Dehiscence of posterior semicircular canal.
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Humans↗
Biomedical subjects
Paolo Piazza
Publications and source records attributed to Paolo Piazza.
Development and implementation of a direct detection, quantitation and validation system for class I MHC self-peptide epitopes.
Gene and protein expression studies demonstrate that viral-infected and malignant cells undergo a complex series of transcriptional and translational changes. As class I MHC molecules reflect the proteome (and changes therein) by presenting intracellular peptide epitopes, the development of a direct discovery and validation technology for the identification of these epitopes is needed. We developed our technology using HIV-1-infected cells as a model. A combination of hollow fiber class I HLA protein production and mass spectrometric epitope analysis indicated a 3-fold increase in the host-peptide VLMTEDIKL(720-728), [eIF4G((720))] presented by the HLA-A*0201 of HIV-1-infected cells. This peptide is derived from the host-protein translation of eukaryotic initiation factor 4-gamma (eIF4G) that plays a pivotal role in cellular protein synthesis. Direct confirmation of expression of this self-encoded antigen was performed through development of a T cell receptor mimic (TCRm) monoclonal antibody (mAb). The resulting 4F7 TCRm demonstrated specific recognition of the eIF4G((720))-A*0201 complex. Staining of normal PBMCs with 4F7 showed only low levels of endogenous eIF4G((720)) presentation by HLA-A*0201, while 4F7 staining of HIV-1-infected PBMCs revealed an approximately 3-fold increase in eIF4G((720))-A*0201. The MHC-peptide complex was initially detectable by 4F7 at 3 days post-infection, with a steady increase through day 8. We therefore demonstrate the successful development and implementation of an integrated discovery and validation technology system for direct identification and confirmation of class I MHC-peptide epitopes on cells.
Antibodies, Monoclonal↗
DC-SIGN is a receptor for human herpesvirus 8 on dendritic cells and macrophages.
Human herpesvirus 8 (HHV-8) causes Kaposi's sarcoma and pleural effusion lymphoma. In this study, we show that dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN; CD209) is a receptor for HHV-8 infection of myeloid DCs and macrophages. DC-SIGN was required for virus attachment to these cells and DC-SIGN-expressing cell lines. HHV-8 binding and infection were blocked by anti-DC-SIGN mAb and soluble DC-SIGN, and mannan, a natural ligand for DC-SIGN. Infection of DCs and macrophages with HHV-8 led to production of viral proteins, with little production of viral DNA, similar to HHV-8 infection of vascular endothelial cells. Infection of DCs resulted in down-regulation of DC-SIGN, a decrease in endocytic activity, and an inhibition of Ag stimulation of CD8+ T cells. We propose that DC-SIGN serves as a portal for immune dysfunction and oncogenesis caused by HHV-8 infection.
Adult↗
Revision glomus tumor surgery.
The infratemporal fossa approach type A is the best way to deal with recurrent tympano-jugular paragangliomas because facial nerve rerouting is fundamental to reaching the area of the internal carotid artery, where recurrence is likely to occur. Preservation of lower cranial nerve function is not feasible when there is tumor infiltration of the medial wall of the jugular bulb; any attempt at nerve dissection increases the risk of leaving some tumor remnants. Correct management of the internal carotid artery, including preoperative stent insertion or permanent preoperative balloon occlusion, is usually a fundamental step when dealing with these highly vascularized lesions. Because of the tumor tendency to infiltrate the bony structures, aggressive drilling of the temporal bone is also advised, especially at the level of the petrous apex. Patients affected by uncontrolled recurrences still die of this disease.
Adult↗
DC-SIGN on B lymphocytes is required for transmission of HIV-1 to T lymphocytes.
Infection of T cells by HIV-1 can occur through binding of virus to dendritic cell (DC)-specific ICAM-3 grabbing nonintegrin (DC-SIGN) on dendritic cells and transfer of virus to CD4+ T cells. Here we show that a subset of B cells in the blood and tonsils of normal donors expressed DC-SIGN, and that this increased after stimulation in vitro with interleukin 4 and CD40 ligand, with enhanced expression of activation and co-stimulatory molecules CD23, CD58, CD80, and CD86, and CD22. The activated B cells captured and internalized X4 and R5 tropic strains of HIV-1, and mediated trans infection of T cells. Pretreatment of the B cells with anti-DC-SIGN monoclonal antibody blocked trans infection of T cells by both strains of HIV-1. These results indicate that DC-SIGN serves as a portal on B cells for HIV-1 infection of T cells in trans. Transmission of HIV-1 from B cells to T cells through this DC-SIGN pathway could be important in the pathogenesis of HIV-1 infection.
