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Biomedical subjects

E Maggi

Publications and source records attributed to E Maggi.

At least 127 records · Page 7Linked to original sources

Management of primary megaureter in infancy.

The natural history of primary megaureter was evaluated in 26 infants (20 boys, 6 girls) with 38 nonrefluxing primary megaureters. Prenatal ultrasound diagnosis had been made in 21 infants. In all patients, primary megaureter was associated with pelvicaliceal dilatation. Two patients with urinary tract infection and two with agenesis of the contralateral kidney underwent surgical treatment. Asymptomatic infants with good differential renal function on DTPA scanning were managed conservatively regardless of their postfurosemide drainage curve. One of these infants later developed a slight deterioration in function and was submitted to surgery. One patient was lost to follow-up. Twenty patients, after a period ranging from 4 months to 8 years, showed partial or complete regression of ureteral dilatation with stable good renal function. In conclusion, many asymptomatic primary megaureters in infancy improve spontaneously and do not require surgical treatment.

Child↗

Low-density lipoprotein oxidation in essential hypertension.

OBJECTIVES: To investigate the occurrence of enhanced low-density lipoprotein (LDL) oxidation as an additional factor promoting atherosclerosis progression in hypertensive patients. DESIGN: The oxidation of plasma LDL was investigated in a group of untreated patients with mild-to-moderate essential hypertension without clinically evident target organ damage and in a group of control subjects. METHODS: LDL oxidation was evaluated as both the susceptibility to oxidation in vitro and the presence of plasma anti-oxidized LDL antibodies (as an index for oxidation in vivo). RESULTS: LDL from hypertensive subjects exhibited enhanced susceptibility to oxidation in vitro as revealed by early and accelerated generation of conjugated dienes after exposure to CuSO4. Vitamin E concentration in LDL from hypertensive subjects was slightly but significantly decreased and its efficiency in protecting LDL from oxidation was impaired. Furthermore, a higher plasma anti-oxidized LDL titre was found in hypertensive patients. Subclass analysis revealed that the contemporary presence of hypercholesterolaemia did not significantly modify either the increased susceptibility of LDL to oxidation or the presence of plasma anti-oxidized LDL antibodies detected in hypertensive patients. Moreover, no correlation was found between LDL oxidation parameters and blood pressure values. CONCLUSIONS: LDL from hypertensive patients is more susceptible to oxidation in vitro and is more promptly oxidized in vivo. These findings suggest a possible participation of LDL oxidation in promoting and accelerating the atherosclerosis that often develops in hypertensive patients.

Adult↗

Specificity of autoantibodies against oxidized LDL as an additional marker for atherosclerotic risk.

BACKGROUND: LDL oxidation is a crucial step in the development and progression of atherosclerotic lesions. The detection of an increase in the anti-oxidized LDL antibody titre may thus represent a biological marker of enhanced LDL oxidation in vivo. METHODS: The occurrence of anti-oxidized LDL autoantibodies was investigated in control patients, in patients with atherosclerotic coronary artery disease, in those without clinically relevant signs of atherosclerosis, but considered at risk, and in patients with chronic alcohol-related liver disease. RESULTS: Anti-oxidized LDL autoantibodies were present in the plasma of the majority of patients with overt coronary atherosclerosis. An increased antibody titre can also be detected well before the onset of clinically relevant signs of the atherosclerotic disease in patients classically considered at risk, indicating the occurrence of in-vivo LDL oxidation during atherosclerosis development. The specificity of molecular targets (LDL) for oxidative modifications is supported by the demonstration that anti-oxidized LDL autoantibodies are absent in the plasma of alcoholic patients who exhibit a marked increase in biological markers of oxidative stress but do not classically develop atherosclerosis. CONCLUSION: These data demonstrate that the occurrence of anti-oxidized LDL autoantibodies could be specifically related to the promotion and progression of atherosclerosis and is not a simple epiphenomenon of any oxidative process occurring in vivo.

