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F Spertini

Publications and source records attributed to F Spertini.

At least 73 records · Page 4Linked to original sources
PubMed1996

[Multiple evanescent white dot syndrome: a genetic predisposition?].

BACKGROUND: Multiple evanescent white dot syndrome (MEWDS) is a benign acquired isolated chorioretinal disorder. Symptoms include photopsia, visual blur and scotomas. Ocular examination reveals multiple white dots at the level of the deep retina. A parainfectious disorder was suggested but the exact mechanism of MEWDS is still unknown. Postulating that MEWDS might be an antigen driven inflammatory reaction, we analyzed HLA subtypes in patients with MEWDS. PATIENTS AND METHODS: Sixteen patients were diagnosed with MEWDS in Lausanne from 1985 to 1994. Blood was withdrawn in 9/16 patients. HLA-A, -B and -DR were sought. RESULTS: HLA-B51 was detected in 4/9 patients (44.4%). Other HLA subtypes were detected sporadically. CONCLUSIONS: The frequency of HLA-B51 haplotype was found to be 3.7 times more elevated than in a normal control caucasian group. This suggests the possibility that MEWDS might be a genetically determined disorder as it is the case for other ocular diseases like Birdshot chorioretinopathy (HLA-A29), Harada's disease (HLA-DRMT3), acute anterior uveitis (HLA-B27) or Behçet's disease (HLA-B51). We have no explanation for the presence of HLA-B51 in both Behçet's disease and MEWDS. The association of HLA-B51 and MEWDS needs confirmation by further testing.

Chorioretinitis↗
PubMed1996

Viral load and immunophenotype of cells obtained from lymph nodes by fine needle aspiration as compared with peripheral blood cells in HIV-infected patients.

We wished to establish the feasibility of fine needle aspiration of lymph nodes as a noninvasive method for measuring subsets of immune cells and viral load in HIV-infected patients. Twenty-five patients (CD4+ T cell range 4-760/microl, median 362) were selected. Lymph node aspiration was attempted in 21 patients. Lymph node cells (LNC), ranging from 6 x 10(3) to 2 x 10(6) (median 6 x 10(5)) were obtained in 17 subjects, and compared with peripheral blood mononuclear cells (PBMC) obtained simultaneously. Immunophenotype could be determined by flow cytometry in 9 patients. Mean percent of CD4+ CD3+ T cells in LNC and PBMC and 23.2 and 14.6. Mean percent of CD8+ CD3+ T cells in LNC and PBMC was 23.1 and 45.0, respectively. Therefore, CD4+/CD8+ ratios were much higher in LNC (mean +/- SD: 1.06 +/- 0.31) than in PBMC (0.35 +/- 0.13). The amount of HIV DNA (11 patients) and RNA (8 patients) was determined in the plasma, LNC, and PBMC by competitive reverse transcriptase-polymerase chain reaction (RT-PCR). The number of copies of viral DNA/10(5) cells was higher in LNC than in PBMC (LNC/PBMC ratio ranger: 0.54-25, median 3.4). The number of copies of unspliced viral RNA/10(5) cells was much higher in LNC than in PBMC (LNC/PBMC ratio range 65-1,159, median 435). The plasma RNA copy number, a measure of circulating cell-free virus, was correlated with the RNA copy number in PBMC, but not in LNC. A RT-PCR system specific for spliced transcripts was also used to assess the level of transcripts independent of genomic RNA. This assay also detected more signal in LNC than in PBMC. The level of spliced transcripts in LNC and PBMC correlated with the amount of full-length RNA detected by competitive PCR. A semiquantitative coculture assay with lymphoblasts from healthy donors was used to assess the infectivity of LNC as compared with PBMC in 14 patients. The minimum number of LNC necessary to cause a positive coculture ranged from 10(3) to > 10(5) (median 10(4)); the corresponding number for PBMC ranged from 10(3) to > 10(6) (median 5 x 10(5)). In most patients selected for palpable lymph nodes, LNC could be obtained by fine needle aspiration, thus allowing noninvasive monitoring of viral burden in lymphoid tissue. The present study also suggests that both T-cell subsets and viral load differ in the blood and lymphoid tissue, which raises the question of whether the study of the lymphoid tissue would yield better prognostic markers of disease course.

