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Biomedical subjects

D Vercelli

Publications and source records attributed to D Vercelli.

At least 91 records · Page 5Linked to original sources

[Use of betamethasone in heart surgery].

Clinical experience carried out on 88 high risk patients subjected to open-heart surgery with ECC is reported. The series was subdivided into two groups of patients (A and B) and to these were applied the same surgical and anaesthesiological approaches and the same extracorporeal perfusion technique. In Group B, however, a different method of myocardial protection was employed, in the form of preventive administration of pharmacological doses of betamethasone (3 mg/kg). The results point to a marked reduction in the incidence of postoperative complications in the heart, lungs and bloodstream in Group B compared with Group A.

Adolescent↗

A comparison of two staging systems for myeloma.

The data were evaluated for 43 myeloma patients who had had complete follow-up. A comparison was made of the prognostic significance of the staging systems proposed by Durie and Salmon (DS) and by Merlini, Waldenström, and Jayakar (MWJ) for multiple myeloma. Both of the three-stage systems show good statistical correlation with survival in our global analysis, although a higher log-rank P value was found for DS. Moreover, only stage I and III survival curves are really heterogeneous in MWJ, while each curve is significantly different from the other in DS.

Actuarial Analysis↗

Bone marrow percentage of plasma cells in the staging of monoclonal gammopathies.

In the present study, the relationships between percentage of bone marrow plasma cells (BMP%), tumor cell mass, stage, and survival are statistically analyzed in a large number (90) of monoclonal gammopathies (MG). Though BMP% has not been included among the criteria for the staging of multiple myeloma, our results indicate that the above mentioned parameters correlate at highly significant degrees. BMP% is therefore proposed as a new, useful parameter in the staging of MG.

Bone Marrow↗

Analysis of gamma4 germline transcription in human B cells.

BACKGROUND: Allergic reactions occur rarely in patients with chronic helminth infections, although FcepsilonRI-bearing cells are sensitized with anti-parasite IgE and are exposed to antigen. The inhibition of allergic reactivity is due to 'blocking antibodies', predominantly IgG4. IgG4 antibodies represent 50-95% of anti-filarial IgG, and have blocking activity because they compete with cell-bound IgE for allergen binding. Blocking IgG4 antibodies have also been detected in patients treated with immunotherapy. However, the molecular mechanisms of IgG4 regulation have remained unexplored. We address this issue starting with the IL-4-dependent induction of gamma4 germline transcription, an essential step in the commitment to isotype switching. RESULTS: gamma4 germline transcripts were cloned and shown to contain Igamma4 spliced to the 5' portion of Cgamma4 using the splice donor site shared by gamma1 and gamma3 germline transcripts. Sequence analysis located the human Igamma4 exon thick approximate0.6 kb upstream of the Sgamma4 region. Four major transcription start sites located 547-583 bp upstream of the Igamma4 splice donor site were identified by primer extension analysis. A HindIII/NaeI construct (-413/+466) had the highest activity in reporter assays. Transcription was induced 4.6-fold by IL-4, 2.1-fold by CD40 engagement, and 14.5-fold by a combination of the two signals. Thus CD40 crosslinking enhanced IL-4-dependent transcription by 3.1-fold, showing that the two stimuli act synergistically. CONCLUSION: As we understand more about IgG4 regulation, our hope is to apply to allergy the lesson we learnt from helminth infections.

Antibodies, Blocking↗

The monocyte/IgE connection: may polymorphisms in the CD14 gene teach us about IgE regulation?

BACKGROUND: Total IgE levels are known to be under genetic control. Linkage studies have indicated that one or more loci on chromosome 5q may control total IgE, as well as asthma and bronchial hyperresponsiveness to nonspecific stimuli. Our group has undertaken a systematic analysis of chromosome 5q, and has recently characterized five single nucleotide polymorphisms at position -1619, -1359, -1145, -809 and -159 in the promoter of the gene encoding CD14, the myeloid pattern recognition receptor that is critical for efficient innate immune response to lipopolysaccharide (LPS) and bacterial ligands. METHODS: Carriers of the major CD14 haplotypes were analyzed for serum levels of IgE and soluble CD14. In vitro IgE synthesis was assessed in peripheral blood mononuclear cells stimulated with IL-4 in the presence or absence of LPS or anti-CD14 monoclonal antibodies. RESULTS: An inverse correlation was found between serum levels of IgE and soluble CD14. On the other hand, in vitro IL-4-dependent IgE synthesis was strongly upregulated by LPS, but suppressed by anti-CD14 monoclonal antibodies. CONCLUSION: Our results highlight the complex role played by monocytes in IgE regulation.

Cells, Cultured↗

Interleukin-13 regulates the phenotype and function of human monocytes.

The monocyte glycosylphosphatidylinositol (GPI)-linked protein CD14 serves as the receptor for lipopolysaccharide (LPS), and regulates monocyte-lymphocyte interactions. We investigated whether CD14 expression is regulated by interleukin (IL)-13, a member of the chromosome 5 cytokine family. IL-13 inhibited CD14 expression on human monocytes. CD14 down-regulation resulted in the inhibition of LPS-induced release of tumor necrosis factor alpha, and involved neither shedding nor activation of endogenous GPI-anchor-cleaving enzymes. The CD14/actin RNA ratio was decreased 7-fold in IL-13-treated monocytes. Our results suggest that IL-13 down-regulates CD14 by suppressing CD14 RNA expression. Down-regulation of CD14, the LPS receptor, may play a major role in the anti-inflammatory effects of IL-13.

Antibodies, Monoclonal↗

Regulation of human epsilon germline transcription: role of B-cell-specific activator protein.

Germline transcripts initiate from promoters upstream of the immunoglobulin switch region, and are necessary to target the appropriate switch region for recombination and switching. Different cytokines activate transcription at the appropriate germline promoter. Because binding sites for B-cell-specific activator protein (BSAP) are located upstream of several switch regions in the immunoglobulin heavy chain gene cluster, BSAP might play a role in the regulation of germline transcription and isotype switching. We investigated whether BSAP plays a role in the transcriptional regulation of the epsilon germline promoter in human B cells. Our results showed that BSAP plays a role in both IL-4-dependent induction and CD40-mediated upregulation of human epsilon germline transcription. BSAP is unique among the transcription factors that regulate epsilon germline expression, because it is B cell specific, and is at the merging point of two signalling pathways that are critical for IgE switching.

B-Lymphocytes↗

Regulation of IgE synthesis.

The role of IgE in allergic disease is by now well recognized. The study of the cellular basis of IgE regulation has been actively pursued to gain insights into the pathogenesis of a disease that affects a considerable proportion of the population. More recently, the molecular events underlying IgE synthesis have become the focus of intense interest, in an attempt to characterize the signals involved in isotype-specific regulation of immunoglobulin synthesis. Recent evidence from different laboratories indicates that induction of IgE synthesis requires two signals: one is IgE isotype-specific, and is delivered by IL-4, the other is a B cell activating signal that can be delivered through a variety of pathways. We will herein review what is currently known about the mechanisms underlying the synthesis of IgE in humans, as they are revealed through cellular and molecular biology studies.

Antibodies, Monoclonal↗