Publications

No abstract is provided for this article.

Stimulation of muscarinic receptors in bovine tracheal smooth muscle (BTSM) causes a sustained increase in muscle tone, but a transient increase in the second messenger Ins(1,4,5)P3. To examine whether this brief increase in Ins(1,4,5)P3 mass results from transient formation or is due to agonist-stimulation of Ins(1,4,5)P3 metabolism, we have studied the relationship between mass changes in PtdIns(4,5)P2 and Ins(1,4,5)P3 accumulation, and changes in [3H]InsP3, [3H]PtdIns, [3H]PtdInsP1 and [3H]PtdInsP2 in carbachol-stimulated myo-[3H]inositol-prelabelled BTSM slices. Carbachol (0.1 mM) caused a rapid transient increase in Ins(1,4,5)P3 concentration (basal, 12.9 +/- 0.8 pmol/mg of protein; 5 s carbachol treatment, 27.1 +/- 1.5 pmol/mg of protein), with values returning to basal levels by 30 s, but a sustained accumulation of total [3H]InsP3s, with [3H]Ins(1,3,4)P3 being the predominant isomer present at later time points. In contrast, PtdIns(4,5)P2 mass, determined by radioreceptor assay of Ins(1,4,5)P3 in desalted alkaline hydrolysates of acidified chloroform/methanol tissue extracts, declined rapidly (basal, 941 +/- 22 pmol/mg of protein; 120 s carbachol, 365 +/- 22 pmol/mg of protein; t1/2 14 s) and remained at this new steady-state level for at least 20 min in the continued presence of carbachol. Addition of 10 microM-atropine 2 min after carbachol caused a prompt return of PtdIns(4,5)P2 concentration to prestimulated values (t1/2 210 s). Ongoing resynthesis of PtdIns(4,5)P2 after carbachol stimulation was demonstrated in [3H]inositol-labelled tissue by observing a persistent increase in the specific radioactivity of [3H]PtdInsP2, shown to be exclusively [3H]PtdIns(4,5)P2, over a 10 min period. These findings strongly suggest the occurrence of persistent receptor-mediated increases in PtdIns(4,5)P2 hydrolysis and Ins(1,4,5)P3 formation which, in conjunction with the transient accumulation of Ins(1,4,5)P3 observed, provide evidence that regulation of the metabolism of Ins(1,4,5)P3 is a major determinant of Ins(1,4,5)P3 concentration in this tissue under agonist-stimulated conditions.

The books and articles devoted to the anatomy of the aortic valvar complex are numerous. Until now, however, little consideration has been given to understanding the anatomy with percutaneous valvar replacement in mind. It is axiomatic that knowledge of the anatomy of the valve is fundamental in understanding key principles involved in valvar replacement. Such an appreciation of the anatomy helps better understand the optimal positioning for the prosthetic valve within the root of the aorta with respect to the coronary arteries, mitral valve, and the conduction system and may circumvent complications that can arise during its implantation. In this review, therefore, we describe the anatomy of the trifoliate aortic valvar complex and its implications for percutaneous valvar replacement.

Background —Intracoronary γ- and β-radiation have reduced restenosis in animal models. In the clinical setting, the effectiveness of β-emitters has not been studied in a broad spectrum of patients, particularly those receiving stents. Methods and Results —A prospective, randomized, sham-controlled study of intracoronary radiotherapy with the β-emitting 32 P source wire, using a centering catheter and automated source delivery unit, was conducted. A total of 105 patients with de novo (70%) or restenotic (30%) lesions who were treated by stenting (61%) or balloon angioplasty (39%) received 0 (control), 16, 20, or 24 Gy to a depth of 1 mm in the artery wall. Angiography at 6 months showed a target site late loss index of 11±36% in radiotherapy patients versus 55±30% in controls ( P <0.0001). A low late loss index was seen in stented and balloon-treated patients and was similar across the 16, 20, and 24 Gy radiotherapy groups. Restenosis (≥50%) rates were significantly lower in radiotherapy patients at the target site (8% versus 39%; P =0.012) and at target site plus adjacent segments (22% versus 50%; P =0.018). Target lesion revascularization was needed in 5 radiotherapy patients (6%) and 6 controls (24%; P <0.05). Stenosis adjacent to the target site and late thrombotic events reduced the overall clinical benefit of radiotherapy. Conclusions —β-radiotherapy with a centered 32 P source is safe and highly effective in inhibiting restenosis at the target site after stent or balloon angioplasty. However, minimizing edge narrowing and late thrombotic events must be accomplished to maximize the clinical benefit of this modality.

