Transgenic mice expressing T antigen (Tag) in pancreatic β cells establish systemic tolerance toward this self-protein. The self-tolerance in two families of rat insulin promoter (RIP)-Tag mice, ...expressing different levels of Tag protein, has been characterized. These mice have impaired antibody responses to Tag, show diminished Tag-specific T-cell proliferation, and evidence an inability to generate Tag-specific cytotoxic T cells. The existence of systemic tolerance toward a β-cell-specific protein motivated examination of transgene expression in the thymus. Indeed, low levels of Tag mRNA were detected intrathymically. Remarkably, this expression is a valid property of the insulin gene regulatory region, since insulin RNA was also expressed in the thymus of nontransgenic mice. RNA for other pancreatic genes was also detected in the thymus, thus raising the possibility that many tissue-specific genes could be expressed intrathymically during immunological development and induction of self-tolerance. These results raise important questions for future research into the role of the thymus in tolerance induction toward so-called tissue-specific antigens.
The pathogenesis of endometriosis, a disease widely believed to arise from an aberrant growth of endometrial tissue outside the uterus, is still unclear. We have previously observed that ...cytokine-stimulated endometrial cells of women with endometriosis secrete in vitro increased amounts of monocyte chemotactic protein-1 (MCP-1). This factor may be important in the recruitment and activation of peritoneal macrophages observed in endometriosis patients. The present study reports that, in the presence of the disease, such an up-regulation of MCP-1 expression arises in vivo and can be encountered in situ in the intrauterine endometrium. In women with endometriosis, MCP-1 expression was elevated in endometrial glands, both at the level of the protein (immunohistochemistry) and the mRNA (in situ hybridization). This was observed throughout the menstrual cycle and varied according to the stage of the disease. These findings strongly argue in favor of the presence of pathophysiological changes in the eutopic endometrium of patients with endometriosis and make plausible MCP-1 as a key effector cell mediator involved in the pathogenesis of the disease.
Using a Filemaker-based database (DNA Pro-FILES, Synchrone Infosystème Inc.), we have conducted a large-scale study on 1000 sexual assault (SA) cases where a standardized kit was submitted to our ...laboratory alone or with other types of exhibits. We looked at the likelihood of obtaining good quality DNA evidence, allegedly from the assailant, according to a number of parameters.
The overall proportion of SA cases with DNA evidence is nearly 50%. A little more than 30% of SA kits provided DNA evidence while for 16% of cases DNA evidence could be obtained only from other exhibits.
The likelihood of obtaining DNA evidence is approximately 50% in teenager and adult SA cases, but much lower for children 10 years old or younger (15%). In children cases, profiles were found mostly on clothing or skin swabs.
The likelihood of obtaining DNA evidence from vaginal swabs remains good for up to 3 days after the assault (from 35% on the first day to 23% on the third day). A DNA profile was obtained from approximately 22% of anal/rectal swabs and 41% of skin swabs taken less than 1 day after the assault. Less than 10% of oral washes provided DNA evidence, all having been collected within 24
h of the assault.
We found that in bodily samples, a negative result for acid phosphate (AP) is a poor predictor of the likelihood of obtaining good quality DNA evidence. Approximately 15% of vaginal swabs and 8% of anal swabs negative for AP nevertheless provided good quality DNA evidence.
Cell polarity is critical in various cellular processes ranging from cell migration to asymmetric cell division and axon and dendrite specification. Similarly, myelination by Schwann cells is ...polarized, but the mechanisms involved remain unclear. Here, we show that the polarity protein Par-3 localizes asymmetrically in Schwann cells at the axon-glial junction and that disruption of Par-3 localization, by overexpression and knockdown, inhibits myelination. Additionally, we show that Par-3 directly associates and recruits the p75 neurotrophin receptor to the axon-glial junction, forming a complex necessary for myelination. Together, these results point to a critical role in the establishment of cell polarity for myelination.
