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F Silvestris

Publications and source records attributed to F Silvestris.

69 records · Page 4Linked to original sources

In vitro inhibition of anti-DNA producing cells from systemic lupus erythematosus patients by autologous anti-F(ab')2 antibodies.

We have previously documented an inverse relationship between serum levels of anti-F(ab')2 antibodies and disease activity in systemic lupus erythematosus (SLE). The present study focused on the specific in vitro inhibition of anti-DNA producing cells from SLE patients by autologous anti-F(ab')2 antibodies. Peripheral blood lymphocytes (PBL) from eleven inactive SLE patients with no apparent disease activity were cultured in vitro to evaluate anti-DNA antibody secretion. Low levels of synthesis of anti-DNA antibody were detected in 3 of 11 SLE patients using unstimulated PBL; on the contrary, pokeweed mitogen stimulation of cultured cells increased production of anti-DNA in all SLE subjects. Parallel cultures were also performed in the presence of heterologous and autologous anti-F(ab')2 antibodies and results on production of anti-DNA evaluated. Lymphocytes from SLE patients in remission showed inhibition of synthesis of anti-DNA antibodies when autologous anti-F(ab')2 antibodies were added to the cultures, whereas production of anti-tetanus toxoid IgG by the same cells was not significantly altered under the same conditions. These data suggest that a functional anti-idiotypic role may be assigned to anti-F(ab')2 antibodies during clinical remission of SLE.

Antibodies, Anti-Idiotypic↗

Human anti-F(ab')2 antibodies and pepsin agglutinators react with Fv determinants.

Affinity-purified human IgG anti-tetanus antibody was subjected to papain and then pepsin digestion, and residual fragments retaining antibody activity were re-isolated by adsorption and elution from Sepharose-tetanus toxoid columns. Both Fab' and Fv fragments isolated by gel filtration showed strong reactivity with anti-F(ab')2 antibodies. Failure of tetanus toxoid to completely block reactivity of anti-F(ab')2 antibody with anti-tetanus Fv fragments indicates that these antibodies react with framework antigens within variable antibody regions.

Antibodies, Anti-Idiotypic↗

IgM, IgA and IgG rheumatoid factors in patients with rheumatoid arthritis and normal donors.

IgM, IgA, and IgG Rheumatoid Factors (RF) were measured by ELISA assay in serum from 26 patients with definite rheumatoid arthritis (RA) and 11 normal controls. IgM-RF was assayed by ELISA, radioimmunoassay, and also by the standard latex fixation test in all sera from RA patients. In patients with RA quantitative amounts of IgM, IgA, and IgG-RF as estimated by ELISA were highly correlated. Significant correlations were found between a physician's rating of disease activity and IgG-RF (r = 0.44; p less than .02) and IgA-RF (r = 0.38; p = .06 but not for IgM-RF as measured in any of the three assays.

Adult↗

Discrepancy in the expression of autoantibodies in healthy aged individuals.

Sera from 50 healthy old subjects and from 51 young controls were tested by ELISA assays for a panel of autoantibodies, including IgM RF, anti-DNA, anti-F(ab')2, antithyroglobulin, anti-human albumin, anti-human hemoglobin, anti-secretory component from human IgA, and anti-gliadin. In vitro production of anti-DNA as well as anti-F(ab')2 antibodies were measured after stimulation of PBMC by pokeweed mitogen (PWM) in 12 healthy elderly subjects and 11 young controls. Sera from elderly donors contained threefold higher amounts of IgM RF than young controls (P less than 0.001). On the contrary, the levels of anti-DNA as well as anti-F(ab')2 antibodies were similar in both groups (P less than 0.3 for the two determinations). Anti-DNA and anti-F(ab')2 antibodies were also measured in supernates of PWM-stimulated glass nonadherent PBMC cultures from both old and young healthy donors without finding any significant difference between the two groups. Additional ELISA tests were also performed in both elderly and young control sera to detect antibodies against six other different antigens. No significant difference was found in the percentages of positive sera between the two groups. This discrepancy in production of IgM RF compared to other autoantibodies in healthy elderly subjects does not provide support for a general increase of autoantibodies with aging. The biological significance of an increase in IgM RF with aging remains to be determined.

Aged↗

Family distribution of anti-F(ab')2 antibodies in relatives of patients with systemic lupus erythematosus.

