A study of factors regulating the autonomous proliferation of the steroid hormone-induced LJ6195 murine reproductive tract tumor

Neonatal estrogen treatment of BALB/c mice results in the unregulated proliferation of the cervicovaginal epithelium and eventually tumorigenesis. The conversion of the normally estrogen responsive cyclic proliferation of the vaginal epithelium to a continuous estrogen-independent pattern of growth is a complex phenomenon. The aim of this study was to gain an understanding of the mechanism(s) by which steroid hormone administration during a critical period of development alters the cyclic proliferation of vaginal epithelium, ultimately leading to carcinogenesis in the adult animal.^ The LJ6195 murine cervicovaginal tumor was induced by treating newborn female BALB/c mice with 20 $\mu$g 17$\beta$-estradiol plus 100 $\mu$g progesterone for the first 5 days after birth. In contrast to proliferation of the normal vaginal epithelium, proliferation of LJ6195 is not regulated by estradiol. Northern blot analysis of RNA from vaginal tracts of normal mice, neonatal-estrogen treated mice, and LJ6195 indicate that there is an alteration in the expression of several genes such as the estrogen receptor, c-fos, and HER2/neu. In response to neonatal estrogen treatment, the estrogen receptor is down regulated in the murine vaginal tract. Therefore, the estrogen-independent nature of this tissue is established as early as 3 months after treatment. There is strong evidence that the proliferation of LJ6195 is regulated through an autocrine growth pathway. The LJ6195 tumor expresses mRNA for the epidermal growth factor receptor. In addition, conditioned medium from the LJ6195 tumor cell line contains a growth factor(s) with epidermal growth factor-like activity. Conditioned medium from the LJ6195 cell line stimulated the proliferation of the EGF-dependent COMMA D mouse mammary gland cell line in a dose-dependent manner. The addition of an anti-mEGF-antibody to LJ6195 cell cultures significantly decreased growth. These results suggest that the EGF-receptor mediated growth pathway may play a role in regulating the estrogen-independent proliferation of the LJ6195 tumor. ^

Rabies control in the developing world: Results of a cross-sectional study in Bohol, Philippines

Rabies remains a significant problem in much of the developed world, where canine rabies is not well controlled, and the bite of an infected dog is the most common means of transmission. The Philippines continues to report several hundred cases of human rabies every year, and many more cases go undetected. In recent years, the province of Bohol has been targeted by the Philippine government and the World Health Organization for a rabies eradication program. ^ The primary objective of this dissertation research was to describe factors associated with dog vaccination coverage and knowledge, attitudes, and practices regarding rabies among households in Bohol, Philippines. Utilizing a cross-sectional cluster survey design, we sampled 460 households and 541 dogs residing within dog-owning households. ^ Multivariate linear regression was used to examine potential associations between knowledge, attitudes, and practices (KAPs) and variables of interest. Forty-six percent of households knew that rabies was spread through the bite of an infected dog. The mean knowledge score was 8.36 (SD: ± 3.4; range: 1–24). We found that having known someone with rabies was significantly associated with an almost one point increase in the knowledge score (β = 0.88; p = 0.02). The mean attitudes score was 5.65 (SD: ± 0.63; range: 2–6), and the mean practices score was 7.07 (SD: ± 1.7; range: 2–9). Both the attitudes score and the practices score were positively and significantly associated with only the knowledge score and no other covariates. ^ Multivariate logistic regression was used to examine associations between dog vaccination coverage and variables of interest. Approximately 71% of owned dogs in Bohol were reported as vaccinated at some time during their lives. We found that a dog's age was significantly associated with vaccination, and the odds of vaccination increased in a linear fashion with age. We also found that dogs had approximately twice the odds of being vaccinated if they were confined both day and night to the household premises or if the owner was employed; however, these results were only marginally significant (p = 0.07) in the multivariate model. ^ Finally, a systematic review was conducted on canine rabies vaccination and dog population demographics in the developing world. We found few studies on this topic, especially in countries where the burden of rabies is greatest. Overall, dog ownership is high. Dogs are quite young and do not live very long due to disease and accidents. The biggest deterrent to vaccination is the rapid dog population turnover. ^ It is our hope that this work will be used to improve dog rabies vaccination programs around the world and save lives, both human and canine.^