Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.     

The nervous system function of patients with periodontitis

Analysis of the function of the nervous system, based on clinical, neurological, and psychological studies in 78 patients with generalized periodontitis, revealed central regulation disorders without signs of organic lesions of the brain in 76% patients. The authors claim that stress and a high level of personal anxiety may be responsible for the development of these disorders, which was confirmed by the results of psychological testing.     

Quenching of chlorophyll fluorescence by quinones

Obese (Lepr(fa)/Lepr(fa)) Zucker rats have a missense mutation in the leptin receptor gene. One amino acid substitution in the extracellular domain common to all known leptin receptor proteins results from this mutation. Obese Zucker rats are unable to respond behaviorally to leptin which is peripherally administered. However, conflicting reports exist on whether obese Zucker rats can respond to centrally administered leptin. The purpose of this study was to determine whether obese Zucker rats responded behaviorally and metabolically to intracerebroventricularly (i.c.v.) administered leptin and to compare the responses of lean and obese Zucker rats. We found that both lean and obese Zucker rats had similar body weight and food intake responses when administered a single i.c.v. leptin injection in a range of doses (1.25, 2.5, 5, and 10 microg), as well as daily i.c.v. administered leptin for five consecutive days. Both single and daily leptin administration also decreased respiratory quotient (RQ) similarly in lean and obese Zucker rats, indicating mobilization of fat as an energy source for leptin-treated rats. After withdrawal of daily leptin treatment, lean and obese Zucker rats exhibited different recovery responses. It is concluded that obese Zucker rats can respond to exogenous leptin when leptin is delivered into the brain ventricles.     

Genetic definition of a new bovine papillomavirus type 1 open reading frame, E5B, that encodes a hydrophobic protein involved in altering host-cell protein processing

We have previously observed that bovine papillomavirus type 1 (BPV-1) induces the appearance of five cellular proteins in C127 mouse fibroblasts, four of which appear to arise by altered processing of resident endoplasmic reticulum proteins. Studies of various cell lines revealed that expression of the 3' end of the BPV early region was sufficient for induction of these changes. To identify the BPV gene responsible, we have utilized the simian virus 40 (SV40)/BPV-1 recombinant virus Pava-1, which expresses the 3' end of the BPV early region behind an SV40 early promoter. C127 cells infected with Pava-1 for 48 h show the expected BPV-associated alterations, as do cells infected with Pava constructs mutated in the E5 or E2 genes. However, a mutation in the start codon of a previously ignored open reading frame extending from nucleotides 4013 to 4170 (E5B) eliminated the BPV-associated changes. Similar results were obtained with COS cells infected with the Pava mutants and C127 cells transformed by full-length mutated BPV. Despite its influence on the processing of cellular endoplasmic reticulum proteins, this mutation in E5B did not alter BPV-transforming efficiency or the ability of transformants to form colonies in soft agar. The E5B open reading frame encodes a hydrophobic 52-amino-acid polypeptide that shares structural similarities with HPV6 E5A and HPV16 E5. Speculations on a role for E5B in the viral life cycle are discussed.     

Health education lessons learned: the H.A.P.I. Kids Program

Challenges exist for effective health communication and health education within diverse populations of the United States. This article addresses the development process for educational materials and lessons learned from the Healthy Asian and Pacific Islander (H.A.P.I.) Kids Program, a vaccination demonstration project funded by the Centers for Disease Control and Prevention to promote catch-up hepatitis B vaccination for older American Asian and Pacific Islander children. Simplicity and a common message were incorporated in multiple strategies to disseminate information to a diverse population. Community representatives from the Cambodian, Hmong, Filipino, Lao, and Vietnamese communities were instrumental in the material development process, which included needs assessment, design, and translation. By making the target community part of the development process, important health messages can be disseminated effectively, carrying great impact to an otherwise hard-to-reach community.