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Biomedical subjects

F Spertini

Publications and source records attributed to F Spertini.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Diagnostic and therapeutic value of synthetic or recombinant allergens].

The field of allergy has markedly benefited of biotechnology progresses leading to the identification and cloning of numerous common allergens. This progresses have contributed to better understand the physiopathology of some complex allergic manifestations such as the oral allergy syndrome. Furthermore, the sensitivity of in vitro diagnostic tests appears to be improved by the use of recombinant allergens; in vivo, they are also able to trigger an immediate hypersensitivity reaction. In a near future, recombinant allergens may advantageously replace classical allergen extracts. Finally, the characterization of IgE binding sites on recombinant allergens, as well as T cell epitopes, open the possibility to use recombinant allergens in various immunotherapeutical approaches based on the administration of allergen peptides, allergen fragments, allergen isoforms or mutated allergens. Since those allergen preparations have a low affinity for IgE, they may substitute for classical allergen extracts in conventional immunotherapy, and improve the security of the treatment.

Allergens↗
PubMed1999

[Inhaled steroids effect on bones].

Inhaled corticosteroids (ICS) are the mainstay of asthma treatment, when an antiinflammatory agent is warranted. The development of the ICS has permitted to diminish the adverse effects associated with oral steroids and with equipotent doses there are less adverse effects with ICS on bone metabolism compared to oral steroids. There is now reassuring evidence that doses of < or = 400 micrograms for children and < or = 1000 micrograms for adults are safe and do not appear to have clinically significant adverse effect on bone density or bone growth. When exceeding the recommended thresholds for more than 3 months, osteoporosis prevention would be appropriate. Furthermore a mineral bone density measurement might be done in this context in order to identify those persons who are at risk of developing or worsening preexisting osteoporosis. Growth monitoring is justified in any child taking ICS. Biochemical markers of bone formation and resorption might give complementary information to the mineral bone density measurement. The addition of a leukotriene receptor antagonist and or of a chromone may allow a reduction in the requirement for ICS in mild to moderate asthma. Finally the achievement of an increased glucocorticoid potency combined with an improved airway selectivity and a shorter plasmatic half-life of the ICS will further contribute to diminish their effects on bone metabolism.

Administration, Inhalation↗
PubMed1999

[A society on the move and allergy].

The prevalence of allergic diseases has significantly increased over the last two decades. Rather than genetic factors, which may not have played a significant role over such a short period of time, factors related to the Western style of life and to the socio-economical level of our society have been incriminated. Indeed, significant differences were demonstrated in terms of sensitization to various allergens, and expression of allergic diseases such as allergic rhinitis, atopic dermatitis or asthma between former East Socialist and Western countries, between highly industrialized and under developed regions. The shaping of the immune system by exposition to infections may play a crucial role very early in life; the absence of exposure in contrast may lead to preferential expression of an atopic phenotype. Other factors may also play a role such as breast feeding, fat consumption, and of course allergen exposure. These epidemiological observations open new questions on the possible need for changes in our style of life.

Diet↗
PubMed1999

Idiotypic vaccination with a murine anti-dsDNA antibody: phase I study in patients with nonactive systemic lupus erythematosus with nephritis.

OBJECTIVE: To determine the safety and immunogenicity of an idiotypic anti-dsDNA vaccine in patients with nonactive systemic lupus erythematosus (SLE) and stable lupus nephritis. METHODS: Patients with SLE with a history of nephritis were randomized for vaccination with the murine anti-dsDNA monoclonal antibody (Mab) 3E10 in a dose ranging, double blind, placebo controlled study (phase I). RESULTS: Of the 9 patients injected with Mab 3E10, 5 showed a human anti-mouse antibody (HAMA) response, in large part antiidiotypic, which developed within the first 3 months in 3 strong HAMA responders, and more than one year after immunization in an initially weak HAMA responder. All but one nonresponder were receiving low dose prednisone. No adverse events, in particular no evidence of lupus flares, and no untoward laboratory findings were reported over a followup of 2 years. CONCLUSION: In patients with stable lupus nephritis, immunization with Mab 3E10 appears safe and can generate a significant antiidiotypic response. Idiotypic vaccination may be an approach to specific immunotherapy of autoimmune lupus nephritis.

Adult↗
PubMed1999

Plasmodium falciparum CS C-terminal fragment: preclinical evaluation and phase I clinical studies.

