Combined evaluation of regional coronary artery calcium and myocardial perfusion by 82Rb PET/CT in predicting lesion-related outcome

European Journal of Nuclear Medicine and Molecular Imaging - Cardiac imaging with positron emission tomography/computed tomography (PET/CT) allows measurement of coronary artery calcium (CAC),...     

Basic fibroblast growth factor: effects on matrix remodeling, receptor expression, and transduction pathway in human periosteal fibroblasts with FGFR2 gene mutation.

The Crouzon syndrome, which is associated with fibroblast growth factor receptor (FGFR2) mutations, is characterized by premature fusion of cranial sutures. We used an in vitro model of cultured periosteal fibroblasts from normal subjects and from Crouzon patients with FGFR2 mutation. We analyzed the matrix turnover rate and the effects of adding FGF2 by evaluating fibronectin synthesis and the activity of some proteolytic enzymes. To assess the role of some FGF signaling molecules involved in FGFR2 regulation, we studied Grb2 tyrosine phosphorylation and the phosphotyrosine proteins associated with Grb2. The iodinate FGF binding assay was performed to quantify FGFR expression. Compared with normal fibroblasts, fibronectin synthesis was decreased in Crouzon fibroblasts, and protease activities in cells and medium were enhanced, suggesting that excess fibronectin catabolism is present. Differences were more marked when FGF2 was added. Very few phosphoproteins were visible in anti-Grb2 immunoprecipitations from Crouzon fibroblasts, which showed a significant increase in the number of high-affinity and low-affinity FGF2 receptors. These results suggest that the abnormal genotype and the Crouzon cellular phenotype are related. To compensate the low levels of tyrosine phosphorylation, Crouzon cells might increase the numbers of FGFR2, thus increasing the cell surface binding sites for FGF2.     

Selective Inhibition of Ii-dependent Antigen Presentation by Helicobacter pylori Toxin VacA

A major virulence factor in the stomach chronic infection by Helicobacter pylori is a protein toxin (VacA), which alters cell membrane trafficking of late endosomal/prelysosomal compartments. Its role in the chronic infection established by H. pylori is unknown. To test the possibility that VacA alters antigen processing taking place in prelysosomal compartments, we have used the well-established model of antigen processing and presentation consisting of tetanus toxoid–specific human (CD4⁺) T cells stimulated by autologous antigen-pulsed Epstein-Barr virus-transformed B cells. We found that VacA interferes with proteolytic processing of tetanus toxin and toxoid and specifically inhibits the Ii-dependent pathway of antigen presentation mediated by newly synthesized major histocompatibility complex (MHC) class II, while leaving unaffected the presentation pathway dependent on recycling MHC class II. The results presented here suggest that VacA may contribute to the persistence of H. pylori by interfering with protective immunity and that this toxin is a new useful tool in the study of the different pathways of antigen presentation.More than 50% of the world population is infected with Helicobacter pylori, but most infections remain asymptomatic and only 10% of infected people become sick at some point in their life (1, 2). A close correlation has been established between the prolonged infection of the human stomach mucosa by H. pylori and the development of gastritis, and gastroduodenal ulcers, and with an increased risk of developing adenocarcinomas and other gastric tumors (1–3). In fact, H. pylori has been classified as a class I cancerogenic agent, being one of the factors involved in the development of stomach cancers. This bacterium enters the mucus layer covering the stomach epithelium and colonizes the human gastric mucosa: such infection may persist for decades. Bacterial factors necessary for colonization (for review see reference 1) are the flagella, which make this bacterium highly motile, adhesins, which strongly bind the saccharide moiety of glycoproteins and glycolipids, and a powerful urease, which buffers the acid stomach environment by releasing ammonia. Biopsies from patients affected by gastroduodenal ulcers almost invariably contain H. pylori strains harboring a pathogenicity island (4), characterized by the presence of the gene encoding for the 128-kD CagA protein, the major H. pylori antigen. Such strains also produce a 145-kD precursor that is processed and released in the culture medium as a 95-kD protein toxin (VacA), whose role in H. pylori infection is unknown (5).VacA perturbs endocytosis at a prelysosomal stage in a process requiring the activity of the small GTPase Rab7 (6). This causes the formation and accumulation of compartments endowed with the vacuolar ATPase and with membrane markers both of late endosomes and lysosomes (6–8). In particular, the presence of Rab7 and lysosomal membrane glycoproteins, and the parallel absence of the cation-independent mannose 6-P receptor, allows the identification of those vesicles as an intermediate between late endosomes and lysosomes (7). A similar profile of markers is present in the compartments of APCs, where antigen proteolytic processing takes place (for review see reference 9).Here, we have considered the possibility that VacA inhibits antigen processing by interfering with late endocytic membrane trafficking by APCs. This would in turn lower the proliferation of autologous human (CD4⁺) T cells triggered by recognition of antigenic epitopes bound to MHC class II molecules exposed on APC surfaces (10). We have used the well-defined cellular system of antigen processing and presentation consisting of human tetanus toxoid (TT)– specific (CD4⁺) T cells stimulated by autologous antigen-pulsed EBV-transformed B cells (10). TT is the most used human vaccine and its proteolytic processing and presentation by human lymphoid cells in culture has been intensively investigated (10–13). By using T cell clones with different specificity, we found that VacA interferes with the generation of T cell epitopes loaded on newly synthesized MHC class II molecules (the Ii-dependent pathway of antigen presentation), leaving unaffected generation and presentation of epitopes by class II molecules that recycle through early endosomal compartments (invariant chain [Ii]–independent pathway).     

