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Biomedical subjects

A Fattorossi

Publications and source records attributed to A Fattorossi.

At least 73 records · Page 4Linked to original sources
PubMed1995

Protective actions of L-carnitine and acetyl-L-carnitine on the neurotoxicity evoked by mitochondrial uncoupling or inhibitors.

The mechanism for the pathological increase in cell death in various disease states e.g. HIV immunodefficiency or even ageing or Alzheimer's disease, occurs by complex and as yet undefined mechanism(s) related to immunological, virological or biochemical disturbances (i.e. energy depletion, oxidative stress, increased protein degradation). We have studied mitochondrial uncoupling or inhibitor toxicity on neurones at the cellular level and at the mitochondrial level using rhodamine (Rh123) and 10-nonylacridine orange (NAO) fluorescence with confocal microscopy. Blockade of the mitochondrial chain complexes at various points was studied. The possible protective effects of the compound L-carnitine, which plays a central role in mitochondrial function, was tested in this form of neurotoxicity. It appears that L-carnitine and its acetylated form, acetyl-L-carnitine, can attenuate the cell damage, as assessed by lactate dehydrogenase (LDH) release, evoked by the uncoupler, p-(trifluoromethoxy)phenylhdyrazone (FCCP), or by the inhibitors, 3-nitropropionic acid (3-NPA) or rotenone. Further, the FCCP-induced inhibition of Rh123 uptake was antagonized by the preincubation of cells with L-carnitine. Since such neurotoxic mechanisms may be operating in the various pathological forms of myotoxicity and neurotoxicity, these observations suggest potential for a therapeutic approach.

Acetylcarnitine↗
PubMed1995

Influence of gingival crevicular washing on the expression of polymorphonuclear leukocyte membrane receptors before and after periodontal therapy.

Extensive data demonstrate that polymorphonuclear leukocytes (PMN) are the predominant cell type involved in periodontal disease and that gingival crevicular fluid constituents are influenced by the inflamed gingiva. The aim of the present study was to evaluate the ability of gingival crevicular washing (GCW) (a dilution of gingival crevicular fluid) from periodontal sites in different clinical conditions of modulating the PMN membrane receptors involved in motility, adhesion and phagocytosis before and after periodontal treatment. 10 patients affected by adult periodontitis (AP) were selected. From each patient, 2 test sites (TS) were chosen on the basis of a probing depth > 5 mm and attachment loss, and 2 control sites (CS) with probing depth < 3 mm without. Modifications of membrane receptor density of PMN from healthy donors incubated with GCW harvested from TS and CS was evaluated using fluorescent probes and flow cytometry. Compared to CS-GCW, TS-GCW before therapy increased the expression of the beta 2 integrin CD11b and the chemotactic receptor for the oligopeptide N-formyl methionyl leucyl phenylalanine (FMLP-R) while it reduced the expression of L-selectin. GCW collected from the same TS after the successful completion of periodontal treatment did not influence PMN receptors, indicating that the clinical improvement paralleled the disappearance of the PMN modulating capability contained in TS-GCW before therapy. In conclusion, the present data illustrate the relevant modifications occurring at PMN membrane in chronic adult periodontitis exerted by GCW obtained by a simple fluid collection technique. Thus, monitoring gingival crevicular fluid PMN activating capability may help disclose the presence of chronic periodontitis and may be useful in assessing successful treatment.

Adult↗
PubMed1994

Androgen receptors and hormone sensitivity of a human prostatic cancer cell line (PC-3) are modulated by natural beta-interferon.

Androgen receptors are expressed at a low level in the cell line PC-3, which does not respond to either androgens or antiandrogens. If these cells are exposed to natural beta-interferon (beta-IFN) a reduction in cell growth and an increase in androgen receptors, evaluated by both biochemical and immunocytochemical techniques, occur. This increase seems not to be related to a selective block of PC-3 in any phase of the cell cycle. Pretreatment with beta-IFN determines in PC-3 cells a partial responsiveness to the androgen dihydrotestosterone as reflected by the increase in cell number. Moreover, the antiandrogen hydroxyflutamide shows agonistic properties by increasing the cell number of PC-3 cells pre-exposed to beta-IFN. When the antiandrogen is tested in combination with interferon, it produces a reduction in the beta-IFN-induced inhibition of cell growth. It is not known whether these unexpected effects are due to the increase in androgen receptors or to other mechanisms.

