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S Signorini

Publications and source records attributed to S Signorini.

At least 19 recordsLinked to original sources
PubMed2006

Auditory attention at the onset of West syndrome: correlation with EEG patterns and visual function.

At the onset of West syndrome a specific impairment of visual function has been clearly demonstrated, while other aspects of sensorial development, and in particular of the auditory function, have been less studied. The aim of this study was to evaluate auditory function and orienting responses at the onset of West syndrome, and to relate the results with EEG patterns, visual function and neurodevelopmental competence. A prospective multicentric study was performed on 25 successively enrolled infants with West syndrome; all the patients underwent a full clinical assessment, including MRI and video-EEG, visual function and auditory orienting responses (AORs) as well as Griffiths' developmental scales. The whole assessment performed at the onset of spasms (T0) was repeated after two months (T1). AORs resulted significantly impaired both at T0 and T1. At the onset of spasms a highly significant relationship of auditory attention with visual function and neurodevelopmental competence was shown in both cryptogenic and symptomatic forms, but it was no longer present after two months. Our results may suggest a possible pervasive effect of the epileptic disorder on sensory processing, associated to a deficit of neurodevelopment. Although we failed to show a significant correlation between auditory orienting responses and EEG patterns, some evidence seems to support at least partially an influence of the epileptic disorder per se on the genesis of the sensorial impairment. A longer follow up and a larger cohort will be useful for a better clarification of these findings.

Acoustic Stimulation↗
PubMed2005

Prevalence and incidence of antibodies to Borrelia burgdorferi and to tick-borne encephalitis virus in agricultural and forestry workers from Tuscany, Italy.

The ticks Ixodes persulcatus and Ixodes ricinus are the main vectors of both Borrelia burgdorferi sensu lato and tick-borne encephalitis (TBE) virus in Eurasia. Borrelia burgdorferi is the cause of Lyme borreliosis, and TBE is a biphasic meningoencephalitis induced by an arbovirus belonging to the flavivirus family. The principal aims of the current investigation were (i) to determine the frequency of serological evidence of Borrelia burgdorferi sensu lato and TBE infections in healthy agricultural and forestry workers, (ii) to determine the incidence of seroconversion for antibodies against Borrelia burgdorferi sensu lato and TBE virus in Tuscan workers during a 1-year survey; and (iii) to assess the occupational risk for agricultural and forestry activities in a defined area (Tuscany, Italy). A total of 412 blood samples were taken from agricultural and forestry workers, and information on age, duration of employment, and history of tick bites was collected in a questionnaire to establish the risk factors for the diseases. Three hundred sixty-five blood donors from the same region served as controls. To estimate the rate of seroconversion, 176 of the agricultural and forestry workers were tested 1 year later. IgG and IgM antibodies against Borrelia burgdorferi sensu lato and TBE virus were detected in serum by an enzyme-linked immunosorbent assay and confirmed by Western blot analysis for Borrelia burgdorferi and by a test for inhibition of hemagglutination for TBE. Antibodies against Borrelia burgdorferi were more frequent among the workers than in the control group (7.8% vs. 4.9% in the IgG-IgM enzyme-linked immunosorbent assay and 7.03% vs. 3.56% in the confirmatory test). No seropositivity was observed for TBE virus. Eighteen of 176 subjects who underwent a second blood test developed specific antibodies against Borrelia burgdorferi within 1 year.

Adult↗
PubMed2004

Prevalence of pathogenic mutations in an Italian clinical series of patients with familial dementia.

Genetic factors are involved in the aetiology of dementias. Three genes have been identified which, when mutated, cause Familial Alzheimer disease (FAD): the presenilin-1 (PS1), the presenilin-2 (PS2) and the amyloid precursor protein (APP) genes. Together, these mutations are responsible for 30-50% of the cases with autosomal dominant Alzheimer disease (AD), and for about 5% of all AD cases. While over 130 mutations have been identified in PS1, mutations in PS2 and APP are rarer, since only 10 and 22 mutations, respectively, have been found in these FAD genes. Instead, mutations in the MAPT gene were associated with Familial Frontotemporal dementia (FFTD) linked to chromosome 17 (FTDP-17). Frontotemporal dementia (FTD) can occur in a sporadic form, but in 30-50% of cases there is a positive family history of dementia. In this study, we determined the spectrum of mutations and the relative contribution of the above mentioned four genes in our Italian clinical series of patients with a positive family history of dementia.

