The M variant of encephalomyocarditis (EMC) 1 virus produces a diabetes-like syndrome in mice by infecting and destroying pancreatic beta cells (1-3). The severity of the diabetes correlates with the degree of virus-induced beta cell damage (4, 5). Only certain inbred strains of mice develop diabetes, and susceptibility to EMC virusinduced diabetes is inherited as an autosomal recessive trait (2, 6-8). The genetic factors controlling susceptibility operate at the level of the beta cell, and whether a particular strain of mouse develops diabetes appears to be related to differences in the permissiveness of beta cells to infection with EMC virus (9, 10).Previous experiments (5) showed that when mice were inoculated with a high concentration of mouse-passaged EMC virus (10 8 plaque-forming units [PFU]), fewer animals developed diabetes than when inoculated with a low concentration of the same virus (10 ~ PFU). Moreover, the diabetogenic capacity of the virus was markedly diminished after passage in mouse fibroblast cultures, but was restored when passaged in mice. This raised the possibility that the stock pool of EMC virus was made up of two populations of virus: one that had a tropism for beta cells and produced diabetes and the other that did not have a tropism for beta cells and was nondiabetogenic (5).The present investigation was initiated to see, first, whether our stock pool of the M variant of EMC virus was made up of a mixture of diabetogenic and nondiabetogenic virus and, second, whether the nondiabetogenic virus inhibited the development of diabetes. Materials and MethodsMice. Unless otherwise indicated, SJL/J male mice, 5-6 wk old, obtained from The Jackson Laboratory, Bar Harbor, Maine, were used in all experiments. Animals were inoculated with virus by the intraperitoneal route.Pancreatic Beta Cell Cultures. Pancreata were aseptically removed from suckling SJL/J mice, and beta cell cultures were prepared as described previously (9). The cultures were refed at 2-d intervals, and at 6 d the monolayers were used to passage virus. Staining of the monolayers with fluorescein isothiocyanate-labeled antibody to insulin indicated that 40-70% of the cells were beta cells (9).Virus. The M variant of EMC virus (1), prepared as described elsewhere, was passaged five J Abbrev.iations used in this paper: EMC, encephalomyocarditis; FITC, fluorescein isothiocyanate; IRI, immunoreactive insulin; PFU, plaque-forming units; SME, secondary mouse embryo; VSV, vesicular stomatitis virus.

Plamenac P, Nikulin A, Pikula B. Cytology of the respiratory tract in former smokers. Acta Cytol 1972;16:256-60. Schreiber H, Bibbo M, Wied GL, Saccomanno G, Nettesheim P. Bronchial metaplasia as a benign or premalignant lesion. Altogether 26 lesions were induced in 13 patients, whereas none occurred in the controls (p <0 001). Sutures caused most of the lesions (15), and those so induced had a mean maximum diameter of 2-3 mm and lasted for an average of four days. Ulcers induced mechanically were clinically indistinguishable from those usually seen in the patients, except that they were generally smaller and healed more quickly.These findings confirm that mechanically induced injury of the oral mucosa may cause ulceration in people susceptible to aphthous stomatitis. Such a procedure may therefore be helpful in identifying subsets of patients.

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We have used a panel of anti-gp160 MAbs to construct anti-HIV immunotoxins by coupling antibodies to ricin A chain (RAC). The ability of the immunotoxins to kill HIV-1-infected cells and halt the spread of infection was tested in tissue culture on persistently and acutely infected cell lines and primary lymphocyte cultures stimulated with phytohemagglutinin (PHA blasts). Laboratory strains and clinical isolates of HIV both were tested. The constitution and antigen-binding capacity of the immunotoxins were confirmed by ELISA and indirect immunofluorescence. Immunotoxins that bind epitopes exposed on the cell surface effectively killed persistently infected cells, although killing was not directly proportional to binding of immunotoxin to cell. The activity of anti-gp41, but not anti-gp120, immunotoxins was markedly enhanced in the presence of soluble CD4 or peptides corresponding to the CDR3 region of CD4. CD4-mediated enhancement of anti-gp41 immunotoxin activity was observed for laboratory strains neutralized by sCD4 and for clinical isolates that were resistant to neutralization by sCD4. Immunotoxin action was potentiated by brefeldin A, bafilomycin A1, cortisone, and an amphipathic fusion peptide, but not by cytochalasin D, nocodazol, monodansyl cadaverine, or trans-retinoic acid. Anti-HIV immunotoxins are useful tool with which to study the functional expression of gp120/gp41 antigens on the surface of HIV-infected cells, as well as potential AIDS therapeutics. Because these studies relate to the accessibility of viral antigens to antibody-mediated attack, these studies also have relevance for vaccine development.

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