Biomedical subjects

M Fiore

Publications and source records attributed to M Fiore.

At least 73 records · Page 4Linked to original sources

PubMed1996

Progressive deficiencies in blood T cells associated with a 10p12-13 interstitial deletion.

We report on a 8-year-old patient affected by a selective T-cell defect associated with mental retardation and dysmorphic signs. At birth thymic aplasia and hypoparathyroidism were noted, suggesting a DiGeorge-like anomaly. The immunological evaluation during the 8 years follow-up revealed a progressive decrease of CD3+CD4+ lymphocytes, which paralleled deficiencies of blood T cells. Chromosome analysis using GTL banding revealed an interstitial deletion of the short arm of chromosome 10. We next investigated whether the expression of IL-2R alpha chain and Nil-2-a genes, which are located on the short arm of chromosome 10, was affected by the deletion. Transcription of these two genes was normal, thus suggesting that the two regions were preserved. In situ hybridization studies with the painting libraries #G3A7 and #G9 confirmed that the two regions were preserved and allowed us to define the breakpoint as 10p12-10p13. Due to the similarities between DiGeorge and 10p syndromes, we suggest that the 10p13-10p12 region contains a gene(s) potentially related to gene products of the 22q11 region, frequently altered in patients with DiGeorge.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1996

Schistosoma mansoni: influence of infection on mouse behavior.

Schistosoma mansoni infection in humans and animals induces abnormal neurobehavioral responses following granuloma formation. In mice, granulomas in the liver are observed 8 weeks after infection, while after 15-20 weeks, the presence of eggs and granulomas in the brain has been reported. In this study, outbred CD-1 female mice were infected with S. mansoni and examined in several behavioral tests (open field, novel object investigation, black/white box, and hot plate) 8 and 15 weeks after infection. The detected effects of schistosome infection were a reduction of body weight in 8-week infected mice, marked changes in exploration/activity, rearing, and wall-rearing in 8- and 15-week infected mice, an enhancement of sniffing and grooming in 8-week infected mice, and finally an increase in the threshold of pain response to the hot plate in 15-week infected mice. The results of the present study indicate that S. mansoni infection markedly alters exploratory behavior of mice, affecting particularly the vertical movements of the animals, and suggests that the differences in behavioral abnormalities between 8- and 15-week infected mice might be associated with modifications in the levels of nerve growth factor and cytokines induced by granulomas.

Analysis of Variance↗

PubMed1996

Behavioural disturbances in adult CD-1 mice and absence of effects on their offspring upon SO2 exposure.

Adult male and female CD-1 mice were exposed to different SO2 concentrations (0,5,12, or 30 ppm) for 24 days, from 9 days before the formation of breeding pairs to pregnancy day 12-14. This exposure was near-continuous, covering about 80% of the total time indicated. The offspring of exposed dams were cross-fostered shortly after birth to dams not previously exposed. Videorecordings of the adult subjects' activities during the first hour after the start of exposure showed marked, acute transient behavioural effects such as increase of rearing and social interactions, which were more pronounced in males than in females. Subsequent activity tests on exposure days 3, 6, and 9 showed subacute effects including a dose-dependent decrease of grooming and an increase of digging as well as changes in chamber crossing and wall-rearing which were not dose-dependent; most of these effects were more pronounced in females than in males. Food and water consumption and body weight declined in a dose-dependent fashion only after the formation of breeding pairs, when consummatory responses were enhanced in the controls. Reproductive performance as well as postnatal somatic and neurobehavioural development of the offspring (the latter assessed by an observational test battery including eight reflexes and responses) were not affected by SO2. Passive avoidance acquisition and retention at the young adult stage (60 days) and response changes produced by repeated apparatus exposure in non-reinforced animals (habituation) were similarly unaffected. Overall, the data indicate that SO2 produces transient, acute behavioural disturbances and more subtle subacute response changes in adult mice which may be due, at least partly, to a functional interference with olfactory modulation of mouse behaviour. The absence of effects on reproductive performance and neurobehavioural development of the offspring suggests that the risk to the developing organism from gestational SO2 exposure is low.

Animals↗

PubMed1996

Chronic parasite infection in mice induces brain granulomas and differentially alters brain nerve growth factor levels and thermal responses in paws.

