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Biomedical subjects

G Valesini

Publications and source records attributed to G Valesini.

At least 109 records · Page 6Linked to original sources

Markers of vascular injury in Behçet's disease associated with retinal vasculitis.

The pathogenesis of vascular damage in Behçet's disease (BD) is still unknown. We investigated anticardiolipin antibodies (AC) in a genetically homogeneous group of Italian patients with BD and retinal vasculitis. In a subset, we examined the level of factor VIII-related antigen and antiendothelial cell antibodies (AECA). We found a high prevalence of AC; AECA were not found in most of our patients. Only three patients had raised levels of factor VIII-related antigen, all of whom had systemic involvement. We believe BD may be considered as a vasculitis of unknown origin in which several and different pathogenetic factors may play a role.

Adolescent↗

Production of a nef-specific monoclonal antibody by the use of a synthetic peptide.

Monoclonal antibodies have been generated against a synthetic peptide of the nef protein of human immunodeficiency virus type 1 (HIV-1) in order to further characterize the biochemical and functional nature of this protein and its role in the control of HIV-1 transcriptional regulation. Earlier studies indicated nef to be a negative regulatory factor for viral transcription, whereas more recent studies report evidence against this original hypothesis. Nef is a protein of 206 amino acids of approximately 27 kD in most HIV-1 isolates; however, in some other isolates a truncated form of 124 amino acids has been described. A peptide sequence of six amino acids, corresponding to a region of the nef protein exhibiting high-sequence homology to thymosin alpha 1 protein, has been synthesized by Merrifield solid-phase methodology. This peptide is coded by a sequence located upstream to the stop codon described in some HIV-1 isolates and then is maintained in both complete and truncated forms of the nef protein. F14.11 is a nef peptide-specific monoclonal antibody (IgG2a/k) exhibiting the ability to recognize natural nef protein in either radioimmunoassay, radioimmunoprecipitation assay, or immunocytochemical analysis. Since F14.11 is able to identify nef protein in the cytoplasm of lymphocytes from HIV-infected seronegative subjects it may prove useful in monitoring the expression of nef during the silent HIV-1 infection.

Amino Acid Sequence↗

[Biopsy of the minor salivary glands in Sjögren's syndrome].

Twenty subjects, 17 females and 3 males, mean age 55.9, with Sjögren's syndrome (13 cases: classical or secondary form--7 cases: sicca syndrome) were submitted to biopsy of the minor salivary glands of the lower lip. The histopathological findings from the salivary glands and the clinical aspects of each patient were separately evaluated, in order to find a possible connection between the degree of glandular impairment and the severity of the disease. As a result of their findings, the authors conclude that the biopsy of the salivary glands, while constituting an important element for diagnosis, cannot be considered a determining factor for making a prognosis, or for therapy, because of the extreme polymorphism in the histopathological findings, and for the relative nature of the respondents with the severity of the clinical aspects.

Adult↗

Specificity and sensitivity of diluted aPTT and anticardiolipin antibodies towards thrombosis and miscarriages in patients with systemic lupus erythematosus.

In 36 patients suffering from systemic lupus erythematosus (SLE), lupus anticoagulant (LA), as assessed by aPTT and diluted aPTT, and anticardiolipin antibodies (aCL) were studied. 14 patients, had a clinical history complicated by thrombosis and/or miscarriages. Among patients with thrombosis LA was positive in 42% and in 100% of patients when assessed by aPTT and diluted aPTT respectively; aCL were positive in 85.7% of patients. Among patients without a clinical history of thrombosis, 1 had prolonged aPTT, 3 had prolonged diluted aPTT and 5 had aCL positivity. Diluted aPTT was more sensitive than aPTT and aCL (p less than 0.01) to thrombosis and miscarriages; specificity to thrombosis and miscarriages ranged from 77.3% for aCL and 86.4% for diluted aPTT to 95.5% for aPTT but not significant differences were found. The study suggests that LA, as assessed by a sensitive test like diluted aPTT, is strongly associated to thrombosis and should therefore be considered an important risk factor.

Abortion, Spontaneous↗

Tissue plasminogen activator inhibitor in patients with systemic lupus erythematosus and thrombosis.

