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Showing papers by "University of Siena published in 2003"


Journal ArticleDOI
TL;DR: The usage of protein CO groups as biomarkers of oxidative stress has some advantages in comparison with the measurement of other oxidation products because of the relative early formation and the relative stability of carbonylated proteins.

2,097 citations


Journal ArticleDOI
TL;DR: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions.
Abstract: Background: There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions. Objective: The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms. Methods: Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. κ Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features. Results: Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean κ value: 0.53). Conclusion: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions. (J Am Acad Dermatol 2003;48:679-93.) J Am Acad Dermatol 2003;48:679-93.

971 citations


Journal ArticleDOI
TL;DR: Rapid recent progress in the identification of carbonylated proteins should provide new diagnostic (possibly pre-symptomatic) biomarkers for oxidative damage, and yield basic information to aid the establishment an efficacious antioxidant therapy.

908 citations


Journal ArticleDOI
TL;DR: The properties of the polyhedral partition of the state space induced by the multi-parametric piecewise affine solution are studied, and a new mp-QP solver is proposed that adopts a different exploration strategy for subdividing the parameter space, avoiding unnecessary partitioning and QP problem solving.

659 citations


Journal ArticleDOI
TL;DR: A surveillance guideline is proposed using TSH-stimulated Tg levels for patients who have undergone total or near-total thyroidectomy and (131)I ablation for DTC and have no clinical evidence of residual tumor with a serum Tg below 1 micro g/liter during THST.
Abstract: Recent studies have provided new information regarding the optimal surveillance protocols for low-risk patients with differentiated thyroid cancer (DTC). This article summarizes the main issues brought out in a consensus conference of thyroid cancer specialists who analyzed and discussed this new data. There is growing recognition of the value of serum thyroglobulin (Tg) as part of routine surveillance. An undetectable serum Tg measured during thyroid hormone suppression of TSH (THST) is often misleading. Eight studies show that 21% of 784 patients who had no clinical evidence of tumor with baseline serum Tg levels usually below 1 micro g/liter during THST had, in response to recombinant human TSH (rhTSH), a rise in serum Tg to more than 2 micro g/liter. When this happened, 36% of the patients were found to have metastases (36% at distant sites) that were identified in 91% by an rhTSH-stimulated Tg above 2 micro g/liter. Diagnostic whole body scanning, after either rhTSH or thyroid hormone withdrawal, identified only 19% of the cases of metastases. Ten studies comprising 1599 patients demonstrate that a TSH-stimulated Tg test using a Tg cutoff of 2 micro g/liter (either after thyroid hormone withdrawal or 72 h after rhTSH) is sufficiently sensitive to be used as the principal test in the follow-up management of low-risk patients with DTC and that the routine use of diagnostic whole body scanning in follow-up should be discouraged. On the basis of the foregoing, we propose a surveillance guideline using TSH-stimulated Tg levels for patients who have undergone total or near-total thyroidectomy and (131)I ablation for DTC and have no clinical evidence of residual tumor with a serum Tg below 1 micro g/liter during THST.

632 citations


Journal ArticleDOI
TL;DR: The extent of the changes suggests that neocortical GM pathology may occur early in the course of the disease in both RR and PP MS patients and contribute significantly to neurologic impairment.
Abstract: Objective: To assess cortical gray matter (GM) changes in MS and establish their relevance to clinical disability and to inflammatory changes of white matter (WM) in patients with the relapsing–remitting (RR) and primary progressive (PP) forms of the disease. Methods: Conventional MRI examinations were obtained in patients with definite MS who had either the RR or the PP form of the disease. An automated analysis tool was used with conventional T1-weighted MR images to obtain total and cortical brain volumes normalized for head size. Total brain lesion load was estimated on conventional proton density and T2-weighted MR images. The relationship between volumetric MR measures and scores of clinical disability was assessed. Results: Normalized cortical volumes (NCV) were lower for both RR and PP MS patients than for normal control subjects ( p p > 0.5). NCV decreases in both patients groups were detected even in those patients with short disease duration ( p p p p r = −0.47, p r = −0.25, p p r = −0.64, p r = −0.27, p = 0.04) MS patients. Conclusions: These data confirm substantial neocortical volume loss in MS patients and suggest that neocortical GM pathology may occur early in the course of the disease in both RR and PP MS patients and contribute significantly to neurologic impairment. Although a proportion of this neocortical pathology may be secondary to WM inflammation, the extent of the changes suggests that, especially in patients with PP MS, an independent neurodegenerative process also is active.