Recently we reported an inverse relationship between the levels of anti-F(ab')2 antibodies and disease activity in systemic lupus erythematosus (SLE). The present study focused on anti-F(ab')2 antibodies in unaffected relatives of SLE patients. Sixty sera from first degree family members from 11 SLE families and 49 sera from 8 control families were studied. Percentage of SLE family members with anti-DNA antibodies (15%) was higher than than control family sera (8%, P less than 0.05). Anti-F(ab')2 antibodies were measured using ELISA assays. The SLE family sera had higher amounts of anti-F(ab')2 antibodies than the normal control family group (P = 0.0051). In an effort to determine if anti-F(ab')2 antibodies found in high titres in the sera of some SLE family members had specificity for the F(ab')2 fragment of anti-DNA antibodies of the SLE relative patients, DNA-anti-DNA inhibition experiments were performed using anti-F(ab')2 prepared from the relative in parallel with anti-F(ab')2 prepared from normal controls with equivalent high titres of serum anti-F(ab')2. Inhibition exhibited by anti-F(ab')2 of first degree relatives was higher than that obtained from control normal donors (P less than 0.02). Such differences in inhibition were not recorded using a control tetanus toxoid-anti-tetanus toxoid assay. In direct binding ELISA experiments, peroxidase-conjugated anti-F(ab')2 antibodies from the same first degree relative showed high relative specificity against purified anti-DNA antibodies of his SLE proband when compared to those obtained against different anti-DNA antibodies isolated from unrelated SLE patients (P less than 0.001). Such a substantial difference was not observed in parallel experiments using peroxidase conjugated anti-F(ab')2 antibodies from normal controls unrelated to SLE subjects.

Adolescent↗

Studies of anti-F(ab')2 antibodies and possible immunologic control mechanisms in systemic lupus erythematosus.

Studies of anti-DNA and anti-F(ab')2 antibodies were performed by enzyme-linked immunosorbent assay in 51 patients with systemic lupus erythematosus (SLE). Patients with severe, uncontrolled disease showed high levels of anti-DNA and low levels of anti-F(ab')2 antibodies. Patients with quiescent SLE usually showed high levels of anti-F(ab')2 and low levels of anti-DNA antibodies. Isolated anti-F(ab')2 antibodies from autologous SLE remission serum or from the sera of unaffected siblings of SLE patients showed maximum inhibition in test systems using affinity-purified SLE anti-DNA antibodies reacting with single-stranded DNA.

Adult↗

In vitro modulation of cell-mediated immunity by prostaglandin E2. I. Enhancing-inhibitory effects on antibody-dependent cellular cytotoxicity.

The modulating effects of Prostaglandin E2, solubilized in medium, were observed in the antibody-dependent cytotoxic system. The pretreatment of effector cells with PGE2 up to 5 hours increased significantly the cytotoxic activity. The enhancement was distributed in both Non-T and T lymphocyte fractions suggesting a more pronounced activation of K cells. The effect was abrogated by pretreating lymphocyte suspensions with Indomethacin before exposure to prostaglandin. On the other hand, the addition of PGE2 during the test led to an inhibition of the cytotoxic capacity. Taken together, these results imply either a relationship between endogenously produced PGE2 and the concentration of exogenous PGE2 or the influence of PGE2 on microenvironment (i. e. exchange of calcium and magnesium through the cell membrane) during the cytolytic phenomenon.

Antibody-Dependent Cell Cytotoxicity↗

Familial systemic sclerosis following exposure to organic solvents and the possible implication of genetic factors.

Both genetic and environmental factors are suspected to play a role in the pathogenesis of systemic sclerosis. We compare its occurrence in 3 sisters working in a dry cleaner's shop and exposed to occupational inhalation of organic solvents. Two sisters showing the human leukocyte antigens (HLA)-DR11/DQ7 haplotype were affected. The third has maintained the same job as the others for over 10 years and has no signs of the disease. The fact that she has a different HLA haplotype points to the significance of genetic factors in increasing the risk of systemic sclerosis. It is suggested that the DR11/DQ7 haplotype enhances the development of a clinical subset of systemic sclerosis associated with production of anti-topoisomerase-I antibodies, and that environmental triggers prime the disease in subjects with this genetic background.

Female↗

[Apoptosis or programmed cell death: regulatory and pathophysiological mechanisms].

