Bioterror, agroterror, and new diseases.

As research techniques and biotechnology advance, the risk for potential bioterrorism increases due to the ease of creating or modifying virulent pathogenic microorganisms. In addition, the destruction of natural habitats to a range of animals and microbial species that are normally sequestered in these areas may bring forth new diseases to humans.

Attempts to induce differentiation of neoplastic cells to normal.

Extract: It was a long time dream of oncologists to find agents which would cause differentiation to normal of neoplastic cells, thus "taming cancer" without harming normal cells. Our group was involved in such attempts for several decades. Here we summarize some of these studies as well as those of other investigators. Regulation of the differentiation of embryonic cells has been the subject of investigation for many decades. It was thought that "original organizers" appear in the upper lip of the gastrula stage of the mammalian embryo which then induces the production of further "sub organizers" and "sub-sub organizers" which are involved in eventually bringing the entire early embryo to a stage of differentiation. In early experiments we found that in tadpole embryos removal of part of the upper lip of the gastula could be substituted by local insertion of gels containing adenosine triphosphate (ATP), adenosine-3-phosphoric acid, or adenosine-5-phosphoric acid.

Hemophilia D factor (factor XII), red-cell deformability and platelet aggregates in raptors.

In a spectrum of raptorial birds hemorrheologic factors were determined compared to normal human values. Significant findings were that Hageman factor (factor XII) levels were very low, the red-cell filteration rate was low, but the platelet-aggregate ratio was in the normal range. Relatively large, nucleated red cells appeared to be less flexible-deformable--than normal human red cells. Microvessel density (MVD) appeared to be in the normal range, but increased average capillary diameter may explain the lack of microvascular abnormalities. Hageman factor deficiency in raptors is comparable to human hemophilia D. However, the mechanisms of the lack of obvious thromboembolic and/or hemorrhagic phenomena may require further investigation.

Studies on splenic population size feedback control regulatory mechanisms.

In previous studies, experimental splenosis was produced in normal rodents and in animals following splenectomy. Splenosis was more in splenectomised than in normal animals. In the present study, in animals into whom splenic fragments were implanted subcutaneously, there were less peritoneal splenic growth areas than in controls. The hypothesis is presented that there is a population size feedback control regulatory mechanism operating in splenic growth and regeneration. If such regulators are present in the circulation, administration of normal plasma should inhibit splenosis and this may serve as a model to isolate such regulators. This was not the case in these experiments.

Studies on the radioprotective effect of etiocholanolone.

One-hundred forty male mice of an inbred strain (C3H/St) were divided into four groups of thirty-five each and were given total body irradiation of 750 cGy. After X-irradiation, one group was given etiocholanolone alone, the other was given bone marrow alone, a third was given both of these. One group was used as a control and was given no treatment after irradiation. The bone marrow used was obtained from the same inbred strain of mice. The most remarkable hematologic recovery was seen in the group which was given both etiocholanolone and bone marrow. The groups given only etiocholanolone or only bone marrow recovered better than the control group. Overall survival was best for the group receiving both modes of treatment and worst for the control group. Survival for the groups receiving a single mode of treatment lay in between the other two mentioned above.

Breast cancer in intraductal carcinogen-treated non-human primates.

Eight female Macaca arctoides monkeys were given dimethylbenzanthracene (DMBA) directly into the milk ducts. During a 4-year observation period, ending with euthanasia and autopsy, no mammary cancers were noticed. However, one animal developed a superficial localized squamous cell carcinoma. DMBA is highly carcinogenic in rodents, e.g. producing a high incidence of breast cancer in C3H mice. It was concluded that carcinogenicity testing should be extended beyond testing in rodents to non-human primates in order to distinguish "primary rodent carcinogens" from those highly active in primates as well. Studies are in progress to study carcinogens in human cell lines transplanted into nu/nu mice.