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R Scorza

Publications and source records attributed to R Scorza.

At least 19 recordsLinked to original sources
PubMed2007

Bias in association studies of systemic lupus erythematosus susceptibility due to geographical variation in the frequency of a programmed cell death 1 polymorphism across Europe.

We obtained eight collections of DNA samples from ethnically matched systemic lupus erythematosus (SLE) patients and controls from five European countries totaling 783 patients and 1210 controls. A highly significant cline in the frequency of the PD1.3 A allele was found among controls but not among SLE patients. The frequency of the PD1.3 A allele increased from the Northeast to the Southwest of Europe. The cline was clearly apparent (P=1.2 x 10(-6)) when data from controls of other five SLE susceptibility studies were included in the analysis. This variation has severely biased SLE association studies owing to the lack of parallel changes in SLE patients. As a consequence, the PD1.3 A allele was more common in SLE patients than in controls in the Northeast and Center of Europe, similar to controls in Southeast Europe, and less frequent than in the controls in the Southwest of the Continent. This dissociation in allele frequencies between SLE patients and controls in different subpopulations indicated that programmed cell death 1 variation and disease susceptibility are not independent but the type of relationship is currently unclear. As allele frequency clines are common in other polymorphisms their impact in genetic epidemiology studies should be carefully considered.

Antigens, CD↗
PubMed2006

Validity of the Saint George's Respiratory Questionnaire in the evaluation of the health-related quality of life in patients with interstitial lung disease secondary to systemic sclerosis.

OBJECTIVES: Interstitial lung disease (ILD) profoundly affects the health-related quality of life (HRQoL) in patients with systemic sclerosis (SSc). We tested the validity of the Saint George's Respiratory Questionnaire (SGRQ), a lung-specific HRQoL-evaluation tool, in a population of SSc patients with ILD. METHODS: Twenty-eight consecutive SSc patients with a restrictive pulmonary involvement, defined as a forced vital capacity <80% of the predicted, with no pulmonary hypertension were considered. All the patients filled in the Medical Research Council (MRC) scale for perceived breathlessness, the SGRQ and the Disability Index of the Health Assessment Questionnaire (HAQ DI), and underwent evaluation with complete pulmonary function testing (PFT), 6-minute walk distance (6MWD) and high-resolution computed tomography (HRCT). RESULTS: The SGRQ 'activity' scores inversely correlated with the 6MWD (r = -0.86, P < 0.001) and forced vital capacity percentage of predicted values (r = -0.47) and directly correlated with HRCT (r = 0.41, P < 0.05), MRC (rho = 0.64, P < 0.001) or HAQ DI scores (r = 0.62, P < 0.001), independently of disease duration or subset. On the contrary, HAQ DI scores were influenced by those variables and corrected correlations with 6MWD (r = 0.56, P < 0.001) or HRCT scores (r = 0.36, P = NS) were less strong than those observed with the SGRQ. CONCLUSIONS: The SGRQ, although not specifically designed for scleroderma, is a valid respiratory-specific questionnaire for the evaluation of HRQoL in patients with SSc-related ILD. The SGRQ performs better in relation to exercise capacity and lung imaging than other non-respiratory-specific questionnaires widely used in scleroderma studies. Further studies are needed to address its ability to assess changes over time or in response to therapy.

Adult↗
PubMed2006

Gastrodia anti-fungal protein from the orchid Gastrodia elata confers disease resistance to root pathogens in transgenic tobacco.

Diseases of agricultural crops are caused by pathogens from several higher-order phylogenetic lineages including fungi, straminipila, eubacteria, and metazoa. These pathogens are commonly managed with pesticides due to the lack of broad-spectrum host resistance. Gastrodia anti-fungal protein (GAFP; gastrodianin) may provide a level of broad-spectrum resistance due to its documented anti-fungal activity in vitro and structural similarity to insecticidal lectins. We transformed tobacco (Nicotiana tabacum cv. Wisconsin 38) with GAFP-1 and challenged transformants with agriculturally important plant pathogens from several higher-order lineages including Rhizoctonia solani (fungus), Phytophthora nicotianae (straminipile), Ralstonia solanacearum (eubacterium), and Meloidogyne incognita (metazoan). Quantitative real-time PCR and western blotting analysis indicated that GAFP-1 was transcribed and translated in transgenic lines. When challenged by R. solani and P. nicotianae, GAFP-1 expressing lines had reduced symptom development and improved plant vigor compared to non-transformed and empty vector control lines. These lines also exhibited reduced root galling when challenged by M. incognita. Against R. solanacearum expression of GAFP-1 neither conferred resistance, nor exacerbated disease development. These results indicate that heterologous expression of GAFP-1 can confer enhanced resistance to a diverse set of plant pathogens and may be a good candidate gene for the development of transgenic, root-disease-resistant crops.

