No abstract

Superantigens are products of bacteria with dual affinity for HLA-DR and the variable region of the ft chain of the T cell receptor, leading to the stimulation of large numbers of T cells. Because there is evidence for the involvement of superantigens in various disease conditions in which intravenous IgG (IVIgG) is used as therapy, the purpose of the present study was to determine if IVIgG contains antibodies inhibitory to T cell stimulation by the superantigens. ELISA and Western assays revealed high concentrations of antibodies in the pooled IgG against eight different staphylococcal toxin (Staph-toxin) superantigens. The IVIgG inhibited in vitro stimulation of human peripheral blood T cells by the Staph-toxins, but did not inhibit responses elicited by phytohemagglutinin or anti-CD3. Inhibition was mediated by Staph-toxin-specific antibodies as shown by affinity adsorption depletion studies. The antibodies functioned by inhibiting the binding and/or presentation of Staphtoxins by DR' accessory cells. In conclusion, this report is the first to show that normal pooled IgG contains antibodies against a major group of the superantigens, the Staph-toxins, and that the antibodies can inhibit Staph-toxin-elicited T cell activation, suggesting a possible immunoregulatory role for the antibodies in vivo. (J. Clin. Invest. 1993. 91:602-607.)

Cancer cells can invade three-dimensional matrices by distinct mechanisms, recently defined by their dependence on extracellular proteases, including matrix metalloproteinases. Upon treatment with protease inhibitors, some tumour cells undergo a 'mesenchymal to amoeboid' transition that allows invasion in the absence of pericellular proteolysis and matrix degradation. We show here that in HT1080 cells, this transition is associated with weakened integrin-dependent adhesion, consistently reduced cell surface expression of the a2b1 integrin collagen receptor and impaired signalling downstream, as judged by reduced autophosphorylation of focal adhesion kinase (FAK). On examining cancer cells that use defined invasion strategies, we show that distinct from mesenchymal invasion, amoeboid invasion is independent of intracellular calpain 2 proteolytic activity that is usually needed for turnover of integrin-linked adhesions during two-dimensional planar migration. Moreover, an inhibitor of Rho/ROCK signalling, which specifically impairs amoeboid-like invasion, restores cell surface expression of a2b1 integrin, downstream FAK autophosphorylation and calpain 2 sensitivity -features of mesenchymal invasion. These findings link weakened integrin function to a lack of requirement for calpain 2-mediated integrin adhesion turnover during amoeboid invasion. In keeping with the need for integrin adhesion turnover, mesenchymal invasion is uniquely sensitive to Src inhibitors. Thus, the need for a major pathway that controls integrin adhesion turnover defines and distinguishes cancer cell invasion strategies.

The aim of the present study was to identify specific behavioral patterns that contribute to diminished estrus expression in lame cows. Behavioral scan and focal sampling were used to examine the effect of lameness on daily activity budgets, sexual behavior, feeding activities, and body condition score. A total of 59 milking cows (51.8 +/- 1.4 d postpartum) were monitored on a commercial dairy farm for 5 d following estrus synchronization. Overall, lame cows (n = 39) spent proportionately less time elevated on their feet and more time lying down compared with nonlame cows (n = 20). This included lame cows spending less time walking or standing. Overall, the total proportion of scans in which an estrous behavior was observed was very small but tended to be smaller for lame compared with nonlame cows. Throughout a day, lame cows displayed a lower proportion of estrous behaviors in the early morning. Lameness did not affect durations of drinking, grazing, or ruminating, or how these behavioral states fluctuated throughout the day. Similarly, rumination chewing rates were the same for lame and nonlame cows, and there was no association between lameness and dominance/displacement while feeding at a feed-fence. Lame cows did, however, have a slower bite rate at pasture and had a lower body condition score. Lame cows were also nearer the rear of the herd, both as they left the field and when entering the milking parlor. In conclusion, lame cows have longer lying times and spend less time standing, walking, and expressing an estrous behavior. Lame cows also have a lower bite rate at pasture and are more likely to be of lower body condition score.

No abstract