Adult↗
PubMed1995

[Polyarthralgia, fever and purpura in a patient known to have splenomegaly].

A 43-year-old patient was admitted for swollen and painful ankles, knees and elbows, palpable purpura of the lower extremities and fever. Splenomegaly had been diagnosed 5 years previously. At clinical workup, spleen and liver size were increased and purplish papular skin lesions were noted above the ankles. Erythrocyte sedimentation rate was 2 mm/h. ASAT and ALAT as well as rheumatoid factor were moderately elevated. Serology was positive for hepatitis C. Differential diagnosis of palpable purpura and complementary diagnostic procedures are discussed.

Adult↗
PubMed1995

[Occupational activities and allergic respiratory manifestations].

The authors review aspects of occupational asthma that are important for the practitioner. Insurance problems are dealt with in the light of local regulations. Detailed chapters are devoted to baker's asthma (various aeroallergens), to plastic workers and painters (isocyanates) and to respiratory diseases among farmers. Finally, a list of other occupations in which asthma typically occurs is given. The responsibility of practitioners in charge of young patients about to choose their future profession is underlined.

Agricultural Workers' Diseases↗
PubMed1995

Role of two-dimensional electrophoretic analysis in the diagnosis and characterization of IgD monoclonal gammopathy.

Over a period of 5 years, an isolated light chain (kappa = 9, lambda = 12) was detected in 21 sera by immunofixation electrophoresis. Further analysis with anti-delta- and anti-epsilon-specific antisera identified four delta heavy chains, all associated with a lambda light chain, and no epsilon heavy chains. For evaluation of the role of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) in the diagnosis of IgD paraproteins, as a possible alternative or complement to immunofixation, IgD paraproteins were retrospectively analyzed by 2D-PAGE. Delta Heavy chains migrated to gel areas clearly distinguishable from other heavy chains alpha, gamma, or mu, and in a wide range of isoelectric points (pI: 5.4-8). In one serum, the monoclonal delta chain had a pI range comparable to that of albumin and was undetectable. However, all four delta chains were easily identified when analyzed from affinity-purified immunoglobulin fractions. These observations showed the following: 1) IgD paraproteins are not rare among apparently isolated monoclonal light chains detected by routine immunofixation, strongly confirming the need for further analysis with anti-delta antisera, before assumption of a light-chain disease. 2) 2D-PAGE analysis of affinity-purified immunoglobulin fractions allowed correct identification of IgD monoclonal gammopathies in all cases. 3) However, although 2D-PAGE analysis is now easy to perform, well standardized, and highly sensitive, this technique remains time-consuming and expensive, and does not appear suitable for routine practice as a first-line diagnostic procedure. 2D-PAGE should find its place as a complement to immunofixation and in the definitive demonstration, in selected ambiguous cases, of the clonal pattern of a suspected gammopathy at immunofixation.

Blotting, Western↗
PubMed1995

[Churg-Strauss syndrome].

Allergic granulomatosis and angiitis (Churg-Strauss syndrome) is characterized by a systemic vasculitis in the context of bronchial asthma and eosinophilia. Pathologically, there is a necrotizing vasculitis of small arteries and veins with extravascular granulomas, infiltration of vessels and perivascular tissue with eosinophilia. Pulmonary, peripheral nervous system, cardiovascular and cutaneous manifestations are most frequently encountered. Renal failure and high blood pressure are more rare. These features, within the setting of bronchial asthma and eosinophilia, differentiate Churg-Strauss syndrome from polyarteritis nodosa. Steroid associated to cyclophosphamide have considerably improved the prognosis and risk of relapse.

Adult↗
PubMed1994

Engagement of the common leukocyte antigen CD45 induces homotypic adhesion of activated human T cells.

