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Biomedical subjects

M Vanoli

Publications and source records attributed to M Vanoli.

At least 37 records · Page 2Linked to original sources

Relationship between antibodies to dsDNA and to soluble cellular antigens and histologically defined glomerulonephritis in patients with SLE.

To better define the relationships between circulating autoantibodies and renal involvement in systemic lupus erythematosus (SLE), antibodies to both dsDNA and soluble cellular antigens were detected in sera from a large series of SLE patients. Significantly higher dsDNA binding activities and lower complement levels at onset were found in patients with renal disease; however, this was uniquely due to subjects with diffuse or focal proliferative glomerulonephritis. Patients with membranous nephropathy (MGN) showed very low dsDNA binding activities (6/9 of them being negative for dsDNA antibodies) and normal mean C3 and C4 levels. A comparison between patients with proliferative nephritis and patients without renal involvement with high dsDNA binding activities revealed significantly lower complement levels in the former group. No significant difference was observed in the prevalence of antibodies to soluble cellular antigens between patients with or without renal disease; however, nRNP antibody was two-fold more frequent in patients with MGN than in all other subgroups. This study highlights the close relationship between concurrently high anti-dsDNA and low complement levels and proliferative glomerulonephritis in SLE, and suggests that subjects with MGN may represent a subgroup of SLE patients showing peculiar serological features. Different mechanisms possibly involved in the pathogenesis of MGN in SLE are discussed.

Adolescent↗

Effects of cyclosporin A on in vitro lymphocyte response to autologous or allogeneic stimulation: influence of HLA phenotypes.

In this study we investigated whether the interindividual variability of lymphocyte sensitivity to cyclosporin A (CsA) could be controlled by the HLA region. The models used were the in vitro primary and secondary autologous (AMLR) and allogeneic mixed lymphocyte (MLR) cultures of cells from 32 healthy subjects from our HLA reference panel. Our results show that CsA inhibited primary allogeneic MLR to a much greater extent than primary AMLR (-81 +/- 2% vs -38 +/- 8%, P less than 0.001). The same pattern was observed when cells harvested from CsA-treated primary cultures were rechallenged in secondary cultures with the original sensitizing stimulator cells (-40 +/- 6% vs -17 +/- 9%, P less than 0.05). No differences were observed in primary autologous and allogeneic cultures among responders of different HLA phenotypes. In contrast, the secondary responses did vary according to the HLA types: in secondary AMLR, CsA-priming did not lower, or even enhance, the proliferative responses of DR5+ and/or DR2+ lymphocytes (+7 +/- 13%), whereas it significantly lowered the responses of DR2-5- cells (-46 +/- 8%). In secondary MLR, lymphocytes proliferation was lowered by CsA-priming in all but DRW11(5)+ subjects (-45 +/- 7% vs +2 +/- 23%, P less than 0.05). It is concluded that the individual HLA phenotype influences the pattern of lymphocyte sensitivity to CsA.

Adult↗

Effect of cyclosporin A on 2ry MLR in patients with progressive systemic sclerosis.

We have studied the effects of the immunosuppressive agent Cyclosporin A (CsA) on the allogenic stimulation of human lymphocytes from 10 patients with progressive systemic sclerosis (PSS) and 10 healthy controls, when activated in vitro during 1ry and 2ry MLR. CsA markedly suppressed 1ry MLR in both PSS subjects and controls. In contrast to the marked suppression of 2ry MLR observed for most of the PSS subjects and all control subjects, lymphocytes from 3 out of 10 PSS patients had paradoxically amplified allogenic responses when primed in the presence of CsA. The possibility is discussed that in these patients the recruitment of suppressor-effector cells by CsA-resistant suppressor-inducer lymphocytes is impaired.

Adult↗

Age- and sex-dependent changes in natural killer cell activity.

Peripheral blood mononuclear cells (PBMC) from 40 normal individuals, 20 men and 20 women, divided according to age were evaluated for their ability to mediate natural killer (NK) cytotoxicity, using the K562 erythroleukemic cells as target. The results of a specific 51Cr release assay demonstrated that NK activity was greater in men than in women. There was a significant correlation between NK activity and the percentages of Leu 11a+ cells in younger women, but not in the other groups and no correlation between NK activity and Leu 7+ cells.

Age Factors↗

AMLR and MLR stimulating activity of human T lymphocytes activated in vitro by soluble HLA-DR antigens.

