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ABSTRACT: Growing evidence demonstrates that extracellular matrices (ECMs) regulate many aspects of megakaryocyte (MK) development; however, among the different ECM receptors, integrin alpha2beta1 and GPVI are the only collagen receptors studied in platelets and MKs. In this study, we demonstrate the expression of the novel collagen receptor Discoidin Domain Receptor 1 (DDR1) by human MKs at both mRNA and protein levels and provide evidence of DDR1 involvement in the regulation of MK motility on type I collagen through a mechanism based on the activity of SHP1 phosphatase and Syk tyrosine kinase. Specifically, we demonstrated that inhibition of DDR1 binding to type I collagen, preserving the engagement of the other collagen receptors, GPVI, alpha2beta1 and LAIR-1 determines a decrease in MK migration due to the reduction in SHP1 phosphatase activity and consequent increase in the phosphorylation level of its main substrate Syk. Consistently, inhibition of Syk activity restored MK migration on type I collagen. In conclusion, we report the expression and function of a novel collagen receptor on human MKs and we point out that increasing level of complexity is necessary to better understand MK-collagen interactions in the bone marrow environment.
Journal of Biological Chemistry 03/2013; · 4.77 Impact Factor
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ABSTRACT: In AL amyloidosis prognosis depends on the severity of heart dysfunction which is best assessed by natriuretic peptides (BNP and NT-proBNP). However, their clearance relies on glomerular filtration rate (GFR) and their concentration increases with renal failure. We evaluated the diagnostic and prognostic performance of NT-proBNP and BNP in 248 patients with AL amyloidosis with different degrees of renal failure. Patients were grouped according to GFR. Group 1 comprised 109 patients with GFR ≥60 mL/min/1.73 m(2) , Group 2, 77 subjects with GFR <60 and ≥15 mL/min/1.73 m(2) , and Group 3, 62 patients with GFR <15 mL/min/1.73 m(2) . The ability of natriuretic peptides to detect heart involvement and to predict survival in the three groups was assessed. Decreasing eGFR required higher cutoffs of both NT-proBNP and BNP for detecting heart involvement and predicting survival. Both natriuretic peptides were independent prognostic markers in Groups 1 and 2, whereas in Group 3 only BNP independently predicted survival. Natriuretic peptides are powerful and useful markers of cardiac dysfunction and prognosis, provided that eGFR is considered in interpreting their clinical meaning. BNP should be preferred in patients with end-stage renal failure.
American Journal of Hematology 01/2012; 87(5):465-71. · 4.67 Impact Factor
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ABSTRACT: Serial measurement of NT-proBNP is performed routinely in the monitoring and assessment of the effectiveness of therapy in patients being treated for chronic heart failure (CHF). Intra-individual changes in NT-proBNP levels over time are compared typically to a reference change value (RCV) determined using either a standard [i.e., nested analysis of variance (nANOVA)] or a lognormal approach. The RCV defines the minimum percent change in serial analyte values that exceeds the percent change expected due to biological variation alone. Currently, there is no consensus on which approach (nANOVA or lognormal) to determining RCV is better.
Based on these considerations, we aimed to illustrate the impact of data transformation on the calculation of the biological variation of NT-proBNP and discuss the utility of logarithmic transformation in monitoring patients with heart failure.
15 healthy subjects were enrolled after informed consent; 5 blood specimens were collected twice a week. Nested ANOVA from replicate analyses was applied to obtain components of biological variation, on the raw data and after data transformation.
NT-proBNP distribution being highly skewed required data transformation. Natural log transformation yielded normalization. An example demonstrates that for untransformed values the RCV was overestimated for low concentrations of NT-proBNP and underestimated for higher concentrations.
Log-transformed data are often used in the establishment of reference intervals for evaluating laboratory tests results in clinical practice, especially when the reference interval data are not Gaussian distributed. As log-normal approach is the best approach to determining RCV values we encourage its use assessing the clinical utility of NT-proBNP serial testing. We propose that the log-normal approach becomes the standard approach to determining RCV and replaces the use of nANOVA.