Schistosoma mansoni infection, both in humans and in animal models, is known to induce granulomas in the liver and intestine. It has also been reported that in humans the eggs of this parasite can reach the brain, causing psychiatric and neuropathological disorders. Whether this also occurs in rodents is unknown. To answer this question, mice were infected with this parasite and the central nervous system (CNS) examined at various time intervals. The results show that schistosomiasis induced granulomas in several regions of the CNS and increased nerve growth factor (NGF) levels in the cortex, hypothalamus and brain stem, but not in the hippocampus. The infection also caused paw hyperalgesia, as determined by the hot-plate test, and a local increase in NGF, but not in substance P. These findings indicate that the murine model of infection can be used for studying mechanisms leading to human neuroschistosomiasis and suggest that the neuropathological disorders and the sensory deficits observed in human schistosomiasis are associated with impaired levels of NGF in the peripheral and central nervous system.

Animals↗

PubMed1996

Topoisomerase I activity and cellular response to radiation in Chinese hamster cells.

The aim of the present study was to investigate the synergistic potential of the combination of camptothecin, a specific inhibitor of topoisomerase I, and radiation in the the induction of chromosome aberrations and cell cycle delay in actively proliferating mammalian cells. Synergistic effects of the combined treatments were obtained for induced frequencies of aberrations in exponentially growing Chinese hamster ovary cells. The potentiating effects were more pronounced for aberrations of the exchange type, suggesting that interaction of unrepaired radiation- and camptothecin-induced lesions during replication may be involved in the observed drug-radiation synergism. Cytofluorimetric analysis of cell cycle progression in cells receiving the combined treatments displayed enhanced responses of CHO cells to S- and G2 phase delay induced by the single treatments. To investigate the determinants of the synergistic response, the influence of radiation exposure on the catalytic activity of topoisomerase I was assayed. A decreased plasmid supercoiled DNA relaxation capacity of crude extracts derived from irradiated CHO cells was found which suggests a decrease in the topoisomerase I catalytic activity following irradiation. In addition, a lower sensitivity of the enzyme from irradiated cells to inhibition of topoisomerase I activity by camptothecin was also observed using the same DNA relaxation test.

Animals↗

PubMed1995

A comparison of behavioural effects of prenatally administered oxazepam in mice exposed to open-fields in the laboratory and the real world.

Prenatal benzodiazepine exposure has been reported to result in abnormal neurobehavioural development in laboratory animals but little is known about the behavioural relevance of this effect ina naturalistic environment. In this study, outbred CD-1 male mice were prenatally exposed to oxazepam (15 mg/kg per os, twice daily) on days 12-16 of fetal life and fostered at birth to untreated dams. At adulthood, each mouse was fitted with a radio collar and its first reactions assessed. Three hours later, behavioural and exploratory activities were recorded in a laboratory open field, and 24 h later in a natural setting. Immediate reactions to the radio collar were higher in the oxazepam-treated mice than in controls consisting of more attempts to remove it and an increase of push-digging. The attempts to remove the collar were still evident in oxazepam treated mice tested in the laboratory open-field 3 h later. Moreover, oxazepam increased the frequency of grooming and reduced walking in both the laboratory and the natural settings. In the natural settings running was increased during the initial 30-min test, while a pronounced level of grooming and a lower frequency of eating were observed 140 min after release. Frequency of sniffing, grooming, and rearing behaviours were higher in the laboratory test when compared to the natural settings. On the other hand, prolonged bouts of sniffing were recorded in the natural environment. These findings permit separation of robust drug effects (increased grooming, reduced walking) from situation-dependent effects, the natural environment revealing, in addition, more subtle effects.

Animals↗

PubMed1995

Neurobehavioral development of CD-1 mice after combined gestational and postnatal exposure to ozone.

