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.     

AN ASSESSMENT OF CRACK CLOSURE AND THE EXTENT OF THE SHORT CRACK REGIME IN Q1N (HY80) STEEL

Abstract— The paper addresses some aspects of the differences in fatigue crack growth rate behaviour and threshold values obtained for long through-cracks, short through-cracks and surface cracks. Attention is focused on plasticity induced closure in the wake behind the growing crack tip. For long cracks at high K _max, closure is found to depend in a linear manner on K _max, i.e. K _op, increases with the size of the monotonic plastic zone. Closure increases at low δ K and this is primarily a consequence of the load shedding procedure. If short through-cracks are prepared by machining specimens containing long cracks, a substantial part of the plastic wake is removed and this can produce marked effects on the closure contribution during subsequent growth. The length of crack "closed" in a long crack threshold test was found to be of the order of 1 mm. Cracks less than this length exhibited "short crack" behaviour: greater than this length, they behaved as "long cracks", with plastic wake effects apparently fully operative. Small surface cracks exhibit "long crack" behaviour at lengths as short as 0.2 mm and reasons for this are discussed.     

Foundations'' impact on policy making: results from a pilot study

Thirty-two consecutive patients with haematological disorders, in need of a permanent central venous catheter (CVC) were randomly allocated to have their CVC bandages (Tegaderm) changed once (OAW, n = 20) or twice (TAW, n = 19) a week. The two randomization arms were balanced in respect of age, sex, and underlying disease. The exit site of the CVC was inspected daily through the transparent bandage and erythema was noted. If severe erythema occurred, daily wet gauze dressings were applied. Samples for bacterial cultures were taken from the exit site of the CVC at every change of bandages. There was no difference in complications leading to removal of the CVC between the two groups (7/20 OAW vs. 7/19 TAW) or in CVC survival-time (P = 0.4). However, the OAW group had more positive CVC tip cultures (OAW 11/14 vs. TAW 2/9; P < 0.05) and a tendency to: (i) more extra dressings (P = 0.08); (ii) more cultures from the exit skin site showing high numbers of colony forming units (P = 0.07); (iii) shorter time to first exit site infection (P = 0.09); and (iv) more Gram-positive septicaemias (P = 0.08). Both clinical and bacteriological data in this study indicate that changing transparent polyurethane CVC bandages twice a week is superior to once a week.     

Percutaneous transhepatic drainage of the nondilated biliary system

Although reticulocyte counts can be reliably performed for up to 48 h after storage in EDTA, it is unclear whether this is applicable to the pediatric age group. In order to evaluate this, manual reticulocyte counts were performed on 20 specimens from pediatric patients stored at 4 degrees C for up to 24 h post collection. Samples were evaluated at 1-3, 6, 12, 18, and 24 h after storage in EDTA vacutainer tubes at 4 degrees C. The age of the subjects ranged from 1 day to 9 years with a median age of 3 years. Patients' reticulocyte counts ranged from 0 to 27% (5.89 +/- 7.21). No clinically significant changes were evident in the reticulocyte count over 24 h after specimen collection. The mean of the 20 specimens at 1-3 h was 5.50 and at 24 h was 5.40 (P > .05). The standard deviation of the mean values ranged from 7.03 to 7.26 (P > .05). The results indicate that reticulocyte counts may be performed on previously drawn blood held at 4 degrees C for up to 24 h post collection in a pediatric population without significant difference from baseline values.     

Structure and gene expression of avian cyclin D2

Avian cyclin D2 (Cyl D2)-encoding cDNA clones were isolated from a chicken UG9 T-cell lambda gt10 library. Sequence analysis revealed a high degree of sequence conservation with both the mouse and human Cyl D2, and somewhat lower similarity with the mouse and human Cyl D1 and D3. The homology is highest between species in the Cyl-box domain which is well conserved among human, mouse and chicken. A single 6.0-kb CYL2 mRNA is produced in both avian B- and T-cells, as expected.     

Microstructure-composition relationships and Ms temperatures in Fe-Cr-Mn-N alloys

Microstructure-composition relationships and M_s temperatures have been determined in high purity nitrided Fe-Cr-Mn alloys, as part of a program to develop improved corrosion-abrasion resistant steels with unstable austenitic microstructures. Compositions in the range 8 to 12 pct Cr, 0 to 10 pct Mn, and 0 to 0.6 pct N were investigated by a resistivity technique to determine M_s temperatures and by X-ray diffraction and metallography to determine constitution. Hardness measurements were also made. At the low alloy end of the range, microstructures after annealing and air cooling are fully martensitic while at the high alloy end they are fully austenitic. At intermediate compositions, mixed martensite-austenite microstructures (with epsilon present as a minor phase in some cases) and unstable austenitic microstructures are obtained. The austenitic alloys contain a high density of stacking faults and the unstable austenitic alloys transform to martensite on deformation. At low N contents (up to at least 0.25 pct N) the M_s-composition relationship is linear and described by: M_s = 555 - 9(Cr - 8) - 40Mn - 450N [1] where M_s is in °C and Cr, Mn, and N are the weight percentages of these elements. At higher N contents, the M_s generally falls more rapidly with increasing nitrogen content. Nitrogen solubility at 1050 °C exceeds about 0.3 pct in all alloys and increases with increasing Cr and Mn content. In commercial purity steels, unstable austenitic microstructures are expected to be obtained in compositions around 10 to 14 pct Cr, 8 to 12 pct Mn, and 0.1 to 0.3 pct N when the total level of these elements is selected to ensure the M_s is below room temperature.     