Cell polarity is critical in various cellular processes ranging from cell migration to asymmetric cell division and axon and dendrite specification. Similarly, myelination by Schwann cells is ...polarized, but the mechanisms involved remain unclear. Here, we show that the polarity protein Par-3 localizes asymmetrically in Schwann cells at the axon-glial junction and that disruption of Par-3 localization, by overexpression and knockdown, inhibits myelination. Additionally, we show that Par-3 directly associates and recruits the p75 neurotrophin receptor to the axon-glial junction, forming a complex necessary for myelination. Together, these results point to a critical role in the establishment of cell polarity for myelination.
Cell polarity is critical in various cellular processes ranging from cell migration to asymmetric cell division and axon and dendrite specification. Similarly, myelination by Schwann cells is ...polarized, but the mechanisms involved remain unclear. Here, we show that the polarity protein Par-3 localizes asymmetrically in Schwann cells at the axon-glial junction and that disruption of Par-3 localization, by overexpression and knockdown, inhibits myelination. Additionally, we show that Par-3 directly associates and recruits the p75 neurotrophin receptor to the axon-glial junction, forming a complex necessary for myelination. Together, these results point to a critical role in the establishment of cell polarity for myelination.
Cell polarity is critical in various cellular processes ranging from cell migration to asymmetric cell division and axon and dendrite specification. Similarly, myelination by Schwann cells is ...polarized, but the mechanisms involved remain unclear. Here, we show that the polarity protein Par-3 localizes asymmetrically in Schwann cells at the axon-glial junction and that disruption of Par-3 localization, by overexpression and knockdown, inhibits myelination. Additionally, we show that Par-3 directly associates and recruits the p75 neurotrophin receptor to the axon-glial junction, forming a complex necessary for myelination. Together, these results point to a critical role in the establishment of cell polarity for myelination.
In 2000, Canada established a CODIS-based National DNA Databank (NDDB) composed of two indices: a Convicted Offender Index (COI) and a Crime Scene Index (CSI). Our laboratory populates the CSI index ...with single-source and mixed profiles on the 13 P+/COfiler
® loci. These mixtures are coded based on the number of mixed loci (loci with more than 2 alleles).
We first compared the behaviour of several hundreds low complexity mixtures (≤3 mixed loci), moderate complexity mixtures (4–6 mixed loci) and single-source profiles uploaded over the past 9 years, when run against 180
000 COI profiles. We demonstrated the value of searching a databank with mixtures as hundreds of matches were reported to investigators, while the proportion of rejected matches was similar across the 3 types of samples.
Based on these results, we designed a new study to evaluate 130 complex (7–13 mixed loci), two-contributor mixtures which were run against the COI. Results show that such mixtures return a manageable number of candidate matches in spite of their complexity: 70% returned no candidates while only a few generated more than one candidate.
Databanking strategies coupled with mixture interpretation guidelines and review of original electropherograms maximise the use of a databank while minimising the risk of adventitious hits.
In the heart, brief repeated episodes of ischemia prior to a sustained occlusion (ischemic preconditioning; PC) significantly delay the onset of necrosis and arrhythmogenesis. Ischemia has been ...reported to influence gap junction organization and connexin43 (Cx43) content, but whether PC affects these structures is not known. We investigated the effect of PC (2 cycles of 5-min ischemia plus 10-min reperfusion) followed by prolonged reperfusion without concomitant regional coronary occlusion on the myocardial Cx43 content and its spatial distribution in rabbit hearts. We also compared the effect of sustained ischemia with or without PC on Cx43 spatial distribution. In experiments with PC only, there was an initial decrease in Cx43 levels within the ischemic zone followed by a progressive increase after 48 h reperfusion. Endtoend immunolabeling of Cx43 was augmented in the ischemic region between 24 and 48 h reperfusion; labeling was not uniquely confined to myocyte abutments, but was also dispersed along the sarcolemma. Cx43 immunolabelling was more intense and diffuse in hearts subjected to PC before sustained coronary occlusion (compared to non-PC). These data indicate that gap junctions are significantly altered during brief episodes of ischemia. Reorganization of the gap junction complex could contribute to PC-mediated reductions in cardiac arrhythmias.Key words: ischemic preconditioning, connexin43, gap junction, reperfusion, heart.
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