Clinica chimica acta; international journal of clinical chemistry 12/2011; 413(5-6):544-7. · 2.54 Impact Factor
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Giovanni Palladini,
Alessandra Barassi,
Stefano Perlini,
Paolo Milani,
Andrea Foli,
Paola Russo,
Riccardo Albertini,
Laura Obici,
Francesca Lavatelli,
Gabriele Sarais,
Simona Casarini, Remigio Moratti,
Gian Vico Melzi d'Eril,
Giampaolo Merlini
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ABSTRACT: Cardiac biomarkers play a major role in the identification of patients at risk of early death in AL amyloidosis, and a staging system based on amino-terminal pro-natriuretic peptide type-B (NT-proBNP) and troponins (cTn) is used for prognostic stratification. Adrenomedullin is produced by several tissues including the heart, and portends a poor prognosis in heart diseases. We investigated the ability of midregional proadrenomedullin (MR-proADM) to predict early death in AL amyloidosis.
One-hundred and thirty consecutive patients with newly-diagnosed AL amyloidosis were prospectively enrolled. The impact on survival of NT-proBNP, cTnI and MR-proADM was evaluated.
The concentration of MR-proADM correlated with systolic and diastolic function, but did not reflect the amount of amyloid deposited in the heart. Moreover, MR-proADM was associated with non-cardiac markers of advanced disease. The staging system based on NT-proBNP and cTnI identified high-risk subjects, but could not discriminate good-risk and intermediate-risk patients. Conversely, a staging system based on MR-proADM and cTnI identified 3 groups with significantly different survivals.
Midregional-proADM is a powerful prognostic marker in AL amyloidosis, which may not only reflect cardiac dysfunction but also widespread systemic disease, and can be combined with cTn for detecting patients at risk of early death.
Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 11/2011; 18(4):216-21. · 2.12 Impact Factor
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ABSTRACT: The mechanisms by which megakaryocytes (MKs) differentiate and release platelets into the circulation are not well understood. However, growing evidence indicates that a complex regulatory mechanism involving MK-matrix interactions may contribute to the quiescent or permissive microenvironment related to platelet release within bone marrow. To address this hypothesis, in this study we demonstrate that human MKs express and synthesize cellular fibronectin (cFN) and transglutaminase factor XIII-A (FXIII-A). We proposed that these 2 molecules are involved in a new regulatory mechanism of MK-type I collagen interaction in the osteoblastic niche. In particular, we demonstrate that MK adhesion to type I collagen promotes MK spreading and inhibits pro-platelet formation through the release and relocation to the plasma membrane of cFN. This regulatory mechanism is dependent on the engagement of FN receptors at the MK plasma membrane and on transglutaminase FXIII-A activity. Consistently, the same mechanism regulated the assembly of plasma FN (pFN) by adherent MKs to type I collagen. In conclusion, our data extend the knowledge of the mechanisms that regulate MK-matrix interactions within the bone marrow environment and could serve as an important step for inquiring into the origins of diseases such as myelofibrosis and congenital thrombocytopenias that are still poorly understood.
Blood 12/2010; 117(8):2476-83. · 9.90 Impact Factor
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Giovanni Palladini,
Alessandra Barassi,
Catherine Klersy,
Rosana Pacciolla,
Paolo Milani,
Gabriele Sarais,
Stefano Perlini,
Riccardo Albertini,
Paola Russo,
Andrea Foli,
Letizia Zenone Bragotti,
Laura Obici, Remigio Moratti,
Gian Vico Melzi d'Eril,
Giampaolo Merlini
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ABSTRACT: In light-chain (AL) amyloidosis, prognosis is dictated by cardiac dysfunction. N-terminal natriuretic peptide type B (NT-proBNP) and cardiac troponins (cTn) are used to assess the severity of cardiac damage. We evaluated the prognostic relevance of a high-sensitivity (hs) cTnT assay, NT-proBNP, and cardiac troponin I in 171 consecutive patients with AL amyloidosis at presentation and 6 months after treatment. Response and progression of NT-proBNP were defined as more than 30% and more than 300 ng/L changes. All 3 markers predicted survival, but the best multivariable model included hs-cTnT. The hs-cTnT prognostic cutoff was 77 ng/L (median survival 10.6 months for patients with hs-cTnT above the cutoff). After treatment, response and progression of NT-proBNP and a more than 75% increase of hs-cTnT were independent prognostic determinant. In AL amyloidosis, hs-cTnT is the best baseline prognostic marker. Therapy should be aimed at preventing progression of cardiac biomarkers, whereas NT-proBNP response confers an additional survival benefit.