Aged↗
PubMed2003

BACE-2 is overexpressed in Down's syndrome.

Brain deposition of the amyloid-beta protein (Abeta) is a frequent complication of Down's syndrome (DS) patients. Abeta peptide is generated by endoproteolytic processing of Abeta precursor protein by gamma and beta secretases. Recently a transmembrane aspartyl protease, BACE, has been identified as the beta-secretase, and its homologous BACE-2 has also been described. BACE-2 gene resides on chromosome 21 in the obligate DS region. It cleaves Abeta precursor protein at its beta site and more efficiently at a different site within Abeta. In the present study we characterized the BACE-2 gene and protein expression in the DS patients and healthy control. We analyzed, by using a nonradioactive ribonuclease protection assay, the levels of BACE-2 mRNA expression in primary skin fibroblasts. The analysis revealed a 2.6-fold increase in BACE-2 mRNA levels in the DS group compared to the levels observed in the control group. Western blot analysis revealed no difference between DS and control in BACE-2 protein levels in the intracellular compartment. In the medium conditioned by fibroblast, we revealed an evident secretion of BACE-2 protein, represented by two different molecular weights, remarkably increased in DS fibroblasts. BACE-2 overexpression was also confirmed in the DS fetal brains and human neural embryonic DS stem cells in which conditioned media BACE-2 was secreted. These data highlight the importance of the extracellular compartment where BACE-2 overexpression could play a role in plaque formation in DS patients.

Adult↗
PubMed2001

Analysis of HIV-1 mutation patterns in patients failing antiretroviral therapy.

The emergence of mutations encoding drug resistance is supposed to be a significant limitation to the clinical efficacy of inhibitor compounds directed against specific HIV-1 enzymatic targets. We have used a commercial test (Visible Genetics Inc., Paris, France) to study the prevalence of mutations occurred in HIV-1 protease and reverse transcriptase (RT) genes in 93 HIV-1 infected patients treated with at least one regimen containing a protease inhibitor (PI) and failing to the current therapeutic regimen. Protease mutations conferring resistance to at least one PI were detected in 46/93 (49.4%) of strains, 25 (26.8%) of which showed resistance to all PIs. Reverse transcriptase mutations conferring resistance to at least one RT inhibitor were detected in 57/93 (61.2%) of strains, 18 (19.3%) of which showed resistance to all RT inhibitors. The most frequent RT mutations were T215Y/F, M41L, and M184V (41.9, 40.8, and 40.8%, respectively), while L63P, L10R/V, and A71V/T (58, 41.9, and 34.4%, respectively) were the most represented protease substitutions. We have found no mutations encoding for multiple dideoxynucleoside resistance (Q151M or T69SS). Twelve of our patients (12.9%) had no mutation encoding drug resistance and were completely sensitive to all RT and protease inhibitors. Therefore, not all virological failures are caused by HIV-1 genomic resistance.

Acquired Immunodeficiency Syndrome↗
PubMed2001

HIV-1 multi-dideoxynucleoside resistance mutation (Q151M): prevalence, associated resistance mutations and response to antiretroviral salvage treatment.

The prevalence and clinical implications of the Q151M multidrug-resistance mutation gene (mut) to antiretroviral drugs in the HIV reverse transcriptase (RT) gene have not yet been fully explained. In the present study three out of 350 (0.85%) of HIV-infected patients who underwent a drug-resistance genotyping assay because of therapeutic failure showed the Q151M mut. All these patients had been previously treated with zidovudine in association with didanosine. One such patient failed to respond to all salvage regimens tried and was shown to harbour some of the characteristic mut associated with Q151M (77L and 116Y). Another two patients partially responded to salvage regimens, both virologically and immunologically, and harboured the M184V mut in the RT gene. The prevalence of Q151M mut in our group was less (0.85%) than in other studies, which ranged from 2 to 19%. The M184V mut seemed to confer some viro-immunological benefit when associated with the Q151M mutation, compared with the latter alone.

Adult↗
PubMed2000

Expansion of rare CD8+ CD28- CD11b- T cells with impaired effector functions in HIV-1-infected patients.