Preclinical evaluation of synthetic peptides corresponding to the C-terminal regions of the circumsporozoite (CS) protein in various Plasmodia showed that these preparations were immunogenic and safe upon injection in various animal models. Additionally, the corresponding peptide from Plasmodium falciparum was widely recognized by sera and PBL obtained from semi-immune adults living in malaria endemic areas. Moreover, the CS C-terminal peptide derived from P. berghei conferred protection upon challenge with live sporozoites in mice. A GLP preparation of the synthetic peptide corresponding to residues 282-383 of the Pf CS, NF-54 strain is currently evaluated in a open, non-randomized, Phase I human trial. Data obtained after the second antigen injection show that the malaria vaccine Pf CS 282-383 is safe, well tolerated and gives rise to high antibody titre, CD4+ and CD8+ lymphocyte responses.

Adult↗
PubMed1998

HLA typing in patients with multiple evanescent white dot syndrome (MEWDS).

BACKGROUND: Multiple evanescent white dot syndrome (MEWDS) is an acquired chorioretinal disorder of unknown etiology. We investigated the possibility that MEWDS might be related to a specific HLA subtyping. METHODS/RESULTS: Blood was obtained from nine patients affected by MEWDS. HLA-B51 was found in four of these nine patients with MEWDS. CONCLUSION: There was a 3.7-fold increased frequency of HLA-B51 in patients affected by MEWDS (relative risk 5.86). MEWDS might then be related to the presence of a specific HLA subtype, HLA-B51. However, due to the small sample size, our results need to be confirmed by further testing.

HLA Antigens↗
PubMed1998

Trace element supplementation modulates pulmonary infection rates after major burns: a double-blind, placebo-controlled trial.

Infections remain the leading cause of death after major burns. Trace elements are involved in immunity and burn patients suffer acute trace element depletion after injury. In a previous nonrandomized study, trace element supplementation was associated with increased leukocyte counts and shortened hospital stays. This randomized, placebo-controlled trial studied clinical and immune effects of trace element supplements. Twenty patients, aged 40 +/- 16 y (mean +/- SD), burned on 48 +/- 17% of their body surfaces, were studied for 30 d after injury. They consumed either standard trace element intakes plus supplements (40.4 micromol Cu, 2.9 micromol Se, and 406 micromol Zn; group TE) or standard trace element intakes plus placebo (20 micromol Cu, 0.4 micromol Se, and 100 micromol Zn; group C) for 8 d. Demographic data were similar for both groups. Mean plasma copper and zinc concentrations were below normal until days 20 and 15, respectively (NS). Plasma selenium remained normal for group TE but decreased for group C (P < 0.05 on days 1 and 5). Total leukocyte counts tended to be higher in group TE because of higher neutrophil counts. Proliferation to mitogens was depressed compared with healthy control subjects (NS). The number of infections per patient was significantly (P < 0.05) lower in group TE (1.9 +/- 0.9) than in group C (3.1 +/- 1.1) because of fewer pulmonary infections. Early trace element supplementation appears beneficial after major burns; it was associated with a significant decrease in the number of bronchopneumonia infections and with a shorter hospital stay when data were normalized for burn size.

Adult↗
PubMed1997

Modulation of T-cell response to phospholipase A2 and phospholipase A2-derived peptides by conventional bee venom immunotherapy.

BACKGROUND: Immunologic mechanisms of desensitization are still incompletely understood. Safer methods of immunotherapy with reduced risks of anaphylaxis need to be developed. OBJECTIVE: To study the effects of conventional venom immunotherapy (VIT) on phospholipase A2(PLA2)-specific T cells and on T-cell reactivity to short and long synthetic peptides that map the PLA2 molecule. METHOD: Proliferation of a CD4+ cell-enriched peripheral blood mononuclear cell fraction and cytokine secretion by T cell lines from patients hypersensitive to bee venom and undergoing VIT in response to PLA2 and PLA2 synthetic peptides were measured. RESULTS: T-cell proliferation in response to three synthetic peptides, 40 to 60 amino acids long and mapping the entire PLA2 molecule with an overlap of 10 residues (1 to 59, 51 to 99, and 90 to 134) steadily increased during the first 14 weeks of VIT corresponding to the treatment period with incremental doses of antigen. These results are in contrast to the low proliferation indices obtained with short (15 amino acid-long) peptides, and the inability to characterize the immunodominant region of the molecule with short peptides. At the end of VIT (after 3 to 5 years), there was correspondingly, a marked decrease in T cell responsiveness to PLA2 and to its long synthetic peptides. This response was paralleled by a shift in the pattern of cytokine secretion by T cell lines from a T(H0)-type to a T(H1)-type pattern. CONCLUSION: After a transient increase in T-cell proliferation, late VIT was characterized by T-cell hyporesponsiveness to allergen and by modulation of cytokine secretion from a T(H0)-type to a T(H1)-type pattern. Because of their capacity to recruit multiple T-cell epitopes, long peptides mapping the entire PLA2 molecule appear to be efficient T cell stimulators and may represent potential candidates for peptide immunotherapy.