Base Sequence↗
PubMed2006

HLA-B35 upregulates the production of endothelin-1 in HLA-transfected cells: a possible pathogenetic role in pulmonary hypertension.

HLA-B35 is associated with an increased risk for developing isolated pulmonary hypertension (iPHT) in systemic sclerosis, but the mechanisms underlying this association have not been fully elucidated yet. Endothelin-1 (ET-1) is the main pathogenetic molecule implied in the development of iPHT; therefore, we sought to determine if ECV304 cells transfected with the HLA-B35 allele produce increased amounts of ET-1 after incubation with physiological concentrations of interleukin-1 beta (IL-1beta). ECV304 cells transfected with HLA-B*3501 and HLA-B*0801 polymorphic alpha chain or with pIRESneo2 were incubated with 100 U/ml of IL-1beta for 6, 12, 24, 36 and 48 h. ET-1 levels were determined using EIA kit (CAYMAN Chemical, Ann Arbor, MI) in supernatants from different cell cultures; the relative expression of the preproendothelin-1 (PPET-1) gene was also determined by reverse transcription-polymerase chain reaction. Cells expressing the HLA-B35 allele showed significantly increased levels of ET-1 at all the selected times compared with controls or HLA-B8-transfected cells. The relative expression of the PPET-1 gene was also increased in a proportionally direct manner. The HLA-B35 allele influences the production of ET-1 in HLA-B35-transfected ECV304 cells by promoting the expression of its precursor, PPET-1. Our results provide an explanation for the epidemiological association existing between iPHT and HLA-B35.

Alleles↗
PubMed2005

Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the "Euro-Lupus Project".

The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium--the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Age of Onset↗
PubMed2005

Two single-nucleotide polymorphisms in the 5' and 3' ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus.

OBJECTIVE: To test the association of osteopontin (OPN) polymorphisms with systemic lupus erythematosus (SLE). METHODS: The coding 5' and 3' flanking regions of the OPN gene were scanned for polymorphisms by denaturing high-performance liquid chromatography. A case-control association study was performed in 394 Italian SLE patients and 479 matched controls. OPN serum levels were determined by enzyme-linked immunosorbent assay in 40 patients and 124 controls, and the mean levels were compared between the different OPN genotypes. RESULTS: Among the 13 detected single-nucleotide polymorphisms (SNPs), alleles -156G (frequency 0.714 versus 0.651; P = 0.006, corrected P [P(corr)] = 0.036) and +1239C (0.377 versus 0.297; P = 0.00094, P(corr) = 0.0056) were significantly increased in the SLE patients compared with the controls. The presence of the associated allele in single or double dose conferred an odds ratio (OR) of 2.35 (95% confidence interval [95% CI] 1.38-4.02) for SNP -156 and an OR of 1.57 (95% CI 1.16-2.13) for SNP +1239. These effects were independent of each other, i.e., not a consequence of linkage disequilibrium between the 2 alleles. The risk associated with a double dose of susceptibility alleles at both SNPs was 3.8-fold higher (95% CI 2.0-7.4) relative to the complete absence of susceptibility alleles. With regard to individual clinical and immunologic features, a significant association was seen between lymphadenopathy and -156 genotypes (overall P = 0.0011, P(corr) = 0.046). A significantly increased OPN serum level was detected in healthy individuals carrying +1239C (P = 0.002), which is indicative of an association between the SLE susceptibility allele and OPN levels. CONCLUSION: These data suggest the independent effect of a promoter (-156) and a 3'-untranslated region (+1239) SNP in SLE susceptibility. We can speculate that these sequence variants (or others in perfect linkage disequilibrium) create a predisposition to high production of OPN, and that this in turn may confer susceptibility to SLE.

Disease Susceptibility↗
PubMed2004

Ser128Arg gene polymorphism for E-selectin and severity of atherosclerotic arterial disease.

