Pathogenesis of ECL cell tumors in humans.

In ECL cell tumors developed in the setting of hypergastrinemic conditions (ECL cell carcinoids type 1 and 2), hypergastrinemia is the dominant agent acting as a promoter in all steps (hyperplasia-dysplasia-neoplasia) of the tumorigenic sequence. In contrast, it apparently lacks transforming properties as shown by the absence of ECL cell carcinoids in patients exposed to hypergastrinemia alone, i.e., those with sporadic Zollinger-Ellison syndrome. The potential transforming factors include: the allelic loss of the MEN-1 suppressor gene in the genetically predisposed MEN-1 patients, an alteration that may induce ECL cell tumors even in the absence of hypergastrinemia; the still unknown factor(s) associated with atrophic corporal gastritis; agents whose role in the induction of human ECL cell tumors is still unclarified, such as basic Fibroblast Growth Factor, human Chorionic Gonadotropin-alpha and Transforming Growth Factor-alpha; and agents having a favoring role on the ECL exposure to mitogens such as BCL-2. No information is currently available on the pathogenesis of gastrin-independent, sporadic ECL cell carcinoids (type 3) or of gastric neuroendocrine carcinomas.     

Coronary stent implantation throughout technical evolution: immediate and follow-up results

Coronary stenting (stent implantation) has evolved over the last 5 years with changes in stent design, stent material and the implantation technique. The use of high-pressure balloon inflation (HP), intravascular ultrasound (IVUS) and appropriate antiplatelet therapy have contributed to the abolishment of the need for subsequent anticoagulation, allowing extended stent applications. We compared results in three groups of patients having stent implantation throughout the period of evolution: group A: no IVUS, no HP, with subsequent anticoagulation treatment (n 3 434); group B: no IVUS, yes HP, without subsequent anticoagulation treatment (n 3 192); and group C: yes IVUS, yes HP, without subsequent anticoagulation treatment (n 3 588). The primary success rates were comparable in all groups. There was a clear change in indications for stenting in groups B and C compared with group A (elective stenting: group A 3 32%; group B 3 66%; group C 3 69%; P < 0.0001), in reference vessel size (group A 3 3.22 3 0.37 mm; group B 3 2.92 3 0.56 mm; group C 3 2.98 3 0.57 mm; P < 0.0001), and for presence of type B2 and C lesions (group A 3 57%; group B 3 72%; group C 3 74%; P < 0.001). The complication rate significantly decreased in group C (group A 3 3.6%; group B 3 4.1%; group C 3 1.2%; P < 0.001) and the mean patient hospital stay decreased to 2 days in groups B and C due to the abolition of the need for anticoagulant treatment. The angiographic restenosis rate increased in groups B and C (group A 3 20%; group B 3 34%; group C 3 32%; P < 0.001). The need for a repeat procedure increased as stenting of more complex lesions and smaller vessels was attempted: target lesion revascularization (TLR) was performed in 16% of patients in group A (73/434), in 18% of group B (35/192) and in 22% of group C (129/588) (P 3 0.04 for A versus C). Major cardiac events (MACE) occurred in 142 patients in group A (33%), 60 patients in group B (31%) and in 181 patients in group C (30%). The evolving technique of coronary stenting has expanded the spectrum of indications and range of coronary vessels attempted, and decreased the complication rates and hospital stay. However, in less-favorable subsets, additional improvements are needed to affect the long-term outcome.     

In human chromosomes telomeric regions are enriched in CpGs relative to R-bands

Human chromosomes were in situ nick-translated using as nicking agents the endonucleases MspI (CCGG), its methyl-sensitive isoschizomer HpaII, HaeIII (GGCC), SacII (CCGCGG), EcoRI (GAATTC) and DNaseI. We show that in metaphase chromosomes R-bands are enriched, as compared with G-bands, in the dinucleotide CpG but no more than what is expected on the basis of their relative G+C content. The telomeric regions, on the contrary, besides having a chromatin conformation that is particularly relaxed and accessible to endonucleases, also show an enrichment in CpGs.     

Effect of experimental obesity and subsequent weight reduction upon circulating atrial natriuretic peptide

The effect of obesity and weight reduction upon circulating concentrations of atrial natriuretic peptide was assessed in an experimental model of the disease. Obese rats weighing in excess of 750 g were compared with formerly obese animals subjected to a 15-week period of caloric restriction resulting in a 40% reduction in body weight. Mean adipocyte size was significantly reduced with weight loss, as was estimated body fat. Mean arterial blood pressure remained normotensive for both groups, but a significant reduction in heart rate was associated with weight reduction. Circulating atrial natriuretic peptide was significantly elevated in the lean rats, which also exhibited decreased plasma renin activity and a negative sodium balance. Analysis of heart to body weight ratios implied that an obesity-associated, volume-induced cardiac hypertrophy remained even after the normalization of body fat. These results suggest that the diuresis and natriuresis accompanying weight reduction may be facilitated by atrial natriuretic peptide, which was elevated in part due to a persistent left ventricular hypertrophy following the transition from the obese to lean condition.     

