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Biomedical subjects

F Aiuti

Publications and source records attributed to F Aiuti.

At least 163 records · Page 9Linked to original sources

[In vitro effects of lysozyme on some specific and non-specific functions of the immune system].

In this paper the in vitro effects of lysozyme on several immunological function was investigated. Henn-egg-white lysozyme (at concentrations ranging between 1 and 10 micrograms/ml) has shown an inhibitory action on mitogen-induced lymphoblastigenesis and autologus mixed lymphocyte reaction. On the other hand, NK activity against K 562 cell line resulted to be increased in the presence of lysozyme. In addition lysozyme has shown to behave as chemokinetic factor increasing PMN random locomotion and inhibiting PMN response only towards complement derived chemotaxins, whereas there was no effect against other chemotactic factors. Then, in addition to its enzymatic activity, a role of lysozyme as modulator of the inflammatory response may be proposed.

Adult↗

Evidence for disregulation in the control of Epstein-Barr virus latency in patients with AIDS-related complex.

Patients affected by AIDS-related complex (ARC) show several immunological abnormalities which may lead to a disregulation of immunosurveillance against viral latent infections. In this paper evidence for Epstein-Barr virus (EBV) reactivation in seven out of eight affected by persistent generalized lymphadenopathy is given. These patients showed either elevated levels of circulating EBNA-positive transformed cells or depressed EBV-specific T cell cytotoxicity, as assessed by the regression assay, or both. A direct involvement of EBV in the pathogenesis of ARC is thus suggested. Natural killer cell activity was found decreased, correlating to the evidence of circulating EBV-infected cells and of impaired EBV-specific immune control. These data provide evidence that, when specific immune mechanisms lose control on ubiquitous latent viruses, the risk for reactivation becomes higher. In the case of EBV, direct evidence of this event is provided by the emergence in the peripheral blood of clones of infected cells with unlimited growth potential.

AIDS-Related Complex↗

Immunological responses of patients with recurrent herpes genitalis.

Immunological responses of patients with recurrent herpes genitalis (RHG) were assayed in comparison to those of patients affected by recurrent herpes labialis (RHL) and to those of normal seropositive and seronegative controls. Total T cells were normal while a significant (p less than 0.001) reduction of cells with helper phenotype was found only in people with RHG, who were also lacking specific cell-mediated immunity (CMI) to herpes simplex virus (HSV) antigen. HSV-type 2 was demonstrated in their active lesions. Number of human NK-1 positive (HNK-1 +) cells was increased in RHG showing an inverse correlation with depressed natural killer (NK) activity. These abnormalities were found irrespective or not if tests were carried out during the active phase of the disease or during quiescence and were confirmed during the 2-year follow-up period to which patients were submitted. Similar abnormalities were found in RHL only during the active phase and reversed to normal during quiescence. Our data indicate the presence of specific cellular and NK unresponsiveness in subjects with severe and long-lasting herpes genitalis.

Adolescent↗

Persistent generalized lymphadenopathy in drug addicts: immunological studies.

The persistent generalized lymphadenopathy (PGL) in drug addicts displays the same immunological abnormalities previously found in homosexual and haemophiliac men with PGL: impaired in vivo and in vitro T cell functions, inverted T4/T8 ratio in blood and B cell abnormalities. The peripheral blood B-lymphocytes, in fact, show a reduced in vitro immunoglobulin synthesis after pokeweed mitogen and Staphylococcus aureus activation, with an increased spontaneous IgG secretion. In the lymph node biopsies, the immuno-histological studies reveal an infiltration of OKT8 positive cells in the germinal centers, a depletion of OKT4 positive lymphocytes slighter than in the blood and an explosive follicular hyperplasia with a striking destruction of the dendritic reticulum cell framework. This latter finding, together with the high levels of serum IgG and the presence of preactivated B cells in the blood, seems to be consistent with the presence of an in vivo polyclonal B cell activation. A high incidence of anti-HTLV III antibodies was also found in the PGL drug addicts. The significance of these findings is discussed in this report.

Adult↗

T-helper phenotype chronic lymphocytic leukaemia and "adult T-cell leukaemia" in Italy. Endemic HTLV-I-related T-cell leukaemias in southern Europe.

