A human protein kinase, p53-related protein kinase (PRPK), was cloned from an interleukin-2-activated cytotoxic T-cell subtraction library. PRPK appears to be a homologue of a growth-related yeast serine/threonine protein kinase, YGR262c. However, a complementation assay using YGR262c-disrupted yeast indicated that PRPK is not functionally identical to the yeast enzyme. PRPK expression was observed in interleukin-2-activated cytotoxic T-cells, some human epithelial tumor cell lines, and the testes. The intrinsic transcriptional activity of p53 was up-regulated by a transient transfection of PRPK to COS-7 cells. PRPK was shown to bind to p53 and to phosphorylate p53 at Ser-15. These results indicate that PRPK may play an important role in the cell cycle and cell apoptosis through phosphorylation of p53.

In order to investigate the mechanism of Bell's palsy, we developed an animal model of facial nerve paralysis induced by the reactivation of herpes simplex virus type 1 (HSV-1). Eight weeks after recovery from facial nerve paralysis caused by inoculation with HSV-1, the mice were treated with auricular skin scratch at the site of the previous inoculation, or with intraperitoneal injection of anti-CD3 monoclonal antibody (mAb), or combination of both procedures. No mice developed facial nerve paralysis when they were treated with either auricular scratch or mAb injection alone. In contrast, 20% of mice developed facial nerve paralysis with the combined treatment. With one exception, no mouse treated with either auricular scratch or mAb injection showed HSV-I DNA in their facial nerve tissue, whereas 4 out of 6 mice receiving both treatments showed HSV-1 DNA on day 10 after treatment. Histopathological findings showed neuronal degeneration in the geniculate ganglion and demyelination of the facial motor nerve in paralyzed mice. These findings suggest that a combination of stimuli, local skin irritation, and general immunosuppression is essential for successfully inducing facial nerve paralysis in mice with latent HSV-1 infection.

IL-6 titres in sera and peritoneal exudate fluids (PEF) derived from pristane injected DBA/1 and CBA/Igb mice were measured. Arthritic DBA/1 mice had significantly higher serum IL-6 titres than nonarthritic or normal mice at 160 days post pristane injection. By contrast, although both arthritic and non-arthritic CBA/Igb mice had higher serum IL-6 titres than normal mice, there was no significant difference in serum IL-6 titre between these two groups at day 200-230. In both strains of mice, the IL-6 titres in PEF were more than 10 times serum levels regardless of arthritis. As previously reported for CBA/Igb mice, agalactosyl IgG levels are raised in pristane injected DBA/1 mice and the percentage is higher in arthritic animals than that in non-arthritic mice. An association between serum agalactosyl IgG levels and PEF IL-6 in pristane injected DBA/1 was demonstrated. Moreover, the injection of recombinant IL-6 into normal mice increased their serum agalactosyl IgG levels. However, it is considered that IL-6 is not the only factor involved in the production of agalactosyl IgG.

No abstract

Human lymphokine-activated killer (LAK) cells expressed a membrane-associated lymphotoxin-related molecule (mLT) which was detected by flow cytometric analysis with anti-lymphotoxin antibody. Upon removal of exogenous interleukin-2 from LAK cell culture medium and another 24 h cultivation, the expression of mLT was decreased. Corresponding to the decrease of mLT expression, the killing activity of LAK cells towards L929 cells was remarkably reduced and killing of MIA PaCa-2 and U937 cells was moderately reduced, whereas killing of Daudi and K562 cells was fully restored. The supernatant of mLT-expressing LAK cells had no cytotoxic activity towards L929 cells in the absence of actinomycin D. Moreover, not only the killing of L929 cells but also that of human tumor cell lines (MIA PaCa-2, U937) by mLT-expressing LAK cells was partially inhibited in the presence of anti-lymphotoxin antibody. These results suggest an involvement of mLT in the killing of some tumor target cells by LAK cells.

We have developed transmission-blocking monoclonal antibodies (MAbs) against Plasmodium yoelii 21-kDa (Pys21) and 28-kDa (Pys25) ookinete surface proteins. These MAbs block infectivity of P. yoelii to Anopheles stephensi. One MAb, 14, cross-reacted by Western blotting with a 28-kDa surface protein (Pbs25) of P. berghei ookinetes and blocked oocyst development, as assayed by direct mosquito feeds on passively immunized P. berghei-infected mice. In total, we have identified two ookinete surface proteins in P. yoelii, one of which is also present in P. berghei. The transmission-blocking activity of the anti-Pys25 MAb 4 was complete and more potent than that of the anti-Pys21 MAb 2. Moreover, Fab fragments of MAb 4 had transmission-blocking activity in mice. In comparison, Fab fragments of MAb 2 did not have detectable transmission-blocking effect, although F(ab) 2 did. Furthermore, MAb 2 and MAb 4 appeared to block the in vitro formation and development of zygotes as well.

No abstract

SUMMARYThe effecl of pregnancy on Ihe incidence and severity of pristane-induced arlhrilis was examined along with the glycosylation status of IgG during the ante-natal and post-partum periods. Il was found that pristane-induced arthritis is prevented by pregnancy. In addition, the levels of agalactosyl IgG fall during pregnancy but rise lo greater than normal wilhin a few days of parturition, before resetting towards Ihe norm shortly afterwards. Interestingly, the level of agalactosyl igG correlates with the severity of arthritis. As previously reported iL-6may bean important factor, not necessarily the only one, in the production of agalactosyl IgG. Here it is clearly demonstrated that llic kinetics of lL-6 activity posl-prislane injection parallels the kinetics of agalactosyl IgG production. In addition, the overshoot in agalactosyl IgG levels immediately post-partum coincides with a burst in IL-6 activity. It is considered that these changes in IgG glycoform levels, or the factors which control them, may be related to the mechanisms underlying prevention/remission of arthritis during pregnancy.