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Biomedical subjects

M Montroni

Publications and source records attributed to M Montroni.

At least 37 records · Page 2Linked to original sources
PubMed1993

HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease.

Primary infection with the human immunodeficiency virus (HIV) is generally followed by a burst of viraemia with or without clinical symptoms. This in turn is followed by a prolonged period of clinical latency. During this period there is little, if any, detectable viraemia, the numbers of infected cells in the blood are very low, and it is extremely difficult to demonstrate virus expression in these cells. We have analysed viral burden and levels of virus replication simultaneously in the blood and lymphoid organs of the same individuals at various stages of HIV disease. Here we report that in early-stage disease there is a dichotomy between the levels of viral burden and virus replication in peripheral blood versus lymphoid organs. HIV disease is active in the lymphoid tissue throughout the period of clinical latency, even at times when minimal viral activity is demonstrated in blood.

Acquired Immunodeficiency Syndrome↗
PubMed1993

HIV-1 infection in the lymphoid organs.

AIM: To develop a model of HIV disease progression. METHOD: Comparative analysis of viral burden and replication between peripheral blood and lymphoid organs and of the changes in viral distribution in the lymphoid tissue. RESULTS: In early-stage disease HIV-1-infected cells were sequestered in the lymphoid tissue, and the viral particles were concentrated and trapped in the germinal centers. The dichotomy in viral burden and viral replication between peripheral blood and lymphoid tissue was related to the histopathologic abnormalities associated with different stages of disease. CONCLUSIONS: These histopathologic abnormalities may not only explain the changes in viral distribution observed in the lymphoid tissue in different stages of the disease, but may also reflect different functional states of the immune system during the progression of HIV-1 infection from early- to late-stage disease.

DNA, Viral↗
PubMed1992

Targeting antiretroviral nucleoside analogues in phosphorylated form to macrophages: in vitro and in vivo studies.

A number of nucleoside analogues are active against the infectivity of human immunodeficiency virus (HIV); however, their use is limited by toxic side effects and by limited phosphorylation in the infected cells. In an attempt to overcome these problems, a drug delivery system has been developed. A prototype of these drugs in a form already phosphorylated (2',3'-dideoxycytidine 5'-triphosphate; ddCTP) was encapsulated into erythrocytes. Subsequently, by the addition of Zn, an arrangement of band 3 in clusters was induced (band 3 is the major transmembrane protein in erythrocytes). The immune system recognizes these clusters as nonself, promoting autologous IgG binding and phagocytosis by cells of the monocyte-macrophage lineage. In this way, ddCTP encapsulated into erythrocytes was delivered to macrophage cells, where concentrations greater than 2 microM were found. Addition of ddCTP-loaded erythrocytes to macrophages previously infected by HIV-1 results in almost complete inhibition of HIV production over 3 weeks in culture. Administration of ddCTP-loaded erythrocytes to LP-BM5-infected mice at 10-day intervals over a period of 3 months results in reduction of lymphoadenopathy, splenomegaly, and hypergammaglobulinemia. Thus, the delivery of nucleoside analogues in phosphorylated form is feasible, and selective targeting to virus reservoirs (macrophage cells) can be accomplished by the use of autologous erythrocytes.

Animals↗
PubMed1991

Detection of human immunodeficiency virus type 1 transcripts in peripheral blood lymphocytes by the polymerase chain reaction.

A simplified application of the polymerase chain reaction (PCR) to the routine detection of human immunodeficiency virus type 1 (HIV-1) transcripts from peripheral lymphocytes of infected subjects is described. This technique is simpler than previously described assays and was shown to be highly sensitive after ethidium bromide staining of polyacrylamide gel electrophoresis of amplified material. The method can be used for the virologic evaluation of HIV-1-infected subjects, thus allowing early identification of seropositive patients with signs of active infection.

Cell Line↗
PubMed1988

A retrospective study of antibodies against basement membrane antigens (type IV collagen and laminin) in patients with primary and secondary Raynaud's phenomenon.

Antibodies against type IV collagen were detected in the sera of 21% of patients with primary Raynaud's phenomenon (PRP) and 68% of patients with systemic sclerosis. Sera from 25% of the PRP patients and 48% of systemic sclerosis patients displayed antibodies to laminin. Eighty percent of the patients with PRP and antibodies to basement membrane antigens developed additional serologic or clinical manifestations, whereas only 16% of patients with PRP and no anti-basement membrane antibodies developed such manifestations.

