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991.
-This review focuses on the regression of atherosclerosis in humans and experimental animals. It highlights the difficulties to determine unequivocally whether with a given therapeutic intervention, such as diet, drugs, or apheresis, the progression of lesions was curtailed or bona fide regression of atherosclerotic lesions was achieved. It seems appropriate to mention that 2 very different ways to measure regression were used in experimental animals and in humans. Regression in animals was determined mainly in the aorta or coronary arteries isolated at post mortem, and the criteria used were degree of sudanophilia and/or aortic wall thickness and cellular composition or cholesterol content. In humans, the evaluation of regression relied mainly on quantitative coronary angiography. The literature of the past decade is reviewed selectively but not exhaustively, and in some instances, a brief historical overview is given. 相似文献
992.
Human diploid fibroblasts that undergo a senescent-like differentiation have elevated ceramide and diacylglycerol 总被引:1,自引:0,他引:1
Miller CJ Stein GH 《The journals of gerontology. Series A, Biological sciences and medical sciences》2001,56(1):B8-19
Senescent human diploid fibroblasts (HDF) have elevated levels of ceramide and diacylglycerol (DAG) compared with young HDF. DNA fragmentation analysis demonstrated the increased ceramide in senescent HDF was not associated with apoptosis, whereas in young HDF, exogenous ceramide induced apoptosis. In young HDF treated with both exogenous ceramide and DAG, less DNA fragmentation was observed. Thus, elevated DAG levels in senescent HDF might protect against ceramide-induced apoptosis. To determine which characteristics of senescent HDF (aging per se, cell cycle arrest, elevated p21Sdi1,Waf1,Cip1, and senescent-like differentiation) might influence ceramide and DAG, we examined transformed or mitomycin C-treated HDF that shared some of these properties with senescent HDF. The elevation of ceramide and DAG did not depend on aging per se, cell cycle arrest, or elevation of p21. Rather, ceramide and DAG may be elevated as part of a program of differentiation that is induced by either aging or DNA damage. 相似文献
993.
Stein RC 《Endocrine-related cancer》2001,8(3):237-248
The phosphoinositide 3-kinases (PI3-kinases) are a family of lipid kinases that have a key role in the regulation of many cellular processes including proliferation, survival, carbohydrate metabolism, and motility. There is now strong evidence that some members of the PI3-kinase family have an important role in cancer. Emerging evidence for functional specialisation of PI3-kinase isoforms suggests that isoform selective inhibitors, in contrast to the existing non-selective inhibitors wortmannin and LY294002, may prove to be useful anticancer drugs. 相似文献
994.
995.
In neural crest-derived sensory ganglia, approximately half of the neuronal population expresses the transmembrane trkA receptor that is required for neuronal binding of target-derived nerve growth factor (NGF). These same neurons also express the p75 neurotrophin receptor (NTR) that increases the affinity of trkA for NGF. Depleting p75NTR expression reduces both the survival of trkA-positive sensory neurons and their afferent innervation of peripheral targets. In this investigation, we assessed the neurochemical and structural plasticity of trigeminal sensory neurons in p75NTR-deficient mice in response to either normal or elevated levels of NGF during postnatal development and into adulthood. Although p75NTR-deficient mice have 30% fewer trigeminal neurons, levels of trkA mRNA expression are modestly elevated in these mutant mice as compared to control mice. The density of central afferent axons and local levels of NGF are, however, comparable between mutant and control animals. Thus, despite the survival of fewer trigeminal neurons, neither ganglionic levels of trkA mRNA expression nor the density of central afferent projections are depleted in p75NTR-deficient mice. In response to elevated levels of NGF protein, transgenic mice with and without p75NTR expression display both increased levels of trkA mRNA expression and a greater density of trigeminal central afferent axons as compared to control mice. These data further reveal that an absence of p75NTR function in trigeminal sensory neurons does not diminish their capacity for NGF-dependent plasticity, namely trkA mRNA expression and collateral growth of central afferent axons. 相似文献
996.
997.
998.
Lebedeva IV Stein CA 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》2000,13(3):195-216
The activation of dominant oncogenes and inactivation of tumour suppressor genes may result in cancer. These genetic events may represent novel targets for cancer therapy. Antisense nucleic acids can be used to modulate the expression of selected genes, and to suppress malignant behaviour in cancer cells. Nevertheless, in practice, the selection of suitable antisense targets still remains a trial-and-error procedure. Promising targets for antisense cancer therapy that have been extensively studied include proteases and protease receptors, telomerase, fusion genes, the Bcl family of proteins and various protein kinases. Combinations of antisense oligonucleotides with cytotoxic agents offer important advantages in cancer therapy. However, control oligonucleotides must be carefully chosen to separate the antisense effect from the many potential nonspecific effects. Several antisense drugs have been very effective in in vitro experiments, and have entered clinical trials. Successive generations of antisense drugs, including molecules with novel backbones or other structural modifications, chimeric oligonucleotides and peptide nucleic acids, are currently in development. 相似文献
999.
1000.
Stein J Eliachar I Myles J Munoz-Ramirez H Strome M 《The Annals of otology, rhinology, and laryngology》2000,109(2):221-226
This research investigated the histopathologic and migratory properties of injectable alternatives for vocal fold medialization. Thirteen dogs underwent sectioning of the recurrent laryngeal nerve followed by vocal fold injection with 1 of 4 substances: Teflon, autologous fat, silicone suspension, or hydroxyapatite cement. Six months later, the animals were painlessly sacrificed and histopathologic analysis of the larynx and regional lymph nodes was performed. Although regional lymph node migration was noted, Teflon injection resulted in minimal vocal fold inflammatory reaction. Vocal folds injected with autologous fat exhibited persistence of fat at the injection site without significant inflammation or migration. Silicone suspension caused a localized giant cell reaction without regional lymph node migration, and 1 study subject died secondary to acute inflammation with critical respiratory compromise. Hydroxyapatite cement was well tolerated without inflammation or migration. This pilot study indicates that a wide range of possible substances for vocal fold medialization exist. Many of these may produce results superior to those obtained with Teflon and are thus far untested. 相似文献