Glucocorticoids stimulate growth of human papillomavirus type 16 (HPV16)-immortalized human keratinocytes and support HPV16-mediated immortalization without affecting the levels of HPV16 E6/E7 mRNA

We investigated the effects of the glucocorticoids hydrocortisone and dexamethasone on human papillomavirus type 16 (HPV16)-mediated human cell carcinogenesis using normal human keratinocytes (HKc) and HKc immortalized by transfection with HPV16 DNA (HKc/HPV16). Normal HKc did not require glucocorticoids for proliferation. In contrast, growth of early passage HKc/HPV16 strictly required these hormones, although glucocorticoid dependence became less stringent during in vitro progression. Glucocorticoid dependence was acquired by HKc early after immortalization with HPV16 DNA, and glucocorticoids were required for efficient HKc immortalization. However, treatment of HKc/HPV16 with hydrocortisone or dexamethasone did not increase the steady-state levels of HPV16 E6/E7 mRNA or protein. Firefly luciferase activity expressed under the control of the HPV16 upstream regulatory region and P97 promoter increased by about fourfold following dexamethasone treatment of HeLa, but only twofold in HKc/HPV16, and less than twofold in SiHa. However, all of these cell lines expressed sufficient endogenous glucocorticoid receptors to allow for a dexamethasone response of the mouse mammary tumor virus promoter. These results indicate that mechanisms other than a direct influence by glucocorticoids on HPV16 early gene expression may contribute to the striking biological effects of these steroids on HPV16-mediated human cell carcinogenesis.     

Dystrophic kyphoscoliosis in neurofibromatosis type I: a report of two cases and review of the literature

As the Department of Defense initiates Tricare, its new system of integrated health delivery, outcome assessment will become increasingly important. Traditional outcomes have focused on disease and its more serious consequences, disability and death. Patient satisfaction is only recently emerging as an important measure of the quality of health care delivery. In this paper, we focus on patient satisfaction, exploring its historical roots, its evolution as an outcome measure, and its potential utilities and weaknesses in quality assessment.     

Comparison of fatty acid tracers FTHA and BMIPP during myocardial ischemia and hypoxia

To study the sensitivity of two fatty acid tracers to changes in beta-oxidation, the myocardial retention kinetics of 125I-iodine-15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) and 14-18F-fluoro-6-thia-heptadecanoic acid (FTHA) were compared in states of oxygen deprivation due to ischemia and hypoxia. METHODS: Nineteen swine were studied by extracorporeal perfusion of the three coronary arteries. Fatty acid beta-oxidation rates were determined by infusion of tritiated palmitate into the left anterior descending artery (LAD) and by measurement of labeled water production in the LAD perfusion bed. After a baseline period of 30 min, animals were divided into three groups and subjected to a 50-min intervention period. For the control group, there was no change in perfusion; for the ischemia group, there was a 60% decrease in LAD perfusion; and for the hypoxia group, the perfusion rate was unchanged, but venous blood was used as the LAD perfusate. Continuous infusion of FTHA and BMIPP into the LAD started 10 min into the intervention period and continued until the end of the intervention period. Retention rates of the two tracers were compared between the LAD and circumflex perfusion beds. RESULTS: No difference in beta-oxidation rate occurred from the baseline to the intervention period in the control group. A 50% reduction in beta-oxidation occurred in the ischemia group, and an 80% reduction occurred in the hypoxia group. No difference in retention of BMIPP or FTHA occurred in the control group. In the ischemia group, reduction in retention of both tracers occurred. However, in the hypoxia group, FTHA uptake was unchanged, whereas BMIPP retention increased compared to the circumflex arterial bed. CONCLUSION: Decreased retention of both BMIPP and FTHA occurred with ischemia, despite the known differences in metabolism of the two tracers. This difference in metabolism was further highlighted in the setting of hypoxia with increased BMIPP uptake. Thus, these results suggest that uptake of both FTHA and BMIPP tracks reduction of fatty acid utilization in myocardial ischemia but fails in tracking reduction of fatty acid oxidation during hypoxia.     

Cognitive, adaptive, and behavioral characteristics of Williams syndrome

The difference of morphological injury between rabbit aorta and pulmonary artery was compared after the animal was exposed to the altitude 5 km (PO2 = 10.8 kPa) for 24 h. Hypoxia caused subendothelial edema, increased vacuoles and injured mitochondria and endoplasmic reticulums in both kinds of endothelial cells. The impairment of pulmonary artery was obviously more severe than aorta and its smooth muscle cells were also affected. Forthermore, the exposure increased mitochondria in pulmonary artery endothelial cells. Bubbled with a mixture air of 95% N2-5% CO2 (PO2 = 4 kPa) led to an increase of pulmonary in tension, while hypoxia to the same extent induced aorta relaxation. These results indicate that hypoxia produces the differential effects on these two kinds of vessels, providing a possible explanation for the production of hypoxic pulmonary hypertension.