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Biomedical subjects

L Conti

Publications and source records attributed to L Conti.

At least 19 recordsLinked to original sources
PubMed2005

Comparative expression profiles of ShcB and ShcC phosphotyrosine adapter molecules in the adult brain.

Shc family of adaptor molecules has been demonstrated to play an important role during the transition from proliferating neural stem cells to postmitotic neurons. Previous studies from our group demonstrated a progressive decrease of ShcA levels occurring in coincidence with the end of embryonic neurogenesis and neuronal maturation, being ShcB and ShcC the major Shc molecules expressed in the mature brain. A growing body of evidence indicates that ShcB and ShcC are neuronal specific molecules exerting important roles in neuronal survival and phenotypic stability thus becoming potential attracting target molecules for development of drugs for interfering with brain demises. Here, we examine the expression pattern of ShcB and ShcC in neuronal populations composing the adult central and peripheral nervous system, in order to better elucidate their roles in vivo. We found a heterogeneous and peculiar presence and subcellular localization of ShcB and ShcC in specific neuronal populations, enlightening a potential specific requirement of these two molecules in the survival/maintenance of defined neuronal subtypes.

Animals↗
PubMed2005

Genotoxicity of the disinfection by-products resulting from peracetic acid- or hypochlorite-disinfected sewage wastewater.

Wastewater disinfection is routinely carried out to prevent the spread of human pathogens present in wastewater effluents. To this aim, chemical and physical treatments are applied to the effluents before their emission in water bodies. In this study, the influence of two widely used disinfectants, peracetic acid (PAA) and sodium hypochlorite (NaClO), on the formation of mutagenic by-products was investigated. Wastewater samples were collected before and after disinfection, in winter and in summer, at a pilot plant installed in a municipal wastewater-treatment plant. Samples were adsorbed using silica C18 cartridges and the concentrates were tested for mutagenicity in the Salmonella typhimurium reversion test with strains TA98 and TA100. Non-concentrated water samples were tested with two plant genotoxicity assays (the Allium cepa root anaphase aberration test and the Tradescantia/micronucleus test). Mutagenicity assays in bacteria and in Tradescantia showed borderline mutagenicity in some of the wastewater samples, independent of the disinfection procedure applied. Negative results were obtained in the A. cepa anaphase aberration test. These results indicate that, in the conditions applied, wastewater disinfection with PAA and NaClO does not lead to the formation of significant amounts of genotoxic by-products.

Disinfectants↗
PubMed2004

When pain is not fully explained by organic lesion: a psychiatric perspective on chronic pain patients.

Recent literature demonstrates the relationship between psychopathology and medically unexplained pain, even if the results of several studies show a high degree of variability. The present study was planned with the aim of analysing both the possible relationship between the level (low/high) of organicity and the presence of psychopathology, and the degree to which these differences are related to methodological problems. Between 1998 and 2000, four hundred and thirty six consecutive patients seen at the Pisa Pain Therapy and Palliative Care Unit were requested to fill in a questionnaire, the GHQ-12, to screen the subjects probably with (GHQ-12>3) or without (GHQ-12</=3) psychopathology. All the patients scoring above the GHQ-12 threshold (score of 3), and a randomised sample of those scoring below the GHQ-12 threshold, were included in the study. These patients were then interviewed using three different instruments: the Mini International Neuropsychiatric Interview (MINI) for a standardised psychiatric diagnosis, the Semistructured Interview for Depression (SID) for the characterisation of temperament, and the Italian Pain Questionnaire (IPQ) for the evaluation of pain. Our results suggest that Somatisation Disorders are more frequent in the medically unexplained pain group than in the medically explained pain group, whereas the other psychiatric disorders have a similar prevalence in the two pain groups. Mood and anxiety disorders are correlated with high scores on GHQ-12 and medically explained pain has a higher prevalence of GHQ-12>3 than the medically unexplained pain group. These results confirm that methodology is an important factor that could modify results in psychiatric research. Both medically unexplained pain and the presence of psychopathology are significantly correlated with sex, and age: females and young patients have a higher prevalence of psychopathology and of medically unexplained pain. Our results suggest that in the correlation between the low organicity of pain and psychopathology, the age and sex play a relevant role.

Age Factors↗
PubMed2003

Analysis of micronuclei in peripheral blood lymphocytes of traffic wardens: effects of exposure, metabolic genotypes, and inhibition of excision repair in vitro by ARA-C.

