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.     

Reduction of sodium-accelerated oxidation of silicon nitride ceramics by aluminium implantation

Norton NBD 200 silicon nitride ceramics were implanted with sodium to a dose of 7.0×10¹⁵cm^-2 at 72 keV (1 at% peak sodium content at 100 nm). The sodium-implanted samples were further implanted with aluminium to 7.3×10¹⁵cm^-2 at 87 keV (1 at% peak aluminium content at 100 nm). The implanted and unimplanted samples were oxidized in 1 atm dry oxygen at 1100 and 1300°C for 2–6 h. Profilometry and scanning electron microscopy measurements indicated that sodium implantation led to up to a two-fold increase in the oxidation rate of silicon nitride. The sodium effect was effectively neutralized when aluminium was co-implanted. The opposite effects of sodium and aluminium on the oxidation resistance of silicon nitride can be attributed to their different roles in modifying the structure and properties of the oxide formed. This revised version was published online in November 2006 with corrections to the Cover Date.     

An effective rhodium catalyst system on the synthesis of acetic acid from methyl formate

Rh/Lil/SnR₄ is an effective catalyst system for the conversion of methyl formate to acetic acid under carbon monoxide pressure. The effects of solvent and initial CO partial pressure on the turnover rate of the reaction were investigated. The possibility of replacing some of the iodide promoters by tin compounds has been probed.     

Quality of data regarding diagnoses of spinal disorders in administrative databases. A multicenter study

The purpose of the present study was to evaluate the accuracy of data regarding diagnoses of spinal disorders in administrative databases at eight different institutions. The records of 189 patients who had been managed for a disorder of the lumbar spine were independently reviewed by a physician who assigned the appropriate diagnostic codes according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). The age range of the 189 patients was seventeen to eighty-four years. The six major diagnostic categories studied were herniation of a lumbar disc, a previous operation on the lumbar spine, spinal stenosis, cauda equina syndrome, acquired spondylolisthesis, and congenital spondylolisthesis. The diagnostic codes assigned by the physician were compared with the codes that had been assigned during the ordinary course of events by personnel in the medical records department of each of the eight hospitals. The accuracy of coding was also compared among the eight hospitals, and it was found to vary depending on the diagnosis. Although there were both false-negative and false-positive codes at each institution, most errors were related to the low sensitivity of coding for previous spinal operations: only seventeen (28 per cent) of sixty-one such diagnoses were coded correctly. Other errors in coding were less frequent, but their implications for conclusions drawn from the information in administrative databases depend on the frequency of a diagnosis and its importance in an analysis. This study demonstrated that the accuracy of a diagnosis of a spinal disorder recorded in an administrative database varies according to the specific condition being evaluated. It is necessary to document the relative accuracy of specific ICD-9-CM diagnostic codes in order to improve the ability to validate the conclusions derived from investigations based on administrative databases.     

Lowered antioxidant status of red blood cells in post-parturient haemoglobinuria of buffaloes

Vaccination against tick-borne encephalitis with FSME-Immun vaccine was started in the Department of Infectious Diseases, University Medical School of Bia?ystok, Poland, in 1992. No serious adverse reactions after vaccine administration were observed. Post-vaccine side effects were reported in 242 (11.3%) persons after the first dose (n = 2,135) and only in 14 patients (1.2%) after the second one (n = 1,183). These effects were mild and transitory. No relationship was observed between the frequency of adverse reactions, general or local, and the initial anti-TBE virus antibody titres or the age of the immunized individuals. Post-vaccine side effects were reported significantly more frequently among people not bitten by ticks.     

Temporal order and functional analysis of mutations within the Fli-1 and p53 genes during the erythroleukemias induced by F-MuLV

The erythroleukemias induced by Friend murine leukemia virus (F-MuLV) result from the accumulation of a number of genetic changes, including activation of the Fli-1 proto-oncogene and inactivation of the p53 tumor suppressor gene. We have determined the temporal order of mutation of the genes involved in this multistage malignancy, by serial in vivo transplantation of F-MuLV induced primary erythroleukemias into syngenic Balb/c mice. These primary tumors are capable of growing when transplanted into syngenic mice, but die after several days of in vitro culture. From the transplanted tumors grown in syngenic mice, erythropoietin-dependent cell lines were established in culture that are clonally related to cells in the primary tumors. We show that retroviral insertional activation of the Fli-1 ets family member is the first detectable genetic event in F-MuLV induced primary erythroleukemias. Mutations in the p53 gene were observed in the Epo-dependent cell lines but not in the transplanted erythroleukemias used to establish these cell lines in culture. These data suggest that activation of Fli-1 plays an important role in the early stages of F-MuLV-induced leukemia, perhaps by altering the self-renewal probabilities of erythroid progenitor cells and that p53 mutations immortalize these cells, enabling them to grow in vitro in the presence of Epo.     

Family practice physicians' firearm safety counseling beliefs and behaviors

The purpose of this study was to identify family physicians' firearm safety counseling beliefs and behaviors. A survey was mailed to a random sample of 600 members of the American Academy of Family Physicians. A three wave mailing technique was used to maximize the response rate and yielded 271 usable surveys (55% response rate). Outcome measures included training experience in firearm safety counseling, the prevalence of firearm safety counseling by family physicians, and their perceptions regarding such counseling. The majority (78%) of family physicians lacked formal training on how to counsel patients about firearm safety and 49% believed more time should be spent in residency programs on firearm safety counseling. The majority (84%) of respondents never or rarely counseled patients on firearm safety and 50% believed firearm safety counseling should be a low priority in their delivery of primary care. The majority of respondents did not regularly counsel patients about firearm safety, did not believe firearm safety counseling should be a priority, and did not believe firearm safety counseling would be effective in reducing firearm-related trauma.