Glycosylated forms of nuclear lamins

Chromatin and pore complex-lamina preparations were obtained from pig and chicken tissues, and their proteins were analysed by mono- and bidimensional electrophoresis. A glycosylated form of lamin A, recognized by concanavalin A, was shown to be present in at least 3 of the tissues examined. Glycosylation is suggested to be a further postsynthetic modification, besides phosphorylation and methylation, which can modify the properties of lamins.     

Letter to Editor: Carpal tunnel syndrome due to an atypical deep soft tissue leiomyoma: The risk of misdiagnosis and mismanagement

A response to Chalidis et al: Carpal tunnel syndrome due to an atypical deep soft tissue leiomyoma: The risk of misdiagnosis and mismanagement. World J Surg Oncol 2007, 5:92.     

Flow cytometry-assisted purification and proteomic analysis of the corticotropes dense-core secretory granules

The field of organellar proteomics has emerged as an attempt to minimize the complexity of the proteomics data obtained from whole cell and tissue extracts while maximizing the resolution on the protein composition of a single subcellular compartment. Standard methods involve lengthy density-based gradient and/or immunoaffinity purification steps followed by extraction, 1-DE or 2-DE, gel staining, in-gel tryptic digestion, and protein identification by MS. In this paper, we present an alternate approach to purify subcellular organelles containing a fluorescent reporter molecule. The gel-free procedure involves fluorescence-assisted sorting of the secretory granules followed by gentle extraction in a buffer compatible with tryptic digestion and MS. Once the subcellular organelle labeled, this procedure can be done in a single day, requires no major modification to any instrumentation and can be readily adapted to the study of other organelles. When applied to corticotrope secretory granules, it led to a much enriched granular fraction from which numerous proteins could be identified through MS.     

Effects of decorin and biglycan on human airway smooth muscle cell proliferation and apoptosis

Proteoglycans (PG) are altered in the asthmatic airway wall. Because PGs are known to affect cell proliferation and apoptosis, we hypothesized that alterations in PG might influence the airway smooth muscle (ASM) hyperplasia observed in the asthmatic airway. Human ASM cells were seeded on plastic or plates coated with decorin (Dcn), biglycan (Bgn), or collagen type I (Col I) (1, 3, and 10 microg/ml). Cells were stimulated with platelet-derived growth factor (PDGF), and cell number was assessed at 0, 48, and 96 h. Cell proliferation was measured by bromodeoxyuridine (BrdU) incorporation and apoptosis by annexin V and propidium iodide staining at 48 h post-PDGF stimulation. A significant decrease in cell number was observed with cells seeded on Dcn (10 microg/ml) at 0, 48, and 96 h (P < 0.01). Dcn induced both decreases in BrdU incorporation and increases in annexin V staining (P < 0.05). Bgn decreased cell number at time 0 only (P < 0.05) and affected neither proliferation nor apoptosis. Col I (10 mug/ml) caused a significant increase in cell number at 48 and 96 h (P < 0.01). Adding exogenous Dcn (1-30 microg/ml) to the medium had no effect on cell number. Exposing Dcn-coated matrices to chondroitinase ABC, an enzyme that degrades glycosaminoglycan side chains, reversed the Dcn-induced decrease in cell number. These studies demonstrate that different PGs have variable effects on ASM cell proliferation and apoptosis. Recently described decreases in Dcn in the asthmatic airway wall could potentially permit more exuberant ASM growth.     

Purification and properties of Sandercyanin, a blue protein secreted in the mucus of blue forms of walleye, Sander vitreus

A blue protein present in the mucus coating blue forms of walleye, Sander vitreus, was purified to homogeneity by a combination of ion exchange and hydrophobic interaction chromatography. The purified protein has a molecular mass of 87,850 and is a homotetramer with a subunit molecular mass of 21,836. Solutions of the protein are deep blue in color and show absorbance maxima at 383 and 633 nm, respectively. Acetone treatment of the protein releases a blue chromophore with the spectral characteristics of biliverdin IXα. The results suggest that the blue protein is a new biliprotein that we have termed Sandercyanin. The function of Sandercyanin is unknown, but limited amino acid sequence analysis suggests it is a lipocalin that may be involved in the transport of heme degradation products.