OBJECTIVE: To examine the relations among tissue plasminogen activator antigen, plasminogen activator inhibitor, the lupus anticoagulant, and anticardiolipin antibodies in patients with systemic lupus erythematosus. DESIGN: Prospective study of blood samples (a) from selected patients with systemic lupus erythematosus whose disease was and was not complicated by a history of thrombosis or recurrent abortions, or both, and (b) from a series of healthy controls with a similar age and sex distribution. SETTING: University based medical clinic. SUBJECTS: 23 Patients with definite systemic lupus erythematosus (American Rheumatism Association criteria), of whom 11 (eight women) aged 26-51 had a history of thrombosis or recurrent abortions, or both, and 12 (10 women) aged 23-53 had no such history. 15 Healthy subjects (10 women) aged 25-58 served as controls. MAIN OUTCOME MEASURES: Tissue plasminogen activator concentrations, plasminogen activator inhibitor activities, detection of the lupus anticoagulant, and values of anticardiolipin antibodies in the two groups of patients and in the patients with a history of thrombosis or abortions compared with controls. Other measurements included concentrations of proteins that are known to change during the acute phase of systemic lupus erythematosus--namely, fibrinogen, C3 and C4, and C reactive protein. RESULTS: Patients with a history of thrombosis or abortions, or both, had significantly higher values of tissue plasminogen activator and plasminogen activator inhibitor than patients with no such history. A significant correlation between tissue plasminogen activator and plasminogen activator inhibitor (r = 0.80) was found only in the patients with a history of complications of their disease. The lupus anticoagulant was detected in six of the 11 patients with a history of thrombosis or abortions when tested by measuring the activated partial thromboplastin time but was found in all 11 patients when tested by measuring the diluted activated partial thromboplastin time. Nine of these 11 patients had raised values of anticardiolipin antibodies. The findings showed no relation to the activity of the disease. CONCLUSIONS: A significant correlation between tissue plasminogen activator concentrations and plasminogen activator inhibitor activities was found only in patients whose systemic lupus erythematosus was complicated by a history of thrombosis or recurrent abortions. The findings show that these patients have raised plasminogen activator inhibitor activities, and the frequent association between these raised activities and the presence of the lupus anticoagulant suggests that the two may be linked.

Abortion, Habitual↗

Dilute aPTT prolongation by antiphospholipid antibodies in patients with liver cirrhosis.

The behaviour of aPTT, as assessed by standard or diluted phospholipid mixture, was investigated in 20 patients suffering from liver cirrhosis. Standard aPTT was prolonged in 13 but it was corrected by 1:1 mixture with normal plasma. Dilute aPTT performed in samples mixed 1:1 with normal plasma and calculated by the difference in time between 1:80 and 1:5 phospholipid mixture was prolonged in 9 patients, who had also significantly higher titre of anticardiolipin antibodies (p less than 0.005). Unlike patients' plasma with normal dilute aPTT, the addition of 0.05 M PC/PS liposomes to patient's plasma with prolonged dilute aPTT significantly shortened dilute aPTT (p less than 0.001). This study shows the presence of antiphospholipid antibodies in some patients with liver cirrhosis; this seems to be responsible for the prolongation of dilute aPTT.

Aged↗

Autoantibodies and common idiotypes in men and women with sperm antibodies.

Antisperm antibodies have been implicated as a causative factor of infertility and pregnancy wastage. Since concomitant autoimmune phenomena were reported in men with antisperm antibodies, we investigated known antisperm antibody-positive sera from 25 women, 27 men, and the respective seminal plasma samples. The investigated autoimmune panel included a search for antinuclear antibodies, autoantibodies (in IgG, IgM and IgA isotypes) to seven phospholipids (cardiolipin, phosphatidylserine, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid), to four histone subfractions (H1, H2A, H3, H4), and to four polynucleotides [ssDNA, dsDNA, poly(I), and poly(dT)], total immunoglobulin levels, and sperm antibody titers. The sera were also evaluated for the presence of a common anti-deoxyribonucleic acid antibody, and anticardiolipin antibody idiotypes. Levels of sperm antibody titers were significantly lower in women than in men. Both men and women with antisperm antibodies demonstrated elevated total IgG levels compared with those of normal control subjects. Only women showed elevated levels of total IgM. Sera from 24% of women and 11% of men with antisperm antibodies demonstrated antinuclear antibody titers greater than 1:40. The most striking autoantibody abnormalities were found among antiphospholipid antibodies. Sera from women with antisperm antibodies demonstrated higher autoantibody production than was found in their male counterparts. A significant correlation was found between antisperm antibodies and IgM anticardiolipin and IgA anti-phosphatidylinositol in women and between sperm antibodies and IgA phosphatidylserine antibodies in men. The presence of anticardiolipin and anti-deoxyribonucleic acid antibody idiotypes was significantly more frequent in women than in men. By means of discriminant analysis and variables selected by this mathematical model, the identification of 24 of 25 women and 26 of 27 men with antisperm antibodies was correctly predicted. These results suggest that women and men respond differently to sperm antigens. The apparent cross-reactivity between sperm antibodies and other autoantibodies, usually associated with autoimmune disease, suggests that a polyclonal B cell activation, similar to that seen in autoimmune diseases, occurs in patients with sperm antibodies.