Blood 11/2010; 116(18):3426-30. · 9.90 Impact Factor
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ABSTRACT: To compare the performance of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc).
Between January 2008 and March 2009, outpatients referred to our unit and satisfying LeRoy criteria for SSc were assessed for PAH. Doppler echocardiography, BNP measurement, and NT-proBNP measurement were done concomitantly for a complete clinical, instrumental, and biochemical evaluation. Right-heart catheterization was carried out in cases of suspected PAH [estimated pulmonary arterial pressure (PAP) ≥ 36 mm Hg; diffusion capacity for carbon monoxide (DLCO) ≤ 50% of predicted value; 1-year DLCO decline ≥ 20% in absence of pulmonary fibrosis; unexplained dyspnea].
One hundred thirty-five patients were enrolled (124 women, 11 men; 96 limited SSc, 39 diffuse SSc); precapillary PAH was found in 20 patients (15 limited SSc, 5 diffuse SSc). The estimated PAP correlated with both BNP (R = 0.3; 95% CI 0.14-0.44) and NT-proBNP (R = 0.3, 95% CI 0.14-0.45). BNP [area under the curve (AUC) 0.74, 95% CI 0.59-0.89] was slightly superior to NT-proBNP (AUC 0.63, 95% CI 0.46-0.80) in identification of PAH, with diagnosis cutoff values of 64 pg/ml (sensitivity 60%, specificity 87%) and 239.4 pg/ml (sensitivity 45%, specificity 90%), respectively. BNP (log-transformed, p = 0.032) and creatinine (p = 0.049) were independent predictors of PAH, while NT-proBNP was not (p = 0.50).
In our single-center study, the performance of BNP was slightly superior to that of NT-proBNP in PAH screening of patients with SSc, although normal levels of these markers do not exclude diagnosis. We observed that impaired renal function is associated with an increased risk of PAH in SSc. Further multicenter studies are needed to confirm our results (ClinicalTrials.gov ID NCT00617487).
The Journal of Rheumatology 10/2010; 37(10):2064-70. · 3.69 Impact Factor
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ABSTRACT: Conventional diagnostic tests (such as radioallergosorbent test [RAST] and skin prick test [SPT]) use native raw pollen allergen extracts to establish allergy. However, recombinant allergens may offer important advantages compared with their natural counterparts.
This study evaluated serum immunoglobulin E (IgE) in patients with grass-induced allergic rhinitis (AR) or AR with asthma (ARA), comparing assays with natural or recombinant grass allergens.
Sixty patients (33 AR, 27 ARA) positive with SPT and serum IgE for Phleum pratense were enrolled in the study. Serum IgE specific for conventional and recombinant Phleum pratense: rPhl p 1, rPhl p 2, nPhl p 4, rPhl 5b, rPhl p 6, rPhl p 7, rPhl p 11, rPhl p 12, were measured by the IFMA procedure (ImmunoCAP, Phadia, Uppsala, Sweden). Data were expressed as the median (md) and percentiles. Recombinant allergen results were expressed also as the percentage of positive concentrations. The Wilcoxon test was used to compare samples. Because diagnosis is a binary variable (AR/ARA), logistic regression analysis was performed to identify possible correlates.
IgE concentrations assessed with recombinant allergens were significantly higher in ARA patients (p = .05) than in AR patients. A value >5.8 kU/L is the optimal cut-off to discriminate AR and ARA patients. Model specificity was 76%, sensitivity 78%, and efficiency 77%.
This study shows that IgEs for natural and recombinant grass pollen allergens are significantly higher in patients with AR and asthma. Moreover, using recombinant allergens it is possible to define a prediction model for diagnosis with 77% efficiency. Therefore, this study may suggest that there are advantages of using recombinant or purified, native allergens over crude extracts.
