Predictive Value of Mean Platelet Volume in Saphenous Vein Graft Disease

Abstract Objective: To determine whether mean platelet volume (MPV), platelet distribution width (PDW), and platelet count could be used as determinants of mortality following coronary artery bypass graft (CABG) surgery and patency of saphenous vein grafts (SVG). Methods: The records of 128 patients who underwent emergency or elective coronary angiography after CABG surgery, and who died at an early stage were retrospectively reviewed. Patients were divided into three groups as early death, no SVG disease (SVGD), and SVGD group. MPV, PDW, and platelet count were evaluated at different times. Results: MPV was significantly higher in the stenotic group than in the nonstenotic group (9.7±1.8 fl and 8.2±0.9 fl, P<0.05). The postoperative MPV ratio was found to be higher in the stenotic group when compared to the preoperative period (9.6±1.8 fl and 7.8±0.9 fl, P<0.05). MPV values were also found to be higher in patients who died during the early stage than in surviving patients (9.4±1.9 fl and 8.0±1.0 fl, P<0.05). There was no statistically significant difference regarding platelet count and PDW ratios between the early deaths group and surviving patients. An MPV value higher than 10.6 predicted SVGD with 85% sensitivity and 45% specificity; and an MPV higher than 7.9 predicted early death with 80% sensitivity and 68% specificity were observed. Conclusion: MPV may be a useful indicator for the prediction of SVGD and mortality following CABG surgery

DNA end-independent activation of DNA-PK mediated via association with the DNA-binding protein C1D

DNA-dependent protein kinase (DNA-PK), which is involved in DNA double-strand break repair and V(D)J recombination, is comprised of a DNA-targeting component termed Ku and an ∼465-kD catalytic subunit, DNA-PK(cs). Although DNA-PK phosphorylates proteins in the presence of DSBs or other discontinuities in the DNA double helix in vitro, the possibility exists that it is also activated in other circumstances via its association with additional proteins. Here, through use of the yeast two-hybrid screen, we discover that the recently identified high affinity DNA binding protein C1D interacts with the putative leucine zipper region of DNA-PK(cs). Furthermore, we show that C1D can interact with DNA-PK in mammalian cells and that C1D is a very effective DNA-PK substrate in vitro. Finally, we establish that C1D directs the activation of DNA-PK in a manner that does not require DNA termini. Therefore, these studies provide a function for C1D and suggest novel mechanisms for DNA-PK activation in vivo

Tbx3 represses PTEN and is over-expressed in head and neck squamous cell carcinoma

Abstract Background Despite advances in diagnostic and treatment strategies, head and neck squamous cell cancer (HNSCC) constitutes one of the worst cancer types in terms of prognosis. PTEN is one of the tumour suppressors whose expression and/or activity have been found to be reduced in HNSCC, with rather low rates of mutations within the PTEN gene (6-8%). We reasoned that low expression levels of PTEN might be due to a transcriptional repression governed by an oncogene. Tbx2 and Tbx3, both of which are transcriptional repressors, have been found to be amplified or over-expressed in various cancer types. Thus, we hypothesize that Tbx3 may be over expressed in HNSCC and may repress PTEN, thus leading to cancer formation and/or progression. Methods Using immunohistochemistry and quantitative PCR (qPCR), protein and mRNA levels of PTEN and Tbx3 were identified in samples excised from cancerous and adjacent normal tissues from 33 patients who were diagnosed with HNSCC. In addition, HeLa and HEK cell lines were transfected with a Tbx3 expressing plasmid and endogenous PTEN mRNA and protein levels were determined via qPCR and flow cytometry. Transcription assays were performed to demonstrate effects of Tbx3 on PTEN promoter activity. Mann–Whitney, Spearman’s Correlation and Wilcoxon signed-rank tests were used to analyze the data. Results We demonstrate that in HNSCC samples, Tbx3 mRNA levels are increased with respect to their normal tissue counterparts (p Conclusions We show that Tbx3 is up-regulated in tissue samples of HNSCC patients and that Tbx3 represses PTEN transcription. Thus, our data not only reveals a new mechanism that may be important in cancer formation, but also suggests that Tbx3 can be used as a potential biomarker in cancer.</p

Interleukin-1β secretion in hippocampal sclerosis patients with mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a common medically intractable epilepsy syndrome. Although pathogenesis of HS still remains highly controversial, genetics may play a role as a predisposing factor. Previous evidence in a Japanese population revealed that the homozygotes for allele T at position −511 of the interleukin (IL)-1β gene promoter region (IL-1β-511 T/T) confers susceptibility to the development of HS. However, whether this polymorphism has an effect on IL-1β levels in MTLE-HS patients was not demonstrated. This study aimed to analyze the distribution of this particular polymorphism in a group of Turkish HS patients and correlate the polymorphism with IL-1β secretion from the lymphocytes, thus revealing a functional role for IL-1β in the etiopathogenesis of HS. A single base pair polymorphism at position −511 in the promoter region of the IL-1β gene was analyzed. The spontaneous and 1 ng/mL lipopolysaccharide-stimulated production of IL-1β by peripheral blood mononuclear cells after 4 and 24 h of incubation were measured by ELISA method. The heterozygous type (−511 C/T) was the most common genotype. There was no difference in frequency of allele −511 T between patients and controls. Analysis of IL-1β levels, genotype and allele distributions showed no significant difference among the groups (P&gt;0.05). Nevertheless, it was seen that patients who carry a T allele at position -511 of the IL-1β gene had increased IL-1β levels. T-allele carriage may be important. Only IL-1β secretion from the lymphocytes has been assessed in this study. Considering the importance of IL-1β in the etiopathogenesis of HS, further studies are needed to evaluate locally produced IL-1β levels