The nature of the Fe-graphene interface at the nanometer level.

The emerging fields of graphene-based magnetic and spintronic devices require a deep understanding of the interface between graphene and ferromagnetic metals. This paper reports a detailed investigation at the nanometer level of the Fe-graphene interface carried out by angle-resolved photoemission, high-resolution photoemission from core levels, near edge X-ray absorption fine structure, scanning tunnelling microscopy and spin polarized density functional theory calculations. Quasi-free-standing graphene was grown on Pt(111), and the iron film was either deposited atop or intercalated beneath graphene. Calculations and experimental results show that iron strongly modifies the graphene band structure and lifts its π band spin degeneracy.

Hormonal parameters and sex hormone receptor gene polymorphisms in men with autoimmune diseases.

Autoimmune diseases (ADs) are more common in women than in men. Sex hormones may play a role. Sex hormone receptors (SHR) are expressed in cells of the immune system. We investigated the possible role of hormonal parameters and of common polymorphisms of the estrogen receptor alpha (ESR1), beta (ESR2), and androgen receptor (AR) genes in the appearance of AD in men. 277 men were studied; 125 with ≥1 AD: Hashimoto's autoimmune thyroiditis (n = 65), Graves' disease (n = 12), SLE (n = 10), and RA (n = 38). 152 were controls. Hormonal and biochemical parameters were measured after discontinuation for ≥1 month of any corticosteroid therapy. ESR1 PvuII, ESR2 AluI, and the AR (CAG)n repeats polymorphisms were analyzed. AD patients had higher estradiol levels (31.32 ± 12.10, controls 20.37 ± 7.91 pg/ml, p < 0.001). In multivariate analysis, significant predictors for AD were estrogen and BMI. The allele frequency of ESR1 PvuII and ESR2 AluI did not differ between patients and controls (AD: 47.8 %, 37.6 %; controls 49.8 %, 39.9 %). The distribution of (CAG)n did not differ between groups. In AD group, shorter (CAG)n alleles were associated with younger age of AD onset (short: 38.52 ± 14.8, long: 47.14 ± 17.34 years, p = 0.048). Carriers of ESR1 PvuII presented less frequently ≥2 AD (carriers 6.5 %, non-carriers 25.1 %, p = 0.019); carriers of AluI had lower SHBG levels and higher ΒΜΙ compared to non-carriers (p < 0.04). Higher estradiol may play a role in AD in men. Distribution of SHR gene polymorphisms is similar between patients and controls. Shorter AR (CAG)n repeats may predispose for younger AD onset. Coexistence of ≥2 AD is less frequent in carriers of ESR1 PvuII. ESR2 AluI may adversely affect obesity parameters.

Abnormal spatial QRS-T angle, a marker of ventricular repolarisation, predicts serious ventricular arrhythmia in systemic sclerosis.

OBJECTIVES: Cardiac involvement may be under-diagnosed in asymptomatic patients with systemic sclerosis (SSc). Standard electrocardiography-derived spatial QRS-T angle (spQRS-Ta) is an established marker of ventricular repolarisation heterogeneity, and a strong independent predictor of cardiac morbidity and mortality, including sudden death, in the general population. We examined whether spQRS-Ta is abnormal in asymptomatic SSc patients and assessed its predictive value for possibly concurrent, serious ventricular arrhythmia. METHODS: SpQRS-Ta and 24-hour Holter recordings were obtained from 69 SSc patients (aged 51±13 years, 63 women) without clinically evident cardiac involvement and having left ventricular ejection fraction at least 50% by echocardiography. 'Healthy' subjects matched 1:1 with patients for age, gender and body mass index served as controls. RESULTS: SpQRS-Ta was wider in SSc (median value 15.6°, interquartile range 10.6-24.3°) than controls (10.5°, 7.3-13.5°, p=0.0001) and not associated with skin fibrosis extent or specific clinical manifestations and autoantibodies. Twenty-four-hour Holter recordings revealed couplets of ventricular beats in six (Lown class IVa) and non-sustained ventricular tachycardia in five patients (Lown class IVb); spQRS-Ta was wider in those eleven patients with serious ventricular arrhythmia than the remaining patients (24.9°, 14.9-31.3° vs. 14.4°, 9.6-22.3°; p=0.02). A spQRS-Ta>19.3° demonstrated 80% sensitivity and 68% specificity (area under the curve 0.81, p=0.02) to predict the presence of non-sustained ventricular tachycardia in Holter monitoring. CONCLUSIONS: Ventricular repolarisation heterogeneity, as reflected by wider spQRS-Ta, is common in SSc. Increased spQRS-Ta could serve as a simple screening test for further investigation to identify patients at risk or prone to develop life-threatening ventricular arrhythmia.