484 citations


Journal ArticleDOI
TL;DR: This is the first time that a protocol for protein extraction from olive leaf appears to give satisfactory and reproducible results, and is expected to be applicable to other recalcitrant plant tissues and could be of interest to laboratories involved in plant proteomics.
Abstract: The purpose of this research is to establish a routine procedure for the application of proteomic analysis to olive tree. Olive leaf tissue is notoriously recalcitrant to common protein extraction methods due to high levels of interfering compounds. We developed a protocol for isolating proteins suitable for two-dimensional electrophoresis (2-DE) from olive leaf. The remarkable characteristics of the protocol include: (i) additional grinding dry acetone powder of leaf tissue to a finer extent, (ii) after extensive organic solvent washes to remove pigments, lipids etc., using aqueous tricholoroacetic acid washes to remove water-soluble contaminants, and (iii) phenol extraction of proteins in the presence of sodium dodecyl sulfate. The final protein preparation is free of interfering compounds based on its well-resolved 2-DE patterns. The protocol can be completed within 3 h, and protein yield is approximately 2.49 mg.g(-1) of aged leaf. We also evaluated the protocol by immunoblotting with anti-tyrosinate alpha-tubulin antibody. To our knowledge, this is the first time that a protocol for protein extraction from olive leaf appears to give satisfactory and reproducible results. The protocol is expected to be applicable to other recalcitrant plant tissues and could be of interest to laboratories involved in plant proteomics.

385 citations


Journal ArticleDOI
TL;DR: An algorithm for generating a binary search tree that allows efficient computation of piecewise affine (PWA) functions defined on a polyhedral partition is presented, useful for PWA control approaches, such as explicit model predictive control, as it allows the controller to be implemented online with small computational effort.

375 citations


Journal ArticleDOI
21 Mar 2003-Science
TL;DR: It is shown that Collembola, a wingless group traditionally considered as basal to all insects, appears instead to constitute a separate evolutionary lineage that branched much earlier than the separation of many crustaceans and insects and independently adapted to life on land.
Abstract: Recent morphological and molecular evidence has changed interpretations of arthropod phylogeny and evolution. Here we compare complete mitochondrial genomes to show that Collembola, a wingless group traditionally considered as basal to all insects, appears instead to constitute a separate evolutionary lineage that branched much earlier than the separation of many crustaceans and insects and independently adapted to life on land. Therefore, the taxon Hexapoda, as commonly defined to include all six-legged arthropods, is not monophyletic.

375 citations


Journal ArticleDOI
01 Aug 2003-Stroke
TL;DR: The data suggest that percutaneous stenting of the carotid artery when a cerebral protection device is used is feasible and effective but not without potential complications, however, a long learning curve may exist for the proper use of some embolic protection devices.
Abstract: Background and Purpose— Periprocedural embolization of debris during carotid stenting interventions may result in neurological deficit. This study was designed to evaluate in-hospital and 30-day adverse events in patients percutaneously treated for carotid artery disease with embolic protection devices. Methods— From 1999 to June 2002, a total of 442 consecutive patients underwent percutaneous angioplasty and/or stenting of the extracranial carotid artery. The endovascular procedure was conducted under embolic protection devices. Results— The percutaneous procedure was successful in 440 of 442 patients (99.5%). No periprocedural death occurred with any embolic protection device. All in-hospital stroke/death and 30-day ipsilateral stroke/death rate was 1.1%. The overall complication rate was 3.4%. Major adverse events included 1 major stroke (0.2%), 4 intracranial hemorrhages (0.9%), 1 carotid artery wall fissuration (0.2%), and 1 diffuse cardioembolism (0.2%). Minor adverse events included 4 minor strokes...

