Publications (52)180.43 Total impact
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Article: Hypertransaminasemia and fatal lung disease: a case report.
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ABSTRACT: Glycogenosis type II (Pompe disease) is a rare autosomal recessive genetic disorder caused by mutations in the gene encoding the lysosomal enzyme acid alpha-glucosidase. The classic form is characterized by severe cardiac involvement, generalized hypotonia and exitus early in life. Presenting symptoms and signs of the disease may be neglected or underestimated, thus delaying the diagnosis. Respiratory manifestations mainly occur because of respiratory muscle weakness. However, additional mechanisms can favor the development of pulmonary complications that result in fatal respiratory failure. We herein describe a case of an infant with glycogenosis type II presenting with hepatomegaly and hypertransaminasemia, who rapidly developed fatal lung disease.Italian Journal of Pediatrics 02/2013; 39(1):9. -
Article: Non-autoimmune subclinical hypothyroidism due to a mutation in TSH receptor: report on two brothers.
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ABSTRACT: Subclinical hypothyroidism (SH) is a condition characterized by a mild persistent thyroid failure. The main cause is represented by autoimmune thyroiditis, but mutations in genes encoding proteins involved in TSH pathway are thought to be responsible for SH, particularly in cases arising in familial settings. Patients with the syndrome of TSH unresponsiveness may have compensated or overt hypothyroidism with a wide spectrum of clinical and morphological alterations depending on the degree of impairment of TSH-receptor (TSH-R) function. We describe the case of two brothers with non autoimmune SH carrying the same heterozygous mutation in the extracellular domain of TSH-R and presenting with different clinical, biochemical and morphological features. The first one had only a slight persistent elevation of TSH, a normal thyroid ultrasound and did never require l- thyroxine (L-T4) replacement treatment. The second one had a neonatal persistent moderate TSH levels increase associated with a thyroid gland hypoplasia and was treated with L-T4 since the first months of life.These two cases support the recent association of TSH-R mutations inheritance as an autosomal dominant pattern with variable expressivity and suggest that the decision to start replacement therapy in patients with persistent SH due to TSH resistance should be individualized.Italian Journal of Pediatrics 01/2013; 39(1):5. -
Article: Reduced Atherosclerotic Burden in Subjects With Genetically Determined Low Oxidative Stress.
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ABSTRACT: OBJECTIVE: NADPH oxidase, one of the most important enzymes producing reactive oxidant species, is suggested to play a role in experimental atherosclerosis, but its role in human atherosclerosis is still unclear. We hypothesized that a reduced activity of NADPH oxidase might be linked to a reduced atherosclerotic burden. METHODS AND RESULTS: Thirty-one women carriers of hereditary deficiency of NOX2, the catalytic subunit of NADPH oxidase, were matched for sex and age with 31 controls and 31 obese women. Flow-mediated dilation and intima-media thickness, 2 surrogate markers of atherosclerosis, serum activity of NOX2, urinary isoprostanes, serum levels of nitrite/nitrate, and platelet production of isoprostanes and nitrite/nitrate were determined.Compared with controls (5.7±3.0% and 0.60±0.11 mm), carriers of NOX2 deficiency had higher flow-mediated dilation (9.2±5.0%; P<0.001) and lower intima-media thickness (0.50±0.11 mm; P=0.002), whereas obese women had lower flow-mediated dilation (3.2±2.1%; P=0.007) and higher intima-media thickness (0.71±0.15 mm; P<0.001). Compared with controls, carriers of NOX2 deficiency had lower urinary isoprostanes (132.6±87.3 versus 82.3±46.0 pg/mg creatinine; P=0.007) and serum NOX2 activity (24.9±19.3 versus 12.8±11.9 pg/mL; P=0.004) and higher serum nitrite/nitrate (23.8±7.6 versus 30.5±6.3 µmol/L; P<0.001), whereas obese women had higher urinary isoprostanes (132.6±87.3 versus 182.2±84.6 pg/mg creatinine; P=0.008) and serum NOX2 activity (24.9±19.3 versus 36.1±18.6 pg/mL; P=0.008) and lower serum nitrite/nitrate (23.8±7.6 versus 12.6±4.2 µmol/L; P<0.001). Flow-mediated dilation correlated with intima-media thickness (r=-0.433; P<0.001), serum NOX2 activity (r=-325; P<0.001), and urinary isoprostanes (r=-0.314; P=0.002). Ex vivo study showed that, compared with controls, platelets from carriers of NOX2 deficiency had lower isoprostanes (P<0.001) and higher nitrite/nitrate (P<0.001), whereas platelets from obese women had higher isoprostanes (P<0.001) and lower nitrite/nitrate (P=0.013). CONCLUSIONS: The study shows reduced atherosclerotic burden in carriers of NOX2 deficiency, suggesting that oxidative stress generated by this enzymatic pathway is implicated in human atherosclerosis.Arteriosclerosis Thrombosis and Vascular Biology 01/2013; · 6.37 Impact Factor -
Article: The R156H variation in IL-12Rβ1 is not a mutation.