The transmembrane tyrosine phosphatase CD45 plays an important role in TCR/CD3-mediated signaling. We demonstrate in this study that ligand binding to the CD45 molecule induces homotypic cell adhesion of activated, but not resting, T lymphocytes. mAbs to CD45 (4B2 and 10G10) and to CD45RO (UCHL1), but not to CD45RA (IOL2), caused sustained adhesion of alloreactive T cell lines. In contrast, none of the anti-CD45 mAbs induced aggregation of resting peripheral T cells. CD45-mediated adhesion of activated T cells involved both CD11a/18-dependent as well as CD11a/18-independent mechanisms. mAb 4B2 induced a strictly CD11a/18-dependent adhesion that was completely inhibited by both the protein kinase C (PKC) inhibitor sphingosine and the protein tyrosine kinase (PTK) inhibitors genestein and herbimycin A. In contrast, mAb 10G10, which recognized an epitope on CD45 distinct from the one recognized by mAb 4B2, induced CD11a/18-independent adhesion that was inhibited by sphingosine, but not by genestein or herbimycin A. Biochemical studies revealed direct evidence for activation of protein kinase C and protein tyrosine kinase after engagement of CD45 on activated T cells by mAb 4B2. These results indicate that in addition to its role in TCR/CD3-mediated activation, engagement of CD45 transduces signals that result in enhanced adhesiveness of activated T cells.

Antigens, CD↗
PubMed1994

Two-dimensional polyacrylamide gel electrophoresis analysis of cryoglobulins and identification of an IgM-associated peptide.

The clonality of immunoglobulins (Igs) in cryoprecipitates (n = 41) was studied by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Our series included 24 cryoglobulins characterized by immunofixation electrophoresis (IF), 12 'trace amount' cryoglobulins, defined by a protein content in the precipitate of less than 0.05 mg/ml of serum, and five cryoglobulins of undetermined protein composition by IF. 2-D PAGE analysis showed polyclonal IgG associated either with monoclonal Igs (type II cryoglobulins; n = 14) or with polyclonal IgM (type III cryoglobulins; n = 14). In ten cryoprecipitates (two 'trace amount' cryoglobulins as well as seven of 19 type II and as one of five type III cryoglobulins by IF) polyclonal IgG were associated with a mixture of polyclonal and monoclonal IgM. These cryoglobulins were tentatively named type II-III cryoglobulins. A monoclonal IgM was observed in one cryoprecipitate (type I cryoglobulins). Two cryoglobulins presented unexpected 2-D patterns, characterized by the presence of oligoclonal IgM, with trace amounts of Igs of different isotypes (tentatively named type II-III(variant) cryoglobulins). A peptide of 44 kDa with a pI of 5.45 was observed in all cryoglobulins containing IgM (n = 40). This peptide was also present in purified monoclonal or polyclonal IgM fractions. N-terminal microsequencing (12 amino acid residues) revealed that this IgM-associated peptide was an unknown protein. Our results highlight the role of 2-D PAGE as an aid in the analysis of cryoglobulins.

Amino Acid Sequence↗
PubMed1993

Immunoglobulin heavy chain constant region determines the pathogenicity and the antigen-binding activity of rheumatoid factor.

An IgG3 monoclonal antibody, 6-19, derived from unmanipulated MRL/MpJ-lpr/lpr mice, exhibiting cryoglobulin and anti-IgG2a rheumatoid factor activities, induces skin leukocytoclastic vasculitis and glomerulonephritis when injected into normal mice. To determine the role of the gamma 3 heavy chain constant region in the generation of cryoglobulins and associated tissue lesions, we have established an IgG1 class switch variant, clone SS2F8, from the 6-19 hybridoma by sequential sublining. Here we report that the SS2F8 monoclonal antibody, which loses the cryoglobulin activity but retains the rheumatoid factor activity, fails to generate skin and glomerular lesions. The lack of pathogenicity of the IgG1 SS2F8 switch variant is not due to mutations in variable regions, since nucleotide sequence analysis shows no differences between both clones. In addition, we have observed that the IgG1 SS2F8 switch variant exhibits < 10% of the rheumatoid factor activity, as compared with the IgG3 6-19 monoclonal antibody, suggesting that the self-associating property of the gamma 3 isotype promotes antibody-binding activity. The present study indicates that the cryoglobulin activity associated with the gamma 3 isotype is critically involved in the pathogenicity of 6-19 anti-IgG2a rheumatoid factor monoclonal antibody and highlights the pathogenic relevance of autoantibodies of the IgG3 subclass in murine systemic lupus erythematosus.

