Numbers of Foxp3-expressing CD4+CD25high T cells do not correlate with the establishment of long-term tolerance after allogeneic stem cell transplantation

OBJECTIVE: Regulatory CD4 T cells that express high levels of CD25 play a vital role in the maintenance of tolerance to self antigens and are required for the induction of nonresponsiveness to alloantigens. The long-term CD4+CD25high T-cell reconstitution after allogeneic stem cell transplantation is unknown. Here, we evaluated whether recovery of this T-cell subset might be linked to the establishment of full donor/recipient tolerance. METHODS: The frequency of CD4+CD25high T cells was determined by Fluorescence Activated Cell Sorter (FACS) analysis in 31 patients, with a mean follow-up of more than 31 months posttransplant. The expression levels of Foxp3 mRNA were assessed by quantitative real-time polymerase chain reaction (RT-PCR). RESULTS: Patients with or without graft-versus-host disease (GvHD) had significant and persistent CD4 T-cell lymphopenia. The relative frequency of CD25high cells and the expression levels of FoxP3 mRNA within this subset were similar between all patients and healthy controls. No significant difference was found in the number of Foxp3-expressing CD4+CD25high T cells in patients with or without GvHD. Finally, younger age and absence of previous GvHD were significantly linked to CD4+CD25high T-cell recovery. CONCLUSION: The low number of Foxp3-expressing CD4+CD25high T cells in grafted patients is not a specific default of this compartment but a consequence of global CD4 T-cell lymphopenia after allogeneic stem cell transplantation. Moreover, levels of Foxp3 mRNA in the CD25+ T-cell compartment do not allow predicting the development of GvHD in the long term.     

Exclusive ileal endometriosis

Endometriosis is a common condition, but its exclusive localization on the ileum is very rare. Unless there is catamenial exacerbation of symptoms, and considering the lack of specificity of results, diagnosis can be difficult. We report the case of a 50 year-old woman presenting with chronic pain in the right lower quadrant. Initial explorations revealed an ileal tumor which was not characterized before the occurrence of acute small bowel obstruction. Ileo-caecal resection by laparotomy relieved the symptoms and alllesions were removed. Diagnosis of ileal endometriosis was made by pathological examination of the resected specimen.     

Evolution through genetically controlled allometry space

Understanding evolutionary change requires phenotypic differences between organisms to be placed in a genetic context. However, there are few cases where it has been possible to define an appropriate genotypic space for a range of species. Here we address this problem by defining a genetically controlled space that captures variation in shape and size between closely related species of Antirrhinum. The axes of the space are based on an allometric model of leaves from an F2 of an interspecific cross between Antirrhinum majus and Antirrhinum charidemi. Three principal components were found to capture most of the genetic variation in shape and size, allowing a three-dimensional allometric space to be defined. The contribution of individual genetic loci was determined from QTL analysis, allowing each locus to be represented as a vector in the allometric space. Leaf shapes and sizes of 18 different Antirrhinum taxa, encompassing a broad range of leaf morphologies, could be accurately represented as clouds within the space. Most taxa overlapped with, or were near to, at least one other species in the space, so that together they defined a largely interconnected domain of viable forms. It is likely that the pattern of evolution within this domain reflects a combination of directional selection and evolutionary tradeoffs within a high dimensional space.     

Adrenomyeloneuropathy: report of a new mutation in a French Canadian female

BACKGROUND: X-linked adrenoleukodystrophy is a peroxisomial disorder caused by mutations in the ABCD1 gene. Adrenomyeloneuropathy is the second most frequent phenotype (25-46%) of this disease and classically presents in adulthood with spastic paraparesis. Female heterozygotes can be symptomatic, but they are frequently misdiagnosed as having multiple sclerosis. CASE REPORT: We report a novel missense mutation in the ABCD1 gene in a 47-year-old French-Canadian female with spastic paraparesis and no confirmed family history of X-linked adrenoleukodystrophy. The mutation is located on exon 1 and causes the amino acid substitution of a valine for an alanine in a region of the protein highly conserved between mouse and man. CONCLUSION: Adrenomyeloneuropathy must be considered in the differential diagnosis of spastic paraparesis in men or women. This is an initial report of an ABCD1 gene mutation in the French-Canadian population, which should lead to the recognition of other cases in the future.     

The structure and response properties of Golgi tendon organs in control and hypodynamia-hypokinesia rats

The Golgi tendon organs (GTOs) are encapsulated mechano-receptors that, in normal conditions, monitor via Ib afferent fibers the contractile force. A 14-day period of hypodynamia, absence of weight bearing and hypokinesia, and reduction of motor activity (HH) is known to induce changes in postural muscles such as the soleus. At present, there is no data available regarding the Ib afferent feedback in normal rats (CONT group) and in rats after a hypodynamia-hypokinesia (HH group) period. Consequently, the aim of our study was to determine the HH effects on the morphological (histochemistry on gross morphology) and electrophysiological properties of the GTOs in rat soleus muscle. In the histological study, nine CONT and nineteen HH GTOs of the soleus muscle were identified. The results demonstrated that HH GTOs were morphologically similar to the CONT GTOs. Regarding the electrophysiological study, a L2-L6 laminectomy was performed under deep anesthesia (sodium pentobarbital, 60 mg kg(-1)). Responses in single Ib fibers from the L5 dorsal root to the isometric twitch and tetanic fused contractions of "in-series" motor units (MUs) were recorded. Twenty-three and twenty-eight GTO/MU pairs were studied in the CONT and HH groups, respectively. In the HH group, the Ib afferent response exhibited a decrease in dynamic peak for the high stimulation frequencies and an increase in static sensitivity for all stimulation frequencies. Our results suggest that after an HH period, the GTOs continue to fulfil their mechano-sensory function to signal the contractile force but with a higher static sensitivity.     

Memory and action: an experimental study on normal subjects and schizophrenic patients

Psychologists have shown that recall of sentences describing previously performed actions is enhanced compared to recall of heard-only action-phrases (enactment effect). One interpretation of this effect argues that subjects benefit from a multi-modal encoding where movement plays a major role. In line with this motor account, it is conceivable that the beneficial effect of enactment might rely, at least in part, on procedural learning, thus tapping more directly implicit memory functions. Neuropsychological observations support this hypothesis, as shown by the fact that the enactment effect is quite insensitive to perturbations affecting declarative memories. i.e. Alzheimer disease. Memory for subject performed tasks in patients with Korsakoff syndrome. The present study attempts to evaluate whether pure motor activity is sufficient to guarantee the described memory facilitation or alternatively, whether first-person experience in carrying out the action (i.e. true enactment) would be required. To this purpose, in a first experiment on healthy subjects, we tested whether sentence meaning and content of the executed action should match in order to produce facilitation in recall of enacted action-phrases. In a second experiment, we explored whether the enactment effect is present in patients suffering from psychiatric disorders supposed to spare procedural memory but to alter action awareness (e.g. schizophrenia). We show that better recall for action phrases is found only when the motor component is a true enactment of verbal material. Moreover, this effect is nearly lost in schizophrenia. This latter result, on the one hand, queries the automatic/implicit nature of the enactment effect and supports the role of the experience of having performed the action in the first-person. On the other hand, it questions the nature of the memory impairments detected in schizophrenia.