Acquired Immunodeficiency Syndrome↗
KNOX action in Arabidopsis is mediated by coordinate regulation of cytokinin and gibberellin activities.
The shoot apical meristem (SAM) is a pluripotent group of cells that gives rise to the aerial parts of higher plants. Class-I KNOTTED1-like homeobox (KNOX) transcription factors promote meristem function partly through repression of biosynthesis of the growth regulator gibberellin (GA). However, regulation of GA activity cannot fully account for KNOX action. Here, we show that KNOX function is also mediated by cytokinin (CK), a growth regulator that promotes cell division and meristem function. We demonstrate that KNOX activity is sufficient to rapidly activate both CK biosynthetic gene expression and a SAM-localized CK-response regulator. We also show that CK signaling is necessary for SAM function in a weak hypomorphic allele of the KNOX gene SHOOTMERISTEMLESS (STM). Additionally, we provide evidence that a combination of constitutive GA signaling and reduced CK levels is detrimental to SAM function. Our results indicate that CK activity is both necessary and sufficient for stimulating GA catabolic gene expression, thus reinforcing the low-GA regime established by KNOX proteins in the SAM. We propose that KNOX proteins may act as general orchestrators of growth-regulator homeostasis at the shoot apex of Arabidopsis by simultaneously activating CK and repressing GA biosynthesis, thus promoting meristem activity.
Arabidopsis↗
Evolution of leaf developmental mechanisms.
Leaves are determinate organs produced by the shoot apical meristem. Land plants demonstrate a large range of variation in leaf form. Here we discuss evolution of leaf form in the context of our current understanding of leaf development, as this has emerged from molecular genetic studies in model organisms. We also discuss specific examples where parallel studies of development in different species have helped understanding how diversification of leaf form may occur in nature.
Biological Evolution↗
Virus infection of dendritic cells: portal for host invasion and host defense.
Dendritic cells (DCs) act as a portal for virus invasion and as the most potent antigen-presenting cells in antiviral host defense. Human immunodeficiency virus (HIV)-1 has served as the paradigm for virus interaction with DCs. HIV-1 infection of DCs via its primary CD4 receptor and secondary chemokine receptors leads to full virus replication (cis infection), whereas binding to C-type lectin receptors results both in cis replication, as well as transfer and replication of virus in CD4(pos) T cells (trans infection). DCs respond to this invasion by processing viral proteins through MHC class I and II pathways and undergoing a maturation that enhances their presentation of antigen to T cells for induction of adaptive antiviral immunity. HIV-1 and other viruses have evolved mechanisms to subvert this immune function. Engineering of DCs with various forms of viral immunogens and co-treatment with cytokines and chemokines is being used as an immunotherapy for HIV-1 and other viral infections.
Animals↗
Management of the internal carotid artery in tumors of the lateral skull base: preoperative permanent balloon occlusion without reconstruction.
OBJECTIVE: To present our experience with permanent preoperative balloon occlusion of the internal carotid artery while dealing with different abnormalities of the lateral skull base and a comparison with the results mentioned in the literature. STUDY DESIGN: Retrospective case review. SETTING: Private neurotologic and skull base tertiary referral center. PATIENTS: Fifteen patients who underwent preoperative balloon occlusion of the internal carotid artery and surgery subsequently for various abnormalities of the lateral skull base between 1989 and 2002. INTERVENTIONS: Each patient was subjected to four-vessel angiography along with the manual cross-compression test and balloon test occlusion to assess the efficacy of the collateral circulation. After angiography, each patient underwent a preoperative balloon occlusion, after which a lateral skull base procedure was performed for removal of the abnormality. MAIN OUTCOME MEASURES: Only those patients showing evidence of adequate collateral cerebral circulation and a less than 1-second delay between the angiographic phases of the two cerebral hemispheres on angiography were considered fit for preoperative balloon occlusion. While under going the preoperative balloon occlusion, the patients were clinically assessed for the development of any neurologic symptoms and signs. Long-term follow-up after surgery was also based on the development of symptoms and signs of neurovascular compromise. RESULTS: A major complication in the form of long-lasting hemiplegia occurred in one patient (6.7%). This complication was the result of technical factors rather than an effect of cerebral ischemia, because it was caused by an intimal dissection produced by the catheter. A defect in the visual field occurred in one patient (6.7%) that resolved partially after antiplatelet therapy. There was no mortality in our series related to preoperative balloon occlusion of the internal carotid artery. CONCLUSION: Preoperative balloon occlusion of the internal carotid artery can still be considered a viable option for the management of the internal carotid artery during lateral skull base surgery. Proper preoperative evaluation of the adequacy and efficacy of the collateral cerebral circulation reduces the chances of postoperative neurovascular complications.