329 citations


Journal ArticleDOI
TL;DR: It is reported that VacA also interferes with T cell activation by two different mechanisms, one of which involves activation of intracellular signaling through the mitogen-activated protein kinases MKK3/6 and p38 and the Rac-specific nucleotide exchange factor, Vav.
Abstract: Helicobacter pylori toxin, VacA, damages the gastric epithelium by erosion and loosening of tight junctions. Here we report that VacA also interferes with T cell activation by two different mechanisms. Formation of anion-specific channels by VacA prevents calcium influx from the extracellular milieu. The transcription factor NF-AT thus fails to translocate to the nucleus and activate key cytokine genes. A second, channel-independent mechanism involves activation of intracellular signaling through the mitogen-activated protein kinases MKK3/6 and p38 and the Rac-specific nucleotide exchange factor, Vav. As a consequence of aberrant Rac activation, disordered actin polymerization is stimulated. The resulting defects in T cell activation may help H. pylori to prevent an effective immune response leading to chronic colonization of its gastric niche.


Journal ArticleDOI
29 Sep 2003-Oncogene
TL;DR: Some of the recent developments and results in microarray technology in cancer research are highlighted, potentially problematic areas associated with it are discussed, the eventual use of micro array technology for clinical applications are described and future trends and issues are commented on.
Abstract: Cancer is a highly variable disease with multiple heterogeneous genetic and epigenetic changes. Functional studies are essential to understanding the complexity and polymorphisms of cancer. The final deciphering of the complete human genome, together with the improvement of high throughput technologies, is causing a fundamental transformation in cancer research. Microarray is a new powerful tool for studying the molecular basis of interactions on a scale that is impossible using conventional analysis. This technique makes it possible to examine the expression of thousands of genes simultaneously. This technology promises to lead to improvements in developing rational approaches to therapy as well as to improvements in cancer diagnosis and prognosis, assuring its entry into clinical practice in specialist centers and hospitals within the next few years. Predicting who will develop cancer and how this disease will behave and respond to therapy after diagnosis will be one of the potential benefits of this technology within the next decade. In this review, we highlight some of the recent developments and results in microarray technology in cancer research, discuss potentially problematic areas associated with it, describe the eventual use of microarray technology for clinical applications and comment on future trends and issues.

Journal ArticleDOI
TL;DR: In a high percentage of patients, treatment with metformin is followed by regularization of menstrual cycle, reduction in hyperandrogenism and in cardiovascular risk factors, and improvement in response to therapies for induction of ovulation.
Abstract: Polycystic ovary syndrome (PCOS) is a medical condition that has brought multiple specialists together. Gynecologists, endocrinologists, cardiologists, pediatricians, and dermatologists are all concerned with PCOS patients and share research data and design clinical trials to learn more about the syndrome. Insulin resistance is a common feature of PCOS and is more marked in obese women, suggesting that PCOS and obesity have a synergistic effect on the magnitude of the insulin disorder. Hyperinsulinemia associated with insulin resistance has been causally linked to all features of the syndrome, such as hyperandrogenism, reproductive disorders, acne, hirsutism, and metabolic disturbances. Women with PCOS should be evaluated for cardiovascular risk factors, such as lipid profile and blood pressure. Modification of diet and lifestyle should be suggested to those who are obese. Several insulin-lowering agents have been tested in the management of PCOS. In particular, metformin is the only drug currently in widespread clinical use for treatment of PCOS. In a high percentage of patients, treatment with metformin is followed by regularization of menstrual cycle, reduction in hyperandrogenism and in cardiovascular risk factors, and improvement in response to therapies for induction of ovulation.

Journal ArticleDOI
01 Feb 2003-Bone
TL;DR: It is demonstrated that the effects of risedronate over 3 years on vertebral fracture and BMD are maintained with a further 2 years of treatment, as well as rapid and significant decreases in markers of bone turnover observed in the first 3 years were similarly maintained in the next 2 Years of treatment.

