Soluble HLA class I induces NK cell apoptosis upon the engagement of killer-activating HLA class I receptors through FasL-Fas interaction

The engagement of the activating isoforms of C-type lectin inhibitory receptor (CLIR) or killer Ig-like receptor (KIR) by their natural ligands, represented by soluble HLA-I (sHLA-I) molecules, induced programmed cell death of natural killer (NK) cells. Indeed, NK cell apoptosis elicited by either putative HLA-E and HLA-F (sHLA-I non-A, -B, -C, and -G) or sHLA-I-Cw4 or -Cw3 from untransfected or -Cw4 or -Cw3 alleles transfected HLA-A(-), B(-), C(-), G(-), E(+), F(+) 721.221 lymphoblastoid cell line, respectively, was blocked by covering the corresponding activating receptor with either anti-CLIR- or anti-KIR-specific monoclonal antibodies (mAbs). After sHLA-I-activating receptor interaction, NK cells produced and released Fas ligand (FasL), which in turn led to NK cell apoptosis by interacting with Fas at the NK cell surface. Blocking anti-Fas mAb, or anti-FasL mAb, inhibited sHLA-I-mediated apoptosis via activating receptor in NK cell clones. This apoptosis was inhibited by NK cell treatment with cyclosporin A, whereas this drug had no effect on activating receptor-mediated activation of cytolysis. Conversely, concanamycin A, an inhibitor of vacuolar type H(+)-adenosine triphosphatase (H(+)-ATPase) of granules, inhibited activating receptor-induced NK cell cytolysis, suggesting that activating receptor-mediated apoptosis and cytolysis can use different intracellular pathways. Furthermore, a large amount of interferon-gamma (IFN-gamma) was detectable in culture supernatant of activating receptor(+) NK cells incubated with the appropriate sHLA-I ligand. Again, cyclosporin A, but not concanamycin A, strongly reduced activating receptor-mediated IFN-gamma production. This suggests that activating receptor-induced apoptosis of NK cells could play a role in eliminating potentially harmful NK cell clones and, at the same time, it leads to production of IFN-gamma, an antiviral cytokine able to amplify immune responses.     

Effect of ionizing radiation on cell-cycle progression and cyclin B1 expression in human melanoma cells

In the present study we investigated the effect of γ-irradiation (2.5 and 10 Gy) on cell-cycle progression of a human melanoma cell line, M14, characterized by a moderate radiosensitivity (SF2 = 0.5). Flow cytometric analysis showed a dose-dependent S-phase accumulation, which was detectable 8 hr after treatment with 2 and 5 Gy and was still persistent at 12 hr after 10 Gy exposure. Such a delay in S-phase was paralleled or followed by an accumulation of cells in G₂M, which was transient at the lowest radiation doses and still persistent at 72 hr after 10 Gy. Such an accumulation was, at least in part, due to a block in G₂-M transition, as demonstrated by mitotic index analysis. Bivariate flow cytometric analysis of DNA content and cyclin B₁ expression showed that, following 2 and 5 Gy, the fraction of cyclin B₁-expressing cells was superimposable upon that of G₂M cells. Conversely, in cells treated with 10 Gy, the fraction of cyclin B₁-expressing cells was half the G₂M cell fraction. Northern-blot analysis indicated that the radiation-induced decrease in cyclin B₁ protein expression was accompanied by a reduced cyclin B mRNA level. On the whole, our results indicate a direct inhibitory effect of 10 Gy irradiation on cyclin B₁ expression as a possible cause for the persistent G₂ block in irradiated M14 cells. © 1996 Wiley-Liss, Inc.     

Renal vascular damage in systemic sclerosis patients without clinical evidence of nephropathy

Objective. To evaluate the use of color-flow Doppler ultrasonography, a direct, noninvasive technique, for measurement of kidney blood flow in patients with systemic sclerosis (SSc). Methods. Twenty-five normal volunteers and 25 SSc patients (median disease duration 8 years, range 2–21 years) were studied. All were free of clinical symptoms of renal damage. The resistance index (RI) was determined on main, interlobar, and cortical vessels. Results. In SSc patients, the RI was significantly increased at every sampling site examined (P < 0.001). RI values were strongly correlated with disease duration (main artery r = 0.56, P < 0.04; interlobar artery r = 0.63, P < 0.02; cortical artery r = 0.75, P < 0.002). Regression analysis showed no relationship between RI and creatinine clearance values. Conclusion. Color-flow Doppler ultrasonography is a sensitive and noninvasive technique for evaluating vascular damage of the kidney in patients with SSc.     

Eating behavior following biliopancreatic diversion for obesity: Study with a three-factor eating questionnaire

The eating behavior of obese patients and of subjects who had normalized their body weight following biliopancreatic diversion (BPD) was assessed by a three-factor eating questionnaire (TFEQ), constructed to measure cognitive dietary restraint, the tendency to disinhibition, and susceptibility to hunger. In the obese patients higher values of both disinhibition and hunger score were found than in normoweight persons. In BPD subjects a negative association between the time elapsed from the operation and both the disinhibition and hunger score values was observed. In patients operated more than 2 years before, the eating behavior, as assessed by the TFEQ, was similar to that of normoweight persons. After BPD the operated subjects do not have to respect any dietary advice, the loss of weight and the maintenance of a normal body weight occurring in spite of an absolutely free food consumption. Similarity to the control values of disinhibition and hunger score following BPD suggests that in the long term, when the preoccupation with food and diet is abandoned, a normal eating pattern can be achieved. © 1993 by John Wiley & Sons, Inc.     

Minimally invasive transoral robotic surgery for hiloparenchymal submandibular stone: Technical note on Flex Robotic System

Flex Robotic System allows a minimally invasive approach for transoral removal of submandibular salivary stones.