The cytokinesis-block micronucleus (MN) assay in peripheral lymphocytes was used to assess the genetic effects of the occupational exposure to traffic fumes in policemen from the Municipality of Rome. The study population consisted of 192 subjects engaged in traffic control (exposed, 134 subjects), or in office work (controls, 58 subjects). Groups were balanced for age, gender, and smoking habits. The average benzene exposure during the workshift was 9.5 and 3.8 microg/m(3) in exposed individuals and controls, respectively. All subjects were genotyped for CYP1A1, CYP2E1, GSTM1, GSTT1, and DT-diaphorase polymorphisms. The incidence of micronuclei and micronucleated cells was recorded in 1,000 binucleated cells harvested 66 hr after mitogen stimulation. Regression analysis of data showed that MN frequency was mainly modulated by the age (P = 0.001) and gender (P = 0.001) of the study subjects (relatively higher in the elderly and females), whereas it was unaffected by the occupational exposure to traffic fumes and smoking habits. A weak (P = 0.02) association between lower MN frequency and the GSTM1 null genotype was also observed. In order to improve the sensitivity of the method to excision-repairable lesions, a modified protocol, with exposure of cells to the repair inhibitor cytosine arabinoside (Ara-C) during the first 16 hr of growth, was applied to 78 subjects (46 exposed and 32 controls). The results confirmed the higher MN frequency in females (P < 0.05), but failed to demonstrate any significant effect of chemical exposure (occupational or related to smoking habits). When the frequency of MN induced by Ara-C (i.e., spontaneous values subtracted) was considered, a significant inverse correlation with age was observed (P = 0.005), possibly related to the age-dependent decrease in repair proficiency.

Adult↗
PubMed2002

Experimental measurement of the dynamic photothermal effect in Fabry-Perot cavities for gravitational wave detectors.

We report the experimental observation of the frequency dependence of the photothermal effect. The measurements are performed by modulating the laser power absorbed by the mirrors of two high-finesse Fabry-Perot cavities. The results are very well described by a recently proposed theoretical model [M. Cerdonio, L. Conti, A. Heidmann, and M. Pinard, Phys. Rev. D 63, 082003 (2001)]], confirming the correctness of such calculations. Our observations and quantitative characterization of the dynamic photothermal effect demonstrate its critical importance for interferometric displacement measurements towards the quantum limit, as those necessary for gravitational wave detection.

Journal Article↗
PubMed2001

Wideband dual sphere detector of gravitational waves.

We present the concept of a sensitive and broadband resonant mass gravitational wave detector. A massive sphere is suspended inside a second hollow one. Short, high-finesse Fabry-Perot optical cavities read out the differential displacements of the two spheres as their quadrupole modes are excited. At cryogenic temperatures, one approaches the standard quantum limit for broadband operation with reasonable choices for the cavity finesses and the intracavity light power. A molybdenum detector, of overall size of 2 m, would reach spectral strain sensitivities of 2x10(-23) Hz(-1/2) between 1000 and 3000 Hz.

Journal Article↗
PubMed2001

Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease.

Huntingtin is a 350-kilodalton protein of unknown function that is mutated in Huntington's disease (HD), a neurodegenerative disorder. The mutant protein is presumed to acquire a toxic gain of function that is detrimental to striatal neurons in the brain. However, loss of a beneficial activity of wild-type huntingtin may also cause the death of striatal neurons. Here we demonstrate that wild-type huntingtin up-regulates transcription of brain-derived neurotrophic factor (BDNF), a pro-survival factor produced by cortical neurons that is necessary for survival of striatal neurons in the brain. We show that this beneficial activity of huntingtin is lost when the protein becomes mutated, resulting in decreased production of cortical BDNF. This leads to insufficient neurotrophic support for striatal neurons, which then die. Restoring wild-type huntingtin activity and increasing BDNF production may be therapeutic approaches for treating HD.

3T3 Cells↗
PubMed2001

Identification of distinct signaling pathways leading to the phosphorylation of interferon regulatory factor 3.