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ABSTRACT: Palamaro et al. describe a child with recurrent bronchopneumonia and very high IgE levels in which a variation, R156H, was found in the IL12RB1 gene that encodes the IL-12Rβ1 chain. Based on the absence of this variation in 50 unrelated individuals they conclude it is a mutation. We (van de Vosse and van Dissel) feel there is no reason to suspect a defect in IL-12 signaling based on the clinical data, nor evidence for a functional defect in IL-12 signaling in this patient. In addition, the variation is not novel and known as a polymorphism. Without any functional evidence that R156H is a mutation, the current claim is not substantiated.Palamaro et al. respond to argue that the amino acid substitution, R156H described in the described case exerts a summatory effect, as a genetic cofactor, along with an additional and still unidentified molecular alteration of the same pathway.Italian Journal of Pediatrics 01/2013; 39:12. -
Article: Alterations of the autoimmune regulator transcription factor and failure of central tolerance: APECED as a model.
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ABSTRACT: Self-nonself discrimination plays a key role in inducing a productive immunity and in preventing autoimmune reactions. Central tolerance within the thymus and peripheral tolerance in peripheral lymphoid organs lead to immunologic nonresponsiveness against self-components. The central tolerance represents the mechanism by which T cells binding with high avidity to self-antigens are eliminated through the so-called negative selection. Thymic medullary epithelial cells and medullary dendritic cells play a key role in this process, through the expression of a large number of tissue-specific self-antigens involving the transcription factor autoimmune regulator (AIRE). Mutations of AIRE result in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy, a rare autosomal recessive disease (OMIM 240300), which is the paradigm of a genetically determined failure of central tolerance and autoimmunity. This review focuses on recent advances in the molecular mechanisms of central tolerance, their alterations and clinical implication.Expert Review of Clinical Immunology 01/2013; 9(1):43-51. · 2.07 Impact Factor -
Article: Does NADPH Oxidase Deficiency Cause Artery Dilatation in Humans?
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ABSTRACT: Abstract NADPH oxidase is known to modulate the arterial tone, but the role of its specific subunits is still unclear. The objective of this study was to compare the role of p47 and gp91phox (NOX2) on artery dilatation. We conducted a multicenter study enrolling 30 patients with chronic granulomatous disease (CGD) (25 with NOX2 deficiency and 5 with p47(phox) deficiency) and 30 healthy subjects (HS), matched for gender and age, in whom flow-mediated dilation (FMD), serum activity of NOX2 (soluble NOX2-derived peptide [sNOX2-dp]), urinary isoprostanes (8-iso-PGF2α), and platelet production of isoprostanes and NOX2 were determined. Compared to HS, patients with CGD had significantly higher FMD and lower sNOX2-dp and 8-iso-PGF2α levels. Compared to patients with NOX2 deficiency and HS, patients with p47(phox) hereditary deficiency had intermediate FMD and oxidative stress, that is, higher and lower FMD and lower and higher isoprostanes compared to HS and patients with NOX2 deficiency, respectively. In agreement with this finding, an ex vivo study showed higher inhibition of NOX2 activity and lower isoprostane formation in platelets from patients with NOX2 deficiency compared to platelets from ones with p47(phox) deficiency. Our observations lead to the hypothesis that oxidants are implicated in artery vasoconstriction. Antioxid. Redox Signal. 00, 000-000.Antioxidants & Redox Signaling 12/2012; · 8.20 Impact Factor -
Article: New strategies for the treatment of lysosomal storage diseases (Review).