Adolescent↗
PubMed1988

Immunity assessment in the early stages of amyotrophic lateral sclerosis: a study of virus antibodies and lymphocyte subsets.

Serum and CSF from 32 patients with idiopathic ALS, 30 age-matched controls and 30 MS patients were investigated regarding immunoglobulin concentration and virus-specific antibodies, the lymphocytes in the peripheral blood and lymphocyte subsets were also investigated. ALS patients' results were compared with findings in MS and controls. The ALS patients had significantly higher IgG concentration in serum than the controls, marked lymphopenia, reduction of CD2, CD8 and Leu 7 positive cells and increase of the CD4/CD8 ratio and of SIg-positive lymphocytes. Compared with the MS patients, the ALS patients showed similarity in T-subset distribution with a lower standard deviation. No HTLV-I and HIV antibodies were found in any group and no significant differences in antibody distribution to Toxoplasma G, herpes simplex, cytomegalovirus, measles and mumps viruses were evident. All ALS patients were investigated at an early disease stage, therefore, our findings seem to support the conclusion that the immune alterations are related to the mechanisms of the disease and not to complications of its evolution.

Adult↗
PubMed1987

Evidence of immune deposits and of basement membrane alterations in dermal vessels of normal skin of patients with essential mixed cryoglobulinemia.

To gain insight into the pathogenic mechanisms of immune complex-mediated vasculitis, clinically normal skin specimens from the forearms of 12 patients with essential mixed cryoglobulinemia were investigated by light microscopy, immunofluorescence microscopy, and electron microscopy. Basement membrane alterations were documented in 9 patients. Eleven patients had deposits in vessel walls, but only in 1 was there evidence of inflammation. The same immunoglobulins of the cryoproteins could be demonstrated in the tissue deposits by immunofluorescence analysis and by immunoelectron microscopy. These findings suggest that, in essential mixed cryoglobulinemia, immune reactants in dermal vessels of normal skin are more common than is evidenced by clinical examination. Moreover, it seems that cryoglobulins, as such, are not sufficient to trigger an inflammatory process: Additional local or plasma factors are required. Deposits were absent in 7 patients with cryoglobulinemia that was associated with a primary disorder. This could be ascribed to the lower cryocrit levels documented in this group of patients, or to the shorter duration of their disease.

Adult↗
PubMed1987

Does activity of pulmonary sarcoidosis depend on disease duration? A correlation between bronchoalveolar lavage, scintigraphic, radiologic, and physiologic parameters and time of onset of the disease.

In pulmonary sarcoidosis the alveolitis is thought to precede and modulate granuloma formation and fibrosis. Thus, patients with early disease may have a more active pulmonary process, while patients with long standing sarcoidosis are thought to have fibrotic, stabilized lesions. The aim of the present study is to correlate radiographic stage, alveolitis activity, and respiratory function changes with the length of the disease. For this purpose 116 patients with biopsy-proven untreated pulmonary sarcoidosis have been divided in three groups according to time of onset of the illness: group A (48 patients with sarcoidosis duration less than or equal to 3 months), group B (25 patients with sarcoidosis duration greater than 3 less than or equal to 6 months), and group C (43 patients with sarcoidosis duration greater than 6 months less than or equal to 3 years). We found a progression with time from roentgenographic stage I to III, but no correlation was present between the disease duration and T lymphocytes of BAL, results of gallium lung scans, and respiratory function values. Our results suggest that the activity of alveolitis and the derangement of respiratory function in pulmonary sarcoidosis are unrelated to the time of onset of the disease.

Adolescent↗
PubMed1985

Immune deposits in normal skin of patients with systemic lupus erythematosus: relationship to the serum capacity to solubilize immune complexes.