Modeling ethanol decomposition on transition metals: a combined application of scaling and Brønsted-Evans-Polanyi relations.

Applying density functional theory (DFT) calculations to the rational design of catalysts for complex reaction networks has been an ongoing challenge, primarily because of the high computational cost of these calculations. Certain correlations can be used to reduce the number and complexity of DFT calculations necessary to describe trends in activity and selectivity across metal and alloy surfaces, thus extending the reach of DFT to more complex systems. In this work, the well-known family of Brønsted-Evans-Polanyi (BEP) correlations, connecting minima with maxima in the potential energy surface of elementary steps, in tandem with a scaling relation, connecting binding energies of complex adsorbates with those of simpler ones (e.g., C, O), is used to develop a potential-energy surface for ethanol decomposition on 10 transition metal surfaces. Using a simple kinetic model, the selectivity and activity on a subset of these surfaces are calculated. Experiments on supported catalysts verify that this simple model is reasonably accurate in describing reactivity trends across metals, suggesting that the combination of BEP and scaling relations may substantially reduce the cost of DFT calculations required for identifying reactivity descriptors of more complex reactions.

Mitral valve prolapse in young healthy individuals. An early index of autoimmunity?

Mitral valve prolapse (MVP) is a benign valvular abnormality. However, an increased prevalence of MVP is reported in patients with systemic lupus erythematosus and autoimmune thyroid disease. Our aim was to evaluate whether the presence of MVP in healthy individuals might indicate a premature index of subclinical autoimmune disorder. A total of 75 individuals with MVP and 44 individuals without MVP were identified by echocardiography. Serum samples were examined for various organ and non-organ specific autoantibodies. In all, 35 of the 75 individuals with MVP had at least one autoantibody. ANA were detected in 17/75 in MVP(+) versus 1/44 in the MVP(-), (P < 0.05), and anti-ENA in 6/75 in the MVP(+) versus 0/44 in the control group, P = ns. In the MVP(+) group, thyroid autoantibodies, IgA and IgG RF were found at a statistically significant higher incidence, 16/75, 11/75 and 10/75 versus 1/44, 0/44 and 0/44 in the MVP(-)group, respectively (P < 0.05). The levels of IgG anticardiolipin antibodies were significantly higher in the MVP(+) group, P < 0.05. The presence of organ and non-organ specific autoantibodies in young healthy MVP(+) individuals insinuate the presence of subclinical autoimmunity and might suggest that autoimmune mechanisms might be involved in its pathogenesis. A follow-up of these individuals might elucidate whether MVP constitutes an early index of autoimmunity.

Weak molecular chemisorption of N(2)/Pt(111).

The ordering in a higher-order-commensurate monolayer solid of Pt(111)- (3 × 3)-4  N(2), which has coexisting physisorbed and weakly chemisorbed N(2) species, is analyzed with model calculations. Density functional theory calculations are also used to evaluate properties of chemisorbed N(2) in a (2 × 2) unit cell on Pt(111). The relation of these results to the orientational ordering of N(2) on other metal surfaces is discussed.

Lung scintigraphy with nonspecific human immunoglobulin G ((99m)Tc-HIG) in the evaluation of pulmonary involvement in connective tissue diseases: correlation with pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT).