Animals↗
PubMed1993

Two-dimensional electrophoresis as an aid in the analysis of the clonality of immunoglobulins.

In this paper, we summarize our five-year observation of two-dimensional polyacrylamide gel electrophoretic (2-D PAGE) analysis of immunoglobulin (Ig) light (L) chain patterns on serum/plasma and/or purified human Ig, and compare this technique with agarose electrophoresis and/or immunofixation examination. Polyclonal Ig L chains were seen as large "fuzzy" areas with several zones of high density. The majority (71%) of the monoclonal Ig L chains of monoclonal gammopathy detected by conventional electrophoresis appeared as a single large and well-defined spot on 2-D PAGE analysis, with the remaining appearing as multiple spots. The presence of oligoclonal Ig, reflected by multiple spots in 2-D PAGE, and several bands in immunofixation, was observed in 5 of 26 patients after allogeneic bone marrow transplantation and in 5 patients with tumors. In the majority (77%) of hypergammaglobulinemia, L chains appeared as a wide spread of small and well-defined spots in 2-D PAGE analysis. This pattern suggested oligoclonal Ig-secreting B cell clone expansion, and corresponding abnormalities were not detected with immunofixation. 2-D PAGE analysis also detected oligoclonal Ig expansions whereas conventional electrophoretic examination was normal in 10 additional patients after bone marrow transplantation, and in 6 of 10 immunocompetent patients with acute severe infections. Analysis of the Ig L chain pattern of a severe combined immune-deficient mouse populated with human peripheral blood leukocytes confirmed the skewed human Ig production in the model. In summary, 2-D PAGE appears to be a sensitive tool for the analysis of Ig diversity in various clinical situations.

Animals↗
PubMed1993

Pattern variations of polyclonal and monoclonal immunoglobulins of different isotypes analyzed by high-resolution two-dimensional electrophoresis.

High-resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was used to analyze serum samples and purified immunoglobulins (Ig) obtained from "normal" individuals and from patients diagnosed with monoclonal gammopathies (MG) (n = 47; 5 IgA, 15 IgM, 15 IgG, 4 biclonal IgG, 1 IgD, 7 Bence Jones proteins). Polyclonal and monoclonal heavy (H) chains were located at different restricted gel positions according to their isotype. Monoclonal H chains appeared as sets of spots characterized by charge (pI) and size (M(r)) microheterogeneity. Most of the monoclonal gamma chains were not seen on the gels (12/15). Supplementary polypeptides of 45-48 kDa were detected in serum samples containing monoclonal IgM, but were not seen in MG of other isotypes. However, these polypeptides were not specifically associated with monoclonal IgM because they were also found on protein maps of purified polyclonal IgM. Polyclonal light (L) chains appeared as cloudy bands containing several zones of higher density, whereas monoclonal L chains were usually resolved as single sharp spots. In 6 samples, monoclonal L chains were not seen, and in 9 samples, they appeared as two or more spots, characterized by different pI and/or M(r). In one sample obtained from a patient with a biclonal gammopathy, the L chains were resolved as 4 different spots. Our results confirm that 2-D PAGE is an excellent tool to study Ig. Analysis of the L chain region of the gels was particularly informative. Several monoclonal L chains exhibited heterogeneous two-dimensional spot patterns, suggesting that "subtile" clonal mutations of B-cell lineage and/or posttranslational modifications were involved in their production.

Antibodies, Monoclonal↗
PubMed1992

[Global approach to the treatment of chronic asthma in adults].

