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Introduction: There is no consensus on which voice outcome indicators (VOIs) should be used to compare the merits of the various surgical treatments for unilateral vocal fold paralysis (UVFP). Authors performed a literature review to identify which VOIs are most frequently used and most relevant, in terms of significant change in pre- and post-operative measurements, to assess UVFP surgical treatments.Method: A Medline/Pubmed literature review was performed and the most frequently used VOIs were identified using a Pareto diagram. For these most frequently used VOI’s, the number of studies that showed a statistically significant change in pre- and post-operative results were compared to the total number of studies found using that same VOI, this portion was expressed in percent. This percentage was defined as the “percentage of significance” and used to assess changes of each VOI.Results: Eleven VOIs were identified using the Pareto analysis. These were, in decreasing order of frequency of citation: maximum phonation time (MPT), jitter, Shimmer, video-stroboscopic examination, noise to harmonic ratio (NHR/HNR), mean air flow (MeAF), fundamental frequency (F0), “Infrequent Perceptional Scales”, GRBAS scale, mean subglottic pressure (MSGP). MPT, MeAF, factor G of GRBAS-I, Jitter, shimmer and VHI-30 had respective “percentage of significance” of 90, 86, 85, 74, 68 and 64%, respectively.Conclusion: The results indicate that MPT, MeAF and GRBAS-I, represent the top-three most frequently used and the most relevant VOIs in terms of “percentage of significance”. VHI-30 showed a relatively low rate of use and low “percentage of significance”. The role of Jitter and Shimmer remains unclear. Finally, MSGP and the F0 appear to be less relevant VOIs for the evaluation of UFVP surgical treatments in terms of significant change in pre- and post-operative measurements. [ABSTRACT FROM AUTHOR]

Chimeric transcription factor E2A-PBX1 induces the development of acute lymphoblastic B-cell leukemia in children. Using a transgenic mouse model, we previously demonstrated that homeobox ( HOX) gene HOXA9 genetically interact with E2A-PBX1 gene in the development of B-cell leukemia in mice. HOXA9 itself is a potent oncogene resulting in myeloid leukemia when overexpressed, which is strongly accelerated by its collaborator Meis1. HOX, PBX1 and MEIS1 proteins have been shown to form hetero dimeric or trimeric complexes in different combinations. Cooperative interaction between PBX1 and HOX proteins enhances their DNA binding specificity, essential for HOX dependent developmental programs. PBX1 is retained in E2A-PBX1, and thus the strong transcriptional activator properties of E2A-PBX1 may lead to aberrant activation of normally repressed targets of HOX-PBX complexes. However, although there is evidence that E2A-PBX1 could bind to HOX and MEIS1 proteins it is still unclear whether such complexes are actually required for leukemic transformation or whether E2A-PBX1 and HOXA9 are each part of larger protein complexes acting in independent complementing oncogenic pathways. In this study we aim to search for other HOXA9 and E2A-PBX1 interacting proteins. To identify novel proteins interacting with human E2A-PBX1 or HOXA9 we used tandem affinity purification (TAP) of protein complexes from 697 pre-B leukemic and HeLa cell lines transduced to express E2A-PBX1 or HOXA9, respectively, with covalently attached FLAG/HA peptides. The protein composition of each complex was determined using tandem mass-spectrometry. In the E2A-PBX1 containing complex we identified lymphoid transcription factor IKAROS, chromatin remodeling factors of SWI/SNF family while multiple subunits of translation initiation factor eIF3, E3 ubiquitin ligase UBR5 emerged from the HOXA9 complex as potential critical protein partners. This is the first time the protein partners of either E2A-PBX1 or HOXA9 oncoproteins were identified using an unbiased biochemical approach. The identification of translation initiation factors associated with HOXA9 might indicate a novel function for HOX proteins independent of their transcriptional activity. [ABSTRACT FROM AUTHOR]

In the last decade it has become clear that homeobox containing genes (HOX genes) not only play a significant role in regulating body formation, but in addition, they are contributing to organization and regulation of hematopoiesis. Modern molecular technologies showed that deregulated expression or disruption of Hox genes can lead to altered characteristics of blood cells or disturbance of blood cell development. In this paper we review the role of HOX proteins in hematopoiesis and leukemogenesis and speculate about their possible target genes and involvement in lymphomagenesis. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment of desmoid tumours is controversial. We evaluated desmoid management in Dutch familial adenomatous polyposis (FAP) patients.Methods: Seventy-eight FAP patients with desmoids were identified from the Dutch Polyposis Registry. Data on desmoid morphology, management, and outcome were analysed retrospectively. Progression-free survival (PFS) rates and final outcome were compared for surgical vs non-surgical treatment, for intra-abdominal and extra-abdominal desmoids separately. Also, pharmacological treatment was evaluated for all desmoids.Results: Median follow-up was 8 years. For intra-abdominal desmoids (n=62), PFS rates at 10 years of follow-up were comparable after surgical and non-surgical treatment (33% and 49%, respectively, P=0.163). None of these desmoids could be removed entirely. Eventually, one fifth died from desmoid disease. Most extra-abdominal and abdominal wall desmoids were treated surgically with a PFS rate of 63% and no deaths from desmoid disease. Comparison between NSAID and anti-estrogen treatment showed comparable outcomes. Four of the 10 patients who received chemotherapy had stabilisation of tumour growth, all after doxorubicin combination therapy.Conclusion: For intra-abdominal desmoids, a conservative approach and surgery showed comparable outcomes. For extra-abdominal and abdominal wall desmoids, surgery seemed appropriate. Different pharmacological therapies showed comparable outcomes. If chemotherapy was given for progressively growing intra-abdominal desmoids, most favourable outcomes occurred after combinations including doxorubicin. [ABSTRACT FROM AUTHOR]