Adult↗

Aeroallergen sensitization can occur during fetal life.

Umbilical cord blood lymphocytes showed consistent proliferation in response to Dermatophagoides group I (Der p I) and occasionally even to Lolium group I (Lol p I) allergen. These data suggest sensitization in utero of T cells due to inhalation of these allergens by the mother during pregnancy.

Aerosols↗

Preventive effects of beclomethasone on histamine-induced changes in breathing pattern in asthma.

Bronchial mucosa inflammation is a hallmark of asthma. Epithelial damage due to inflammatory process may contribute to induce a pattern of rapid and shallow breathing (RSB). Probably due to its effects on inflammatory process, beclomethasone dipropionate (BDP) decreases bronchial hypersensitivity (BH), as assessed in terms of histamine concentration causing a 20 percent FEV1 decrease from saline solution (PC20FEV1); however, no data are available on the effect of BDP on RSB. We studied 32 asymptomatic asthmatic subjects with a severe to moderate levels of BH (PC20FEV1 0.01 to 1.7 mg/ml). After they were randomly assigned to one month of either BDP (2 mg daily, 17 patients) or placebo (15 patients), they inhaled progressively doubling concentrations of histamine phosphate by tidal breathing method. With histamine in seven BDP-treated and in five placebo-treated patients, decrease in FEV1 > or = 20 percent from saline solution was paralleled by a significant decrease in tidal volume (VT), inspiratory time (Ti), and expiratory time (Te), and increase in respiratory frequency (RF). In the remaining patients, histamine failed to change the breathing pattern. In the seven RSB patients, BDP resulted in a smaller VT decrease (p < 0.02) and a smaller RF increase (p < 0.02) with histamine. The five RSB placebo-treated patients were then given one month BDP (2 mg daily): inhaled BDP, but not placebo, resulted both in a significant increase in PC20FEV1 and modulation in histamine-induced changes in breathing pattern. We conclude that high doses of BDP seem to be able to modulate histamine-induced RSB, an effect that might be linked to reversal of airway inflammation.

Adolescent↗

Low-density lipoprotein oxidation and antioxidized LDL antibodies in peritoneal dialysis patients.

Due to the potential atherogenic effects of oxidized low-density lipoproteins (LDLs), LDL oxidation was studied in a group of uremic patients on chronic peritoneal dialysis. The results were compared with those obtained in a group of 70 controls, 10 uremic patients on predialytic conservative therapy, and 11 patients on repetitive hemodialysis. LDL oxidation was evaluated in all subjects as the susceptibility to in vitro oxidation (monitoring the resistance to Cu(2+)-induced formation of conjugated dienes, lag-phase minutes) and the presence of plasma antioxidized LDL antibodies, expressed as the ratio anti-ox-LDL/antinative LDL antibodies. Vitamin E (main antioxidant agent) content in LDLs was also measured and the lipid profile studied. No significant changes in vitamin E concentration were found, although LDLs from uremic patients appeared more susceptible to in vitro and in vivo oxidation (as demonstrated by an earlier production of conjugated dienes and by the presence of a higher antibody ratio), as compared to control subjects. Analysis of the different groups of uremic patients revealed that peritoneal dialysis, not hemodialysis, significantly ameliorated the oxidation markers. However, prolonged treatment with peritoneal dialysis caused a decrease in vitamin E concentration in LDLs and increased their susceptibility to oxidation.

Antibodies↗

Prenatal diagnosis of deletion 11q23-->qter. Report of two unrelated cases.

Two cases of de novo deletion of the region distal to 11q23 were detected at cordocentesis, following sonographic evidence of malformations. Consistent findings in both fetuses were an abnormal amount of amniotic fluid, growth retardation, heart and renal defects. At delivery, the characteristic facial dysmorphisms of del(11q23) syndrome were also detected, including trigonocephaly, hypertelorism, abnormal slant of palpebral fissures, micrognathia and abnormal ears.

