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Biomedical subjects

A Gibelli

Publications and source records attributed to A Gibelli.

At least 19 recordsLinked to original sources
PubMed2000

Hepatitis C virus (HCV) in lymphocyte subsets and in B lymphocytes expressing rheumatoid factor cross-reacting idiotype in type II mixed cryoglobulinaemia.

The IgMk rheumatoid factors (RF) of type II mixed cryoglobulinaemia (MC) react, in 95% of cases, with MoAbs against the cross-reactive idiotypes (CRI) Cc1 or Lc1 (corresponding to the products of the VH1 and VH4 genes). MC is closely associated with HCV infection, a virus which infects lymphocytes and may replicate in B cells. It has been suggested that HCV may induce clonal selection of B cells producing monoclonal IgMk RF in type II MC. To verify whether HCV is enriched in B cells, and in the subsets expressing Cc1 and Lc1 CRI, we studied peripheral blood lymphocytes from eight patients with MC and HCV RNA-positive sera. Seven patients had RF reacting with anti-Cc1, the other with anti-Lc1 CRI. Total lymphocytes, T cells, B cells, and Cc1+ or Lc1+, Cc1- or Lc1- B cells were purified using MoAb-coated magnetic beads. Lymphocyte subsets were then diluted to give a range of 1 x 106-1 x 103 cells and tested for HCV RNA by reverse transcriptase-polymerase chain reaction. HCV was found exclusively in B cells in seven out of eight patients. In three patients HCV was enriched in the Cc1+ cells. In one of these patients, HCV was found exclusively in Cc1+ cells, with Cc1- cells being HCV-. The data indicate that B cells from type II MC patients are almost constantly infected by HCV. In selected cases, B cell subsets expressing IgMk RF CRI are the prevalent cell type infected by HCV. Our data suggest HCV involvement in B cell dysregulation leading to cryoprecipitable IgMk RF production.

Adult↗
PubMed1998

High prevalence of antiphosphatidylinositol antibodies in young patients with cerebral ischemia of undetermined cause.

BACKGROUND AND PURPOSE: Anticardiolipin antibodies (aCL) are associated with thrombotic phenomena including cerebral ischemia in young adults. Although aCL are directed to a neoepitope formed by phospholipid and beta2-glycoprotein I (beta2-GPI), immunoassays based on cardiolipin as target antigen are widely used. We previously demonstrated that 47% of aCL-negative systemic lupus erythematosus (SLE) patients had antiphospholipid antibodies (aPL) to epitopes other than cardiolipin, and we found an association between aPL to noncardiolipin antigens and thrombosis. We now assess the prevalence and clinical significance of noncardiolipin aPL in young adults with cerebrovascular disease of undetermined etiology. METHODS: Seventy-seven non-SLE patients, aged <51 years, with cerebral ischemia were studied. Specificity of aPL were characterized by ELISAs using 7 different phospholipids: cardiolipin (CL), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), phosphatidic acid (PA), phosphatidylcholine, and phosphatidylethanolamine. RESULTS: Thirty-four patients (44.1%), had aPL to 1 or more of the following antigens: 23.4% to CL, 18.2% to PS, 15.6% to PG, 14.3% to PA, and 28.6% to PI. Fifty-nine patients (76.6%) were aCL negative. Of these subjects 23.4% showed aPL to noncardiolipin epitopes. PI was the specificity with highest prevalence in all subgroups, and in 6 patients anti-PI antibodies were the only detectable aPL. The binding of aPL to the different antigens was beta2-GPI dependent. CONCLUSIONS: Our data demonstrate a high prevalence of aPL in young adults with cerebral ischemia of undetermined cause. PI was the specificity with highest prevalence, suggesting that anti-PI antibodies may be an immunological marker in young patients with cerebrovascular disease.

Adult↗
PubMed1995

Anti-mesangial and anti-endothelial cell antibodies in IgA mesangial nephropathy.

In the present study we verified by solid phase ELISA the presence of antibodies against mesangial and endothelial cell constituents in patients with IgA-GN and Schoenlein-Henoch syndrome (SH). An antigen extract was prepared by sonication of human mesangial cell (MC) monolayers between third and fifth subculture and coated at 20 micrograms/ml on microtiter plates where sera were tested by incubation for 2 h at 37 degrees C and addition of peroxidase-conjugated anti-human IgG or IgA. In comparison to 86 normal controls, increased levels of IgG anti-MC antibodies were found in 15/84 patients with IgA-GN and 4/11 with SH. IgA antibodies were always negative. Furthermore anti-endothelial cell antibodies (AECA) were sought in the same patients and controls by ELISA as previously described. Increased levels of IgG and IgA AECA were found in 25/62 and 24/46 patients respectively. A cross-inhibition test showed that preadsorbment of positive sera for both IgG anti-MC and IgG AECA on endothelial cells in culture resulted in an inhibited binding of IgG to MC. HPLC-ELISA and Western blot analysis of the MC extract showed a significant binding of IgG from ELISA-positive sera to a protein band of 25-50 kD. Similar results were obtained by Western blot analysis of an endothelial cell extract. These results suggest the identity of the antigens recognized by IgG antibodies on endothelial cells and MC in patients with IgA-GN.