AIM: Genetic factors appear to be important in the pathogenesis of cardiovascular and cerebrovascular disease. Adhesion molecules like the members of the selectin family participate in the interaction between leukocytes and the endothelium. They are also involved in the pathogenesis of the atherosclerotic process. In E-selectin, exchange from serine to arginine (position 128, S128R) is correlated with early atherosclerosis. The aim of this study was to assess E-selectin Ser128Arg polymorphism in subjects with clinical and instrumental evidence of atherosclerosis and to analyze the correlations with clinical severity. METHODS: A total of 144 subjects (100 men and 44 women, mean age 72 years, range 48-78) with atherosclerotic disease in different vascular sites documented by angiography were studied; 138 volunteers were recruited as a control group. Whole blood was collected; DNA was extracted with a commercial kit and amplified with 2 primers. The PCR was performed by standard procedure. To assess the disease severity all patients were classified by an arbitrary clinical and angiographic score scale. RESULTS: The genotype distribution between patients and controls was different, although statistical significance was not achieved (p=0.06). In patients a significant difference in Arg allele frequency was observed between mild and severe atherosclerotic disease (OR 2.28; 95% CI 1.15-4.52; p=0.017). Four ho-mozygous cases for S128R were found in patients, none in controls. All these 4 patients had the highest severity score, that means a more severe atherosclerotic disease. CONCLUSION: Our study suggests that the E-selectin polymorphism may be associated with severity of atherosclerotic disease, but does not allow us to conclude that it is actually a risk factor for atherosclerosis.

Aged↗
PubMed2003

Early antibiotic selection and efficient rooting and acclimatization improve the production of transgenic plum plants (Prunus domestica L.).

We describe here an improved system for routinely developing transgenic plum plants (Prunus domestica L.) through the use of Agrobacterium tumefaciens. The production of non-transformed "escapes" has been virtually eliminated, and rates of plant establishment in the greenhouse have been dramatically improved. The system is based on the regeneration of shoots from hypocotyls extracted from mature seed. The shoot regeneration medium is Murashige and Skoog (MS) salts and vitamins supplemented with 7.5 microM thidiazuron and 0.25 microM indole-butyric acid. Transferring the explants after co-cultivation to shoot regeneration medium containing 80 mg l(-1) of kanamycin and 300 mg l(-1) of Timentin reduced the total number of regenerated shoots without affecting the transformation rate. Transformation rates using the described system averaged 1.2% of the hypocotyl slices producing transgenic plants, with a range of 0-4.2%. The transgenic shoots rooted at a rate of 90% on half-strength MS salts and vitamins supplemented with 5 microM alpha-naphthaleneacetic acid and 0.01 microM kinetin. Plantlets were transferred to a greenhouse directly from culture tubes with a 90% average survival.

Acclimatization↗
PubMed2003

HLA-DPB1 alleles association of anticardiolipin and anti-beta2GPI antibodies in a large series of European patients with systemic lupus erythematosus.

Our objective was to determine the HLA-DPB1 allele associations of anticardiolipin (aCL) and anti-beta2GPI (a(beta)2GPI) antibodies, and of clinical manifestations of the antiphospholipid syndrome (APS), in systemic lupus erythematosus (SLE). We studied 577 European patients with SLE. aCL and a(beta)2GPI antibodies were measured by ELISA. Molecular typing of HLA-DPB1 locus was performed by polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. aCL showed positive association with -DPB1*1501 (P = 0.005, OR = 7.4), and -DPB1*2301 (P = 0.009, OR = 3.3). a(beta)2GPI showed positive association with -DPB1*0301 (P = 0.01, OR = 1.9), and -DPB1*1901 (P = 0.004, OR = 8.1). In addition, livedo reticularis was associated with -DPB1*1401, and Raynaud's phenomenon with -DPB1*2001. In conclusion, HLA-DPB1 locus may contribute to the genetic predisposition to develop antiphospholipid antibodies and clinical manifestations of the APS in patients with SLE.

Adolescent↗
PubMed2003

Assessment of vascular involvement.

Our objective was to identify a core set of variables for the assessment of vascular involvement in scleroderma that is simple, reproducible, and reflects the presence of vascular disease in SSc. To do so we carried out an extensive literature review of published studies relating to the assessment of vascular involvement in SSc, i.e. studies dealing with clinical parameters, functional vascular studies, cold presser testing, nailfold capillary microscopy and circulating vascular markers. After extensive review of published studies and critical assessment of proposed vascular parameters, the subcommittee endorsed what it considers to be the minimal requirements for the documentation of vascular involvement in SSc. The core set variables include two parameters: Raynaud's phenomenon and digital ulcers. This set is simple, reproducible and should be included in the assessment of SSc patients in clinical investigational studies. The subcommittee also however recognizes that there exists a promising set of vascular variable that still needs further investigation.

