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Biomedical subjects

Daniela Giordano

Publications and source records attributed to Daniela Giordano.

10 recordsLinked to original sources

17beta-estradiol (E2) modulates cytokine and chemokine expression in human monocyte-derived dendritic cells.

The effects of estrogen on the immune system are still largely unknown. We have investigated the effect of 17beta-estradiol (E(2)) on human monocyte-derived immature dendritic cells (iDCs). Short-term culture in E(2) had no effect on iDC survival or the expression of cell surface markers. However, E(2) treatment significantly increased the secretion of interleukin 6 (IL-6) in iDCs and also increased secretion of osteoprotegerin (OPG) by DCs. Furthermore, E(2) significantly increased secretion of the inflammatory chemokines IL-8 and monocyte chemoattractant protein 1 (MCP-1) by iDCs, but not the production of the constitutive chemokines thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). However, after E(2) pretreatment the lipopolysaccharide (LPS)-induced production of MCP-1, TARC, and MDC by DCs was clearly enhanced. Moreover, mature DCs pretreated with E(2) stimulated T cells better than control cells. Finally, we found that E(2) provides an essential signal for migration of mature DCs toward CCL19/macrophage inflammatory protein 3beta (MIP3beta). In summary, E(2) may affect DC regulation of T-cell and B-cell responses, as well as help to sustain inflammatory responses. This may explain, in part, the reason serum levels of estrogen correlate with the severity of certain autoimmune diseases.

CD40 Antigens↗

Interactive online program to improve cephalometric tracing skills.

Cephalometric analysis has a key role in orthodontic clinical practice and research. The skills needed to accurately trace radiographs can be acquired only through practice. We developed an interactive, Internet-based system to help students hone their cephalometric tracing skills. The online system allows students to practice any time and at their own pace, and receive immediate graphical feedback on the quality of their work. It also allows instructors to update the collection of cases available to students for practice.

Cephalometry↗

Differentiation of human monocytes in vitro with granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor produces distinct changes in cGMP phosphodiesterase expression.

The cytokines macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) promote differentiation of monocytes into macrophages with distinct phenotypes and unique functional abilities. In this report, we characterize how monocytes and macrophages differentiated from monocytes with M-CSF and GM-CSF regulate their cGMP levels by controlling which phosphodiesterases (PDEs) and guanylyl cyclases (GCs) are expressed. We find that PDE1B and PDE2A are expressed at low levels in monocytes, but are the major cGMP PDEs expressed in macrophages. M-CSF differentiation triggers increased expression of PDE1B and PDE2A, while GM-CSF causes a large increase only in PDE1B. Based on PDE expression, we identified THP-1 and U937 cell lines as possible models for studying the roles of PDE1B and PDE2A in macrophage function. We additionally characterized changes in expression of GCs upon differentiation. We found that GM-CSF differentiation triggers a small decrease in soluble guanylyl cyclase (sGC) and a large increase in GC-A, while M-CSF significantly decreases sGC.

Cell Culture Techniques↗

Cyclic nucleotides promote monocyte differentiation toward a DC-SIGN+ (CD209) intermediate cell and impair differentiation into dendritic cells.

Recruitment of monocytes into tissues and their differentiation into macrophages or dendritic cells (DCs) depend on the microenvironment of the inflammatory site. Although many factors affecting this process have been identified, the intracellular signaling pathways implicated are poorly understood. We found that cyclic nucleotides regulate certain steps of monocyte differentiation into DCs. Increased levels of the cyclic nucleotides, cAMP or cGMP, inhibit differentiation of CD14(+)/CD1a(low) monocytes into CD14(-)/CD1a(high) DCs. However, DC-specific ICAM-3-grabbing nonintegrin (CD209) up-regulation was not affected by cyclic nucleotides, indicating that DC development was not blocked at the monocyte stage. Interestingly, Ag-presenting function was increased by cyclic nucleotides, as measured by the higher expression of MHC class II, CD86, and an increased ability to stimulate CD4(+) T cell proliferation in allogeneic MLRs. Although cyclic nucleotides do not completely block DC differentiation, they do block the ability of DCs to be induced to mature by LPS. Treatment during DC differentiation with either cAMP or cGMP analogues hampered LPS-induced expression of CD83, DC-LAMP, and CCR7 and the ability of DCs to migrate toward CCL19/macrophage-inflammatory protein 3beta. Interestingly, the induction of a CD16(+) subpopulation of cells was also observed. Thus, signals causing an increase in either cAMP or cGMP levels during monocyte recruitment to inflammatory sites may restrain the activation of acquired immunity by blocking DC development and migration to lymph nodes. At the same time, these signals promote development of an active intermediate cell type having properties between those of macrophages and DCs, which might contribute to the innate immune response in the periphery.

8-Bromo Cyclic Adenosine Monophosphate↗

Systemic reactions to allergen immunotherapy: a review of the literature.

