed to
confirm our findings. Trial Registration EudraCT Number: 2006-003110-1
Contactless conductivity detection for analytical techniques Developments from 2014 to 2016
The development of capacitively coupled contactless conductivity detection for the two-year period from mid-2014 to mid-2016 is covered in this review. This includes a survey of fundamental studies and further developments of the measuring technique reported as well as a discussion of new applications. These mostly concern capillary electrophoresis carried out in conventional capillaries as well as on microchip electrophoresis devices. The main focus is on the determination of small non-UV-absorbing organic ions and inorganic ions in different types of samples of clinical, nutritional or environmental interest. Outside of electrophoresis contactless conductivity detection is finding uses in detection in column chromatography, flow-injection analysis and industrial applications
Molecular Patterns of Subclinical and Clinical Rejection of Kidney Allograft: Quantity Matters
Background/Aims: Subclinical rejection diagnosed from protocol biopsies is thought to be a risk factor of long- term allograft dysfunction. The reason why in some patients subclinical rejection does not represent risk for progression is not fully understood. Methods: The intragraft expression of 376 target genes involved in chemokine defense, apoptosis, inflammation, tolerance and TGF-β signalling pathways was measured using quantitative real-time RT-PCR (2-∆∆Ct) method in subclinical inflammation (SCI, n=10), clinical inflammation in acute T-cell mediated rejection (CI, n=10) and no rejection samples (n=9). Results: Clinical inflammation group showed a increased expression of genes for chemotaxis mediating cytokines (CCL1, CCL17, CCL24, CCL25, CCL26), cytokine receptors (CCR1, CCRL2, IL1RAPL2, CXCR5), proinflammatory cytokines (IL12A, LTA), inflammatory mediator (PTAFR), complement protein C3, executioner protein of apoptosis (CASP7), growth factor (TGFA), colony stimulating factor (CSF-2), proteins involved in dendritic cells differentiation and interaction (CD209, LAMP3), regulation of immune response (LILRB2, LILBRB4). The quantitative difference in transcripts signature between SCI and CI is consistent with stronger proinflammatory setting of CI. Prostaglandin E2 receptor gene expression was independently associated with lower risk of further graft function deterioration (OR 0.11, CI 0.01-0.78, pConclusion: Subclinical acute kidney inflammation has transcriptional profile of immune injury of lower extend compared to clinical acute inflammation
Interface-free capillary electrophoresis-mass spectrometry system with nanospray ionization—Analysis of dexrazoxane in blood plasma
Origin of migmatites by deformation-enhanced melt infiltration of orthogneiss: a new model based on quantitative microstructural analysis.
International audienc