Colchicine attenuates compensation to negative but not to positive lenses in young chicks

Optic nerve-sectioned (ONS) chick eyes are capable of emmetropisation, but these eyes also exhibit increased hyperopia without any visual manipulations, which suggests altered eye growth regulation. These altered growth changes may be related to the loss of retinal ganglion cells that follows nerve lesioning. Colchicine, which also destroys retinal ganglion cells in chicks, was used to further examine the effects of retinal ganglion cell loss on emmetropisation. Growth responses of +10D and -10D lens-wearing colchicine-injected eyes were compared to those of +10D and -10D lens-wearing saline-injected eyes, respectively. Changes after removal of lenses were also analysed. Prior to lens-wear, colchicine-injected eyes exhibited longer optical axial lengths (OL; distance from cornea to retina; p=0.0185) but no differences in refractive error (RE; p=0.6588). Although myopic shifts were not significant for -10D lens-wearing colchicine-injected eyes (p=0.5913), but were for the saline-injected eyes (p=0.0034), these changes were not different (p=0.1646). However, -10D lens-induced OL changes in colchicine-injected eyes showed insignificant (p=0.2214) and reduced (p=0.0102) changes compared to those of saline-injected eyes. +10D lens-treated colchicine-injected eyes showed significant hyperopic shifts (p<0.0001) and significant reductions in OL (p<0.0001) that were similar to those of saline-injected eyes (p=0.7990 and p=0.1495, respectively). Growth responses in eyes recovering from -10D lenses were minimal, with REs unaffected (p=0.3325), but OL reductions affected (p=0.0199) by colchicine. Colchicine-injected eyes recovering from +10D lenses showed significant myopic shifts (p=0.0003) and OL elongations (p<0.0001) that were similar to those of saline-injected eyes (p=0.3999 and p=0.4731, respectively). The results showing that colchicine suppresses the ability to respond to negative lenses but leaves compensation to positive lenses relatively unchanged, are opposite to those of optic nerve sectioned eyes. We speculate that the differences are probably related to the way retinal cells are lost.     

Tolerance, suppression and the fetal allograft

In solid organ transplantation the recipient immune system recognises foreign alloantigens expressed by the graft. This results in an immune attack of the transplanted organ leading to rejection, which can be prevented only by therapeutic immunosuppression. During pregnancy the fetus should also be rejected by the maternal immune system, since it expresses antigens derived from the father. Whilst the immune system retains the ability to respond to foreign antigen, tolerance mechanisms ensure that inappropriate responses against self-antigen are prevented. Maternal immune aggression directed against the fetus is partly inhibited by peripheral tolerance mechanisms that act locally to deplete cells capable of attacking the fetus. Other local mechanisms inhibit the pathways that cause tissue damage after immune activation. Recent studies in mice and humans indicate that the maternal immune system undergoes a more systemic change that promotes materno-fetal tolerance. Naturally occurring regulatory T cells, which are commonly associated with maintaining tolerance to self-antigens, can also suppress maternal allo-responses targeted against the fetus. We review the mechanisms that mediate materno-fetal tolerance, with particular emphasis on changes in regulatory T cell function during pregnancy and discuss their implications.     

Validation of supervised automated algorithm for fast quantitative evaluation of organ motion on magnetic resonance imaging

PURPOSE: To validate a correlation coefficient template-matching algorithm applied to the supervised automated quantification of abdominal-pelvic organ motion captured on time-resolved magnetic resonance imaging. METHODS AND MATERIALS: Magnetic resonance images of 21 patients across four anatomic sites were analyzed. Representative anatomic points of interest were chosen as surrogates for organ motion. The point of interest displacements across each image frame relative to baseline were quantified manually and through the use of a template-matching software tool, termed "Motiontrack." Automated and manually acquired displacement measures, as well as the standard deviation of intrafraction motion, were compared for each image frame and for each patient. RESULTS: Discrepancies between the automated and manual displacements of > or =2 mm were uncommon, ranging in frequency of 0-9.7% (liver and prostate, respectively). The standard deviations of intrafraction motion measured with each method correlated highly (r = 0.99). Considerable interpatient variability in organ motion was demonstrated by a wide range of standard deviations in the liver (1.4-7.5 mm), uterus (1.1-8.4 mm), and prostate gland (0.8-2.7 mm). The automated algorithm performed successfully in all patients but 1 and substantially improved efficiency compared with manual quantification techniques (5 min vs. 60-90 min). CONCLUSION: Supervised automated quantification of organ motion captured on magnetic resonance imaging using a correlation coefficient template-matching algorithm was efficient, accurate, and may play an important role in off-line adaptive approaches to intrafraction motion management.