Since its introduction the safety of specific immunotherapy (SIT) was assessed by many well-designed studies. SIT is accepted as an effective treatment of allergic diseases despite the occurrence of side-effects, among which systemic reactions (SRs) are the most dangerous. The reported frequency of SRs after SIT varies among the studies and several factors influence it. Asthma is a particular risk factor for systemic side-effects. Furthermore, SRs occur more often in patients with high allergen sensitivity as determined by skin testing or RAST. Making dosage errors is also considered to be a high risk. It is reported that reactions are more common during rush and clustered induction treatment, whereas a significantly lower incidence of SRs occurred with the use of standardized modified allergen vaccines than with aqueous extracts. On the basis of valuable guidelines, precautions to minimize the risk of SRs from SIT were recommended. Injections should be given or supervised by doctors well-trained in this form of treatment in a clinic where there is the immediate availability of a resuscitative equipment. Consideration should be given to evaluate the patient's conditions and to monitor subjects for a minimum of 30 minutes after the injections. Therefore, if appropriately done, the risk of SIT is negligible.

Antigen-Antibody Reactions↗

Decrease of specific and total IgE levels in allergic patients after BCG vaccination: preliminary report.

BACKGROUND: A systemic reaction to mycobacteria biases the balance of T helper cell types 1 and 2 toward T helper cell type 1. BCG vaccination mimics some characteristics of mycobacterial infection. Children who have undergone tuberculin conversion after BCG vaccination seem to be more likely to lose their atopic symptoms. Inhibition of both allergic response and airway hyperreactivity after vaccination for mycobacteria has been observed in animal experiments. OBJECTIVE: To evaluate the effects that BCG vaccination has on the serological status of allergic people. PARTICIPANTS AND METHODS: This study included 20 volunteers with a history of allergic rhinitis who were required to undergo BCG vaccination by Italian law. Epicutaneous allergy testing with a panel of common seasonal and perennial inhalational allergens and 2 blood withdrawals were performed. The serum total IgE levels and the serum allergen-specific IgE levels of each individual were measured just before BCG vaccination and again 4 months later. Total IgE levels were determined using the paper radioimmunosorbent test, and allergen-specific IgE levels were determined using the radioallergosorbent test. RESULTS: Total IgE and allergen-specific IgE levels were significantly decreased after BCG vaccination (P =.004 and P<.001, respectively). CONCLUSION: BCG, an effective stimulus for cell-mediated immunity, deserves further study to evaluate its ability to modulate the immune response associated with allergic rhinitis.

Adult↗

Type 5 phosphodiesterase expression in the human vagina.

OBJECTIVES: It has been demonstrated that clitoral and vaginal tissues express nitric oxide synthase isoforms in a way that parallels that of the penile corpus cavernosum. Considering the role of the vagina in the female sexual response and the anatomic connection between the clitoris and the anterosuperior vaginal wall, our aim was to study the distribution of type 5 phosphodiesterase (PDE5) in the anterosuperior wall of the human vagina. METHODS: Immunohistochemistry was performed on the vaginal tissue of 14 women obtained at autopsy and on exfoliated cells of the vaginal epithelium obtained from 5 healthy female donors. Specific antibodies against PDE5 were tested on both paraffin sections and cytologic smears. Immunoblotting experiments were performed in parallel with the same antibodies. RESULTS: The histologic analysis of human cadaveric vaginal tissue revealed that PDE5 immunoreactivity was mostly localized in the smooth muscle of vessels, forming a pseudocavernous tissue in the vaginal wall and endothelium. The Skene periurethral glands and vaginal epithelium were also positive for the antibody. The latter finding was confirmed using exfoliated cells of the vaginal epithelium harvested in vivo. CONCLUSIONS: The presence and tissue distribution of PDE5 in the human vagina suggest that the integrated system of nitric oxide synthase-PDE5 may play a physiologic role not only in the male sexual response but also in female sexual arousal.

3',5'-Cyclic-GMP Phosphodiesterases↗

Differential expression and localization of calmodulin-dependent phosphodiesterase genes during ontogenesis of chick dorsal root ganglion.

The level and characteristics of 3'-5'-cyclic nucleotide phosphodiesterase (PDE) activity in chick dorsal root ganglion (DRG) extracts of 5-day posthatching chicken (P5) and E10 and E18 embryos were studied. At all stages, PDE activity is stimulated by calcium and calmodulin. A 5-fold increase in basal cAMP and cGMP PDE activity is evident from E10 to E18, while from E18 to P5 basal PDE activity remains constant. Ion exchange chromatography elution profile indicates that PDE1 isoforms represent the bulk of the PDE activity present. Inhibition studies were performed in order to distinguish the activity due to PDE1A, B and C. Western blot analysis using anti-mammalian PDE1A, B and C specific antibodies was also performed. Densitometric analysis of the stained bands reveals that PDE1B and PDE1C display a prominent increase between day 10 and day 18 of development (eight- and 3.6 fold, respectively) while a more limited increase (1.6- and 1.5-fold) is observed between E18 and P5; on the other hand PDE1A shows continuously increasing levels throughout development. Immunohistochemical analysis was performed with isoform specific antibodies used for western blot analysis. PDE1A immunoreactivity is found in the cytoplasm and fibers of several neurons differing in size and distributed throughout the ganglion. PDE1B staining is evident on all neurons, however, fibers appear very faintly labelled. All neurons appear stained by PDE1C antibody, although the intensity of immunostaining is always heterogeneous in different neuronal populations: no staining was evident on fibers or in non-neural cells. The distinct spatial and temporal expression patterns of PDE1 isoforms may indicate their different physiological roles in developing and mature chick DRG.

3',5'-Cyclic-AMP Phosphodiesterases↗