We have examined the allogeneic mixed lymphocyte reaction (MLR) and autologous mixed lymphocyte reaction (AMLR) stimulating activities of T cells precultured in vitro with soluble allogeneic or autologous HLA-DR antigens. These cells (Ts) are known to suppress the human MLR: this suppression is specific in that it occurs only when stimulator cells have the same HLA-DR antigen as that used to induce differentiation of suppressor cells. Ts cells express new membrane specificities; they can be separated by immunoabsorption into two populations: Ts enriched (Tx+; with suppressive activity) and Ts depleted (Ts-; with helper function). In the present study, we have demonstrated that both Ts cell subsets activated by soluble HLA-DR alloantigens are able to stimulate both MLR and AMLR. Ts cells activated by soluble autologous HLA-DR antigens are able to stimulate MLR, but not AMLR.

Adult↗

Phagocyte function and immunological findings in a Wiskott-Aldrich syndrome long-term survivor.

The case reported concerns a 19-year-old man who presented with clinical and laboratory findings compatible with the Wiscott-Aldrich Syndrome. Our patients is the eighth reported case of a long-term survivor with this syndrome. Immunologic studies revealed, in spite of a normal lymphocyte number, an impaired delayed hypersensitivity and a failure of response to mitogens and irradiated allogeneic cells. IgE and IgA levels were high while IgM levels were low. Studies of phagocytic cells showed normal phagocytosis, candidacidal activity, IgG receptors and phagocytic metabolic burst. However, the patient's neutrophils and monocytes responded poorly to chemoattractants and the serum generated less chemotactic activity than normal sera. Detailed studies revealed the presence in the patient's serum of 2 different inhibitors of chemotaxis: a cell-directed inhibitor and an inhibitor of chemotactic factors.

Adult↗

Histocompatibility in Italian couples with recurrent spontaneous abortions of unknown origin and with normal fertility.

We investigated HLA antigen and haplotype frequencies in 47 couples with primary recurrent abortions of unknown origin, in 65 fertile couples, and in a control panel of 98 males and 92 females. A significant increase of HLA-B17 was found in abortion couples in comparison with fertile couples. No difference between abortion and control fertile couples was observed regarding HLA sharing.

Abortion, Habitual↗

HLA antigens and the reactivity of lymphocytes to some drugs and PHA.

Peripheral blood lymphocytes from 15 healthy subjects, selected on the basis of their HLA types, were cultured in vitro in the presence of PHA and of a number of drugs which bind adrenergic or dopaminergic receptors (dopamine, norepinephrine, chlorpromazine, haloperidol, propranolol and apomorphine). The results obtained are consistent with an interference between HLA-A1 and cross-reacting specificities and the effect explained by these drugs on the lymphocyte activation by PHA. The possibility is suggested that HLA-A1 and cross-reacting antigens interfere with the binding of such drugs to the cell membrane receptors.

Adult↗

MLC-specific suppressor T lymphocytes in man. I. Their induction in vitro by soluble HLA-DR antigens.

Human T lymphocytes precultured for 36 hr in the presence of soluble HLA-DR antigens suppress the MLR response of autologous peripheral blood lymphocytes to allogeneic stimulating cells. The suppression is DR antigen-specific in that it appears that the MLR stimulating cell donor and the soluble suppressor-inducing antigen must share DR specificities. The soluble DR antigens were fractionated from the sera of normal donors using QAE-Sephadex chromatography and CNBr-activated Sepharose immunoadsorption. Similarly prepared HLA-A and -B antigens failed to induce suppressive activity. The suppressive activity of DR-antigen cultured T cells is resistant to mitomycin C treatment and, further, the antigen specificity is maintained with or without mitomycin C treatment. The kinetics of suppressor cell induction as well as the kinetics of suppression in the test MLR cultures are presented. The implications of these results are discussed.

Adult↗

MLR-specific suppressor T lymphocytes in man. II. Functional and membrane characteristics of a specific MLR suppressor subpopulation.

Human MLR-specific suppressor T lymphocytes were induced by in vitro cultivation of human peripheral T lymphocytes in the presence of soluble HLA-DR alloantigens isolated from normal serum. The suppression is specific in that responder cells autologous to the suppressor cells respond to allogeneic stimulating cells that express the same HLA-DR specificity as that recovered from serum and used to induce the suppressor cells. This antigen-specific suppressor T cell population could be divided into suppressor and non-suppressor subpopulations as a function of adherence to a 6MB Sepharose immunoadsorbent coated with the inducing HLA-DR soluble antigen. As a consequence of activation by soluble DR antigen, the suppressor T lymphocyte population as well as the column-enriched suppressor subpopulation express new membrane specificities that can be recognized by antisera from pluriparous women. The specificities that are recognized are not found on autologous, unstimulated B and T cells, nor do they appear to recognize conventional HLA-A,B,C or DR determinants.

Antigens, Surface↗

Non-invasive assessment of pulmonary artery involvement in Takayasu's arteritis.

