Biomedical subjects

M Fiore

Publications and source records attributed to M Fiore.

At least 55 records · Page 3Linked to original sources

PubMed1997

Role of TNF-alpha but not NGF in murine hyperalgesia induced by parasitic infection.

Using adult mice infected with the trematode Schistosoma mansoni, we observed that this infection induces both thermal hyperalgesia and an increase in the levels of nerve growth factor in the paws. To explore the mechanism involved in peripheral hypersensitivity during chronic infection, mice were infected with 60 cercariae of S. mansoni and injected 17 weeks later with nerve growth factor, anti-nerve growth factor or with other molecules known to be associated with hyperalgesic processes. The results of these studies showed that antibodies against tumor necrosis factor-alpha, but not against nerve growth factor, reduce thermal sensitivity in schistosome infected mice, suggesting that this cytokine but not NGF plays a crucial role in schistosome-induced thermal hyperalgesia. Treatments with anti-inflammatory drugs support this hypothesis.

Animals↗

PubMed1997

Removal of the submaxillary salivary glands and infection with the trematode Schistosoma mansoni alters exploratory behavior and pain thresholds in female mice.

In this study, CD-1 female mice, deprived of the submaxillary salivary glands, were infected with S. mansoni and their behavior was observed 15 weeks after infection, when the eggs of the parasite are present in the brain. Sialectomized infected mice showed changes in exploratory activity, sniffing, and wall-rearing in the open-field and in the black/white box, but no differences in pain sensitivity were observed on the hot plate. The present results suggest that the modifications in the behavior of sialectomized infected mice might be associated with the inability of the animals to cope with the aversive effects of the infection and, most probably, with modifications in the levels of polypeptides released into the bloodstream by the salivary glands, affecting the NGF-responsive cells of the nervous, endocrine, and immune systems.

Animals↗

PubMed1997

Combined immunodeficiency phenotype associated with inappropriate spontaneous and activation-induced apoptosis.

Programmed death of T cells has been proposed as one of the mechanisms by which HIV induces a decline in the number and functions of T cells in advanced AIDS. In this study we report on a patient affected by a congenital form of combined immunodeficiency presenting as a profound T cell activation deficiency. Subsequently, a gradual loss of T cells occurred, eventually resulting in a classical form of severe combined immunodeficiency (SCID). In this patient a sizeable fraction of apoptotic cells was documented in the first phase of the disease by either propidium iodide staining or DNA fragmentation analysis. The presence of anergic T cells of maternal origin and engrafted in the child was excluded by analysis of DNA polymorphic regions. At 4 years of age the patient died of disseminated interstitial pneumopathy, while still awaiting an HLA-matched bone marrow transplantation. On the occasion of a new pregnancy in the mother, the prenatal immunological evaluation of the female fetus revealed a T B+ SCID phenotype. This is the first observation of a primary immunodeficiency associated with inappropriate apoptosis.

Apoptosis↗

PubMed1997

Defective interleukin-2 production in children with chronic hepatitis B: role of adherent cells.

BACKGROUND: Chronic hepatitis B (CHB) virus infection is associated with functional abnormalities of cell-mediated immunity, defective interferons alpha and gamma synthesis, and interleukin-2 receptor expression. In this study, interleukin-2 (IL-2) production and the role of adherent cells was evaluated in 25 children chronically infected with hepatitis B virus. METHODS: IL-2 activity was measured by bioassay in supernatants of phytohemoagglutinin-stimulated peripheral blood mononuclear cells. In a few patients, IL-2 concentration was also immunochemically determined. Coculture experiments using a mixture of adherent cells and lymphocytes from healthy children and patients with CHB were also performed. RESULTS: Children with CHB showed lower IL-2 production than healthy controls. In patients, IL-2 activity was 34.7 +/- 22.5 U/ml as compared to 152.6 +/- 78.5 U/ml of controls. Immunochemical quantitation of IL-2 confirmed a lower IL-2 production in patients. No correlation was found between the functional T-cell defect and the severity of liver damage, degree of viral replication, and duration of the disease. In co-culture experiments, adherent cells from HBsAg-positive patients inhibited IL-2 production following mitogen stimulation of control non-adherent cells by 67%. The inhibitory effect, mediated by patients adherent cells, was abolished by blocking with indomethacin prostaglandins, that are potent local immunomodulators released by adherent cells. CONCLUSIONS: Our results further support the observation that in children with CHB virus infection adherent cells play an important role in the inappropriate regulation of immune response, an effect being likely mediated by prostaglandins.