PURPOSE: In patients with connective tissue diseases (CTD), the early detection and evaluation of the severity of the pulmonary involvement is mandatory. High-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) are considered to be valuable noninvasive diagnostic modalities. Radiopharmaceuticals have also been used for this purpose. Our aim was the evaluation of technetium-labeled human polyclonal immunoglobulin G (HIG) lung scintigraphy in the early detection and assessment of the severity of the pulmonary involvement in CTD patients. METHODS: Fifty-two nonsmoking CTD patients were studied by PFTs, HRCT, and HIG. According to PFTs, patients were divided in group A (impaired PFTs-abnormal pulmonary function) and group B (normal pulmonary function). Semiquantitative analysis was done on HIG and HRCT and corresponding scores were obtained. RESULTS: Significant difference was found between HIG scores in the two groups (0.6 +/- 0.07 vs 0.51 +/- 0.08, P < 0.001). There was a statistically significant negative correlation between HIG scores and PFTs results and a positive correlation between HIG and HRCT scores. HIG demonstrated similar clinical performance to HRCT. At the best cut-off levels of their score (0.56 and 7, respectively), HIG had a superior sensitivity (77.5 vs 57.5%) with lower specificity (75 vs 91.7%). The combination of the two methods increased the sensitivity of abnormal findings at the expense of specificity. CONCLUSIONS: HIG scintigraphy can be used in the early detection and evaluation of the severity of the pulmonary involvement in CTD, whereas, when used in combination with HRCT, the detection of affected patients can be further improved.

Improvement of vascular endothelial function using the oral endothelin receptor antagonist bosentan in patients with systemic sclerosis.

OBJECTIVE: Increased endothelin activity may play a role in the pathogenesis of vascular injury, a primary feature of systemic sclerosis (SSc; scleroderma). Our goal was to test the hypothesis that treatment with the oral endothelin receptor antagonist bosentan might improve vascular endothelial function in SSc patients. METHODS: A 4-week, prospective, parallel-group study compared 12 SSc patients who did not receive bosentan treatment with 12 patients who did receive treatment (125 mg/day) for pulmonary hypertension and/or digital ulcers. There were no differences in demographic and clinical characteristics or medications between the 2 groups. Baseline endothelial dysfunction was documented by decreased brachial artery ultrasound-derived flow-mediated dilation (FMD%; <5.5). Pulse wave analysis, venous occlusion plethysmography, and measurement of serum vascular markers were performed in parallel. RESULTS: FMD%, the main end point, increased significantly from a mean +/- SD of 3.1 +/- 1.3% to 8.4 +/- 2.6% after 4 weeks of bosentan treatment (P < 0.001, compared with a change from 2.4 +/- 1.6% to 2.4 +/- 2.2% in control patients). Arterial blood pressure, endothelium-independent vascular function, augmentation index, peripheral flow reserve, as well as circulating intercellular adhesion molecule 1, E-selectin, vascular endothelial growth factor, and endothelin 1 were not significantly affected by bosentan treatment. In patients continuously treated for 4 months, during which the dosage of bosentan remained at 125 mg/day (n = 5) or increased to 250 mg/day (n = 5), the 4-week results remained unchanged. CONCLUSION: Small doses of bosentan improve endothelial function without affecting hemodynamic parameters or endothelial activation-related processes, thus supporting a direct, reversible effect of endothelin in SSc-associated vascular injury. A long-term, controlled trial to examine the potentially global clinical benefit of endothelin receptor blockade in patients with early SSc may be warranted.

Common carotid arterial stiffness and the risk of ischaemic stroke.

In the present case-control study we aimed to investigate the association of common carotid arterial (CCA) stiffness with ischaemic stroke (IS) and to determine whether this relationship was independent of conventional risk factors including CCA intima-media thickness (CCA-IMT). CCA distensibility, defined as the change of CCA-diameter during the cardiac cycle, and CCA-IMT were evaluated by means of high-resolution B-mode carotid ultrasound examination in consecutive, first-ever IS patients (n=193) and in age- and sex-matched control subjects (n=106). The CCA distensibility (inverse of CCA stiffness) was significantly (P=0.007) lower in IS (0.353 mm, 95% CI: 0.326-0.379) than in control subjects (0.415 mm, 95% CI: 0.378-0.451) even after adjusting for blood pressure values, diastolic CCA-diameter and height. The multivariate logistic regression procedure selected CCA-IMT and CCA distensibility as the only independent predictor variables of IS. Each 1 SD increase in the CCA-IMT and each 1 SD decrease in the CCA distensibility independently increased the likelihood of IS by 167.0% (OR: 2.67, 95% CI: 1.80-3.96, P<0.001) and 59.0% (OR: 1.59, 95% CI: 1.22-2.07, P=0.001) respectively. Increased CCA stiffness is associated with IS independent of conventional risk factors and CCA-IMT. The causal interrelationship between the elastic properties of the CCA and the risk of stroke deserves further investigation by longitudinal studies.