The decline in the number of CD4+ T cells in HIV-1-infected patients is known to be related to the increased number of CD8+CD28- T cells. In this paper, we show that CD8+CD28- T cells from HIV-positive patients have an impaired capability to interact with human endothelial cells. This is due to the dramatic expansion, within this subset, of rare CD11b- cells lacking cell-cell adhesion functions. In 50 HIV-positive patients, 19.5% +/- 6.5% of all T cells were CD8+CD28-CD11b-, whereas only 0.8% +/- 0.4% of all T cells from healthy donors showed this uncommon phenotype. The percentage of circulating CD8+CD28-CD11b- T cells was strongly related to the percentage of CD4+ T cells (r = -0.82). This population is peculiar in terms of HIV infection and was found to possess some characteristics associated with effector functions but its cytotoxic properties were impaired. The percentage of target cells lysed by CD8+CD28-CD11b- was significantly lower than that of cells lysed by its CD11b- counterpart (p <.05) both at low (5:1) or at relatively high (20:1) effector/target ratios. CD8+CD28-CD11b- T cells, which lack the ability to interact with endothelial cells, are likely to accumulate and persist in circulation. The biologic properties of CD8+CD28-CD11b- T cells suggest that these cells might be endstage or aberrant differentiated effector cells. Lack of cell-cell adhesion and impaired cytolytic functions favor the hypothesis of a role for CD8+CD28-CD11b- T cells in the development of immunodeficiency.

CD28 Antigens↗
PubMed2000

PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans.

BACKGROUND: Inflammation is an important component of ischemic heart disease. PTX3 is a long pentraxin whose expression is induced by cytokines in endothelial cells, mononuclear phagocytes, and myocardium. The possibility that PTX3 is altered in patients with acute myocardial infarction (AMI) has not yet been tested. METHODS AND RESULTS: Blood samples were collected from 37 patients admitted to the coronary care unit (CCU) with symptoms of AMI. PTX3 plasma concentrations, as measured by ELISA, higher than the mean+2 SD of age-matched controls (2.01 ng/mL) were found in 27 patients within the first 24 hours of CCU admission. PTX3 peaked at 7.5 hours after CCU admission, and mean peak concentration was 6.94+/-11.26 ng/mL. Plasma concentrations of PTX3 returned to normal in all but 3 patients at hospital discharge and were unrelated to AMI site or extent, Killip class at entry, hours from symptom onset, and thrombolysis. C-reactive protein peaked in plasma at 24 hours after CCU admission, much later than PTX3 (P<0.001). Patients >64 years old and women had significantly higher PTX3 concentrations at 24 hours (P<0.05). PTX3 was detected by immunohistochemistry in normal but not in necrotic myocytes. CONCLUSIONS: PTX3 is present in the intact myocardium, increases in the blood of patients with AMI, and disappears from damaged myocytes. We suggest that PTX3 is an early indicator of myocyte irreversible injury in ischemic cardiomyopathy.

Aged↗
PubMed2000

Paternal concentrations of dioxin and sex ratio of offspring.

BACKGROUND: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin), is commonly considered the most toxic man-made substance. We have previously shown that high serum concentrations of TCDD in parents from Seveso, Italy, were linked to their having a relative increase in the number of female births after the parents exposure to a release of dioxin in 1976. We have continued the study to determine whether the parents' sex and/or age at exposure affected the sex ratio of their children. METHODS: We measured the TCDD concentrations in serum samples from potentially exposed parents collected in 1976 and 1977, and investigated the sex ratio of their offspring. FINDINGS: Serum samples were collected from 239 men and 296 women. 346 girls and 328 boys were born to potentially exposed parents between 1977 and 1996, showing an increased probability of female births (lower sex ratio) with increasing TCDD concentrations in the serum samples from the fathers (p=0.008). This effect starts at concentrations less than 20 ng per kg bodyweight. Fathers exposed when they were younger than 19 years of age sired significantly more girls than boys (sex ratio 0.38 [95% CI 0.30-0.47]). INTERPRETATION: Exposure of men to TCDD is linked to a lowered male/female sex ratio in their offspring, which may persist for years after exposure. The median concentration of dioxin in fathers in this study is similar to doses that induce epididymal impairments in rats and is about 20 times the estimated average concentration of TCDD currently found in human beings in industrialised countries. These observations could have important public-health implications.

Adolescent↗
PubMed2000

Non-specific influx of T-cell receptor alpha/beta and gamma/delta lymphocytes in mucosal biopsies from a patient with orofacial granulomatosis.

