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1.
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.  相似文献   
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Effects of 5-fluorouracil (5-FU) and UFT on an experimental liver metastasis model were compared at equi-effective dosage levels against subcutaneous tumor of mouse colon 26. 5-FU at the dosage level of 40 mg/kg suppressed the subcutaneous tumor growth by 70.0% and 45.0% on day 13 and day 18, respectively, and UFT at 20 mg/kg provided almost equal suppression (63.0% and 48.0%). In the liver metastasis model, 5-FU at 40 mg/kg showed more potent prevention of the formation of metastatic foci (94.9%) than did UFT (60.4%) at 20 mg/kg. 5-FU at 40 mg/kg produced a much higher peak serum level of 5-FU than did UFT at 20 mg/kg and also showed a much higher AUC (area under the curve) level in the portal blood. These results suggest that oral administration of 5-FU might be useful in prevention of liver metastasis of colorectal cancer.  相似文献   
4.
Tissue composition and the distribution of body mass are described for four genera of East African Bovidae (Madoqua, Gazella, Damaliscus, Hippotragus) with supporting data from four others (Neotragus, Oryx, Tragelaphus, Connochaetes). These species are high in muscle mass, an adaptation convergent with other high-speed terrestrial cursors, bounders, and saltators. The segments below the elbow/cubitus and knee/stifle/genu joints in small bovids are both lighter in percent of total body mass (8.6% TBM) and less heavily muscled (10-15% of total limb musculature) than those segments in macaques (13.6% TBM, 20-25% of the limb musculature). Bovid species differ from one another in the regional distribution of muscle mass. Madoqua kirkii (4-5 kg) concentrates muscle in the lumbar extensors and hindlimbs; large species such as Damaliscus doreas (50-60 kg) and Hippotragus niger (160-220 kg) distribute it more evenly between the lumbar and cervical regions and between the hindlimbs and forelimbs. Gazella dorcas (10-20 kg) is quantitatively intermediate in those characteristics. The redistribution of muscle mass with increasing size correlates with the loss of axial bending of the vertebral column: in small, hindlimb dominant, 'dorsomobile' species such as Madoqua sagittal mobility increases stride length through 'extended' suspension; in large 'dorsostable' species such as Damaliscus and Hippotragus the vertebral column resists bending, consequently abbreviating or omitting this non-contact phase of the gait cycle. Locomotor adaptation as it is reflected in size, shape, and musculoskeletal structure is the key to habitat choice, dietary specialization, social structure, and male agonistic behavior and, therefore, central to the fabric of behavioral ecology.  相似文献   
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A case of histologically confirmed Paget's disease of the breast in a 72 year old man, without underlying breast carcinoma, is reported. This report raises questions about the pathogenesis of this condition and suggests that Paget's disease is an independent, intraepidermal carcinoma rather than a direct extension of intraductal carcinoma of the breast to the nipple and areola.  相似文献   
6.
We report two cases of successful pregnancy in women with chronic, infantile onset, or type II spinal muscular atrophy, both of whom delivered healthy, unaffected babies. The patients required concurrent management by a physiatrist, pulmonologist, and perinatologist throughout the pregnancy. Complications included recurrent urinary tract infections, dyspnea and worsening of pulmonary function, wheelchair seating and positioning problems, and musculoskeletal and low back pain. These problems resolved postpartum. One woman had vaginal delivery, the other had caesarean section, both of which were well-tolerated. Because of severe musculoskeletal deformity, pelvic assessment is necessary to determine the mode of delivery. The uterus has normal contractility and effective labor patterns can be established. Spinal/epidural anesthesia may be contraindicated because of spine deformity. The pregnancies had no deleterious effect on the progression of the disease in our patients, both of whom reported a positive experience with great personal fulfillment.  相似文献   
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The pharmacological profile of a novel dual inhibitor, tepoxalin and of its carboxylic acid metabolite on cyclooxygenase and lipoxygenase pathways was evaluated by in vitro incubation with synovial tissue. Tissue specimens obtained at surgery in rheumatoid arthritis (RA, n = 10) or osteoarthritis (OA, n = 11) patients were incubated. Tepoxalin (10(-7), 10(-6), 10(-5) M) decreased eicosanoid release calculated in % of tyrode control for OA: LTC4 to 71-33%, 6-keto-PGF1a to 37-20%, PGE2 to 29-6%. For RA: LTC4 to 56-22%, 6-keto-PGF1a to 43-22%, PGE2 to 57-32%. Similarly, its metabolite (10(-7), 10(-5)M) decreased release in OA: LTC4 to 99 and 60%, PGE2 to 42 and 20%, 6-keto-PGF1a to 54 and 25%. In RA:LTC4 to 81 and 45%, PGE2 to 61 and 30%, 6-keto-PGF1a to 46 and 18%. Significance (P < 0.05) was achieved for all but 1 group (LTC4 metabolite at 10(-7)M vs tyrode). In summary a marked and dose dependent decrease of LT and PG release was obtained when incubating the dual inhibitor tepoxalin and its active carboxylic acid metabolite with synovial tissue at doses expected to be reached in the joint during therapy.  相似文献   
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This paper deals with an advanced static Var compensator (ASVC) using quad-series voltage-source PAM inverters. The ASVC consists of four three-phase voltage-source inverters with a common dc capacitor and four three-phase transformers, each primary winding of which is connected in series with each other. Each inverter outputs a square-wave voltage, while the synthesized output voltage of the ASVC has a 24-step wave shape. This results not only in a great reduction of harmonic currents and dc voltage ripples but also in fewer switching and snubbing losses. In this paper, transient analysis is performed with the focus on the response of reactive power and the resonance between the dc capacitor and ac reactors. Experimental results obtained from a small-rated laboratory model of 10 kVA are also shown to verify analytical results based on the p-q transformation. The analytical results help in the design of system parameters such as the capacity of the dc capacitor and feedback gains.  相似文献   
9.
Luteinizing hormone releasing hormone (LHRH) stimulates the development of cellular FSH immunoreactivity in the perinatal hamster adenohypophysis. Because neuropeptide Y (NPY) can act directly on rat adenohypophysial cells to stimulate FSH and LH release and potentiate the stimulatory effect of LHRH on FSH and LH release, we investigated the effects of NPY alone and in combination with a low, ineffective dose of LHRH on inducing cellular FSH immunoreactivity in the neonatal hamster adenohypophysis. Neonatal female pituitary glands were grafted beneath the right renal capsules of hypophysectomized-ovariectomized adult hamster hosts with a catheter implanted in the external jugular vein. After treatment, hosts were decapitated and graft tissue was stained for FSH and LH immunoreactivity. The mean percentage of adenohypophysial cells that stained for FSH was low (2.8%) in grafts in hosts infused continuously with heparinized saline vehicle for 7 days. In other hosts, peptides were pulsed through the catheter every 12 h for 7 days. The mean percentage of FSH cells also was low after pulsing 6 ng LHRH or 2 micrograms NPY but increased substantially when the two peptides were pulsed simultaneously. No differences in the mean percentage of LH cells existed between any of the groups. The results demonstrate that NPY and LHRH can synergize to induce cellular FSH immunoreactivity in the neonatal female hamster.  相似文献   
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