Androgen Antagonists↗
PubMed1994

Lack of evidence for a superantigen in lymphocytes from HIV-discordant monozygotic twins.

OBJECTIVE: An HIV-associated superantigen (SAg) has been hypothesized. Here we test whether an SAg is functionally detectable in peripheral blood mononuclear cells (PBMC) from monozygotic twins discordant for HIV infection. DESIGN AND METHODS: The V beta selective T-cell depletion found in minor lymphocyte stimulation (Mls)-positive mice is caused by an SAg encoded by the mouse mammary tumour virus. Mls is a locus whose gene product stimulates a mixed lymphocyte reaction (MLR) in mice strains identical at the major histocompatibility complex locus. If an SAg is present in PBMC and/or sorted CD4+ cells from one HIV-infected monozygotic twin, it would stimulate PBMC from the corresponding healthy monozygotic twin in an MLR. In addition, if an SAg causes V beta-selective T-cell depletion in AIDS patients, a differential proliferation to a panel of staphylococcal enterotoxins (SE) of T lymphocytes from healthy and HIV-infected monozygotic twins should become measurable. RESULTS: No positive MLR or significant differences in the SE-driven proliferation between the healthy and the HIV-infected twins were observed. CONCLUSIONS: Our results suggest that PBMC from the two HIV-infected twins do not express a functionally detectable SAg.

Adult↗
PubMed1994

Flow cytometric analysis of cell function: cytosolic Ca++ modulation in human polymorphonuclear leukocytes and T lymphocytes.

Flow cytometry and fluo-3/AM have been used to track cytosolic Ca++ modulation in human polymorphonuclear leukocytes (PMN) and T lymphocytes. The chemotactic peptide N-formylmethionyl-phenylalanine (FMLP) but not the phorbol ester PMA induced cytosolic Ca++ modulation in PMN along with forward and side scatter modification. PMA inhibited FMLP activity when preincubated with PMN. T lymphocytes were antigen specific T cell clones and were stimulated with various amounts of diverse superantigens or PHA. Data show that superantigens can induce either activation or anergy depending on culture conditions. The biological significance of these data are discussed.

Aniline Compounds↗
PubMed1993

Dramatic reduction of meningococcal meningitis among military recruits in Italy after introduction of specific vaccination.

Meningococcal meningitis is still a serious infectious disease with a mortality rate that can be as high as 10% even in developed countries. Military recruits are generally a high-risk group for meningococcal disease, with a reported incidence of four to ten times greater than that of the general population. In Italy the results of the National Meningitis Surveillance Programme showed a high attack rate of the disease among recruits in 1985 as well as in 1986, with 92 and 95% of the cases, respectively, caused by serogroup C and thus preventable. These findings led to the authorities' decision to make vaccination against meningococcal disease mandatory for recruits starting from January 1987. After almost 5 years from the introduction of meningococcal vaccination, we here sum up the epidemiological and immunological effects of the vaccination. From the epidemiological point of view we have observed a dramatic reduction of the prevalence of the disease. In 1987, the year in which we had 150,000 unvaccinated and 150,000 vaccinated recruits, the protective efficacy was 91.2%. From the immunological point of view, vaccination is highly effective, as seroconversion against polysaccharide (PS) A and C is 84 and 91%, respectively. The spectrotypic analysis of the sera before and after vaccination shows that the type of response is mainly oligoclonal, like the majority of the responses to PSs, and the antibodies induced by a sole PS are not qualitatively different from the antibodies induced by natural immunization. In addition, the efficacy is not modified by environmental factors like hypoxia, as demonstrated during permanence at 16,174 feet for 20 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Clinical and immunological response to typhoid vaccination with parenteral or oral vaccines in two groups of 30 recruits.