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ABSTRACT: The lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders caused by the deficiency of any of the lysosomal functions, in most cases of lysosomal hydrolases. LSDs are typically characterized by storage of a variety of substrates in multiple tissues and organs and by the variable association of unusual clinical manifestations that are often responsible for physical and neurological handicaps. During the past two decades, research in the field of LSDs has made marked progress, particularly with the development of a variety of innovative therapeutic approaches. These include several strategies aimed at increasing the residual activity of the missing enzyme, such as hematopoietic stem cell transplantation, enzyme replacement therapy, pharmacological chaperone therapy and gene therapy. An alternative approach is based on reducing the synthesis of the stored substrate. More recently, the improved knowledge on LSD pathophysiology has indicated additional targets of therapy. The recent progress made in the treatment of LSDs represents a good model that may be extended to other genetic disorders.International Journal of Molecular Medicine 11/2012; · 1.98 Impact Factor -
Article: Bone health in children with long-term idiopathic subclinical hypothyroidism.
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ABSTRACT: BACKGROUND: Subclinical hypothyroidism (SH) is a relatively common condition characterized by a mild persistent thyroid failure. The management of children with SH is still a controversial issue and the decision to treat with L-thyroxine represents a clinical dilemma. Thyroid hormone and TSH play an important role in skeletal growth and bone mineral homeostasis. Aim To evaluate whether untreated idiopathic SH may affect bone health in childhood and to compare two different diagnostic tools such as dual-energy X-ray densitometry (DXA) and quantitative ultrasound (QUS). Patients and Methods Twenty-five children and adolescents (11 males) aged 9.8 +/- 3.5 years (range 4.2-18.7) with untreated idiopathic SH were enrolled in the study. SH was diagnosed on the basis of normal FT4 levels with TSH concentrations between 4.2 and 10 mU/l. Children have been followed for 3.3 +/- 0.3 years from the time of SH diagnosis. Twenty-five healthy children, age- and sex-matched, were enrolled as controls. Patients and controls underwent DXA to evaluate lumbar spine bone mineral density (BMD) and QUS at proximal phalanges of the nondominant hand to assess bone quality, measured as amplitude-dependent speed of sound (Ad- SoS) and bone transmission time (BTT). RESULTS: Mean BMD Z-score was 0.4 +/- 1.36 in patients and 0.2 +/- 1.2 in controls. Mean Ad-SoS Zscore was 0.01 +/- 1.0 in patients and 0.1 +/- 1.2 in controls and mean BTT Z-score was 0.03 +/- 0.8 and 0.04 +/- 1.1 respectively. All values were within the normal range, both in patients and in controls. There were no statistically significant differences between the two groups. CONCLUSION: Bone health, evaluated by lumbar spine DXA and phalangeal QUS, is not impaired in our children, despite long-term duration of idiopathic SH. Data about bone status provided by QUS are comparable to those provided by DXA. Therefore, QUS may represent a good, cheaper and safe screening test for bone evaluation in children with SH.Italian Journal of Pediatrics 10/2012; 38(1):56. -
Article: Precocious puberty in Turner Syndrome: report of a case and review of the literature.
