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M Fiorilli

Publications and source records attributed to M Fiorilli.

At least 55 records · Page 3Linked to original sources
PubMed1986

Phenotypically immature IgG-bearing B cells in patients with hypogammaglobulinemia.

We investigated the prevalence of phenotypically immature IgG B cells (i.e., coexpressing surface IgG and IgM) in the peripheral blood of 12 patients with hypogammaglobulinemia and in normal individuals. Patients had ataxia-telangiectasia (N = 1), hyper-IgM combined immunodeficiency (N = 1), or common variable immunodeficiency (CVI). IgG/IgM-positive B cells were evaluated by two-color immunofluorescence using fluorescein- or rhodamine-conjugated goat antiserum; to minimize artifacts due to in vivo cytophilic binding of autologous IgG, cell-bound cytophilic Ig were eluted at pH 4 and Fc receptors were blocked by heat-aggregated rabbit IgG before fluorescent staining. All patients, except two with late-onset CVI, had markedly increased proportions of double-stained IgG B cells (56 to 100% of IgG-bearing B cells) in comparison with normal individuals (11 to 33%).

Adult↗
PubMed1986

Hypogammaglobulinemia with hyper-IgM, severe T-cell defect, and abnormal recirculation of OKT4 lymphocytes in a girl with chronic lymphadenopathy.

We describe here one 8-year-old girl with an unusual form of immunodeficiency, characterized by hypogammaglobulinemia with hyper-IgM, severe T-cell defect, and chronic lymphadenopathy. Patient's B cells failed to produce IgG or IgA in vitro following stimulation with either pokeweed mitogen or Epstein-Barr virus, suggesting an intrinsic B-cell defect. Abnormal T-cell function was demonstrated by impaired in vivo delayed type hypersensitivity, reduction of mitogen-induced proliferation and interleukin 2 production, reduction of interferon-gamma production, and marked decrease of circulating OKT4+ cells. The latter cells were found in normal proportion in the patient's lymph node tissue. This finding suggests that the decrease of OKT4+ cells in peripheral blood was due to the abnormal recirculation of these cells. The identity of this syndrome with the infantile form of the acquired immunodeficiency syndrome was apparently ruled out by the failure to demonstrate HTLV-III-related sequences in patient's lymphocytes or virus-specific serum antibodies.

Agammaglobulinemia↗
PubMed1986

Abnormalities of in vitro immunoglobulin production in apparently healthy haemophiliacs: relationship with alterations of T cell subsets and with HTLV-III seropositivity.

The pokeweed mitogen (PWM)-induced immunoglobulin (Ig) production by cultures of peripheral blood mononuclear cells (PBMC) was reduced in healthy haemophiliacs treated with commercial factor VIII (or IX) concentrate, whereas the spontaneous IgG synthesis in vitro was enhanced. PWM-induced Ig production was lower in those who had received greater amounts of concentrate, in those with inverted T4/T8 lymphocyte ratios and in those with antibody to HTLV-III. The spontaneous IgG production in vitro was higher in haemophiliacs who had received larger amounts of concentrate, in those with inverted T4/T8 ratio and in those with antibody anti-HTLV-III. However, some patients with normal T4/T8 ratio and some with HTLV-III antibody also had raised spontaneous IgG production.

Antibodies, Viral↗
PubMed1985

Activity of azelaic acid on cultures of lymphoma- and leukemia-derived cell lines, normal resting and stimulated lymphocytes and 3T3 fibroblasts.