The clinical and immunological responses to typhoid vaccination with parenteral and oral vaccines in two groups of 30 adult male subjects were studied. Specific anti-Salmonella typhi cell-mediated immunity and total or specific anti-lipopolysaccharide faecal immunoglobulin (Ig) A titres in vaccinated subjects were monitored. Cellular antibacterial activity was significantly increased only in orally vaccinated subjects. Serum arming activity and inhibition experiments suggested an IgA-dependent cellular cytotoxicity in those orally vaccinated. In these subjects, a total and anti-lipopolysaccharide faecal IgA increase was observed lasting up to 8 months after completion of the vaccination schedule. In parenteral vaccinated subjects, an early onset transitory increase of IgM rheumatoid factor was observed. Oral vaccine was well tolerated and free of side effects, whereas 65% of parenterally vaccinated subjects reported side effects such as fever, headache, malaise and local tenderness in the injection site.

Administration, Oral↗
PubMed1993

CD23/Fc epsilon RII expression on phytohemagglutinin-A- or phorbol-12myristate-13acetate-Ca(2+)-activated human tonsil T cells.

The low-affinity Fc receptor for IgE, CD23/Fc epsilon RII, has been expressed in T cell lines and pathologic T cells, but its presence on normal human T cells is still debated. We studied the expression of CD23/Fc epsilon RII on purified T cells from normal peripheral blood mononuclear cells (PBMC) or tonsil T cells stimulated with 10 micrograms/ml phytohemagglutinin A (PHA) or phorbol-12myristate- 13acetate (PMA) Ca2+. Using two-dimensional flow cytometry, the tonsil T-cell-enriched population showed > 10% of CD23/Fc epsilon RII expression when coexpressed with the CD3 antigen. CD4+ T cells appear to be principally involved in the expression of CD23/Fc epsilon RII, although we were unable to detect a clear expression of CD23/Fc epsilon RII in PBMC that were activated with either PHA or PMA Ca2+. PHA stimulation resulted in the release of IgE binding factor (IgEBF). The induction of CD23/Fc epsilon RII expression in PHA- and PMA-Ca(2+)-activated T cells was enhanced by IL-4, but not by IgE or IL-6. IL-4 also augmented the PHA- and PMA-Ca(2+)-induced release of IgEBF. The addition of supernatant from the Epstein-Barr virus (EBV)-infected cell line to PHA- or PMA-Ca(2+)-stimulated tonsil T cells did not increase CD23/Fc epsilon RII expression. The expression of CD23/Fc epsilon RII mRNA was detected in RNA prepared from a tonsil T-cell-enriched population by Northern blot analysis.

Blotting, Northern↗
PubMed1993

Influence of stress on lymphocyte subset distribution--a flow cytometric study in young student pilots.

Stressors can induce sizable modifications on immunocompetent cells. Major circulating lymphocyte subsets were quantitated in Italian Air Force student pilots undergoing intensive training and continuous evaluation, a stressful situation both physically and psychologically. Instructor pilots matched for age and assayed in parallel were used as controls. A typical flight training session was not able per se to induce immediate significant modifications of the lymphocyte subset distribution either in the students or instructors, although it did affect plasma levels of stress-related hormones such as growth hormone, prolactin and cortisol in the former. Irrespective of the time of flying, however, the percentage of CD4+ lymphocytes and the CD4/CD8 ratio were lower in students than in instructors, and the absolute number of CD8+ lymphocytes was higher in students than in instructors. In a second series of experiments, 30 student pilots were tested at the beginning and at the end of a flight course (duration 30 days). Although the percentage of CD29+ lymphocytes comprised in the CD8+ subset was reduced at the end of the course in all individuals, such a reduction was more evident in those students who failed to pass the final examination, an additional cause of psychological stress. In light of the functional significance of the lymphocyte subsets investigated, it is suggested that the present stress-induced alterations may have practical implications.

Adult↗
PubMed1992

Presentation of superantigen by human T cell clones: a model of T-T cell interaction.