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ABSTRACT: INTRODUCTION: Turner Syndrome (TS) is caused by monosomy or structural abnormalities of the X chromosome, with a prevalence of about 1/2000 females live birth. Most important clinical features of TS are short stature and gonadal failure. Approximately one third of girls with TS may undergo spontaneous puberty. Here we report on the case of a girl with a rare 45X0/47XXX mosaic TS exhibiting a precocious puberty. Case report The patient was diagnosed with TS at the age of 4 years, upon a diagnostic work-up for dysmorphic features. Chromosome analysis revealed a mosaic karyotype (45X0/47XXX). She presented with normal height and normal growth velocity so that Growth Hormone (GH) therapy was not started. She was referred to our Department at the age of 7 years and 10 months, because of vaginal bleeding. A physical examination revealed a Tanner stage III for breast and Tanner stage III for pubic hair development. Height and weight were within the normal range for age. Psychological evaluation showed moderate global developmental delay, together with emotional and social immaturity and reading difficulties. The growth rate was accelerated. Her bone age was 10 years. Pelvic ultrasound demonstrated increased size for age of both the uterus and the ovaries, with bilateral ovarian follicles. GnRH stimulation test revealed pubertal response of gonadotropins (peak LH 22.5 mIU/ml). MRI of the brain was normal. These clinical, radiologic and laboratory findings were consistent with a diagnosis of idiopathic central precocious puberty; therefore, GnRH analog therapy was started, in order to slow pubertal progression and to preserve adult stature. Furthermore, GH treatment was added to further improve adult height. CONCLUSION: Our case highlights the possibility of precocious puberty as an atypical clinical feature of TS. Thus, precocious puberty may occur in TS girls when a dosage compensation by the cell line with more than two X chromosomes allows normal ovarian function. GnRH analog therapy in addition to GH treatment should be recommended in TS girls with precocious puberty in order to slow pubertal progression and to preserve adult stature.Italian Journal of Pediatrics 10/2012; 38(1):54. -
Article: Therapeutic options in pediatric non alcoholic fatty liver disease: current status and future directions.
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ABSTRACT: The epidemics of overweight and obesity has resulted in a significant increase of non alcoholic fatty liver disease (NAFLD), a potentially progressive condition. Currently, obesity related hepatopathy represents therefore the main cause of pediatric chronic liver disease. The first choice treatment at all ages is weight loss and/or lifestyle changes, however compliance is very poor and a pharmacological approach has become necessary. In the present article we present a systematic literature review focusing on established pediatric NALFD drugs (ursodeoxycholic acid, insulin sensitizers, and antioxidants) and on innovative therapeutic options as well. Regarding the former ones, a pediatric pilot study highlighted that ursodeoxycholic acid is not efficient on transaminases levels and bright liver. Similarly, a recent large scale, multicenter randomized clinical trial (TONIC study) showed that also insulin sensitizers and antioxidant vitamin E have scarce effects on serum transaminase levels. Among a large series of novel therapeutic approaches acting on recently proposed different pathomechanisms, probiotics seem hitherto the most interesting and reasonable option for their safety and tolerability. Toll-like receptors modifiers, Pentoxifylline, and Farnesoid X receptors agonists have been still poorly investigated, and will need further studies before becoming possible promising innovative therapeutic strategies.Italian Journal of Pediatrics 10/2012; 38(1):55. -
Article: Genetic Basis of Altered Central Tolerance and Autoimmune Diseases: A Lesson from AIRE Mutations.
