Comparative immunotoxicity of 2,2'-dichlorodiethyl sulfide and cyclophosphamide: evaluation of L1210 tumor cell resistance, cell-mediated immunity, and humoral immunity.

The immunotoxicity of 2,2'-dichlorodiethyl sulfide (sulfur mustard, SM), on humoral and cell-mediated immunity was compared with that of the nitrogen mustard 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazophosphorine 2-oxide (cyclophosphamide, CP). SM and CP had similar effects on thymic and splenic weights, spleen cell number, and the formation of antibody producing cells to sheep red blood cells (sRBC) when examined 5 days after exposure, but differed in their effects on body weights. Although there were no differences in the delayed hypersensitivity response to keyhole limpet hemocyanin, CP and SM had different effects in the L1210 tumor cell allograft rejection assay. CP, but not SM, decreased the 28 day survival rate of allogeneic mice exposed to a sublethal L1210 tumor challenge. The differing effects on survival to the L1210 tumor challenge could not be attributed to a direct cytotoxic effect of SM on the L1210 tumor cells as SM did not increase the survival rate or median survival time of syngeneic mice exposed to a lethal L1210 tumor cell challenge. In summary, SM and CP had immunosuppressive effects in the humoral immune assay. Although neither compound suppressed the delayed hypersensitivity response, CP was found to suppress host resistance to L1210 tumor cells.

Collagenase inhibitors retarding invasion of a human tumor in nude mice.

Tumor invasion has been correlated with the ability of tumor cells to produce collagenolytic enzymes which are capable of degrading normal host tissues. However, the human small cell carcinoma implanted subcutanouesly and growing progressively in athymic (nude) mice produced large quantities of collagenase but did not appear to significantly infultrate adjacent host tissue. In comparison, subcutaneously implanted murine Lewis lung tumors produced similar quantities of collagenase and were locally invasive. The human tumors were surrounded by a compact layer of fibroblast cells in a fibrous matrix. This fibrous sheath exhibited anticollagenase activity and indicated a mechanism of host tissue resistance to invasion via the formation of inhibitors to degradative enzymes produced by tumor cells.

Prophylactic and therapeutic use of tetracycline during an epizootic of ehrlichiosis among military dogs.

An epizootic of canine ehrlichiosis at the Military Working Dog Center, Pakchong, Thailand, was arrested by prophylactic and therapeutic use of tetracycline and by control of ticks. Oral treatment with tetracycline (66 mg/kg of body weight daily for 14 days) effected remission of signs of disease in 60 of 62 clinically affected dogs and resulted in disappearance of serum antibody in 119 (60%) of 198 seropositive dogs treated during the 2-year study period. Transmission of Ehrlichia canis was interrupted by control of ticks and by daily oral administration of tetracycline at a dosage of 6.6 mg/kg of body weight. When the control program was initiated, 100 (57%) of 174 dogs were seropositive, with one-third of these manifesting clinical signs of ehrlichiosis. The proportion of seropositive reactions progressively decreased to 11% after control was established, and the impact of the disease on health and performance of the dogs was greatly reduced. Eight dogs died before institution of control. Two additional dogs died within the first 2 months after control was established. There was no mortality thereafter.

Modification of Venezuelan equine encephalomyelitis virus infection in mice by X radiation.

A highly virulent strain of Venezuelan equine encephalomyelitis (VEE) virus produced less severe histopathologic changes in brain tissues of mice previously exposed to sublethal total-body x-irradiation than it caused in nonirradiated mice. Prior exposure to 600 R of x-irradiation virtually eliminated the lesions of vasculitis and encephalitis that were found in the infected nonirradiated control mice. Mean peak brain lesion scores generally decreased as radiation exposure dose was increased. Irradiation of mice before inoculation often decreased median time to death, whereas the severity of pathologic changes in brain tissues from inoculated irradiated mice was often reduced, without significantly altering ultimate host survival. The inflammatory response did not appear to have a significant role in clearance of this virus from the brain. There was no evidence that participation of the immune response contributed to total mortality from VEE virus encephalitis, as indicated by the failure of radiation immunosuppression to reduce mortality. Death apparently was caused by the direct cytocidal effects of VEE virus replication.

Canine ehrlichiosis (tropical canine pancytopenia) in Thailand.

An epizootic of canine ehrlichiosis has occurred in military working dogs in Thailand. During the epizootic, 161 cases of ehrlichiosis were identified serologically in a population of 316 dogs, and 54 dogs exhibited clinical signs of disease. The epizootic is being controlled by elimination of ticks, by serologic identification and treatment of carriers with 30 mg/lb body weight/day of tetracycline for 14 days, and by continuous daily prophylactic administration of 3 mg/lb body weight/day of tetracycline. Clinical and serologic recognition of ehrlichiosis among pet dogs in widely separated regions of Thailand suggest that the disease has been endemic in Thailand for an extended time. Under such circumstances it is possible that pet and stray dogs have served as a source of infection for the epizootic in military working dogs.

A comparison of the tissue lesions produced in adult hamsters by two strains of avirulent Venezuelan equine encephalomyelitis virus.

Adult hamsters were infected with two avirulent strains of Venezuelan equine encephalomyelitis virus, TC-83 and the small plaque variant (SPV) of Fe 3-7c. Histologic examination showed that significant brain lesions were produced by both strains and affected primarily the olfactory bulbs, lateral olfactory tracts and the pyriform lobes of the cerebral cortex. The type of lesions produced by both strains were similar, but when the two groups were compared, more of the hamsters inoculated with SPV had lesions and they were of greater severity. Outstanding lesions observed were: vasculitis, lymphocytic perivascular cuffing and hemorrhage, demyelination of the lateral olfactory tracts and neuronal necrosis of the olfactory bulbs.