Metformin administration improves endothelial function in women with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to investigate the endothelial status in young women with polycystic ovary syndrome (PCOS), using a simple and easily reproducible hemodynamic method combined with a biological marker and to evaluate the effect of metformin treatment on these parameters. DESIGN: Descriptive clinical trial. METHODS: Forty young women, 20 with PCOS and 20 normal women of similar age and body mass index were studied. Metformin (1700 mg daily) was administered for 6 months to the PCOS group. The endothelium status and the metabolic and hormonal profile were studied in both groups, as well as after metformin, by flow-mediated dilatation (FMD) on the brachial artery and by measurements of plasma endothelin-1 (ET-1) levels. RESULTS: FMD was impaired in the PCOS group when compared with controls (3.24+/-0.71% vs 8.81+/-1.07% respectively, P<0.0001), but this difference normalized after metformin treatment (PCOS(post-metformin) vs controls: 8.17+/-1.26 vs 8.81+/-1.07%, P = 0.70) since the values significantly improved after metformin treatment (PCOS(pre-metformin) vs PCOS(post-metformin): 3.24+/-0.71 vs 8.17+/-1.26%, P=0.003). ET-1 levels were significantly higher in the PCOS women compared with the control group (7.23+/-0.50 vs 4.99+/-0.69 fmol/l, P=0.01), they improved significantly after metformin treatment (PCOS(pre-metformin) vs PCOS(post-metformin): 7.23+/-0.50 vs 3.57+/-0.60 fmol/l, P<0.0001) and their difference compared with the control group was reversed (PCOS(post-metformin) vs controls: 3.57+/-0.60 vs 4.99+/-0.69 fmol/l, P=0.13). Metformin administration improved hyperandrogenemia. However, in this study, mathematical methods used to assess insulin resistance failed to show any detected alteration after treatment with metformin. CONCLUSIONS: PCOS women were found to exhibit endothelial dysfunction compared with controls, which was reversed 6 months after metformin administration.

Common carotid artery intima-media thickness for the risk assessment of lacunar infarction versus intracerebral haemorrhage.

BACKGROUND AND PURPOSE: Arterial hypertension is the major risk factor for intracerebral haemorrhage (ICH) and lacunar infarction (LI) and both types of cerebral lesions originate from pathology of the same deep perforating small arteries. We aimed to evaluate the relationship between vascular risk factors including common carotid artery intima-media thickness (CCA-IMT) with LI versus ICH. METHODS: We prospectively collected data from 159 first ever stroke patients (67 cases with ICH and 92 cases with LI) with documented history of hypertension. All subjects underwent B-mode ultrasonographic measurements of the CCA-IMT. Logistic regression modelling was used to determine the factors (established vascular risk factors, severity and duration of hypertension, concomitant medications and CCA-IMT) that may significantly differentiate LI from ICH. RESULTS: Patients with LI had significantly (p=0.002) larger CCA-IMT values (0.926 mm, 95% CI: 0.881-0.971) than subjects with ICH (0.815 mm, 95% CI: 0.762-0.868) even after adjusting for baseline characteristics and cardiovascular medications. The multivariate logistic regression procedure selected CCA-IMT, diabetes mellitus and hypercholesterolaemia as the only independent factors able to discriminate between LI and ICH. The risk for LI versus ICH increased continuously with increasing CCA-IMT. For each increment of 0.1 mm in CCA-IMT the probability of suffering from LI versus ICH increased by 36.6% (95 % CI: 13%-65.2%, p=0.001) even after adjustment for cardiovascular risk factors. CONCLUSIONS: Increased CCA-IMT values are a factor favouring LI over ICH in hypertensive patients. The measurement of CCA-IMT may be a useful non-invasive diagnostic tool for the risk assessment of LI with respect to ICH in such patients.

U-shaped relationship between mortality and admission blood pressure in patients with acute stroke.