Blood Vessels↗
PubMed2003

Assessment of disease severity and prognosis.

The Subcommittee members initially agreed on the concepts of disease activity, damage and severity, defining severity as the total effect of disease on organ function. It was decided to start with the assessment of severity using the Medsger's severity scale. A revised version of this scale was constructed. The rationale for the exclusion of other variables was provided.

Humans↗
PubMed2003

Multidetector helical angio CT oblique reconstructions orthogonal to internal carotid artery for preoperative evaluation of stenosis. A prospective study of comparison with color Doppler US, digital subtraction angiography and intraoperative data.

AIM: The recent introduction to clinical practice of multidetector helical angio CT (MHACT) has generated a new interest in the diagnosis of carotid artery atherosclerosis. In recent years there has been a redefinition of the indications to carotid artery endarterectomy; there is a tendency to appraise plaque morphology and composition, and not only stenosis degree. The aim of this prospective study is to analyze the validity of MHACT in the diagnosis of atheromasic stenosis of the carotid bifurcation, in comparison with US color Doppler (USCD), digital subtraction angiography (DSA) and intraoperative evidence (OP). Special emphasis is given to the analysis of plaque composition and to precise evaluation of the stenosis percentage computed as an area rate on oblique reconstructions performed exactly orthogonal to the axis of the vessel at the point of maximal stenosis. METHODS: Twenty-seven carotid stenosis (in 24 patients) were preoperatively evaluated by USCD, MHACT, DSA. We calculated the stenosis degree with USCD, by the ECST method, both as a diameter rate and as a bidimensional value. By MHACT we computed the percentage of stenosis as an area rate, in an MPR oblique plane orthogonal to the vessel axis, at the point of maximal stenosis; by DSA we used NASCET and the common carotid artery method (CC). DSA measurements have been mathematically converted as area rate (NASCET2 and CC2). All the patients were operated on with the eversion technique (EEA); it was always possible to obtain an intact cylindrical specimen of the plaque and to perform a reliable and accurate evaluation of the degree of stenosis by sectioning and measuring it on the desk. We gave a score to the presence and amount of lipid and calcium components, and these data were compared to those obtained with the different diagnostic instruments. RESULTS: Statistical analysis of the 7 data sets showed an important underestimate of the angiographical method (DSA), even if the measurements were carried on by a precision caliper. The mathematical conversion of a linear stenosis rate into an area rate gives these values more reliability, indicating, as for NASCET2, non statistically significant differences when compared to surgical evidence, notwithstanding a high standard deviation. The rates obtained by USCD (area rate) and MHACT proved to be very accurate with respect to surgical evidence. In this study there was no significant difference in the detection of various components (lipid and calcium) of the atheromasic lesion, by MHACT and surgical evidence (OP). CONCLUSION: MHACT promises to be a very accurate instrument in the detection of plaque components and identification of the stenosis degree. It shows some limits in very calcific lesions and occasionally, in relevant cardiac failure, may be useless. Hence one feels the need to reassess the role of DSA, once considered the "gold standard", with more extensive prospective studies, including comparison with MHACT and USCD.

Angiography, Digital Subtraction↗
PubMed2002

Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5' regulatory region.

Many lines of evidence suggest that IL10 is a strong candidate gene for systemic lupus erythematosus (SLE) susceptibility. In our previously reported study an allele (IL10.G-140bp) of the microsatellite IL10.G located at position -1100 was significantly increased in Italian SLE patients in comparison with controls. Starting from this observation, we tested if sequence variations in the vicinity of IL10.G were more strongly associated with SLE. We performed a comprehensive association study including 26 SNPs (of which four were newly identified in the present study by DHPLC analysis) spanning 8.5 Kb of the 5' flanking and the transcribed region of the IL10 gene. The association study was performed by the DNA pool method on an extended panel of Italian patients (205) and controls (631). Haplotypic associations were studied by individual typing of seven selected markers surrounding IL10.G. Gene, genotype and haplotype frequencies were not significantly different in patients and controls. Thus the IL10.G microsatellite remains to date the only IL10 marker associated with SLE in our population. A meta-analysis of all published results indicates a possible direct role of the IL10.G repeat number in SLE susceptibility.

5' Flanking Region↗
PubMed2002

Clinical and serological associations of ribosomal P autoantibodies in systemic lupus erythematosus: prospective evaluation in a large cohort of Italian patients.

