Pulse mTOR inhibitor treatment effectively controls cyst growth but leads to severe parenchymal and glomerular hypertrophy in rat polycystic kidney disease
ABSTRACT The efficacy of mammalian target of rapamycin (mTOR) inhibitors is currently tested in patients affected by autosomal dominant polycystic kidney disease. Treatment with mTOR inhibitors has been associated with numerous side effects. However, the renal-specific effect of mTOR inhibitor treatment cessation in polycystic kidney disease is currently unknown. Therefore, we compared pulse and continuous everolimus treatment in Han:SPRD rats. Four-week-old male heterozygous polycystic and wild-type rats were administered everolimus or vehicle by gavage feeding for 5 wk, followed by 7 wk without treatment, or continuously for 12 wk. Cessation of everolimus did not result in the appearance of renal cysts up to 7 wk postwithdrawal despite the reemergence of S6 kinase activity coupled with an overall increase in cell proliferation. Pulse everolimus treatment resulted in striking noncystic renal parenchymal enlargement and glomerular hypertrophy that was not associated with compromised kidney function. Both treatment regimens ameliorated kidney function, preserved the glomerular-tubular connection, and reduced proteinuria. Pulse treatment at an early age delays cyst development but leads to striking glomerular and parenchymal hypertrophy. Our data might have an impact when long-term treatment using mTOR inhibitors in patients with autosomal dominant polycystic kidney disease is being considered.
Conference Paper: The product-process-market path: new road maps[Show abstract] [Hide abstract]
ABSTRACT: Global competition is causing management to rethink the way design and production are done. To cut time to market, industry is aiming to shorten both the manufacturing and engineering cycles. New road maps are being developed and experimented with. It is noted that the traditional throw-it-over-the-wall road map has been discarded and the focus has turned to group technology, concurrent engineering, design for manufacture, and design for assembly. Dictaphone Corporation's products aim at the industrial voice recording market, and in late 1990 it formed a team to explore the feasibility of a new product. The team sized up the proposed product's technical feasibility by reviewing Dictaphone's analog/digital technology, PCB (printed circuit board) product process technology, and test requirements. The focus of the case study described is on PCB technology, the PCB being a component of the new product. The concept-design-production path is described. The PCB design-manufacture approach described here provides a road map aimed at product reliability and robustness as well as reduced cycle time, all of which means an improved competitive edge in the market placeTechnology Management : the New International Language; 11/1991
Conference Paper: Multinational issues in R&D management[Show abstract] [Hide abstract]
ABSTRACT: Summary form only given. It is pointed out that multinational R&D is more complex than single-location R&D. One must consider non R&D related factors, such as tax regimes, governmental influence, cultural differences, and modes of communication. Both internal and external influences determine how an organization will perform R&D. How these factors impact R&D management often depends on the size of the organization. In particular, mid-size companies with 500 to 2000 employees have both the most flexibility and the most difficulty in establishing and maintaining multinational R&D facilities. The author has considered R&D management for multinational organizations, examining multinational R&D finance, and giving a framework for its managementTechnology Management : the New International Language; 11/1991
Conference Paper: Modeling of 2D photonic crystals by using the method of lines[Show abstract] [Hide abstract]
ABSTRACT: In our work we examined 2-dimensional photonic crystals. For modeling we used the method of lines (MoL). We analyzed waveguides, filters and concatenation of two bends. Results are in good agreement with results presented in the literature.Transparent Optical Networks, 2002. Proceedings of the 2002 4th International Conference on; 02/2002