Azelaic acid (C9- -dicarboxylic acid) is a competitive inhibitor of tyrosinase and some oxidoreductase in vitro, and in vivo has a beneficial effect on lentigo maligna and malignant melanoma. A definite cytotoxic effect in cultures of malignant melanocytes was also reported. In order to establish if the cytotoxic effect of the diacid is exerted equally in the absence of tyrosinase, lymphoma- and leukemia-derived cell lines were cultured for 72 hr with 10(-3) M, 10(-2) M and 5 X 10(-2) M C9 disodium salt. Normal resting lymphocytes, lymphocytes activated by phytohemoagglutinin, and mouse Balb/c 3T3 fibroblasts were also tested to study a possible effect of azelaic acid on DNA synthesis and cell duplication. At 10(-3) M C9 had no effect on the viability of all the cells tested; at 10(-2) M and 5 X 10(-2) M, C9 2Na had a 50-80% cytotoxic effect on lymphoma- and leukemia-derived cell lines, while at the same concentrations it was not toxic to normal lymphocytes, either resting or stimulated, or to 3T3 fibroblasts. The experiments on cellular incorporation of (1-9 14C) azelaic acid showed that the radiocarbon uptake was two to three times higher for lymphoma- and leukemia-derived cell lines than for lymphocytes, either resting or stimulated, or 3T3 fibroblasts. Biochemical analysis revealed that the diacid underwent beta-oxidation in all the cell cultures. Fractionated centrifugations of 3T3 fibroblasts cultured in the presence of radiolabelled azelaic acid (2 X 10(-4) M) plus cold C9 2Na (10(-2) M), showed that the radioactivity was mainly concentrated in the cytoplasm. The results, being similar to those obtained by adding azelaic acid to cultures of melanoma cells, suggest that the cytotoxic effect of azelaic acid may be due to interference with mitochondrial oxido-reductase enzymes, rather than with tyrosinase. The difference in reaction between lymphoma- and leukemia-derived cell lines and normal or stimulated lymphocytes, and 3T3 fibroblasts, could be explained on the basis of a different degree of permeability of the cell membrane, and/or to a possible different sensitivity of reaction of mitochondrial functions. A similar argument could be used to explain the absence of an effect of dicarboxylic acids upon normal as compared with hyperactive or malignant melanocytes in vivo.

Animals↗
PubMed1985

Variant of ataxia-telangiectasia with low-level radiosensitivity.

In the present study we examined cells from several patients clinically diagnosed as having ataxia-telangiectasia (AT), for the capacity of their cells to inhibit DNA synthesis following exposure to gamma irradiation, and for the rate of spontaneous or bleomycin-induced chromosomal aberrations. Cells from two patients showed normal inhibition of DNA synthesis and levels of induced chromosomal aberrations intermediate between normal and AT cells. These two patients had only minimal immunologic impairment. These findings appear to define one distinct subset of AT.

Adolescent↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

A placebo-controlled trial of thymic hormone treatment of recurrent herpes simplex labialis infection in immunodeficient host: results after a 1-year follow-up.

Twenty-one immunodeficient patients with recurrent herpes simplex labialis (HSL) were randomly allocated to either the saline or the bovine thymus extract Thymostimulin (TS) group and treated for a period of 6 months. A total of 17 recurrences with a mean severity index of 266.2 +/- 192 in the TS-treated group versus a total of 62 recurrences in the placebo group (score 458.8 +/- 299.6) were observed after 12 months of follow-up. A significant increase of total WBC (P less than 0.05 versus control group), lymphocyte count, and T-cell number (P less than 0.001) were detected in the TS group after 6 months as well as after 12 months. In vitro lymphoproliferative responses to herpes simplex virus antigen and natural killer cell activity were also significantly higher (P less than 0.05) in the TS group, whereas no significant difference in antibody titers to herpes simplex could be detected between the two groups. TS may be potentially useful in preventing viral reactivation in immunocompromised hosts by potentiating cell-mediated immune responses. Further studies evaluating TS for prophylaxis of infection in patients at risk should be considered.

Adolescent↗
PubMed1983

Thymopoietin pentapeptide treatment of primary immunodeficiencies.