Sixteen Italian patients with chronic T-cell lymphocytic leukaemia (T-CLL) and leukaemic T-helper phenotype lymphocytes (Thp-CLL) were investigated for serum antibodies against human T-cell leukaemia virus I (HTLV-I) or its integrated DNA sequences. Common features of this series of patients were an aggressive clinical course with poor response to treatment, high white blood-cell count, bone-marrow infiltration, splenomegaly, and chromosome abnormalities. Three patients had skin infiltration and one had hypercalcaemia. Immunological analysis showed a Thp (OKT4+) in all cases, and a heterogeneity, within the OKT4 population, of phenotypes and functional activities. Three patients had either HTLV-I integrated DNA sequences or anti-HTLV-I serum antibodies, or both. These patients had not received any blood transfusions, denied intimate contact with foreigners, and had always lived in small towns of central or southern Italy. Clinical and immunological findings in this series of patients suggest that both HTLV-I related and unrelated cases of Thp-CLL should be regarded as one disease arising from the same subpopulation of mature T-lymphocytes.

Adult↗

IgM and IgG antibodies to human T cell lymphotropic retrovirus (HTLV-III) in lymphadenopathy syndrome and subjects at risk for AIDS in Italy.

A study was performed to assess the prevalence of specific antibodies to human T cell lymphotropic retrovirus (HTLV-III) in patients with lymphadenopathy syndrome, patients with the acquired immune deficiency syndrome (AIDS), and those at risk of AIDS. Serum samples were obtained from these groups and from healthy controls in selected cities in Italy, and antibodies to HTLV-III were measured by immunofluorescence assay and, in a few patients, by Western blotting. In addition, IgM antibody values were measured in 82 of those positive for HTLV-III. Altogether, 235 out of 320 patients with lymphadenopathy syndrome had antibodies to HTLV-III, the proportions being highest in haemophiliacs, homosexuals, and drug addicts from Rome; 11 out of 12 patients with AIDS had antibodies; 78 out of 439 subjects at risk for AIDS had antibodies; and six out of 30 patients with lymphadenopathy syndrome and positive for HTLV-III antibodies and nine of 52 patients at risk of AIDS had a detectable titre of IgM. HTLV-III is widespread in groups at risk of AIDS in Italy, and antibodies to HTLV-III are highly prevalent in patients with lymphadenopathy syndrome. A higher proportion of drug abusers were positive for antibodies than in previous studies. HTLV-III "infection" would appear to be spread mainly in compromised hosts, as none of the controls were positive for antibodies.

Acquired Immunodeficiency Syndrome↗

Epidemiological aspects of HTLV-III infection in Italy.

An epidemiological survey on the presence of serum antibodies to human T lymphotropic retrovirus III (HTLV-III) is reported. The study was carried out on people living in large as well as small cities in different Italian regions. Serum samples of 21 patients with AIDS, 402 with ARCS, and 920 from individuals at risk for these diseases were analyzed. The percentage of positive sera varied from 81% in AIDS, to 100% -33.3% in ARC according to the different geographical areas and/or the various categories of people with ARC. The percentage of positive sera in individuals at risk for AIDS or ARC varied from 11.9% in homosexuals, to 21% in drug abusers and 23.1% in haemophiliacs. No positive sera were observed among 660 normal individuals, relatives of patients with AIDS or ARC and in 114 patients suffering from immunological or infectious disease and among people at risk living in small cities. Sera were also negative in patients with classical Kaposi's sarcoma or T-cell chronic lymphocytic leukemia. Since none of the 660 unselected normal adults were positive while a significant percentage of people at risk for AIDS showed antibodies to HTLV-III, we may presume that this infection is prevalent in the Italian categories in which AIDS and ARC are most likely to develop.

AIDS-Related Complex↗

Immunological and virological investigation in patients with lymphoadenopathy syndrome and in a population at risk for acquired immunodeficiency syndrome (AIDS), with particular focus on the detection of antibodies to human T-lymphotropic retroviruses (HTLV III).

