Oncogenic H-Ras V12 promotes anchorage-independent cytokinesis in human fibroblasts

Cell anchorage is required for cell proliferation of untransformed cells, whereas anchorage-independent growth can be induced by oncogenes and is a hallmark of transformation. Whereas anchorage-dependent control of the progression of the G(1) phase of the cell cycle has been extensively studied, it is less clear whether and how anchorage may control other cell cycle phases and whether oncogenes may affect such controls. Here, we found that lack of cell anchorage did not influence progression through the cell cycle S phase, G(2) phase, or most of mitosis of primary human fibroblasts. However, unanchored fibroblasts could not complete cytokinesis. The cleavage furrow and central spindle were still formed in the absence of anchorage, but cells were unable to complete ingression, causing binucleation. Importantly, V12 H-Ras-transformed fibroblasts and two cancer cell lines progressed through the entire cell cycle without anchorage, including through cytokinesis. This indicates that oncogenic signaling may contribute to anchorage-independent growth and tumorigenesis by promoting the final cleavage furrow ingression during cytokinesis.     

Red Blood Cell Distribution Width (RDW) and long-term survival in patients with ST Elevation Myocardial Infarction

Introduction

High RDW values are associated with adverse prognosis in many clinical conditions including short and medium term outcome of patients with ST Elevation Myocardial Infarction (STEMI). The aim of the present study was to evaluate the association between RDW and long term mortality in STEMI patients undergoing primary angioplasty (PPCI).

Material and methods

A cohort of 535 STEMI patients undergoing PPCI were divided into two groups (RDW > 14%, RDW ≤ 14%) using CHAID and CART methods. The association between RDW and 5-year all-cause mortality was assessed using Cox’s proportional hazards analysis.

Results

A total of 37 patients died during follow up of 5 years (mean: 1059, median: 1013, range 2–2130 days). RDW > 14% was associated with increased risk of all-cause mortality (HR = 5, CI 95% 2.7– 9.9, p < 0.001). In multivariate analysis, RDW > 14 remained significantly associated with increased risk for all-cause mortality (HR = 3.8, CI 95% 1.8– 7.99, p < 0.001). Patients with RDW above 14% did not have lower ejection fraction, higher CPK or more conventional risk factors.

Conclusion

RDW value above 14 is independently associated with increased long term all-cause mortality in patients with STEMI undergoing PPCI.     

Contrast enhanced spiral computerized tomography in patients with chronic obstructive uropathy and normal serum creatinine: a single session for anatomical and functional assessment

PURPOSE: We evaluated contrast enhanced spiral computerized tomography (CT) as a single session for the anatomical and functional assessment of patients with chronic obstructive uropathy and normal serum creatinine. MATERIALS AND METHODS: The study included 65 patients with unilateral or bilateral chronic renal obstruction and normal serum creatinine. Five patients had bilateral obstruction and the remaining 60 had unilateral obstruction and a normal contralateral kidney. Therefore, the total number of renal units was 130, that is 70 obstructed and 60 normal. All patients underwent contrast enhanced spiral CT together with excretory urography (IVP) and Tc-mercaptoacetyltriglycine renal scan. CT was used to identify the cause of obstruction and selectively determine the glomerular filtration rate (GFR) of the 2 kidneys. The diagnostic accuracy of CT for identifying the cause of hydronephrosis was compared with that of IVP. Moreover, a correlation was made between CT GFR and isotope GFR. RESULTS: Obstruction was caused by ureteropelvic junction narrowing in 25 cases, ureteral stones in 21, ureteral stricture in 20 and extrinsic ureteral obstruction in 4. Contrast enhanced spiral CT identified the cause of hydronephrosis in all obstructed kidneys (100% sensitivity), while IVP identified the cause in 52 (74% sensitivity), which was a significant difference (p <0.05). CT and IVP excluded obstruction in all normal kidneys (100% specificity). A comparison between the isotope GFR of obstructed kidneys with the corresponding CT GFR showed a perfect correlation (r = 0.78, p <0.0001). Moreover, a similar comparison between isotope GFR and CT GFR of normal kidneys showed an excellent correlation (r = 0.73, p <0.0001). In obstructed and normal kidneys mean isotope clearance was not significantly different from that of mean CT clearance. CONCLUSIONS: Contrast enhanced spiral CT is more sensitive than IVP for identifying the cause of chronic obstructive uropathy. Moreover, it is as accurate as radioisotope renal scan for calculating the total and separate kidney function. We recommend spiral CT with contrast medium as a single radiological diagnostic modality for the assessment of patients with chronic renal obstruction and normal serum creatinine.     

