DNA recognition by the aberrant retinoic acid receptors implicated in human acute promyelocytic leukemia.

Human acute promyelocytic leukemias (APLs) are associated with chromosomal translocations that replace the NH2 terminus of wild-type retinoic acid receptor (RAR) alpha with portions of the promyelocytic leukemia protein (PML) or promyelocytic leukemia zinc-finger protein (PLZF). The wild-type RARalpha readily forms heterodimers with the retinoid X receptors (RXRs), and these RAR/RXR heterodimers appear to be the principal mediators of retinoid signaling in normal cells. In contrast, PML-RARalpha and PLZF-RARa display an enhanced ability to form homodimers, and this enhanced homodimer formation is believed to contribute to the neoplastic properties of these chimeric oncoproteins. We report here that the DNA recognition specificity of the RXRalpha/RARa heterodimer, which is presumed to be the dominant receptor species in normal cells, differs from that of the PML-RARalpha and PLZF-RARalpha homodimers, which are thought to prevail in the oncogenic cell. We suggest that differences in target gene recognition by the normal and oncogenic RARalpha proteins may contribute to the leukemogenic phenotype.

Active prevention in diabetic eye disease. A 4-year follow-up.

Ten years after the foundation of a national diabetic eye screening program in 1980, we have established a low prevalence of blindness and partial sight in type 1 and type 2 diabetics in Iceland. We ask whether the screening program is also associated with a low incidence of blindness in diabetics. We now report the results of a prospective study on the 4-year incidence of diabetic retinopathy and visual impairment in type 1 diabetics with age at onset less than 30 years. Out of 205 patients participating at baseline, 175 patients (85.4%) participated over the full 4-year period. Patients were examined annually and received laser treatment according to Diabetic- and Early Treatment Diabetic Retinopathy Study criteria. The 4-year incidence of any retinopathy was 38.1%, of proliferative retinopathy 6.6%, and of macular edema 3.4%. Out of 174 patients, 7.4% showed improvement in visual acuity of 2 Snellen lines while 2.5% experienced worsening of visual acuity of 2 Snellen lines during the 4-year period. No diabetic suffered more than 2 lines deterioration of vision and none became legally blind. The incidence of retinopathy in Icelandic type 1 diabetics participating in our annual eye screening program is low and the visual acuity stable. Our results suggest that visual impairment in diabetics can be prevented with active regular screening and standard laser therapy.

[Eye injuries in Icelandic children.].

UNLABELLED: The purpose was to establish the incidence and nature of serious eye injuries in Icelandic children. The method used was a retrospective study of 133 children aged 16 and younger admitted to the Landakots Hospital in Reykjavik, from January 1984 to December 1993. The results were: one hundred thirty three children were admitted because of eye injuries during the study period. There were 109 boys (82%) and 24 girls (18%). They were divided into four age groups. The incidence of eye injuries has decreased in all age groups except in children four years and younger. The most frequent diagnosis was eye contusion (51%), eye perforation (26%), eyelid trauma (14%) and minor injuries (8%). Fifty eight had hyphema, five of them rebled. Most of the accidents happened at play. Contusion of the eye because of beanbag shot was common (20.6%). In the years from 1984 to 1989 there were 84 children who had eye trauma whereas in 1989 to 1993 there were only 49 children who required hospitalization. CONCLUSION: Severe eye trauma in children has decreased in frequency, except in the youngest age group.