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ABSTRACT: The thymus is a specialized organ that provides an inductive environment for the development of T cells from multipotent hematopoietic progenitors. Self-nonself discrimination plays a key role in inducing a productive immunity and in preventing autoimmune reactions. Tolerance represents a state of immunologic nonresponsiveness in the presence of a particular antigen. The immune system becomes tolerant to self-antigens through the two main processes, central and peripheral tolerance. Central tolerance takes place within the thymus and represents the mechanism by which T cells binding with high avidity self-antigens, which are potentially autoreactive, are eliminated through so-called negative selection. This process is mostly mediated by medullary thymic epithelia cells (mTECs) and medullary dendritic cells (DCs). A remarkable event in the process is the expression of tissue-specific antigens (TSA) by mTECs driven by the transcription factor autoimmune regulator (AIRE). Mutations in this gene result in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), a rare autosomal recessive disease (OMIM 240300). Thus far, this syndrome is the paradigm of a genetically determined failure of central tolerance and autoimmunty. Patients with APECED have a variable pattern of autoimmune reactions, involving different endocrine and nonendocrine organs. However, although APECED is a monogenic disorder, it is characterized by a wide variability of the clinical expression, thus implying a further role for disease-modifying genes and environmental factors in the pathogenesis. Studies on this polyreactive autoimmune syndrome contributed enormously to unraveling several issues of the molecular basis of autoimmunity. This review focuses on the developmental, functional, and molecular events governing central tolerance and on the clinical implication of its failure.International Reviews Of Immunology 10/2012; 31(5):344-62. · 3.43 Impact Factor -
Article: Clinical Heterogeneity in two patients with Noonanlike Syndrome associated with the same SHOC2 mutation.
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ABSTRACT: Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM #607721) has been recently related to the invariant c.4A > G missense change in SHOC2. It is characterized by features reminiscent of Noonan syndrome. Ectodermal involvement, short stature associated to growth hormone (GH) deficiency (GHD), and cognitive deficits are common features. We compare in two patients with molecularly confirmed NS/LAH diagnosis, the clinical phenotype and pathogenetic mechanism underlying short stature. In particular, while both the patients exhibited a severe short stature, GH/IGFI axis functional evaluation revealed a different pathogenetic alteration, suggesting in one patient an upstream alteration (typical GHD) and in the other one a peripheral GH insensitivity. Since only a few cases of NS/LAH associated to SHOC2 mutations have been so far described, the complex phenotype of the syndrome and the exact mechanism impairing GH/IGFI axis still remain to be elucidated and studies on larger cohort of subjects are needed to better delineate this syndrome.Italian Journal of Pediatrics 09/2012; 38(1):48. -
Article: Acute adrenal failure as the presenting feature of primary antiphospholipid syndrome in a child.
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ABSTRACT: INTRODUCTION: Antiphospholipid syndrome (APS) is characterized by recurrent arterial and venous thrombosis and detection of antiphospholipid antibodies (aPLs). This syndrome may be associated with connective tissue disorders, or with malignancies, but it may also appear in isolated form (primary APS). We report on a pediatric patient presenting with acute adrenal failure as the first manifestation of primary APS. Case report A previously healthy 11-year-old boy developed fever, abdominal pain, and vomiting. An abdominal computed tomography scan showed nodular lesions in the adrenal glands. He was referred to our Department and a diagnosis of APS and acute adrenal failure was considered, based on positive aPLs (IgG and IgM), elevated ACTH levels and low cortisol levels. Other features were anemia, thrombocytopenia, elevated inflammatory parameters, hypergammaglobulinemia, prolonged partial thromboplastin time, positive antinuclear, anticardiolipin, anti-platelet antibodies, with negative double-stranded DNA antibodies. Lupus anticoagulant and Coomb's tests were positive. MRI revealed a bilateral adrenal hemorrhage. A treatment with intravenous metylprednisolone, followed by oral prednisone and anticoagulant, was started, resulting in a progressive improvement. After 2 months he also showed hyponatremia and elevated renine levels, indicating a mineralcocorticoid deficiency, requiring fludrocortisones therapy. CONCLUSION: The development of acute adrenal failure from bilateral adrenal haemorrhage in the context of APS is a rare but life-threatening event that should be promptly recognized and treated. Moreover, this case emphasizes the importance of the assessment of aPLs in patients with acute adrenal failure in the context of an autoreaction.Italian Journal of Pediatrics 09/2012; 38(1):49. -
Article: Hyper IgM syndrome presenting as chronic suppurative lung disease.