Adult↗

IL-4 and IFN (alpha and gamma) exert opposite regulatory effects on the development of cytolytic potential by Th1 or Th2 human T cell clones.

The cytolytic potential of a total number of 118 CD4+ human T cell clones specific for purified protein derivative (PPD) from Mycobacterium tuberculosis, tetanus toxoid, Lolium perenne group I allergen (Lol p I), Poa pratensis group IX allergen (Poa p IX), or Toxocara canis excretory/secretory antigen(s) (TES) was assessed by both a lectin (PHA)-dependent and a MHC-restricted lytic assay and compared with their profile of cytokine secretion. The majority of clones with Th1 or Th0 cytokine profile exhibited cytolytic activity in both assays, whereas Th2 clones usually did not. There was an association between the cytolytic potential of T cell clones and their ability to produce IFN-gamma, even though IFN-gamma produced by T cell clones was not responsible for their cytolytic activity. IL-4 added in bulk culture before cloning inhibited not only the differentiation of PPD-specific T cells into Th1-like cell lines and clones, but also the development of their cytolytic potential. The depressive effect of IL-4 on the development of PPD-specific T cell lines with both Th1 cytokine profile and cytolytic potential was dependent on early addition of IL-4 in bulk cultures. In contrast, the addition in bulk culture of IFN-gamma enhanced both the cytolytic activity of PPD-specific T cell lines, as well as the proportion of PPD-specific T cell clones with cytolytic activity. The addition in bulk cultures before cloning of IFN-gamma or IFN-alpha favored the development of TES-specific and Poa p IX-specific T cells into T cell clones showing a Th0 or even a Th1, rather than a Th2, cytokine profile. Accordingly, most of TES- and Poa p IX-specific T cell clones derived from cultures containing IFN-gamma or IFN-alpha displayed strong cytolytic activity. These data indicate that the majority of human T cell clones that produce IFN-gamma, but not IL-4 (Th1-like), as well as of T cell clones that produce IFN-gamma in combination with IL-4 (Th0-like) are cytolytic. More importantly, they demonstrate that the addition of IFN (alpha and gamma) or IL-4 in bulk cultures before cloning may influence not only the cytokine profile of human CD4+ T cell clones but also their cytolytic potential.

Antigens, Helminth↗

Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Th1 and Th2 clones.

The effects exerted on the in vitro development of purified protein derivative (PPD)-specific or Dermatophagoides pteronyssinus group I (Der p I)-specific T cell lines (TCL) and T cell clones (TCC) by IL-4 or IFN-gamma addition or neutralization in human PBMC cultures were examined. PBMC from two normal individuals, which were stimulated with PPD and then cultured in IL-2 alone, developed into PPD-specific TCL and TCC able to produce IFN-gamma and IL-2 but not IL-4 and IL-5 (Th1-like). IFN-gamma or anti-IL-4 antibody addition in bulk cultures before cloning did not influence the PPD-specific TCL profile of cytokine production. In contrast, the addition of IL-4 resulted in the development of PPD-specific TCL and TCC able to produce not only IFN-gamma and IL-2 but also IL-4 and IL-5. PBMC from one atopic Der p I-sensitive patient, which were stimulated with Der p I and then cultured in IL-2 alone, developed into Der p I-specific TCL and TCC able to produce IL-5 and large amounts of IL-4 but no IFN-gamma (Th2-like). The addition in bulk cultures, before cloning, of either IFN-gamma or anti-IL-4 antibody markedly inhibited the development of Der p I-specific T cells into IL-4- and IL-5-producing TCL. Accordingly, the development into Der p I-specific Th2-like TCC was significantly reduced by the addition of IFN-gamma in bulk culture and was virtually suppressed by the presence of both IFN-gamma and anti-IL-4 antibody. These data suggest that the presence or the absence of IL-4 and IFN-gamma in bulk cultures of PBMC before cloning may have strong regulatory effects on the in vitro development of human CD4+ T cells into Th1 or Th2 clones.