Journal of Asthma 09/2010; 47(7):750-3. · 1.52 Impact Factor
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Giovanni Palladini,
Paola Russo,
Tiziana Bosoni,
Gabriele Sarais,
Francesca Lavatelli,
Andrea Foli,
Letizia Zenone Bragotti,
Vittorio Perfetti,
Laura Obici,
Franco Bergesio,
Riccardo Albertini, Remigio Moratti,
Giampaolo Merlini
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ABSTRACT: IgM-associated AL amyloidosis is rare and may represent a distinct entity. Sixty (7%) of 868 consecutive AL patients referred to our center had an IgM monoclonal protein. They were significantly older than non-IgM patients (median, 67 years vs. 62 years), had a higher frequency of lymph-node involvement (25% vs. 2%) and significantly lower median proteinuria (1.2 g/24h vs. 3.4 g/24h), N-terminal pro-natriuretic peptide type-B (1177 ng/L vs. 2135 ng/L) and troponin I (0.02 ng/mL vs. 0.05 ng/mL). In IgM patients, kappa light-chains were more frequent (42% vs. 23%) and the involved free light-chain concentration was lower (median 63 mg/L vs. 182 mg/L). Serum albumin and NT-proBNP were independent prognostic determinants. Response to treatment improved survival. The 14 patients who received melphalan/dexamethasone showed a 64% hematologic (complete remissions, 29%) and a 43% organ response rate. IgM-associated AL amyloidosis is a distinct entity, with less advanced organ dysfunction. Treatment with melphalan/ dexamethasone might be effective in these patients.
Clinical Lymphoma & Myeloma 03/2009; 9(1):80-3. · 1.13 Impact Factor
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ABSTRACT: To evaluate the risk of fetal growth restriction (FGR) associated with first-trimester maternal serum concentrations of pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG).
A longitudinal study of 2,178 women who underwent first-trimester evaluation of serum PAPP-A and free beta-hCG. FGR was defined as a decrement of the fetal abdominal circumference to below the 10th percentile of our standard growth curve in the presence of Doppler signs of impaired placental perfusion. Logistic regression was used to compute multivariable odds ratios and the estimated prevalences of outcomes associated with first-trimester serum marker concentrations.
The prevalences of small for gestational age (SGA, <10th percentile birth-weight) neonates and FGR were significantly higher among women with serum PAPP-A concentrations below the 10th percentile than in controls: 40/206 compared to 183/1,928, for SGA, adjusted odds ratio = 2.1, 95% confidence intervals (CI) 1.4-3.03; 24/75 compared to 182/1,900, for FGR, adjusted odds ratio = 3.9, 95% CI 2.3-6.5. The adjusted prevalences of FGR and SGA among women with simultaneous low first-trimester values of PAPP-A and free beta-hCG were 0.21 (95% CI 0.13-0.33) and 0.26 (95% CI 0.17-0.36), respectively.
Low first-trimester maternal serum PAPP-A concentrations are significantly associated with reduced fetal size and increased risk of FGR with Doppler signs of impaired placental perfusion.
Fetal Diagnosis and Therapy 03/2009; 25(1):130-5. · 1.05 Impact Factor
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ABSTRACT: Protein misfolding and deposition as amyloid, with consequent tissue damage, plays a key role in the group of diseases generically termed amyloidoses. In the systemic forms, amyloid deposition is widespread and causes severe dysfunction of vital organs. Proteomic analysis, thanks to its versatility and the comprehensiveness of information obtained, is an ideal tool for the study of systemic amyloidoses. It has been successfully employed in the characterization of the circulating amyloidogenic precursors and the analysis of affected tissues, for the diagnostic identification of the fibril components and for characterizing disease-related changes in protein expression. We present the developments in the field of proteomics applied to systemic amyloidoses, and discuss the perspectives opened in the study of these diseases.
