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Biomedical subjects

D Caccavo

Publications and source records attributed to D Caccavo.

At least 37 records · Page 2Linked to original sources
PubMed1997

Long-term treatment of systemic lupus erythematosus with cyclosporin A.

OBJECTIVE: To evaluate the efficacy of long-term treatment with cyclosporin A (CSA) in systemic lupus erythematosus (SLE). METHODS: Thirty patients with SLE whose condition was either poorly responsive or unresponsive to treatment with steroids and/or cytotoxic drugs were enrolled in a prospective, nonrandomized study of CSA. Patients with hypertension or hypercreatinemia were excluded. Disease activity was evaluated according to the systemic lupus activity measure. Assessments were made prior to study entry and after 6, 12, 18, and 24 months. RESULTS: Twenty-seven patients completed at least 24 months of treatment with CSA. The mean disease activity score significantly decreased after 6 months of therapy (P < 0.01); this result was maintained throughout the study. A conspicuous steroid-sparing effect was observed following administration of CSA (P < 0.01). Side effects included hypertrichosis (63% of patients), paresthesias (23%), gastrointestinal symptoms (20%), gingival hyperplasia (17%), hypertension (10%), tremors (7%), and nephrotoxicity (13%). No significant changes in serum creatinine levels were observed. CONCLUSION: CSA represents a helpful second-choice treatment for patients with active SLE. Administration of CSA necessitates expert and careful followup of patients.

Adolescent↗
PubMed1997

Expression of lactoferrin on human granulocytes: analysis with polyclonal and monoclonal antibodies.

Lactoferrin (LF), an iron-binding protein present in specific granules of neutrophils, is expressed on membrane after granulocyte activation. It may represent a target for anti-neutrophil cytoplasmic antibodies (ANCA) in patients affected by some immunomediated diseases. We recently produced two MoAbs, AGM 2.29 and AGM 10.14, that recognize two spatially distant epitopes of human LF. In this study we perform a cytometric analysis in order to evaluate the expression of LF on the surface of granulocytes obtained from freshly drawn blood or after purification, in both the presence and absence of stimuli. Our results demonstrate that LF is not constitutively expressed on membrane of circulating neutrophils. After priming with phorbol myristate acetate (PMA) or tumour necrosis factor-alpha (TNF-alpha), an increased mean fluorescence intensity (MFI) was obtained on neutrophils stained with polyclonal anti-LF antibodies and with AGM 2.29. The kinetics of LF expression during activation demonstrated a progressive increase in MFI within 45 min. No increase in MFI was documented when primed granulocytes were stained with MoAb AGM 10.14, thus indicating that the epitope recognized by AGM 10.14 is not exposed at the cell surface. Following membrane permeabilization, performed in order to analyse the binding of anti-LF MoAbs to cytoplasmic LF, a marked increase in MFI was obtained by staining granulocytes with both anti-LF MoAbs. Indirect immunofluorescence (IIF) analysis confirmed that AGM 2.29 and AGM 10.14 reacted with human granulocytes, showing a cytoplasmic pattern on formalin-acetone-fixed neutrophils and a perinuclear one on ethanol-fixed cells.

Animals↗
PubMed1997

Coexpression of CD69 and HLADR activation markers on synovial fluid T lymphocytes of patients affected by rheumatoid arthritis: a three-colour cytometric analysis.