Immunofluorescent deposits at the dermal-epidermal junction (DEJ) of the skin (lupus band test or LBT) were evaluated in 134 patients with various connective tissue diseases. LBT was found positive in 23 of 32 (71.8%) patients with systemic lupus erythematosus (SLE), in 3 of 53 (5.6%) patients with rheumatoid arthritis (RA), and in 1 of 5 cases of mixed connective tissue disease (MCTD). No deposits were found in patients with systemic sclerosis and with vasculitis. In patients with SLE a positive LBT showed a direct correlation with serum Clq binding activity (ClqBA) and with hypocomplementemia. The mean ClqBA was 13.49 +/- 12.85 and 2.38 +/- 2.27% in SLE patients with positive and negative band test, respectively (P less than 0.005). Likewise depressed mean serum levels of C3 and C4 were detected in patients with skin deposits (P less than 0.005). Sera from SLE patients showed an overall decreased capacity to solubilize preformed immune complexes when compared to normal sera. Furthermore 10 band-positive patients were less able to solubilize immune complexes than sera from LBT-negative lupus patients (45 +/- 16 and 62 +/- 11%, respectively; P less than 0.01). Also the capacity to inhibit the precipitation of immune complexes was decreased in SLE patients with negative LBT (P less than 0.05). In conclusion our data suggest that in SLE patients a decreased complement-mediated solubilization of immune complexes is involved in the persistence of high levels of circulating immune aggregates and, considered its correlation with positive LBT, may be responsible for the deposits of immunoglobulins at the dermal-epidermal junction of the skin.

Adolescent↗
PubMed1983

An extended C1q-binding assay using lactoperoxidase- and chloramine-T-iodinated C1q. Immediate distinction between immune-aggregate-mediated and non-immune-aggregate-mediated C1q binding.

An extension of the C1q-binding assay for the detection of immune-aggregate-mediated and non-immune-aggregate-mediated C1q binding is reported. The assay involves the use of two different C1q preparations, one radioiodinated by means of lactoperoxidase (LPO-125I-C1q) and the other by means of chloramine-T (CT-125I-C1q). The treatment with CT for 20 min at room temperature before iodination for 1 min led to abolishment of the C1q-binding capacities to complexed IgG: approximately 50% of LPO-125I-C1q but only 2% of CT-125I-C1q bound to 80 micrograms/ml of IgG forming part of tetanus toxoid/anti-tetanus toxoid complexes or to 200 micrograms/ml of heat-aggregated human gamma globulin. Similar results were obtained with staphylococcal protein-A-aggregated IgG. CT-treated C1q was haemolytically inactive. In contrast to the results with complexed IgG, CT treatment did not markedly reduce binding capacities of C1q to heparin: approximately 55% of LPO- and CT-125I-C1q were bound by 127 U/ml of commercial heparin in normal human serum. Both C1q preparations bound to a comparable extent to fibronectin, fibrinogen, and various bacterial endotoxins. When the LPO- and CT-125I-C1q-binding patterns obtained on serum samples from patients with systemic lupus erythematosus, rheumatoid arthritis, or essential mixed cryoglobulinaemia were compared with binding patterns observed using laboratory reactants, an immediate detection of non-immune-aggregate-mediated C1q binding became possible.

Antigen-Antibody Complex↗
PubMed1983

Complement activation and impaired capacity to solubilize immune complexes or to prevent their formation in essential mixed cryoglobulinemia.

The complement profile, the immune complex solubilizing capacity (ICSC), the immune complex precipitation inhibition capacity (ICPIC), the presence of cryoprecipitable material, and the presence of immune-aggregate- and non-immune-aggregate mediated C1q-binding activity was assessed in serum samples from 23 patients suffering from essential mixed cryoglobulinemia (EMC). No correlation between the levels of cryoglobulins and the clinical activity of EMC was found. The mean C1q-binding activity in EMC serum samples was abnormally elevated 28 +/- 29% (mean +/- SD). In six out of eight serum samples that contained C1q-binding material, evidence was obtained that such material was of the complexed immunoglobulin G (IgG) type. Among the levels of C1q, C1r, C2, C4, C3, C5, C6, C1-inhibitor, C3d, B, I, H, as well as the total hemolytic activity and the activity of the alternative pathway of the complement, the mean serum concentrations of C1, C2, and C4 and in consequence the mean total hemolytic activity were significantly reduced, whereas the mean levels of C3d were significantly elevated in the EMC serum samples. The capacity of the 23 EMC serum samples to solubilize preformed immune precipitates from bovine serum albumin (BSA) and rabbit anti-BSA antibodies as well as their capacity to prevent the formation of the precipitable form of such complexes was analyzed. Compared to the ICSC and the ICPIC of 30 normal human sera, the ICSC and the ICPIC of EMC serum samples were reduced to 57 +/- 24% and 38 +/- 33%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