Outbred CD-1 mice were exposed continuously to ozone (O3, 0.6 ppm) from 6 days prior to the formation of breeding pairs to the time of weaning of the offspring on postnatal day 22 (PND 22) or to PND 26. One half of the mice in each of eight O3 and eight control litters were subjected on PND 24 to a 20-min open-field test after IP treatment by either saline or scopolamine (2 mg/kg). The remaining mice (those exposed until PND 26) were subjected on PNDs 28-31 to a conditioned place preference (CPP) test, using a short schedule with a single IP injection on PND 29 of either d-amphetamine (3.3 mg/kg) or saline. Subsequently, the saline mice of the open-field experiment were used on PND 59 for an activity test in one of the CPP apparatus compartments after IP treatment by either d-amphetamine (same dose) or saline. In addition, the saline mice of the CPP experiment underwent a multi-trial, step-through passive avoidance (PA) acquisition test on PND 59 or 60, followed 24 h later by a single-trial retention test. In the absence of effects on reproductive performance (proportion of successful pregnancies, litter size, offspring viability, and sex ratio), O3 offspring showed a long-lasting reduction in body weight without modification of sex differences. Ozone effects on neurobehavioral development were not large and quite selective, including: attenuation of the sex differences in several responses (rearing and sniffing in the open-field, activity in the final CPP test session); a change in response choices in the final CPP test, in the absence of a main effect on conditioning; a reduction of grooming in the activity test on PND 29; and impairment of PA acquisition limited to the initial period of training.

Amphetamine↗

PubMed1995

Genetic effects of petroleum fuels: cytogenetic monitoring of gasoline station attendants.

Workers in the petroleum distribution trades experience relatively high-level exposures to fuel vapours whose consequences have not been fully elucidated. In this study, the possible relationship between occupational exposure to petroleum fuels and cytogenetic damages in peripheral lymphocytes was investigated. Twenty-three male, non-smoking workers from the area of Rome were enrolled in the study, together with age-paired controls with no occupational exposure to fuels. Peripheral lymphocyte cultures were set up for the analysis of structural chromosome aberrations (CAs), sister chromatid exchanges (SCEs) and micronuclei (MN) in cytokinesis-blocked lymphocytes. Frequencies of CAs, SCEs and MN were compared between exposed and control groups, and evaluated in relation to blood lead level (as an indicator of engine exhausts exposure) for the whole group under study, and to yearly averaged exposure to benzene (8-h time weighted averages, as determined by repeated personal sampling) for fillingstation attendants only. Both CAs and SCEs were slightly increased in station attendants: 1.97 versus 1.46 aberrations per 100 cells, and 4.73 +/- 0.15 versus 4.48 +/- 0.11 SCEs/cell in exposed and control individuals, respectively. The difference between cumulative CA rates in the exposed and control populations was of borderline statistical significance (p = 0.066). However, when the exposed population was dichotomized for benzene exposure, a significant (p = 0.018) correlation of CAs with benzene exposure was found. The analysis of SCE data highlighted a significant increase of cells with more than 6 exchanges (HFCs), corresponding to the 75 degrees percentile of the overall distribution, in fillingstation attendants (relative risk (RR) = 1.3, 95% CI = 1.1-1.5) in comparison with controls. In the pooled population, the frequency of HFCs showed a statistically significant upward trend at increasing blood lead levels (chi 2 for trend = 27.8, p < 0.0001). A complex relationship between SCEs and benzene exposure was observed, with an increased frequency of HFCs in the medium exposure intensity class (RR = 1.5, 95% CI = 1.2-1.7), and no difference for exposure to higher benzene levels (RR = 1.0, 95% CI = 0.9-1.2), compared to reference subjects. Finally, the analysis of MN in both phytohemagglutinin- and pokeweed-stimulated cell cultures did not show significant excess of MN in binucleated lymphocytes of exposed workers with respect to the age-paired controls.

Adult↗

PubMed1995

Low environmental radiation background impairs biological defence of the yeast Saccharomyces cerevisiae to chemical radiomimetic agents.

Background radiation is likely to constitute one of the factors involved in biological evolution since radiations are able to affect biological processes. Therefore, it is possible to hypothesize that organisms are adapted to environmental background radiation and that this adaptation could increase their ability to respond to the harmful effects of ionizing radiations. In fact, adaptive responses to alkylating agents and to low doses of ionizing radiation have been found in many organisms. In order to test for effects of adaptation, cell susceptibility to treatments with high doses of radiomimetic chemical agents has been studied by growing them in a reduced environmental radiation background. The experiment has been performed by culturing yeast cells (Saccharomyces cerevisiae D7) in parallel in a standard background environment and in the underground Gran Sasso National Laboratory, with reduced environmental background radiation. After a conditioning period, yeast cells were exposed to recombinogenic doses of methyl methanesulfonate. The yeast cells grown in the Gran Sasso Laboratory showed a higher frequency of radiomimetic induced recombination as compared to those grown in the standard environment. This suggests that environmental radiation may act as a conditioning agent.