Adult↗

Aberrant interleukin (IL)-4 and IL-5 production in vitro by CD4+ helper T cells from atopic subjects.

The cytokine secretion profiles of T cell lines (TCL) specific for purified protein derivative (PPD) or streptokinase (SK), contemporarily derived from nine atopic and nine nonatopic individuals, were compared. Upon stimulation with phorbol myristate acetate (PMA) plus anti-CD3 monoclonal antibody (mAb), all TCL from both atopics and nonatopics produced interleukin (IL)-2 and interferon (IFN)-gamma. The mean IL-2 production by PPD- or SK-specific TCL from both atopics and nonatopics was similar, whereas the mean IFN-gamma production by TCL derived from atopics was significantly lower. In addition, both PPD- and SK-specific TCL from atopics produced detectable amounts of IL-4 and IL-5, whereas the corresponding TCL derived from nonatopics did not. A total number of 107 and 99 PPD-specific CD4+ T cell clones (TCC) were then derived from TCL of 4 atopic and 4 nonatopic donors and assessed for their profile of cytokine production in response to stimulation with either PMA plus anti-CD3 mAb or the specific antigen. Under both these experimental conditions, virtually all PPD-specific TCC from both atopic and nonatopic individuals produced IL-2 and IFN-gamma. In contrast, the great majority of PPD-specific TCC derived from nonatopic individuals did not produce IL-4 and IL-5, whereas high proportions of PPD-specific TCC derived from atopic donors displayed the ability to produce noticeable amounts of IL-4 and IL-5 besides IL-2 and IFN-gamma. These data indicate that CD4+ T cells from atopic individuals are able to produce IL-4 and IL-5 in response to bacterial antigens, such as PPD and SK, that usually evoke responses with a restricted type-1 T helper (Th1)-like cytokine profile in nonatopic individuals. Aberrant IL-4 production by Th cells may represent one of the immune alterations responsible for enhanced IgE antibody production in atopic people.

Adult↗

Prenatal sonographic diagnosis of diastematomyelia in a diabetic woman.

Diastematomyelia is a structural anomaly which concerns primarily the spine and secondarily the nervous structures contained in it. A case of early prenatal diagnosis (20th week) by ultrasound of diastematomyelia with associated diplomyelia in a diabetic woman is reported. Radiological and pathological examination of the fetus after therapeutic abortion confirmed the diagnosis.

Abortion, Therapeutic↗

Both CD8+ and CD16+ human T cell clones can provide B cell help for immunoglobulin production.

The functional properties of two CD4+CD8-CD16-, five CD4-CD8+CD16- and three CD4-CD8-CD16+ human T cell clones were compared. All CD4- T cell clones displayed strong cytolytic activity in the lectin-dependent lytic assay against the P815 murine mastocytoma cell line, but only the CD4-CD8-CD16+ T cell clones exhibited lytic activity against the natural killer-sensitive K562 cell line. Upon activation with anti-CD3 monoclonal antibody, all T cell clones were able to support IgM and IgA synthesis in autologous B cells. Both CD4+ and CD4- T cell clones required cell-to-cell interaction with the B cells in order to exert their helper activity for immunoglobulin production. However, unlike CD4+, CD4-CD8+CD16- and CD4-CD8-CD16+ T cell clones provided helper function for immunoglobulin synthesis only when low T/B cell ratios were used in culture. At higher T/B cell ratios, there was a decline in the B cell helper activity of CD4- T cell clones that was probably related to the expression of cytolytic capacity against the antigen-presenting B cell. These data support the notion that under certain experimental conditions even cytotoxic T lymphocytes and natural killer cells may provide B cell helper function.

Adult↗

Skin-derived aeroallergen-specific T-cell clones of Th2 phenotype in patients with atopic dermatitis.

