The isolation of a T-cell tropic retrovirus from three immunodeficient macaques and one macaque with lymphoma is described. The morphology, growth characteristics, and antigenic properties of this virus indicate that it is related to the causative agent of acquired immune deficiency syndrome in humans (HTLV-III or LAV). This virus is referred to as simian T-lymphotropic virus type III (STLV-III) of macaques. The existence of a cytopathic, T-cell tropic virus resembling HTLV-III in monkeys may facilitate study of disease induction and vaccine development in an animal model.

Results suggest that cholecystectomy is an effective treatment for gallbladder mucocele. Although perioperative mortality rate is high, prognosis after discharge from the hospital is excellent. Rupture of the gallbladder warrants emergency surgical intervention but does not preclude a positive outcome.

The T-cell tropic retrovirus of macaque monkeys STLV-III has morphologic, growth, and antigenic properties indicating that it is related to HTLV-III/LAV, the etiologic agent of the acquired immune deficiency syndrome (AIDS) in humans. Four of six rhesus monkeys died within 160 days of STLV-III inoculation with a wasting syndrome, opportunistic infections, a primary retroviral encephalitis, and immunologic abnormalities including a decrease in T4+ peripheral blood lymphocytes. These data show that an immunodeficiency syndrome can be produced experimentally in a nonhuman primate by an agent from the HTLV-III/LAV group of retroviruses. The STLV-III-macaque system will thus provide a useful model for the study of antiviral agents and vaccine development for human AIDS.

Recent studies have demonstrated the induced expression of endothelial adhesion molecules including E-selectin (also called endothelial leukocyte adhesion molecule-i), vascular cell adhesion molecule and intercellular adhesion molecule in actively involved mucosa of patients with ulcerative colitis and Crohn's disease. Similar induction has been demonstrated in the colon of the Cotton-top tamarin (CTU), a New World primate that experiences a spontaneous acute and chronic colitis resembling ulcerative colitis.To assess the potential importance of leukocyte adhesion as a necessary step in acute colitis, the effect of parenteral mAb directed against adhesion molecules on CIT colitis was evaluated in placebo-controlled blinded trials. Serial administration ofeither of two anti-E-selectin mAb designated BB1 1 and EH8 effectively coated endothelial surfaces expressing this vascular adhesion molecule. Although colitis activity was slightly diminished after the 10-d treatment period in CIT receiving either BB1 1 or EH8, this reduction was not significantly different than that seen in animals given a placebo control when assessed by a previously validated standardized scale of inflammatory activity: mean histologic activity grade 2.2±0.2 pretreatment vs 1.5±0.5 posttreatment in group receiving mAb and 2.1±0.1 pretreatment vs 1.3±0.5 posttreatment in the placebo group (P > 0.2). In contrast, administration of an anti-a4 integrin mAb designated HP1 /2 that binds VLA4 (a4f31) and presumably a4187 integrins resulted in significant attenuation of acute colitis when compared to both pretreatment activity index (P = 0.005) and the placebo control group (P < 0.01 ): mean histologic activity grade 1.6±0.3 pretreatment vs 0.2±0.1 posttreatment in the group receiving HP1 /2 and 1.8±0.5 pretreatment and 1.2±0.2 posttreatment in the placebo control group.These studies using a model of spontaneous colitis in the CMT demonstrate the feasibility of modulation of leukocytevascular adhesion and/or other integrin-mediated events possibly including T cell aggregation and T cell-stromal interactions, as well as lymphocyte homing. These results suggest both that these processes are important and possibly essential elements in sustaining acute colitis and that their disruption may result in therapeutic benefit. (J. Clin. Invest. 1993. 92: Address correspondence to Daniel K. Podolsky, M.D., GI Unit, Jackson 7,

Rhesus monkeys were immunizd by multiple inoculations with purified, disrupted, noninfectious sinmian immunodeficiency virus (SIV) in adjuvant. Immunized monkeys developed anti-SIV antibodies detectable by whole-virus ELISA and by immunoblot reactivity; these antibodies had weak neutralizing activity. One week after the last immuniza-

Herpesvirus samiri is an oncogenic herpesvirus that induces rapidly progressing lymphonias in New World primates. Using retrovirus vectors for gene transfer, specific open reading frames of H. saimiri were tested for their ability to transform rodent cells in culture. One open reading frame, designated STP-C488 (for saimiri-transformation-associated protein of the subgroup C strain 488), phenotypically transformed Rat-i cells, resulting in formation of foci, growth at reduced serum concentration, and growth to higher cell densities. Cells transformed by STP-C488 formed invasive tumors in nude mice. The STP-All reading frame of strain 11 (subgroup A) was much less potent in its transforming ability than STP-C488. These results demonstrate the oncogene nature of these two open reading frames and provide a means for studying their transforming functions independent of the rest of the H. saimiri genome.

Human T-lymphotropic virus type III (HTLV-III) is thought to play an etiologic role in the development of the acquired immune deficiency syndrome (AIDS). In this study the serologic characterization of a new simian retrovirus that is related to HTLV-III is described. This new virus, here referred to as STLV-III, was isolated from sick macaques at the New England Regional Primate Research Center. Radioimmunoprecipitation analysis revealed STLV-III-specific proteins of 160, 120, 55, and 24 kilodaltons, all similar in size to the major gag and env proteins of HTLV-III. These antigens were recognized by representative macaque serum samples and human reference serum samples positive for HTLV-III antibodies. Monoclonal antibodies directed to p24, the major core protein of HTLV-III, also immunoprecipitated a 24-kilodalton species in lysates of cells infected with the macaque virus. This HTLV-III-related virus, which naturally infects a nonhuman primate species, may provide a useful model for the study of HTLV-III and the pathogenesis of AIDS.

Herpesvirus saimiri naturally infects squirrel monkeys (Saimiri sciureus) without producing signs of disease; infection of other New World primates, however, results in a rapidly progressing, malignant, T-cell lymphoma. Results described in this report identify a region of the viral genome that is required for oncogenicity in owl monkeys (Aotus trivirgatus); this region is not required for replication of the virus. This is believed to be the first such genomic region identified in a herpesvirus system.