Adolescent↗
PubMed1995

Hepatitis C virus genotype in patients with essential mixed cryoglobulinaemia.

We studied 54 patients with essential mixed cryoglobulinaemia (EMC), (23 males, 31 females) mean age 61 years (range 28-77). Forty-one (76%) had type II cryoglobulinaemia and 13 (24%) type III. Antibodies to HCV were detectable by second-generation ELISA in 49 patients (91%) with confirmed or indeterminate RIBA results. HCV RNA was detected by RT PCR using 5' UTR nested primers; HCV genotypes 1a, 1b, 2 and 3a were identified by genotype-specific core-region nested primers. All patients (49) with antibodies to HCV in their serum were HCV-RNA positive; 27 (55.1%) had HCV subtype 1b and 21 (42.8%) type 2. In one patient the HCV genotype could not be determined. The genotype distribution was not different from that found in patients with chronic hepatitis C without cryoglobulinaemia. However, the presence of HCV subtype 1b correlated significantly with signs of chronic hepatitis and presence of peripheral neuropathy. Severity of disease tended to be worse in patients infected with HCV subtype 1b, but this was mainly due to liver disease. HCV genotypes may influence the clinical expression and, in particular, the severity of liver involvement in patients with EMC. Extent and severity of EMC disease in general may also be affected by the different HCV genotypes. These findings may have therapeutical implications, since the different HCV genotypes respond differently to interferon treatment.

Adult↗
PubMed1993

The hyperfibrinolytic state of liver cirrhosis: possible pathogenetic role of ascites.

We evaluated coagulation and fibrinolytic parameters in both plasma and ascitic fluid of 39 patients with ascites secondary to liver cirrhosis and in 14 cirrhotic patients without ascites, in order to verify if the peritoneal compartment could be involved in the pathogenesis of the hyperfibrinolytic state of the disease. An activation of fibrinolysis, as suggested by increased levels of FDP, D-dimer and tissue plasminogen activator (t-PA) was demonstrated in both ascitic fluid and to a lesser extent in plasma. A positive correlation was also observed between plasma and ascitic fluid plasminogen, anti-plasmin and fibrinogen, while a negative correlation was found between plasma and ascitic fluid plasminogen activator inhibitor-1 (PAI-1). Moreover, plasma PAI-1 was significantly lower in patients with ascites than in those without ascites and among ascitic patients in those who had bleeding into soft tissues when compared to those who did not present haemorrhagic events. Finally, a significant association was also shown between positivity for plasma D-dimer (> 200 ng/ml) and the presence of ascites. Taken together, our data suggest an exchange of some coagulation and fibrinolytic proteins between plasma and ascitic fluid and point out the key role of PAI-1 in regulating plasma fibrinolytic potential and in bleeding complications in cirrhotic patients.

Adult↗
PubMed1992

Structural and functional characterization of plasma fibronectin in patients with essential mixed cryoglobulinaemia.

Experimental studies suggest that plasma fibronectin may be involved in the cryoprecipitation of cryoglobulins in essential mixed cryoglobulinaemia; reduced plasma concentrations of the glycoprotein have been shown in the disease. The present work was undertaken in order to verify this latter finding and to detect a possible structural alteration of plasma fibronectin as result of enzymatic digestion of the molecule in vivo. This could, in turn, induce a decreased reactivity of the protein in immunometric assays and a reduced opsonic activity, which is normally due to the affinity of fibronectin to the C1q component of complement. Moreover, since a polymorphic variant of fibronectin has been described in plasma during experimental vascular injury and in patients with autoimmune vascular diseases, the aim of this study was also to verify the presence of a polymorphism of the glycoprotein in cryoglobulinaemic vasculitis. Twenty seven patients with essential mixed cryoglobulinaemia and 26 normal subjects were included in the study. Significantly reduced concentrations of plasma fibronectin, as assessed by ELISA, were found in patients when compared with controls (231.7 +/- 15.3 vs 316.1 +/- 16.6 mg/l, P less than 0.0002). In contrast, when affinity-purified plasma fibronectin from 10 patients with essential mixed cryoglobulinaemia and 8 healthy subjects were analysed by western blotting, employing a panel of five monoclonal antibodies to different regions of the molecule, no differences were observed between patients and controls, suggesting integrity of the glycoprotein in the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Clinical significance of endothelial damage markers in essential mixed cryoglobulinemia.

