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Biomedical subjects

R Nisini

Publications and source records attributed to R Nisini.

At least 37 records · Page 2Linked to original sources

Infection of circulating and liver infiltrating T cells by hepatitis C virus of different subtypes.

Hepatitis C virus (HCV) infection display a very high rate of progression to chronicity and, like many other viruses causing persistent infections, it displays a tropism for the cells of the immune system. Peripheral blood mononuclear cells (PBMCs) from 21 HCV chronic carriers and long-term T cell clones derived from circulating or liver infiltrating T lymphocytes were tested by cDNA "nested" PCR for positive and negative strand HCV-RNA. The presence of HCV genomes in PBMCs is a frequent, although not constant, finding and can be accompanied by active viral replication, as suggested by the coexistence of negative strand HCV-RNA. Infected T cells are more represented in livers than in periphery, as indicated by comparing HCV-RNA detection in T cell clones isolated from both the compartments. Sequencing of viral genomes present in PBMCs and liver infiltrating lymphocytes showed that all the three major HCV genotypes present in our population of chronic carriers can infect lymphoid cells. Although each clonal population of T cells is infected by a single strain of HCV, in the same patient lymphoid cells can harbor different viral populations, different from those circulating at that moment in the serum.

Adult↗

Spectrotypic analysis of antibodies to Helicobacter pylori in patients with antral gastritis and duodenal ulcer.

AIMS: To investigate the anti Helicobacter pylori (H pylori) spectrotype associated with (a) antral gastritis and duodenal ulcer; (b) the H pylori eradicating treatment. METHODS: Spectrotypic analysis was performed by isoelectric focusing and reverse blotting (IEFRB) in a cross sectional study on sera from 70 patients with antral gastritis and duodenal ulcer. In addition, a longitudinal study was performed on 40 of these patients (20 with antral gastritis and 20 with duodenal ulcer) who underwent eradicating treatment. RESULTS: The cross sectional study showed that the oligoclonal spectrotype was present in 74% of antral gastritis patients and in 85% of duodenal ulcer patients. In only a minority of subjects (23% with antral gastritis and 3% with duodenal ulcer) was a polyclonal spectrotype observed. The longitudinal study showed a reduction in the intensity of the spectrotypic bands in 5/10 antral gastritis patients with eradicated H pylori as opposed to only 2/10 patients without eradication. A reduction was also observed in 6/11 eradicated v 0/9 non-eradicated patients with duodenal ulcer. Collectively, a reduction in the spectrotype was observed in 11/21 patients (52%) who--independently of the disease--underwent H pylori eradication, as opposed to 2/19 of the non-responder patients (10.5%). The polyclonal spectrotype was found exclusively in four patients with antral gastritis, all belonging to the group without eradication of H pylori after eradicating treatment. CONCLUSIONS: The anti H pylori oligoclonal spectrotype is the most common pattern observed in patients with antral gastritis and duodenal ulcer. After H pylori eradicating treatment the spectrotype does not change qualitatively, but the polyclonal pattern seems to be predictive of a poor response to eradication.

Adolescent↗

Humoral response to influenza hemagglutinin: oligoclonal spectrotype and failure of thymopentin as immunoadjuvant.

Influenza remains a serious cause of illness and death among certain populations. Influenza vaccines in use at present are of limited effectiveness due to the high variability of the virus, and trials all over the world are in progress to enhance their immunogenicity. Conflicting results, in fact, have been reported about the immune response to influenza vaccination in diverse populations. In this paper we analyzed the antibody response to the hemagglutinin (HA) of the H3N2 A/Shangai 16/89 strain, which was included into the trivalent 1991-92 influenza vaccine, in four groups of subjects: 8 healthy young, 13 human immunodeficiency virus (HIV)-infected and 37 elderly healthy people, 9 of whom were treated with thymopentin (TP-5). Our results show levels of anti-HA IgG before vaccination in HIV-infected and elderly people significantly lower than those of normal young subjects. After vaccination, HIV-infected and elderly healthy people showed a significant increase of specific antibodies, whereas a failure in the specific response in normal young subjects was observed, thus differences among the groups were no longer present. Moreover, the spectrotypic analysis of antibody response, by isoelectric focusing and reverse blotting, showed oligoclonal but polymorphic pattern in the majority of subjects, irrespective of the group, and more frequently lack of expansion of the spectrotype after vaccination, thus demonstrating the lack of the recruitment of antigen-specific B cells. Finally, the treatment with TP-5 did not influence the outcome of the vaccination in the group of elderly people. These results further emphasize the limited immunogenicity of influenza vaccination and the inefficacy of TP-5 as immunoadjuvant, in this model of vaccination.

Adjuvants, Immunologic↗

Low prevalence of anti-HCV antibodies among Italian Air Force recruits.