Adolescent↗
Erbium:YAG laser and cultured epidermis in the surgical therapy of stable vitiligo.
OBJECTIVE: To induce complete and reproducible repigmentation of large "stable" vitiligo lesions by means of autologous cultured epidermal grafts using a rapid, simple, and minimally invasive surgical procedure. DESIGN: Achromic epidermis was removed by means of appropriately settled erbium:YAG laser, and autologous epidermal grafts were applied onto the recipient bed. Melanocyte content was evaluated by dopa reaction. The percentage of repigmentation was calculated using a semiautomatic image analysis system. SETTING: A biosafety level 3-type cell culture facility, a surgical ambulatory department, and a dermatological department in a hospital. PATIENTS: Twenty-one patients with different types of vitiligo were admitted to the study and treated with autologous cultured epidermal grafts. Inclusion criteria were failure of at least 2 standard medical approaches; no therapy for at least 12 months; no progression of old lesions or appearance of new lesions; no Koebner phenomenon within the past 18 months; and no autoimmune disorders. RESULTS: The average percentage of repigmentation in 21 patients was 75.9% (1759.7 cm2 repigmented/2315.8 cm2 transplanted). Three patients showed a reactivation of their vitiligo and did not show repigmentation. The remaining 18 patients, with 43 distinct lesions, showed an average percentage of repigmentation of 90% (1759.7 cm2 repigmented/1953.4 cm2 transplanted). CONCLUSIONS: Under appropriate conditions, cultured epidermal grafts induce complete repigmentation of stable vitiligo lesions. Erbium:YAG laser surgery can supply a fast and precise tool for disepithelialization, hence allowing treatment of large vitiligo lesions during a single surgical operation.
Adolescent↗
pl-bol3, a complex allele of the anthocyanin regulatory pl1 locus that arose in a naturally occurring maize population.
The pl1 gene encodes a MYB-related transcriptional activator committed to the regulation of anthocyanin biosynthesis in maize. Here, we report the genetic and molecular characterisation of pl-bol3, an Andean allele displaying features that make it different from all the known pl1 alleles. pl-bol3 has partial, light-independent expression, and it is active mainly in the juvenile phase of growth. It has a complex molecular structure, containing multiple pl1 gene copies, thus being the first complex locus discovered in the c1/pl1 family. Although the composite genes of the complex locus encode proteins identical to other functional PL1 proteins, the putative promoters of the pl-bol3 gene are different from the promoters of Pl-Rhoades (Pl-Rh) and pl1 sun-red alleles. The intensity and the tissue specificity of anthocyanin production directed by pl-bol3 differ significantly from that of Pl-Rh and the original pl-W22, and are specified by the interaction of pl-bol3 with the different r1/b1 gene family members and the competence of pl-bol3 to different pigment tissues. This allele represents a natural example of gene duplication and diversification of expression, giving rise to a significant change in phenotype and, in this way, is analogous to the complex r1 locus in maize. Analysis of the pl-bol3 allele contributes to understanding the generation of diversity associated with multiple-copy genes and the molecular basis of allele-specific gene expression.
Alleles↗
CD8+ T-cell immunity to HIV infection.