Thirteen patients affected with unexplained lymphoadenopathy, fever, weight loss, and diarrhea (lymphoadenopathy syndrome; LAS) were evaluated for the possible appearance of acquired immunodeficiency syndrome (AIDS) and for immunological and virological characterization. The patients belonged to categories of individuals at risk for AIDS and were homosexual and/or drug abusers or hemophiliacs. Lymph node biopsy showed the histological picture of a follicular hyperplasia. The study of cell-mediated immunity (CMI), humoral immune response, and natural killer (NK) activity demonstrated a significant decrease in T cells with the helper/inducer phenotype (OKT4+ cells) and a relatively increased number of lymphocytes with the suppressor/cytotoxic phenotype (OKT8+ cells). NK activity was significantly lower than in normal controls. The in vitro response to polyclonal activators (phytohemagglutinin; PHA) and the cutaneous responsiveness to recall skin tests were impaired, whereas immunoglobulin production was increased, mainly in the IgG fraction. Virological studies showed high serum antibody titers to cytomegalovirus (CMV) but a lack of specific CMI as assayed by the leukocyte migration inhibition test (LMIT). CMV was also isolated from the urine specimen of one patient. The antibody pattern to Epstein-Barr virus (EBV) showed the uncommon contemporary presence of both Epstein-Barr nuclear antigen (EBNA) and early antigen (EA) antibodies. Antibodies to human T-lymphotropic retroviruses (HTLV III) were positive in 10 patients and the virus was isolated in 3 of them. In some patients the presence of serum antibodies to HTLV III was not associated with an impairment of the immune function. A group of individuals at risk for AIDS without LAS was also evaluated for the presence of HTLV III antibodies; the percentage of positive sera was 11.4.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Thymopentin treatment of selective IgA deficiency.

Thymic hormones have been shown to modulate immunoglobulin production in a number of experiments and it is generally agreed that this action is mediated by modulation of helper and/or suppressor T cell activities. The possibility of upregulating the immunoglobulins is of particular relevance in patients with hypogammaglobulinemias and this paper reports on the results of thymopentin treatment in 9 patients with selective IgA deficiency. Two out of 4 patients responded positively in an open-label trial; in one the serum IgA values remained stable up to 8 weeks after discontinuation of treatment whereas there was a rapid fall in the other. Both responders had consistently normal T4/T8 ratios during the treatment, whereas the nonresponders revealed high ratios with large fluctuations of the T4/T8 ratio. In a subsequent (still ongoing) double-blind trial in 5 patients (3 thymopentin, 2 placebo) no significant change of serum or secretory IgA levels has been observed. Taken together, the data suggest that the tested dose regimen of thymopentin (i.e. daily i.m. injections of 1 mg/kg for 2 weeks, then same dose 3 time weekly for 10 weeks) may only work in a subset of patients with selective IgA deficiency. In the present study we did not attempt to distinguish to which of the three known subgroups the 9 patients belonged, nor did we try alternative dose regimens of thymopentin.

Adjuvants, Immunologic↗

Impaired gamma interferon production by cells from patients with lymphoproliferative disorders of mature T and NK cells.

We investigated interferon (IFN) production by peripheral blood mononuclear cells from four patients with chronic OKT4 T-lymphocytic leukaemia and three patients with abnormal expansions of granular lymphocytes. No spontaneous production of IFN-gamma was found in supernatants of cultures from both patients and normal controls. However, whereas the enzyme galactose oxidase or staphylococcal enterotoxin B was able to induce IFN-gamma production by normal cells, no production could be obtained in the cells under study. The possibility that this lack of production might have been attributed to an excess of N-acetylneuraminic acid masking galactose residues or to a defect of monocyte accessory cells was ruled out either by pre-treating the cells with neuraminidase or by adding normal adherent cells to the cultures, both of which resulted in a lack of production. On the contrary, the calcium ionophore A23187 (considered to act as a second specific step, following oxidation of galactose residues, toward genetic derepression of IFN-gamma) induced considerable IFN-gamma production in all the three tested patients. It can be concluded that, although in rare cases, as previously reported by other authors, cells from patients with T or NK lymphoproliferative disorders may spontaneously produce IFN-gamma, this is not a general mechanism that underlies the disease. In fact, in all our cases a defect of IFN-gamma production was found. This defect seems due to an alteration at the membrane level of the galactose-containing glycoproteins and can be restored by induction with a calcium ionophore.

Adult↗

Isotypic analysis of antibody response to a food antigen in inflammatory bowel disease.

We studied the class-specific antibody response to the cow's milk antigen beta-lactoglobulin (beta-LG) in sera from patients with ulcerative colitis and Crohn's disease. IgG and IgM to beta-LG were significantly higher in patients when compared to healthy non-atopic controls, whereas IgA values were similar, and specific IgE absent in all groups. No correlation between IgG- or IgM-containing immune complexes was found with the corresponding isotype of antibody to beta-LG; however, IgM complexes correlated with serum total IgM in ulcerative colitis. In these patients, IgG antibodies were higher in active cases, whereas IgM increased in patients without signs of disease activity. Antibody titers did not correlate with disease duration or administration of antiinflammatory drugs. This pattern of anti-beta-LG reactivity suggests that the presence of intestinal lesions may be revealed by the selective increase of some antibody isotypes to orally administered antigens. Enhanced mucosal permeability may be studied by this type of serological analysis.