OBJECTIVE: To evaluate the relationship between systolic blood pressure (SBP) or diastolic blood pressure (DBP) on admission and early or late mortality in patients with acute stroke. DESIGN: Prospective study of hospitalized first-ever stroke patients over 8 years. SETTING: Stroke unit and medical wards in a University hospital. SUBJECTS: A total of 1121 patients admitted within 24 h from stroke onset and followed up for 12 months. MAIN OUTCOME MEASURES: Mortality at 1 and 12 months after stroke in relation to admission SBP and DBP. RESULTS: Early and late mortality in patients with acute ischaemic or haemorrhagic stroke in relation to admission SBP and DBP followed a 'U-curve pattern'. After adjusting for known outcome predictors, the relative risk of 1-month and 1-year mortality associated with a 10-mmHg SBP increase above 130 mmHg (U-point of the curve) increased by 10.2% (95% CI: 4.2-16.6%) and 7.2% (95% CI: 2.2-12.3%), respectively. For every 10 mmHg SBP decrease, below the U-point, the relative risk of 1-month and 1-year mortality rose by 28.2% (95% CI: 8.6-51.3%) and 17.5% (95% CI: 3.1-34.0%), respectively. Low admission SBP-values were associated with heart failure (P < 0.001) and coronary artery disease (P = 0.006), whilst high values were associated with history of hypertension (P < 0.001) and lacunar stroke (P < 0.001). Death due to cerebral oedema was significantly (P = 0.005) more frequent in patients with high admission SBP-values, whereas death due to cardiovascular disease was more frequent (P = 0.004) in patients with low admission SBP-values. CONCLUSION: Acute ischaemic or haemorrhagic stroke patients with high and low admission BP-values have a higher early and late mortality. Coincidence of heart disease is associated with low initial BP-values. Death due to neurological damage from brain oedema is associated with high initial BP-values.

Systemic sclerosis is not associated with clinical or ambulatory blood pressure.

BACKGROUND: Raynaud's phenomenon is often the first symptom and occurs eventually in more than 95% of patients with systemic sclerosis (SSc). Angiographic studies disclose narrowing and obstruction of the digital arteries, which on autopsy histologic study show prominent subintimal connective tissue proliferation without inflammation, as well as adventitial fibrosis. It is also known that primary cardiac problems include pericarditis, left ventricular or biventricular failure, serious supraventricular or ventricular arrhythmias emerge in patients with SSc. It is not known if these patients present hypertension or hypotension and which parameter of the ambulatory blood pressure may influence such a disease course. METHODS: A total of 85 subjects underwent clinical blood pressure (BP) readings, 24-hour ambulatory BP monitoring, left ventricular assessment by echocardiography and measurement of intima media thickness (IMT) of the right-left internal carotid arteries (RICA and LICA) and right-left common carotid arteries (RCCA and LCCA). The population consisted of 40 subjects with SSc according to the criteria of the American College of Rheumatology (SCL-group) who were not receiving any antihypertensive treatment and 45 healthy volunteers (control group). The two groups did not differ in age. RESULTS: Clinical systolic and diastolic blood pressure, clinical heart rate, mean 24 h systolic blood pressure, SD systolic blood pressure, mean 24 h diastolic blood pressure, SD 24 h diastolic blood pressure, mean 24 h heart rate, SD 24 h heart rate, pulse pressure 24 h, serum glucose, cholesterol, triglycerides, HDL, LDL, creatinine, urea, potassium and natrium did not statistically significant differ between the two groups. Furthermore, the left ventricular mass/BSA and IMT of both carotid arteries did not show a statistically significant difference between the groups. CONCLUSION: Systemic sclerosis is not associated with clinical blood pressure or the parameter of 24 h blood pressure monitoring.

Mitral valve prolapse in systemic lupus erythematosus patients: clinical and immunological aspects.