Fifteen years after the first, definitive reports of HIV-1-specific, CD8+ T cells [147,148], there is ample evidence for the importance of these cells in control of HIV-1 infection. As much is known of their role in the natural history of HIV-1 infection and their cellular and molecular mechanisms of reactivity than of T-cell responses to any other human virus. Indeed, HIV-1-related research has led the scientific field in revealing many new, fundamental principles of cellular immunity in the last 15 years. From these data, there are multiple, posited mechanisms for loss of CD8+ T-cell control of HIV-1 infection. These include both intrinsic defects in T-cell function and loss of T-cell recognition of HIV-1 because of its extraordinary genetic diversity and disruption of antigen presentation. Efforts have begun on devising approaches to reverse these immune defects in infected individuals and develop vaccines that induce T-cell immunity for protection from infection. Combination antiretroviral drug regimens now provide exceptional, long-lasting control of HIV-1 infection, even though they do not restore anti-HIV-1 T-cell immunity fully in persons with chronic HIV-1 infection. Very encouraging results show that such treatment can maintain normal T-cell reactivity specific for this virus in some persons with early HIV-1 infection. Unfortunately, the antiviral treatment does not cure the host of this persistent, latent virus. This has led to new strategies for immunotherapeutic intervention to enhance the level and breadth of the T-cell repertoire specific for the host's residual virus in persons with chronic HIV-1 infection. Although the principles of immunotherapy stem from early in the last century, modern era approaches are integrating highly sophisticated, molecular and cell biology reagents and methods for control of HIV-1 infection. The most promising immunotherapies are autologous virus activated in vivo by STI or administered in autologous DC that have been engineered ex vivo. There are also compelling rationales supported by animal models and early clinical trials for use of cytokines and chemokines as recombinant proteins or DNA to augment anti-HIV-1 T-cell reactivity and trafficking of T cells and APC to tissue sites of infection. For prevention of HIV-1 infection, the discouragingly poor results of vaccine development in the late 1980s and early 1990s have led to very encouraging, recent studies in monkeys that show partially protective and possibly sterilizing immunity. Finally, clinical trials of new-generation DNA and live vector vaccines already have indications of improved induction of HIV-1-specific T-cell responses. Knowledge of HIV-1-specific T-cell immunity and its role in protection from HIV-1 infection and disease must continue to expand until the goal of complete control of HIV-1 infection is accomplished.
CD8-Positive T-Lymphocytes↗
Members of the c1/pl1 regulatory gene family mediate the response of maize aleurone and mesocotyl to different light qualities and cytokinins.
We investigated the role of transcription factors (R, SN, C1, and PL) in the regulation of anthocyanin biosynthesis by different light qualities (white, red, blue, and ultraviolet) and by cytokinin in maize (Zea mays). We analyzed anthocyanin accumulation, structural gene expression, and regulatory gene expression in the seed aleurone and the seedling mesocotyl. In the mesocotyl, white, blue, and ultraviolet-B light strongly induced anthocyanin accumulation and expression of two key structural genes. In contrast, red light had little effect. Cytokinin enhanced the response to light but was not sufficient to induce anthocyanin accumulation in darkness. Plants with the pl-bol3 allele showed high levels of anthocyanin accumulation in response to light, whereas those with the pl-W22 allele did not, demonstrating the importance of pl1 in the light response. The expression of the pl-bol3 gene, encoding an MYB-related transcription factor, was induced by light and enhanced by cytokinin in a very similar manner to the structural genes and anthocyanin accumulation. Expression of the bHLH (basic helix-loop-helix) Sn1-bol3 gene was stimulated by several light qualities, but not enhanced by cytokinin, and was less well correlated with the induction of anthocyanin biosynthesis. In the aleurone, white, red, and blue light were effective in stimulating anthocyanin accumulation and expression of the MYB-related gene C1. The bHLH R gene was constitutively expressed. We conclude that specific members of the MYB-related c1/pl1 gene family play important roles in the regulation of anthocyanin synthesis in maize in response to different light qualities and cytokinin.
Adenine↗
Brain apparent diffusion coefficient evaluation in pediatric patients with neurofibromatosis type 1.
OBJECTIVE: The most frequent intracranial appearance in children with neurofibromatosis type 1 (NF1) is represented by the presence of hyperintense lesions on T2-weighted images, the so-called "unidentified bright objects" (UBOs). Di Paolo demonstrated that these lesions represent foci of myelin vacuolization with increased water content. The aim of this study was to investigate the isotropic apparent diffusion coefficient (ADC) values within the UBOs and normal-appearing brain and at the regressed UBO sites. METHODS: Fifteen consecutive children with NF1 underwent magnetic resonance diffusion evaluation of the brain. Fifteen healthy age- and sex-matched children constituted the control group. Apparent diffusion coefficient maps were obtained, and regions of interest were placed bilaterally in 8 different areas. Two cortical areas were evaluated using single-pixel analysis. Apparent diffusion coefficient values within the UBOs were calculated by using irregular regions of interest. Regressed UBO sites were investigated by using circular regions of interest. Apparent diffusion coefficient values within the different areas were compared using a t test. RESULTS: Compared with the controls, NF1 patients showed higher ADC values (P < 0.001) in all locations. In the NF1 group, the mean ADC value in the UBOs was higher than in other locations (P < 0.001). The mean ADC value within the regressed UBO sites was higher than in the normal-appearing locations (P < 0.001). CONCLUSIONS: The higher ADC values in children with NF1 suggest an increase in water content of the normal-appearing brain. The UBOs are the areas with the highest water content. The regressed UBOs sites show higher water content than the normal-appearing areas.
Adolescent↗