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ABSTRACT: The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders resulting in defects of immunoglobulin class switch recombination. Affected patients show humoral immunodeficiency and high susceptibility to opportunistic infections. Elevated serum IgM levels are the hallmark of the disease, even though in few rare cases they may be in the normal range. Hyper IgM is associated with low to undetectable levels of serum IgG, IgA, and IgE. In some cases, alterations in different genes may be identified. Mutations in five genes have so far been associated to the disease, which can be inherited with an X-linked (CD40 ligand, and nuclear factor-kB essential modulator defects) or an autosomal recessive (CD40, activation-induced cytidine deaminase, and uracil-DNA glycosylase mutation) pattern. The patient herein described presented with recurrent upper and lower respiratory infections and evidence of suppurative lung disease at the conventional chest imaging. The presence of low serum IgG and IgA levels, elevated IgM levels, and a marked reduction of in vivo switched memory B cells led to a clinical and functional diagnosis of HIGM although the genetic cause was not identified.Italian Journal of Pediatrics 09/2012; 38(1):45. -
Article: Interleukin 12 receptor deficiency in a child with recurrent bronchopneumonia and very high IgE levels.
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ABSTRACT: Interleukin-12 (IL-12) is involved in cellular immune responses against intracellular pathogens by promoting the generation of T naive in T helper 1 (Th1) cells and by increasing interferon-gamma (IFN-gamma) production from T and natural killer (NK) cells. A defective induction of a Th1 response may lead to a higher risk of infections, and, in particular, infections due to typical and atypical Mycobacteria. We report on the case of a girl with suffering from recurrent bronchopneumonia associated with very high serum IgE levels, who exhibited a profound impairment of the Th1 generation associated with a novel mutation in the exon 5 of the IL-12R beta1 gene (R156H). Our data suggest that in children with severe and recurrent infections, even in the absence of a mycobacterial infection, functional and/or genetic alterations of the molecular mechanisms governing Th1/Th2 homeostasis might be responsible for an atypical immunodeficiency and, therefore, should be investigated in these patients.Italian Journal of Pediatrics 09/2012; 38(1):46. -
Article: A case of galactosemia misdiagnosed as cow's milk intolerance.
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ABSTRACT: We report on a female patient affected by galactosemia in whom the diagnosis was obscured by the concomitant presence of manifestations suggesting a cow's milk intolerance. This case exemplifies the problems in reaching a correct diagnosis in patients with metabolic diseases.Italian Journal of Pediatrics 09/2012; 38:47. -
Article: Altered regulatory mechanisms governing cell survival in children affected with clustering of autoimmune disorders.
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ABSTRACT: Clustering of Autoimmune Diseases (CAD) is now emerging as a novel clinical entity within monogenic immune defects with a high familial occurrence. Aim of this study is to evaluate the regulatory mechanisms governing cell survival, paying a particular attention to Fas-induced apoptosis, in a cohort of 23 children affected with CAD. In 14 patients, Fas stimulation failed to induce cell apoptosis and in 1 case it was associated with Fas gene mutation. Our study highlights the importance to evaluate cell apoptosis in the group of children with CAD, which, with this regard, represents a distinct clinical entity.Italian Journal of Pediatrics 09/2012; 38:42. -
Article: De novo 13q12.3-q14.11 deletion involving BRCA2 gene in a patient with developmental delay, elevated IgM levels, transient ataxia, and cerebellar hypoplasia, mimicking an A-T like phenotype.
