Temporal order and functional analysis of mutations within the Fli-1 and p53 genes during the erythroleukemias induced by F-MuLV

The erythroleukemias induced by Friend murine leukemia virus (F-MuLV) result from the accumulation of a number of genetic changes, including activation of the Fli-1 proto-oncogene and inactivation of the p53 tumor suppressor gene. We have determined the temporal order of mutation of the genes involved in this multistage malignancy, by serial in vivo transplantation of F-MuLV induced primary erythroleukemias into syngenic Balb/c mice. These primary tumors are capable of growing when transplanted into syngenic mice, but die after several days of in vitro culture. From the transplanted tumors grown in syngenic mice, erythropoietin-dependent cell lines were established in culture that are clonally related to cells in the primary tumors. We show that retroviral insertional activation of the Fli-1 ets family member is the first detectable genetic event in F-MuLV induced primary erythroleukemias. Mutations in the p53 gene were observed in the Epo-dependent cell lines but not in the transplanted erythroleukemias used to establish these cell lines in culture. These data suggest that activation of Fli-1 plays an important role in the early stages of F-MuLV-induced leukemia, perhaps by altering the self-renewal probabilities of erythroid progenitor cells and that p53 mutations immortalize these cells, enabling them to grow in vitro in the presence of Epo.     

Biology of chronic radiation effect on tissues and wound healing

Radiation therapy exerts both acute and chronic effects on normal tissue included within treatment fields. The physics of radiation therapy and treatment techniques to minimize deleterious effects of radiation are presented. Management of radiation-damaged skin is discussed. Radiation effect on tissue, wound healing, and tumorigenesis also are reviewed.     

Decision-making in the treatment of subfoveal neovascularization in age-related macular degeneration. An analysis from the patient''s perspective

The human mineralocorticoid receptor of the steroid receptor family contains a modular structure with domain E which is considered to be a hormone binding domain. Recombinant protein approaches enabled us to clearly determine that this domain is also able to interact with F-actin (Kd about 2 microM) and G-actin. Moreover, it was revealed that this mineralocorticoid receptor domain/actin interaction was modulated by specific mineralocorticoid ligands. Agonist (aldosterone) steroid binding almost totally (91%) abolished the interaction with F-actin, while antagonist (progesterone) binding allowed more than 30% of this binding. Steroid modulation of the interaction between domain E and actin indicated that this actin binding is specific and could be essential for cellular mineralocorticoid receptor activity.     

Effect of postischemic reperfusion on microcirculation and lipid metabolism of skeletal muscle

To study the effect of ischemia reperfusion injury on microvascular reactivity and tissue metabolism in skeletal muscle, a Sprague-Dawley rat cremaster muscle was prepared as a tourniquet ischemia model and subjected to 2 hr ischemia followed by 1 hr reperfusion to simulate the timing of ischemia during microvascular surgery. The dose-response curve of arteriolar reactivity to norepinephrine, lipid peroxidation, and ultrastructure of capillaries was determined in both the control and postischemic reperfusion stages. Judging from the results, we summarize our observations as follows: (1) Postischemic reperfusion significantly increased arteriolar reactivity to norepinephrine, in which the EC50 for vasoconstriction decreased in all three orders of arterioles. These results suggest that reperfusion could have impaired the vasodilation control mechanism, possibly being endothelium dependent. (2) Lipid peroxidation increased sixfold in the reperfusion group, suggesting that oxygen free radicals have produced significant tissue damage under the created conditions. (3) Significant endothelial damage in the capillaries shown by electron microscope observation supports these studies, indicating that ischemia/reperfusion in clinically transplanted skeletal muscles could cause significant damage to the tissue microcirculation both physiologically and metabolically.     

Composite finger metacarpophalangeal joint reconstruction in combined second and third free toe-to-hand transfers

Composite metacarpophalangeal joint reconstruction using the toe proximal phalanx and the metacarpal head, with a capsular repair, is an option during free toe transfer procedures for absent fingers. Eleven composite metacarpophalangeal finger joint reconstructions were performed in four patients concurrent with combined second and third toe-to-hand transfer. The average follow-up period was 5 years. Postoperative assessment included range of motion, stability, radiographic changes, and pain. The average range of motion was 52 degrees, average ulnar stress deviation was 14 degrees. No patients complained of pain. Composite metacarpophalangeal joint reconstruction should be considered in free toe-to-hand procedures when metacarpal head articular cartilage is preserved.     

Pulsed-current duty cycle dependence of electromigration-inducedstress generation in aluminum conductors

The effect of duty cycle of pulsed dc currents on the critical length-current density product, (jl_c), was measured using the Blech-Kinsbron edge-displacement technique [Thin Solid Films 25, 327 (1975)]. Unencapsulated Al edge-displacement segments mere stressed at various duty cycles and the critical lengths, the so-called “Blech lengths”, were measured. It was found that jl_c increased with decreasing duty cycle. We measured a factor of 2.6 increase in jl_c for the 25% duty cycle as compared to dc. This duty cycle dependence of Blech length implies that electromigration resistance for an integrated circuit would be increased for small duty cycle operation by increasing the fraction of interconnects which are sub-Blech-length and are not susceptible to EM damage     

Electromigration drift and threshold in Cu thin-film interconnects

The electromigration-induced ionic drift velocity and critical length-current density product, (jl_c) of Cu thin film conductors, were measured using the Blech-Kinsbron edge-displacement technique. Unencapsulated Cu edge-displacement segments on TiN conductors were stressed in vacuum at a modest current density of 6×10⁵ A/cm² in the temperature range of 175-275°C. Drift velocity was observed to be between 1-1/2 to 3 orders-of-magnitude lower than that previously measured for unencapsulated Al in this temperature range. We measured an activation energy for EM-induced drift of 1.25±0.08 eV which corresponds to grain boundary diffusion in Cu. Critical lengths were measured and the jl_c threshold was estimated to range between 900-1600 A/cm. We calculated a Cu grain boundary Z* value of -0.7, to our knowledge, this study is the first to measure Z* for electromigration in Cu thin film conductors     

Lyapunov‐stable discrete‐time model reference adaptive control

Discrete‐time model reference adaptive control (MRAC) is considered with both least squares and projection algorithm parameter identification. For both cases complete Lyapunov proofs are given for stability and convergence. The results extend the approach of Johansson (Int. J. Control 1989; 50 (3):859–869) to include Lyapunov stability for MRAC when the normalized projection algorithm is used for parameter identification. Copyright © 2005 John Wiley & Sons, Ltd.