Two Different Manifestations of Locked-InSyndrome

Locked-in syndrome (LIS) is an entity that usually occur a consequence of the lesion of ventral part of pons. Etiology of locked-in syndrome can be vascular and nonvascular origin. Locked-in syndrome usually occurs as a consequence of thrombosis of intermedial segment of basilar artery that induces bilateral infaction of the ventrobasal part of the pons. Additionally, LIS can be caused by trauma which often leads to posttraumatic thrombosis of basilar artery. The incidence of locked-in syndrome is still unknown. The basic clinical features of locked-in syndrome are: quadriplegia (a consequence of disruption of corticospinal pathways located in ventral part of pons), different stages of paralysis of mimic musculature, paralysis of pharynx, tongue and palate with mutism and anarthria. The patient can not move, but is conscious and can communicate only by eye movements. Two patients with locked-in syndrome were present in this article. In the first case, the patient had classic locked-in syndrome that was first described by Plum and Posner1. Other patient had incomplete form of locket-in syndrome which was first described by Bauer2. In these two patients locked-in syndrome occurred as a consequence of trauma. In the first patient locked-in syndrome was caused by direct contusion of ventral part of pons while in other patient locked-in syndrome was a consequence of posttraumatic thrombosis of vertebrobasilar artery. The introduction of anticoagulant therapy, besides the other measures of intensive therapy, has shown complete justification in the second patient. The gradual partial recovery of neurologic deficit has developed in the second patient without any additional complications

Perforin Is Required for Innate and Adaptive Immunity Induced by Heat Shock Protein Gp96

Tumor-secreted gp96-Ig is highly immunogenic and triggers CD8 T cell-mediated tumor rejection. In vivo secreted gp96-Ig and gp96-myc cause NK activation and clonal expansion of specific CD8+ CTL in wild-type and in Fas-ligand-deficient (gld) mice but not in perforin- (PKO) or IFN-γ-deficient (GKO) mice. Transfer of perforin-competent NK cells restores the ability of PKO mice to clonally expand CD8 CTL in response to gp96-Ig. The data demonstrate an essential role for perforin-mediated functions in the activation of innate and adaptive immunity by heat shock protein gp96-peptide complexes. Crosspresentation of antigens by heat shock proteins seems to require a perforin-dependent positive feedback loop between NK and DC for both sustained NK activation and clonal CTL expansion. The studies also explain how depressed NK activity in patients with tumors or after viral infections could diminish CTL responses

Early pregnancy decidual lymphocytes beside perforin use Fas ligand (FasL) mediated cytotoxicity

Decidual natural killer (NK) cells are the predominant lymphocytes at the maternal–fetal interface. They are involved in defense against virally infected, parasitized and transformed cells and may contribute to the control of trophoblast invasion. The presence of perforin and other possible cytolytic mediators suggests these functions. Cytolytic mechanisms of unstimulated and Th1 cytokine stimulated decidual lymphocytes (DL), as well as purified decidual CD56+ cells, were analyzed against NK sensitive and resistant targets. DL were isolated from decidual mononuclear cells (DMC) cultured in the medium only or in the presence of Th1 cytokines: IL-2, IL-12, IL-15, IL-18 and their combinations (IL-12/IL-18 or IL-15/IL-18). Fas ligand (FasL), perforin and granzyme B mRNAs expression and cytotoxicity were analyzed by flow cytometry and/or RT-PCR. DL (containing 72.19±7.53% of CD56+ cells), obtained from 18h-cultured DMC in the medium only, expressed perforin, FasL and granzyme B mRNAs and lysed the NK-sensitive K-562 cell line, and also the NK-resistant P815 and P815-Fas transfected cell lines. Concanamycin A, a blocker of granule exocytosis, decreased significantly K-562 lysis, but not P815 lysis. However, the addition of anti-FasL antibody diminished significantly P815 lysis as well. IL-2 and IL-15, known inducers of perforin and FasL mRNAs and protein expression, could not additionally increase P 815 cell lysis by DL cultured within DMC. These results suggest that DL cultured in DMC for 18h, have the characteristics of lymphokine-activated killer (LAK) cells and are able to use efficiently both the perforin and the FasL cytolytic pathways