Clinical Chemistry and Laboratory Medicine 02/2009; 47(6):627-35. · 2.15 Impact Factor
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Giovanni Palladini,
Paola Russo,
Tiziana Bosoni,
Laura Verga,
Gabriele Sarais,
Francesca Lavatelli,
Mario Nuvolone,
Laura Obici,
Simona Casarini,
Simona Donadei,
Riccardo Albertini,
Gabriella Righetti,
Maddalena Marini,
Maria Stella Graziani,
Gian Vico Melzi D'Eril, Remigio Moratti,
Giampaolo Merlini
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ABSTRACT: The diagnosis of systemic immunoglobulin light-chain (AL) amyloidosis requires demonstration of amyloid deposits in a tissue biopsy and amyloidogenic monoclonal light chains. The optimal strategy to identify the amyloidogenic clone has not been established. We prospectively assessed the diagnostic sensitivity of the serum free light chain (FLC) kappa/lambda ratio, a commercial serum and urine agarose gel electrophoresis immunofixation (IFE), and the high-resolution agarose gel electrophoresis immunofixation (HR-IFE) developed at our referral center in patients with AL amyloidosis, in whom the amyloidogenic light chain was unequivocally identified in the amyloid deposits.
The amyloidogenic light chain was identified in 121 consecutive patients with AL amyloidosis by immunoelectron microscopy analysis of abdominal fat aspirates and/or organ biopsies. We characterized the monoclonal light chain by using IFE and HR-IFE in serum and urine and the FLC kappa/lambda ratio in serum. We then compared the diagnostic sensitivities of the 3 assays.
The HR-IFE of serum and urine identified the amyloidogenic light chain in all 115 patients with a monoclonal gammopathy. Six patients with a biclonal gammopathy were omitted from the statistical analysis. The diagnostic sensitivity of commercial serum and urine IFE was greater than that of the FLC kappa/lambda ratio (96% vs 76%). The combination of serum IFE and the FLC assay detected the amyloidogenic light chain in 96% of patients. The combination of IFE of both serum and urine with the FLC kappa/lambda ratio had a 100% sensitivity.
The identification of amyloidogenic light chains cannot rely on a single test and requires the combination of a commercially available FLC assay with immunofixation of both serum and urine.
Clinical Chemistry 02/2009; 55(3):499-504. · 7.91 Impact Factor
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Sofia Giorgetti,
Sara Raimondi,
Silvia Cassinelli,
Monica Bucciantini,
Massimo Stefani,
Gina Gregorini,
Giulia Albonico, Remigio Moratti,
Giovanni Montagna,
Monica Stoppini,
Vittorio Bellotti
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ABSTRACT: In dialysis-related amyloidosis, beta2-microglobulin accumulates as amyloid fibrils preferentially around bones and tendons provoking osteoarthritis. In addition to the pathologic role played by the amyloid fibrils, it can be speculated that a pathogenic role is also played by the high concentrations of soluble beta2-microglobulin because it is toxic for certain cell lines like HL60 and mitogen for other cells such as the osteoclasts. The discovery that beta2-microglobulin can influence the biology of certain cells may lead to the assumption that it might affect neuronal cells that are quite sensitive to amyloidogenic proteins in the oligomeric state. Such a concern might be supported by clinical evidence that haemodialysis is associated with the risk of a cognitive impairment.
The cytotoxicity of beta2-microglobulin on the SH-SY5Y neuroblastoma cells was assayed by the MTT test. The beta2-microglobulin concentration was determined in the cerebrospinal fluid of four different patients by means of immunonephelometry and western blot.
Oligomeric beta2-microglobulin is cytotoxic for the SH-SY5Y cells at a concentration that can be easily reached in the plasma of patients on haemodialysis. However, the beta2-microglobulin concentration, measured in the cerebrospinal fluid of a haemodialysis patient, appears to be independent of its plasma concentration and is maintained under the lower limit of cytotoxicity we have determined in the cell culture.
Although beta2-microglobulin is potentially neurotoxic, it is unlikely that this protein plays a role in the pathophysiology of cognitive impairment observed in haemodialysis patients due to the protective effect of the blood brain barrier that maintains a low concentration of beta2-microglobulin in the cerebrospinal fluid.
