In re Estate of Dorone.
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THE PURPOSE OF THIS STUDY: To evaluate the safety and efficacy of an enhanced magnetic resonance-guided focused ultrasound (MRgFUS) emission protocol that results in more extensive treatment by increasing the volume of each focal ablation using the same energy. MATERIALS AND METHODS: Six pigs were treated with an MRgFUS system combined with real-time MR, for imaging and temperature mapping, with 102 "enhanced" and 97 "regular" focal ablations performed on both buttock muscles. Real-time imaging, temperature mapping, and acoustic reflected spectrum data enabled immediate evaluation of the results. MR contrast-enhanced images and pathology examinations were used for confirmation. RESULTS: The location of the ablated volume by "enhanced" sonication is predictable, with a maximum possible shift of 6 mm toward, and 3 mm away, from the transducer. The ablated volume after enhanced sonication was, on average, 1.8 times larger than after a regular sonication of the same energy. Pathology results showed the same thermally induced damage patterns in the enhanced sonications and the regular sonications. CONCLUSION: Accelerated MRgFUS with enhanced sonication is a safe, controllable, and more effective tissue ablative modality than standard sonication. This new technology may significantly reduce the length of tumor ablation procedures. (Isn't the new technology you're talking about MRgFUS? If so, you don't need to repeat it at the end of this sentence.).
The advent of complete mitochondrial DNA (mtDNA) sequence data has ushered in a new phase of human evolutionary studies. Even quite limited volumes of complete mtDNA sequence data can now be used to identify the critical polymorphisms that define sub-clades within an mtDNA haplogroup, providing a springboard for large-scale high-resolution screening of human mtDNAs. This strategy has in the past been applied to mtDNA haplogroup V, which represents <5% of European mtDNAs. Here we adopted a similar approach to haplogroup H, by far the most common European haplogroup, which at lower resolution displayed a rather uninformative frequency distribution within Europe. Using polymorphism information derived from the growing complete mtDNA sequence database, we sequenced 1580 base pairs of targeted coding-region segments of the mtDNA genome in 649 individuals harboring mtDNA haplogroup H from populations throughout Europe, the Caucasus, and the Near East. The enhanced genealogical resolution clearly shows that sub-clades of haplogroup H have highly distinctive geographical distributions. The patterns of frequency and diversity suggest that haplogroup H entered Europe from the Near East approximately 20,000-25,000 years ago, around the time of the Last Glacial Maximum (LGM), and some sub-clades re-expanded from an Iberian refugium when the glaciers retreated approximately 15,000 years ago. This shows that a large fraction of the maternal ancestry of modern Europeans traces back to the expansion of hunter-gatherer populations at the end of the last Ice Age.
PURPOSE: The tension-free transvaginal tape (TVT) procedure has apparently become the most popular technique for genuine stress urinary incontinence (GSUI). Long-term followup data on the outcome of the procedure are sparse. We evaluated the long-term results of TVT for treating women with GSUI. MATERIALS AND METHODS: We performed a retrospective analysis of the records of 55 patients 37 to 83 years old (mean age 63.4) with GSUI, for which they underwent the TVT procedure at our department as of December 1999. RESULTS: Of the 52 patients who were followed a mean of 55 months (range 48 to 65) 41 (78.9%) were dry. There were 4 intraoperative complication (7.3%), including bladder injury in 3 patients and urethral injury in 1. None required surgical re-intervention. Urgency was reported in 6 women (11.5%). There were 5 postoperative tape related complications (9.6%), consisting of bladder erosion in 1 woman, vaginal erosion in 2 and an obstructed urethra in 2. Four of these 5 women underwent corrective surgery, after which all remained dry. CONCLUSIONS: TVT is a safe and effective procedure for female stress urinary incontinence with an enduring, high success rate. There is a significant rate of intraoperative complications, which do not cause further problems when identified and treated during surgery. One must be alert to the significant rate of postoperative complications that usually require repeat surgery, which is relatively simple and causes practically no long-term morbidity. It also does not influence the continence rate in most cases.
Inactivation of p53 and activation of telomerase occur in the majority of human cancers, raising the possibility of a link between these two pathways. Overexpression of wild-type p53 down-regulates the enzymatic activity of telomerase in various cancer cell lines through transcriptional repression of its catalytic subunit, human telomerase reverse transcriptase (hTERT). In this study, we re-evaluated the role of p53 in telomerase regulation using isogenic cell lines expressing physiological levels of p53. We demonstrate that endogenous wild-type p53 was able to down-regulate telomerase activity, hTERT mRNA levels, and promoter activity; however, the ability to repress hTERT expression was found to be cell type-specific. The integrity of the DNA-binding core domain, the N-terminal transactivation domain, and the C-terminal oligomerization domains of p53 was essential for hTERT promoter repression, whereas the proline-rich domain and the extreme C terminus were not required. Southwestern and chromatin immunoprecipitation experiments demonstrated lack of p53 binding to the hTERT promoter, raising the possibility of an indirect repressive mechanism. The down-regulation of hTERT promoter activity was abolished by a dominant-negative E2F1 mutant. Mutational analysis identified a specific E2F site responsible for p53-mediated repression. Knockdown of the key p53 transcriptional target, p21, was sufficient to eliminate the p53-dependent repression of hTERT. Inactivation of the Rb family using either viral oncoproteins or RNA interference attenuated the repression. Inhibition of histone deacetylases also interfered with the repression of hTERT by p53. Therefore, our results suggest that repression of hTERT by endogenous p53 is mediated by p21 and E2F.