Angiogenesis is an early event in the development of chemically induced skin tumors

In this study we have analyzed the vascular response induced in the two- stage carcinogenesis model in SENCAR mice. The role of angiogenesis has not been explored in this model, which is the paradigm of multistage carcinogenesis and a model for neoplastic lesions derived from exophytic premalignant lesions (e.g. colon carcinoma, bladder papilloma). We investigated if angiogenesis is involved in the formation of papillomas and in the progression from papilloma to carcinoma. To this end we analyzed the vasculature of normal and hyperplastic skin, focal epidermal hyperplasias that are precursors of papillomas, papillomas at different stages and squamous cell carcinomas. We also analyzed the vascularization of papillomas induced in two strains of mice that differ in their susceptibility to malignant progression. We show here that angiogenesis is turned on in the earliest stages of papilloma formation. In late stages, regardless of state of progression, the predominant response is an increase in the size of blood vessels. Thus, in the SENCAR mouse model, representative of exophytic tumors, the angiogenesis switch is a very early event, probably mechanistically related to the development of the primarily exophytic lesions. Therefore, the density of blood vessels cannot be used as a predictor of malignant progression in this model.      

Infestation of Tunga penetrans in villages near Zomba Central Hospital

An outbreak of Tunga Penetrans (Jigger Flea) infestation affecting a number of villages near to a Central Hospital in Malawi is described. Due to the large number of affected individuals, high parasitic load, and extended duration of infection an alternative to the recommended approach of surgical removal of the flea was required. Benzyl benzoate paint and liquid paraffin had been used in local Primary Healthcare settings previously and topical treatment with antiparasitic agents has been advocated in the literature, particularly for severe infestation. Benzyl benzoate and liquid paraffin were applied topically to four adults with numerous jigger flea burrows, and their progress assessed regularly. After completion of 7 days of treatment patients noted that fleas were dislodging spontaneously, and that embedded parasites had not increased in size to the same extent that untreated fleas had in previous infestations. Following confirmation of the viability of its implementation in a resource-poor setting, this treatment regimen has subsequently been adopted by the local branch of the District Health Office for distribution to infected communities.     

Alpha-particle Irradiation of Haemopoietic Tissue in Pre- and Postnatal Mice

Summary

Pregnant mice (at 13 days gestation) and age-matched controls were injected with 30 kBq ²³⁹Pu/kg and the distribution of plutonium in maternal and foetal tissues measured. Approximately 2% of the activity injected into the mother reached each foetus in 24 h, 95% of which was contained in membranes and placenta. The concentration of plutonium in foetal liver was 3 times the average foetal body concentration; both liver and body concentrations in the foetus increased by the end of gestation. Each pup accumulated only 0.01% extra injected activity after 9 days lactation and, as the resulting concentrations in the neonatal skeletion were low, we conclude that the greatest haemopoietic risk to the offspring from mid-term contamination in utero is in the foetal liver (which received an average dose of 10–14 mGy between the time of mid-term contamination and birth). By the end of gestation about one-quarter of the original activity was transferred to foetal tissues from the maternal liver and skeleton. No significant changes in maternal distribution were detected as a result of lactation. The results of this study are discussed, along with a compilation of previously published data.     

Expansion in vitro of retrovirally marked totipotent hematopoietic stem cells

A large number of biologic, technological, and clinical studies await the development of procedures that will allow totipotent hematopoietic stem cells to be expanded in vitro. Previous work has suggested that hematopoiesis can be reconstituted using transplants of cells from long- term marrow cultures. We have used retrovirus mediated gene transfer to demonstrate that marked totipotent hematopoietic stem cells are both maintained and can be amplified in such cultures, and then subsequently regenerate and sustain lympho-myeloid hematopoiesis in irradiated recipients. Marrow cells from 5-fluorouracil-treated male mice were infected with a recombinant virus carrying the neomycin resistence gene and seeded onto irradiated adherent layers of pre-established, long- term marrow cultures of female origin. At 4 weeks, cells from individual cultures were transplanted into single or multiple female recipients. Southern blot analysis of hematopoietic tissue 45 days posttransplantation showed retrovirally marked clones common to lymphoid and myeloid tissues in 14 of 23 mice examined. Strikingly, for 3 of 4 long-term cultures, multiple recipients of cells from a single flask showed marrow and thymus repopulation with the same unique retrovirally marked clone. These results establish the feasibility of retroviral-marking techniques to demonstrate the maintenance of totipotent lympho-myeloid stem cells for at least 4 weeks in the long- term marrow culture system and provide the first evidence of their proliferation in vitro. Therefore, such cultures may serve as a starting point for identifying factors that stimulate totipotent hematopoietic stem cell expansion.