Mitral valve prolapse (MVP) has been reported to be associated with systemic lupus erythematosus (SLE). The aim of the present study was to determine the prevalence of MVP in SLE patients, assess its clinical significance and examine the possible association of this entity with other autoimmune indices. Eighty-seven consecutive SLE patients attending the rheumatology clinic and 73 normal control subjects were examined by M-mode, two-dimensional color-Doppler echocardiography. Serum samples were examined for various organ and non-organ specific autoantibodies. MVP was detected in 19/87 patients with SLE and in four of the healthy controls(P = 0.0057). SLE patients with MVP were younger (33.6 +/- 12.4 years) than those without MVP (41. +/- 12.9, P = 0.04) and with shorter duration of the disease (P = 0.03). We found a statistically higher prevalence of anticardiolipin antibodies (aCL) in SLE patients with prolapse (11/19) compared with SLE patients without prolapse (15/68, P = 0.04). This association was independent of age. The aCL-lgG levels were significantly higher in SLE patients with MVP (32.37 +/- 43.26) compared with SLE patients without MVP (22.24 +/- 29.95, P = 0.04). Thyroid autoantibodies tended to be more common in S LE patients with MVP. Th e prevalence of MVP is increased in SLE patients. The presence of aCL and of organ-specific autoantibodies in SLE patients with MVP might indicate the autoimmune origin of MVP. The possibility that SLE patients with MVP may be predisposed to further autoimmune diseases should be considered.

The androgen receptor gene CAG polymorphism is associated with the severity of coronary artery disease in men.

OBJECTIVE: The role of androgens in the pathogenesis of coronary artery disease (CAD) remains controversial. The length of the polyglutamine stretch of the transactivation domain (CAG repeat) of the androgen receptor (AR) inversely affects androgen activity. The aim of this study was to investigate the effect of this polymorphism of the AR gene in the extent of CAD in male patients. DESIGN AND PATIENTS: The relationship of the length of the AR gene CAG repeat on the severity of CAD was examined in 131 men (36-86 years old) undergoing coronary angiography. MEASUREMENTS: The severity of CAD was assessed by the number (0-3) of coronary vessels with > 50% reduction in the luminal diameter. The interaction of the AR gene polymorphism with the intima media thickness (IMT) of peripheral arteries and serum levels of sex steroids, insulin and biochemical parameters were also studied. RESULTS: The upper quartile of CAG length (range 9-30) was > or = 23 repeats (longAR). The mean body mass index (BMI) of patients with shorter repeats (< 23; shortAR) was significantly lower than in men with longAR (26.1 vs. 27.6, respectively; P = 0.043 M-W Rank test). There was no correlation between the AR gene repeat length and serum testosterone. Oestradiol levels were significantly higher in longAR (0.19 +/- 0.08 nmol/l vs. 0.14 +/- 0.07 in shortAR, P = 0.031). This difference was independent of BMI. Men with shortAR had significant CAD (i.e. one to three arteries with stenosis) more frequently (79.5%) than men with longAR (20.5%); of the subjects with stenosis in no arteries, 56.5% had shortAR and 43.5% longAR (chi2 = 4.3, P = 0.038). This association was independent of age and BMI. The IMT of peripheral arteries, lipid parameters, basal insulin resistance, blood pressure and family history for early CAD, did not differ according to AR length. CONCLUSIONS: The shorter CAG repeat of the AR gene is associated with more severe CAD, which suggests a role for the sensitivity to androgens in the increased frequency of CAD in males. In addition, a protective role of endogenous oestrogen, which is higher in the longAR subgroup, can contribute to the observed difference.

CD40L overexpression on T cells and monocytes from patients with systemic lupus erythematosus is resistant to calcineurin inhibition.

To explore the regulatory defects underlying the overexpression of CD40 ligand (CD40L, CD154) in human lupus we studied the effects of cyclosporin-A (CsA), which blocks Ca2+/calcineurin-dependent CD40L gene expression, on peripheral blood-derived T cells and monocytes. In contrast to control subjects, CsA failed to inhibit the prolonged CD40L expression observed in vitro on anti-CD3-activated lupus T cells. Resistance to CsA was not restricted to CD4+ or CD8+ T cell subsets and was disease activity-independent. Experiments assessing the effects of dexamethasone on CD40L expression, as well as of CsA on the early activation marker CD69 expression and on surface CD40L cleavage, confirmed the unique regulation of CD40L in lupus T cells. On the other hand, co-culture with anti-CD3-activated T cells caused surface CD40L expression on monocytes, which was not an Fc receptor-mediated event. Lupus monocytes clearly overexpressed CD40L comparing to healthy and disease-control monocytes, and, similarly to lupus T cells, displayed a prominent resistance to CsA inhibitory effects. These findings indicate that, besides Ca2+/calcineurin-dependent mechanisms, other pathways are involved in the dysregulation of CD40L in SLE immune cells, dissection of which may have important therapeutic implications.