T-cell lines have been derived from aeroallergen-induced eczematous patch test sites of patients with atopic dermatitis (AD). Biopsy specimens were obtained 24 hours after allergen application to the skin, and only in vivo-activated T cells were propagated. From one patient, the T-cell lines were subcloned at 0.3 cells per well. With allergen-induced interleukin (IL) production, all clones tested (n = 13) were found to be specific for the allergen, producing IL-4 and granulocyte-macrophage-colony-stimulating factor. No IL-2 or interferon-gamma was found. The allergen-specific proliferative response of these clones, although the response was dependent on exogenous IL-2 or IL-4, also proved that all clones were allergen specific. Under optimal stimulation (aCD3 plus phorbol myristate acetate), 15% of the clones appeared to be of Th0 phenotype and 70% of Th2 phenotype. In 15% of the clones, IL-4 was produced in the absence of IL-2, IL-5, or interferon-gamma. Supernatants of all clones tested induced IgE production by B cells from normal non-atopic donors. The T-cell lines of the other patient demonstrated similar results; allergen-specific proliferation was dependent on exogenous IL-2 or IL-4 and stimulation with aCD3 plus phorbol myristate acetate demonstrated that the T cells in these lines were of the Th2 phenotype. In conclusion, our data reveal that, in AD, percutaneous sensitization to aeroallergens may occur and indicate that allergen-specific Th2 type T cells may be responsible for the high levels of (specific) IgE found in 80% of patients with AD.

Allergens↗

Infection of peripheral mononuclear blood cells by hepatitis C virus.

We investigated the infection of peripheral blood mononuclear cells (PBMNC) by hepatitis C virus (HCV) in 5 patients with HCV-related chronic hepatitis. The presence of HCV-RNA-positive and -negative strands was tested with the polymerase chain reaction (PCR) method. In all subjects, HCV-RNA was shown in PBMNC. In 3 cases, HCV-RNA was shown in the T- and B-cell populations, with viral RNA also present in the monocyte-macrophage fraction of two of these. HCV-RNA-negative stranded molecules, indicative of the viral multiplication, were significantly increased in cells maintained in cultures with PHA/PMA stimulation. The results indicate that HCV infect blood mononuclear cells, thus suggesting that this cellular tropism may play a role in HCV infection.

Adult↗

Human bone marrow non-B, non-T cells produce interleukin 4 in response to cross-linkage of Fc epsilon and Fc gamma receptors.

Human bone marrow (BM) cells lacking T- and B-cell markers expressed RNA encoding interleukin (IL) 4 and secreted detectable amounts of IL-4 in supernatants in response to Fc epsilon or Fc gamma receptor (Fc epsilon R or Fc gamma R) cross-linking. In some experiments, IL-5 RNA expression in response to Fc epsilon R cross-linkage could also be detected. In contrast, RNA transcripts for, and secretion of, IL-2, IL-6, and interferon gamma were never observed. The presence of IL-3 in the cultures was essential for IL-4 production by non-B, non-T BM cells in response to Fc gamma R cross-linking and enhanced IL-4 RNA expression in response to Fc epsilon R cross-linking. Under the same experimental conditions, BM T and B lymphocytes, as well as peripheral blood T, B, and non-B, non-T cells, did not express IL-4 RNA. Prolonged incubation of non-B, non-T cells in IgE-free medium followed by extensive washing did not inhibit IL-4 production induced by anti-IgE antibodies, suggesting that the Fc epsilon R involved in the response has the characteristics of a high-affinity receptor. The Fc epsilon R+ cells were separated from the Fc epsilon R- cells by sorting non-B, non-T BM cell suspensions with fluorescein isothiocyanate-conjugated IgE and then assessed for both IL-4 RNA expression and alcian blue staining. Both IL-4-producing and alcian blue-positive cells segregated with the Fc epsilon R+ fraction. These data suggest that human BM cells, probably belonging to the mast cell and/or basophil lineage, are capable of producing IL-4 in response to Fc epsilon R or Fc gamma R cross-linkage.

