Inhibition of G1 cyclin-dependent kinase activity during growth arrest of human breast carcinoma cells by prostaglandin A2

Prostaglandin A2 (PGA2) potently inhibits cell proliferation and suppresses tumor growth in vivo, but little is known regarding the molecular mechanisms mediating these effects. Here we demonstrate that treatment of breast carcinoma MCF-7 cells with PGA2 leads to G1 arrest associated with a dramatic decrease in the levels of cyclin D1 and cyclin-dependent kinase 4 (cdk4) and accompanied by an increase in the expression of p21. We further show that these effects occur independent of cellular p53 status. The decline in cyclin D and cdk4 protein levels is correlated with loss in cdk4 kinase activity, cdk2 activity is also significantly inhibited in PGA2-treated cells, an effect closely associated with the upregulation of p21. Immunoprecipitation experiments verified that p21 was indeed complexed with cdk2 in PGA2-treated cells. Additional experiments with synchronized MCF-7 cultures stimulated with serum revealed that treatment with PGA2 prevents the progression of cells from G1 to S. Accordingly, the kinase activity associated with cdk4, cyclin E, and cdk2 immunocomplexes, which normally increases following serum addition, was unchanged in PGA2-treated cells. Furthermore, the retinoblastoma protein (Rb), a substrate of cdk4 and cdk2 whose phosphorylation is necessary for cell cycle progression, remains underphosphorylated in PGA2-treated serum-stimulated cells. These findings indicate that PGA2 exerts its growth-inhibitory effects through modulation of the expression and/or activity of several key G1 regulatory proteins. Our results highlight the chemotherapeutic potential of PGA2, particularly for suppressing growth of tumors lacking p53 function.     

Common region of ALL-1 gene disrupted in epipodophyllotoxin-related secondary acute myeloid leukemia

Translocations at chromosomal band 11q23 characterize most de novo acute lymphoblastic leukemias (ALL) of infants, acute myeloid leukemias (AML) of infants and young children, and secondary AMLs following epipodophyllotoxin exposure. The chromosomal breakpoints at 11q23 have been cloned from isolated cases of de novo ALL and AML. Using an 859-base pair BamHI fragment of human ALL-1 complementary DNA that recognizes the genomic breakpoint region for de novo ALL and AML, we investigated two cases of secondary AML that followed etoposide-treated primary B-lineage ALL. In the first case, the translocation occurred between chromosomes 9 and 11 and the breakpoint at 11q23 localized to the same 9-kilobase region of the ALL-1 gene that is disrupted in most of the de novo leukemias. In the second case the translocation was between chromosomes 11 and 19. The breakpoint occurred outside of the ALL-1 breakpoint cluster region.     

NMR spectroscopy of human post mortem cerebrospinal fluid: distinction of Alzheimer''s disease from control using pattern recognition and statistics

Mutations of ras oncogenes in 37 human stomach cancers and 13 adenomas were investigated with regard to the histological phenotypes using polymerase chain reaction (PCR), allele-specific oligonucleotide hybridization and/or direct sequencing of the PCR products. The ras mutation was found only in one case (2.7%), the histology of which was poorly differentiated adenocarcinoma. We found no mutation in stomach adenomas. The mutation consisted of a guanine-to-adenine transition in the first base of codon 13 of c-Ki-ras which replaced wild-type glycine with serine, indicating that a putative glycine-to-aspartic acid change is not necessarily the critical event for c-Ki-ras gene activation in codon 13. These results further confirm the infrequency of ras mutation in stomach tumors and also suggest that ras mutations are not specific to the differentiated type of stomach cancer.     

Intraocular pressure fluctuations during scleral buckling surgery

PURPOSE: The purposes of this study are to measure real-time intraocular pressure (IOP) during scleral buckling and to determine the effects of elevated IOPs on ocular perfusion. PATIENTS AND METHODS: A standard 4-mm, 20-gauge infusion cannula was inserted through the pars plana, connected to a standard hemodynamic monitoring unit with an electronic pressure transducer, and calibrated. The authors measured real-time IOP in 20 eyes undergoing scleral buckling surgery for primary rhegmatogenous retinal detachments and determined the IOP required to close the central retinal artery. Pressure measurements were read from the monitor videoscreen intraoperatively and from a continuous paper tracing postoperatively. RESULTS: The patients ranged in age from 24 to 88 years (mean, 59.7 years). The highest IOP elevations occurred during scleral depression and cryopexy, ranging up to 210 mmHg (mean, 116 mmHg). Pressures at which the central retinal artery closed ranged from 48 to 110 mmHg (mean, 79.2 mmHg). Manipulations of the globes caused IOPs greater than the central retinal artery perfusion pressures in 13 of the 20 patients. The duration of pressures in excess of the central retinal artery perfusion pressure ranged from 6 to 402 seconds (mean, 118.8 seconds). There were no intraoperative or postoperative complications from the infusion cannula. CONCLUSIONS: Conventional scleral buckling surgery causes wide fluctuations in IOP and may impair ocular perfusion. Additional studies are needed to determine the long-term consequences of these pressure elevations.     

低价、高效、微波产品用的TPA覆铜版

随着信息产业的飞速发展,高频信号设备,如高速计算机、移动电话、卫星通信等,都已从兆赫频段扩展到千兆赫,这就意味着对它们所用的微波电路基板提出了更高的要求.长期以来,高频微波基板几乎没有越出使用聚四氟乙烯的老传统,但是,它有若干缺点玻璃化温度低,故刚性差;加工复杂,故成本高;金属化孔镀层与孔壁的结合力弱,故可靠性不高. 多年来,美国GIL科技公司一直在研制替代聚四氟乙烯的材料,经过姐妹公司的合作,终于研制成功了TPA板材,这种材料克服了上述缺点,从而获得了美国专利.本文介绍了TPA层压板的电气特性、机械特性和热效应,给出了许多宝贵数据.