Essential mixed cryoglobulinemia (EMC) is a rheumatic disorder characterized by widespread vasculitis. To better define the nature of the vasculitic process and to possibly outline assessment methods reliable for using in a clinical context, we studied plasma levels of three endothelial related peptides: fibronectin (FN), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA), and those of thrombin-antithrombin III complexes (TAT) as markers of activation of the coagulation in 21 patients and in 16 controls. In EMC we found a picture consisting of reduced FN and increased vWF, t-PA, and TAT levels, suggesting a condition of endothelial cell damage with thrombin formation in vivo. Since we previously demonstrated the presence of chronic disseminated intravascular coagulation in these patients, we may assume that endothelial cells stressed by cryoprecipitation or stimulated by soluble mediators may be actively involved in the vasculitic process and possibly express procoagulant properties. This is a good example of the complex interplay existing between autoimmunity and coagulation mechanisms. We also suggest that FN, vWF, t-PA and TAT should be considered as additional clinical parameters when evaluating patients with EMC.

Adult↗
PubMed1988

Clinical significance of cross-linked fibrin degradation products in essential mixed cryoglobulinemia.

Cross-linked fibrin degradation products (XDP) were measured with a highly sensitive and specific ELISA in 21 patients with essential mixed cryoglobulinemia (EMC) and in 16 controls. Patients had significantly increased levels of XDP, together with abnormalities in routine coagulation tests. Moreover, XDP were higher in patients with more severe disease. These results support the hypothesis that EMC patients have a chronic disseminated intravascular coagulation (DIC), and underline the significance of XDP measurement in the evaluation of these patients.

Adult↗
PubMed1987

Ticlopidine administration to patients does not inhibit the ability of their monocytes to form rosettes and to phagocytize erythrocytes in vitro.

Inhibition of monocyte function is known to have important clinical consequences and to be present in a variety of diseases: Accordingly we evaluated the effect of Ticlopidine, a powerful and widely employed inhibitor of platelet aggregation, on the capacity of peripheral blood monocytes to ingest IgG-coated erythrocytes. Our results show that in vivo administration of this drug has no effect on monocyte phagocytosis, when tested with an in vitro assay. This finding suggests that Ticlopidine can be safely used in patients with depressed monocyte function and in those in whom an impairment of monocyte phagocytosis could lead to a deterioration of the clinical picture.

Aged↗
PubMed1986

Increased monocyte procoagulant activity (tissue factor) in patients with essential mixed cryoglobulinemia.

Procoagulant activity (PCA) of peripheral blood mononuclear cells was studied in vitro in 14 consecutive patients with essential mixed cryoglobulinemia (EMC). Mononuclear cells tested immediately after isolation expressed significantly higher PCA than cells from a matched control group (P less than 0.01). PCA generated by patients' cells after incubation at 37 degrees C for four hours without any stimulant was significantly higher than that produced by control cells (P less than 0.001). Lower mononuclear cell PCA was observed in the subgroup of patients treated with low doses of prednisone than in untreated patients. In two patients given high-dosage prednisone, cell PCA was markedly reduced. These findings suggest that mononuclear cells may be activated for PCA production in vivo by cryoglobulins or other unknown stimuli. Mononuclear phagocytes, by producing PCA in vivo, might be directly implicated in the local fibrin deposition in tissue lesions of EMC.

Adult↗
PubMed1985

[Changes in the in vitro antibody formation in B lymphoproliferative diseases].

Peripheral blood mononuclear cells from three patients with multiple myelomas (M.M.), four patients with Essential Mixed Cryoglobulinaemia (E.M.C.) and four normal adults as controls were cultivated with or without poke weed mitogen (PWM); in vitro immunoglobulin (Ig) production was measured after seven days using the enzyme-linked immunosorbent assay method (ELISA). No significant differences in Ig production were noted between patients and controls: E.M.C. patients, on the other hand, displayed considerable spontaneous IgM production (without appreciable differences, however, between spontaneous and PWM-stimulated production). M.M. patients, on the other hand, displayed only scanty spontaneous IgM production and in two cases the PWM response was completely lacking. These results were then integrated and correlated with a parallel study of similar groups of patients and controls carried out with the aim of investigating modifications in the distribution of B and T lymphocyte subpopulations. Possible interpretations of the results are discussed.