Journal ArticleDOI
TL;DR: The present findings showed for the first time an association between DEHP plasma concentrations and endometriosis, suggesting a possible role for phthalate esters in the pathogenesis.
Abstract: BACKGROUND: Emerging evidence suggests a potential role for ubiquitous environmental contaminants in the physiopathology of endometriosis. Di-(2-ethylhexyl)-phthalate (DEHP), the most commonly used plasticizer in flexible polyvinylchloride (PVC) formulations, is a widespread environmental contaminant with potentially adverse effects on fertility in animal models. In the present study, we tested the hypothesis that DEHP and/or and its main metabolite, mono-ethylhexyl phthalate (MEHP), play a role in the pathogenesis of endometriosis. METHODS: Specimens of blood and peritoneal fluid were collected in a group of women with endometriosis (n = 55), and in agematched control women (n = 24). Concentrations of DEHP and MEHP were measured in plasma and peritoneal fluid by using high performance liquid chromatography (HPLC). Differences between groups were tested using the Fisher’s exact test, Wilcoxon-test, and Kruskal‐Wallis analysis of variance. RESULTS: Endometriotic women showed significantly higher plasma DEHP concentrations than controls (median 0.57 mg/ml, interquartile range: 0.06‐1.23; values range: 0‐3.24 versus median 0.18 mg/ml, interquartile range: 0‐0.44; values range: 0‐1.03; P = 0.0047) and 92.6% of them had detectable DEHP and /or MEHP in the peritoneal fluid. No significant differences in either the DEHP/MEHP plasma concentrations (P > 0.31) or DEHP/MEHP peritoneal fluid concentrations (P > 0.66) were observed in the endometriotic patients as a function of the disease stage at the time of diagnosis. CONCLUSIONS: The present findings showed for the first time an association between DEHP plasma concentrations and endometriosis, suggesting a possible role for phthalate esters in the pathogenesis.

Journal Article
TL;DR: The statistical analysis did not reveal any significant difference in the survival rate of the tested posts, suggesting that all are equally and sufficiently reliable for clinical use.
Abstract: Purpose This study prospectively evaluated the clinical performance of three types of translucent posts over a follow-up period of between 2 and 3 years. Materials and methods Selected were 225 patients with one premolar in need of endodontic treatment, followed by restoration with a fiber post and porcelain crown. The sample was randomly divided into three groups of 75 patients each. The same type of post was used in all patients within a group: group 1 = Aesthetic Plus; group 2 = DT; and group 3 = FRC Postec. For bonding the post, a light-curing adhesive (One-Step) and a dual-curing resin cement (Duo-Link) were applied in group 1 and 2 roots, whereas self-curing materials (Excite DSC as adhesive and MultiLink as resin cement) were used in group 3. After 6, 12, and 24 months, patients were recalled, and a clinical and radiographic examination was performed. For some patients, 30-month follow-up data were also collected. Results Debonding of the post occurrred in eight cases (3.5%); in another six cases, a recurrence of the periapical lesion was reported. Conclusion The statistical analysis did not reveal any significant difference in the survival rate of the tested posts, suggesting that all are equally and sufficiently reliable for clinical use.

Journal ArticleDOI
TL;DR: High-dose short-term therapy with simvastatin may improve walking performance, ankle-brachial pressure indexes, and symptoms of claudication in hypercholesterolemic patients with peripheral vascular disease.

Journal ArticleDOI
TL;DR: In this article, the authors address the validity of assumptions about the importance of co-locality for innovation, by analyzing whether or not co-location matters for formal knowledge collaboration in the Swedish biotechnology-pharmaceutical sector, or biotech-pharma sector.

Journal ArticleDOI
TL;DR: The Italian version of WOMAC is a reliable and valid instrument for evaluating the severity of OA of the knee, with metric properties in agreement with the original, widely used version.

