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Biomedical subjects

A Lazzarin

Publications and source records attributed to A Lazzarin.

At least 307 records · Page 17Linked to original sources
PubMed1979

The role of superoxide anion generation in antibody-dependent polymorphonuclear leukocyte-mediated cytotoxicity.

Human polymorphonuclear leukocytes (PMNs) can act as killer cells in an antibody-dependent cellular cytotoxicity (ADCC) system. Cytolysis is rapid and detectable at low effector/target cell ratios. PMNs from a patient affected by chronic granulomatous disease (CGD) exhibit an absolute defect in ADCC. In order to investigate the role of the toxic oxygen derivatives (H2O2 and superoxide anions) lacking in CGD, experiments in presence of specific inhibitors were carried out. Superoxide dismutase, an O-2 scavenger, displayed a significant inhibition activity in a dose dependent way. On the other hand neither catalase, which degrades H2O2, nor sodium azide, a myeloperoxidae inhibitor, affect the cytotoxic activity. Our results suggest that the importance of the intact oxidative metabolism in PMN-mediated ADCC against chicken red blood cells could be referred to the correlated production of O-2 anions.

Animals↗
PubMed1977

IgG and C3 receptors on polymorphonuclear leukocytes in phagocytosis. Role of C3-receptors in the attachment and ingestion phases.

The role of IgG and complement (C3) receptors in the adhesion and ingestion phases of immune complexes by normal human polymorphonuclear leukocytes (PMN) were examined. The immune complexes were sheep red cells (E) sensitized with IgG (EA) or IgM antibodies plus complement (EAC'). Both types of receptor sites are involved in the adhesion phase. Moreover IgG receptors are primarily involved in the ingestion phase. Nevertheless even C3-receptors may be sufficient for complete phagocytosis. Even if EAC' adhesion was still high, C3-receptor specific phagocytosis decreased parallel with the amount of the complement used for EA19S sensibilization. The role of receptor sites on human PMN in adhesion and ingestion phases is discussed.

Binding Sites, Antibody↗
PubMed1976

[Demonstration of a granulocyte defect in aged persons correlated with the presence of autoantibodies].

Assessment of PMN leukocyte function and search for autoantibodies were performed in 36 aged human subjects (more than 60 years of age) and in 15 younger controls (40 to 60 years of age). Autoantibodies were found in 15 of the 36 aged subjects, and in none of the controls. Leukocyte function defects were therefore correlated to old age and to markers of autoimmunity. Phagocytosis of bacteria was significantly impaired in both groups of old-aged subjects, irrespective to the presence or absence of autoimmunity. Intracellular killing of bacteria was shown to be normal in all the examined subjects. Nitroblue tetrazolium reduction by resting and latex-stimulated leukocytes was significantly impaired only in the group of old-aged subjects with autoimmunity. These leukocyte function defects are similar to those already described in human autoimmune diseases -- particularly S.I.E. -- and confirm the possible association between P.M.N. dysfunction and autoimmunity.

Adult↗
PubMed1976

[The immunofluorescence technique detecting antibody-coated bacteria for diagnosis of site of UTI (author's transl)].

The immunofluorescente technique detecting antibody-coated bacteria for diagnosis of site of UTI has been applied to 52 urine samples coming from : 11 patients with clinical diagnosis of pylonephritis, 21 infections of the lower urinary tract, 8 asymptomatic bacteriurias and 2 samples of urine obtained directly by pyelocentesis. The technique confirmed to be specific and sensible: strongly fluorescent germs were observed only in samples coming from pyelonephritis or urine from pyelocentesis. Repeatedly, from single samples were isolated more bacterial strains; only one of them was present in significant quantity. The some observation has been made also in 5 patients clinically affected with P.N., where 2 strains were isolated from each sample. In only one sample both strains were fluorescent, white in the remaining 4 samples the strain present in insignificative quantity was fluorescent. These observations, rather than a double localization (pyelo-renal and lower urinary tract) with different aetiologic agents, were interpreted to be the outcome of repeated antibiotic treatments. It is possible that they could have reduced the fluorescent "bacterial load" of the pyelo-renal region under significant number, simultaneously facilitating the emergence of superinfecting germs at the level of the lower urinary tract. We discuss the therapeutic involvements for a proper antibiotic treatment and the usefulness of flanking the test at the quantitative urine culture.

Antibodies, Bacterial↗
PubMed1975

[Effects of thymectomy on the natural bactericidal power of thymectomized mice].

T and B-dependent systems are correlated between themselves and with the macrophage system in eliciting the immune humoral response. Not all immunogens require T-B interactions to elicit the antibody response: consequently, the problem of the limits of T-dependence, with regard to different immunogen stimulations, remains open. The comparative study of the serum antibody response in mice, thymectomized at birth and in the normal ones, inferred from the values of bactericidal activity (b.a.), detected versus E. coli, S. typhi and S. albus strains did point out evident variation. Thymectomy has impaired b.a. against E. coli; it seems to have no consequence on b.a. against S. typhi; is not possible to the results of our investigation, it seems that the response to the immunogens, responsible for the so-called natural antibodies does require T-B cooperation only for some bacterial species and not for others. A higher bactericidal capacity of normal serum with regard to Gram positive as compared with Gram negative bacteria, is confirmed.