Fractional carbon dioxide (CO2) laser combined with topical tretinoin for the treatment of different forms of cystic acne

Nodulocystic acne is prone to scarring and difficult to treat with treatments other than oral isotretinoin. The aim of this article is to discuss the role of a single session of a fractional carbon dioxide (CO₂) laser combined with a topical treatment with a tretinoin and antibiotic gel for a month as a successful treatment to improve nodulocystic acne and chronic microcystic acne. Two cases were involved: the first with nodulocystic acne lesions that persisted after oral retinoids and the second with chronic microcystic acne resistant to topical treatments. After only one session of treatment with the CO₂ laser and the topical treatment, a complete healing of the nodulocystic acne lesions was observed with minimal secondary effects. The microcystic acne showed great improvement. No other topical or oral treatment was needed. This treatment could be a safe and effective treatment for nodulocystic acne lesions and microcystic acne when other treatments fail. More studies should be performed to confirm our results.     

Video-Assisted Thyroidectomy Significantly Reduces the Risk of Early Postthyroidectomy Voice and Swallowing Symptoms

Background Voice and swallowing symptoms are frequently reported after thyroidectomy even in absence of objective voice alterations. We evaluated the influence of the video-assisted approach on voice and swallowing outcome of thyroidectomy. Methods Sixty-five patients undergoing total thyroidectomy (TT) were recruited. Eligibility criteria were: nodule size ≤30 mm, thyroid volume ≤30 ml, no previous neck surgery. Exclusion criteria were: younger than aged 18 years and older than aged 75 years, vocal fold paralysis, history of voice, laryngeal or pulmonary diseases, malignancy other than papillary thyroid carcinoma. Patients were randomized for video-assisted (VAT) or conventional (CT) thyroidectomy. Videostrobolaryngoscopy (VSL), acoustic voice analysis (AVA), and maximum phonation time (MPT) evaluation were performed preoperatively and 3 months after TT. Subjective evaluation of voice (voice impairment score = VIS) and swallowing (swallowing impairment score = SIS) were obtained preoperatively, 1 week, 1 month, and 3 months after TT. Results Fifty-three patients completed the postoperative evaluation: 29 in the VAT group, and 24 in the CT group. No laryngeal nerves injury was shown at postoperative VSL. Mean postoperative MPT, F ₀, F _low, F _high, and the number of semitones were significantly reduced in the CT group but not in the VAT group. Mean VIS 3 months after surgery was significantly higher than preoperatively in CT group but not in the VAT group. Mean SIS was significantly decreased 1 and 3 months after VAT but not after CT. Conclusions The incidence and the severity of early voice and swallowing postthyroidectomy symptoms are significantly reduced in patients who undergo VAT compared with conventional surgery. Presented at the ISW2007—IAES free paper session, Montreal, Canada, August 26–30, 2007.