Orofacial granulomatosis (OFG) represents an inflammatory disorder of the facial and oral mucosa, histologically characterized by non-caseating epithelioid cell granulomas. Since other granulomatous diseases have been shown to be characterized by a limited heterogeneity of alpha/beta and gamma/delta T cells, we investigated the T-cell diversity of both types of lymphocytes obtained from the same OFG patient. When we compared the T-cell receptor diversity of the lymphocytes accumulating at the site of the lesions with that of the peripheral blood counterpart, we did not find significant differences. Furthermore, no exclusive expansions of different T-cell clones were seen in the patient. From these data we conclude that, in this OFG patient, the majority of T cells have no specificity for a single or for a few antigens and that tissue accumulation of T lymphocytes is the result of a random influx of cells at the site of inflammation.

Adult↗
PubMed2000

Restriction of T-cell receptor repertoires in idiopathic CD4+ lymphocytopenia.

We report that alpha/beta and gamma/delta T-cell repertoires of three patients with idiopathic CD4+ lymphocytopenia, who showed different clinical manifestations and outcomes over time, were highly restricted. The disruption of T-cell repertoires does not influence the susceptibility to infections: the first patient was unable to attain a protective response to mycobacterium, the second showed clinical improvement and the third did not develop opportunistic infections. These results indicate that idiopathic CD4+ lymphocytopenia could give rise to mono-/oligoclonal T-cell expansions, but the degree of repertoire disturbance is not indicative of the severity of disease progression.

Aged↗
PubMed2000

Environmental exposure to dioxin: the Seveso experience.

The toxicity in humans of 2,3,7,8-tetrachlorodibenzo-p-dioxin, a man-made compound and environmental pollutant, is still debated. The industrial accident at Seveso, Italy, in 1976 exposed a large population of both sexes and of all ages to a massive concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Monitoring of soil and measurement of blood samples allowed classification of the exposed population into three categories: A, B and R (high, medium and low exposure, respectively). This article presents data from longitudinal health monitoring of the population, including liver function, immune function, neurological impairment, dermatological effects, reproductive pathology, and mortality.

Accidents, Occupational↗
PubMed1999

Intrathymic restriction and peripheral expansion of the T-cell repertoire in Omenn syndrome.

Mutations in the human RAG genes that impair, but do not abolish, recombination activity lead to Omenn syndrome, a severe primary immune deficiency that is associated with clinical and pathological features of graft-versus-host disease and oligoclonal expansion of activated, autologous T cells. We have analyzed the mechanisms accounting for peripheral oligoclonality of the T-cell repertoire. Predominance of few T-cell receptor clonotypes (both within TCRAB- and within TCRGD-expressing lymphocytes) is already detectable in the thymus and is further selected for in the periphery, with a different distribution of clonotypes in different tissues. These data indicate that oligoclonality of the T-cell repertoire in Omenn syndrome is due both to intrathymic restriction and to peripheral expansion. Moreover, the RAG genes defect that causes Omenn syndrome directly affects early stages of V(D)J recombination, but does not alter the process of double-strand-break DNA repair, including N and P nucleotide insertion.

Base Sequence↗
PubMed1999

Detection of identical T-cell clonotype expansions in both the donor and recipient after allogeneic bone marrow transplantation.

Using phenotypic, functional and molecular techniques, this study was performed to compare the complexity of the T-cell receptor repertoire of a bone marrow transplanted patient with that of his HLA-matched related donor, both of whom developed a chronic lymphocytosis sustained by CD3+CD8+CD57+CD16-CD56- granular lymphocytes 3 years after transplantation. Although Southern blot analysis revealed the presence of extra bands in both subjects, thus indicating the presence of at least one clonal T-cell population, the study of the different T-cell receptor Vbeta (TCRBV) usage did not demonstrate discrete overexpression of any TCRBV segments. On the contrary, heteroduplex analysis of TCRBV transcripts suggested the presence of oligoclonal T-cell expansions in the two subjects. Cloning and sequencing studies demonstrated that T-cell clones expressing identical TCRBV chains were expanded both in the donor and in the recipient. Furthermore, clones with similar, but not identical, junctional regions were also found in the two subjects. These data indicate that, at the time of the graft, a few cells with a monoclonal/oligoclonal pattern that were present in the donor were transferred to the recipient, where they may have found the same environmental in vivo conditions and/or the antigenic pressure favouring their abnormal expansion.