Journal ArticleDOI
TL;DR: Saccular carriers containing either the large supramolecular cargo procollagen or the small diffusible cargo protein VSVG arise through cargo concentration and direct en bloc protrusion of specialized ER domains in the vicinity of COPII-coated exit sites, providing an alternative framework for analysis of ER-to-Golgi traffic.

Journal ArticleDOI
TL;DR: Results from the present study indicate an important role of estrogens, and particularly of the ability to aromatize T to E(2), in the regulation of bone loss and bone metabolism in elderly men.
Abstract: Male osteoporosis is an increasingly important health problem. It is known that sex steroid hormones play an important role in regulating bone turnover and bone mass in males as well as in females. However, the exact mechanism of bone loss in men remains unknown. In the present study, 200 elderly men (age range, 55-85 yr) were followed for 4 yr to evaluate the relationships between hormone levels, bone turnover markers, bone mineral density, and rates of bone loss. Femoral and lumbar bone mineral density, bone ultrasound parameters at the os calcis, serum testosterone (T), serum estradiol (E(2)), SHBG levels, and bone turnover markers (urinary crosslaps and bone alkaline phosphatase) were evaluated for each man at enrollment and 4 yr afterward. The free androgen index (FAI) and free estrogen index (FEI) as well as measures of the bioavailable sex hormones [calculated bioavailable E(2) (c-bioE(2)) and T (c-bioT)] were calculated from total hormone levels and SHBG. In the total population, T, c-bioT, c-bioE(2), FAI, and FEI, but not E(2), decreased significantly with age, whereas SHBG increased significantly. Subjects with FEI, c-bioE(2), and E(2) levels below the median showed higher rates of bone loss at the lumbar spine and the femoral neck as well as higher speed-of-sounds decrease at the calcaneus with respect to men with FEI, c-bioE(2), and E(2) levels above the median. Serum bone alkaline phosphatase and urinary crosslaps were significantly higher in men with FEI, c-bioE(2), and E(2) in the lower quartile than in men with FEI, c-bioE(2), and E(2) levels in the higher quartile. No statistically significant differences were observed in relation to T, c-bioT, or FAI levels. Finally, the ratio between E(2) and T, an indirect measure for aromatase activity, increased significantly with age and was higher in normal than in osteoporotic subjects. In conclusion, results from the present study indicate an important role of estrogens, and particularly of the ability to aromatize T to E(2), in the regulation of bone loss and bone metabolism in elderly men.

Journal ArticleDOI
TL;DR: The data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures, and the important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.
Abstract: The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR = 0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.

Journal ArticleDOI
TL;DR: Findings indicate that CTX-M enzymes of various types are present also in Italy and underscore that different CTx-M determinants can be found in a single hospital and can show different dissemination patterns.
Abstract: Twelve isolates of Enterobacteriaceae (1 of Klebsiella pneumoniae, 8 of Escherichia coli, 1 of Proteus mirabilis, and 2 of Proteus vulgaris) classified as extended-spectrum beta-lactamase (ESBL) producers according to the ESBL screen flow application of the BD-Phoenix automatic system and for which the cefotaxime MICs were higher than those of ceftazidime were collected between January 2001 and July 2002 at the Laboratory of Clinical Microbiology of the San Matteo University Hospital of Pavia (northern Italy). By PCR and sequencing, a CTX-M-type determinant was detected in six isolates, including three of E. coli (carrying bla(CTX-M-1)), two of P. vulgaris (carrying bla(CTX-M-2)), and one of K. pneumoniae (carrying bla(CTX-M-15)). The three CTX-M-1-producing E. coli isolates were from different wards, and genotyping by pulsed-field gel electrophoresis (PFGE) revealed that they were clonally unrelated to each other. The two CTX-M-2-producing P. vulgaris isolates were from the same ward (although isolated several months apart), and PFGE analysis revealed probable clonal relatedness. The bla(CTX-M-1) and bla(CTX-M-2) determinants were transferable to E. coli by conjugation, while conjugative transfer of the bla(CTX-M-15) determinant from K. pneumoniae was not detectable. Present findings indicate that CTX-M enzymes of various types are present also in Italy and underscore that different CTX-M determinants can be found in a single hospital and can show different dissemination patterns. This is also the first report of CTX-M-2 in P. vulgaris.

