David J. Giron

Poly(cis-dihaiodiamine Platinum(II)) Compounds: Synthesis and Biological Activity

Abstract Poly(cis-dihalodiamine platinum(II)) compounds are synthesized through solution condensation of solutions of tetrahaloplatinum(II) salts with diamines. Preliminary testing of five of these polymers shows that several affect virus and bacterial replication, and that all are toxic to HeLa (human) and L929 (mouse) tumor cells at concentrations above 300 μg/mL but are apparently nontoxLc to mice at doses of up to 20 μg/g Swiss-Webster mouse.

Inhibition of Viral Replication in Cell Cultures Treated with Prostaglandin E1

Abstract A study has been initiated to determine the influence of prostaglandins on virus replication and its relationship to the interferon system. In the present study, data are presented which show that pretreatment of cells in culture with prostaglandin E1 results in (i) a reduction in the yields of Mengo, MM and polio viruses, (ii) enhanced yields of interferon, and (iii) inhibition of cell division.

Structural and Biological Characterization of Antimony(V) Polyamines

Abstract The condensation of organoantimony(V) dihalides with diamines forming antimony(V) polyamines employing the interfacial technique is described. Structural characterization was accomplished by employing elemental analysis, light-scattering photometry, infrared spectroscopy, control reactions, and mass spectroscopy. The products exhibit mild inhibition to a wide range of bacteria and to HeLa, BHK-21, and L929 cancer-related cell lines.

Effect of Interferon Inducers and Interferon on Bacterial Infections

The effect of interferon inducers and exogenous L-cell interferon on the infection of mice by Pasteurella tularensis or Diplococcus pneumoniae was investigated. The results indicate that the degree of protection is dependent on the type of inducer used. A variety of defense mechanisms with limited nonspecific activity appear to be involved.

Tilorone Hydrochloride: Lack of Correlation Between Interferon Induction and Viral Protection

The protection of mice against MM virus infection and the induction of circulating interferon by tilorone hydrochloride were determined. Whereas protection was evident with doses of 0.15 and 1.5 mg/kg, interferon was not detected with doses lower than 150 mg/kg. Protection was apparently not dependent on interferon induction.

Inhibition of Virus-Induced Diabetes Mellitus by Interferon is Influenced by the Host Strain

Abstract The diabetogenic variant of encephalomyocarditis virus (EMC-D) induces a diabeteslike syndrome in certain strains of mice. A study was done to determine if virus-induced diabetes could be prevented by interferon (IFN). It was found that the production of diabetes by EMCD was blocked by either IFNβ or a variety of IFN-inducers in SWR/J, but not ICR Swiss mice. The replication of EMC-D in cell culture was inhibited by IFNβ. It is concluded that the response of pancreatic beta cells to the protective effect of IFN, is probably under genetic control.

Interferon Levels and Resistance to Viral Infection Associated with Selected Interferon Inducers

Summary Comparative studies of protection of mice against infection with MM virus and levels of interferon induced by graded amounts of Escherichia coli endotoxin, statolon, maleic acid-divinyl ether copolymer, and polyinosinic-polycytidylic acid complex have been carried out. In every instance, both protection and interferon response were dose-dependent, but interferon titers did not correlate with protection. The degree of protection could not be correlated to any specified amount of interferon. Possible explanation of these results would include: (i) protective potency of interferon may differ with the type of inducer, (ii) different interferons are utilized for protection in different ways, or (iii) the protective effect of inducers used may be unrelated to interferon.

A Murine Model of Insulin-dependent Diabetes Mellitus Resulting from the Cumulative Effects of the Nondiabetogenic Strain of Encephalomyocarditis Virus and a Single Low Dose of Streptozocin

The induction of insulin-dependent diabetes in outbred male and female mice was examined using a combination of the usually nondiabetogenic B-variant of encephalomyocarditis (EMC-B) virus and single low doses of streptozocin (STZ). Neither EMC-B virus nor low doses of STZ were overtly diabetogenic when administered alone; however, when these two insults occurred 1 day apart, diabetes resulted in male but not in female mice. The induction of diabetes was dependent on the time interval between these two insults, since EMC-B virus and STZ given 4 days apart did not induce diabetes. Unexpectedly, when the order of these two insults was reversed, diabetes occurred. The absence of diabetes when EMC-B virus was given before STZ suggested the possibility that virus-induced interferon blocked the cytotoxic effects of STZ. This suggestion was supported by the observation that an antiserum against beta interferon abrogated the virus-mediated protection against STZ-mediated cytotoxicity. Also, Poly I:C administered before a single diabetogenic dose of STZ delayed the onset of severe hyperglycemia.

Virus-induced Murine Diabetes: Enhancement by Immunosuppression

Adult, male ICR Swiss mice are susceptible to the diabetogenic effects of the D-variant of encephalomyocarditis virus (EMC-D) in contrast to adult C3H/HeJ male mice, which are relatively resistant. To date, experimental evidence suggests that the immune system plays a role in the pathogenesis of this infection. We have investigated the potential involvement of the immune system in the pathogenesis of EMC-D-induced diabetes using cyclosporin-A (CyA), a potent immunosuppressive drug. The data show that treatment with CyA results in increased severity and incidence of diabetes in susceptible ICR Swiss mice and induction of diabetes in resistant C3H/HeJ mice. It is concluded that immune mediation probably is not involved in the early pathogenesis of EMC-D-induced diabetes in mice.

Replication of Diabetogenic and Nondiabetogenic Variants of Encephalomyocarditis (EMC) Virus in ICR Swiss Mice

Abstract The replication of the diabetogenic D (EMC-D) and nondiabetogenic B (EMC-B) variants of encephalomyocarditis virus in various tissues of the murine host was determined. Pancreatic insulin levels were also measured. EMC-D replicated in the spleen, pancreas, heart, lung, and intestines, while EMC-B was limited to the spleen and pancreas. EMC-B interfered with the replication of EMC-D in each of the tissues examined. Insulin levels were initially increased by both viruses. By 4 days postinfection, insulin levels were either normal or undetectable in (EMC-D)-infected animals, but were dramatically elevated in those infected with EMC-B.