Organomegaly and tumors in transgenic mice with targeted expression of HpaII methyltransferase in smooth muscle cells.

Current data suggest that angiogenesis, smooth muscle cell migration, differentiation and proliferation may be epigenetically regulated. Prokaryotic DNA methyltransferases have been proposed as tools to modify mammalian DNA methylation. In order to assess the impact of DNA hypermethylation on smooth muscle pathophysiology, we expressed an HpaII site-specific methyltransferase transgene in smooth muscle cells in mice. The enzyme is expected to target only a subset (CCGG) of unmethylated CpG dinucleotides, thus avoiding possible deleterious effects of widespread hypermethylation. Transgenics of two independent lines were born at expected frequencies, showed no obvious abnormalities and were fertile. Nevertheless, ~30% of > 1 year-old transgenics developed organomegaly and ~20% showed a range of tumors. Global DNA methylation was unchanged in transgenic tissue whether hyperplastic or normal, but tumor DNA showed a pronounced global hypermethylation. DNA hypermethylation was not indiscriminate, as five tested tumor suppressor genes showed promoter CpG and non-CpG hypermethylation and transcriptional down-regulation, whereas the methylation status of one intergenic CpG islands, repeated elements (n=2) and non-tumor suppressor gene promoters (n=3) was unchanged. Our work is the first report on the effects of HpaII methyltransferase on endogenous chromatin and in a whole animal. Furthermore, our data expand previous findings that imply that global DNA hypomethylation is not an obligate oncogenic pathway at least in the tumor types examined here.

[Effect of hyaluronic acid on ureteropyelic anastomosis healing. Experimental study]. / Efecto del ácido hialurónico en la cicatrización de la anastomosis ureteropiélica. Estudio experimental.

BACKGROUND: Ureteropyelic obstruction is the most frequent congenital cause of obstructive uropathy in the newborn. Its repair is based on surgical procedures and has a very high rate of relapse of secondary stenosis to fibrosis (5-12%) in open repair and 10-20% in endo-urological pyeloplasties. Hyaluronic acid has demonstrated therapeutic utility in modulating the healing process and its effect in scar formation from ureteropyelic anastomosis is determined. METHODS: An experimental, controlled, comparative, double blind study was performed. Sample n = 20 per protocol with d = 26%, alpha = 0.05, beta = 0.80. Two groups of Wistar rats, 4 months of age and weighing between 250 and 350 g, were used. Under general anesthesia, Vision 12 x was used and bevel section was realized in the left ureteropyelic union and end-to-end anastomosis with Vicryl 7-0. Experimental group was treated with 25 microg of hyaluronic acid and group B was treated with placebo. The rats were reoperated on the 15th day and adherences in cavity were quantified. To quantify the degree of fibrosis, samples of ureteropyelic anastomosis tissue were dyed with Masson Trichrome and observed microscopically. Inferential statistics were used with a = 0.05. RESULTS: Macroscopic: there were adherences in 75 % of group A and 90 % of the group B (p >0.05). Microscopic: anastomotic fibrosis in group A (534 +/- 292 micro) was significantly lower (p = 0.043) than that of group B (728 +/- 295 micro). CONCLUSIONS: Hyaluronic acid plays a role in diminishing the formation of fibrosis from ureteropyelic anastomosis in an animal model.

On the algebra of binary codes representing close-packed stacking sequences.

A systematic use of binary codes derived from the Hagg symbol are used to study close-packed polytypes. Seitz operators acting over the corresponding binary codes are defined and used. The number of non-equivalent polytypes of a given length are calculated through the use of the Seitz operators. The same procedure is applied to the problem of counting the number of polytypes complying with a given symmetry group. All counting problems are reduced to an eigenvector problem in the binary code space. The symmetry of the binary codes leads to the different space groups to which polytypes can belong.