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101.
p53 transactivates the expression of a variety of genes by binding to specific DNA sequences within the promoter. We have investigated the ability of wild-type p53 and a non-DNA binding p53 mutant to activate the hepatocyte growth factor/scatter factor (HGF/SF) promoter using chloramphenicol acetyltransferase reporter constructs. We also used deletion sequences of the HGF/SF promoter to identify which regions, if any, were responsible for p53 binding. Our results show that wild-type but not mutant p53 activates the HGF/SF promoter when using -3000 and -755 bp upstream of the HGF/SF gene. This activation is lost when promoter sequences covering -365 and -239 bp are used. Analysis of the DNA sequence between -365 and -755 bp shows one putative p53 half-site with 80% homology to the consensus sequence and another half-site 3 bases downstream of this with 100% homology to the consensus sequence. In contrast to previously identified p53 binding DNA sequences, the downstream half-site is inverted. We propose that the HGF/SF promoter can be activated by wild-type p53 in vivo and that this could be as a result of a novel form of sequence-specific DNA binding. 相似文献
102.
GK Matheson A Knowles D Guthrie D Gage D Weinzapfel J Blackbourne 《Canadian Metallurgical Quarterly》1997,29(5):823-828
1. The effects of ipsapirone, nefazodone, tiaspirone, BMS-20661, buspirone and gepirone on the hypothalamic-pituitary-adrenal (HPA) axis were studied. These drugs were selected because they have serontonin 1A (5-HT1A) receptor-binding capability and have the potential for therapeutic activity in the treatment of major affective or anxiety disorders or both. 2. Plasma corticosterone level was used as the end point for determining the effect of each drug on the HPA axis. Each drug increased the plasma corticosterone levels in a dose-dependent manner. The ED50 values were 0.8 mg/kg for BMS-20661, 3.5 mg/kg for gepirone, 3.9 mg/kg for buspirone, 5.3 mg/ kg for tiaspirone, 10.5 mg/kg for ipsapirone and 73.5 mg/kg for nefazodone. Ipsapirone and buspirone were more efficacious than the other four drugs. 3. The effect of a 10-mg/kg (35 mg/kg for nefazodone) test dose of each drug reached a peak between 30 min and 1 hr, and plasma corticosterone levels generally returned to control levels after 2 hr. 4. When the drugs were given 30 min before decapitation, in conjunction with a rotatory stress, BMS-20661 significantly inhibited the stress-induced rise, whereas ipsapirone and gepirone caused a significant increase in plasma corticosterone levels. However, when the drugs were given 2 hr before decapitation, nefazodone caused a significant decrease, whereas ipsapirone, BMS-20661 and gepirone produced significant increases in HPA axis activity. An 0800 hr dose of 0.1 mg/kg of dexamethasone suppressed the 1500 hr HPA activity by 73.1%. The 0.1-mg/kg dose of dexamethasone significantly reduced the drug-activated HPA axis activity of all of the drugs from their saline-control levels. The rank order, from least to greatest inhibitory effect, produced by this dexamethasone treatment on the drug-control levels was gepirone (-42.6%), tiaspirone (-48.9%), buspirone (-56.1%), nefazodone (-68.5%), insapirone (-70.0%), and BMS-20661 (-74.3%). 相似文献
103.
Acute choroidal ischemia as a complication of photocoagulation 总被引:2,自引:0,他引:2
MH Goldbaum SO Galinos D Apple GK Asdourian K Nagpal L Jampol MB Woolf B Busse 《Canadian Metallurgical Quarterly》1976,94(6):1025-1035
Acute choroidal vascular insufficiency as a complication of photocoagulation has been little noticed. In 17 eyes of 16 patients photocoagulated with either xenon or argon sources for proliferative sickle cell retinopathy, gray lesions of the fundus developed peripheral to the photocoagulation sites. Histologic examination of similar gray lesions produced in monkeys showed necrosis and atrophy of the outer half of the retina. Intense photocoagulation of the human fundus, even with smaller spot sizes, may occlude a choroidal artery, producing separate gray lesions of distinctive shape. The lesions in both the patients and the monkeys progressed to granular hyperpigmentation by two to three weeks after photocoagulation. 相似文献
104.
GK Asdourian KC Nagpal B Busse M Goldbaum D Patriankos MF Rabb MF Goldberg 《Canadian Metallurgical Quarterly》1976,60(6):431-453
The posterior pole vasculature of 100 patients with different sickling haemoglobinopathies was studied prospectively over a period of three years. Various abnormalities of the posterior pole vasculature were seen in 29 per cent of the patients. Continuous remodelling of the macular and perimacular vasculature occurred. Visual acuity was variably affected and sometimes remained intact. 相似文献
105.
A range of health behaviors was related to beliefs concerning health practices and health knowledge. A questionnaire dealing with health-related practices, health beliefs and knowledge of health risk factors was answered by 166 male and 179 female students aged 18-30 years at Stockholm University. Female students reported engaging in better health behavior than males. Beliefs about the importance of health behaviors were closely related to their frequency of occurrence. There was only a weak relationship between health behaviors and knowledge of specific health matters. It is concluded that health attitudes rather than health knowledge determine health behavior. 相似文献
106.
107.
Twenty-six patients with severe COPD or asthma completed standard questionnaires before, and 2 months after, starting home nebulized bronchodilator therapy. Patients' perceived illness severity and their expectations of treatment with regard to symptoms were examined in the first questionnaire, and outcome was assessed in the second. Before treatment started patients expected a definite improvement in all symptoms studied. After treatment the group showed only a marginal subjective improvement in all symptoms. The improvement attained with regard to breathlessness, ability to get out and about, and general quality of life was significantly lower than had been expected. While home nebulized bronchodilator therapy is well tolerated and confers some subjective benefit in selected individuals, patients appear to have unrealistically high expectations of treatment. 相似文献
108.
BJ Mehrara RJ Mackool JG McCarthy GK Gittes MT Longaker 《Canadian Metallurgical Quarterly》1998,102(6):1805-17; discussion 1818-20
Craniosynostosis is a common disorder with an unknown etiology. Recent genetic mapping studies have demonstrated a strong linkage between several familial craniosynostotic syndromes and mutations in fibroblast growth factor receptor 1 (FGF-R1) and 2 (FGF-R2). The purpose of this experiment was to investigate by immunohistochemistry the protein production of these receptors as well as of their most prevalent ligand, basic fibroblast growth factor (bFGF), before, during, and after sutural fusion in rat cranial sutures. The posterior frontal (normally fuses between postnatal days 12 and 22) and sagittal (remains patent) sutures of embryonic day 20 and neonatal days 6, 12, 17, 22, and 62 (n = 3 per group) were harvested, fixed, and decalcified. Five-micrometer sections were stained with polyclonal antibodies against bFGF, FGF-R1, and FGF-R2, and patterns of immunohistochemical staining were assessed by independent reviewers. Our results indicate that increased bFGF production correlates temporally with suture fusion, with increased staining of the dura underneath the fusing suture prior to fusion followed by increased staining within osteoblasts and sutural cells during fusion. FGF-R1 and, to a lesser extent FGF-R2 immunostaining revealed a different pattern of localization with increased immunostaining within the patent sagittal suture at these time points. These results implicate bFGF in the regulation of sutural fusion and may imply autoregulatory mechanisms in fibroblast growth factor receptor expression. 相似文献
109.
110.