26 patients with primary immunodeficiencies (3 infants with severe combined immunodeficiency [SCID] 3 with DiGeorge syndrome, 6 with T-cell defect or SCID with B cells, 4 with common variable hypogammaglobulinaemia and associated T-cell defect, 5 with ataxia-telangiectasia, and 5 with hyper-IgE syndrome) were treated with thymopoietin pentapeptide (TP-5) at a dose of 0 . 5 mg/kg daily for 2 weeks and then 3 times a week at 0 . 5 mg/kg for 10 weeks, 3 patients with DiGeorge syndrome and 3 with primary T-cell defect demonstrated pronounced clinical and immunological improvement during treatment. None of the patients with SCID and 3 of 6 patients with SCID with B cells or primary T-cell defect showed any clinical or immunological changes during therapy. In 5 patients with ataxia-telangiectasia clinical manifestations and immunological tests were unchanged by TP-5. Abnormality of T cells in cases of hyper-IgE syndrome was not corrected by TP-5 treatment.

Adolescent↗
PubMed1983

Heterogeneity of immunological abnormalities in ataxia-telangiectasia.

Peripheral blood mononuclear cells from five patients with ataxia-telangiectasia were evaluated for their reactivity with a panel of monoclonal antibodies directed against T-cell subsets and for their in vitro functions in a pokeweed mitogen-induced immunoglobulin biosynthesis assay. All the patients had significantly reduced proportions of cells identified by monoclonal antibodies to subpopulations of T lymphocytes with helper activity (OKT4 and 5/9) and produced low amounts or no IgA and IgG in vitro. Immunoglobulin biosynthesis was increased by the addition of normal x-irradiated peripheral blood mononuclear cells in one of three patients, suggesting a helper T-cell deficiency in this patient and intrinsic B-cell defects in the other two. Two patients had increased proportions of cells identified by a monoclonal antibody to a subpopulation of T lymphocytes which includes suppressor T cells (OKT8), and their cells were able to suppress immunoglobulin biosynthesis by peripheral blood mononuclear cells from normal donors. These findings indicate heterogeneous disturbances of immunoregulatory mechanisms in ataxia-telangiectasia.

Adolescent↗
PubMed1983

In vitro enhancement of bone marrow natural killer cells after incubation with thymopoietin32-36 (TP-5).

Natural killer (NK) activity and interferon (IFN) production of spleen and bone-marrow lymphocytes were investigated in 8 to 10-wk-old C3HeB/FeJ/Cne mice, before and after in vitro exposure to the synthetic pentapeptide corresponding to positions 32-36 of the sequence of thymopoietin (TP-5). NK activity was studied against the 51Cr-radiolabelled Moloney virus-induced lymphoid cell line YAC 1, while IFN titres were determined by the inhibition of cytopathology of vesicular stomatitis virus on L929 cells, scored for CPE after 24 h from viral infection. A part of the lymphocytes from the spleen and bone marrow were incubated with different preselected doses (0.1, 1 and 10 micrograms/ml) of TP-5 for 1 h at 37 degrees C, and a part were left unincubated. At the end of the incubation time they were tested, without being washed, for NK activity and IFN production. TP-5 was able to significantly enhance (P less than 0.001 chi 2 test with Yate's correction) bone-marrow NK activity at a dose of 1 microgram/ml, while it was ineffective on spleen cells. A decrease of NK activity, seemingly due to a toxic effect, was observed both in bone-marrow and spleen lymphocytes, after incubation with a dose of 10 micrograms/ml. IFN production was not enhanced after exposure to TP-5. In all, our experiments suggest that TP-5 may enhance bone-marrow NK cells, perhaps by permitting the maturation of their precursors, as already known for T-cell-mediated cytotoxicity. Its effect is independent on IFN production and might be able to induce the rearrangement of certain surface specific receptors.

Animals↗
PubMed1983

Defect of T helper lymphocytes, as identified by the 5/9 monoclonal antibody, in patients with common variable hypogammaglobulinaemia.

Peripheral blood lymphocytes from 17 patients with common variable hypogammaglobulinaemia (CVH) were tested for reactivity with the 5/9 monoclonal antibody which reacts with about 15% of normal T-PBL in which all helper activity is found. In PBL from CVH patients, the proportions of OKT4 and OKT8 positive cells were also determined. Five patients had normal percentages of 5/9 cells and a normal OKT4/OKT8 ratio. Twelve patients had significantly decreased (or absent) 5/9 lymphocytes. Among these, five had decreased 5/9 cells and a normal OKT4/OKT8 ratio and seven had decreased 5/9 cells and an inversion of the OKT4/OKT8 ratio. The deficiency of the helper phenotype T cell subpopulation identified by the 5/9 monoclonal antibody in many patients with CVH may be relevant in the pathogenesis of this disease.