Journal ArticleDOI
TL;DR: A novel algorithm for solving multiparametric linear programming problems that follows a geometric approach based on the direct exploration of the parameter space and has computational advantages, namely the simplicity of its implementation in a recursive form and an efficient handling of primal and dual degeneracy.
Abstract: We propose a novel algorithm for solving multiparametric linear programming problems. Rather than visiting different bases of the associated LP tableau, we follow a geometric approach based on the direct exploration of the parameter space. The resulting algorithm has computational advantages, namely the simplicity of its implementation in a recursive form and an efficient handling of primal and dual degeneracy. Illustrative examples describe the approach throughout the paper. The algorithm is used to solve finite-time constrained optimal control problems for discrete-time linear dynamical systems.

Journal ArticleDOI
TL;DR: It is shown that glutathionylated actin (GS-actin) has a decreased capacity to polymerize compared to native actin, filament elongation being the polymerization step actually inhibited, indicating that S-glutathionyation does not induce any protein denaturation and is therefore a reversible oxidative modification.

Journal ArticleDOI
TL;DR: It is reported here that ank1.5, a small splice variant of the ank1 gene localized on the sarcoplasmic reticulum membrane, is capable of interacting with a sequence of 25 aa located at the COOH terminus of obscurin, a giant sarcomeric protein of ∼800 kD that binds to titin and has been proposed to mediate interactions between myofibrils and other cellular structures.
Abstract: Assembly of specialized membrane domains, both of the plasma membrane and of the ER, is necessary for the physiological activity of striated muscle cells. The mechanisms that mediate the structural organization of the sarcoplasmic reticulum with respect to the myofibrils are, however, not known. We report here that ank1.5, a small splice variant of the ank1 gene localized on the sarcoplasmic reticulum membrane, is capable of interacting with a sequence of 25 aa located at the COOH terminus of obscurin. Obscurin is a giant sarcomeric protein of ∼800 kD that binds to titin and has been proposed to mediate interactions between myofibrils and other cellular structures. The binding sites and the critical aa required in the interaction between ank1.5 and obscurin were characterized using the yeast two-hybrid system, in in vitro pull-down assays and in experiments in heterologous cells. In differentiated skeletal muscle cells, a transfected myc-tagged ank1.5 was found to be selectively restricted near the M line region where it colocalized with endogenous obscurin. The M line localization of ank1.5 required a functional obscurin-binding site, because mutations of this domain resulted in a diffused distribution of the mutant ank1.5 protein in skeletal muscle cells. The interaction between ank1.5 and obscurin represents the first direct evidence of two proteins that may provide a direct link between the sarcoplasmic reticulum and myofibrils. In keeping with the proposed role of obscurin in mediating an interaction with ankyrins and sarcoplasmic reticulum, we have also found that a sequence with homology to the obscurin-binding site of ank1.5 is present in the ank2.2 isoform, which in striated muscles has been also shown to associate with the sarcoplasmic reticulum. Accordingly, a peptide containing the COOH terminus of ank2.2 fused with GST was found to bind to obscurin. Based on reported evidence showing that the COOH terminus of ank2.2 is necessary for the localization of ryanodine receptors and InsP 3 receptors in the sarcoplasmic reticulum, we propose that obscurin, through multiple interactions with ank1.5 and ank2.2 isoforms, may assemble a large protein complex that, in addition to a structural function, may play a role in the organization of specific subdomains in the sarcoplasmic reticulum.