Apoptosis is an active death process genetically encoded to eliminate abnormal or unwanted cells. The phenomenon is induced by a cascade of molecular events leading to nucleolysis by endonucleases and involves a number of membrane receptors and cytoplasmic proteins. These structures (including Fas, müllerian inhibiting substance, p53 and the c-myc oncogene) contribute, by interactive regulatory mechanisms, to the promotion or inhibition of apoptosis, on the basis of both external stimulus and cell activation state. Since apoptosis is a selective process to suppress defective cells, deregulation of genes encoding for such apoptosis-related proteins could be relevant in the growth of several tumors. Remarkably, overexpression of the bcl-2 gene in a few experimental lymphomas has been associated with neoplastic proliferation because of its inhibitory effect on apoptosis. Conversely, early activation of Fas, an apoptosis-inducing gene on HIV-infected CD4+ lymphocytes, is thought to aggravate T cell lymphopenia in HIV infection by increasing the level of normal apoptosis. Genetic deregulation of apoptosis has also been postulated in the pathogenesis of several diseases. Indeed, while preliminary studies suggest that apoptosis plays a role in autoimmune disorders including systemic lupus erythematosus, the pathogenesis of a few degenerative neuropathies, such as Alzheimer's disease, could depend on a similar altered mechanism in apoptosis of neuronal cells. However, no studies are presently available to suggest that exploitation of molecular events of apoptosis would imply therapeutic progress.

Acquired Immunodeficiency Syndrome↗

[Methods for assessing programmed cell death].

Apoptosis, namely programmed cell death, is a fundamental mechanism involved in both organogenesis and tissue homeostasis. Since this process is genetically controlled, its defective regulation plays a role in the pathogenesis of several diseases including inflammatory and degenerative disorders, autoimmunity and neoplasia. Several methods have been suggested to identify the cellular events including the modification of cell size, cytoplasmic condensation and nuclear degradation occurring during this phenomenon. The cell morphologic changes can be observed in detail by electronic microscopy, while the chromatin cleavage is well detected by both electrophoretic and flow cytometry techniques, using various fluorochromes able to bind specifically the double-stranded DNA. Here we review the different techniques to evaluate apoptosis with respect to their sensitivity in both qualitative and quantitative analyses.

Apoptosis↗

Benign monoclonal gammopathy with IgG anti-DNA, anti-Sm and anti-F(ab')2 activity.

OBJECTIVE: To study anti-DNA idiotypic markers and anti-DNA activity in human monoclonal immunoglobulin proteins. METHODS: Seventy human IgG M-components intentionally selected for cationic electrophoretic characteristics were studied for F4 and 31 anti-DNA idiotypic markers and anti-DNA as well as anti-F(ab')2 antibody activity. RESULTS: Eight of 70 M-components showed significant anti-DNA activity. In two both anti-DNA and anti-F(ab')2 activity occurred together. One IgG-2 kappa M-component showed extremely high anti-ds DNA, anti-Sm, anti-F(ab')2 and anti-Sm/ RNP ELISA activity. Cross inhibition studies showed that each reactive antigen inhibited the other. N-terminal V-region sequencing showed the VH3, VK3 subgroup. Anti-idiotypic rabbit antibody produced against this M-component showed strong reactivity with affinity purified IgG anti-DNA and anti-F(ab')2 from most SLE patients and normal subjects. CONCLUSION: Monoclonal human immunoglobulins may contain multiple autoantibody specificities including anti-DNA; anti-Sm, anti-Sm/RNP, and anti-F(ab')2. Many antibodies with these specificities share common V-region antigens. Such relationships could contribute to idiotypic immune regulation and control.

Aged↗

[Malignant neoplasms and AIDS. Review of the literature and critical considerations on a case of epidermoid carcinoma of the anus].

During the past few years the neoplasms defining the diagnosis of AIDS are in apparent evolution and a new distribution of specific tumors is currently reported in the literature. Besides the Kaposi's sarcoma, non-Hodgkin's lymphomas, and uterine cervical carcinoma, other malignancies are frequently diagnosed in HIV+ population, particularly during the advanced stages of the infection. The pathogenesis of such an increase of tumor diffusion is apparently related to the persistence of several herpes viruses including HHV8 and HPV whose molecular interaction with HIV may contribute to the genetic variations suitable for tumor development. The epidermoid anal carcinoma is a tumor whose appearance is increasingly recurrent in HIV+ patients, although it is not considered as an AIDS-defining neoplasia. This tumor is prevalent in HIV+ homosexual men, in particular during the full-blown immunodeficiency disease. Here we report the case of a patient whose diagnosis of AIDS was emphasized by the concurrent presence of the anal tumor.

Acquired Immunodeficiency Syndrome↗