Using murine Moloney leukemia virus (MMLV)-based proviral insertional mutagenesis, we previously showed a preferential targeting of a small region in the Hoxa gene locus in E2A–PBX1-induced lymphoid leukemia resulting in the overexpression of several Hoxa genes including Hoxa10, Hoxa9 and Hoxa7. This observation suggested a functional interaction between Hox gene overexpression and E2A–PBX1 in lymphoid tumors. To further explore this possibility, we generated a series of compound E2A–PBX1 × Hox transgenic mice and tested the genetic interaction between these genes in the generation of lymphoid leukemia in vivo. Results presented in this report show that the onset of T-cell leukemia is significantly accelerated in E2A–PBX1 × Hoxb4 compound transgenic animals when compared with control E2A–PBX1 or Hoxb4 littermates. Hoxa9 appears less potent than Hoxb4 to accelerate E2A–PBX1-induced T-cell leukemia in mice. E2A–PBX1-induced T-cell leukemias express much higher levels of Hoxa genes than MMLV-induced counterparts, possibly suggesting a contribution of these genes to T-cell transformation by E2A–PBX1. Collectively, these data provide the first genetic evidence showing oncogenic collaboration between E2A–PBX1 and a Hox gene in lymphoid malignancies in vivo and document the specific deregulation of a subgroup of Hoxa genes in these leukemias.Oncogene (2008) 27, 6356–6364; doi:10.1038/onc.2008.233; published online 4 August 2008 [ABSTRACT FROM AUTHOR]

Although restoration of laryngeal function after laryngeal transplantation depends on appropriate reinnervation, non-selective reinnervation procedures result in synkinesis and poor function restoration. This study was performed to test the feasibility of selective reinnervation procedures to restore laryngeal function. Three surgical reinnervation procedures were studied each in a group of ten cats: in group 1 a non-selective procedure in which the recurrent laryngeal nerve (RLN) was cut and reanastomosed; in group 2 selective abductor reinnervation was performed with the phrenic nerve; in group 3 selective abductor reinnervation with the phrenic nerve (PN) was combined with selective adductor reinnervation with the ansa cervicalis. Ten weeks after surgical reinnervation abductor and reflex adductor functions were evaluated with videolaryngoscopy and electromyography. Findings demonstrated that non-selective reinnervation not only gave poor abduction during inspiration but even resulted in paradoxical movement during reflex adduction. Selective abductor reinnervation resulted in good abductor function. Selective adductor reinnervation with the ansa cervicalis brought about muscle tonus in the animals studied but no restoration of reflex adduction. Enhanced activity during respiratory distress gave only slight compromise to the abductor function. In all, selective laryngeal reinnervation with the PN and ansa cervicalis produced good restoration of respiratory laryngeal function. However, deglutition following laryngeal motor and sensory reinnervation with protection of the respiratory tract is probably not sufficient, as in the present group of animals no reflex glottic closure was achieved. More research is required. [ABSTRACT FROM AUTHOR]

Laryngeal reinnervation surgery is a difficult subject due to the fact that the recurrent laryngeal nerve (RLN) is responsible for both adductor and abductor laryngeal activity. Non-selective reinnervation procedures will result in laryngeal synkinesis with restoration of tonicity. Restoration of mobility requires selective reinnervation of the adductor and abductor branches with nerves with similar activity patterns as the initial abductor and adductor branches of the RLN. [ABSTRACT FROM AUTHOR]

For reliable detection of mRNA by non-radioactive in situ hybridization, calibration and standardization of the individual steps involved are essential. We describe a method that allows determination of the size and integrity as well as quantification of biotinylated RNA probes in a single experiment. Serial dilutions of biotinylated RNA probes generated by promotor-mediated in vitro transcription were size-separated by gel electrophoresis in the presence of known amounts of 5′-biotinylated oligomers which served as internal standard. Following immobilization onto nylon membranes and visualization by chemiluminescence, optical densities of probes and internal standards were measured by densitometry and analysed by linear regression. RNA probes complementary to the human homeobox genes HOX-C6, -C8 and -C9 were quantified. Four different 5′-biotinylated oligomers (20, 35, 50 and 75 bases) were tested as internal standards. Concerning the separation of probe and oligomer in the gel, transfer properties and efficiency of binding to the membrane, the oligomer of 35 bases was found to be the best internal standard with highest reproducibility. Comparison of probe concentration by spectrophotometry and the described method showed a good correlation, indicating that our method is a reliable assay for quantitative and qualitative control of biotin-labelled probes. [ABSTRACT FROM AUTHOR]