Adjuvants, Immunologic↗
PubMed1997

Monitoring responses to antiretroviral treatment in human immunodeficiency virus type 1 (HIV-1)-infected patients by serial lymph node aspiration.

Fine-needle aspiration was used to collect lymph node cells (LNC) from 9 antiretroviral-naive patients entering a double-blind single- or combined-drug study of zidovudine, zalcitabine, and saquinavir. LNC were obtained twice before and 1 and 6 months after initiation of treatment. The effect of antiretroviral treatment on virus load ranged from no response to a dramatic decrease in plasma and LNC human immunodeficiency virus (HIV) RNA levels. The decrease in unspliced or spliced (or both) HIV RNAs in LNC was correlated with but consistently smaller than the decrease in plasma viremia. When present, the increase in blood CD4 T cells was, in general, moderate and transient. However, a striking rise in blood CD4 T cell count and in LNC CD4:CD8 ratio was observed in the 1 patient with the deepest sustained decrease in HIV RNA level in both plasma and lymph nodes.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Delineation of PLA2 epitopes using short or long overlapping synthetic peptides: interest for specific immunotherapy.

BACKGROUND: Venom immunotherapy is definitely indicated in severe systemic anaphylactic reactions to bee stings, but is not devoided of risks of anaphylaxis. Safer methods of immunotherapy need to be developed. OBJECTIVE: To delineate phospholipase A2 T-cell epitopes using short 15mer vs long 40-60mer overlapping peptides, and to approach the potential interest of a venom immunotherapy based on the use of long peptides (1-60, 51-99, 90-134) mapping the whole phospholipase A2 molecule vs a restricted number of immunodominant epitopes. METHODS: Proliferation of a CD8+ T cell depleted peripheral blood mononuclear cell fraction and short-term T-cell lines from unselected bee venom hypersensitive patients in response to phospholipase A2 synthetic peptides. RESULTS: Whereas T-cell proliferation to 15mer overlapping peptides was weak, T-cell response to long overlapping peptides was in contrast vigorous in all patients, mostly directed to C-terminal peptide 90-134. Our results did not support the concept of rare dominant T-cell epitopes, and disclosed T-cell responses to multiple epitopes in several patients. No significant IgE-binding to long overlapping peptides was detected except in one patient against peptide 90-134. CONCLUSION: 15mer peptides might not be sensitive enough to fully delineate all potential T-cell epitopes scattered along the allergen. Since they do not bind IgE in vitro or only weakly, and taking into account a T-cell response frequently directed to multiple epitopes, long overlapping peptides may represent ideal tools for immunotherapy.

Bee Venoms↗
PubMed1997

Acute inflammatory reaction associated with endoluminal bypass grafts.

PURPOSE: Nonspecific inflammatory reactions characterized by local tenderness, fever, and flu-like discomfort have been seen in patients undergoing endoluminal graft placement in the abdominal aorta or the femoral arteries. We undertook a study to assess the clinical and laboratory parameters of this inflammation. METHODS: Ten patients with femoropopliteal artery (n = 9) or aortic (n = 1) lesions were treated with EndoPro System 1 stent-grafts made of nitinol alloy and covered with a polyester (Dacron) fabric. Eleven patients implanted with a bare nitinol stent served as the control group. RESULTS: In the stent-graft group, four patients showed clinical signs of acute inflammation manifested by fever and local tenderness. Three of these patients suffered thrombosis of the stent-grafts during the first month of follow-up. Plasma levels of interleukin-1 beta and interleukin-6 in all stent-graft patients were markedly increased 1 day after intervention (7.3 +/- 2.8 versus 90.2 +/- 34.1 pg/mL and 15.6 +/- 5.8 versus 175.5 +/- 66.3 pg/mL, respectively; p < 0.01). This was followed by an increase in fibrinogen (3.0 +/- 0.2 versus 5.0 +/- 0.2 g/L; p < 0.05) and C-reactive protein (14.6 +/- 3.3 versus 77.5 +/- 15.0 mg/L; p < 0.01) at 1 week. No direct correlation between the inflammatory markers and symptoms could be found. In vitro analysis showed that individual components of the stent-graft did not activate human neutrophils, whereas the intact stent-graft itself induced a marked neutrophil activation. CONCLUSIONS: The component of the self-expanding stent-graft responsible for the nonspecific inflammatory reaction was not identified in this study. It is likely that the stent-graft itself or some as yet unrecognized element of the device other than the Dacron fabric or metal alloy may be a potent in vivo inducer of cytokine reaction by neutrophils.