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ABSTRACT: We report on a child with a de novo deletion of approximately 12 Mb detected through array comparative genomic hybridization (CGH). The deletion involved chromosome bands 13q12.3-13q14.11 and determined the loss of ≥50 genes. A second deletion on chromosome 12p11.3p11.22 of 43-167 kb, including about 12 genes, was unlikely of clinical relevance because inherited from the asymptomatic father. The child had developmental delay, dysmorphisms, and many features reminiscent of ataxia-telangiectasia (A-T), as cerebellar ataxia, oculocutaneus telangiectasia, and recurrent upper airway infections. Atraumatic fractures of the metatarsus were noted. Moreover, this is a rare case of 13q deletion syndrome associated with peripheral blood white cells radiosensitivity to bleomycin, reminiscent of what previously reported on X-ray hypersensitivity of fibroblasts from patients with alterations of this chromosome. The immunological evaluation revealed increased IgM serum levels and a low proliferative response to mitogens, PHA, and CD3 cross-linking (CD3 XL). After 12 years of age only a mild dysmetria persisted, while the proliferative response to mitogens became normal by 9 years of age. © 2012 Wiley Periodicals, Inc.American Journal of Medical Genetics Part A 08/2012; 158A(10):2571-6. · 2.39 Impact Factor -
Article: Steroid treatment in Ataxia-Telangiectasia induces alterations of functional magnetic resonance imaging during prono-supination task.
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ABSTRACT: BACKGROUND: Ataxia-Teleangiectasia (A-T) is a rare neurodegenerative disorder characterized by progressive cerebellar degeneration. Till few years ago only supportive care was available to improve the neurological function in A-T patients. Even though A-T remains an incurable disease, we recently demonstrated a drug dependent amelioration of neurological signs in A-T patients during a short-term treatment with oral betamethasone. AIMS: The aim of this study is to evaluate whether the steroid induced motor performance changes in A-T are associated with functional magnetic resonance imaging (fMRI) modifications. This represents a preliminary pilot study, which requires a validation on a larger cohort of patients. METHODS: Six A-T patients received a 10-days cycle of oral betamethasone at 0.03 mg/kg/day. fMRI studies were carried out at T0 and at the end of the cycle. The neurological evaluation was performed through the Scale for the Assessment and Rating of Ataxia (SARA) quantification. The fMRI protocol was a block design with alternating epochs of rest and prono-supination of the dominant (right) hand. RESULTS: The voxel-based comparison showed a remarkable increase in the number of activated voxels within the motor cortex under the on-therapy condition as compared with the cortical activity under baseline condition in the 2 patients who completed the study protocol. CONCLUSIONS: Changes in motor performance in A-T patients treated with betamethasone are coupled with an increase in the activation in relevant cortical areas, thus suggesting that in A-T patients steroid treatment could improve motor performance facilitating cortical compensatory mechanisms.European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 07/2012; · 2.01 Impact Factor -
Article: Role of the common γ chain in cell cycle progression of human malignant cell lines.
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ABSTRACT: The γ-chain (γc) is a transducing element shared between several cytokine receptors whose alteration causes X-linked severe combined immunodeficiency. Recently, a direct involvement of γc in self-sufficient growth in a concentration-dependent manner was described, implying a direct relationship between the amount of the molecule and its role in cell cycle progression. In this study, we evaluate whether γc expression could interfere in cell cycle progression also in malignant hematopoietic cells. Here, we first report that in the absence of γc expression, lymphoblastoid B-cell lines (BCLs) die at a higher extent than control cells. This phenomenon is caspase-3 independent and is associated to a decreased expression of the antiapoptotic Bcl-2 family members. By contrast, increased expression of γc protein directly correlates with spontaneous cell growth in several malignant hematopoietic cell lines. We, also, find that the knockdown of γc protein through short interfering RNA is able to decrease the cell proliferation rate in these malignancies. Furthermore, an increased expression of all D-type cyclins is found in proliferating neoplastic cells. In addition, a direct correlation between the amount of γc and cyclins A2 and B1 expression is found. Hence, our data demonstrate that the amount of the γc is able to influence the transcription of genes involved in cell cycle progression, thus being directly involved in the regulatory control of cell proliferation of malignant hematopoietic cells.International Immunology 03/2012; 24(3):159-67. · 3.41 Impact Factor
Top co-authors
Top Journals
Institutions
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2013
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Leids Universitair Medisch Centrum
- Department of Infectious Diseases
Leiden, South Holland, Netherlands
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2002–2013
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Università degli Studi di Napoli Federico II
- Section of Dermatology
Portici, Campania, Italy
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2012
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National Research Council - Italy
Roma, Latium, Italy
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