Infection of host cells by viruses leads to the activation of multiple signaling pathways, resulting in the expression of host genes involved in the establishment of the antiviral state. Among the transcription factors mediating the immediate response to virus is interferon regulatory factor-3 (IRF-3) which is post-translationally modified as a result of virus infection. Phosphorylation of latent cytoplasmic IRF-3 on serine and threonine residues in the C-terminal region leads to dimerization, cytoplasmic to nuclear translocation, association with the p300/CBP coactivator, and stimulation of DNA binding and transcriptional activities. We now demonstrate that IRF-3 is a phosphoprotein that is uniquely activated via virus-dependent C-terminal phosphorylation. Paramyxoviridae including measles virus and rhabdoviridae, vesicular stomatitis virus, are potent inducers of a unique virus-activated kinase activity. In contrast, stress inducers, growth factors, DNA-damaging agents, and cytokines do not induce C-terminal IRF-3 phosphorylation, translocation or transactivation, but rather activate a MAPKKK-related signaling pathway that results in N-terminal IRF-3 phosphorylation. The failure of numerous well characterized pharmacological inhibitors to abrogate virus-induced IRF-3 phosphorylation suggests the involvement of a novel kinase activity in IRF-3 regulation by viruses.

Active Transport, Cell Nucleus↗
PubMed2001

ST14A cells have properties of a medium-size spiny neuron.

The ST14A cell line was previously derived from embryonic day 14 rat striatal primordia by retroviral transduction of the temperature-sensitive SV40 large T antigen. We showed that cell division and expression of nestin persists at 33 degrees C, the permissive temperature, whereas cell division ceases, nestin expression decreases, and MAP2 expression increases at the nonpermissive temperature of 39 degrees C. In this study, we further characterized the cells and found that they express other general and subtype-specific neuronal characteristics. ST14A cells express enolase and beta III-tubulin. Furthermore, they express the striatal marker DARPP-32, which is up-regulated upon differentiation of the cells by growth in serum-free medium. Stimulation with dopamine, the D2-dopamine receptor agonist quinpirole, or the D1-dopamine receptor agonist SKF82958 results in phosphorylation of CREB. Treatment of the cells with a mixture of reagents which stimulate the MAPK and adenylyl cyclase pathways radically changes the morphology of the ST14A cells. The cells develop numerous neurite-like appearing processes which stain with beta III-tubulin. Moreover, under these conditions, intracellular injection of rectangular depolarizing current stimuli elicits overshooting action potentials with a relatively fast depolarization rate when starting from a strongly hyperpolarized membrane potential. Taken together, these data imply that the ST14A cell line displays some of the characteristics of a medium-size spiny neuron subtype and provides a new tool to elucidate the pathways and molecules involved in medium-size spiny neuron differentiation and disease.

Action Potentials↗
PubMed2001

Ciliary neurotrophic factor may activate mature astrocytes via binding with the leukemia inhibitory factor receptor.

Ciliary neurotrophic factor (CNTF) acts on immature astrocytes that express its trimeric receptor. In contrast, mature astrocytes do not significantly express the specific CNTFalpha receptor subunit, yet they respond to CNTF administration in vivo. Here we show that this controversy may be solved by a shift in astroglial sensitivity to CNTF over time, related to a change in the type of receptor bound by the cytokine on mature astrocytes. A convergent set of results supports the hypothesis that the CNTF effect is due to the illegitimate binding on the leukemia inhibitory factor receptor (LIFR): (i) it requires high concentration of recombinant rat CNTF; (ii) it involves the Jak/Stat and Ras-MAPK pathways; (iii) it is preserved in CNTFRalpha-/- cells; (iv) it is potentiated by soluble CNTFRalpha added to the medium; and (v) it is significantly decreased by a partial antagonist of LIFR. On these bases, we propose a mechanistic model in which, in the adult brain, a CNTF/LIFR interglial system may be modulated by neurons that synthesize CNTFRalpha.

Animals↗
PubMed2001

Shc signaling in differentiating neural progenitor cells.

Previously we found that the availability of ShcA adapter is maximal in neural stem cells but that it is absent in mature neurons. Here we report that ShcC, unlike ShcA, is not present in neural stem/progenitor cells, but is expressed after cessation of their division and becomes selectively enriched in mature neurons. Analyses of its activity in differentiating neural stem/progenitor cells revealed that ShcC positively affects their viability and neuronal maturation via recruitment of the PI3K-Akt-Bad pathway and persistent activation of the MAPK pathway. We suggest that the switch from ShcA to ShcC modifies the responsiveness of neural stem/progenitor cells to extracellular stimuli, generating proliferation (with ShcA) or survival/differentiation (with ShcC).

Adaptor Proteins, Signal Transducing↗
PubMed2001

Age-related prevalence of platelet-associated immunoglobulins G in nonthrombocytopenic patients with autoimmune thyroid disease and autoimmune polyglandular syndrome.