Antigens, Differentiation↗

Allergen- and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production.

We have established a large panel of T-cell clones (TCCs) specific for Dermatophagoides pteronyssinus and Lolium perenne group I grass pollen allergens (total, 61) and for tetanus toxoid and protein purified derivative bacterial antigens (total, 38) from the peripheral blood of two atopic individuals and then analyzed their ability to produce interleukin 4 (IL-4), IL-5, and interferon gamma (IFN-gamma). Upon stimulation with phorbol 12-myristate 13-acetate plus anti-CD3 antibody, the great majority of TCCs specific for bacterial components was able to produce both IL-4 and IFN-gamma, whereas most D. pteronyssinus- and L. perenne group I-specific TCCs produced IL-4, but no, or limited, IFN-gamma. Moreover, the mean amounts of IL-4 and IFN-gamma released by allergen-specific TCCs were significantly higher and lower, respectively, than the mean amounts produced by TCCs specific for bacterial components. Under the same experimental conditions, virtually all allergen-specific TCCs, but only one-third of tested TCCs specific for bacterial components, expressed IL-5 RNA and secreted IL-5 in their supernatants. Eighteen TCCs (nine specific for allergens and nine specific for bacterial components) were also assessed for their ability to induce IgE synthesis by autologous B cells in response to stimulation with the specific antigen. Under these experimental conditions, all allergen-specific TCCs, but only one-third of TCCs specific for bacterial components that produced IL-4 but no, or little, IFN-gamma induced the synthesis of detectable amounts of IgE. The demonstration that most allergen-specific helper T cells in atopic individuals are able to produce high amounts of IL-4 (and IL-5), but no IFN-gamma, may explain why allergens induce production of IgE antibodies and increase eosinophils.

Adult↗

In vitro infection with HIV enables human CD4+ T cell clones to induce noncognate contact-dependent polyclonal B cell activation.

Eleven (nine CD4+ and two CD8+) protein purified derivative-specific and eight tetanus toxoid-specific T cell clones (TCC), established from the peripheral blood of healthy persons, were cocultured in vitro with irradiated mononuclear cells from patients infected by HIV in the presence of PHA and polybrene. Two weeks post-HIV exposure, all 17 CD4+, but neither of the two CD8+, TCC exhibited integration of HIV in their genoma, as detected by polymerase chain reaction analysis, and released HIV into their supernatants, as detected by measuring both reverse transcriptase activity and p24 Ag. When co-cultured with either autologous or allogeneic B cells, all CD4+ HIV-infected TCC induced the synthesis of extraordinarily high amounts of IgM, IgG, and IgA. In contrast, their noninfected counterparts could provide helper function for Ig synthesis by autologous B cells only in the presence of the specific Ag (or anti-CD3 antibody), and induced allogeneic B cells to synthesize Ig only upon stimulation with anti-CD3 antibody. The supernatants of HIV-infected TCC failed to stimulate Ig synthesis in B cells. More importantly, when HIV-infected clonal T blasts and B cells were cultured in different chambers separated by a millipore membrane, permeable to molecules but not to cells, Ig synthesis did not occur. The Ig synthesis induced by HIV-infected TCC was also markedly inhibited by the addition in culture of either anti-CD4 or anti-LFA-1 antibody. In contrast, HIV-infected TCC maintained their ability to provide helper function for Ig synthesis in the absence of any stimulus, even after fixation with p-formaldehyde. These data demonstrate that in vitro infection with HIV enables human T cells to stimulate Ig synthesis by B cells by an Ag-nonspecific, MHC-unrestricted, contact-dependent mechanism. This may explain, at least in part, the hypergammaglobulinemia and other phenomena related to polyclonal B cell activation frequently seen in HIV-infected persons.

B-Lymphocytes↗