Adult↗

Increased number of CD4 cells able to bind to natural killer cell targets in the peripheral blood of AIDS related complex patients.

CD4 cells forming conjugates with natural killer target cells (K562 cells) were measured in the peripheral blood of anti-HIV antibody positive AIDS related complex (ARC) patients and in three control groups (asymptomatic individuals at risk, normal healthy people and patients with acute hepatitis B). These CD4 cells, which are unable to kill K562 cells, were significantly increased in ARC patients as compared to the control groups. Our data indicate that classical CD4 cells are partially replaced, in ARC patients, by a population of natural killer-target binding granular CD4 lymphocytes, and suggest that the functional abnormalities of helper T cells in these patients may be in part a consequence of the relative predominance of these non IL-2 and BCGF producing cells within the circulating CD4 population.

AIDS-Related Complex↗

A calf thymus acid lysate improves clinical symptoms and T-cell defects in the early stages of HIV infection: second report.

Thymomodulin is a calf thymus acid lysate capable of inducing T lymphocyte maturation. Fifteen patients with HIV infection at different stages according to the Walter Reed classification were treated with 60 mg/day of thymomodulin syrup for more than 50 days. Two WR6B subjects had clinical and immunological parameters unchanged and died, while the patient suffering from Kaposi's sarcoma presented an evident clinical and laboratory improvement with remission of the neoplasia. The other 12 patients ranging from WR2 to WR5B showed an improvement of clinical symptoms after thymomodulin therapy accompanied by the normalization of CD4/CD8 ratio (P less than 0.001). This helpers/suppressors increase was due to a significant increase of CD4 cells (P less than 0.01) and also to a decrease of the CD8 lymphocytes (P less than 0.05). Thymomodulin administration did not cause an enhancement of the urinary levels of neopterin, a marker of T-cell activation.

Acquired Immunodeficiency Syndrome↗

"Anti-Ia reactivity in sera from patients with chronic active hepatitis (CAH)".

Anti-Ia reactivity in sera from patients with chronic active hepatitis (CAH) were characterized by determining cross-reacting specificities with the antigen defined by anti-Ia monoclonal antibody (MoAb) and by studying the effect of CAH sera on the autologous mixed leukocyte reaction (MLR). Preincubation with autoimmune CAH sera lowered the percentage of Ia+ non-T cells stained by anti-Ia MoAb. HBsAg+ve/HBeAg+ve sera did not exert any blocking activity while 4 out of 11 HBsAg+ve/anti-HBe+ve sera exerted a significant blocking effect. Preincubation of cells with normal human serum (NHS) plus aggregated IgG did not block the binding of MoAb anti-Ia. Sera from patients with autoimmune or HBsAg+ve/anti-HBe+ve CAH, that blocked the binding of anti-Ia MoAb to Ia positive target cells by more than 20%, clearly inhibited the autologous mixed lymphocyte reaction (MLR). Both IgG and IgM fractions obtained by affinity chromatography from CAH sera inhibited the autologous MLR and blocked the binding of anti-Ia antibody to Ia positive target cells. A significant positive correlation (p less than 0.001) between serum anti-Ia reactivity and serum liver membrane antibodies (LMA) was observed. In 4 "autoimmune" CAH patients, steroid treatment induced a dramatic decrease in the anti-Ia reactivity.

Antigen-Antibody Reactions↗

Use of monoclonal antibodies to identify shared idiotypes on anticardiolipin and anti-DNA antibodies in human sera.

Using hybridoma technology we produced monoclonal antibodies (MoAb) to idiotypic determinants on human anti-cardiolipin antibodies purified from a patient with SLE. Hybridomas were screened by inhibition of cardiolipin binding activity of sera from patients with SLE. Seven hybridomas were selected, two of which were studied extensively. Sera from a number of patients with SLE were found to share idiotypic determinants. This cross-reacting idiotype was not detectable on anti-cardiolipin antibodies in syphilis sera. The cross-reacting idiotype was present in sera with anti-ssDNA antibodies even though some of these sera had no anti-cardiolipin antibodies. We propose that these MoAb may recognize a regulatory idiotype.

Animals↗

Unusual dermatologic toxicity of long-term therapy with hydroxyurea in chronic myelogenous leukemia.

The unusual appearance of extensive skin ulcerations was observed in 17 patients with chronic myelogenous leukemia on continuous chemotherapy with hydroxyurea. The strict relationship between ulcers and therapy was proved by the complete (14 cases) or almost complete (3 cases) healing of lesions after therapy was discontinued. The possible pathogenetic mechanisms responsible for skin alterations are considered. The particular importance of the continuous hydroxyurea administration modality clearly emerges, suggesting the use of different administration modalities to reduce such serious side effects.

Adult↗