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Biomedical subjects

G Danieli

Publications and source records attributed to G Danieli.

At least 19 recordsLinked to original sources

Juvenile rheumatoid arthritis patients manifest immune reactivity to the mycobacterial 65-kDa heat shock protein, to its 180-188 peptide, and to a partially homologous peptide of the proteoglycan link protein.

Immune reactivity to the 65-kDa mycobacterial heat shock protein (hsp65) has been associated with arthritis in rats and humans. In this report we evaluated patients with juvenile rheumatoid arthritis for such immunity. A high proportion of affected children showed both antibody and T lymphocyte responses to hsp65 and to two related peptides: the nonapeptide 180-188 sequence of hsp65 and a partially homologous peptide of the cartilage proteoglycan link protein. The titer of circulating antibodies was generally higher in patients with clinically active disease. In contrast to the juvenile rheumatoid arthritis patients, patients with adult rheumatoid arthritis tended to have lower responses of their peripheral blood T lymphocytes to the whole hsp65 molecule. Moreover, the adult rheumatoid arthritis patients did not respond to the peptides. Thus, there appear to be immunological differences between juvenile and adult forms of rheumatoid arthritis related to hsp65 reactivity.

Adolescent

Antibodies to mycobacterial 65 kDa heat shock protein in systemic sclerosis (scleroderma).

It has been reported that immunity to the 65 kDa heat shock protein of Mycobacterium tuberculosis (MT-hsp65) not only accompanies rheumatoid arthritis (RA), but may also be characteristic of chronic inflammation. We now report serum antibodies to MT-hsp65 in 47% of systemic sclerosis (SSc), 38% of primary Raynaud's phenomenon (PRP) and 5% of systemic lupus erythematosus (SLE). Antibody levels were higher in patients with active or progressive SSc and correlated with the degree of skin fibrosis. Thus, immunity to MT-hsp65 appears in SSc and is not limited to RA. However, it does show some degree of specificity beyond chronic inflammation: PRP patients have a higher reactivity than do SLE patients.

Adolescent

Low number of complement C3b/C4b receptors (CR1) on erythrocytes from patients with essential mixed cryoglobulinemia, systemic lupus erythematosus and rheumatoid arthritis: relationship with disease activity, anticardiolipin antibodies, complement activation and therapy.

Our aim was to assess whether the amount of complement C3b/C4b receptors (CR1) on erythrocytes shows a correlation to disease activity in various connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and essential mixed cryoglobulinemia (EMC). Using an anti-CR1 monoclonal antibody, 26 patients with SLE, 34 with RA and 22 patients with EMC were investigated for erythrocyte CR1 expression. The control group consisted of 30 healthy individuals. The mean number of CR1/erythrocyte in the control group was 568 +/- 197 (range 174-1060), significantly higher than studied (EMC:379 +/- 248; p = 0.0005;SLE 147 +/- 56, p less than 0.0001; RA 298 +/- 177, p less than 0.0001). In patients with RA and in SLE, but not in patients with EMC, the number of CR1 numbers and anticardiolipin antibody (aCl) titers (r2 = 0.493; p = 0.034). A statistically significant correlation between CR1 numbers and CH50 values was found in patients with SLE, while in 3 patients with RA 4 months of therapy with cyclosporine A led to a further 30% reduction in CR1 number. Our conclusions are that (a) the decreased expression of erythrocyte CR1 is apparently a common feature of patients with various connective tissue diseases; (b) several acquired factors such as disease activity, complement activation, aCl and drugs may contribute to the loss of CR1 from erythrocytes; (c) in patients with RA and SLE, but not in patients with EMC, CR1 enumeration on erythrocytes may serve as a variable for clinical monitoring.

Adult

Hepato-atrial anastomosis as emergency treatment for traumatic rupture of suprahepatic inferior vena cava and hepatic veins.

The case of a 21-year-old patient operated on as an emergency for traumatic rupture of the suprahepatic inferior vena cava (IVC) and hepatic vein (HVs) is presented. Since anatomic reconstruction of the ruptured vessels was considered unfeasible, a direct anastomosis was instituted between the right atrium and the liver capsule around the disrupted IVC and HVs, using extracorporeal circulation, deep hypothermia and circulatory arrest. Hemorrhage was easily controlled and the patient survived. As far as we know, this operation, originally developed for the treatment of the Budd-Chiari syndrome, has never been used before as a life saving procedure under the circumstances described.

Adult

Cyclosporin effect on sodium and potassium transport across erythrocytes in rheumatoid arthritis.

