Self-organization of actin networks by a monomeric myosin.

The organization of actomyosin networks lies at the center of many types of cellular motility, including cell polarization and collective cell migration during development and morphogenesis. Myosin-IXa is critically involved in these processes. Using total internal reflection fluorescence microscopy, we resolved actin bundles assembled by myosin-IXa. Electron microscopic data revealed that the bundles consisted of highly ordered lattices with parallel actin polarity. The myosin-IXa motor domains aligned across the network, forming cross-links at a repeat distance of precisely 36 nm, matching the helical repeat of actin. Single-particle image processing resolved three distinct conformations of myosin-IXa in the absence of nucleotide. Using cross-correlation of a modeled actomyosin crystal structure, we identified sites of additional mass, which can only be accounted for by the large insert in loop 2 exclusively found in the motor domain of class IX myosins. We show that the large insert in loop 2 binds calmodulin and creates two coordinated actin-binding sites that constrain the actomyosin interactions generating the actin lattices. The actin lattices introduce orientated tracks at specific sites in the cell, which might install platforms allowing Rho-GTPase-activating protein (RhoGAP) activity to be focused at a definite locus. In addition, the lattices might introduce a myosin-related, force-sensing mechanism into the cytoskeleton in cell polarization and collective cell migration.

[Primary pulmonary artery sarcoma in 36-year-old women: 3-years follow-up after partial resection and radiotherapy]. / Pierwotny miesak tetnicy plucnej u 36-letniej pacjentki: obserwacja 3-letnia po czesciowej resekcji i radioterapii.

Intimal sarcoma of the heart and pulmonary artery is a very rare, malignant, primary tumour. The prognosis in patients with primary sarcoma of the pulmonary artery, including intimal sarcoma, is poor. We present the case and 3-years follow-up of 36-year-old woman who was successfully treated with surgical, partial resection of the tumour followed by radiotherapy.

Prognostic value of renal fractional flow reserve in blood pressure response after renal artery stenting (PREFER study).

BACKGROUND: The aim of our study was to determine a potential relationship between resting translesional pressures ratio (Pd/Pa ratio), renal fractional flow reserve (rFFR) and blood pressure response after renal artery stenting. METHODS: Thirty five hypertensive patients (49% males, mean age 64 years) with at least 60% stenosis in angiography, underwent renal artery stenting. Translesional systolic pressure gradient (TSPG), Pd/Pa ratio (the ratio of mean distal to lesion and mean proximal pressures) and hyperemic rFFR - after intrarenal administration of papaverine - were measured before stent implantation. Ambulatory blood pressure measurements (ABPM) were recorded before the procedure and after 6 months. The ABPM results were presented as blood pressure changes in subgroups of patients with normal (≥ 0.9) vs. abnormal (< 0.9) Pd/Pa ratio and normal (≥ 0.8) vs. abnormal (< 0.8) rFFR. RESULTS: Median Pd/Pa ratio was 0.84 (interquartile range 0.79-0.91) and strongly correlated with TSPG (r = -0.89, p < 0.001), minimal lumen diameter (MLD; r = 0.53, p < 0.005) and diameter stenosis (DS; r = -0.51, p < 0.005). Median rFFR was 0.78 (0.72-0.82). Similarly, significant correlation between rFFR and TSPG (r = -0.86, p < 0.0001), as well as with MLD (r = 0.50, p < 0.005) and DS (r = -0.51, p < 0.005) was observed. Procedural success was obtained in all patients. Baseline Pd/Pa ratio and rFFR did not predict hypertension response after renal artery stenting. Median changes of 24-h systolic/diastolic blood pressure were comparable in patients with abnormal vs. normal Pd/Pa ratio (-4/-3 vs. 0/2 mm Hg; p = NS) and with abnormal vs. normal rFFR (-2/-1 vs. -2/-0.5 mm Hg, respectively). CONCLUSIONS: Physiological assessment of renal artery stenosis using Pd/Pa ratio and papaverine- induced renal fractional fl ow reserve did not predict hypertension response after renal artery stenting.

Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea.

Percutaneous renal sympathetic denervation by radiofrequency energy has been reported to reduce blood pressure (BP) by the reduction of renal sympathetic efferent and afferent signaling. We evaluated the effects of this procedure on BP and sleep apnea severity in patients with resistant hypertension and sleep apnea. We studied 10 patients with refractory hypertension and sleep apnea (7 men and 3 women; median age: 49.5 years) who underwent renal denervation and completed 3-month and 6-month follow-up evaluations, including polysomnography and selected blood chemistries, and BP measurements. Antihypertensive regimens were not changed during the 6 months of follow-up. Three and 6 months after the denervation, decreases in office systolic and diastolic BPs were observed (median: -34/-13 mm Hg for systolic and diastolic BPs at 6 months; both P<0.01). Significant decreases were also observed in plasma glucose concentration 2 hours after glucose administration (median: 7.0 versus 6.4 mmol/L; P=0.05) and in hemoglobin A1C level (median: 6.1% versus 5.6%; P<0.05) at 6 months, as well as a decrease in apnea-hypopnea index at 6 months after renal denervation (median: 16.3 versus 4.5 events per hour; P=0.059). In conclusion, catheter-based renal sympathetic denervation lowered BP in patients with refractory hypertension and obstructive sleep apnea, which was accompanied by improvement of sleep apnea severity. Interestingly, there are also accompanying improvements in glucose tolerance. Renal sympathetic denervation may conceivably be a potentially useful option for patients with comorbid refractory hypertension, glucose intolerance, and obstructive sleep apnea, although further studies are needed to confirm these proof-of-concept data.

Assessment of renal artery stenosis using both resting pressures ratio and fractional flow reserve: relationship to angiography and ultrasonography.

BACKGROUND. Clinical benefit from renal artery revascularization remains controversial, probably because of inaccurate stenosis severity assessment. Objective. The aim of the study was to evaluate resting translesional pressures ratio and renal fractional flow reserve (rFFR) in relation to angiography and Doppler duplex ultrasonography in patients with at least moderate renal artery stenosis (RAS). METHODS. 44 hypertensive patients (48% of males, mean age 65 years) with at least moderate RAS were investigated. Translesional systolic pressure gradient (TSPG), resting Pd/Pa ratio (the ratio of mean distal to lesion and mean proximal pressures) and hyperemic rFFR - after intrarenal administration of papaverine - were evaluated. Quantitative angiographic analysis of stenosis severity was performed including minimal lumen diameter (MLD) and percent diameter stenosis (DS) assessment. Renal/aortic ratio (RAR), resistive index (RI) and deltaRI (side-to side difference) were obtained in Doppler-duplex ultrasonography. The predictive value of selected variables was calculated using receiver-operating characteristics curves. RESULTS. Mean Pd/Pa ratio was 0.86 ± 0.12 and decreased to 0.79 ± 0.13 after papaverine administration. Both Pd/Pa ratio and rFFR strongly correlated with TSPG (r = -0.92, p < 0.0001 and r = -0.88, p < 0.0001, respectively) and moderately with MLD (r = 0.62, p < 0.0001 and r = 0.66, p < 0.0001) and DS (r = -0.63, p < 0.0001 and r = -0.70, p < 0.0001). To identify more than 70% RAS, considered severe, the most predictive cut-off values were 0.93 for Pd/Pa ratio and 0.80 for rFFR. CONCLUSIONS. Mean Pd/Pa ratio and rFFR strongly correlated with angiographic data and in less pronounced manner with ultrasound parameters reflecting intrarenal blood flow. The best accuracy cut-off points for severe RAS predicting were 0.93 and 0.80, respectively.