The anti-tumor activity of anti-CTLA-4 is mediated through its induction of IFN gamma.

The T-cell-specific receptor, CTLA-4, has been demonstrated to be a potent negative regulator of lymphocyte activation, the functional significance of which has been demonstrated in murine tumor models using blocking antibodies. However, the mechanism(s) involved in enhancing tumor regression has not been identified. In this study, we determined whether IFN gamma was playing a role in this activity. In vitro, anti-CTLA-4 enhanced IFN gamma production by lymph node cells obtained from tumor-bearing mice (351 pg/ml vs 77 pg/ml). Additionally, fibrosarcoma-challenged animals treated with anti-CTLA-4 had elevated levels of the IFN-inducible enzyme 2-5-OAS in draining lymph nodes (850 pM vs 260 pM for controls) and an increased amount of IFN gamma in tumor lysates (at day 7, 620 pg/100 micrograms vs 160 pg/100 micrograms in controls). The importance of IFN gamma was demonstrated by the ability of neutralizing antibodies to completely abrogate the anti-tumor effects of anti-CTLA-4. Moreover, fibrosarcoma cells were shown to be exquisitely sensitive to IFN gamma-mediated class I upregulation and histological examination of tumors from anti-CTLA-4-treated mice revealed a trend toward increased tumor cell apoptosis and decreased angiogenesis. These studies have demonstrated that one mechanism for the anti-tumor effects of anti-CTLA-4 relates to its ability to augment IFN gamma production, resulting in an increased expression of class I on the tumor, enhanced apoptosis, and a decrease in blood vessel growth.

Identity patterns and self- and teacher-perceptions of problems for deaf adolescents: a research note.

The present study investigated self- and teacher-perceptions of deaf adolescents in relation to cultural identity. Fifty-one deaf adolescents completed the Porteous Checklist and Deaf Identity Scale presented in British Sign Language. Subjects were assigned to deaf, hearing or dual identity groups. Results suggest that deaf adolescents' self-perceived concerns are not dissimilar in content or severity to those of their hearing peers, although certain issues may assume a particular significance in the presence of deafness. The hypothesis that the hearing identity group would report most problems was not supported. Teachers rated the dual identity group as having the fewest difficulties.

Severe ocular injuries from orthodontic headgear.

Dislocation of extraoral orthodontic tractional devices (headgear) resulted in penetrating ocular injuries in three eyes of two patients. An endophthalmitis caused by mixed flora developed in each injured eye. Despite medical and surgical therapy, only one eye retained useful vision two years following injury. All wearers of headgear and their families should be educated in the proper use of these devices and about the potential for severe facial injuries. Penetrating ocular injuries initially may be relatively asymptomatic. Thus, even persons with seemingly minor injuries from such devices should seek immediate and thorough ophthalmic evaluation. In eyes with penetrating injuries, culture of intraocular fluids should be performed at the time of initial repair. Because the penetrating device is heavily contaminated with oral flora, broad-spectrum antibiotics should be administered by intravenous, subconjunctival, and intravitreal injection. Such injuries, although rare, may have a grave prognosis.