Synthesis,SAR studies,and insecticidal activities of certain N-heterocycles derived from 3-((2-chloroquinolin-3-yl)methylene)-5-phenylfuran-2(3H)-one against Culex pipiens L. larvae

An acid hydrazide derivative was synthesized and transformed into a variety of valuable N-heterocycles such as pyridazinone, oxadiazole, triazolopyridazinone, and triazole derivatives via reactions with certain carbon electrophiles such as 4-methoxybenzaldehyde, indole-3-carbaldehyde, pentan-2,4-dione, and carbon disulfide. The chemical structures of all prepared compounds were verified via their analytical and spectroscopic data. The insecticidal activity of the N-heterocycles was evaluated against field and lab strains of the third larval instar of Culex pipiens. All tested compounds exhibited higher larvicidal activity against the lab strains compared to the field strains, with dissimilar ratios. The obtained results demonstrate that the high toxicity achieved by oxadiazole followed the order of furanone, pyridazinone and hydrazide, with lower LC₅₀ values of the hydrazone and N-acetylpyridazinone derivatives compared to that of imidacloprid. Interestingly, these compounds are promising agents for insect pest control, especially since they are insoluble in water and can overcome the disadvantages of neonicotinoid applications in pest management programs.

A new series of N-heterocycles including pyridazinone, oxadiazole, triazolopyridazinone, and triazole derivatives were synthesized from the acid hydrazide via its reaction with certain carbon electrophiles.     

Scaling of morphogen gradients by an expansion-repression integral feedback control

Despite substantial size variations, proportions of the developing body plan are maintained with a remarkable precision. Little is known about the mechanisms that ensure this adaptation (scaling) of pattern with size. Most models of patterning by morphogen gradients do not support scaling. In contrast, we show that scaling arises naturally in a general feedback topology, in which the range of the morphogen gradient increases with the abundance of some diffusible molecule, whose production, in turn, is repressed by morphogen signaling. We term this mechanism “expansion–repression” and show that it can function within a wide range of biological scenarios. The expansion-repression scaling mechanism is analogous to an integral-feedback controller, a key concept in engineering that is likely to be instrumental also in maintaining biological homeostasis.     

Bacteriological aspects of Darier’s disease

Background There are no established data on the prevalence of bacterial colonization of lesional skin, nares and perineum in Darier’s disease (DD), or its contribution to the clinical manifestations of the disease. Objective To determine the prevalence of bacterial colonization of lesional skin and Staphylococcus aureus (S. aureus) in nares and perineum in 75 patients with DD, the association of these parameters with disease and patient characteristics, and the features of the bacterial skin infection in this group. Methods Medical interviews and physical examinations were performed. Bacteria were isolated from swabs taken from lesional skin, nares and perineum. Results S. aureus was isolated in 68%, 47% and 22% of lesional skin, nares and perineum cultures respectively. Subjects with positive S. aureus culture from lesional skin and/or nares had a statistically significant higher percentage of skin area affected and a more severe disease than patients with negative culture. Thirty of the 75 patients (40%) recalled bacterial skin infection, most often on the chest. Conclusions Patients with DD have high prevalence of S. aureus colonization in lesional skin and nares, with a correlation between disease severity and extent of the colonization. Further studies examining the consequences of S. aureus eradication in those sites may establish the need for S. aureus lesional skin and nares colonization screening and eradication as part of the treatment of DD exacerbations.