The aim of the present study was to evaluate the coexpression of very early (CD69), early (CD25) and late (HLADR) antigens and to analyse the mean fluorescence intensity (MFI) of such activation markers on synovial fluid (SF) and peripheral blood (PB) lymphocytes of patients affected by rheumatoid arthritis (RA) and other types of chronic synovitis (OCS). A three colour cytometric analysis was performed using a peridinin chlorophyll protein conjugated anti-CD3 antibody in combination with fluorescein isothiocyanate or phycoerythrin labelled anti-CD69, anti-HLADR, anti-CD25 monoclonal antibodies (mAbs). A T cell gating method was utilized, so that three sets of bivariant dot plot quadrant displays were obtained (CD69/HLADR, CD69/CD25, CD25/HLADR). A large percentage of SF T lymphocytes in RA showed the coexpression of very early and late activation antigens (CD3 + CD69 + HLADR +), whereas CD3 + CD69 + CD25 + bearing cells and CD3 + CD25 + HLADR + lymphocytes were only a small percentage. Similar results were obtained in patients with OCS, although to a lesser extent. No statistically significant differences in MFI of CD69 and HLADR positive SF T cells between RA and OCS were observed. The CD69 + CD25-HLADR + T cell subset is the most commonly represented in the synovial environment, among those we have evaluated; this phenotype may be characteristic of chronic inflammatory arthritis.

Adult↗
PubMed1997

Postoperative changes in serum interleukin-2 concentrations.

OBJECTIVE: To evaluate the postoperative changes in circulating interleukin-2 (IL-2) concentration according to the severity of the surgical injury and other postoperative variables that could influence IL-2 production. DESIGN: Prospective observational study. SETTING: University hospital, Italy. SUBJECTS: 43 patients about to undergo major operations (gastric and colo-rectal resection for cancer), intermediate operations (open cholecystectomy or mastectomy for cancer), and minor operations (hernia repair or breast lump); 24 healthy age and sex matched controls. MAIN OUTCOME MEASURES: Postoperative changes in serum concentrations of IL-2 after different degrees of surgery on the 1st, 3rd and 8th postoperative days correlated with changes in in vivo cellular mediated immunity (skin tests), duration of operation, blood transfusion or postoperative H2-blockers and antiprostaglandins. RESULTS: There were no significant variations in IL-2 serum concentrations postoperatively on ANOVA, and when the data were normalised, there were no significant changes in the median postoperative values after minor and intermediate operations. There was a slight but not significant increase in IL-2 concentrations after major operations. Neither blood transfusion nor duration of operation correlated with postoperative changes in IL-2, while postoperative antiprostaglandins and H2-blockers seemed to provide slight but not significant protection against a reduction in IL-2 concentrations. CONCLUSIONS: Circulating IL-2 does not necessarily correlate with reported in vitro postoperative production of IL-2 and therefore seems to be of little use in monitoring immunosuppression in surgical patients.

Adult↗
PubMed1996

Two spatially distant epitopes of human lactoferrin.

Lactoferrin (LF) is an iron binding protein, which may represent a target for antineutrophil cytoplasmic antibodies (ANCA) in patients affected by rheumatoid arthritis, ulcerative colitis, and primary sclerosing cholangitis. Here we describe the production and characterization of two new monoclonal antibodies (MAbs) against human LF. These MAbs (AGM 10.14, an IgG1, and AGM 2.29, an IgG2b) recognize spatially distant epitopes of LF as assessed by cross-blocking experiments. We also demonstrated by indirect immunofluorescence that both MAbs react with ethanol-fixed neutrophil granulocytes showing a perinuclear staining pattern. AGM 2.29 and AGM 10.14 have been utilized as capture and labeled tracer antibody, respectively, in a double determinant immunoassay (DDIA) to measure soluble LF. The results obtained show that this DDIA allows us to quantify even low concentrations of LF, the maximal range of the assay sensitivity being between 12 and 780 ng/ml. Therefore, AGM 10.14 and AGM 2.29 may represent useful reagents for studying the role of autoantibodies to LF as well as for measuring soluble LF, which is a reliable secretory marker of neutrophil activation.

Animals↗
PubMed1996

Antineutrophil cytoplasmic antibodies in synovial fluid and in serum of patients with rheumatoid arthritis and other types of synovitis.

OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) are present in several vasculitides and in other immunomediated diseases. The reported prevalence of ANCA in rheumatoid arthritis (RA) is variable. In addition, the presence of such autoantibodies has been poorly investigated in synovial fluid (SF). The objectives of this study were (1) to investigate the presence of ANCA both in the serum and in SF from patients with RA and other forms of synovitis (OS); (2) to analyze the reactivity of ANCA against isolated antigens proteinase 3 (PR3), myeloperoxidase (MPO) and lactoferrin (LF); and (3) to evaluate the clinical relevance of these autoantibodies. METHODS: Twenty-eight patients with RA, 13 with OS, and 17 with osteoarthritis (OA) of the knee joint were studied. No patient had clinical manifestations of vasculitis. SF and serum samples were investigated for the presence of ANCA by indirect immunofluorescence (IIF); the reactivity against PR3, MPO and LF was assessed by ELISA. RESULTS: ANCA were detected by IIF in SF of 39.3% patients with RA, 38.5% with OS, and 5.9% with OA. With 2 exceptions, patients who had ANCA in SF showed positivity also in serum. The presence of both anti-MPO and anti-LF antibodies was found in 3 patients with RA and 1 with OA; a patient with RA showed antibodies only against LF and another one with RA only against MPO. No reactivity was found against PR3. In patients with RA ANCA were not associated with disease activity. CONCLUSION: We found an increased incidence of ANCA both in SF and serum from patients with RA and OS. The pathogenic role and the clinical relevance of such autoantibodies in these diseases remain to be established.

Adult↗
PubMed1994

Anti-idiotypes against antiphospholipid antibodies are present in normal polyspecific immunoglobulins for therapeutic use.

In the present study we found that antiphospholipid activity in sera from patients with anticardiolipin antibodies was inhibited in vitro by therapeutic polyspecific normal immunoglobulins (IVIg). In fact, F(ab')2 fragments from IVIg (IVIg-F(ab')2) inhibited the binding of anticardiolipin antibodies to the corresponding antigen in a dose-dependent fashion, thus suggesting that the interaction between IVIg-F(ab')2 and anticardiolipin antibodies occurred within or near the antigen combining site. The maximal inhibition ranged from 35.25 +/- 5.56 to 64 +/- 5.48%. In addition, patients' IgG containing antiphospholipid activity specifically bound insolubilized IVIg-F(ab')2, as assessed by enzyme-linked immunosorbent assay (ELISA). These results indicate that IVIg obtained from a large pool of normal donors contain anti-idiotypic antibodies directed against idiotypes located on antiphospholipid antibodies. Moreover, our observations suggest that the reported favourable effect of high dose infusion of IVIg in patients with recurrent abortions due to antiphospholipid antibodies may depend, at least in part on inhibition of the binding of such autoantibodies to the corresponding antigens (s) and/or inactivation of idiotype bearing B cell clones.

Abortion, Habitual↗
PubMed1994

Comparative effects of arginine and other amino acid deprivation on in vitro expression of lymphocyte activation markers.

Enteral or parenteral arginine supplementation enhances lymphocyte activation after mitogenic stimulation, in rats and humans. Arginine deprivation in culture media is associated with a reduction of lymphocyte activation; this effect, however, has not yet been proven to be specific for arginine. This study was designed to evaluate the specificity of arginine deprivation from culture media on the reduction of in vitro lymphocyte activation. Peripheral blood mononuclear cells, obtained from 11 healthy volunteers, were cultured in RPMI 1640, selectively deprived of single amino acids (i.e. arginine, phenylalanine, leucine, methionine, and threonine) and supplemented with phytohemagglutinin (PHA). The expression of interleukin-2 receptor and transferrin receptor was evaluated by cytometric analysis; the levels of soluble IL-2 receptor were determined by immuno-enzymatic assay. Results were compared with those obtained by culturing cells in non-deprived, RPMI 1640 medium. The expression of transferrin and IL-2 receptor, as well as the levels of IL-2 soluble receptor, were significantly reduced in all deprived media irrespective of the lacking amino acid. These results suggest that the reduction of in vitro lymphocyte activation is not an arginine specific effect. Therefore, the known enhancement of immune response, following arginine supplementation in vivo, is likely to involve a more complex series of events.