The aim of the present work was to evaluate the action of cyclosporin (CsA) both in vivo and in vitro on the active sodium transport across the erythrocyte membrane of rheumatoid arthritis (RA) patients. The in vivo study was performed on 20 patients affected by refractory RA and treated with CsA (5 mg/kg/die) or with azathioprine (2 mg/kg/die) before and after 7 days' therapy. The control group was formed of 25 healthy subjects. RA patients before treatment showed increased intra-erythrocyte Na+ concentration and decreased Na+, K+ ATPase activity in comparison with normal subjects. A rise in the activity of the sodium pump and a reduction in the intra-erythrocyte Na+ concentration were observed after cyclosporin treatment, but not after azathioprine. The in vitro study was performed on intact RBCs and on erythrocyte membranes from 15 healthy subjects and from 12 patients affected by classical RA, in the presence or absence of CsA (0.5-1-2 micrograms/ml). CsA (0.5 micrograms/ml) increased the Na+, K+ ATPase activity in intact RBCs and in erythrocyte membranes from both groups of subjects. Intracellular Na+ was decreased only in erythrocytes from RA patients after addition of 0.5 micrograms/ml CsA. A direct action of CsA on the membrane hydrophobic environment of the Na+, K+ ATPase is hypothesized on the basis of the present results.

Adult

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

Assessment of disease activity in essential cryoglobulinemia by serum levels of a basement membrane antigen, laminin.

When compared with 40 normal controls, 46 patients with essential cryoglobulinemia had higher serum concentrations of a basement membrane antigen, laminin fragment P1 (LP1). Serum LP1 values were more pronounced in patients with visceral involvement, compared with those with skin vasculitis only. Asymptomatic patients or those with arthralgia usually had normal values. Increased disease activity was associated with a significant increase in LP1 (P less than 0.01). For evaluation of disease activity, determination of serum LP1 was a more sensitive measure than any complement factor assay.

Adolescent

Abnormal membrane cation transport in pregnancy-induced hypertension.

An abnormality of sodium handling has been suggested as one of the mechanisms responsible for the development of pregnancy-induced hypertension. We analysed the plasma and urinary concentrations, and the intraerythrocyte activities of Na and K, and the RBC membrane Na+/K+-ATPase activity of 77 hypertensive and 133 normal pregnant women. Umbilical cord blood of infants from 21 hypertensive and 28 control women was studied. The Na+/K+-ATPase activity was determined by measuring the inorganic phosphate released by incubation in a reaction medium in the presence and absence of K ions or ouabain. The intra-erythrocyte sodium and potassium activities were measured by ion-selective electrode analysis of the haemolysates, after washing the RBCs in 110 mmol/l MgCl2. We found a significant increase in intracellular sodium and a reduction in Na+/K+-ATPase activity in the hypertensive women in comparison with the control subjects during pregnancy. No difference was observed in early puerperium. Cord blood from infants of pregnancy-induced hypertensive women showed an increase in intracellular Na+ activity and a decrease in the erythrocyte membrane Na+/K+-ATPase activity in comparison with cord blood samples from control subjects. The observed abnormalities in the plasma membrane sodium transport may play a major role in the pathophysiology of pregnancy-induced hypertension.

Biological Transport

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

Decreased NA+, K+-ATPase activity in erythrocyte membrane from rheumatoid arthritis patients.

The activity of the plasma membrane Na+/K+-ATPase and cellular sodium (Nai) and potassium (Ki) content were analysed in RBCs from 15 rheumatoid arthritis (RA) and 30 reference subjects (11 healthy controls, 12 osteoarthritis and 7 gouty patients). Na+/K+-ATPase activity was determined by measuring the inorganic phosphate (Pi) released by incubation in a reaction medium in the presence and absence of K ions or ouabain. Nai and Ki were measured with an ion-selective electrode analyser on the hemolysates, after washing the RBCs in 110 mM MgCl2. The Na/K-ATPase activity was significantly lower in RA patients than in both healthy controls and patients with osteoarthritis or gout. A slight but significant increase in Nai was observed in rheumatoid subjects. It is hypothesized that the decrease in the Na+/K+-ATPase activity in RA may be the result of a defective expression of membrane proteins, which is probably related to the altered cell sensitivity observed.

Adult

Multicenter double-blind randomized clinical trial of imidazole salicylate versus ibuprofen in patients with osteoarthrosis.

Imidazole salicylate (750 mg t.i.d.) was compared with ibuprofen (400 mg t.i.d.) in a 30-day multicenter double-blind clinical trial in patients with osteoarthrosis. Both drugs were effective in relieving joint pain and in reducing the duration of morning stiffness. A statistically significant reduction of the severity of these symptoms was observed already one week after the start of treatment, lasting until the end of the study. No significant differences in efficacy were demonstrated between the two drugs throughout the trial. The systemic tolerability, assessed by changes in tests of hematological, liver and kidney function, was excellent with both treatments. The incidence of side effects (mostly gastrointestinal complaints) was fairly low in both groups, and lower in the group treated with imidazole salicylate.

Adult

Human growth hormone induced modulation of hepatitis B virus (HBV) gene expression.

A well characterized human hepatocellular carcinoma cell line (PLC/PRF/5) containing complete sequences of HBV-DNA in integrated form into host DNA and growing under serum-free conditions was used to test the effect of human growth hormone (hGH) on the expression of the integrated viral DNA. Data in our hands point to an early, specific effect of hGH on HBV-DNA integrated sequences which appears to be unrelated to the late effect on total protein synthesis. Moreover this approach enabled us to detect specific hGH receptors on the cell membrane of PLC/PRF/5 cell line.

Animals

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