Adult↗
PubMed1985

[Various parameters of hemostasis in patients with chronic liver diseases].

The aim of the study was to investigate the nature and the possible correlations between abnormalities of platelet function and haemostatic and fibrinolytic activity in a group of 33 patients with biopsy-proven chronic liver disease. A slight decrease in prothrombin activity, AT III and plasminogen levels was noticed in the patients studied. Significantly enhanced levels of intraplatelet 5HT was also found in patients with cirrhosis and in those with chronic active hepatitis. Changes in these parameters were generally independent from each other, the only correlation being found between prothrombin activity and AT III levels in patients with cirrhosis.

Adult↗
PubMed1985

AIDS-like immunologic alterations in clinically unaffected drug users.

Peripheral blood lymphocyte subpopulations (PBLS) and HLA-DR phenotype have been evaluated in 30 IV drug users who were not affected by acquired immune deficiency syndrome (AIDS). A strongly significant reduction in helper/suppressor ratio was found in these subjects as compared to the control population. When the group under study was subdivided according to the presence or absence of signs of lymphadenopathy syndrome (LAS), the apparently unaffected individuals still had significant modifications in PBLS when compared with controls. These modifications were more marked in subjects within the LAS+ subgroup, who also showed a greater DR5 frequency than those belonging to the LAS- subgroup. The authors concluded that AIDS-like laboratory alterations are present in clinically unaffected IV drug users; the possible role of DR5 in conditioning different individual susceptibility is considered.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Bacillus subtilis selectively stimulates the synthesis of membrane bound and secreted IgA.

Peripheral blood lymphocyte subpopulations and IgA production in vitro have been studied in 30 elderly subjects. Fifteen patients were treated with Bacillus subtilis (Enterogermina, Midy) and 15 with a placebo preparation. At the end of the treatment, a significant increase was noticed in lymphocytes bearing membrane IgA and Ia+ cells in the group treated with Bacillus subtilis, but not in the controls. Similarly, a significantly enhanced spontaneous production of IgA in vitro was seen in the treated subjects. The relevance of these findings to the understanding of the mode of action of Bacillus subtilis and its usefulness in different immunodeficiency states is discussed.

Aged↗
PubMed1984

Acquired factor VIII inhibitor in a non-haemophilic patient: successful treatment with plasma exchange associated with factor VIII concentrate and immunosuppressors.

We report the successful treatment of a 55-year-old man with an acquired factor VIII inhibitor, the appearance of which followed surgery for a carcinoma of the biliary tract. The patient, who had recurrent life-threatening bleeding episodes, was treated with intensive plasmapheresis, factor VIII concentrates, azathioprine and methylprednisolone. Disappearance of the inhibitor was observed after the second series of plasma exchanges. Controls 2 and 3 months after treatment confirmed the complete absence of the inhibitor and normal levels of factor VIII. The crucial role of plasma exchange is considered and discussed.

Autoantibodies↗
PubMed1983

[Rehabilitation in myocardial infarct. Study of various coagulation parameters and platelet function].

In order to evaluate coagulation and platelet function modifications in patients undergoing a rehabilitation trial after myocardial infarction, we have studied 26 patients (24 males and 2 females) of age comprised between 37 and 62 years. The effectiveness of the trial was assessed on the basis of an increased mechanical work (expressed in Kgm) at the end of the period. Modifications in platelet number, AT III and plasminogen levels were noticed at the same time, while platelet aggregation and the levels of platelet 5 HT, plasma alfa2 macroglobulin and alfa1 antitrypsin remained unchanged. The possible effects of the trial on coagulation and platelet function are discussed.

Adult↗
PubMed1983

T-lymphocyte subsets in primary and secondary glomerulonephritis.

T-lymphocyte subsets, using the monoclonal antibodies OKT3 (peripheral T-cells), OKT4 (helper/inducer T-cells) and OKT8 (suppressor/cytotoxic T-cells) were measured in peripheral blood from 110 patients with various forms of primary and secondary glomerulonephritis (GN) (Berger's disease, membranous GN, focal glomerulosclerosis, membranoproliferative GN, lupus nephritis and mixed essential cryoglobulinaemia with GN). We have found a significantly higher OKT4+/OKT8+ ratio in patients with Berger's disease and membranous GN and a rather low OKT4+/OKT8+ ratio in patients with lupus nephritis and mixed essential cryoglobulinaemia, due to a significant decrease in OKT4+ cells. Our results suggest an imbalance in immunoregulatory mechanisms in some forms of GN.

Adolescent↗