Nephrology Dialysis Transplantation 12/2008; 24(4):1176-81. · 3.40 Impact Factor
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Giovanni Palladini,
Paola Russo,
Francesca Lavatelli,
Mario Nuvolone,
Riccardo Albertini,
Tiziana Bosoni,
Vittorio Perfetti,
Laura Obici,
Stefano Perlini, Remigio Moratti,
Giampaolo Merlini
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ABSTRACT: Patients with primary (AL) amyloidosis and heart failure have a very poor prognosis and cannot tolerate aggressive therapy, such as autologous stem cell transplantation and high-dose dexamethasone-based regimens. We prospectively treated 22 patients with advanced cardiac amyloidosis combining oral melphalan, thalidomide, and reduced intensity dexamethasone (MTD). Six patients died due to cardiac amyloidosis before completing cycle 3. Early death was associated with reduced ejection fraction. Eight patients achieved a hematological response and four achieved a durable improvement of cardiac dysfunction. Treatment with MTD is feasible in patients with advanced cardiac AL amyloidosis and effective in subjects with preserved systolic function.
Annals of Hematology 10/2008; 88(4):347-50. · 2.62 Impact Factor
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ABSTRACT: Citrulline (CIT), a non-protein amino acid in circulating blood, is almost exclusively contained in the enterocytes of small bowel mucosa and may represent a reliable marker of functioning enterocyte mass. The aim of this study was to evaluate the clinical utility of measuring serum citrulline levels in a group of patients affected by coeliac disease (CD). Fifty healthy volunteers, 21 patients with untreated coeliac disease and 6 patients with refractory coeliac disease took part in the study. Serum citrulline levels and duodenal lesions were evaluated at the time of diagnosis, and after at least 24 months of gluten-free diet. Serum citrulline concentrations were determined by ion exchange chromatography. In comparison to healthy volunteers, serum citrulline concentrations were significantly lower in untreated and refractory coeliac disease patients. No significant difference was found between untreated and refractory coeliac disease patients and between patients with different patterns of clinical presentation or various degrees of duodenal lesions. After a gluten-free diet, the mean of serum citrulline concentration was increased in all but one patient. Although, as expected, serum citrulline levels turned out to be low in coeliac disease, the clinical utility of their measurement is, at least, questionable in this condition.
Internal and Emergency Medicine 05/2008; 3(3):233-6. · 2.06 Impact Factor
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ABSTRACT: This article will focus on the relationship between serum levels of anti-citrullinated peptide antibodies (anti-CCP) or rheumatoid factor (RF) and clinical response to TNF-alpha blockers in order to evaluate whether these antibodies may have a role as serological markers of response to therapy in rheumatoid arthritis (RA). The changes induced in anti-CCP levels after TNF blocking therapy still remain a controversial issue even though a marked reduction following conventional DMARDs has been reported in early disease. On the other hand, a drop in RF levels during treatment has been reported by many authors. Decreased IgM RF levels seem to parallel clinical response suggesting that this antibody can also be regarded as a marker of response to treatment. Pre-treatment RF positivity or negativity does not influence response to TNF-alpha blocking therapy while high pre-treatment levels of IgA RF seem to be associated with a poor response rate.
Annals of the New York Academy of Sciences 09/2007; 1109:287-95. · 3.15 Impact Factor
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Francesco Passamonti,
Maria Luigia Randi,
Elisa Rumi,
Ester Pungolino,
Chiara Elena,
Daniela Pietra,
Margherita Scapin,
Luca Arcaini,
Fabiana Tezza, Remigio Moratti,
Cristiana Pascutto,
Fabrizio Fabris,
Enrica Morra,
Mario Cazzola,
Mario Lazzarino
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ABSTRACT: Essential thrombocythemia (ET) may occur in women of childbearing age. To investigate the risk of pregnancy complications, we studied 103 pregnancies that occurred in 62 women with ET. The 2-tailed Fisher exact test showed that pregnancy outcome was independent from that of a previous pregnancy. The rate of live birth was 64%, and 51% of pregnancies were uneventful. Maternal complications occurred in 9%, while fetal complications occurred in 40% of pregnancies. The Mantel-Haenszel method showed that fetal loss in women with ET was 3.4-fold higher (95% confidence interval [CI]: 3-3.9; P < .001) than in the general population. Half of the women studied carried the JAK2 (617V>F) mutation, and a multivariate logistic regression model identified this mutation as an independent predictor of pregnancy complications (P = .01). Neither the platelet count nor the leukocyte count was a risk factor. JAK2 (617V>F)-positive patients had an odds ratio of 2.02 (95% CI: 1.1 - 3.8) of developing complications in comparison with JAK2 (617V>F)-negative patients. Aspirin did not prevent complication in JAK2 (617V>F)-positive patients and appeared to worsen outcome in JAK2 (617V>F)-negative patients. A relationship was found between JAK2 (617V>F) and fetal loss (P = .05). This study indicates that patients carrying the JAK2 (617V>F) mutation have higher risk of developing pregnancy complications.