OBJECTIVE: The prevalence of platelet-associated IgG (paIgG) in nonthrombocytopenic patients with autoimmune thyroid disease (AITD) alone or associated with autoimmune polyglandular syndrome (APS) has been studied. SUBJECTS: A total of 164 individuals were enrolled in this study: 81 patients with AITD alone, 33 patients with APS, and 50 healthy controls. RESULTS: The presence of paIgG was recorded in 41 of 81 patients with AITD (51%) as compared with 2 of 50 control subjects (4%, p < 0.0001). The prevalence of paIgG in patients with APS was higher even when compared with patients with AITD alone (25/33, 76%; p = 0.02). The presence of paIgG was not related to the functional thyroid parameters. The prevalence of paIgG was higher in the older than in the younger patients (75 vs. 47%, p = 0.0037). CONCLUSIONS: The results indicate that the prevalence of paIgG in patients with AITD is higher than previously thought, namely in elderly patients and in patients with APS, and not related to the thyroid function.

Adult↗
PubMed2001

No correlation between aggression and platelet (3)H-paroxetine binding in obsessive-compulsive disorder patients.

Different findings suggest that the serotonin (5-HT) system may be involved in both the regulation of aggression and the pathophysiology of obsessive-compulsive disorder (OCD). Our study aimed to evaluate the aggressive features of a group of OCD patients and to explore possible correlations with a serotonergic marker, namely platelet 5-HT transporter. Psychopathological and biological patterns were compared with those of a group of healthy controls and those of patients with major depression. Twenty-one patients affected by OCD, 21 by depression and 21 healthy controls were included in the study. Aggressive features were measured by means of the Buss and Durkee Hostility Inventory (BDHI). The platelet 5-HT transporter was evaluated by means of the (3)H-paroxetine binding parameters (maximum binding capacity, B(max) and dissociation constant, K(d)). The OCD patients showed a total score on the BDHI not significantly different from that of healthy controls and lower than that of depressed patients. The factor profile was similar in the 3 groups, but higher in the depressed patients. The irritability, resentment, guilt, negativism and suspiciousness factors were significantly more pronounced in depressed patients. Some sex-related difference in single factors were also observed. The B(max) of (3)H-paroxetine binding was lower in OCD patients than in depressives or healthy controls. OCD patients were more similar to healthy controls than to depressed patients with regard to aggressive features measured by means of the BDHI. This suggests that aggression in OCD is a complex phenomenon that probably requires specific instruments of evaluation.

Adolescent↗
PubMed2000

First search for gravitational wave bursts with a network of detectors

We report the initial results from a search for bursts of gravitational radiation by a network of five cryogenic resonant detectors during 1997 and 1998. This is the first significant search with more than two detectors observing simultaneously. No gravitational wave burst was detected. The false alarm rate was lower than 1 per 10(4) yr when three or more detectors were operating simultaneously. The typical threshold was H approximately 4x10(-21) Hz-1 on the Fourier component at approximately 10(3) Hz of the gravitational wave strain amplitude. New upper limits for amplitude and rate of gravitational wave bursts have been set.

Journal Article↗
PubMed2000

Dual role of the HIV-1 vpr protein in the modulation of the apoptotic response of T cells.

We investigated the effect of vpr, physiologically expressed during the course of an acute HIV-1 infection, on the response of infected cells to apoptotic stimuli as well as on the HIV-induced apoptosis. At 48 h after infection, Jurkat cells exhibited a lower susceptibility to undergo apoptosis with respect to uninfected cells. This effect was not observed following infection with either a vpr-mutated virus or a wild-type strain in the presence of antisense oligodeoxynucleotides targeted at vpr mRNA. Single-cell analysis, aimed at simultaneously identifying apoptotic and infected cells, revealed that resistance to apoptosis correlated with productive infection. Notably, vpr-dependent protection from induced apoptosis was also observed in HIV-1-infected PBMC. In contrast, at later stages of infection, a marked increase in the number of cells spontaneously undergoing apoptosis was detected in infected cultures. This virus-induced apoptosis involved vpr expression and predominantly occurred in productively infected cells. These results indicate that HIV-1 vpr can exert opposite roles in the regulation of apoptosis, which may depend on the level of its intracellular expression at different stages of HIV-1 infection. The dual function of vpr represents a novel mechanism in the complex strategy evolved by HIV to influence the turnover of T lymphocytes leading to either viral persistence or virus release and spreading.

Acute Disease↗