Journal ArticleDOI
TL;DR: It is recommended, in spite of the greater surgical skill required, submucosal resection combined with lateral displacement as the first-choice technique for the treatment of nasal obstruction due to hypertrophy of the inferior turbinates.
Abstract: In the past 130 years, many surgical procedures for turbinate reduction have been developed. We analyzed the long-term efficacy of 6 of these surgical techniques (turbinectomy, laser cautery, electrocautery, cryotherapy, submucosal resection, and submucosal resection with lateral displacement) over a 6-year follow-up period. We randomly divided 382 patients into 6 therapeutic groups and surgically treated them at the Department of Otorhinolaryngology of the University of Siena. After 6 years, only submucosal resection resulted in optimal long-term normalization of nasal patency and in restoration of mucociliary clearance and local secretory IgA production to a physiological level with few postoperative complications (p < .001). The addition of lateral displacement of the inferior turbinate improved the long-term results. We recommend, in spite of the greater surgical skill required, submucosal resection combined with lateral displacement as the first-choice technique for the treatment of nasal obstruction due to hypertrophy of the inferior turbinates.

Journal ArticleDOI
TL;DR: Both diabetes and admission hyperglycemia in nondiabetic patients are predictors of poor outcome after supratentorial ICH, and may be related to the greater incidence of cerebral and infectious complications in diabetic patients and of cerebral complications in hyperglycemic nondi diabetic patients.
Abstract: Objective: To determine whether diabetes and admission hyperglycemia in nondiabetic patients influence outcome and the occurrence of cerebral and medical complications after intracerebral hemorrhage (ICH). Methods: The study sample included 764 patients with ICH. The effects of diabetes and admission hyperglycemia were examined in relation to 30-day and 3-month mortality using Cox regression models controlling for potential confounders. The analysis was conducted for the entire sample of patients and repeated in comatose and noncomatose patients. Results: Among comatose patients, neither diabetes nor admission hyperglycemia contributed significant predictive information, as nearly all patients died. In noncomatose patients, diabetes was an independent predictor of 30-day (odds ratio [OR] 1.31; 95% CI 1.08 to 1.58) and 3-month (OR 1.30; 95% CI 1.08 to 1.56) mortality and was associated with a greater incidence of infectious (OR 1.24; 95% CI 1.03 to 1.49) and cerebral (OR 1.42; 95% CI 1.10 to 1.83) complications. Among nondiabetic patients with Glasgow Coma Scale score of >8, hyperglycemia was an independent predictor of 30-day (OR 1.29; 95% CI 1.05 to 1.58) and 3-month (OR 1.27; 95% CI 1.05 to 1.53) mortality and was associated with a greater incidence of cerebral complications (OR 1.47; 95% CI 1.12 to 2.94). Conclusions: Both diabetes and admission hyperglycemia in nondiabetic patients are predictors of poor outcome after supratentorial ICH. This may be related to the greater incidence of cerebral and infectious complications in diabetic patients and of cerebral complications in hyperglycemic nondiabetic patients.

Journal ArticleDOI
TL;DR: It is shown that a proportion of apparently sporadic early-onset diffuse gastric carcinomas are associated with germline alterations of the E-cadherin gene, and it is demonstrated that aportion of missense variants areassociated with significant functional consequences, suggesting that the cell model can be used as an adjunct in deciding on the potential pathogenic role of identified E
Abstract: E-cadherin is involved in the formation of cell-junctions and the maintenance of epithelial integrity. Direct evidence of E-cadherin mutations triggering tumorigenesis has come from the finding of inactivating germline mutations of the gene (CDH1) in hereditary diffuse gastric cancer (HDGC). We screened a series of 66 young gastric cancer probands for germline CDH1 mutations, and two novel missense alterations together with an intronic variant were identified. We then analysed the functional significance of the two exonic missense variants found here as well as a third germline missense variant that we previously identified in a HGDC family. cDNAs encoding either the wild-type protein or mutant forms of E-cadherin were stably transfected into CHO (Chinese hamster ovary) E-cadherin-negative cells. Transfected cell-lines were characterized in terms of aggregation, motility and invasion. We show that a proportion of apparently sporadic early-onset diffuse gastric carcinomas are associated with germline alterations of the E-cadherin gene. We also demonstrate that a proportion of missense variants are associated with significant functional consequences, suggesting that our cell model can be used as an adjunct in deciding on the potential pathogenic role of identified E-cadherin germline alterations.