Background Radiation↗

PubMed1995

DNA typing of DQ and DR alleles in IgA-deficient subjects.

IgA deficiency (IgA-D) represents the most common immunodeficiency syndrome of infancy. In most cases IgA-D represents an isolated immunological disorder, while sometimes it is associated with IgG subclass deficiency or with the presence of autoantibodies. We investigated the pattern of association of IgA-D with DRB1 and DQB1 loci of the HLA region by DNA molecular typing, which allows the identification of previously serologically undefined specificities. We also compared the gene frequency of DRB1 and DQB1 allelic variants between IgA-D subjects with or without serum autoantibodies. Our results indicate that the gene frequency of the DRB1*0102 subtype and of the DRB1*0102, DQB1*0501 haplotype is significantly higher in IgA-D than in the general population. Furthermore, the IgA-D subjects with autoantibodies showed a positive association with DR4 and DR13 subtypes, thus supporting the hypothesis that genetic factors are also involved in the association between IgA-D and autoantibodies.

Alleles↗

PubMed1995

Quinoxaline chemistry. Part 4. 2(R)-anilinoquinoxalines as nonclassical antifolate agents. Synthesis, structure elucidation and evaluation of in vitro anticancer activity.

Thirty-five quinoxalines bearing a substituted aniline group on position 2 and various substituents on positions 3,6,7 and 8 were prepared in order to evaluate in vitro anticancer activity. Structural elucidation of some isomeric quinoxalinones formed by ring closure of 4-substituted-1,2-diaminobenzenes with dicarbonyl compounds was achieved by comparison with one isomer coming from an unambiguous independent route. Preliminary in vitro screening at NCI showed that many compounds exhibited a moderate to strong growth inhibition activity on various cell lines between 10(-5) and 10(-4) molar concentrations.

Aniline Compounds↗

PubMed1995

An integrated system to represent and manage medical knowledge.

This paper describes an integrated system in Prolog that permits the creation of a personal Knowledge Base to express and formalize specialist knowledge in medicine. Formalisms used are production rules and frames. The integrated system is able to manage data and knowledge stored in a database built in M Technology (MUMPS).

AIDS-Related Opportunistic Infections↗

PubMed1994

Clastogenic effects of the dithiocarbamate fungicides thiram and ziram in Chinese hamster cell lines cultured in vitro.

We report here the results obtained using the dithiocarbamate fungicides thiram and ziram to investigate the induction of chromosomal aberrations (CAs) in Chinese hamster ovary (CHO) cells both in the absence and presence of S9 metabolism, and in a Chinese hamster epithelial liver (CHEL) cells which retain metabolic competence to activate different classes of promutagens/procarcinogens. Both thiram and ziram proved to be strong chromosome breaking agents in the CHEL cells and CHO cells in the presence of S9 metabolism. These findings suggest that thiram and ziram require metabolic conversion to become genetically active, and corroborate the evidence that CHEL cells are suitable to activate and detect a broad spectrum of chemical procarcinogens including these two pesticides.

Animals↗

PubMed1994

Prenatal cocaine potentiates the effects of morphine in adult mice.

Prenatal cocaine exposure has been reported to result in abnormal neurobehavioral development, both in animals and humans. In this study, outbred CD-1 mice were exposed in utero to cocaine hydrochloride administered daily as i.p. injections to dams from day 10 of gestation to day 16, at the dose 0, 5 or 50 mg/kg. Cocaine did not alter duration of pregnancy while it decreased the difference in maternal body weight from days 10 to 16 in the dams receiving the higher dose of cocaine. The body weight of the offspring from birth to 15 days of age and the physical maturation were not affected by prenatal cocaine exposure. The development of the response to strong tactile stimulation was either slightly delayed in the 5 mg/kg group or markedly accelerated in the 50 mg/kg group. At adulthood, animals were assessed for behavioral responses to a novel environment, for response to painful stimulation (hot-plate test set at 55 +/- 1 degree C), and for the effects of a single morphine injection (30 mg/kg, i.p.). Data showed that in the absence of prenatal cocaine exposure effects, morphine increased the time spent in inactivity, while it decreased rearing, grooming and bar-holding behaviors. In the case of sniffing, morphine increased this behavior, except in the 5 mg/kg cocaine group. Moreover, morphine administration induced the expected increase of locomotion, irrespective of prenatal condition. With respect to pain reactivity, prenatal cocaine exposure resulted in an increase of licking latency in the 5 mg/kg group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Higher G2 sensitivity to the induction of chromosomal damage in the CHO mutant EM9 than in its parental line AA8 by camptothecin, an inhibitor of DNA topoisomerase I.

