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Biomedical subjects

F Aiuti

Publications and source records attributed to F Aiuti.

At least 109 records · Page 6Linked to original sources

Epidemic Kaposi's sarcoma in Italy, a country with intravenous drug users as the main group affected by HIV infection.

The Italian Cooperative Group on AIDS & Tumors (GICAT) is collecting data on the epidemiological and clinical features of Kaposi's sarcoma (KS) in Italy, a country where intravenous drug users (IVDUs) comprise the largest group affected by AIDS. As of December 31st 1989, among 5317 cases of CDC-defined AIDS reported to the National Registry of AIDS, there were 419 (8%) cases of KS. Twenty-five percent of all of the homosexual men with CDC-defined AIDS had KS, while only 3% of the IVDU patients with CDC-defined AIDS had KS. The first case of KS was observed in 1982, 2 cases in 1983, 7 cases in 1984, 17 cases in 1985, 55 cases in 1986, 89 cases in 1987, 120 cases in 1988 and 128 cases in 1989. Of the 226 cases of KS reported to GICAT, 60% were in homosexual men, 21% in IVDUs, and 9% in heterosexuals. An increased number of KS has been observed since 1982, although the number of new cases in the past year seems to have been stable, possibly due to the usual delay in notification. There is, however, an actual decrease of the percentage of KS among AIDS patients, from 18% in 1984 to 6% in 1989. Almost half of the patients had had a diagnosis of AIDS prior to the appearance of KS, but in 25% of the patients KS was the first AIDS manifestation. Almost all patients had skin involvement either alone or in association with other sites, whereas very few patients had only lymph node involvement. Only treatment with alpha-2 interferon was able to obtain complete remission in 9% of evaluable patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

The efficacy and safety of zidovudine with or without acyclovir in the treatment of patients with AIDS-related complex. The European-Australian Collaborative Group.

Our objective was to evaluate the efficacy and safety of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) as treatment for AIDS-related complex (ARC). A double-blind, controlled clinical trial of 6 months therapy was conducted at teaching hospital ambulatory clinics in eight European countries and Australia; 199 patients were studied. Time to development of AIDS-defining opportunistic infections (OI) and AIDS-associated neoplasms, survival, performance status, body weight and CD4+ cell counts were measured. During the study six (9%) zidovudine recipients, five (7%) combination recipients and 12 (18%) placebo recipients developed AIDS-defining OI; the probability of developing an OI was 0.23, 0.09 and 0.08 for the placebo, zidovudine and combination recipients, respectively. Four patients in the placebo group, three in the zidovudine group and one in the combination group died during the study. Patients receiving zidovudine with or without acyclovir had moderate increases in CD4+ cell counts compared with placebo recipients and serum HIV p24 antigen level decreased significantly in all those receiving zidovudine. Fourteen (21%) patients in the zidovudine group and 16 (24%) in the combination group experienced bone-marrow suppression compared with three (5%) placebo recipients. Red-cell transfusions were administered to 6, 19 and 13% of placebo, zidovudine and combination recipients, respectively. These data confirm the efficacy of zidovudine therapy after 4 weeks' treatment in the reduction of development of OI in patients with ARC and support the use of a maintenance dose of 250 mg zidovudine 6-hourly. Given the increased development of OI in the treated groups compared with placebo during the first 4 weeks of therapy, we cannot exclude an initial adverse effect of zidovudine and recommend caution in the use of a loading dose of zidovudine. At 6 months there was no apparent difference in efficacy between the combination of zidovudine and acyclovir compared with zidovudine alone. Moreover, the addition of high-dose acyclovir resulted in a minimal increase in the risk of toxicity.

AIDS-Related Complex↗

Plasma viraemia in seronegative HIV-1-infected individuals.

It has been reported that the period of latency between HIV-1 infection and the production of antibodies against the virus is sometimes prolonged for greater than 6 months. However, the data supporting this are still controversial and it is not known whether these individuals are actually infectious, especially through body fluids. We have performed a prospective study of 65 high-risk HIV-1-antibody-negative individuals who were followed-up for a period of at least 1 year. Twelve of these individuals were shown by polymerase chain reaction (PCR) to be carriers of HIV-1 proviral sequences. The virus was isolated from lymphocytes in five out of 10 PCR-positive subjects and from cell-free plasma in two. Our data indicate that in some cases delayed seroconversions may be associated with productive infection, suggesting that mechanism(s) other than viral latency may be responsible for the absence of antibody responses to HIV-1 proteins.

Blood Cells↗

Evidence for IgE immune complexes and distribution of IgG subclasses with anti-IgE activity in patients with atopic dermatitis.

