Posterior mediastinotomy as an unordinary method of mediastinal drainage in patient with descending necrotizing mediastinitis: a case report.

The authors present a case report of severe descending necrotizing mediastinitis (DNM) of posterior mediastinum, etiologically of vertebral osteomyelitis treated by the drainage through the posterior mediastinotomy. Mediastinitis caused by vertebral osteomyelitis is very rare. The most important diagnostic and surveillance tool for descending mediastinitis is a CT scan of chest and neck. Every surgical approach to the mediastinum has its advantages and disadvantages, so each patient has to be treated individually and the most suitable type of drainage must be chosen. The posterior mediastinotomy is an unusual alternative of drainage of pre- and paravertebrally localized DNM in posterior mediastinum but it is not recommended as a routine strategy.

A multidisciplinary approach to the management of descending necrotizing mediastinitis - case series.

OBJECTIVES: Descending necrotizing mediastinitis (DNM) is a severe potentially fatal disease of the mediastinum which spreads downwards from oropharyngeal region. Mortality varies from 11 to 40%. There is agreement on the importance of early diagnosis, aggressive surgical treatment and the need for a multidisciplinary approach. DESIGN: Retrospective study of series of patient treated for DNM regarding multidisciplinary approach and surgical treatment. PATIENTS AND METHODS: Sixteen patients that were surgically treated for DNM from 2008 to 2017 at our hospital were consecutively enrolled in observational descriptive study. RESULTS: Twelve patients had disease localised above tracheal bifurcation level. Nine of them underwent transcervical drainage, three patients underwent more extensive treatment. Four patients with disease spread below the treacheal bifurcation level were treated with transcervical drainage in combination with posterolateral thoracotomy or videothoracoscopy. Three patients underwent videothoracoscopy - two of them as primary surgical treatment with need of one reoperation - contralateral videothoracoscopy. The third patient was initially treated with a transcervical approach and videothoracoscopy was indicated as a reoperation because of the progression of the disease. One patient died (mortality 6.25%). CONCLUSION: In management of descending necrotizing mediastinitis, early diagnosis, aggressive surgical treatment and use of broad-spectrum antibiotics and nowadays also multidisciplinary approach are crucial. Transcervical drainage combined with posterolateral thoracotomy or videothoracoscopy were used with good results.

pRB2/p130 target genes in non-small lung cancer cells identified by microarray analysis.

The retinoblastoma gene family consisting of RB/p105, p107, and RB2/p130 cooperate to regulate cell-cycle progression through the G1 phase of the cell cycle. Previous data demonstrated an independent role for the reduction or loss of pRb2/p130 expression in the formation and/or progression of lung carcinoma. Rb2/p130 is mutated in a human cell line of lung small cell carcinoma as well as in primary lung tumors. To identify potential pRb2/p130 target genes in an unbiased manner, we have utilized an adenovirus-mediated expression system of pRb2/p130 in a non-small lung cancer cell line to identify specific genes that are regulated by pRb2/p130. Using oligonucleotide arrays, a number of Rb2/p130 downregulated genes were identified and their regulation was confirmed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. As a result, 40 genes showed greater than 2.0-fold modification in their expression level after the RB2/p130 viral transduction. In conclusion, coupling adenoviral overexpression with microarray and semiquantitative RT-PCR analyses proved to be a versatile strategy for identifying pRb2/p130 target genes and for better understanding the expression profiles of these genes. Our results may also contribute to identifying novel therapeutic biomarkers in lung carcinoma.

Activation of MyoD-dependent transcription by cdk9/cyclin T2.

Myogenic transcription is repressed in myoblasts by serum-activated cyclin-dependent kinases, such as cdk2 and cdk4. Serum withdrawal promotes muscle-specific gene expression at least in part by down-regulating the activity of these cdks. Unlike the other cdks, cdk9 is not serum- or cell cycle-regulated and is instead involved in the regulation of transcriptional elongation by phosphorylating the carboxyl-terminal domain (CTD) of RNA polymerase II. While ectopic expression of cdk2 together with its regulatory subunits (cyclins E and A) inhibits myogenic transcription, overproduction of cdk9 and its associated cyclin (cyclin T2a) strengthens MyoD-dependent transcription and stimulates myogenic differentiation in both MyoD-converted fibroblasts and C2C12 muscle cells. Conversely, inhibition of cdk9 activity by a dominant negative form (cdk9-dn) represses the myogenic program. Cdk9, cyclinT2 and MyoD can be detected in a multimeric complex in C2C12 cells, with the minimal cdk9-binding region of MyoD mapping within 101-161 aa of the bHLH region. Finally, cdk9 can phosphorylate MyoD in vitro, suggesting the possibility that cdk9/cycT2a regulation of muscle differentiation includes the direct enzymatic activity of the kinase on MyoD.

Deacetylase recruitment by the C/H3 domain of the acetyltransferase p300.

The balance between acetylation and deacetylation of histone and nonhistone proteins controls gene expression in a variety of cellular processes, with transcription being activated by acetyltransferases and silenced by deacetylases. We report here the formation and enzymatic characterization of a complex between the acetyltransferase p300 and histone deacetylases. The C/H3 region of p300 was found to co-purify deacetylase activity from nuclear cell extracts. A prototype of class I histone deacetylases, HDAC1, interacts with p300 C/H3 domain in vitro and in vivo. The p300-binding protein E1A competes with HDAC1 for C/H3 binding; and, like E1A, HDAC1 overexpression interferes with either activation of Gal4p300 fusion protein or p300-dependent co-activation of two C/H3-binding proteins, MyoD and p53. The exposure to deacetylase inhibitors could reverse the dominant-negative effect of a C/H3 fragment insulated from the rest of the molecule, on MyoD- and p53-dependent transcription, whereas inhibition by E1A was resistant to trichostatin A. These data support the hypothesis that association between acetyltransferases and deacetylases can control the expression of genes implicated in cellular growth and differentiation, and suggest that the dominant-negative effect of the p300 C/H3 fragment relies on deacetylase recruitment.