In 1990, the prevalence of antibodies to hepatitis C virus (anti-HCV) was assessed among 4,978 Air Force recruits aged 18-26 years coming from all regions of Italy. Positivity to anti-HCV was found by both IIIrd generation EIA and RIBA in 24 (0.48%) study participants. The prevalence was twice as high in Southern Italy and the islands as in Northern and Central Italy (0.76% vs. 0.35%), a difference which was not statistically significant. The results of multiple logistic regression showed that no sociodemographic variable (region of birth, father's years of education, number of siblings) was associated with anti-HCV positivity. No anti-HCV-positive individual was positive for HBsAg. Anti-HCV positivity was found in 0.8% (2/236) of the participants who were positive for anti-HBc and in 0.5% (22/4742) of those who were anti-HBc negative, also a difference which was not statistically significant. Thus no association was found between HCV and HBV infections. These findings indicate that in Italy, HCV infection is an uncommon event among young adult males.

Adolescent↗

Soluble transferrin mediates targeting of hepatitis B envelope antigen to transferrin receptor and its presentation by activated T cells.

In a previous study, we identified that transferrin receptor (TfR) is the receptor utilized by hepatitis B virus (HBV) to enter T cells. We demonstrated that hepatitis B envelope antigen (HBenvAg) is taken up by activated T cells via TfR, processed in endosomal compartments, and presented on class II molecules to specific CD4+ T cell clones. Herein, we report that binding to soluble ferric Tf by HBenvAg is needed in TfR-mediated endocytosis. Accordingly, presentation of HBenvAg by activated T cells is not observed in serum-free medium and is restored by addition of soluble Tf. Moreover, we provide evidence that pre-S2 and S regions of HBenvAg contain the critical residues for the interaction with soluble Tf. Our data not only explain HBV entry into a variety of host activated cells, but may also help in developing strategies to alter the course of chronic HBV infection.

Antigen Presentation↗

Incidence of hepatitis B virus infection among an Italian military population: evidence of low infection spread.

In 1990, a prospective serological survey to estimate the rate of clinical and inapparent infection with hepatitis B virus was performed in a cohort of 1324 soldiers, 18-24 years old, during an eight-month period in Italy. At the time of enrollment the prevalence of hepatitis B markers was 4.6% (0.7% subjects positive for hepatitis B surface antigen [HBsAg], 3.0% positive for antibody to hepatitis B surface antigen [anti-HBs], and 0.9% positive for antibody to hepatitis B core antigen [anti-HBc] alone. Among the 1263 susceptible subjects who were followed-up, only 2 (0.24/100 person-years of exposure) had seroconversion for HBV markers, none of which was associated with clinical illness. Among the 9 subjects HBsAg-positive at the time of enrollment, 1 (11.2%) had lost HBsAg at the end of follow-up. These data show a low spread of HBV infection among Italian young generations.

Adolescent↗

Evaluation of the overall degree of sensitization to airborne allergens by a single serologic test: implications for epidemiologic studies of allergy.

In most epidemiologic studies of respiratory allergy, the overall degree of sensitization is usually measured by indices based on skin prick test reactions to a panel of relevant airborne allergens. In the present study we used a single assay (CAP-Phadiatop, Pharmacia, Uppsala, Sweden), which is based on the reaction between serum-specific IgE and a mixture of locally relevant inhalant allergens to measure the degree of sensitization to inhalants in the sera of 1815 young Italian men, in whom a complete diagnostic workup for respiratory allergy was performed in parallel. The intensity of reaction in the CAP-Phadiatop assay was highly correlated with: (1) an allergy index (p < 0.005), based on skin prick test reactivity to seven relevant inhalant allergens (Dermatophagoides pteronyssinus, mixed grass pollens, cat epithelium, Parietaria judaica, Olea europaea, Artemisia vulgaris, Alternaria tenuis); (2) the concentration of specific IgE to the same allergens, measured by CAP-RAST (p < 0.001), in both monosensitized and polysensitized subjects; (3) the rate of respiratory allergic diseases (p < 0.0001). Therefore CAP-Phadiatop intensity of reaction is a reliable indicator of the overall degree of sensitization to inhalant allergens. Furthermore, as demonstrated by relative operating characteristic analysis, it has an acceptable detectability power in identifying subjects with symptomatic expression of the atopy status [P(A) = 0.948]. The evaluation of the degree of sensitization to inhalants by a single and semiautomated assay represents a step forward in the standardization of procedures for epidemiologic studies of inhalant allergic diseases and for mass screening programs, which are aimed at identifying predictive markers of disease susceptibility.

Adolescent↗

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↗

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↗

Breast milk from mothers of children with newly developed atopic eczema has low levels of long chain polyunsaturated fatty acids.