The anti-IgE autoantibody was detected, using a radioimmunoassay, in 17 out of 35 (48.6%) of patients with atopic dermatitis. Significant increased levels of IgG-anti-IgE were seen in the patients studied compared with the control group. The specificity of the anti-IgE autoantibody was confirmed by competitive inhibition assay using IgG, IgM, IgE myeloma. A correlation was observed between the levels of IgG-anti-IgE and serum IgE but not between the IgG subclasses with anti-IgE activity and the clinical status. These data demonstrate that the IgG subclass distribution with anti-IgE activity belongs mostly to the IgG1 and IgG4 subclasses compared with the controls. Moreover, ultracentrifugation analysis indicated that the IgG-anti-IgE in the serum samples from the patients with atopic dermatitis was present in the form of an immune complex with self-IgE. These observations may suggest that the anti-IgE complexes may play a broader role in the modulation of the immune response and that this autoantibody may mask recognition of IgE in conventional assays.

Adolescent↗

Proliferative and cytotoxic responses to mannoproteins of Candida albicans by peripheral blood lymphocytes of HIV-infected subjects.

Mucosal candidiasis is one of the first opportunistic diseases in HIV-infected subjects. In order to understand the relationship between this disease and immunodeficiency to chemically defined, immunodominant Candida antigens, a mannoprotein fraction from C. albicans cell wall (GMP) was used to analyse proliferative and non-MHC-restricted cytotoxic responses of peripheral blood mononuclear cells (PBMC) from normal and HIV-infected subjects. In the former, GMP induced extensive blastogenesis, generation of powerful cytotoxicity against a tumour cell line (K562), and production of substantial amounts of interferon-gamma (IFN-gamma). Cultured PBMC from HIV-infected subjects manifested an early decreased ability for proliferative as well as differentiative cytotoxic responses to the candidal mannoproteins. This inability became clearly evident in subjects with stage III (CDC) of the disease, was total in CDC stage IV and occurred even in some subjects with a normal number of CD4+ cells. Low or absent response to GMP correlated with lack of response to tetanus toxoid. In contrast, both lymphoproliferative and cytotoxic responses to exogenous IL-2 was highly preserved at all stages of infection. The production of IFN-gamma in GMP-stimulated PBMC cultures critically fell to negligible values in most of the subjects in CDC stages II and III. Thus, the lowered or absent cell-mediated immune responses to candidal mannoprotein may be one factor to explain the early, elevated susceptibility of HIV-infected subjects to mucosal candidiasis. This study also shows that our mannoprotein preparation may be used as a probe to detect the overall efficiency of T cell responses in the above subjects.

Acquired Immunodeficiency Syndrome↗

Serum eosinophil cationic protein in patients with atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin, frequently associated with a family history of atopy, raised serum IgE levels and other immunological abnormalities. Both eosinophils and their basic proteins have been detected in the skin lesions of AD patients. We measured the levels of eosinophil cationic protein (ECP) in sera of 24 children with AD and found them to be increased, compared to nonatopic controls, both children and adults. High ECP values were also obtained in 3 patients with the hyper-IgE syndrome. However, no direct relationship between IgE and ECP serum levels could be established. We found no correlation between serum ECP and the number of circulating eosinophils, suggesting that part of ECP was produced by cells infiltrating the tissues. Measurement of ECP might represent a noninvasive tool to assess the activity of AD in relation to eosinophil involvement in this disease.

Adolescent↗

Selective deficiency of interferon-gamma production in the hyper-IgE syndrome. Relationship to in vitro IgE synthesis.

We measured the in vitro production of interferon-gamma (IFN-gamma) in five cases of hyper-IgE syndrome (HIgE), induced by mitogens, calcium ionophores and phorbol ester. The biosynthesis of IFN-gamma was severely reduced or undetectable in HIgE, while it was near normal in most atopic patients. The in vitro spontaneous production of IgE was increased overall in HIgE patients, although no correlation was found with serum IgE levels. Recombinant interleukin-4 (IL-4) induced a further increase in IgE synthesis, and its effect was totally antagonized by recombinant IFN-gamma; the same pattern of response was also observed in atopic subjects with high production of IgE. IFN-alpha synergized with IL-4 on IgE synthesis, whereas recombinant IL-6 gave opposite changes in individual cases tested. We propose that IFN-gamma deficiency may be responsible for some of the features of HIgE patients, including IgE levels and infections.

Adolescent↗

Suicide behavior of target cells after binding with natural killer cells.

Human natural killer (NK) cell activity seems to be related to the integrity and function of the cytoskeletal apparatus. It has been hypothesized that microfilaments and microtubules play a pivotal role. In particular, the binding of the NK cell to the target cell requires microfilament integrity, and the lysis of bound targets seems to depend on microtubule assembly. We focused on the changes occurring in cytoskeletal elements and surface structures of NK cells and of target cells highly sensitive to NK activity (K562). Our observations, performed by fluorescence and scanning electron microscopy, besides confirming a rearrangement of the cytoskeletal apparatus in the effector cell, provide evidence that target cell cytoskeletal elements are involved in NK cell function. In K562 cells, after binding with NK cells, there is marginal rearrangement of actin and polarization of tubulin and vimentin in the contact regions, accompanied by modification of surface structures. These findings suggest that the target cell plays an active role in its own death by participating in the formation of an extended area of intimate contact with the killer cell. In addition, they lend credence to the surprising proposal that NK cells may induce a suicide mechanism in target cells.