An investigation of crack closure and the propagation of semi-elliptical fatigue cracks in Q1N (HY80) pressure vessel steel

The results of an experimental investigation of the effect of crack closure on the propagation of semi-elliptical fatigue cracks are presented. Load-shedding fatigue threshold tests were carried out at stress ratios of 0.2, 0.35, 0.5 and 0.7. Crack closure was measured at the surface and depth positions using backface strain gauges, near-tip gauges, and a clip gauge. Differences between the surface and depth growth behaviour are explained by considerations of the effects of the transition from plane stress conditions at the surface to plane strain conditions at the depth. The effects of stress ratios are attributed largely to differences in the crack opening displacement, which result in asperities coming into contact to induce roughness-induced crack closure.     

The long string as a field probe

We show how a long string can be used to probe the incident field across the target zone of a radar cross section (RCS) test range. The string may be stretched horizontally from wall to wall, or vertically from floor to ceiling. One end of the string is fixed and the other end is moved by an actuator mounted in the wall or ceiling. The resulting motion changes the angle of the string with respect to the incident-field direction, during which time the coherent radar echo is recorded as a function of the string angle. The coherent signal-as-a-function-of-angle data are then transformed to the cross-range domain using the fast Fourier transform (FFT), whence we obtain a chart of the incident field amplitude as a function of cross-range distance. Numerical examples are presented that show how variations in the incident field influence the string echo. A sample of experimental data shows that the processed data are readily interpreted.     

Effects of vesnarinone, a novel orally active inotropic agent with an immunosuppressive action, on experimental cardiac transplantation in rats

BACKGROUND: Vesnarinone (VES) has been used for treatment of patients with congestive heart failure. In addition to inotropic effects, it seems to have immunosuppressive action. We tested the hypothesis that VES suppresses graft rejection, inotropic dysfunction caused by early rejection, and chronic coronary obstruction in a heterotopic rat cardiac transplantation model. METHODS: (1) To study acute rejection, hearts from Lewis-Brown Norway (LBN) rats were transplanted into Lewis rats, which were treated with or without VES (50 or 100 mg/kg/day orally). (2) In a functional study, LBN hearts with or without VES (100 mg/kg/ day) were isolated and perfused on day 3 after transplantation to assess inotropic response to isoproterenol (3 x 10(-8) M). (3) To study chronic rejection, Lewis hearts were transplanted into Fisher 344 rats, which were treated with or without VES (50 mg/kg/day) for 90 days. Coronary obstructive disease was assessed by morphometric analysis. There were five to six animals in each group. RESULTS: (1) VES (100 mg/kg/day) prolonged LBN heart survival (11.7 +/- 0.7 vs. 9.6 +/- 0.7 days in control; P < 0.05). (2) Left ventricular developed pressure was depressed in transplanted hearts regardless of VES treatment (84 +/- 12, 90 +/- 8 vs. 144 +/- 16 mmHg in untransplanted hearts; P < 0.01). The developed pressure after administration of isoproterenol in VES-treated hearts (184 +/- 20 mmHg) was higher than transplanted hearts without VES (118 +/- 16 mmHg; P < 0.05), and similar to untransplanted hearts (203 +/- 27 mmHg; P = NS). (3) Transplanted hearts treated with or without VES showed similar grades of rejection (2.0 +/- 0.3 vs. 2.6 +/- 0.2; P = NS), intimal area (6,996 +/- 3,186 vs. 13,441 +/- 5,165 microns2; NS), and coronary luminal obstruction (45 +/- 16% vs. 67 +/- 14%; NS). CONCLUSIONS: VES produces mild prolongation in survival of rat heart grafts, but has no significant effect on chronic graft atherosclerosis. VES preserves the positive inotropic effects of isoproterenol that are otherwise deteriorated by early acute rejection.     

Fluorescence in situ hybridization analysis of chromosome 1p36 deletions in human MYCN amplified neuroblastoma

Artificial illumination is an important factor in the management of layers. In this study, a new monochromatic light system was developed for egg layers. Prelaying pullets (Lohmann) were marked and housed in nine light and temperature control rooms (15 battery cages, 3 hens per cage; n = 45), divided into three light treatments: 0.1 and 0.01 W/m2 light intensity using light emitting diode (LED) lamps and 0.1 W/m2 using mini-fluorescent bulbs (PL) (control). In each of the LED rooms, three wavelengths were tested: 560 (n = 9), 660 (n = 9), 880 (n = 6), and 660 intermitted lighting (15 min light 45 min dark, 660IN) (n = 9). Birds were exposed to 12 h light and 12 h of darkness using PL lamps. At 21 wk of age, the light period was increased to 12.75 h by using 5.5 h of LED lamps and 7.25 of PL light source for Groups 1 and 2, the third group received 12.75 h of PL light. Until 28 wk of age, light hours increased by 0.5 h/w using LED light for Groups 1 and 2 and PL source for the third group, reaching 16 h of light at 28 wk of age. Egg production and feed consumption were recorded daily; egg components were recorded weekly for 10 mo. A significant reduction in egg production was observed in all 880nm groups; no differences in egg production and quality were found in the other groups. Feed consumption was significantly lower by 7% in all 0.01 W/m2 groups. We suggest that an important reduction in rearing costs of laying hens may be obtained by using this system.