Adult↗
PubMed1998

Detection of skewed T-cell receptor V-beta gene usage in the peripheral blood of patients with multiple sclerosis.

The ex vivo analysis of the T-cell receptor V-beta (TCRBV) gene usage by circulating T lymphocytes in Multiple Sclerosis (MS) patients may contribute to understanding disease pathogenesis. In the present study, TCRBV gene usage was analyzed in freshly collected unstimulated peripheral blood mononuclear cells (PBMC) isolated from 40 MS patients and 20 healthy controls. Nine patients presented abnormal repertoires, with expansion of one or more TCRBV segments. Among these patients, six presented expansion of TCRBV9 chain expression, three also having an expansion of TCRBV1, TCRBV11 and TCRBV22 segments. The most frequently observed TCRBV chain expansion, TCRBV9, was further analyzed and identified as polyclonal. Evaluation of clinical variables showed that median disease duration was shorter in patients with TCRBV gene expression abnormalities. Longitudinal evaluation of five patients with a skewed repertoire showed regression of expanded TCRBV chains expression to normal values. These data indicate that certain MS patients have abnormal TCRBV gene expression. Such abnormalities are caused by polyclonal expansions of T lymphocyte subpopulations that use the same TCRBV gene families, are unstable and preferentially observed early in the course of the disease.

Adult↗
PubMed1998

Development of autologous, oligoclonal, poorly functioning T lymphocytes in a patient with autosomal recessive severe combined immunodeficiency caused by defects of the Jak3 tyrosine kinase.

Defects of the common gamma chain subunit of the cytokine receptors (gamma c) or of Jak3, a tyrosine kinase required for gamma c signal transduction, result in T-B+ severe combined immunodeficiency (SCID). However, atypical cases, characterized by progressive development of T lymphocytes, have been also reported. We describe a child with SCID caused by Jak3 gene defects, which strongly but not completely affect Jak3 protein expression and function, who developed a substantial number (> 3,000/microL) of autologous CD3+CD4+ T cells. These cells showed a primed/activated phenotype (CD45R0+ Fas+ HLA-DR+ CD62L(lo)), defective secretion of T-helper 1 and T-helper 2 cytokines, reduced proliferation to mitogens, and a high in vitro susceptibility to spontaneous (caused by downregulation of bcl-2 expression) as well as activation-induced cell death. A restricted T-cell receptor repertoire was observed, with oligoclonal expansion within each of the dominant segments. These features resemble those observed in gamma c-/y and in Jak3-/- mice, in which a population of activated, anergic T cells (predominantly CD4+) also develops with age. These results suggest that residual Jak3 expression and function or other Jak3-independent signals may also permit the generation of CD4+ T cells that undergo in vivo clonal expansion in humans; however, these mechanisms do not allow development of CD8+ T cells, nor do they fully restore the functional properties of CD4+ T lymphocytes.

Cell Death↗
PubMed1998

Cytochrome P450 1B1 mRNA measured in blood mononuclear cells by quantitative reverse transcription-PCR.

Cytochrome P450 (CYP) 1B1 activates polycyclic aromatic hydrocarbons and aryl aromatic hydrocarbons to carcinogens. We describe a competitive reverse transcription-PCR (RT-PCR) assay for the quantification of CYP1B1 mRNA in blood mononuclear cells (BMCs) by simultaneous RT and PCR amplification of cellular RNA with decreasing amounts of an internal standard. The concentration of CYP1B1 mRNA is derived from the ratio between the intensities of the bands corresponding to the amplified products. To reduce the variability of mRNA extraction efficiency, the measured amount of CYP1B1 has been calculated in relation to the beta-actin gene products. We measured CYP1B1 expression in the BMCs of 75 human subjects; no significant differences in the CYP1B1:beta-actin ratio were detected between women (range, 0.47-4.35; median, 2.0) and men (range, 0.72-3.85; median, 2.09). The analytical imprecision (CV) of duplicates was 14% (n = 25 pairs), and the intraindividual CV for two samples, 1 month apart, was 22% (n = 20). No significant differences were detected in smokers (n = 25; range, 0.77-3.55; median, 2.14) compared with nonsmokers (n = 50; range, 0.47-4.35; median, 2.0). The method has a wide range of linearity, good sensitivity and precision, and is suitable for studies of individual susceptibility as indicated by CYP1B1 expression in BMCs.

Actins↗