Animals↗
PubMedDate not supplied

Attempted treatment of fulminant viral hepatitis with human fibroblast interferon.

Beta-interferon was administered by intravenous infusion to 16 patients affected with fulminant hepatitis B virus infection in third or fourth-grade coma. Ten patients presented a superinfection or a co-infection due to the delta (delta)-agent. None had detectable interferon (IFN) activity before therapy was begun. Besides fever, no significant side-effects were observed during treatment. Both the IFN-treated group as well as the "historical" control group, made up of 70 cases of fulminant virus hepatitis, not treated with IFN and observed during a previous ten year-period, received supportive therapy; survival rates were similar in both groups. Furthermore, the presence or absence of the delta-agent did not appear to affect survival rates significantly.

Adolescent↗
PubMedDate not supplied

Outbreak of persistent, unexplained, generalized lymphadenopathy with immunological abnormalities in drug addicts in Milan.

Persistent unexplained lymphadenopathy (LAS) with intermittent fever, weight loss, night sweats and malaise was observed from March to October 1983 in 16 of 133 intravenous drug addicts who had been followed for at least two years in a Center for Drug Addicts Assistance in Milan, Italy. All the subjects lived in a restricted suburban area and indulged in frequent toxicomanic practices and mutual sexual intercourse. The subjects showed immunological alterations such as lymphopenia (50%), decreased T helper/T suppressor ratio (93%), both these abnormalities (43%), decreased T helper cells (75%), increased T suppressor cytotoxic cells (81%), decreased natural killer (NK) activity (77%), anergy (50%) or hypoergy (43%) to recall skin testing and elevated levels of IgG (87%). Anti-HTLV III antibodies were found in 14 of 16 (87%) patients with LAS and in 3 of 11 (27%) symptom-free drug addicts belonging to the same group. It will be important to assess in the future whether this clinical and immunological picture results in acquired immunodeficiency syndrome in an area so far untouched by this disease.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Epidemic of LAV/HTLV III infection in drug addicts in Milan: serological survey and clinical follow-up.

A clinico-epidemiological study is reported concerning a group of 306 parenteral drug addicts (PDAs), 71 of whom were affected with the lymphadenopathy syndrome (LAS); all were followed-up between 1981 and 1984. Although full-blown acquired immune deficiency syndrome (AIDS) was observed only in one case, none of the other patients examined have undergone complete recovery so far. The results of our study point to a wide circulation of LAV/HTLV III among our group of PDAs, starting at least as early as 1981 and preceding by a few months the development of clinical signs and symptoms of LAS. A peak incidence of the latter was observed during the winter of 1983/1984, running parallel with a marked increase in seropositives for LAV/HTLV III antibody. Drug addiction, sexual promiscuity and a low standard of living all seem to play a decisive role in the spread of the infection and, consequently, of the diseases related to it (LAS, AIDS-related complex and AIDS). In fact, PDAs appear to represent the major source of the disease in Italy.

Antibodies, Viral↗
PubMedDate not supplied

Diagnostic and prognostic significance of beta 2-microglobulin during HIV infection.

The serum levels of beta 2-microglobulin (beta 2-m) were determined in 80 intravenous drug addicts (IVDA) with acquired immunodeficiency syndrome (AIDS), in 128 HIV-positive IVDA with persistent generalized lymphadenopathy (PGL) and in 44 HIV-seronegative IVDA. Seventy-two out of 80 (90%) AIDS patients had elevated serum beta 2-m levels and high levels of beta 2-m were also found in 105 of 128 (82%) HIV-infected subjects without AIDS. The mean beta 2-m level was significantly higher in HIV-infected patients with PGL than in HIV-negative IVDA. Nine out of 64 (14%) PGL patients developed AIDS in a period of 24-54 months. In these patients the mean beta 2-m level (5.16 +/- 2.37 mg/l), obtained from sera stored at the first observation, was significantly higher than in the other PGL patients (3.40 +/- 1.03 mg/l); in particular, 5 out of 7 PGL patients with beta 2-m levels greater than 5.0 mg/l showed an advanced disease.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Managing failure to antiretroviral drugs in HIV-1-infected patients.

Managing failure to antiretroviral therapies implies the addressing of several issues: the clinical stage, the virological and the immunological response to the failing regimen, together with drug history, resistance and exposure. Each of these issues will be discussed with the aim of providing useful data to design an optimal rescue antiretroviral therapy.

Animals↗
PubMedDate not supplied

The rationale for a study on HIV-1 reverse transcriptase mutations and outcome of antiretroviral therapy with two nucleoside analogs.