The induction of chromosomal alterations by camptothecin (CPT), an inhibitor of DNA topoisomerase I, in the G2 stage was studied in a CHO mutant cell line EM9, which has an elevated baseline frequency of SCEs, and in its parental cell line AA8. EM9 cells were found to be more sensitive to CPT than the parental cell line. It is proposed that the effect of camptothecin in this phase of the cell cycle is caused by a 'residual' DNA synthesis which is higher in EM9 than in AA8 cells.

Animals↗

PubMed1993

Sensitivity of lymphocytes from vulcanizers to the in vitro induction of sister chromatid exchanges.

Spontaneous frequencies of sister chromatid exchanges (SCEs) and SCEs induced in vitro by chemicals with different mechanisms of action such as mitomycin C, 4-nitroquinoline oxide, and 3-aminobenzamide were examined in phytohemagglutinin-stimulated peripheral blood lymphocytes from a group of workers in a rubber plant and a control group, both of which had been analyzed for levels of spontaneous SCEs 2 years earlier. An interindividual variability in the induction of SCEs was found after in vitro treatments with the different mutagens, which did not correlate with occupational exposure. This variability in the sensitivity to the induction of SCEs might be correlated to genetic differences among individuals, which have to be taken into account in environmental monitoring programs.

Adult↗

PubMed1991

Multidisciplinary treatment of primary orbital rhabdomyosarcoma. A single-institution experience.

Orbital rhabdomyosarcoma accounts for one-fourth of the primary tumors in the head and neck region. Modern treatment modalities have led to a 2-year survival rate of about 90% in these patients. However, new therapeutic trials are designed to reduce complications and salvage more than 90% of orbital cases. Between 1979 and 1990, 12 children affected by primary orbital rhabdomyosarcoma have been diagnosed and treated at the University of Naples. Ten of them have been uniformly treated by biopsy, followed by immediate radiation and combined chemotherapy. All 12 patients are alive and free of detectable disease, from a minimum of 7 months to a maximum of 123 months after diagnosis. In all children, ocular structures have been spared and the complications observed until now have been few. The above results suggest that the association of immediate radiation therapy and chemotherapy might represent an optimal tool for treatment of orbital rhabdomyosarcoma.

Adolescent↗

PubMed1991

[Dehospitalization of the San Clemente psychiatric hospital in Venice].

The study presented herewith is part of a more comprehensive research work dealing mainly with the de-hospitalisation of the psychiatric hospital San Clemente in Venice since the change in psychiatric care effected by law, and with analysing the present situation of psychiatric care. The article reports on the highlights of this study during the investigated period from 1978 to 1984. The different types of care implemented in Venice are described on a structural plane with reporting on relevant data describing the activities. The importance of the centro di salute mentale = CSM within the Italian psychiatric care scheme is emphasised. Emptying of the psychiatric hospital San Clemente in Venice between 1978 and 1984 was observed systematically. The results show that the decrease in the number of patients of the psychiatric hospital during the period under observation was mainly achieved by genuine discharges. The majority of discharge patients (62%) return to their families, occupy a flat of their own or in residential community with other ex-patients. Transfers to other institutions were effected in exceptional cases only (e.g. home for the blind) (total percentage 4%). Analyses of the quality of life shows the limitations of reintegration of ex-patients. Only few ex-patients have so far succeeded in building up a perceptive for the future: the most marked time dimension is the past. Contrary to the often-lamented neglect of patients after their discharge, our data show that almost 90% of all 138 discharged ex-patients whom we interviewed, have been maintaining contacts to the psychiatric service offices.(ABSTRACT TRUNCATED AT 250 WORDS)

Community Mental Health Services↗