Push-out tests have been conducted on 18 rectangular concrete-filled steel tubular (CFST) columns with the aim of studying the bond behaviour between the steel tube and the concrete infill. The obtained load-slip response and the distribution of the interface bond stress along the member length and around the cross-section for various load levels, as derived from measured axial strain gradients in the steel tube, are reported. Concrete compressive strength, interface length, cross-sectional dimensions and different interface conditions were varied to assess their effect on the ultimate bond stress. The test results indicate that lubricating the steel-concrete interface always had a significant adverse effect on the interface bond strength. Among the other variables considered, concrete compressive strength and cross-section size were found to have a pronounced effect on the bond strength of non-lubricated specimens for the range of cross-section geometries considered, which is not reflected in the European structural design code for composite structures, EN 1994-1-1 (2004). Finally, based on nonlinear regression of the test data generated in the present study, supplemented by additional data obtained from the literature, an empirical equation has been proposed for predicting the average ultimate bond strength for SHS and RHS filled with normal strength concrete.

Myristoylated alanine-rich C kinase substrate (MARCKS) is a central regulatory molecule involved in mucin granule release by normal human bronchial epithelial cells in vitro. Upon stimulation, activated PKC phosphorylates MARCKS (p-MARCKs), causing translocation of p-MARCKS from the plasma membrane to the cytoplasm, where it is then dephosphorylated, thus interacting with mucin granule membranes and mediating their subsequent exocytosis. The aim of our study was to investigate by immunohistochemistry (IHC) the expression of protein p-MARCKS in the bronchial rings, obtained during lung resection surgery, of smokers (current and ex) with or without COPD compared with non-smoker subjects. We examined formalin-fixed paraffin-embedded bronchial rings by IHC for identification of total p-MARCKS+ cells. The number of p-MARCKS+ve cells was determined among the mucous cells in the bronchial submucosal glands. Samples from 10 age-matched non-smokers subjects, 29 smokers with normal lung function and 29 smokers with COPD were obtained. We were unable to detect any significant differences in p-MARCKS in the bronchial mucous glands between the 3 groups of subjects. This data suggests that the p-MARCKS pathway is not critical for mucin secretion in the bronchial glands of COPD patients.

Objectives To assess the clinical profile and long-term mortality in SYNTAX score II based strata of patients who received percutaneous coronary interventions (PCI) in contemporary randomized trials. Background The SYNTAX score II was developed in the randomized, all-comers' SYNTAX trial population and is composed by 2 anatomical and 6 clinical variables. The interaction of these variables with the treatment provides individual long-term mortality predictions if a patient undergoes coronary artery bypass grafting (CABG) or PCI. Methods Patient-level (n=5433) data from 7 contemporary coronary drug-eluting stent (DES) trials were pooled. The mortality for CABG or PCI was estimated for every patient. The difference in mortality estimates for these two revascularization strategies was used to divide the patients into three groups of theoretical treatment recommendations: PCI, CABG or PCI/CABG (the latter means equipoise between CABG and PCI for long term mortality). Results The three groups had marked differences in their baseline characteristics. According to the predicted risk differences, 5115 patients could be treated either by PCI or CABG, 271 should be treated only by PCI and, rarely, CABG (n=47) was recommended. At 3-year follow-up, according to the SYNTAX score II recommendations, patients recommended for CABG had higher mortality compared to the PCI and PCI/CABG groups (17.4%; 6.1% and 5.3%, respectively; P<0.01). Conclusions The SYNTAX score II demonstrated capability to help in stratifying PCI procedures.