Blood 07/2007; 110(2):485-9. · 9.90 Impact Factor
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ABSTRACT: Recruitment and activation of both neutrophils and eosinophils seem to be a characteristic of chronic bronchitis. The purpose of this study was to evaluate whether eosinophil cationic protein and/or myeloperoxidase (ECP/MPO) serum levels differ between patients with chronic obstructive and nonobstructive bronchitis during an exacerbation-free period and if they represent clinical gravity indicators of disease. To identify a correlation between ECP/MPO values in serum and bronco-obstruction, a statistical analysis by logistic regression was used. Study results show that there is a relationship between increased serum levels of ECP and log MPO and an increased risk for forced expiratory volume in 1 second (FEV1) pathologic values associated with obstructive chronic bronchitis, with an ECP odds ratio = 1.04 and logMPO = 4.45.
Journal of Asthma 11/2006; 43(8):593-6. · 1.52 Impact Factor
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Giovanni Palladini,
Francesca Lavatelli,
Paola Russo,
Stefano Perlini,
Vittorio Perfetti,
Tiziana Bosoni,
Laura Obici,
Arthur R Bradwell,
GianVico Melzi D'Eril,
Roberto Fogari, Remigio Moratti,
Giampaolo Merlini
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ABSTRACT: N-terminal natriuretic peptide type B (NT-proBNP) is a marker of cardiac dysfunction in light chain amyloidosis (AL) and a powerful prognostic determinant. Serum NT-proBNP and circulating free light chains (FLCs) were measured at enrollment and after 3 cycles of chemotherapy in 51 patients with cardiac AL. In patients (n = 22, 43%) in whom FLCs decreased by more than 50% (hematologic response), NT-proBNP concentration decreased by a median of 48%, whereas in the remaining patients it increased by 47% (P = .01). The reduction of NT-proBNP was greater in patients (n = 9) in whom amyloidogenic FLCs disappeared at immunofixation (median 53%), than in the remaining responding patients (median 31%, P = .04). Left ventricular wall thickness decreased by at least 2 mm in 3 of 20 patients in whom NT-proBNP improved. Fifteen patients died. Thirteen of them, in whom NT-proBNP and FLCs did not improve, died after a median of 1.8 months. The decrease of FLCs translates into a simultaneous decrease of NT-proBNP and improved survival. Patients in whom chemotherapy fails to induce such a decrease are at risk of early death. Cardiac function in AL can rapidly improve due to a reduction of the circulating amyloidogenic precursor, despite the amount of cardiac amyloid deposits remaining apparently unaltered, as measured by echocardiography.
Blood 06/2006; 107(10):3854-8. · 9.90 Impact Factor
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ABSTRACT: Down's syndrome (DS) associates with genetic-dependent dysregulation of the interferon (IFN) system. We used intracellular cytokine staining to analyse the percentages of IFN-gamma- and interleukin (IL)-4-producing T cells in the peripheral blood of patients with DS, individuals with mental retardation (MR), and healthy controls (HCs). The percentages of IFN-gamma-producing CD4(+) and CD8(+) T cells (IFGCs), namely Th1 (mean, 21.4+/-S.D. 1.3) and Tc1 (12.6+/-1.1), and the Th1/Th2 ratio (6.1+/-0.2) in DS were significantly higher than in MR (15.9+/-1.3, 7.9+/-0.6, 4.8+/-0.3) and in HCs (15.6+/-1.9, 7.2+/-1.1, 4.6+/-0.6). Most of the DS patients with high IFGC percentages were seropositive for anti-transglutaminase IgA. We found no correlation between sex, age, APOE genotypes, coexisting autoimmune diseases, susceptibility to infections, or degree of cognitive impairment and high IFGC percentages. This abnormality might thus contribute to immune dysfunction in DS without manifest clinical correlates.
Neuroscience Letters 03/2006; 395(1):67-70. · 2.11 Impact Factor