Journal Article↗
PubMed1994

Anti-cardiolipin antibodies in autoimmune thyroid diseases.

OBJECTIVE: In recent years anti-phospholipid antibodies have gained much attention since they are frequently associated with thrombosis, recurrent abortion, and thrombocytopenia. Besides disease-specific autoantibodies, other autoantibodies reactive with both organ and non-organ specific autoantigens have been found in patients with autoimmune thyroid diseases. Therefore the objective of this study was to evaluate the presence and significance of anti-phospholipid antibodies in untreated patients with different forms of autoimmune thyroid diseases. PATIENTS AND METHODS: Thirty-one patients (26 females, five males; mean age 42.5 years) affected by different autoimmune thyroid diseases were studied. Fourteen patients were affected by Graves' disease, eight by silent thyroiditis, five by Hashimoto's thyroiditis. Four patients with Graves' disease in remission were also evaluated. Anti-cardiolipin antibodies were detected by enzyme linked immunosorbent assay. In five Graves' disease patients anti-cardiolipin antibodies were evaluated before and after 3 months of therapy with methimazole. RESULTS: Seventeen out of 31 patients were positive for IgG and/or IgM anti-cardiolipin antibodies, the highest levels occurring in three Graves' disease patients with severe thyrotoxicosis. In four of five Graves' patients evaluated before and after methimazole therapy, anticardiolipin antibodies decreased following treatment. None of the patients with increased IgG and/or IgM anticardiolipin antibodies showed clinical manifestations of the anti-phospholipid syndrome during our observation which ranged from 1 to 5 years. CONCLUSIONS: Our results showed an increased incidence of anti-cardiolipin antibodies in patients affected by autoimmune thyroid diseases. However, these autoantibodies seem merely to represent a non-specific marker of immune dysregulation.

Adult↗
PubMed1990

Clinical effects of cyclosporin in dermatomyositis.

Auto-immune mechanisms, mostly cell mediated, have been described as the basic abnormality in polymyositis and dermatomyositis. We report here the case of a patient affected with dermatopolymyositis, resistant to therapy, who was treated with corticosteroids and cyclosporin. She presented with an infiltrative, erythematous rash on the neck, eyelids and cheeks and weakness of the proximal limb and cervical muscles. The dramatic and persistent response to cyclosporin obtained in this case represents a clear demonstration of the action of this drug in cases of dermatomyositis.

Azathioprine↗
PubMed1987

Treatment of idiopathic mixed cryoglobulinemia with alpha interferon.

Seven patients with type II idiopathic mixed cryoglobulinemia were treated with recombinant human leukocyte interferon (alpha interferon). In all of them, a conspicuous reduction of circulating cryoglobulins was noted, together with a definite, remarkable improvement of the clinical pattern. The immunologic parameters (natural killer cell activity and phagocytosis, among others) improved as well; side effects were usually mild and transient. Increases in the cryoglobulin level occurred in a few cases, but they were at least partly sensitive to readministration of alpha interferon treatment. The favorable results obtained in these cases of idiopathic cryoglobulinemia seem to be consistent and prolonged.

Adult↗
PubMedDate not supplied

Relationship among red blood cell polyamine content, phagocytic activities and plasma endotoxins in untreated colorectal cancer patients.

Polyamines are actively involved in immune processes and it is known that patients with cancer often exhibit immune deficits. Twenty-two patients with colorectal cancer were enrolled into this study, before starting conventional treatments. The relationship among the content of polyamines in red blood cells and phagocytosis and killing of monocytes and polymorphonuclear cells, and endotoxemia was investigated. The data show a negative correlation among levels of total polyamines and spermine and monocyte phagocytosis. Higher levels of spermine were present in patients with detectable circulating endotoxins. Our findings suggest a down-modulating effect of polyamines on the monocyte phagocytosis in untreated colorectal cancer patients; this effect could explain the presence of circulating endotoxins in cancer bearing patients.

Adult↗