The development of resistance to antiretroviral drugs has been recognized as an important cause of treatment failure in HIV-1-infected patients; however the correlation between emergence of resistance and treatment failure has not been yet clearly defined. The high rate of viral replication, together with the lack of proof reading activity of HIV-1 reverse transcriptase, accounts for the rapid establishment of extensive genotypic variation, resulting in the emergence of viral mutants showing primary or secondary resistance to antiretroviral drugs. In this regard, phenotyping and genotyping allow the detection of drug resistance. Both tests have advantages and limitations compared to each other. The complete suppression of viral replication seems to be the best way to avoid occurrence of drug resistance, and viral loads below the limit of detection can be usually achieved by a combination of 3 antiretroviral drugs. In this scenario, the proportion of HIV-1-infected patients on dual therapy is still relevant in Italy. We believe that the study of this subset of individuals is very important, as resistance to nucleoside analogues may impair the outcome of a future triple therapy. In addition, this study could contribute to define the role of resistance assays in the management of HIV-1-infected patients.

Anti-HIV Agents↗
PubMedDate not supplied

Viral dynamics and mutations in the pol gene during primary HIV-1 infection.

The understanding of viral dynamics and appearance of mutations during primary infection could be useful for the design of an efficient therapy. For this reason a cohort of samples from naive primary patients was examined. The results pointed out that only a few secondary mutations in protease gene (having no effect on resistance) were found, while a single mutation conferring resistance to non-nucleosides inhibitors of reverse transcriptase was found both in plasma and cerebrospinal fluid of a patient. As both the protease secondary mutations and the single non nucleoside reverse transcriptase mutation map far from the catalytical sites of the enzymes, neither one is able to impair viral fitness. Overall data suggest that treated donors carrying resistant strains may be in part unable to transfer them to the recipient, and/or virus in the recipient tends to revert to wild type. These results should be taken into account in the planning of early HAART treatment of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Ex-vivo purging of circulating monocytes results in immunovirologic improvement in partially HAART responder HIV-infected patients.

AIDS pathogenesis results from a complex array of immune alterations which include, among others, changes in the pattern of cytokine production. Some monocyte-derived cytokines, like TNFalpha play a major role in HIV pathogenesis. TNFalpha transactivates HIV NF-kB thereby inducing viral replication, potentiates HIV replication in lymphomonocytes TNFalpha is one of the main factors of HIV-induced cachexia and might be involved in HAART-associated lipodystrophy. In addition, monocytes are infectable by HIV in vitro and infected monocytes can be recovered from the blood of HIV infected patients. For these reasons, we tested whether renewal of the pool of circulating monocytes by selective monocyte apheresis may improve the immune reconstitution which follows treatment with highly active anti-retrovirals (HAART). HIV-infected HAART receiving (> 1 year) patients who were either virologically non-responders (HIV-1 RNA >50,000 copies/ml) or immunologically non-responders (CD4 counts < 200) were treated with a novel monocyte apheresis device (G-1 Adacolumn). Plasma HIV viral load, proviral DNA and phenotypic and functional immunological analyses were performed. G-1 apheresis was well tolerated, not accompanied by adverse responses, and followed by clinical improvement. TNFalpha production was suppressed and CD4 T cell counts increased. In one G-1 patient with elevated HIV-1 proviral DNA a significant reduction (from 1,500 to 40 copies/10(5) cells) was observed. Neither immunologic nor virologic parameters were modified in the control patients who received HAART alone. Thus, purging of circulating monocytes by G-1 apheresis has a dramatic suppressive effect on TNFalpha production and is followed by both clinical and immunovirological improvement. G-1 apheresis should be considered in patients in whom HAART is only partially effective.

Anti-HIV Agents↗
PubMedDate not supplied

Immunologic reconstitution by interleukin-2: facts and open questions.

Interleukin-2 (IL-2), one of the most potent immunoregulatory and inflammatory cytokines, is being tested in phase III clinical trials in order to demonstrate its efficacy in combination with current antiviral agents in preventing the occurrence of opportunistic infections and death in individuals infected by the human immunodeficiency virus (HIV). In the meantime, its capacity to boost the number of CD4+ T cells in peripheral blood has been confirmed by a number of individual phase I/II trials conducted in different countries by independent investigators. In the face of this remarkable result, little is known of the effects exerted by this cytokine once administered to infected individuals in terms of its impact on different immunologic functions. The recent acquisitions on the important role played by latently infected cells in in vivo infection in reinitiating HIV replication and cytopathicity once antiviral therapy is suspended or becomes suboptimal, has shed new light on the possibility of utilizing immunologic strategies, including IL-2, for eradicating the virus from latent reservoirs. Results from a clinical trial conducted at our Institute indicate a decrease in lymphocyte-associated HIV DNA after IL-2 administration, supporting this hypothesis.

Anti-HIV Agents↗