BACKGROUND: Infants at risk of atopic dermatitis have lower than normal levels of long chain polyunsaturated fatty acids. These fatty acids are normally present in substantial quantities in human breast milk. METHODS: Because of the equivocal evidence concerning the ability of breastfeeding to delay the onset or reduce the severity of atopic dermatitis, we have analyzed the fatty acid composition of breast milk from the mothers of children with newly developed disease with the use of gas chromatography. RESULTS: Breast milk lipids from mothers of children with newly developed atopic dermatitis had increased proportions of linoleic acid and significantly decreased proportions of its long chain polyunsaturated derivatives compared with a control group. The ratio of linoleic acid to the sum of its metabolites, gamma-linolenic acid, dihomo-gamma-linolenic acid, and arachidonic acid was 11.78 in the atopic group and 9.02 in the control group (p < 0.01). CONCLUSIONS: These results are consistent with previous findings of an abnormal fatty acid status in atopic subjects and may account for some of the inconsistent results from studies of the effect of breastfeeding on the subsequent development of atopic dermatitis. We conclude that further studies to examine the effects of supplementation of the diet of breastfeeding mothers with long chain polyunsaturates should be done.

Adult↗

Quantitative and qualitative analysis of anti-tetanus toxoid antibody response in the elderly. Humoral immune response enhancement by thymostimulin.

In order to explore the humoral primary and secondary response to tetanus toxoid (TT), and to define the possible immunopotentiating effect of the thymic hormone thymostimulin, we studied 13 elderly people, selected according to the Senieur Eurage protocol, vaccinated against TT, an antigen never encountered before. Six of them were treated with thymostimulin before and during the immunization protocol. Specific anti-TT antibody level measurement and spectrotypic analysis were performed on the sera collected from the subjects at different times over the immunization protocol. In addition, spontaneous in vitro production of anti-TT antibodies as well as cutaneous delayed hypersensitivity reactions were also studied. Only one patient showed a detectable humoral immune response after the first immunization. After the booster, four of six thymostimulin-treated individuals, compared with only two of seven controls, showed in vivo anti-TT humoral response; at the same time, spontaneous anti-TT production was detected in peripheral blood mononuclear cells from five of six thymostimulin-treated individuals but only three of seven untreated controls. These differences were highly significant (p < 0.0001). In addition, only in thymostimulin-treated subjects were the levels of serum anti-TT antibodies 14, 21 and 28 days after the booster significantly (p < 0.05) higher than the baseline values. The spectrotypic analysis of anti-TT antibodies performed by isoelectric focusing and reverse blotting showed total agreement with the results from enzyme-linked immunosorbent assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Clinical types of HBsAg-positive hepatitis.

Hepatitis B is a parenterally and sexually transmitted disease of global importance. It associates with hepatitis D in a consistent proportion of cases. The disease most frequently runs a subclinical and anicteric course, with a significant number of cases that become chronic. Chronic hepatitis may progress to cirrhosis or cancer. The strategies by which hepatitis B and hepatitis D can be diminished and eventually eliminated are: immunization, measures to prevent exposure to infective blood or blood derivatives and education (in particular awareness that hepatitis B is a sexually transmitted disease).

Adult↗

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↗

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↗

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↗

Spectrotype of anti-gp120 antibodies remains stable during the course of HIV disease.

Human immunodeficiency virus (HIV) infection is characterized by a progressive decline in immune functions. The behavior of B-cell clones specifically engaged in the anti-HIV response could play a relevant role in the pathogenesis of such impairment. The spectrotype observed on isoelectric focusing and reverse blotting after antigen challenge is the serum image of antigen-specific B-cell activity and may provide some insight into Ag-dependent B-cell clone recruitment. In this study, we examined the spectrotype of anti-gp120 antibodies in a group of sera from 56 HIV-infected patients, belonging to groups II, III, and IV of the Centers for Disease Control classification, as well as in a group of 31 sera from 12 patients in a 21-month follow-up evaluation (range 7-36 months). All tested sera were positive for gp120 antibodies on Western blot. In the first group of 56 HIV-infected subjects, only 19 displayed well-focused banding patterns. Among these, the spectrotype was found to be consistently oligoclonal, thus confirming clonal restriction of anti-gp120 antibodies previously described by other investigators. No correlation could be established between a particular spectrotype and phase of the disease. The follow-up evaluation in the second group of 31 sera revealed the tendency in each patient to maintain the same spectrotype throughout the course of the disease. These findings confirm clonal restriction of anti-gp120 antibodies in HIV infection and suggest that the number of B-cell clones recruited in the anti-gp120 response remains stable over the course of the disease, at least in the time range explored by us.

Adult↗

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↗