Glucocorticoid effects on myocardial performance in patients with systemic sclerosis.

OBJECTIVE: Myocardial inflammation andfibrosis are common autopsyfindings in systemic sclerosis (SSc) and, although symptomatic cardiac involvement occurs less often, current therapies remain empiric and do not prevent or modify its course. In this open, uncontrolled study we assessed the short-term effects of glucocorticoid administration on myocardial performance in patients with SSc in the absence of clinically overt cardiac disease. METHODS: Resting radionuclide ventriculography with 99mTc was performed before and 20 days after the administration of prednisolone, 20 mg daily, in 32 patients with SSc without clinically evident myocardial dysfunction at rest; 13 and 19 patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), respectively, were studied in parallel as controls. RESULTS: The mean left ventricular ejection fraction (LVEF) value at baseline was 59% in the SSc group; similar values were found for the SLE (61%) and RA (59%) groups. An impaired LVEF (i.e., <50%) was found in 6 patients with SSc and in 1 patient with SLE. Prednisolone administration resulted in a significant percent improvement in the baseline LVEF (mean 18%, p = 0.0001) in the SSc group; this improvement was greater in the patients with diffuse SSc than in those with limited skin disease (27% vs 10%, p = 0.02). The improvement was most prominent in the 6 patients with an initial impaired LVEF No significant improvement was observed in the SLE or RA control groups. The linear trend betveen the individual baseline LVEF values in patients with SSc and their percent changes after treatment (r2 = 0.55, p: 0.00001) showed that the lower the initial LVEF the greater the improvement caused by prednisolone. The degree of LVEF improvement was also associated with the individual erythrocvte sedimentation rate values and serum IgG concentrations at baseline. Prednisolone-induced changes in LVEF were not associated with any changes in blood pressure, heart rate, blood, plasma, or red cell volumes. CONCLUSION: Glucocorticoid administration may improve myocardial performance in some patients with SSc. Although further double-blind controlled studies of the long-term effects are warranted, such treatment may be useful in those patients with SSc and documented low LVEF if they are kept under careful observation for objective improvement.

B-cell kinase lyn deficiency in patients with systemic lupus erythematosus.

BACKGROUND: To better understand the molecular background of B-cell overactivity characterizing systemic lupus erythematosus (SLE), we examined the expression of the CD22 co-receptor and of kinase Lyn, which are involved in signaling inhibitory pathways, in B cells from patients with SLE. METHODS: Two-color flow cytometry was used to study the expression of surface antigens on freshly isolated peripheral B cells from patients with SLE, disease-control patients, and healthy volunteers. Intracellular kinases Lyn and Syk were analyzed using Western immunoblots, and differences at the messenger RNA (mRNA) level were evaluated using semiquantitative polymerase chain reaction (PCR). RESULTS: Expression of B-cell surface CD22 was intact in patients with SLE, but expression of the B-cell kinase Lyn was significantly decreased in resting, as well as in anti-sIgM-stimulated B-cell-enriched cell lysates obtained from 66% of patients with SLE. Lyn deficiency was disease-specific and unrelated to disease activity. Expression of B-cell kinase Syk was similar in all study groups. Semiquantitative PCR revealed that Lyn mRNA was significantly decreased in lupus patients with decreased Lyn protein expression, suggesting that Lyn deficiency may be caused at least in part by defects at the transcription level. CONCLUSIONS: Decreased expression of Lyn in some patients with SLE represents a B-cell defect that may enhance our understanding of SLE molecular pathogenesis by providing rational therapeutic targets.

Diffusion of N adatoms on the Fe(100) surface

The diffusion of individual N adatoms on Fe(100) has been studied using scanning tunneling microscopy and ab initio density functional theory (DFT) calculations. The measured diffusion barrier for isolated N adatoms is E(d) = (0.92+/-0.04) eV, with a prefactor of nu(0) = 4.3x10(12) s(-1), which is in quantitative agreement with the DFT calculations. The diffusion is strongly coupled to lattice distortions, and, as a consequence, the presence of other N adatoms introduces an anisotropy in the diffusion. Based on experimentally determined values of the diffusion barriers and adsorbate-adsorbate interactions, the potential energy surface experienced by a N adatom is determined.