Biomedical subjects
Publications and source records attributed to S Kung.
We report the case of a patient with NF-1 who presented with gross elephantiasis neuromatosa of her right leg. Prior to plastic surgery, Magnetic Resonance Imaging and Angiography (MRI and MRA) were performed to provide a detailed assessment of the extension as well as the vascular and muscular involvement of the neurofibroma.
A lentiviral vector capable of expressing the HIV-1 vpr gene (Vpr lentiviral vector) was constructed, and its in vivo anticancer effect was determined against cutaneous tumors derived from the AT-84 oral cancer cells in immunocompetent mice. A single intratumoral injection of the Vpr lentiviral vector not only significantly reduced the primary tumor volume but also completely regressed tumors in >40% of animals. More interestingly, the mice of which the primary tumors were completely regressed by the Vpr lentiviral vector were additionally protected from a secondary challenge of AT-84 cells. These data suggest that the Vpr lentiviral vector elicits its anticancer activity in part by the activation of the immune system. The above suggestion is additionally supported by the failure of the lentiviral vector to demonstrate anticancer activity in immunocompromised nude or SCID mice. The Vpr lentiviral vector offers a powerful new strategy for cancer gene therapy and may be useful for the control of solid tumors, such as human oral squamous cell carcinomas.
Phorbol 12-myristate 13-acetate (PMA) uncaps a small number of the fast-growing (barbed) ends of actin filaments, thereby eliciting slow actin assembly and extension of filopodia in human blood platelets. These reactions, which also occur in response to immunologic perturbation of the integrin glycoprotein (GP) IIb-IIIa, are sensitive to the phosphoinositide 3-kinase inhibitor wortmannin. Platelets deficient in GPIIb-IIIa integrins or with GPIIb-IIIa function inhibited by calcium chelation or the peptide RGDS have diminished PMA responsiveness. The effects of PMA contrast with thrombin receptor stimulation by >/=5 microM thrombin receptor-activating peptide (TRAP), which causes rapid and massive wortmannin-insensitive actin assembly and lamellar and filopodial extension. However, we show here that wortmannin can inhibit filopod formation if the thrombin receptor is ligated using suboptimal doses (<1 microM) of TRAP. Phosphatidylinositol 3,4-bisphosphate inhibits actin filament severing and capping by human gelsolin in vitro. The findings implicate D3 polyphosphoinositides and integrin signaling in PMA-mediated platelet stimulation and implicate D3 containing phosphoinositides generated in response to protein kinase C activation and GPIIb-IIIa signaling as late-acting intermediates leading to filopodial actin assembly.
This article reviews the current knowledge about coronary artery calcification in women, concentrating on the pathophysiology of atherosclerotic calcification, the gender and age differences in the detection of calcification by electron beam computed tomography (EBCT), and the clinical significance of detected coronary calcium. The effects of estrogen and vitamin D on vascular calcification are examined with respect to data that point to similarities between the processes of calcification and bone matrix formation. Gender and age differences in EBCT coronary calcium detection, with emphasis on differences and consequences of calcium prevalence, are also examined. Lastly, the diagnostic and prognostic significance of coronary calcification is discussed, noting that it is more significant in symptomatic, older, and high-risk adults than it is in younger individuals of either gender.
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