Adrenal Cortex Hormones↗

Natural killer cells in intravenous drug abusers with lymphadenopathy syndrome.

We have investigated 25 intravenous drug abusers with the clinical and laboratory features of lymphadenopathy syndrome (LAS) and 10 AIDS patients for the expression of NK activity. LAS and AIDS patients had low NK cytotoxicity compared to normal donors. The defective NK cytotoxicity was analysed in the eight LAS subjects with most marked depression. NK effectors were identified by morphology (large granular lymphocytes, LGL) and monoclonal antibody-defined surface markers (B73.1, N901, HNK1). LAS patients had normal percentages of LGL and B73.1+ and N901+ cells. with the exception of two subjects with very low frequency of B73.1+ and N901+ cells. The percentage of HNK1+ cells was increased in LAS, probably because of the reactivity of this reagent with a subset of conventional OKT8+ cells, relatively augmented in LAS subjects. Depletion of monocytes did not enhance NK activity consistently. LAS patients had a normal frequency of cells capable of binding K562. In-vitro exposure to interferon beta (natural) or gamma (recombinant) augmented the defective NK activity of LAS subjects. Thus, patients with LAS have defective NK activity that cannot be accounted for by a low frequency of the relevant effector cells or by monocytic suppressors. These observations suggest a functional defect of NK cells at one or more of the post-binding steps required for the completion of killing.

Acquired Immunodeficiency Syndrome↗

Impairment of cellular immunity and OKT4 lymphocytes in symptom-free hemophiliacs with antibodies to human T leukemia virus III (HTLV III).

Antibodies against the human T-leukemia virus III (HTLV III) were detected by immunofluorescence in the sera of 17 out of 48 hemophiliacs (35.4%) without AIDS or ARC, frozen in 1983-84. Immunological data collected at that time were re-evaluated by separating HTLV III-positive and negative subjects. HTLV III positive patients had significantly reduced OKT4 cells (both in %: 26.1 +/- 10.9 vs 41.2 +/- 15.2; P less than 0.01; and in absolute numbers: 469 +/- 291 vs 1,038 +/- 541; P less than 0.005) and OKT3 lymphocytes (in absolute numbers: 1,234 +/- 550 vs 2,050 +/- 1,067; P less than 0.01). Subpopulations identified by other monoclonal reagents (OKT8, Leu 7, OKM1, anti-Tac) showed no significant differences between the two groups. Patients subsequently found to be seropositive had significantly more frequent anergy to skin tests to recall antigens and often an impairment of in vitro response to phytohemagglutinin A. Despite these relevant defects of some tests of cell-mediated immunity, in HTLV III-positive cases no clinical progression toward AIDS-related complex was observed in a mean period of follow-up of more than 1.5 years.

Acquired Immunodeficiency Syndrome↗

Cellular and molecular studies on ataxia-telangiectasia lymphoblastoid cell lines.

We have examined several AT-related lesions in lymphoblastoid cell lines (LCLs) derived from AT patients. Diminished sensitivity to gamma-irradiation was found in six of seven AT-LCLs. A seventh line, from a patient with apparently normal T-cell immunity, responded normally following radiation. Constitutive proteins from exponentially growing AT-LCLs were assessed by SDS-PAGE analysis and did not differ significantly from normals. IgM synthesis was also normal except for one AT-LCL that contained native IgM molecules of different sizes, corresponding to the presence of pentamers and oligomers. Analysis under reducing conditions showed normal-sized secretory mu-chains. Finally, we examined mRNAs corresponding to two oncogenes, c-myc and c-myb, in AT and normal LCLs and found marked overproduction of c-myc in one AT-LCL (ie,, ATL6). The latter findings suggest that AT cells might be prone to aberrantly express cellular oncogenes as a result of chromosomal instability and consequent transposition of oncogenes.

Ataxia Telangiectasia↗

Thymic factor therapy for herpetic keratitis.

Thirty patients with herpetic keratitis were allocated to a double-blind trial with either local treatment plus placebo (control group) or local treatment plus thymostimulin (TS group). The follow-up at 24 months demonstrated a significant reduction of recurrence rate among patients receiving thymostimulin, along with a significant increase of sheep rosette-forming cells (E rosette). Furthermore, among patients with superficial keratitis, thymostimulin treatment resulted in a significantly quicker corneal re-epithelization than placebo. Thymostimulin seems to be a safe and helpful drug in the management of herpetic keratitis.

Adolescent↗