Adolescent↗
PubMed1983

In vitro interaction with antigen suppresses the differentiation of chronic lymphocytic leukemia cells secreting monoclonal anti-sheep red blood cell antibody.

Leukemic B cells from a patient with chronic lymphocytic leukemia had membrane-bound IgM that reacted against a sheep red blood cell (SRBC) antigen. A small proportion of these cells was able to differentiate into anti-SRBC hemolytic plaque-forming cells when cultured in vitro in the absence of polyclonal stimulators. The addition of pokeweed mitogen or of x-irradiated allogeneic T cells further enhanced their differentiation. The addition of antigen (SRBC) to unstimulated cultures of the patient's mononuclear cells suppressed the anti-SRBC antibody production. Marked suppression was induced by concentrations of SRBC that were found to stimulate anti-SRBC antibody production optimally by normal peripheral blood mononuclear cells. Two lines of evidence suggest this inhibition was not due to the activation of suppressor cells. First, depletion of T cells with the phenotype reported to be associated with suppressor cells, namely OKT8+ cells, did not prevent suppression. Secondly, the patient's mononuclear cells pulsed with SRBC did not suppress anti-SRBC antibody production by untreated autologous cells in co-culture. These findings suggest that leukemic cells were inhibited by the direct interaction with antigen. This suppression might be the result of intrinsic abnormalities of leukemic B cells. Alternatively, it could be the reflection of a tolerogenic response to antigen stimulation displayed by the patient's leukemic cells, which have a surface phenotype, IgM+D-, that is comparable to that of immature normal B cells.

Aged↗
PubMed1983

A placebo-controlled trial of thymic hormone treatment of recurrent herpes simplex labialis infection in immunodeficient hosts.

Twenty-one immunodeficient patients with recurrent herpes simplex labialis (HSL) were randomly allocated to either saline or the bovine thymus extract thymostimulin (TS) and treated for a period of 6 months. An impressive reduction in both number and severity of the recurrences of the infection was observed in TS-treated patients during the trial and for up to 3 months afterward. A significant increase in total WBC, lymphocyte count, and T cells was detected in the TS group after 6 months. In vitro lymphoproliferative responses to herpes simplex virus antigen and natural killer cell activity were also significantly higher in the TS group, whereas no significant difference in antibody titers to herpes simplex could be detected between the two groups. TS can therefore help prevent viral reactivation in immunocompromised hosts by potentiating cell-mediated immune responses and should be considered for use in prophylaxis of infection in patients at risk and also in apparently normal subjects with recurrent HSL.

Adolescent↗
PubMed1982

Nonfebrile seizures after febrile convulsions: possible role of chronic cytomegalovirus infection.

Twelve hundred children with convulsions when feverish were studied during a period of five years. Among them 52 subjects (4.33%) developed nonfebrile seizures after a period of eight months to five years from the first febrile convulsion (group A). Twenty-three children had neither afebrile seizures nor EEG abnormalities during the period of observation (group B). The two groups were comparable for age of the first febrile convulsion onset, sex, and socioeconomic status. None had risk factors for subsequent epilepsy or clinical signs of congenital cytomegalovirus infection. The isolation rate of CMV from urine was 53.84% in patients of group A, 26.09% in children of group B, and 26.83% in healthy control children. Twelve CMV-positive children from group A were followed for one to more than three years. In five of seven children with persisting EEG abnormalities, cytomegaloviruria was still present 13 to 41 months after the first isolation, whereas none of five patients with normal electroencephalograms had viruria after a comparable period. We found that CMV-positive children generally lacked cell-mediated immunity to the virus, whereas CMV-negative patients had positive reactions. Our data suggest a correlation between persistence of neurologic abnormalities and CMV excretion in children with nonfebrile seizures and CMV infection.

Child, Preschool↗