Aged↗
PubMed1996

Epitope-specific engagement of the protein tyrosine phosphatase CD45 induces tumor necrosis factor-alpha gene expression via transcriptional mechanisms.

The common leukocyte antigen CD45 plays a central role in T cell activation in coupling the T cell receptor (TCR) to the phosphatidylinositol pathway via interactions with TCR-associated protein tyrosine kinases lck and fyn. We here demonstrate that engagement of CD45 by monoclonal antibodies (mAb) on activated T cells induces tumor necrosis factor (TNF)-alpha as well as TNF-beta, interleukin (IL)-2 and IL-3 gene expression. When human alloreactive T cells are stimulated with mAb 4B2, which recognizes a determinant common to all CD45 isoforms, a vigorous production of TNF-alpha mRNA was detected, which peaked 2 h later. Anti-CD45 mAb cross-linking was required. In contrast, neither mAb 10G10, which recognizes an epitope distinct from the one recognized by mAb 4B2, nor mAb UCHL-1, a CD45RO-specific antibody, induced any significant increase in TNF-alpha transcription. Nuclear run-on transcription assays demonstrated that CD45 cross-linking caused transcriptional activation of the TNF-alpha gene. De novo protein synthesis was not required, since incubation with cycloheximide (CHX) did not block transcriptional activation. CHX in contrast up-regulated TNF-alpha gene expression and increased transcript half-life, an effect that was under control of post-transcriptional mechanisms. Engagement of CD45 by itself did not affect transcript stability. CD45 ligation resulted in TNF-alpha secretion. These results indicate that in addition to its role in TCR/CD3-mediated T cell activation, CD45, in an epitope-specific manner, may act as a primary signaling molecule, leading to the transcriptional regulation and secretion of a major pro-inflammatory cytokine.

Antibodies, Monoclonal↗
PubMed1996

Transcriptional and translational control of TNF-alpha gene expression in human monocytes by major histocompatibility complex class II ligands.

While non-stimulated primary human monocytes exhibit very low levels of tumor necrosis factor (TNF)-alpha mRNA, direct binding of the staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) to major histocompatibility complex (MHC) class II molecules results in a fast (peak 1 h after stimulation), transient induction (sevenfold) of TNF-alpha mRNA. This induction correlates with a fourfold increase in transcription rates of the TNF-alpha gene, as detected by run-on assays, and does not require de novo protein synthesis. Mapping of DNase-I hypersensitive sites (DHS) discloses two constitutive DHS, one located far upstream (within the TNF-beta promoter) and the other centered at -39 +/- 40 bp relative to the major TNF-alpha transcription start site, suggesting that the TNF-alpha gene was transcriptionally competent even prior to MHC class II engagement. Furthermore, stimulation of human monocytes with either TSST-1 or lipopolysaccharide increases the translational efficiency of TNF-alpha mRNA, as shown by a shift in the distribution of this mRNA species in polysome gradients and the translation rates of TNF-alpha measured by immunoprecipitation from cells pulsed with [35S] methionine. The increase in translation efficiency of TNF-alpha mRNA is independent of the half-life of TNF-alpha transcripts, which under the conditions used is unchanged. Taken together, our data indicate that TNF-alpha expression is tightly regulated by MHC class II ligands, both at the transcriptional and translational levels.

Bacterial Toxins↗
PubMed1996

Comparison of effects of topical levocabastine and nedocromil sodium on the early response in a conjunctival provocation test with allergen.

BACKGROUND: Multiple ocular challenges or seasonal trials have demonstrated the efficacy of levocabastine and nedocromil sodium in the treatment of allergic conjunctivitis. OBJECTIVE: This study was designed to compare the protective effect of levocabastine eye drops with that of nedocromil in a conjunctival provocation test with allergen. METHODS: Twenty-four patients with allergic conjunctivitis to grass pollen were recruited. After a preliminary provocation to determine conjunctival reaction threshold (erythema of at least 50% of the conjunctiva with ocular itching), patients were randomized to receive either topical levocabastine (0.05%) or nedocromil (2%) 15 minutes before provocation. Erythema and pruritus intensity were recorded at each concentration of allergen up to the reaction threshold. RESULTS: The allergen concentration level necessary to reach reaction threshold was increased (p < 0.001) after treatment with both drugs. Comparison between screening and each treatment indicated that the shift in allergen concentration was significantly greater after levocabastine treatment than after nedocromil treatment (p = 0.019). Conjunctival itching (symptom score) and erythema (percent conjunctival surface) were also better controlled by levocabastine than by nedocromil during provocation (p < 0.05). CONCLUSION: In a provocation test with allergen, levocabastine and nedocromil were both effective in increasing the conjunctival tolerance to allergen, with better protection provided by levocabastine.

Administration, Topical↗