Nehama Sharon

Congenital lymphocytic choriomeningitis virus infection in gnotobiotic mice.

Summary The LCM virus penetrated the “germfree barrier,” thus reaffirming the congenital dissemination of the virus. The lesions associated with LCM infection in the gnotobiotic mice were clearly related to a hyperreactive immunologic mechanism, which induced degenerative kidney changes, depletion of cortical thymocytes, lymphoid cell infiltrations of many organs, and hypergam-maglobulinemia.

Virus-like particles in cultures of McCoy cells.

Virus-like particles similar to types A and C tumor viruses as classified by Bernhard and others, were consistently found in association with the human synovial cell line identified as the McCoy cell. It was occasionally possible to observe cylindrical structures among the spherical virus-like particles in the cytoplasmic vacuoles of the cells. The significance of the virus-like particles remains to be demonstrated.

Effects of cyclophosphamide on lesions induced by persistent LCM virus infection in gnotobiotic mice

Cyclophosphamide (CP) has shown therapeutic benefits for treatment of immnoproliferative disease associated with persistent LCM virus infection. Depending on the age of LCM mice at onset of the treatment, the classical lesions were prevented or reversed by treatment with the drug. Reappearance of lesions following cessation of treatment coincided with the time period in which lesions originally appeared in the organs, namely about 5 months. CP can control the symptoms and lesions of the disease, but does not show antiviral activity.

Immunoproliferative Effects of Lymphocytic Choriomeningitis Virus in Germfree Mice

Summary Mice with congenitally-acquired LCM virus infection were maintained under germfree condtions for 12 months. With advancing age, the mice showed histological evidence of uncontrolled immunoproliferative changes: the enlarged lymph nodes and spleens contained large germinal zones and numerous plasma cells. The cortical cells of the thymus glands were progressively depleted of cortical cells, became shrunken, eventually swollen, and infiltrated with large plasma cells. The visceral organs had perivascular infiltrations of lymphoid and plasma cells which displaced significant amounts of parenchyma. The plasmacytomas which developed differed from the lesions associated with murine leukemia.

Induction of prolonged latency in psittacosis-infected cells by aminopterin.

Summary Psittacosis virus was sensitive to aminopterin during the early stages of replication in tissue cultured cells. After hour 20 of virus infection, a factor appeared in the infected cells which reversed the effect of aminopterin on virus. Folinic acid reversed the inhibitory effect of aminopterin on virus and cells. Psittacosis virus, inhibited in tissue culture cells by medium containing aminopterin, remained latent for at least 4 weeks, and resumed replication after addition of folinic acid to the culture medium.

Prevention and Treatment of Spontaneous Leukemia in Germfree AKR Mice

Summary Germfree AKR mice were inoculated with cyclophosphamide at weekly intervals for long periods. Leukemia was prevented for 13 months so long as treatment was continued, but the disease appeared after the treatment was stopped. Similar treatments of leukemic AKR mice deferred the fatal issue significantly. However, the leukemic process was suppressed and not cured. Germfree AKR mice offer distinct experimental advantages for studies on leukemia.

Congenital LCM Virus Infection in “Germ-Free” Haas Strain Mice

“Germ-free” Haas strain mice are congenitally and persistently infected with LCM virus which is associated with a life-limiting immunoproliferative syndrome. The principal lesions are lymphoid infiltrations of visceral organs, elevated levels of serum globulins, and glomerulonephritis. The germ-free mice tolerate maximum subtoxic doses of cyclophosphamide, from which conventional counterpart mice die of bacterial infections. Cyclophosphamide treatments have prevented the development of and have reversed the lesions in young and old Haas strain mice, respectively. Intermittent cyclophosphamide therapy has elicited new reticulum cell sarcomas in Haas strain mice. Thus far, adoptive immunization procedures have not interrupted the congenital passage of LCM virus, and the results with radiation-induced allogeneic chimeras are incomplete. The protean manifestations of disease in Haas mice provide model experimental systems for congenital and persistent infection, immunoproliferative disease, immune complex disease, immunological tolerance, viral and cancer chemotherapy, and tissue transplantation procedures.

Immunohistochemical method for detection of vaccinia virus.

Summary An adaptation of the enzyme-conjugated antibody technique for detection of vaccinia virus in tissue cultures was described. Gamma globulin, precipitated from rabbit antiserum, was conjugated to horseradish peroxidase with the aid of the bifunctional reagent FNPS. Vaccinia virus-infected cells on coverslips which were reacted with the enzyme-antibody complex and stained with diaminobenzidine, demonstrated the dark-brown cytoplasmic locatization of the antigen-antibody enzyme complex. Pretreatment with unlabeled antibody blocked the appearance of the cytoplasmic inclusions. The cell preparations were examined by ordinary light microscopy.

Synthesis of Hepatotoxic Agents in Germfree and Conventional Mice Which Had Been Fed NaNO2 and Dimethylamine

Summary In vivo production of toxic agent(s) was demonstrated in GF and conventional mice by feeding them subtoxic doses of NaNO2 and dimethylamine. Two effects were demonstrated in the mice: acute deaths in some of them within 24 hr after administration of the two drugs; and extensive necrosis in the livers of survivors which were examined 3 days later. GF CFW mice were more sensitive to the toxic effects of NaNO2 than conventional CFW mice, and conventional and GF Swiss-Webster mice. The microbial flora has been excluded as having a role in the in vivo synthesis of this toxic agent (s), which we assume to be nitro-soamine.