The sequential morphological and cytochemical alterations in HeLa cells infected with adenovirus types 1 to 4 are described. Each of the four viruses studied led to consistent and reproducible cytological changes not observed in uninfected control cultures. All four agents produced striking and characteristic changes in the nuclei of infected cells. Alterations in the cytoplasm, though present, were less marked, particularly in the early stages of infection. In cells infected with type 1 or 2 adenovirus, rounded intranuclear inclusions which progressed from eosinophilic and Feulgen-negative to basophilic and Feulgen-positive, together with a homogeneous glassy, Feulgen-positive nuclear background, were prominent features. Cells infected with type 3 or 4 adenovirus exhibited marked rearrangement of basophilic nuclear material and sharply defined crystal-like inclusions, predominantly intranuclear in location, which also varied from Feulgen-negative to positive. In terms of detailed cytological effects, therefore, the four agents could be divided into two subgroups, viz., types 1 and 2 on the one hand and types 3 and 4 on the other. Measurement of DNA in individual nuclei by means of Feulgen microspectrophotometry revealed the values in infected cells to be increased above the levels of the uninfected controls.

Investigations of the biologic characteristics of adenoviruses types 1 to 4 have suggested that natural subdivisions exist within the adenovirus group (1-4). Types 1 and 2 have been found to comprise one subgroup, in that they have similar growth cycles, produce almost identical cytological changes in HeLa cells, and react quantitatively in the same manner with their typespecific neutralizing antibodies. Types 3 and 4, which constitute a second subgroup, resemble each other in the biologic aspects mentioned, yet differ from types 1 and 2. In order to determine whether types 5 and 7 adenoviruses fall into the same subgroups, the cytologic changes they evoked in HeLa cells were studied by light and phase-contrast microscopy. The role of the observed changes in viral development was then investigated by means of the fluoresceinlabelled antibody technique for the localization of intracellular antigen (5). Experiments were also undertaken to explore: (a) the possibility that the alterations produced by the prototype adenovirus strains might not be representative and that other strains of the same virus types might induce different cellular changes, and (b) the possibility that the alterations observed were peculiar to cells of the HeLa strain, which are cells in continuous culture derived from malignant tissue. Additional strains of adenoviruses types 5 and 7 were therefore tested, and the sequence of cytologic changes were followed in human amniotic cells in primary culture.The results of phase and light microscopic investigations which are here described indicate that type 7 resembles types 3 and 4, and that type 5 con-*

HLA-DR4 has been described in association with rheumatoid arthritis (RA) in multiple populations. We have studied HLA antigens in Alaskan Tlingit Indians. HLA-DR4 was decreased in the RA group (n = 32) compared with controls (n = 62) (6% vs 21% p = 0.07). The predominant DR4 allele observed was DRB1*0403 (Dw13.1). The most striking observation in these studies was a marked predominance of the DRB1*1402 allele encoding Dw16 (DRw14). This allele was present in 91% of RA cases, but was also highly prevalent in controls (80%, OR = 2.4 p = 0.20). DRB1*1402 only was observed in 47% of cases and 31% of controls. The DRB3*0101 (DRw52), and the DQA*0501 and DQB*0301 alleles encoding a subset of DQw3 were associated with DRB1*1402 in cases and in controls. HLA-Bw62 was increased in RA cases (28%) compared with controls (8%) (OR = 4.5, p = 0.01, corrected p = ns).

Objective. To evaluate the preliminary classification criteria proposed by the European Spondylarthropathy Study Group (ESSG) in Alaskan Eskimo populations.Methods. We examined, interviewed, and reviewed the records of 104 Eskimo patients with spondylarthropathy and 75 with other rheumatic disorders, and evaluated them according to the proposed criteria.Results. We found an overall sensitivity of 88.5% and a specificity of 89.3%, which is similar to the reported values in European populations.Conclusion. The ESSG criteria performed well in a population very different from that in which they were developed, and deserve further evaluation as a muchneeded and useful epidemiologic tool.Epidemiologic studies of the diseases which make up the spondylarthropathies (SpA) have been hampered by the lack of adequate disease criteria (1-4). In earlier studies of rheumatic disease prevalence in native populations of Alaska, we found that (3,4). Recently, the European Spondylarthropathy Study Group (ESSG) developed classification criteria intended to encompass a broader spectrum of spondylarthropathic disease, with the specific intent of including previously neglected cases of undifferentiated disease (5). We have tested these criteria in a wide variety of rheumatic disorders in Alaskan Eskimos, in order to contribute to the necessary validation of these preliminary criteria. We report the results of our evaluation herein. PATIENTS AND METHODSA total of 104 patients with SPA were included in the evaluation. Sixty-six patients were identified during ongoing epidemiologic studies in the Barrow and Bristol Bay Health Service Units of the Alaska Area Native Health Service (AANHS), and 38 patients were known cases from previous epidemiologic studies in Kotzebue and the YukonKuskowim Delta (3,4). Initial identification of possible cases in the Barrow and Bristol Bay areas was accomplished primarily through the computerized patient care information system used by the AANHS (6,7). The medical records of patients identified as possible cases were then reviewed by the investigators. Those patients considered likely to have SpA were invited to attend special clinics for interview and examination in order to verify their diagnoses and collect the data necessary for evaluating the ESSG criteria (5).