OBJECTIVE: To evaluate pulmonary involvement in Italian patients with Takayasu's arteritis (TA). METHODS: A prospective analysis of 15 Italian patients with TA was carried out, including evaluation by perfusion and ventilation lung scintigraphy (planar and tomographic), standard chest X-ray, spirography and color-doppler echocardiography. All the patients were free of respiratory symptoms when examined. RESULTS: In all patients standard chest X-rays and ventilation scintigraphies were normal. 9/15 patients showed unmatched segmental perfusion defects (41 by planar evaluation vs. 48 by SPET). The number of defects was greater in the right lung than in the left (26 vs 18), with a higher frequency of moderate or large defects. Thirteen patients underwent spirography, which proved to be abnormal in 5 cases. Two of these patients were also positive on scintigraphy. No patient showed alterations attributable to TA on color-doppler echocardiography, except for 3 patients with mild to moderate aortic valve regurgitation. CONCLUSIONS: Our results show that vascular pulmonary involvement is frequent in TA (60% of cases) even in the absence of clinical signs. The planar image, simpler than the SPET to acquire, was sufficient to make an accurate diagnosis. Italian patients seem to show a pattern of extrapulmonary and pulmonary vascular involvement very similar to that reported in Japanese subjects, and different from that observed in other ethnic groups.

Adolescent↗

Five-year follow-up of 165 Italian patients with undifferentiated connective tissue diseases.

OBJECTIVE: To study those conditions with a proven or hypothesised immunologic pathogenesis and denominated under a working definition of undifferentiated connective tissue diseases (UCTD). METHODS: A multicentre prospective study was organised involving 10 tertiary referral centers of internal medicine in Italy, with the aim of describing the natural history of UCTD and the prevalence of its different clinical and immunological manifestations. RESULTS: After a five-year follow-up period, data on 165 patients were available for analysis. UCTDs occur mainly in females in their fourth decade of life. Articular and mucocutaneous features and Raynaud's phenomenon represent the most common findings. Nevertheless, we also detected a relatively high incidence of permanent major organ damage. Regarding the immunologic parameters, we documented some conflicting results in the correlation between serologic abnormalities and clinical features. In 10 patients UCTD evolved to a major disease, generally systemic lupus erythematosus or Sjögren's syndrome. CONCLUSION: A low rate of evolution to a defined autoimmune disease, the limited use of steroid or immunosuppressive therapy, and a favourable course in the majority of cases are the main characteristics of patients with UCTDs.

Adolescent↗

Effects of long-term cyclic iloprost therapy in systemic sclerosis with Raynaud's phenomenon. A randomized, controlled study.

OBJECTIVE: Iloprost is a stable prostacyclin analogue which has been shown to be effective in the short-term symptomatic treatment of Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). The aim of this study was to evaluate the effects of long-term cyclic therapy with iloprost in comparison with nifedipine on the skin score, pulmonary function and Raynaud's severity score in patients with SSc and RP. METHODS: We conducted a 12-month prospective, randomised, parallel-group, blind-observer trial to compare the effects of intravenously infused iloprost (2 ng/kg/min on 5 consecutive days over a period of 8 hours/day and subsequently for 8 hours on one day every 6 weeks) with those of conventional vasodilating therapy with nifedipine (40 mg/day for os) in 46 patients with SSc and RP. RESULTS: At 12 months, iloprost but not nifedipine reduced the skin score (iloprost: from 13.26 +/- 2.05 to 9.26 +/- 1.32, p = 0.002; nifedipine: from 10.83 +/- 2.09 to 12.17 +/- 3.02, p = n.s.; iloprost vs nifedipine: p = 0.016) and the RP severity score (iloprost: from 2.17 +/- 0.2 to 1.22 +/- 0.13, p = 0.02 vs baseline; nifedipine: from 2.08 +/- 0.34 to 1.33 +/- 0.22, p = n.s.). Carbon monoxide diffusing capacity (DLCO), expressed as % of the predicted normal value, worsened significantly in the nifedipine group (from 69.6 +/- 7.4% to 61.5 +/- 6.5%, p = 0.044) and remained stable in patients treated with iloprost (from 53.2 +/- 4.8 to 56.0 +/- 4.6%, iloprost vs nifedipine: p = 0.026). CONCLUSION: In SSc patients, cyclic intravenous iloprost infusion is able to control vasospastic disease. Our results suggest that it might also act as a disease-modifying agent, as it seems to improve the course of the disease. Further studies principally focused on organ involvement and the natural history of the disease are needed to confirm our results.

Adult↗

Takayasu's arteritis: a changing disease.

Takayasu's arteritis (TA) is a chronic, giant-cell vasculitis of unknown etiology, which primarily involves the aorta, its main branches and coronary and pulmonary arteries. This review focuses on the epidemiological, diagnostic, and clinical aspects of the disease, which have been changed since the first description made by Mikito Takayasu in 1908. The article also summarizes the data collected by the Italian Registry of TA in the period 1993-1998.

Asia↗