Superantigens (SAg) interact with T lymphocytes bearing particular V beta sequences as part of their T cell receptor (TcR). The interaction, however, requires the presence of major histocompatibility complex (MHC) class II molecules on antigen-presenting cell (APC). In peculiar circumstances, MHC class II+ T cell clones (TCC) have been shown to present peptides and selected antigens interacting with antigen-specific TCC in the absence of APC. In this report we studied the capacity of SAg to mediate a T-T cell interaction, investigating the TCC ability to present a panel of staphylococcal enteroxins (SE) independently of the presence of added APC. Upon exposure to a broad range of SE concentrations, MHC class II+ TCC showed an intense proliferative response even in the absence of professional APC. Diverse SE optimally stimulated responder TCC at different concentrations. The proliferation was inhibited by anti-DR monoclonal antibodies, both in the presence and in the absence of APC. The SE activation of TCC in the absence of APC induced the same series of phenotypic variations as that observed following the TCC stimulation with APC. Irradiated TCC efficiently presented membrane-bound SE to responder TCC as well as professional APC. These results show that a single cell of a given clone effectively presents the SE to other cells of the same clone, and provide evidence that SAg can efficiently mediate T-T cell interaction. In addition, the possibility also exists that one cell of the clone can actually undergo an auto-stimulation via SAg-mediated interactions between its own TcR and MHC class II molecule. It has recently been suggested that the V beta-selective depletion of T cells observed in acquired immunodeficiency syndrome (AIDS) patients might be a consequence of the interaction between a human immunodeficiency virus (HIV)-encoded SAg and T cells expressing a SAg complementary V beta. We suggest that the hypothesized HIV-encoded SAg might mediate T-T cell interactions that could play a relevant role in the V beta-selective depletion of T lymphocytes observed in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Resistance of HIV-1 to AZT might also involve the cellular expression of multidrug resistance P-glycoprotein.

Resistance of tumor cells to the antigrowth activity of several cytotoxic compounds has been associated with the expression of the so-called multidrug resistance protein or P-glycoprotein. This article addresses the question whether the expression of such protein could also affect the sensitivity of HIV to AZT. Our data indicate that this possibility does exist. In fact, multidrug-resistant CEM VBL100 cells, which express high levels of P-glycoprotein, are less sensitive to both the antiproliferative activity and the antiviral action of AZT. Additionally, our data suggest that this phenomenon is specifically mediated by P-glycoprotein since trifluoroperazine, which is known to circumvent multidrug resistance due to the action on P-glycoprotein, increases the intracellular accumulation of AZT and affects the sensitivity of HIV to AZT. Although the biological and clinical significance of these observations has still to be established, this study suggests that cellular factors, other than virus itself, should be taken into account to address the phenomenon of drug resistance of HIV.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Multiparametric flow cytometric analysis of the kinetics of surface molecule expression after polyclonal activation of human peripheral blood T lymphocytes.

In this report we have analysed the kinetics of modulation of human peripheral blood T lymphocyte membrane molecules upon activation with optimal amounts of phytohaemagglutinin (PHA) and concanavalin A (ConA). The following activation-related and differentiation/adhesion molecules were selectively and concomitantly investigated on CD4+ and CD8+ subsets by dual colour flow cytometry: CD69, CD25 and CD71; CD2, CD45RA and L-selectin. Cultures were assayed after 24, 48, 72, 120 and 168 h of incubation with PHA and ConA. This approach allowed a comprehensive evaluation of membrane phenomena occurring during activation of normal resting human T lymphocytes. Data show that the kinetics of expression of these molecules follows a precise and consistent time-course with no major differences between CD4 and CD8 subsets. CD69 expression peaked at 24 h, whereas CD25 and CD71 expression peaked at 48/72 h with some differences between PHA and ConA activation. L-selectin expression started an evident decrease in step with culture time whose magnitude was dependent on the lectin used, being higher with PHA than with ConA. Conversely, the expression of CD45RA remained stable for 72 h and then briskly decreased with no major differences between PHA and ConA activation. CD2 molecules increased with time in number and density, although the percentage of positive cells remained essentially constant (greater than 85%). After 48/72 h of stimulation about 10% of cells co-expressed CD4 and CD8 molecules. To ascertain whether the phenomenon was restricted to cells in a particular activation state, the phenotype of cells in the diverse phases of the cell cycle was established. Results obtained show that only actively proliferating cells, that is cells in S and G2-M phases, co-expressed the two molecules, suggesting that such a phenomenon reflects a momentary dysregulation of the normal sequence of gene expression. The present data are also discussed in the light of the dynamic role of T lymphocyte activation and adhesion molecules in regulating cell-cell interactions, tissue localization and eventual immunological function.

Adult↗
PubMed1992

Oral polyvalent vaccine (Buccalin Berna) administration activates selected T-cell subsets and regulates the expression of polymorphonuclear leukocyte membrane molecules.