The reduction of the bronchial inflammatory reaction, in itself a triggering event for bronchospasm, is one of the main targets for treatment in bronchial asthma. An early engagement of anti-inflammatory agents is, therefore, as necessary for long-term treatment as the reduction of irritating or antigenic environmental factors. Assessment of therapeutic efficacy necessitates a regular and long-lasting surveillance of the patient. It can be provided by peak-flow measurement, performed by the patient himself. Finally, the close cooperation by patient and physician as well as the elaboration of a training program teaching the patient pathophysiology, symptoms and therapeutic possibilities are decisive for therapeutic success, i.e. the best possible restitution of pulmonary function.

Adrenal Cortex Hormones↗
PubMed1992

Role of protein kinase activation in the induction of B cell adhesion by MHC class II ligands.

Engagement of MHC class II (Ia) molecules on B cells induces tyrosine phosphorylation, phosphoinositide turnover, elevation of intracellular calcium concentrations, and a rise in cAMP levels. However, a role for these biochemical signals in mediating functional responses induced by Ia ligands remains largely undefined. In this study, we utilized the induction of B cell adhesion by Ia ligands to demonstrate a role for signals transduced via Ia molecules in the generation of a functional response. Ia ligands that induced B cell aggregation induced tyrosine phosphorylation, whereas Ia ligands that did not induce B cell aggregation failed to induce any detectable tyrosine phosphorylation. Ia-induced B cell aggregation and tyrosine phosphorylation were inhibited by genistein and by herbimycin A, inhibitors of tyrosine kinases (PTK). Sphingosine and calphostin C, inhibitors of protein kinase C (PKC), also inhibited Ia-induced adhesion whereas HA1004, an inhibitor of cyclic nucleotide-dependent kinases, did not. Ia ligands induced both LFA-1-dependent and LFA-1-independent B cell adhesion. These two pathways of cell adhesion differed in their requirement for activation signals. PKC activation was sufficient for LFA-1-dependent adhesion, whereas LFA-1-independent adhesion required independent phosphorylation events mediated by PKC and by PTK. These results provide functional relevance for biochemical signals transduced via Ia molecules by demonstrating that Ia-induced B cell adhesion is mediated by the activation of PKC and by one or more PTK.

B-Lymphocytes↗
PubMed1992

Signals delivered via MHC class II molecules synergize with signals delivered via TCR/CD3 to cause proliferation and cytokine gene expression in T cells.

We examined the role of MHC class II molecules in transducing signals to activated human T cells. Cross-linking of MHC class II molecules synergized with submitogenic amounts of anti-CD3 mAb in causing proliferation and secretion of the cytokines IL-2, IL-3, IFN-gamma, and TNF-alpha by MHC class II-alloreactive T cell lines. Signaling via MHC class II molecules in T cells resulted in activation of tyrosine kinases, in generation of inositol phosphates, and in Ca2+ mobilization that was abrogated by the tyrosine kinase inhibitor herbimycin A. Thus, like signaling via TCR/CD3, signaling via MHC class II molecules involved tyrosine kinase-dependent activation of phospholipase C, resulting in phosphoinositol turnover and Ca2+ flux. However the signaling pathways coupled to MHC class II molecules and to TCR/CD3 differed, because engagement of the transmembrane phosphatase CD45 inhibited Ca2+ fluxes triggered via TCR/CD3 but not Ca2+ fluxes triggered via MHC class II molecules.

Antigens, CD↗
PubMed1992

Engagement of MHC class I molecules induces cell adhesion via both LFA-1-dependent and LFA-1-independent pathways.

We here demonstrate that ligand binding to MHC class I molecules induces homotypic cell adhesion of lymphocytes and monocytes. mAb to beta 2-microglobulin caused sustained, largely LFA-1-independent adhesion whereas mAb to the MHC class I alpha H chain caused transient LFA-1-dependent adhesion. Both the protein kinase C inhibitor sphingosine and the tyrosine kinase inhibitor genistein abrogated MHC class I-mediated cellular adhesion. These results indicate that MHC class I molecules transduce signals that induce cell adhesion and suggest that interaction between MHC class I-restricted T cells and APC may result in reciprocal enhanced adhesiveness of these cells.

Animals↗