OBJECTIVE: To verify the association of ribosomal anti-P antibodies (anti-P), as detected by a sensitive ELISA, with serological findings and clinical manifestations, including neuropsychiatric involvement evaluated according to the American College of Rheumatology (ACR) nomenclature, in a large cohort of patients with systemic lupus erythematosus (SLE). METHODS: Anti-P were evaluated in the serum of 149 consecutive Italian SLE patients by an ELISA using a multiple antigen peptide carrying four copies of a common P0, P1 and P2 epitope. A complete laboratory evaluation and clinical examination were performed in each patient. In addition, all patients underwent an accurate neuropsychiatric and neuropsychological assessment performed by trained specialists according to the 1999 ACR suggestions. RESULTS: Serum anti-P were detected in 18/149 patients (12.1%). The anti-P prevalence was similar (11.7%) when the analysis was performed in a larger series of sera including 82 additional SLE patients, who were not included in the clinical study. The age of anti-P-positive patients at disease onset was less than 33 yr and, in comparison with the anti-P-negative patients, these patients showed more active disease activity and a higher prevalence of photosensitivity and malar and discoid rash. A strong association between IgG anticardiolipin antibodies and anti-P was also found. However, anti-P were associated with neither neuropsychiatric syndromes nor cognitive impairment. CONCLUSION: This study does not seem to confirm the described association of anti-P with SLE neuropsychiatric manifestations. However, it supports the anti-P association with different skin manifestations as well as the presence of anticardiolipin in a subset of patients with SLE characterized by early disease onset.

Adolescent↗
PubMed2002

Superior mesenteric artery blood flow in systemic sclerosis patients.

OBJECTIVE: Intestinal involvement is frequently observed in systemic sclerosis (SSc) and is associated with malnutrition and a decreased survival rate. Vascular lesions are claimed to underlie and precede these changes. The aim of this study was to establish whether a reduced mesenteric blood flow was present in SSc patients with no signs or symptoms of small bowel involvement. METHODS: Superior mesenteric artery (SMA) blood flow in the fasting state was measured by colour Doppler ultrasonography in 27 SSc patients and in 25 controls. The effect of a balanced liquid meal on mesenteric blood flow was measured in six matched patients and controls. RESULTS: In fasting SSc patients, there were reductions in mean SMA diameter (P<0.001), blood flow (213+/-92 vs 398+/-125 ml/min in controls, P<0.0001) and pulsatility index (3.49+/-1.0 vs 4.13+/-0.97 in controls, P<0.07). In both groups, the meal increased basal flow values and the differences between controls and patients in the fasting state were not significant. CONCLUSIONS: In the absence of symptoms of small bowel involvement, reversible SMA vasoconstriction is demonstrable in the fasting state in SSc patients.

Eating↗
PubMed2002

Temporary spinal cord stimulation for peripheral cholesterol embolism.

Cholesterol embolism is often an unrecognized complication of some cardiac and vascular procedures (i.e. coronarography, angioplasty, aortocoronary bypass, abdominal aortic aneurysmectomy) and of therapies affecting coagulation (thrombolysis, anticoagulation). The degree of pain associated with ischaemic and necrotic lesions secondary to cholesterol embolism involving the lower limbs is disproportionate to the extension of tissue involvement. Spinal cord stimulation (SCS) has been recognized as effective in relief of pain of ischaemic and neuropathic nature, although its mechanism of action is still not completely clear. The authors are unaware of previous reports of peripheral cholesterol embolism treated by SCS. Two case reports of inferior limb ischaemia secondary to cholesterol embolism in patients who had undergone cardiac invasive procedures. Temporary surgical implantation of SCS devices, which were removed after 4 to 6 weeks. Pain relief was achieved within 1 to 4 hours of surgical procedure. Any analgesic medications could be immediately discontinued. Pain control was effective and normal daily activities were rapidly regained. Ischaemic lesions healed within 4 to 6 weeks of SCS. Pain control is the most critical aspect of the management of peripheral cholesterol embolism without visceral organ involvement. SCS provided effective pain relief in the reported cases and its established ability to improve peripheral microcirculation allowed rapid resolution of necrotic lesions. Temporary SCS should be considered in the management of painful necrotic skin lesions secondary to iatrogenic cholesterol embolism.

Analgesia, Epidural↗
PubMed2002

Lessons from the "Euro-Lupus Cohort".

The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Adolescent↗