Acute respiratory tract infections (ARIS) still represent a major clinical problem during influenza outbreaks. The virus-induced impairment of the immune system favors the entry of opportunistic microorganisms into respiratory tract mucosa. A useful strategy to reduce ARIS is to provide at risk subjects an orally administrable polyvalent vaccine (OPV) comprised of bacteria strains recognised as the major ones responsible for ARIS. For the present study, the main circulating leukocyte populations of a group of healthy subjects receiving OPV were monitored as a marker of immune response. Subjects were investigated immediately before taking OPV (day 0) and 10,20, and 30 days later. Data show that T lymphocytes were induced to enhance the expression of class II MHC molecules, whilst a consistent number of CD4+ lymphocytes lost L-selectin, both phenomena indicating an activation status. OPV administration also modulated important molecules on the membrane of polymorphonuclear leukocytes, namely CD11b and CD16, strongly suggesting an activation of these cells and an enhancement of their defensive capacities. Finally, OPV was found to be able to increase the titer of serum antibodies specific for bacteria strains contained in the vaccine preparation in a portion of individuals. We conclude that OPV is able to consistently influence important immune functions and suggest that this property may be of relevance in preventing ARIS. Also, the present data may help to further our understanding of the mechanisms of OPV activity.

Administration, Oral↗
PubMed1992

Influence of ST 789 on murine thymocytes: a flow cytometry study of thymocyte subset distribution and of intracellular free Ca++ increase upon activation. Murine thymocytes and ST 789.

The coordinate expression of CD4 and CD8 antigens defines four major subsets of adult mouse thymocytes (CD4+CD8-, CD4+CD8+, CD4-CD8+ and CD4-CD8-) that represent definite steps in the differentiative pathway of immature T-lymphocytes. Thymocytes from adult C57BL/6 mice were cultured in the presence of ST 789, an L-Arg synthetic derivative of hypoxanthine, (1 to 100 micrograms/ml) or PHA 60.1 to 1 microgram/ml), or both for 48 hours, and then stained with monoclonal antibodies to CD4 and CD8 antigens for dual color flow cytometry analysis. The expression of CD25, was also investigated. ST 789 was ineffective in modifying the distribution of the four thymocyte subsets and did not induce the appearance of CD25 on cortical thymocytes. PHA induced a dramatic dose-dependent decrease of the CD4+CD8+ subset that, however, was neither enhanced nor antagonized by ST 789. We also tested ST 789 for its ability to stimulate intracellular free Ca++ rise in thymocytes. The compound was ineffective in this assay. Conversely, thymocytes promptly responded to PHA stimulation. It is concluded that ST 789 has no effect on normal adult thymocyte differentiation/activation pathway.

Adjuvants, Immunologic↗
PubMed1991

The effects of hypobaric hypoxia on specific B cell responses following immunization in mice and humans.

In order to get some insight on the physiology of the immune system during prolonged exposure to hypobaric hypoxia we evaluated the effects of high altitude on the in vivo immune response to a T-independent antigen. A group of 18 men who participated in a scientific project EV-K2-CNR to Mount Poumori, Nepal for 20 d at 4,930 m (16,174 ft) were immunized with a single subcutaneous dose of antimeningococcal vaccine Menpovax A + C (Sclavo) containing 50 micrograms of polysaccharide A (PsA) and 50 micrograms of polysaccharide C (PsC) of N. meningitidis. A group of 18 men of comparable age were vaccinated at sea level. Antibody titers against both polysaccharides were determined by enzyme-linked immunosorbent assay (ELISA) before and 18 d after vaccination. All subjects examined developed a good antibody response and no statistically significant differences were observed between the two groups. Spectrotypic analysis of antibody response to PsC was also performed by isoelectric focusing. No qualitative differences in the antibody response to PsC were found in the hypoxia-exposed group with respect to the control group. A group of 10 BALB/c inbred mice were kept in a hypobaric chamber at 5,500 m (18,000 ft) for 30 d. After 10 d, the mice were vaccinated with 1 micrograms of Menpovax A + C. Anti-PsA and anti-PsC antibodies were quantified by ELISA in sera collected at day 0 and 30. A control group of 10 mice of the same strain underwent the same study protocol but at sea level. Both groups developed a good antibody response to both polysaccharides and no significant differences were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