Cross-linking of Fas (CD95, APO-1) and Fas ligand (FasL; CD95L) induces apoptosis of Fas-bearing cells. Recent evidence suggests that FasL. expression plays an important role in maintenance of immune privilege in murine testis and eye and in tumour escape from immune rejection in colon cancer, melanoma and hepatocellular carcinoma. Bcl-2 is a membrane protein that suppresses apoptosis in response to a variety of stimuli. In this paper we describe abundant expression of FasL protein and mRNA transcripts within the immune privileged environment of the placenta by immunohistochemistry and reverse transcription in-situ polymerase chain reaction methods. The syncytiotrophoblast layer, the main site of feto-maternal interface, and extravillous trophoblasts, demonstrated consistent immunoreactivity for FasL in term placentae. Co-occurrence of Fas and Bcl-2 were detected with a similar pattern of distribution with FasL. The TUNEL method revealed evidence of apoptosis in the placental tissues. We speculate that abundant presence of FasL in the trophoblast contributes to immune privilege in this unique environment, perhaps by fostering apoptosis of activated Fas-expressing lymphocytes of maternal origin. An apoptotic process mediated by FasL may also play a role in placental invasion during implantation and underscores similarities between the trophoblast and neoplastic cells.

In this report we examine the fate of donor cells injected via different routes. When PKH-26-labeled C57BL/6 (B6) spleen cells were intravenously (i.v.) injected into BALB/c mice, the donor cells were rejected within 3 days. In contrast, when the same B6 spleen cells were portal venously (p.v.) injected, they were trapped in the recipient liver. When allogeneic or syngeneic whole bone marrow cells (BMC) or cells in a hemopoietic stem cell (HSC)-enriched fraction were either i.v. or p.v. injected, the cells accumulated in the liver. The cells trapped in the liver were found to be wheat germ agglutinin (WGA)-positive HSC. When B6 thymocytes were p.v. or i.v. injected into BALB/c mice, they were rapidly rejected. When BALB/c mice were i.v. preimmunized with unlabeled B6 spleen cells, BMC or thymocytes, the p.v. or i.v. injected PKH-26-labeled B6 spleen cells were rejected rapidly (within 2 days). In contrast, when BALB/c mice were p.v. preimmunized with B6 spleen cells or BMC, the p.v. or i.v. injected PKH-26-labeled B6 spleen cells were not rejected. The cells responsible for the tolerance induction were found to be HSC trapped in the liver. Delayed-type hypersensitivity assays revealed that the tolerance could be maintained for more than 49 days by p.v. injection plus i.v. injection (at intervals of 2 weeks) of HSC. These findings indicate that HSC trapped in the liver play a crucial role in the induction and maintenance of p.v. tolerance.

Oedema is considered a key pathogenic factor in the development of venous leg ulcers. The purpose of this study was to determine the localization of oedema in legs with ulcers. Twelve patients with 13 venous leg ulcers (one bilateral), with a duration of 7-18 months, were examined by high-frequency B-mode ultrasound scanner. This was performed at three sites in the leg (low, middle and upper sites of the lower leg). In the same group of patients, the legs without ulcers were used as controls. The echogenicity and the thickness of the whole dermis were quantified by digital image analysis; the echogenicities of the upper (papillary) and lower portions of the dermis were measured. In the upper site no significant difference was found between the legs with ulcers and controls. In the middle and low sites of legs with ulcers, the dermal echogenicities were 34% and 64% (P < 0.01) less than those in controls, and the dermal thicknesses were 0.4 mm and 0.8 mm (P < 0.01) thicker than those in controls, respectively. This indicated intradermal oedema existing in the lower part (gaiter area) of the legs with ulcers. The ratios of low echogenic pixels in the upper and lower portions of the dermis, in the middle and low sites of legs with ulcers, were 0.5 and 0.9 (P < 0.05 and P < 0.01), respectively, higher than those in controls, suggesting the papillary dermis as a preferential site of oedema formation. The present study demonstrates that in the low sites of legs with ulcers, a marked increase in oedema was seen in the papillary dermis. This may add to the understanding of the origin of leg ulcers in the gaiter area of the leg.

The purpose of the present study was to examine whether the magnitude of the changes in the concentration of muscle metabolites influences the recovery of power output following short-term maximal intensity cycle exercise performed at different average pedalling rates. In part A of the study eight female subjects performed four trials on a cycle ergometer. Two trials involved maximal sprints of 30- and 6-s duration separated by a very short (2-3 s) recovery period. Average pedal rate during the first 30-s sprint was manipulated by employing resistances of either 7.5 or 10.1% of body weight; the second sprint always being performed against 7.5% BW. In two further trials subjects performed only a single 30-s sprint against the two resistances with pre- and post-exercise muscle biopsies and blood samples being taken. Peak power in the second sprint was significantly higher (442 +/- 31W vs. 402 +/- 33W; P < 0.05) following prior exercise against the greater resistance during which average pedal rate was lower (approximately 26%; P < 0.01) compared with the lesser resistance. However, despite this the muscle metabolite responses to the first sprint were similar (delta PCr (7.5 vs. 10.1% applied resistance) -55 vs. -59 mmol kg dry muscle-1: delta Lactate + 104 vs. +107 mmol kg dry muscle-1: both P > 0.05). In part B of the study six female subjects performed 19 trials in which the recovery interval between a maximal 30-s sprint (where average pedalling rate was manipulated in a manner similar to part A) and a 6-s sprint ranged from 0 to 300 s. The rate of restoration of power output was influenced by the average pedal rate in sprint 1 only for recovery durations of up to 3 s. These findings suggest that the recovery of power is not exclusively determined by muscle metabolites, in particular PCr, when the recovery duration is very short (< or = 3 s). As it has been previously shown that the pattern of muscle activation influences ionic balance it is speculated that ionic factors may be very important in the early and rapid recovery of power.

We thus report herein the successful prevention of autoimmune disease by transplantation of a sufficiently large number of purified fully allogeneic HSCs in W/B F1 mice.