Adolescent↗

PubMed1997

Patterns of platelet aggregation in menstrual migraine.

We investigated the threshold of the platelet release reaction during the luteal phase of the cycle in 46 patients suffering from menstrual migraine (MM) and 27 healthy normal women. The distribution in both groups of the three types of aggregometric curves (types 1, 2 or 3) obtained in response to ADP 1 microM as aggregating agent was evaluated. Among MM sufferers, 19 (41%) showed a type 1 curve, while 14 (31%) had a type 2 curve and 13 (28%) showed an irreversible aggregation with a type 3 pattern. Curve distribution in controls was 18 (67%) for type 1, 8 (30%) for type 2 and 1 (3%) for type 3. A significantly (p < 0.05) different distribution of the three curve types between MM and controls was present, suggesting that a secondary wave of aggregation is more frequent in MM; the highest difference was due to the observed frequencies of type 3 curves.

Adult↗

PubMed1997

[Native valve infective endocarditis caused by Streptococcus bovis. Efficacy of short-term antibiotic therapy and usefulness of serial echocardiographic evaluation].

We report a case of infective endocarditis on native valve, due to Streptococcus bovis, treated successfully with short time antibiotic therapy (10 days versus minimum suggested treatment of two weeks) by using penicillin G together with streptomycin (six days), followed, by treatment with imipenem (four days) because of allergic reactions. Diagnosis was simpler thanks to Durack's new criteria that include positive echocardiographic findings (valvular vegetations) within major clinical criteria for definite diagnosis of infective endocarditis, different from preceding Von Reyn's criteria which did not provide diagnostic weight for echocardiographic data. Serial echocardiograms have also been useful to evaluate the early response to the treatment and its persistent efficacy in the follow-up.

Anti-Bacterial Agents↗

PubMed1996

Congenital Alopecia and nail dystrophy associated with severe functional T-cell immunodeficiency in two sibs.

We report on two sisters affected by congenital alopecia, nail dystrophy, and a severe T-cell immunodeficiency, presumably inherited as an autosomal-recessive disorder. The T-cell defect was characterized by severe functional impairment, as shown by the lack of proliferative response and upregulation of activation markers following mitogen stimulation. The functional abnormality occurred in spite of the presence of phenotypically mature of the defect. This is the first observation reported on an ectodermal disorder, characterized by alopecia and nail dystrophy, observed at birth, in association with a primary immunodeficiency. The hypothesis that these two events may be casually related is discussed.

Alopecia↗

PubMed1996

Neurobehavioral alterations in developing transgenic mice expressing TNF-alpha in the brain.

During development, neuronal circuitry and memory formation are associated with the synthesis and release of several biological mediators, including cytokines. Among the numerous cytokines, the role of tumor necrosis factor-alpha (TNF-alpha) in neurobehavioral development is largely unknown. Thus, the recently generated transgenic mice expressing murine TNF-alpha in the brain represent a valid animal model for investigating the role of TNF-alpha in neurobehavioral processes. Using these mice, we showed that an overexpression of murine TNF-alpha increases grooming in the novel object investigation test, decreases rearing as a reaction to novel olfactory cues, and produces a retardation of passive avoidance acquisition while enhancing the thermal response in the hot-plate test, a task regulated by both peripheral and central mechanisms. The possibility that these effects are associated with endogenous changes in concentration of the NGF, known to be modulated by TNF-alpha, is discussed.

Animals↗

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↗