Cell Survival↗

Risk of AIDS in HIV seroconverters: a comparison between intravenous drug users and homosexual males.

A multicentre cohort study was conducted in Italy to estimate the risk of developing AIDS in 261 intravenous drug users and 89 homosexual males for whom the seroconversion period was known. Four years after HIV seroconversion, AIDS incidence, estimated by Kaplan-Meier survival technique, was 13.8% for intravenous drug users and 16.2% for homosexual males; the difference was not statistically significant. These findings suggest that four years after seroconversion the risk of developing AIDS in HIV seropositive intravenous drug users is no higher than that of subjects who acquired HIV infection through sexual contact.

Acquired Immunodeficiency Syndrome↗

Antibacterial polysaccharide antibody deficiency after allogeneic bone marrow transplantation.

Allogeneic bone marrow-engrafted adults immunized with meningococcal types A and C and pneumococcal type 14 polysaccharide antigens showed only low antibody titers of the IgM class, no antibody titers of the IgG or IgA classes, and no bactericidal activity in vitro. The analytical isoelectrofocusing showed the appearance of a restricted pattern of clonotypes in a minority of subjects. These observations are consistent with the hypothesis that B cells in bone marrow transplant patients express some characteristics of neonatal B cells and suggest that polysaccharide-protein conjugates, rather than isolated polysaccharide, might be utilized in the setting of bone marrow transplantation.

Adult↗

Pathogenesis of the natural killer cell deficiency in AIDS.

Deficiency in natural killer (NK) cell activity is a common feature of acquired immune deficiency syndrome (AIDS). This is part of a general immune dysfunction in AIDS and may lead to progression of the disease, since NK cells are known to be involved in protection against tumors and against viral infections. The lack of immunological surveillance by NK cells of the growth of pathogens that activate the HIV-1 tat infectivity gene may also favor progression to AIDS. The pathogenesis of NK cell deficiency in AIDS is not known. Previous studies have shown that NK cells from AIDS patients are able to bind but not to lyse the target cell line K562. This results from an inability to rearrange the cytoskeleton microtubular (MT) system and to release the natural killer cytotoxic factor (NKCF). This report by Maria Caterina Sirianni and colleagues evaluates the possible mechanisms leading to this NK cell deficiency.

Acquired Immunodeficiency Syndrome↗

Proviral sequences detection of human immunodeficiency virus in seronegative subjects by polymerase chain reaction.

Human immunodeficiency virus type 1 (HIV-1) can be isolated from lymphocytes and tissues of symptomatic and asymptomatic seropositive subjects. However, in some individuals, virus isolation is not always positive, especially in asymptomatics. In this paper we report the results of HIV-1 DNA detection by means of polymerase chain reaction (PCR), a new technique that permits the amplification of specific DNA sequences. PCR was carried out to amplify two highly conserved env regions on samples from 20 normal individuals used as controls, 20 seropositive patients at different stages of HIV disease and 25 seronegative individuals at high risk for infection, such as sexual partners of seropositive patients and intravenous drug addicts. Eighteen out of 20 seropositive subjects were positive by PCR while among seronegatives HIV DNA was detected in 7/25 individuals. Virus isolation was positive only in 2/7. These subjects, followed for HIV antibody production for a period of 10-12 months, remained seronegative except one case who seroconverted after a few weeks. Long latency of HIV infection without detectable antibodies seems prevalent in these subjects. PCR assay represents a useful technique for identifying proviral sequences in seronegative high-risk individuals, to confirm the infection during its early phases and during the follow-up of patients with HIV disease.

Acquired Immunodeficiency Syndrome↗

Peripheral T-cell subset imbalance in patients with vitiligo and in their apparently healthy first-degree relatives.

Twenty-two patients with vitiligo had lesions stable for at least 1 year and 23 apparently healthy first-degree relatives were studied for T-cell subpopulations using monoclonal antibody technique. High levels of CD4+ lymphocytes and high CD4/CD8 ratios were found in both patients and their relatives, as compared with normal age-matched and sex-matched controls. This immunologic abnormality, together with the presence of autoantibodies previously reported in the apparently normal relatives, seems to be the hallmark of the disease. Further support of this interpretation comes from the observation that two out of the 23 apparently healthy relatives went on to develop vitiligo in a 2-year follow-up.

Adolescent↗